Scott-Brown 's- Otorh inO,laryngology. Head an.d Neck Surgery
Scott-Brown's Otorhinolaryngology, Head and Neck Surgery 7th edition Lead editor: Michael Gleeson
Volume 1 Part 1 Cell biology, edited by Nicholas S Jones Part 2 Wound healing, edited by Nicholas S Jones Part 3 Immunology, edited by Nicholas S Jones Part 4 Microbiology, edited by Nicholas S Jones Part 5 Haematology, edited by Nicholas S Jones Part 6 Endocrinology, edited by Nicholas S Jones Part 7 Pharmacotherapeutics, edited by Martin J Burton Part 8 Perioperative management, edited by Martin J Burton Part 9 Safe and effective practice, edited by Martin J Burton Part 10 Interpretation and management of data, edited by Martin J Burton Part 11 Recent advances in technology, edited by Martin J Burton Part 12 Paediatric otorhinolaryngology, edited by Ray Clarke
Volume 2 Part 13 The nose and paranasal sinuses, edited by Valerie J Lund Part 14 The neck, edited by John Hibbert Part 15 The upper digestive tract, edited by John Hibbert Part 16 The upper airway, edited by John Hibbert Part 17 Head and neck tumours, edited by John Hibbert Volume 3 Part 18 Plastic surgery of the head and neck, edited by John C Watkinson Part 19 The ear, hearing and balance, edited by George G Browning and Linda M Luxon Part 20 Skull base, edited by Michael Gleeson Index CD-ROM
George G Browning MD FRCS Professor of Otorhinolaryngology, MRC Institute of Hearing Research, Glasgow Royal Infirmary, Glasgow, UK Martin J Burton MA DM FRCS Senior Clinical Lecturer, University of Oxford; and Consultant Otolaryngologist, Oxford Radcliffe NHS Trust Oxford, UK Ray Clarke BSc DCH FRCS FRCS (ORL) Consultant Paediatric Otolaryngologist, Royal Liverpool University Children's Hospital, Alder Hey, Liverpool, UK Michael Gleeson MD FRCS Professor of Otolaryngology and Skull Base Surgery, Institute of Neurology, University College London; and Consultant, Guy's, Kings and St Thomas' and the National Hospital for Neurology and Neurosurgery, London UK; and Honorary Consultant Skull Base Surgeon, Great Ormond Street Hospital for Sick Children, London, UK John Hibbert ChM FRCS Formerly Consultant Otolaryngologist, Department of Otolaryngology,~ Guy's Hospital, London, UK Nicholas S Jones MD FRCS FRCS (ORL) Professor of Otorhinolaryngology, Queen's Medical Centre, University C?f Nottingham, Nottingham UK Valerie J Lund MS FRCS FRCS (Ed) Professor of Rhinology, The Ear Institute, University College London, London, UK Linda M Luxon BSc MBBS FRCP Professor of Audiovestibular Medicine, University of London at University College London, Academic Unit of Audiovestibular Medicine; and Consultant Physician, National Hospital for Neurology and Neurosurgery; and Honorary Consultant Physician, Great Ormond Street Hospital for Children, London, UK John C Watkinson MSc MS FRCS (Ed, Glas, Land) DLO Consultant Head and Neck and Thyroid Surgeon, Department of Otorhinolaryngology/Head and Neck Surgery, Queen Elizabeth Hospital, University of Birmingham NHS Trust, Birmingham, UK
Scott-Brown's Otorhinolaryngology, Head and Neck Surgery 7th edition
Volume 2
Edited by
Michael Gleeson George G Browning. Martin J Burton. Ray Clarke. John Hibbert, Nicholas S Jones. Valerie J Lund. Linda M· Luxon. John C Watkinson
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First published in Great Britain in 1952 by Butterworth 8: Co. Second edition 1965 Third edition 1971 Fourth edition 1979 Fifth edition 1987 Sixth edition 1997 This seventh edition published in Great Britain in 2008 by Hodder Arnold An imprint of Hodder Education, a part of Hachette Livre UK, 338 Euston Road, London NWl 3BH http://www.hoddereducation.com
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Contents
How to use this book
PART 13 THE NOSE AND PARANASAL SINUSES - EDITED BY VALERIE J LUND 104
Anatomy of the nose and paranasal sinuses
xi
1313 1315
H Stammberger and Valerie J Lund 105
Nasal endoscopy
1344
Rodney J Schlosser and David W Kennedy 106
Physiology of the nose and paranasal sinuses
1355
Adrian Drake-Lee 107
Measurement of the nasal airway
1372
Ronald Eccles 108
Classification and differential diClgnosis of rhinosinusitis
1380
Ian S Mackay and Valerie J Lund 109
Allergic rhinitis
1386
G/enis Scadding and Stephen Durham 110
Nonallergic perennial rhinitis
1408
Claus Bachert 111
Occupational rhinitis
1415
Hesham Saleh 112
Food allergy and intolerance
1424
Carsten Bindslev-Jensen and Morten Osterballe 113
Rhinosinusitis
1439
Michael S Benninger 114
Fungal rhinosinusitis
1449
Jean Michel Klossek 115
Specific chronic infections
1458
S Bahadur and A Thakar 116
Medical management of chronic rhinosinusitis
1469
Gltinis Scadding 117
Surgical management of rhinosinusitis
1478
Valerie J Lund and Julian Rowe-Jones 118
The frontal sinus
1500
Wolfgang Draf 119
Mucocoeles
1531
Valerie J Lund 120
Complications of rhinosinusitis
1539
Robert Slack and Richard Sim
j
,,' .
-
vi I 121
Contents
Nasal polyposis
1549
Niels Mygind and Valerie J Lund 122
The relationship between the upper and lower respiratory tract
1560
Jean Bousquet and Antonio M Vignolat 123
The septum
1569
Adriaan F van Olphen 124
Nasal septal perforations
1582
Charles East and Santdeep Paun 125
The management of enlarged turbinates
1589
Luisa F Grymer 126
Epistaxis
1596
Gerald W McGarry 127
Nasal fractures
1609
Brent A McMonagle and Michael Gleeson 128
Fractures of the facial skeleton
1618
Simon Holmes and Michael Gleeson 129
Cerebrospinal fluid rhinorrhoea
1636
Andrew H Marshall and Nicholas S Jones 130
Granulomatous conditions of the nose
1645
David J Howard and Valerie J Lund 131
Abnormalities of smell
132
Orbital and optic nerve decompression
1660
Richard L Doty and Steven M Bromley 1677
Valerie J Lund and Geoffrey ERose 133
Dacryocystorh i nostomy
1689
Neil Fergie and Nicholas S Jones 134
Conditions of the external nose
1699
Michael O'Connell 135
The diagnosis and management of facial pain
1718
Tim J Woolford and Nicholas S Jones 136
Medical negligence in rhinology
1730
Maurice Hawthorne
PART 14 THE NECK - EDITED BY JOHN HIBBERT
1737
137
1739
Surgical anatomy of the neck
Chris R Jennings 138
Examination and imaging of the neck
1754
Sheila C Rankin and John Hibbert 139
Neck trauma
1766
Johannes J Fagan and Andrew J Nicol 140
Benign neck disease: infections and swellings
1777
Peter Clarke
PART 15 THE UPPER DIGESTIVE TRACT - EDITED BY JOHN HIBBERT 141
Anatomy of the mouth and dentition
1789 1791
Barry KB Berkovitz 142
Benign oral and dental disease
Crisp ian Scully and Jose-V Sebastian Bagan
1816
<
Contents
143
Abnormalities of taste
A!AN
I vii 1840
Steven M Bromley and Richard L Doty 144
Salivary gland anatomy
1852
Graham J Cox 145
Physiology of the salivary glands
1858
Roderick Cawsont and Michael Gleeson 146
Imaging of the salivary glands
1871
Nicole JM Freling 147
Non-neoplastic salivary gland diseases
1898
Stephen R Porter 148
Cysts and tumours in and around the jaws, including sarcoma
1921
Mark McGurk, Anna Cassoni and Lisa Pitkin 149
Anatomy of the pharynx and oesophagus
1942
Nigel Beasley 150
Physiology of swallowing
1954
Paula Leslie and Stephen McHan well 151
Functional investigations of the upper gastrointestinal tract
1964
Lisa J Hirst 152
Acute and chronic pharyngeal infection
1981
Marcelle Macnamara 153
Causes of dysphagia
2025
E/fy B Chevretton 154
Globus pharyngeus
2037
Petros D Karkos and Janet A Wilson 155
Pharyngeal pouch
2043
Grant Bates 156
Oesophagal diseases
2062
Robert C Mason 157
Neurological disease of the pharynx
2074
Robert J Sandersont, Paul Tierney and Richard Adamson 158
Dysphagia: management and intervention
2084
Alison Perry 159
Management and treatment of intractable aspiration
2094
E/fy B Chevretton
PART 16 THE UPPER AIRWAY - EDITED BY JOHN HIBBERT 160
Anatomy of the nasopharynx
2105 2107
Alexander C Vlantis and C Andrew van Hasselt 161
Benign conditions of the nasopharynx
2116
Victor J Abdullah and C Andrew van Hasselt 162
Anatomy of the larynx and tracheobronchial tree
2130
Nigel Beasley 163
Assessment and examination of the upper respiratory tract
2145
Jean-Pierre Jeannon and Marcelle Macnamara 164
Physiology of the larynx
2155
Lesley Mathieson and Paul Carding 165
Voice and speech production
2164
Paul Carding and Lesley Mathieson 166
Objective evaluation of the voice
2170
Julian McGlashan and Adrian Fourcin
I
·iW'wi
...
viii 167
I Contents
Disorders of the voice
2192
Julian McGlashan
168
The professional voice
2211
Meredydd Harries
169
Speech therapy in ENT practice: scope, science and evidence for intervention
2216
Alison Perry
170
Phonosurgery
2234
Meredydd Harries
171
Acute infections of the larynx
2248
Andrew C Swift
172
Chronic laryngitis
2258
Kenneth MacKenzie
173
Laryngeal trauma and stenosis
2271
Lisa Pitkin
174
Upper airway obstruction
2286
Paul Pracy
175
Tracheostomy
2292
Paul Pracy
176
Physiology of sleep and sleep disorders
2305
John Fleetham
177
Obstructive sleep apnoea: medical management
2313
Dev Banerjee
178
The surgical management of snoring
2325
Marcelle Macnamara
PART 17 HEAD AND NECK TUMOURS - EDITED BY JOHN HIBBERT
2341
179
2343
Epidemiology of head and neck cancer
Randall P Morton and Mark E Izzard
180
Aetiology of head and neck cancer
2351
Nicholas D Stafford
181
Staging of head and neck cancer
2359
Nicholas J Roland
182
Data collection in head and neck cancer
2372
Richard Wight
183
Prognostic indicators and serum markers
2378
Andrew S Jones
184
Skin cancer of the head and neck
2395
Garrick A Georgeu and Michael Gleeson
185
Mucosal malignant melanoma
2406
Andrew S Jones
186
Nasal cavity and paranasal sinus malignancy
2417
Brent A McMonagle and Michael Gleeson
187
Juvenile angiofibroma
2437
Michael Gleeson
188
Nasopharyngeal carcinoma
2445
John Kong Sang Woo and C Andrew van Hasselt
189
Benign salivary gland tumours
2475
Michael Gleeson and Roderick Cawsont
190
Malignant tumours of the salivary glands
Andrew S Jones
2493
Contents I
191
Tumours of the parapharyngeal space
ix
2522
Andrew S Jones
192
Oral cavity tumours including the lip
2543
Keith Webster
193
Oropharyngeal tumours
2577
Patrick J Bradley
194
Tumours of the larynx
2598
Martin A Birchall and Laysan Pope
195
Rehabilitation after laryngectomy
2623
Andrew J Parker
196
Tumours of the hypopharynx and oesophagus
2633
Andrew S Jones
197
Thyroid cancer
2663
James Ramsden and John C Watkinson
198
Management of the patient presenting with neck lymphadenopathy and an unknown primary carcinoma
2702
Jawaher Ansari and John Glaholm
199
Metastatic neck disease
2711
John C Watkinson
200
Developments in radiotherapy for head and neck cancer
2753
John Glaholm
201
Quality of life in head and neck cancer
2766
Randall P Morton and Hisham Mehanna
202
Palliative care for head and neck cancer
2781
Charles Diamond and Claud Regnard
203
Medical negligence in head and neck surgery
2803
Arnold GD Maran
Please note: The table of contents for all three volumes can be found on the Scott-Brown website at: www.scottbrownENT.com. The list of contributors. preface and list of abbreviations are included in the prelims for Volume 1. The index for all three volumes is included in Volume 3.
How to use this book
This new edition of Scott-Brown's Otorhinolaryngology, Head and Neck Surgery incorporates some special features to aid the readers' understanding and navigation of the text. These are described below.
SEARCH STRATEGY The majority of the chapters feature a search strategy indicating the key words used by the author when conducting their literature review in order to prepare the chapter, so that the reader can repeat and develop the search.
EVIDENCE SCORING For the major sections in each chapter, the authors have used a hierarchical system to indicate the level of evidence supporting their statements. This is shown in the text in the form [***], with the number of stars indicating the level of evidence. The key to this system is shown in the table below.
****
Systematic reviews, meta-analyses of randomized controlled trials and randomized controlled trials
***
Non-randomised studies
**
Observational or non-experimental studies
*
Expert opinion
Where no level is shown, the quality of supporting evidence, if any exists, is of low grade only (for example, case reports, clinical experience etc.). For more information on evidence scoring, please refer to Chapter 304, Evidence-based medicine; and 305 Critical appraisal skills.
CLINICAL RECOMMENDATIONS The authors have indicated the basis on which they have made clinical recommendations by grading them according to the level of the supporting evidence. This is shown in the text in the form [Grade A], with the grade indicating the level of evidence supporting the recommendation. The key to this system is shown in the table below.
i
L
xii I
How to use this book
A
Recommendation based on evidence from meta-analyses of randomized controlled trails
B
Recommendation based on evidence from high quality case-controlled or cohort studies
C
Recommendation based on evidence from low quality case-controlled or cohort studies
D
Recommendation based on evidence from clinical series or expert opinion
Recommendations are graded where the author is satisfied that the literature supports such a grading; otherwise a grading may not be given.
REFERENCE ANNOTATION The reference lists are annotated with an asterisk, where appropriate, to guide readers to key primary papers and major review articles. We hope that this feature will render the lists of references more useful to the reader and will encourage self-directed learning among both trainees and practicing physicians.
PART
13
THE NOSE AND PARANASAL SINUSES EDITED BY VALERIE J LUND
104 Anatomy of the nose and parana sal sinuses H Stamm berger and Valerie J Lund
1315
105 Nasal endoscopy Rodney J Schlosser and David W Kennedy
1344
106 Physiology of the nose and parana sal sinuses
1355
Adrian Drake-Lee
107 Measurement of the nasal airway
1372
Ronald Eccles
108 Classification and differential diagnosis of rhinosinusitis Ian S Mackay and Valerie J Lund
1380
109 A11ergic rhinitis
1386
Glenis Scadding and Stephen Durham
110 Nona11ergic perennial rhinitis
1408
Claus Bachert
111 Occupational rhinitis
1415
Hesham Saleh
112 Food allergy and intolerance
1424
Carsten Bindslev-Jensen and Morten Osterballe
113 Rhinosinusitis
1439
Michael S Benninger
114 Fungal rhinosinusitis
1449
Jean Michel Klossek
115 Specific chronic infections
1458
S Bahadur and A Thakar
116 Medical management of chronic rhinosinusitis
'1469
Glenis Scadding
117 Surgical management of rhinosinusitis Valerie J Lund and Julian Rowe-Jones
1478
118 The frontal sinus
1500
Wolfgang Draf
119 Mucocoeles Valerie J Lund
1531
I
L
.oi
120 Complications of rhinosinusitis Robert Slack and Richard Sim
1539
121 Nasal polyposis Niels Mygind and Valerie J Lund
1549
122 The relationship between the upper and lower respiratory tract Jean Bousquet and Antonio M Vignolat
1560
123 The septum Adriaan F van Olphen
1569
124 Nasal septal perforations Charles East and Santdeep Paun
1582
125 The management of enlarged turbinates Luisa F Grymer
1589
126 Epistaxis Gerald W McGarry
1596
127 Nasal fractures Brent A McMonagle and Michael Gleeson
1609
128 Fractures of the facial skeleton Simon Holmes and Michael Gleeson
1618
129 Cerebrospinal fluid rhinorrhoea Andrew H Marshall and Nicholas S Jones
1636
130 Granulomatous conditions of the nose David J Howard and Valerie J Lund
1645
131 Abnormalities of smell Richard L Doty and Steven M Bromley
1660
132 Orbital and optic nerve decompression Valerie J Lund and Geoffrey ERose
1677
133 Dacryocystorhinostomy Neil Fergie and Nicholas S Jones
1689
134 Conditions of the external nose Michael O'Connell
1699
135 The diagnosis and management of facial pain Tim J Woolford and Nicholas S Jones
1718
136 Medical negligence in rhinology Maurice Hawthorne
1730
104 Anatomy of the nose and paranasal sinuses H STAMMBERGER AND VALERIE J LUND
Development of nose and paranasal sinuses
1315
Comparative anatomy
1321
Anatomy of the nose and paranasal sinuses
1322
Key points
1341
Deficiencies in current knowledge and areas for future research
The data in this chapter are supported by a literature search using the nasal cavity and external nose.
1342 1342
References
key words endoscopic anatomy, paranasal sinuses, .
DEVELOPMENT OF NOSE AND PARANASAL SINUSES
more anteriorly placed than the definitive choana due to
The exte rnal nose and nasal cavity
sions of the medial nasal folds to produce the premaxilla
continuous posterior growth of the palate.4 The floor an terior to the choana forms from mesenchymal exten and ultimately the upper lip and medial crus of the lower
The nose develops from a number of mesenchymal processes around the primitive mouth
(Figure 104.1).1,2,
The nasal cavity, is first recognizable in the 5.6 mm (crown-rump distance) embryo week as the
olfactory
or
in the fourth intrauterine
nasal placode,
a thickening of
the ectoderm above the stomatodaeum.3 This placode sinks
to form the
olfactory pit
lying
between
the
proliferating mesoderm of the medial and lateral nasal
lateral cartilages. The maxillary process also grows ventrally from the dorsal end of the mandibular process (first visceral arch) to join the lateral nasal fold around the nasomaxillary groove. Ectoderm in this region eventually canalizes to form the nasolacrimal duct. The lateral nasal folds also form the nasal bones, upper lateral cartilages and lateral crus of the lower lateral cartilages.
folds of the frontonasal process. This deepens to form the
nasal sac
by the fifth week
(Figure 104.2).
In the 12.5 mm embryo, the maxillary process of the
The palate and nasal septum
first branchial arch grows anteriorly and medially to fuse anteriorly with the medial nasal folds and the frontonasal process which closes the nasal pits off to form widely separated primitive, nasal cavities
(Figure 104.3). The
primitive nasal cavity and mouth are separated initially by a bucconasal membrane. This grad ually thins as the nasal
sacs extend posteriorly and eventually breaks down at the 14-15 mm stage to form the primitive choanae. These are
The primitive palate begins to form anteriorly with fusion of the maxillary and frontonasal processes by the 13.5 mm
embryo stage.- A midline ridge develops from the poster
ior edge of the frontonasal process in the roof of the oral
cavity and extends posteriorly to the opening of Rathke's 104.4). This becomes the nasal septum
pouch (Figure
which is continuous anteriorly with the partition between
,
\
/
-
nn
1
1316
I PART 13 THE NOSE AND PARANASAL SINUSES
Lateral nasal Olfactory epithelium
Nasal sac
fold Medial nasal -+---hoo�
Nasal fin
fold
Maxillary process
Rathke's pouch
Fig u re 104.2
The roof of the stomatodaeum of a 12 mm
human embryo illustrating the development of the primitive palate and posterior nares by approximation of the maxillary processes to the lateral and medial nasal folds. The previous site of attachment of the buccopharyngeal membrane is represented by a dotted line and part of the left maxillary process has been removed. After Hami Iton and Mossman 1.
Lateral nasal fold
An te ri or naris
Rudiment of nasal septum
Eye
Primitive palate
Palatal process
Figure 104.1
Development of the nasal sac, nasal cavity and ' primitive palate. After Hamilton and Mossman .
of maxillary mesoderm Rathke's pouch
the primitive nasal cavities. As the nasal cavities enlarge, the palatal processes, derived from the lateral maxillary
Fig u re 104.3
The roof of the stomatodaeum of a 12.5 mm
embryo. After Ham i Iton and Mossman 1.
mesoderm, grow medially towards each other and the septum. Initially, they lie lateral to the tongue, but as this moves ventrally with further growth, the palatal processes swing medially and fuse horizontally
104.6).
(Figures 104.5
and
The fusion begins along the posterior margin of
Primitive Frontonasal palate Anterior process Meclial naris nasal fold
the primitive palate and is c,omplete
Forehead
dehiscence at the future site of the incisive canal. Fusion continues between the palatal processes and the septum
Nasolacrimal furrow
from anterior to posterior, separating the nasal and oral
Maxillary process
cavities and most posteriorly the nasopharynx and oral
Eye
cavity as the palatal processes complete the soft palate and
Primitive posterior naris
uvula. On either side of the anterior septum, in relation to the paraseptal Jacobson's cartilage, an invagination of ectoderm fOnTIS the vomeronasal organ, which largely
Palata! process of maxillary mesoderm
Rathke's pouch
Figure 104.4
The roof of the stomatodaeum of a 13.5 mm
disappears in man, leaving only a blind tubular pouch,
embryo. After Hami Iton and Mossman 1,
in
discrete entities in the adult but more usually involute,
2-6 mm long.s Longitudinal strips of cartilage 7-15 rom length
may
be
identified
in
the
embryo,
lying
adjacent to the vomeronasal organ on either side of
leaving only a .small cartilaginous bulge. The primitive
the septal cartilage. These may occasionally remain as
septum is initially made entirely of cartilage. The superior
/
j
�-
_.'-
-I' <,\",-- ...., .
Chapter 104 Anatomy of the nose and paranasal sinuses I
1317
Septal cartilage
Developing inferior turbinate Vomeronasal cartilage '�+. , ..Ir,::-' ....��
\.
�
Tongue Palatal process of maxilla Tooth bud Meckel's cartilage
Figure 104.5
Section through the developing
palate of a 20 mm human foetus. After Ham i l ton ' and Mossman .
Septal cartilage Developing turbinate
--
......'A,...;.��
_.
Vomeronasal organ -
Fused palatal and septal processes
Tongue
� ,
Figure 104.6
Meckel's cartilage
..
Sect'lon through the develop'lng
palate of a 48 mm human foetus. After Hamilton
and Mossman'.
The paranasal bones and sinuses
part ossifies to form the perpendicuJar plate of the ethmoid
(from
crista
galli
downwards6, 7 )
and
the
vomer in the posteroinferior portion) leaving an ante
THE MAXILLA
roinferior quadrilateral cartilaginous plate. Two ossifica tion
centres
appear
for
the
vomer
at
the
The maxilla arises during the sixth and seventh weeks
eighth
foetal week on either side of the cartilage) uniting to
from :five ossification centres. In the fourth foetal month
form a deep bony groove in which the cartilage sits.
these fuse to form the alveolar, palatine) zygomatic and
As grovvth continues, part of the cartilage absorbs as the two bony lamellae fuse. By puberty, the lamellae are
,
frontal processes and the floor of the orbit . A further centre appears in the medial floor of the pyriform
and an
apert u re, forming the premaxilla in which the upper
anterior groove as'indications of the vomer's bilaminar
incisor teeth develop. The premaxilla forms the anterior nasal spine and fuses with - the vomeronasal cartilages
almost completely united with
everted alae
origin. - The nasal bones arise during the tenth and eleventh weeks.
laterally and septal cartilage superiorly.
i
I
/ \
.(.
1318
I PART 13 THE NOSE AND PARANASAL SINUSES
T H E ETH M O I D BO N E
The ethmoid bone ossifies i n the cartilaginous nasal capsule from three centres; one for each labyrinth and one for the perpendicular plate. The centres for the labyrinth are present from the fourth or fifth intrauterine month, so they are partially ossified at birth. The perpendicular plate and crista galli develop from one centre during the first year after birth and fuse with the labyrinths at the beginning of the second year. Both this centre and those for the labyrinth contribute to the cribiform plate.
TH E FRO N TA L BO N E
The frontal bone ossifies i n membrane from two centres, one in each superciliary ridge appearing in the eighth intrauterine week. At birth, the bone is composed of two halves separated by a frontal or metopic suture, which begin to fuse from the second year. This is usually complete by the eighth year though may persist in some races, such as the Japanese.s
TH E SPH E N O I D BO N E
The sphenoid is divided into two parts, a presphenoidal portion anterior to the tuberculum sellae continuous with the lesser wings made up of six separate ossification centres, and the post-sphenoidal part composed of the sella turcica and dorsum sellae associated with the greater wings and pterygoid processes derived from eight centres. The pre- and post-sphenoidal parts of the body fuse around the eighth intrauterine month. At birth, the bone consists of three pieces, a central portion consisting of the
body and lesser wings and two lateral parts, each consisting of the greater wing and pterygoid process which begin to fuse at one year after birth.
THE TURBI NATE BO N ES
A series of elevations appear on the lateral wall of the nose from the sixth foetal week which will ultimately form the turbinates. The most inferior or maxilloturbinal forms the inferior turbinate. The middle, superior and supreme turbinates result from reduction of the complex ethmo turbinal system found in lower mammals. Similarly, the primitive nasoturbinal is represented by the agger nasi region and uncinate process of the ethmoid.
THE MAXI LLARY S I N US
The maxillary sinus is the first sinus to appear (seven to ten weeks) as a shallow groove expanding from the primitive ethmoidal infundibulum into the mass of the maxilla (Figure 104.7). Absorption and expansion results in a small cavity at birth which measures 7 x 4 x 4 mm.9 It continues to grow during childhood at an estimated annual rate of 2 mm vertically and 3 mm anteroposter iorlylO and in particular with development of the middle third of the face as the dentition erupts. This process slows down around the seventh year of life, followed by a second growth phase thereafter. At the twelfth year of life, pneumatization may reach laterally just under the lateral orbital wall at the insertion of the zygomatic process, inferiorly to the level of the nasal floor and after the second dentition below the nasal floor. After dentition,
Figure 104.7
(a) A coronal section throug h the
lateral nasal wall, orbit and maxilla of a newborn. Clearly the uncinate process can be Identified and lateral to It. the ethmoidal infundibulum. The arrows indicate a small blister-like maxillary sinus, which has already developed from the infundibulum. 1, uncinate process; 2, maxillary
sinus; 3, dental germ; cm, middle turbinate ; ci,
inferior turbinate; s, septum. (b) The development of the maxillary sinus from the ethmoidal infundibulum in the foetus and infant. This evoluti on explains why the ostium of the fully developed maxillary sinus is normally found at the 'floor of the ethmoidal infundibulum. and why drainage and ventilation of the maxillary sinus pass through the ethmoidal infundibulum. i, ethmoidal infundibulum; s, septum. ( Dissection W. Anderhuber, Graz; drawing modified from Peter.)
Chapter 104 Anatomy of the nose and paranasal sinuses I
the sinus only gradually enlarges, reaching its final size in ) the seventeenth to eighteenth year of life. A 'standard ) an
1319
descending portion develops into the uncinate process. The second crest develops into the bulla lamella which
adult has a volume of around 15 cm2
when pneumatized, usually results in the largest and most
and is roughly pyramid shaped. The base of this pyramid
constant cell of the anterior ethmoid complex. Uncinate
is formed by the medial wall of the maxillary sinus with
process) ethmoidal bulla, middle, superior and supreme
maxillary sinus in
the apex of the pyramid towards the zygomatic recess.
turbinate are attached to the lateral nasal wall by their
The sinus may become relatively enlarged in old age as a
basal or ground lamella. This reflects their origin from the
result of resorption of the alveolus secondary to loss of
folds or crests which arose in the lateral wall of the nasal
teeth.
capsule. The attachment of the middle turbinate is considered the most important of these ground lamellae. Cells and clefts opening and draining antero-inferiorly to
THE ETHM O I D S INUS
this lamella by definition are part of the anterior ethmoid)
During the ninth and tenth week of gestation) six to seven folds appear in the lateral wall of the nasal capsule of the foetus. These folds are separated from each other by corresponding grooves. Over the next weeks, the folds fuse into three to four remaining crests with an anterior 'ascending' and a posterior 'descending' portion (ramus ascendens and ramus descendens)
(Figure
104.8). All
permanent ethmoidal structures develop from these crests and the furrows in between. From the main folds, two to a maximum of three ethmoidal turbinates develop: the persisting middle, superior and - if developed - supreme
cells and clefts opening and draining posterior to it are considered cells and spaces of the posterior ethmoid complex.
11
The uncinate process and ethmoidal bulla can already be identified during the first third of gestation. Between these structures develops an initially shallow, then deeper cleft orientated anteriorly and inferiorly, the ethmoidal infundibulum. At birth, these structures can clearly be identified and the initially very small maxillary sinus can be seen developing into the maxilla out of the ethmoidal infundibulum
(Figures
104.7 and 104.9).
nasal turbinate. The persisting inferior turbinate, the so called maxillo-turbinal, develops from the most inferior of the folds and is considered a separate bone not connected to the ethmoid complex. Not all
primary
folds
result in
THE SPHENO I D SINUS
The sphenoid sinus is recognizable at around the third pennanent
nasal
intrauterine month as an evagination from the sphenoeth
turbinates. The crest of the first fold usually regresses
moidal recess and again a small cavity is found at birth
during development, its ascending portion resulting in the agger nasi (sometimes called the naso-turbinal), the
Fig u re 104.9
A view of the lateral nasal wall in a newborn. 1,
inferior turbinate; 2, middle turbinate. This still shows the sharp
Figure 104.8
A schematic drawing of the primary folds and
the lateral wall of the nasal capsule of the human foetus in their original positional relationship. ET, to ET5, primary ethmoturbinals, which fuse into two to three persisting ethmoidal turbinates. MT, maxilloturbinal; NT, nasoturbinal; S, to S6' major furrows (grooves) between primary ethmoturbinal
crease at the transition from its descending part to the
ascending part, which is almost at right angles. 3, longitudinal tor Us above a sagittal groove in the medial surface of the. , middle turbinate, which may occasionally persist in an adult. 4, superior turb'lnate; 5, supreme turbinate; 6, remnants of the last ethmoturbinal in sphenoethmoidal recess; 7, Bertini ossification
ascending and descending portion of Sand ET. Modified from
centres of the nonpneumatized sphenoid; 8, spheno-occipital synchondrosis: 9, dental germ (upper incisor); an, agger nasi. By
Killian and Peter.
permission of W. Anderhuber, Graz.
crests; To, pharyngeal opening of Eustachian. tube. Note:
i
,/ .' i '( ' ; -,'�..-:"_-..L_
.
1320 (2
x
I PART 13
2
x
THE NOSE AN D PARANASAL SIN USES
1.5 mm). At the third year of life, pneumatization
of the sphenoid bone progresses and at age seven has frequently reached the floor of the sella. In adults, degrees
of pneumatization vary greatly, asymmetry being the rule rather than the exception. In extreme cases, internal carotid
continue throughout adolescence. The configuration of
the sinuses and the frontal recess is subject to considerable variation. Diverticula and septation are not uncommon. The frontal recess, although frequently a narrow hourglass segment,
have
may
a
longer,
more
tortuous
path
artery, optic nerve, V2 and the vidian nerve can be exposed
encroached upon by adjacent anterior ethmoidal cells.
in the walls of the sphenoid sinus with almost no protective (Figure 104.10). Pneumatization is said to
These variations are a direct consequence of the sinus'
bony walls
embryological development as it is the last to complete its
progress at a rate of 0.25 mm each year from the age of four
growth, in early adulthood.
years but this is not constant.12
ANO MALI ES
Fusion of the processes takes place from anterior to
THE FRO N TAL SIN US
The frontal sinus is the most variable in size and shape and may be regarded embryologically as an anterior
ethmoidal cell. In the fourth foetal month, development of the frontal sinus out of the so-called frontal recess can be seen. From this most anterior and superior segment of the
anterior
ethmoid
complex,
the
frontal
bone
is
gradually pneumatized, resulting in frontal sinuses of variable size. At birth, the frontal sinuses are small and, on x-rays,
cannot
usually
be
differentiated
from
other
anterior ethmoidal cells. In contrast to the maxillary sinus, the process of pneumatization is initially very slow. However, pneumatization is evident in computed tomo graphy at the end of the first year of life. In the fifth year of life, pneumatization extends superiorly and at twelve years the sinus is largely developed. Pneumatization may
posterior. Partial or complete failure of fusion results in
abnormalities which range from a bifid uvula to clefts of varying severity. Failure of fusion between a maxillary
process and the corresponding premaxilla causes
a
cleft lip.
Failure of the maxillary and lateral processes to fuse produces a facial cleft with an open nasolacrimal furrow. Nonfusion
between
the palatine processes
and
nasal
septum results in a cleft palate. In its most severe form there is a completely deficient palate and bilateral clefts in
the upper lip on either side of the philtrum. Clefts of the lip and palate are seen in just under 0.1
percent of
neonates. Interestingly, more clefts develop on the left than the right.13 Occasionally, median clefts are encountered which can produce anomalies ranging from a widened colwnella and nasal tip to complete dehiscence of the nasal bridge and a bifid nose.
Failure of the oronasal membrane
to rupture results in choanal atresia, which may be either
membranous or bony and may lie at a variable distance from the nasopharynx because of changes in the position of the posterior choana during development. Rarely, the olfactory placode
fails to develop, with
complete or partial absence of the nose. This is usually associated
with bilateral choanal atresia and hypoplastic
maxillae.
Unilateral
choanal
atresia
is
much
more
common. Unilateral maldevelopment of the olfactory placode produces a proboscis yme grows out
lateralis where the mesench in a complete ring resembling a trunk and
the maxilla and eye are often affected. Median facial anomalies result from abnormal first and second arch development and are generally fatal. Premature ossification or the sphenoid or fusion of the
pre-
and
post-sphenoidal
portions may
produce an
abnonnal depression of the nasal bridge (often seen in achondroplasia)
and
anomalous
fusion
of the
pre
sphenoid results in hyperteleorism. Cysts arise from epithelial entrapment in the lines of Fig u re 104.10
CT scan (coronal ) throug h sphenoid si nus of an a d u lt The a n teri or c l i noid processes a re pneumatized, resu lti ng i n a n infra optic recess on both sides. Note the bulgi ng of the i nte rnal carotid a rtery d u ri n g its course through the cavern ous sin us. Pneumatization extends far la tera l ly exposing the round fora men with V2. At the floor of the sinus, the vidian cana l can clea rly be iden tified.
fusion between the various processes. Nasolabial cysts develop in the furrow between the maxillary and median nasal elevation and globulomaxillary cysts at the junction of the primitive palate and palatine processes, in the alveolar process between lateral incisor and canine teeth.
The dermoid cyst is a relatively common congenital abnormality. �t is a median nasal lesion found on the glabella, dorsum or tip of the nose between the alar
/
Chapter
104 Anatomy of the nose and paranasal sinuses
I
1321
cartilages or on the columella. It may be superficial or
and supreme. The nasoturbinal is repres_ented by the
between the nasal bones which may extend intracranially
maxilloturbinal is equivalent to the inferior turbinate.
communicate with a deeper component through a tract
uncinate process and agger nasi of the ethmoid and the
proposed for its formation; the cranial theory postulates
A secondary olfactory organ, the vomeronasal or ) Jacobson s organ, is found lying either side of the anterior
that as dura mater recedes) it pulls nasal ectoderm
nasal septum, usually protected by small cartilages. This
forming a sinus. Pinching off the sinus leads to cyst
organ has an important influence on feeding and oestrus
formation. Alternatively) ectoderm may become trapped
in many mammals) though there is considerable variation ill its morphology?l
through the cribiform plate. TWo theories have been
between the two medial nasal folds.
The paranasal sinuses are a characteristic feature of
terrestrial, placental mammals and are absent in mono
COMPARATIVE ANATOMY
tremes, marsupials and cetacean. The distribution and
There is a basic pattern to the mammalian nasal cavity which can be recognized in man and offers important teleological information and
104.14).14,15
(Figures 104. 11, 104.12, 104.13
In all mammals the nasal fossa is
divided into two by a midline septum and its functions are
respiratory
inspired
air)
(moistening,
and
olfactory.
cleaning This
is
and
warming
evident
in
the
macroscopic and microscopic configuration of the nose. The
lateral nasal
wall bears three sets of turbinals;
ethmoturbinals, nasoturbinals and maxilloturbinals. The ethmoturbinales are arranged in two rows, the ectoturb
configuration of the sinuses is varied and) despite much consideration
and
some
interesting
suggestions,22
a
convincing explanation of their origin and function has not been forthcoming. The maxillary sinus ranges from
an extensive cavity, meeting in the midline of the hard palate, e.g. chimpanzee23 and pneumatizing the nasal) frontal, lacrimal, palatine and nasoturbinal bones, e.g. bears) horses and elephants, to a shallow lateral recess, e.g. the baboon. The size of the maxillary sinus increases with the size of the skull and orbit in monkeys and higher primates) though not with body size?4 However, the
inals laterally and endoturbinals medialJy. They increase surface area for greater olfactory acuity. Ethmoturbinals are particularly well developed in macrosmatic animals and
can
be
very
numerous.
The
olfactory
area
is
augmented by the ethmoturbinals by a factor of 5 in
sheep, 2.S the dog and 1.34 in man.16 The anthropoid and
human nose are remarkably
similar demonstrating the increasing importance of vision
8, 19,20
over 0lfaction!7, 1
There is a reduction in ante-
roposterior length, resulting in a high-roofed between two large
orbits
which
face
cavity
forwards.
The
ectoturbinals disappear during foetal development and the endoturbinals are reduced to three; middle, superior
2cm
Figure 104.11
Fig ure 104.12 Coronal section through midfadal block from
Mandril/us sphinx
(mandrill) showing absence of maxillary sinus.
troglodytes
Coronal section through head of
Pan
(chimpanzee) showing well-developed maxillary
sinus and reduced turbinal structure. i f
\,
/
1322
I PART 13 THE NOSE AND PARANASAL SINUSES
Figure 104.13 S kull of Miopithecus talapoin (dwarf g ueron). The maxilla is encroached u pon by the orbit and dentition. It therefore does not have a functional maxillary sinus. maxillary sinus is not a constant feature and there does not appear to be any specific factor which correlates with its presence or absence among the anthropoids. In the
great apes) the maxillary sinus and nasal configuration of the gorilla and chimpanzee resemble that of man with the natural ostium opening into the middle meatus. Most mammals have additional pneumatized cham bers
communicating
with
the
olfactory
region
olfactory epithelium may extend. These may correspond to ethmoid, frontal or sphenoid sinuses but there is considerable interspecies and intraspecies variation. The big ungulates, elephants and carnivores, have considerable frontal pneumatization. In the majority of monkeys, gib bons and orangs, there is little frontal development. Humans and the African apes can be distinguished by the presence of an ethmoid complex in addition to a true sinus,
though
the
pattern
Coronal section through nasal cavity of Castor (Canad i an beaver) showing extensive ethmoturbinal
1 04.14
system.
and
opening between the ethmoturbinals into which the
frontal and sphenoid
Figure
canadensis
of
mammalian sinl!is· pJ1e�matization does not clarify the
�
purpose ,of, �he] �r�na-sal sinuses.
VESTIBULE AND SKIN
y leading from the
The vestibule is the dilated passagewa
external nares into the nasal fossae) demarcated by the limen nasi, at the superior margin of the lower lateral cartilage. It is lined by skin bearing coarse hairs or vibrissae (though without erector muscles), sebaceous glands and sweat glands. With increasing age, the overall area of the vestibule enlarges at the expense of the respiratory region of the nasal cavity. The thickness of the skin and soft tissues of the nasal bridge vary. Over the dorsum and sides of the nose, it is thin and loosely adherent. It becomes thicker and more adherent over the tip and alar cartilages where it contains
ANATOMY OF THE NOSE AND PARANASAL SINUSES
numerous large sebaceous glands. The elasticity and mobility of the skin over the nose also varies, dependent upon the quality and anchorage of the collagen fibres running between the skin and underlying layers.
External nose and vestibule A considerable literature is available, devoted to descrip
MUSCLES OF THE EXTERNAL NOSE a
tions of the external appearances of the nose as it pertains
The nose has
to cosmetic surgery
assumed an almost vestigial importance
(Figure
104.15).
number of muscles which, in man, have
(Figures
104.16
Chapter 104 Anatomy of the nose and paranasal sinuses I
1323
�-+----Dorsum---
{
SUpratiP
Lobule
area r------Alar groove--�--f
Tip
Columella -----=:::....
Figure 104. 1 5
l
supratiP
area
�-----:=--J'I--- Tip
/}--c-a ----I\l solabial fold.
Lobule
Exte r na l nose showing surface anatomy.
w--��--- Procerus
����� Corrugator
Levator labii superioris
IItII------ Nasalis
...--- Nasalis (alar part)
(transverse part)
'---\--- Depressor septi nasi '?\),":>.---- Nasalis
Figure 1 04.16
104.17).
External musculature of the nose.
all
depress the septum and tip, expanding the external nares
supplied by branches of the facial nerve. The depressor
during forced inspiration. The nasalis muscle is composed
septi nasi muscle attaches between the alveolus and the
of an alar and a transverse part. The transverse fibres run
medial crus of the lower lateral cartilage. Its function is to
from the pyriform aperture onto the dorsum of the nose
and
As muscles of facial expression, they are
j
I
+,'..
1324
I PART 13 THE NOSE AND PARANASAL SINUSES
�---+---- Nasal bones
�
-
'
:: '
-,
-+---Frontal process at maxilla
r=---:,p. :;:::=�'-tc-'r(---- lar cartilages----'r...l.rd:::lfo:-
Laterai----+-.p. cartilage
Latera]---.,I- cartilage
,U-----'.-SAl'"ltl m Figure 104.17
Bony and cartilaginous anatomy of
the nose.
into a thin aponeurosis attached to the transverse muscle
septum, upper and lower lateral cartilages and a variable
fibres of opposite side. Its action is to contract the nasal
number of minor accessory alar cartilages.
aperture. The alar component arises beneath the naso maxillary
suture
and
runs
inferiorly,
laterally
and
anteriorly, attaching by a short thin tendon to the skin of the nasal ala. Contraction produces shortening and dilatation of the nostril. A continuation of frontalis forms the procerus muscle. It shortens the nose when contracted but also produces facial movement of the area between the eyebrows, hence its alternative name, depressor glabeUae?5 The develop ment of this muscle and the associated fat pad is responsible for the shape of the root of the nose. Levator labii superioris alaequae nasi arises from the frontal process of the maxilla and blends with the perichondrium of the lateral crus'
of. the lower lateral cartilage. It pulls this
superiorly, dilating.t ' he upper lip, hence its name. Electromyography shows that the nasal dilators are respiratory muscles, as their action 6 correlates with ventilatory resistance.2 The supporting framework of the external nose is composed of a bony skeleton provided by the nasal bones,
NASAL BONES
The nasal bones unite with each other in the midline, with the frontal bone superiorly at the nasofrontal suture and laterally with the frontal process of the maxilla at the nasolacrimal suture
(Figure
104.18). They are supported
by the nasal spine of the frontal bone and by the perpendicular plate of the ethmoid, both of which groove the bones. The nasal bone is wedge-shaped, usually convex and smooth on its outer surface and concave and roughened internally. The bones are grooved by adjacent neurovascular bundles. There is considerable ethnic and individual variation
in the shape and size of the nasal
bones.27
PYRIFORM APERTURE
::
The pyrifonn aperture is bounded below and laterally by
frontal processes of the maxillae and nasal part of the
the maxilla, and above by the nasal bones. The anterior
frontal bone and a cartilaginous framework consisting of
nasal spine lies in the middle Of
inferior border, It can
",
._,'j"
J
Chapter
1 04
Anatomy of the n ose a n d paranasal sinuses I 1325
supplied by the dorsal branch of the ophthalmic artery
and the infraorbital branch of the maxillary. There are significant anastomoses between these vessels on each side
and between the right and left sides.27
The venous networks do not parallel the arterial supply
but
correspond
to
territories
termed
arteriovenous
unitS.27 The frontomedian area drains to the facial vein and the orbitopalpebral area to the ophthalmic vein with interconnections to the anterior ethmoidal system and thence
cavernous
sinus
which
can
be
of
clinical
significance. The facial vein arises by the confluence of the supratrochlear and supraorbital veins at the inner
canthus where it is termed the angular vein in its superior
portion. Usually, a transverse venous anastomosis exists
Figure 1 04. 1 8 H uman sku l l ( anteri o r aspect) showing bones su rrou nding the pyriform apertu reo
between the right and left supratrochlear veins.
be up to 15 mm in lengtb28 and is related superiorly to the
NERVE SUPPLY
anteroinferior free end of the septal cartilage.
The skin of the external nose receives its sensory supply from the two upper divisions of the trigeminal nerve; ophthalmic
CARTILAGES OF THE EXTERNAL NOSE AND COLUM ELLA
The nasal cartilages are composed of hyaline cartilage which may be ossified. They prevent collapse of the vestibule
on
inspiration.
The
upper
cartilages
are
triangular flat expansions lying inferior to the nasal bones and are overlapped by them, by the adjacent frontal processes of the
cartilages - in
maxillae and by
the
lower
and
maxillary.
The
ophthalmic
has
an
infratrochlear branch supplying the lateral surface -of the
lateral
72 percent of cases,27 to all of which they
are attached by fibrous tissue. The groove between the upper and lower l ateral cartilages is known as the limen
root of the nose and an external nasal branch supplying
the skin over the root and dorsum as far as the tip of the nose. The infraorbital branch of the maxillary nerve gives external and internal nasal branches which supply the nasal alae and skin of th� nasal vestibule respectively, inferior palpebral and superior labial branches which form
the
pes anserinus minor with superior buccal
branches of the facial nerve, and the anterior superior alveolar branch with its supply to the anterior lateral wall.
nasi, which is the site of intercartilaginous incisions. The medial aspect of the upper lateral cartilages are contin uous with the nasal septal cartilage which is bifid in this
LYMPHATI C DRAINAG E
area.
This drains from the external nose with the anterior face
The lower lateral or alar cartilages form the lower third of the nose. They are each composed of a medial and lateral crus which meet at the dome of the tip, though the highest point can be on the lateral crus. The medial crura
are loosely attached to each other in the midline and
to the submandibular and submental nodes, with buccal nodes adjacent to the facial vein sometimes intervening. There may also be bilateral drainage and flow to the parotid region is possible.
contribute to the columella, anterior to the quadrilateral cartilage. The lower margin of the lateral crus does not follow the margin of the nostril but ascends away from
the margin laterally. Between one and four (average
2.3)
minor sesamoid cartilages are found between the upper and lower lateral cartilages.
The part of the septum running between the tip of the
nose and philtrum is called the columella. It bounds the anterior nares medially and is thicker posteriorly because of the contribution made by the medial crura of the lower
lateral cartilages.
Nasal cavity The nasal cavity extends frbm the external nares or nostrils to the posterior choanae, continuous
with
the
nasopharynx
where it becomes and
is
narrower
anteriorly than posteriorly. Vertically, it extends from the palate to the cribiform plate, being broader at its base
than superiorly where it narrows to the olfactory cleft.
The nasal cavity is divided into two by a septum. The configuration and dimensions show considerable indivi
dual and ethnic variation. Each half has a floor, a roof, a
BLOO. D SUPPLY
lateral wall and a medial (septal)
Branches of the facial artery supply the alar region while
almost horizontal. Its anterior three-quarters are com
the dorsum and lateral walls of the external nose are
wall. The floor is
concave from side to side, anteroposteriorly flat and posed of the palatine process of the maxilla, its posterior
I
I _
I
1326 I
PART 13 THE NOSE AN D PARANASAL SINUSES
one-quarter by the ho riwnta I process of the palatine bone. Approximately
12 mm behind the anterior end of
the floor is a slight depression in the mucous membrane
has been termed the footplate. The upper margin of the cartilage also expands where it is connected to the upper lateral cartilages, forming the anterior septal angle, just
overlying the incisive canals. This contains the terminal
cranial to the domes of the lower lateral cartilages. It is
branches of the nasopalatine nerve, the greater palatine
bound firmly by collagenous fibres to the nasal bones, and
artery and a short mucosal canal
(Stenson's organ).
Occasionally, incisor and canine teeth can protrude into the floor of the nasal cavity. The roof is narrow from side to side, except poster iorly, and may be divided into frontonasal, ethmoidal and
to the perpendicular plate of the ethmoid and vomer and, where it sits inferiorly
in the nasal crest of the palatine
process of the maxilla, the fascial attachment effects a pseudoarthrosis. It abuts the maxillary spine at the inferior septal angle. Anteriorly, it is attached by a thin
sphenoidal parts, related to the respective bones. As both
membranous septum to the medial crura of the lower
the frontonasal and sphenoidal parts of the roof slope
lateral cartilages.
downwards, the highest part of the nasal cavity relates to
The
perpendicular
plate
forms
the
superior
and
the cribiform plate of the ethmoid which is horizontal.
anterior bony septum, is continuous above with the
This area is covered by olfactory epithelium which spreads
down a little distance onto the upper lateral and medial
cribriform plate and crista galli and abuts a variable 2 amount of the nasal bones. 7 The vomer forms the
walls of the nasal cavity. The rest of the nasal cavity (with
posterior and inferior nasal septum and articulates by its
the exception of the nasal vestibule) is lined by respiratory
two alae with the rostrum of the sphenoid, thereby
mucous membrane which is intimately adherent to the
creating the vomerovaginal canals which transmit the
underlying periosteum and perichondrium and is con
pharyngeal branches of the maxillary artery. Occasionally,
tinuous with that of the paranasal sinuses, nasolacrimal
the sphenoid sinus may pneumatize the vomer. The
duct and nasopharynx.
inferior. border of the vomer articulates with the
nasal
crest formed by the maxillae and palatine bones. The anterior border articulates with the perpendicular plate
Nasal septum
above
and the quadrilateral cartilage inferiorly. The
posterior edge of the vomer forms the posterior free edge The nasal septum is composed of a small anterior membranous portion, cartilage and several bones: the perpendicular plate of the ethmoid, the vomer and two bony crests of the maxilla and palatine
(Figure 104.19).
The cartilaginous portion is composed of a quadrilateral cartilage with a contribution from the lower and upper lateral alar cartilages forming the anterior nasal septum.
The quadrilateral cartilage is 3-4 mm thick
in its centre
but increases to 4-8 mm anteroinferiorly, an area which
Nasal spine
of the septum. The nasal septum, and
in particular the quadrilateral
cartilage, is of crucial importance in the development of
the middle third of the face. This has been the subject
of considerable experimental and longitudinal clinical studies.
29, 3D, 31,32,33,34,35,36,37,38
The surface area of the
septum measures between 30 and
35 cm2
in adults.39
Deflections may develop at any of the septal articula tions and spurs may also be found where the quadiilateral
Frontal sinus
of .frontal bone Crista galli of Nasal bone
Medial edge
1fJ�����!iiiiC���;.\(-
ethmoid bone Cribriform plate
��,....;.;;;�- Perpendicular
of upper lateral nasal cartilage
plate of ethmoid
Septal cartilage Rostrum of sphenoid
Membranous septum
Medial
Vomer
crus
Crest of palatine bone
of alar cartilage
Greater
Vomeronasal
palatine
cartilage
foramen
InciSive canal
Crest of maxilla
'fig u re 104.1 9
The ca rti lagi nous
septum of the nose.
/
/
/
;
a nd
bony
Chapter
104
Anatomy of the nose a nd pa ranasa l sinuses I 1 327
cartilage sends small processes between the ethmoid and
Axis
vomer. Theile40 found septal deviations were mo re often to the left than the right.27 As such deflections are far
commoner in men than women, they are most likely to be acquired due to trauma than be congenital and this has
been substantiated by work on identical twins in relation to deformities o f the anterior septum . 4 1
Spoke head --tf-�:;A...-----'· r Ciliary membrane
Central microtubule
H I STO LO GY
The mucop erichondrium and mucoperiosteum of the septum are separate from that overlying the maxillary crest, reflecting their embryological development. The mucous membrane is predominantly respiratory with a small area of olfactory epithelium superiorly adjacent to the cribriform plate. Respiratory epithelium is composed o f ciliated and nonciliated pseudostratified columnar
Axoneme
Microtubule 8 Microtubule A
Figure 104.20 Diagra m ma tic cross section through ci l i u m near t h e base, showing the u ltrastructure the axonema and demonstrating the classical 9 + 2 pattern of microtu b u l es.
cells, basal p l uripotential stem cells and goblet cells . The columnar cells are
25 �m in height and 7 Ilm wide,
tapering to 2-4 � at the basement membrane. Each cell bears
300-400 microvilli, irrespective of the presence of
cilia. These are finger-like cytoplasmic extensions, 2 Ilm in length and
0 . 1 Ilm diameter. Their function is to increase
surface area and thus prevent drying. Where cilia are present) there are
50--100 per cell thou gh the number
varies with their position in the nose and age. The cilia are composed of the classical axonema o f nine peripheral doublet
and
two
central
single
microtubules.
Each
(A and B) connects to the next do ublet and to the central microtubule with hexin links. The A
peripheral pair microtubule composed
bears of
an
ATPase
outer which
and
i n ner dyn ein
can
attach
to
arm,
the
B
microtubule, leading to axonemal displacement and cilial beating
(Figure
104.20) .
Seromucinous glands are fo und in the submucosa and are more important in mu cus production in the nasal cavity than the goblet cells which are more nume ro us in
Figure 104.21 Sca nn i ng electron m icrogra p h of respi ratory epithe l i u m showing cil iated cells w ith g lobu les of m u cus (magnifi cation x 3300).
the sinuses. On the septum, the number of goblet cells increases from anterior to posterior and from superior to inferior.42 By contrast, the glands decrease from anterior to posterior and from superior to in ferior. In newborns, the septal mucosal surface is
450 mm2 with 1 7- 1 8 glands/ 1700 mm2 and 104.2 1 ) .
mm2, compared with the adult septum of
8.5 glands/mm2
ni"e
(Figure
olfactory epithelium spreads
down
from
the
cribriform p late onto the upper septu m. It is composed of receptor celis, supporting cells with microvilli and basal stem cells conferring on olfactory ep itheliwn the capacity fo r regeneration . Each receptor cell has app roximately
17
cilia, b u t these differ from their respiratory counterp arts in their radial arrangement, greater length and poorly developed ultrastructure. Dynein arms are not present, preventing linking between the microt ub ules and con ventional beating. The sensory endings have a character istic knob -like vesicular structure from which olfactory fibres join the axonal bundle
(Figure
104.22) . There is a
Figure 104.22 Sca n n i n g e lectron m icrog raph of olfactory epithelium show i ng a senosory b u l b (mag nification x 24,000).
I ' I J I
(
I \
11 '-
1328 I
PART 13 TH E NOSE AND PARANASAL SI N U S ES
sharp transition zone between the olfactory and respira tory epithelium though the relative area of each varies with age and reflects the decrease in olfactory acuity. Secretion for the olfactory epithelium is provided by
100 Anterior ethmoidal � Posterior ethmoidal o Superior labial � Greater palatine [] Sphe nopalatine
Bowman's glands.
B LO O D S U P P LY
The external and internal carotid arteries are responsible for the rich blood supply to the nose. The sphenopalatine artery (branch of the maxillary artery and thus external carotid artery) supplies the posteroinferior septum and the antero-inferior face of the sphenoid sinus,
as
well as
Fig u re 104.23
Blood supply to the nasal septum. Reprinted
sphenopalatine foramen, passing medially across the roof
F i g u re 1 04.24
Coronal CT scan showing anterior septal
of the upper septum and running down and forwards to
tubercle of anterior nasal septum.
the posterior halves of inferior and middle turbinates. The greater palatine artery (also a branch of the maxillary)
from Ref. 43 by courtesy of Georg Thieme Verlag.
supplies the anteroinferior portion entering the nasal cavity via the incisive canal. The superior labial branch of the facial artery contributes anteriorly, in particular to Kiesselbach's plexus, which is composed of unusually long capillary loops and is situated in Little's area on the anterior septum - a common source of epistaxis. The internal carotid artery supplies the septum superiorly via the anterior and posterior ethmoidal arteries and also contributes to Kiesselbach's plexus (Figure 104.23 ) . There i s a sinusoid system i n the nasal submucosa under autonomic control which has been well described in relation to the turbinates but is also present on the septum adjacent to the inferior turbinate and on the most , anterior septum (Figure 104.24) . This anterior septal tubercle or intumescence was first described by Morgagni6 and may be related to control of airflow into the olfactory cleft. A similar structure is seen on the posterior septum in two-thirds of individuals. The cavernous venous system drains via the spheno palatine vessels into the pterygoid plexus posteriorly and into the facial veins anteriorly. Superiorly, the ethmoidal veins communicate with the superior ophthalmic system and there may be direct intracranial connections through the foramen caecum into the superior sagittal sinus.
N E RVE S U P P LY
The maxillary division of the trigeminal nerve provides the sensory supply to the majority of the nasal septum
(Figure 104.25) . The nasopalatine nerve supplies the bulk of the bony septum, entering the nasal cavity via the
the
incisive
canal
to
reach
the
hard
palate.
The
anterosuperior part of the septum is supplied by the anterior ethmoidal branch of the nasociliary nerve and a
The sensory nerves are accompanied by postganglionic
sympathetic fibres to blood vessels and postganglionic
smaller anteroinferior portion receives a branch from the
parasympathetic secretomotor fibres pass to glands with
anterior
the branches from the pterygopalatine ganglion.
superior alveolar nerve. The posteroinferior
septum also receives a small supply from the nerve to
The olfactory epithelium covers the inferior surface of
the pterygoid canal and a posterior inferior �asal branch
the cribiform .opIate spreading down to cover a variable
of the anterior palatine nerve.
area on the upper septum and adjacent lateral wall, over
I
/
• , ,1,
---"-t -=-�'-----'""_. �_ _ .
0 _
Ch a pter 1 04
the medial surface of the superior concha.
With increasing
age,
by
Ana tomy of the nose a n d p a ra nasal sin uses I 1329
anterior and middle third. In adults, this ranges fro m
1.6
respiratory
t o 2.3 c m ( mean 1 . 9 c m ) a t 1.6 cm along the b ony lateral
epithelium and in the adult covers an area of approxi
wall.45 The nasolacrimal duct opens into the inferio r
the
area
is
encroached
upon
mat ely 2-5 cm2. The surface area is considerably increased
by the cilia on the receptor cells. Nerve fibres arising from the o l factory receptors are
slim (0.2
nonmyeli nated. They j oin
llm in
di ame ter ) and 20
up into app roximately
meatus usually j u s t anterior to its highest point. There is
no true valve, the opening being covered by small fol ds o f mucosa. It
can
b e endoscopically identified in life by
gentle massage of the lacrimal sac at the medial canthus.
b undles which traverse the cribiform plate to reach the olfactory bulbs. Each bundle carries a
tubular sheath of which may be sheared in head i nj u ries, destroying olfaction and potentially pr odu cing cereb ro s p inal fluid leakage. The fibres synapse in the glomeruli o f the olfactory bulbs which in turn connect with the olfactory tract and with o ther cells (mitral and tu fted) within the bulb which dura and pia-arachnoid,
contribute to feedback loops from higher cortical centres. The ol facto ry tract
passes to the trigone from which
diverging bundles, the medial and lateral olfact ory striae, pass around the anteri o r perforating substance to connect with the hypothalamus,
amygdala and hippocampus.
These complex linkages subserve the interactions of smell,
INFE R I O R TU RBI NATE
This structure is composed of a separate bone, the i n ferio r
concha which has
an
irre gular surface, perforated and
grooved by vascular channels to which the mucoperios
teum is firmly attached (Figures 1 04.26 and 1 04.27) . The maxillary pro cess which articulates with the inferior margin of th e maxillary hiatus . It also art ic ulates with the ethmoid, palatine and lacri mal bones, complet
bone has a
ing the medial wall o f the nasolacrimal duct. The inferior concha has its own ossification centre which appears around
th e
fifth intrauterine month. The tu rbinate
taste, feeding and reproductive behaviour, representing one of the most pri mitive areas of the
brain.
LYMPHATIC D RAI NAG E
The anterior septum drains with the external nose to the submandibular nodes while drainage is to the retro
p h aryng eal and anterior deep cervical nodes p ost eri orly.
The lateral nasal wall I N FER I OR M EATUS
The inferior meatus44 is that part of the lateral wall of the n ose lateral to the inferior
turbinate. It is th e largest
meatus, extending almost the ent ire l ength of the nasal cavity. The meatus is highest at the junction of the
���w==-������;.;.;.:.,;..;.a..o��.,;-;>:-
��::y;.;���;.;+;*"--
Figure 1 04.2 5
from Ref.
43
Figure 1 04.26 Sagitta l section th rough the nasa l cavity showi ng structures of latera l n asal wa l l . F, fronta l sin us; IT, i nferior turbinate ; MT, m id d le turb i nate ; S, sphe n oid s i n us; S1. su perior tu rbinate.
'''. 'I
OHactory area Anterior ethmoidal branch of nasociliary nerve Nasopalatine nerve Anterior superior alveolar nerve
N erve su pply to the nasa l septum. Reprinted by cou rtesy of Georg Th ieme Verlag.
Figure 1 04.27 I nferior tu rbi nate. m ed i a l surface. A, a n terior; P, posterior. Reprinted from Ref. 43 by cou rtesy of Georg Thieme Verlag.
,r i
1 330 I
PART 1 3
T H E NOSE AN D PARANASAL SIN USES
pos sesses an i mp ress ive submucosal cavernous plexu s with large sinusoids under auto nomic control which
and a nterior ethmoi dal sinuses. Considerable confusion
has arisen with regard to terminology in this area, as
provides the major contribution to nasal resistance. The
many terms origin ally defined in the last century by
turbinate is covered by respiratory epithelium, wi th a high
German and French have been used interchangeably. In
n umber of gob l e t cells ( approximately 8/mm2 ) which
the past, when radical sinus surgery was pr edo minantly
decrease in densi ty towards the posterior end. 42
the
u sed for most pat hology, this was of less significance . The
advent of endoscopic smgery has led to a n increased interest in the detailed anatomy of the region and a need
M IDDLE M EATUS
for consensus in terminology.
The middle mea tu s is that portion of the lateral nasal wall lying lateral to the middle turbinate (Figures 104.28 and 104.29 ) . It receives drainage from the fro ntal, m axill a ry
The configuration of the structures of the
mi ddle
mea tus are complex and variable, but can more readily be understood when the embryological develop men t of the area is considered.
If the
topographical
considered in the sagittal plane, a
anatomy
is
number o f structures
are apparent, covered by the middle turbinate. In a disar ticula ted skull,
the
maxillary bone
has
a
large
opening in its medial wall, the maxilla ry hiat us. In the articulated skull this is filled in by adj acent bones:
•
inferi or: t he maxillary pro ce ss of the inferior turbinate bone;
•
posterior: the perpendicular plate of the pal a ti ne
bone; • •
ante r osuperi o r : a small portion of the lacrimal bone; superior: the uncinate process and bulla of the
e thmoid .
A por t ion of the maxillary hiatus is nevertheless left open by these osseous attachments, which in
life is filled by the muco us membrane of the maxillary sinus and the intervening connective tissue - the membranous portion of the late r al
(0)
m ucous membrane of the middle meatus, the
Figure 1 04.28 (a) Schematic d rawing of relati on of a n terior ethmoid complex to fronta l sinus. " fronta l sinus with fronta l s i n u s infu n d i bu l u m ; 2, fronta l recess; 3, u ncinate p rocess ; 4, h iatus sem i l u n a ris (inferior) ; 5, ethmoidal bu l l a ; 6, su pra bu llar recess ; 7 , retrobu l ia r recess; 8, insertion of basa I lamella of middle turb i n a te. (b) This sag itta l CT reconstruction demonstrates the g round l a m e l l a e persisti ng in a n a d u l t. Note the h o u rg lass-like contour of the floor of the fronta l si nus, n a rrowing towa rd the frontal sinus osti um and widen i n g a ga i n i n t h e fronta l recess (dotted l i nes). 1 , u nci nate l a mel l a ; 2 , b u l l a l a m e l l a ; 3 , g rou n d l a m e l l a of t h e middle tu rbinate ; 4 , grou nd l a mella of the superior tu rbi nate; ci , concha i nferior; em, concha media; osp h , osti u m of sphenoid si n us. .
Figure 1 04.29
Bony structures of l ateral nasal wall. AF, a n terior fontan e l l e ; BE, b u l l a ethmoidalis; F, fron ta l sin us ; HS, h i a tus semi l un a ri s ; IT, i n ferior tu rbinate : attach ment; MT, m iddle tu rbi nate : attachment: PF, posterior fon tanelle ; S, sphenoid sinus; SPF, sph�nopa l atine fora men ; U P, u ncin ate process. Redrawn from Ref. 1 1 .
/
/
;
Chapter
1 04
Anatomy of the nose and para nasal sin uses I 1331
wall. This membranous area can be defined as lying anterior or posterior to the uncinate process, constituting the anterior and posterior fontanelles, respectively. It is in the fontanelles that accessory ostia are found, their formation probably arising as a consequence of infection and, consequently, they have been compared to perfora tions in the tympanic membrane.
It is difficult to
ascertain a 'natural' incidence for accessory ostia but it is probably of the order of 4-5 percent in the general adult population, increasing to 25 percent in patients with chronic rhinosinusitis. Accessory ostia are found most frequently in the posterior fontanelle which is generally larger than its anterior counterpart.
ETH M O I DAL I I\l FU I\l D I B U L U M
The ethmoidal infundibulum is a cleft-like, three dimen sional space in the lateral wall of the nose that belongs to the anterior ethmoid. The medial wall of the space is provided by the entire extent of the uncinate process and its mucosal covering. The major part of the lateral wall of the ethmoidal infundibulum is provided by the lamina papyracea of the orbit, with the frontal process of the maxilla and, in rare cases, the lacrimal bone providing the remainder anterior and superiorly. Anteriorly, the un cinate process attaches to the bones of the lateral nasal wall at a sharp angle and inferiorly, provides the bony connection with the inferior turbinate. Bony defects in this area are covered by connective tissue and the continuation of the periosteum
as well as mucous
membrane, and are thus closed in the area of the anterior nasal fontanelle. Through the attachment of the anterior margin of the uncinate process to the lateral nasal wall, the ethmoidal infundibulum ends blindly anteriorly in an acute angle. Further inferiorly and posteriorly, the lateral wall of the
ethmoidal
infundibulum
is
formed
by
the mucosa-covered connective tissue components of the posterior nasal fontanelle. The posterior border of the ethmoidal infundibulum is composed largely of the anterior surface of the ethmoidal bulla, in front of which the infundibulum opens into the middle meatus through
Figure 1 04.30 Va riations of the u ncinate process : schematic d rawings of uncinate process, va riations and their im pact on the relationsh i p of fronta l recess and the eth moidal infu n d i b u l u m . Red, u ncinate process; 1 , eth moida l infu ndibu l u m ; 2 , frontal recess; 3, fronta l sinus osti u m ; 4, fronta l sinus; 5, maxi l l a ry sinus ostiu m ; ci, concha i nferior; em, concha media. Redrawn from Ref. 11.
the inferior hiatus semilunaris. Superiorly, configuration of the ethmoidal infundibu
recess then opens in!o the middle meatus medial to the
lum depends largely on the uncinate process: if this turns
ethmoidal infundibulum between the uncinate process
laterally thus attaching to
the orbit, the ethmoidal
and the middle turbinate. Ventilation and drainage of the
infundibulum ends in a superior blind alley, the terminal
frontal sinus then run medial to the ethmoidal infundi
recess
uncinate process
bulum. If the uncinate process reaches the skull base or
reaches the skull base superiorly or turns medially to
(recessus terminalis) .
If the
turns medially, the frontal recess and consequently the
attach to the middle turbinate, the ethmoidal infundibu
frontal sinus open directly into the superior part of the
lum is contiguous with the frontal recess superiorly
ethmoidal infundibulum. Numerous configurations of
(Figure 1 04.30) . In these situations, portions of the
these principal uncinate variants can occur. The superior
lacrimal bone may contribute to the lateral wall of the
bony end of the process may become divided into several
ethmoidal infundibulum.
branches that insert into the base of the skull, the lamina
If a terminal recess of the ethmoidal infundibulum is
papyracea and the middle turbinate. Depending on the
present, the ethmoidal infundibulum and frontal recess
development of these branches, various septations and
are separated from each other in this region. The frontal
recesses may be formed. The mucosal membrane may
�
. __
._
_ ._--
---"""===--
1 332 I
PART 1 3 TH E NOSE AND PARANASAL SINUSES
produce partial or complete septations and form addi tional blind bulges near the skull base or the middle
the sagittal cleft between the concave free posterior border of the uncinate process and the convex anterior surface of
varying
the ethmoidal bulla. From the middle meatus, through
numbers and sizes and evolve into so-called infundibular
this 'two-dimensional' cleft, the three-dimensional space
turbinate.
These
can
expand
anteriorly
in
cells. If such a cell develops anteriorly and superiorly, it
of the ethmoidal infundibulum can be approached. The
can extend as far as the lacrimal bone and may be called
hiatus semilunaris thus is the 'door' through which we
an ethmolacrimal cell. No universally accepted terminol
can reach the ethmoidal infundibulum. Grunwald described a second hiatus semilunaris, the
ogy and nomenclature exist in this regard as of today. Posteriorly, the ethmoidal infundibulum tapers parallel
superior
hiatus
semilunaris.
This
cleft between
the
to the tapering of the uncinate process. Depending on the
ethmoidal bulla and the middle nasal meatus exists,
form of the uncinate process, the anterior length of the
when there is a marked recess posterior to the ethmoidal
ethmoidal infundibulum may reach 4-5 cm. Its greatest
bulla, i.e. between this and the frontal portion of the basal
depth (measured from the free posterior margin of the
lamella of the middle turbinate. The hiatus semilunaris
uncinate process) may be as much as 12 mm, and its greatest width from the free margin of the uncinate
superior is also a 'sickle-shaped' cleft, which leads into the retrobullar recess (Figure 104.31 ) .
process to lamina papyracea) 5-6 mm. The maxillary sinus
ostium is
located in the medial wall of the
ethmoidal infundibulum, at the transition of its middle to posterior third. The ethmoidal infundibulum may be almost atelec tatic, when anatomic variations such as a paradoxically curved middle turbinate, concha bullosa or hypoplastic maxillary sinus are present. Occasionally, the uncinate process may be pneumatized, i.e. an ethmoid air cell has developed into the structure. Kaufmann has
coined the term 'doubled middle
turbinate' for an uncinate process, which is bent medially like the brim of a hat and thus may protrude significantly out of the middle meatus, giving the aspect of an
TH E AGG ER NASI
This area has caused considerable confusion but con stitutes, together with the uncinate process, the remnants of the nasoturbinal in lower mammals and is the most anterior part of the ethmoid. It is represented by a small crest or mound on the lateral wall just anterior to the attachment of the middle turbinate. It may be pneuma tized, though the incidence in the normal population is considered to be between 5 and 80 percent. Pneumatiza tion of the agger nasi region may encroach upon the nasolacrimal duct.
additional middle turbinate. This is interpreted by some as the closest the uncinate process can get to its p rimary determination, to form an ethmo-turbinal. l l
THE FRONTAL RECESS
The frontal recess is found in the most anterosuperior portion of the middle meatus. The term 'frontonasal duct' CLEFTS A N D SPACES OF TH E LATERAL NASAL WALL
The mucosal lining of the primary nasal cavity and the paranasal sinuses not only serves a physiological function but also contributes to the shape of these areas. It is only after they are covered by mucous membrane that the spaces and clefts of the lateral nasal wall assume their definitive shape and relationship to each other. Thus, the nasal fontanelles become membranous-mucosal compo nents of the lateral nasal wall only after the maxillary sinus and the nasal passages are covered by mucosa; and
has been generally abandoned as no true duct exists, either histologically or topographically, in most people. The natural ostium of the frontal sinus is somewhat variable in its configuration but most frequently it presents as an hourglass narrowing opening directly into the recess. Rarely, a longer narrowed region is found. In 1 0 percent o f patients, multiple ostia are found,47 though
these openings should not be confused with a more laterally placed suprabullar (superior anterior ethmoidal) cell running into the orbital roof. The frontal recess may be defined as follows:
the natural ostium of the maxillary sinus assumes its definitive form only after it is lined by mucosa.
•
medial: middle turbinate;
•
lateral: lamina papyracea, lacrimal bone;
•
H IATUS SEM I LU NARIS
The term 'hiatus semilunaris' (inferior hiatus semilunaris according to Grunwald)46 was coined who gave this name to both the cleft and the depression that are seen from a
•
superior: skull base; inferior: dependent upon the attachment of the uncinate process;
•
pneumatization of agger nasi cells.
From a developmental point of view, this space is the
medial view lying between the free posterior margin of
superior continuation of the ascending branch of the first
the uncinate process and the anterior surface of the
primary interturbinal furrow, i.e. the groove between the
ethmoidal bulla; The sickle-shaped hiatus semilunaris can
first and second ethmoturbinal crests. The descending
be considered a strictly two-dimensional formation, i.e.
branch of this first groove becomes the ethmoidal ·
I
Chapter 1 04
Anatomy of the nose and paranasal s i n uses I 1 333
infundibulum, thus indicating t h e close topographic relationship between these two spaces. The frontal sinus
an
originates from pneumat izatio n of the frontal recess in
antero-superior direct ion, into the frontal bone. In a sagittal section through the transition of the floor of the frontal sinus (frontal sinus infundibulum) to the frontal an
recess,
hourglass-shaped
structure
is
present.
Its
narrowest part is at the level of the frontal ostium. DNL
PU LP
Whereas the superior portio n of the hourglass
is the
frontal sinus infund ibulum, the inferior portion (the ' inverted funnel' ) is the frontal recess. The
limits, shape
and width of the latter are largely determined by its neighbouring structures. The posterior wall of the frontal recess is only well defined if the bulla lamella ascends in continuity to the roof of the ethmoid. The ground lamella of the bulla then separates the frontal recess from the suprabullar recess. As the ethmoidal bulla lamella is frequently inco mplete and does not reach the roof of the ethmoid over the entire width of the latter, the frontal
GLM
recess may communicate widely posteriorly with the space above (and occasionally behind) the ethmoidal
LP
bulla, namely, supra- and retrobull ar recess. The shape of the ethmo idal bulla
can
significantly affect the configura
recess: if it extends far forward in the case o f a well-developed bull a, the frontal recess will be narrowed from posterio rly. If, in addition, significant tion of the frontal
pneumatization of the agger nasi exist and additional ethmoidal infundibular ceils, the frontal recess may be Fi g u re 1 04.3 1
On this horizontal section through a rig ht lateral nasal wal l, the relationsh i ps of some of the clefts and compa rtments of the an terior ethmoid complex are shown i n a si m plified s chematic way. The view is toward a lateral nasal wall from above, the section b e i ng almost parallel to the hard palate, just above the horizontal portion of the ground lam e l la of the m iddle tu rbi nate. The basal lamella is cut through in its ascending, m i d d le portion. The ethmoidal b u l la is attached laterally to the lamina papyracea. The uncinate process i nserts into the latera l nasal wal l , directly beh i nd the nasolacrimal duct. The eth moidal infundibu l u m can be entered through the inferior h iatus semi l u naris, the retrobulla r space through the su perior h iatus sem i l u naris. Normal ly, the eth moidal b u l la opens into the retrobullar recess (arrow). The position of the su perior hiatus sem ilunaris is chose n somewhat arbitra ri ly. I t cannot be nearly as accurately shown anatomically as can the position of the i nferior hiatus semi l u naris. De pe n d i n g on the shape and d epth of the retrobul lar recess and on the d Istance between middle turbinate and ethmoidal bu l la, the cleft of the su pe rior hiatus semi l u naris can be placed s l i g htly more med ially or latera l ly. This anatomical inconsistency is indicated by n ot showi ng the su perior hiatus sem i l u naris precisely in the sagi ttal plane. The black triang le i n d icates the tip of the nose. 1, inferior h iatus sem i lu naris; 2. ethmoidal infu ndibu l u m ; 3, superior h iatus s e m i lunaris; 4, retrobu l lar recess; BE. b u l la ethmoidal is: eM, concha media; D N L, nasolacrimal d u ct; G LM, ground lamella of middle turbinate. m i d d l e (frontal) portion ; lP, lam i na papyracea ; PU, u ncinate process; S, nasal septu m.
narrowed to a small passage or even have a tubular lumen. It is this configuration that prob ably gave rise to the term 'nasofrontal duct'. Even present, this is not
an
if such a tubular configuration is
independent bony tubular structure
but simply the space wruch other independent bony structures leave between them.. The anatomic situation can be further complicated in that the most anterior ethmoidal cells may develop from the frontal recess. Thus, pneumatization o f the- agger nasi may begin here. The middle turbinate may also become pneu matized from the frontal recess. From here, cells not uncommonly develop into the frontal bone, alongside the frontal sinus proper. These cells have been called b ulla frontalis This variation may range from a bare suggestion of a bulge of the frontal recess into the floor of the frontal sin us to the format;ion of two or more approximately equally large cells on one side of the frontal bone. As all of these
cells open into the frontal recess, it may become
impossible in some cases to determine which of those cells is the true frontal sinus and which a bulla frontalis.
11
TH E ETH M O I DAL B U LLA This is one of the most constant features in the middle meatus containing the largest anterior ethmoidal ceil, but
in 8 percent of patients, 1 1 hence its alternative nomenclature
it may be poorly aerated or completely unpneu matized 6 46
of torus lateralis (lateral bulge ) . '
C . The antenor lace
I
: , ='
/
_ _ _ ____-
--__ , _______________�\ ___'-'--:'........l. \.
�_
_ _
1334
I PART 1 3
TH E N OSE AN D PARANASAL S I N USES
forms the posterior margin of the hiatus semilunaris and ethmoidal infundibulum. Posteriorly) the bulla may fuse with the basal lamella of the middle turbinate and superiorly it may reach the roof of the ethmoids forming the posterior wall of the frontal recess. Sometimes a cleft is encountered between the posterior wall of the bulla and the basal lamella of the middle turbinate, the retrobullar recess. The space between it and the ethmoidal roof is called the suprabullar recess) which may connect ante riorly with the frontal recess if the bulla does not reach the skull base. Suprabullar and retrobullar recess may b e continguous
or
may be
separated b y complete
or
incomplete bony septations. Contiguous) supra- and retrobullar recess may be defined as follows: •
medial: middle turbinate;
•
lateral: lamina papyracea;
• • •
superior: roof of ethmoid; inferior and anterior: unicate process; posterior: basal Lamella of the middle turbinate.
ANATO M I CA L VARIATI O N S
There is a considerable range of anatomical variation in this area which has been implicated in the aetiology of
(Figures 104.32) 104.33 and 104.34) Table 104. 1 ) . 48 This includes pneumatization of the middle
sinus infection
Fig u re 1 04.32
Coronal CT scan showing concha b u l losa (cb).
frontalis) . In this area, the frontal bone is both thicker and
Fig u re 1 04.33
Coronal CT scan showi ng infraorbita I (H a l l e r)
denser than the adjacent bony ethmoidal structures. This
cells (arrow).
turbinate) enlargement of the ethmoidal bulla) a para doxically bent middle turbinate) everted uncinate process and the presence of infraorbital (Haller cells) or a septal deflection. The incidence with which these are seen in a ) 'normal population may appear to be less frequent than in those individuals with chronic rhino sinusitis, but on closer inspection it is clear that it is narrowing of the ostiomeatal complex rather than the existence of the variant which is the important factor.49
R O O F OF ETH M O I D CO M P LEX A N D ANTE R I O R ETH M O I DA L ARTERY
In a disarticulated dry skull) the ethmoid bone is open superiorly, at Least over its anterior two-thirds
(Figure
104.35). The bony cover for these open clefts and cells of the ethmoid is provided by the frontal bone, which covers these open spaces with its foveolae ethmoidales (ossis
difference is greatest medially, in the transition from the thicker bony lamellae of the frontal bone to the much
Kainz have assigned a classification I-III to this surgically
thinner lateral lamella of the cribriform plate. This lateral
very important and critical area. It is here too) where the
lamella constitutes the lateral border of the olfactory
topographic relationships of the anterior ethmoidal artery
fossa) with the lamina cribrosa providing its floor. The lateral 'lamella of the lamina cribrosa is also the medial
are especially important. The artery, in its course from the orbit to the olfactory fossa and back into the nasal cavity)
wall of the dome of the ethmoid) the height -and shape of
traverses thret compartments of the head: the orbit, the
which varies considerably from case to case. Keros and
ethmoidal Labyrinth) the anterior cranial fossa and finally
/ / .I
Chapter
1 04
Anatomy of the nose and pa ranasa l sin uses I 1 335
lamina crib rosa o r where this attaches to the frontal bone of the ethmoidal roof. The longer the lateral lamella of the cribriform plate, i.e. the deeper the olfactory fossa - and with that, the higher the ethmoidal roof above the level o f the cribriform plate - the more likely the ethmoidal artery is to be found travelling freely through the ethmoid cavity and penetrating through the lateral lamella of the cribriform plate. After intracranial entry, the artery turns anteriorly forming a groove in the lateral lamella, the called
ethmoidal
sulcus.
Here,
it
gives
50-
off anterior
meningeat branches and finally reaches the nasal cavity again through
the cribroethmoidal foramen and
the
cribrifo rm plate. It is here where it divides into the anterior nasal artery with superior, lateral and medial nasal branches, as well as a posterior branch. This division may take place before or after its passage through the lamina cribrosa. The anterior ethmoidal artery has been estimated
Figure 1 04.34 Coronal CT sca n show i n g paradoxica l ly bent m id d l e tu rbi nate (a rrow ) .
to
be
bilaterally absent
unilaterally in 2
absent
percent
and
in
14
percent,
multiple in
30
percent. 50 If the anterior ethmoidal artery is absent, it is replaced by a branch of the posterior ethmoidal artery. 51 The bony structures in the immediate vicinity of the anterior ethmoidal artery may show remarkable variation
Table
1 04. 1
in thickness. Those parts of the roof of the ethmoid that
Anatomi ca l variants on CT.
are formed by the frontal bone are much thicker and stronger than the lateral wall of the olfactory fossa, which
Con cha bu l losa Bent unci nate process Pa rad oxical mid d l e tu rbinate Overpneu matized eth moid bu l la Agger nasi cells Haller cel ls
14
24
16
21
17
15
17
18
3
15
2
13
n=
1 00
n=
is formed by the lateral lamell a of the cribrifonn plate. The frontal bone at the roof of the ethmoid has thickness of 0.5
mm,
a
mean
whereas the lateral lamella of the
cribriform plate averages o nl y 0.2
mm.
In the ethmoidal
sulcus, the thickness of the wall may be reduced to
0.05 mm, and is therefore by a factor of ten thinner than
1 00
d own into the nose again. The artery can be the source of
the roof of the ethmoid The length of the ethmoidal sulcus
can
vary between 3 and 1 6 mm. 52 The height of the
lateral lamella of the cribriform plate is also variable
( 1-17 mm) 52 and the ethmoid roofs themselves are often
significant intraoperative bleeding when injured. At the
asymmetric ( 1 0 percent) 53 with the right more often
point where the artery enters the anterior cranial fossa
lower than the left.
through the lateral lamella of the lamina cribrosa, the
structures
At the calvarium, the dura mater is only loosely
of the entire anterior skull base
attached to skull In the region of the olfactory fossa,
can be encountered. It is here where the very thin lateral
however, the dura is not only thinner, but is firmly
lamella of the lamina cribrosa presents the least resistance
attached to the bone, partially where anterior ethmoidal
thinnest bony
to any instrument, with a bony thickness frequently only 10 percent as strong as the roo f of the ethmoid.
artery and the olfactory filaments pass through the
cribrifonn plate. In th� majority of cases, the anterior
After its o rigin from the ophthalmic artery in the orbit,
ethmoidal artery is intraduraJ on its way through the
the anterior ethmoidal a rtery passes between superior
olfactory fossa. Trauma in this region, therefore, may
oblique and medial rectus muscles, through the anterior
easily lead to dural tears with subsequent CSF leakage
ethmoidal foramen into the anterior ethmoid complex. It
crosses the anterior ethmoid either at the level of the
and, possibly, even intracranial bleeding from branches of the anterior ethmoidal artery.
ethmoidal roo f or as much as 5 mm below this level,
running in a mucous membrane fold or a thin bony mesentery in the roof of the anterior etlunoidal sinuses.
The artery may be surrounded by only a thin-walled bony channel, which
can
be dehiscent in over 40 percent
inferiorly. After this occasionally oblique passage through the anterior ethmoid, the artery enters the olfactory fossa, i.e. intracranially through either the lateral lamella of the
. bs _... /___--'--'--"-- -'-__ ___.._ _ - . . �= -_ �.c;.
SU PER I O R M EATUS
This meatus is again defined by its relationship to the superior turbinate. The posterior ethmoidal cells open
into this region.
A supreme turbinate is discernible above the superior
meatus in 60--6 7 percent of subjectsS4, 55 though is well
j
$
1 336
I PART 1 3
TH E NOSE AND PARANASAL SI NUSES
Fig u re 1 04.35
Eth moid bone (a) I nferior view ; (b) superior view; CP, cribriform plate; Ip, lamina papyracea ; mt, middle turbinate ; pp, perpendicular plate of ethmoid ; u p, u ncinate process. Reprinted from Ref. 43 by cou rtesy of Georg Thieme Verlag.
(c) posterior view. cg, crista g a l l ; ;
developed in less than corresponding ethmoidal
20 percent.28 Drainage to the
supreme
system
can
meatus
from
take
place
the
posterior
under
these
circumstances.
o ccasionally
supreme)
meatus.
The
sphenoid
sinus
ostium opens into the sphenoethmoidal recess medial to the superior turbinate. The number of cells that make up the posterior ethmoid varies b etween one and more than five. The topo graphy of the most posterior cell of the posterior
POSTER I O R ETH M O I D CO M P LEX
ethmoid)
The ground lamella of the middle turbinate is the border
however)
is
of great importance
to
sinus
surgeons. since these cells can develop laterally and even
All
superiorly to the sphenoid sinus . In these cases. the optic
clefts and cells op ening posterior to the basal lamella
nerve and even internal carotid artery may bulge into
belong to the posterior ethmoid in the superior ( and
these sphenoethmoidal cells) named previously after the
b etween anterior and posterior ethmoidal sinuses.
,. i
/ /
,--- '/�
Chapte r 1 04
Anatomy of the nose and pa ra nasa l sin uses I 1337
Austro -Hungarian, Onodi.56 The optic nerve tubercle
attachment of the middle turbinate and may be damaged
may appear very prominently on the lateral wall of such a
in excessive enlargement of a middle meatal antrostomy. Its branches to the respective turbinates and meatus enter
cell and may, in fact, be surrounded by such cells.
posteriorly. On the conchae, the vessels are partially embedded in deep grooves. In the inferior meatus, the
SPH ENOETH M O I DAL RECESS
sphenopalatine branch dips below the level of the palate
The sphenoethmoidal recess lies medial to the superior
to re-emerge anteriorly, leaving the central portion of
turbinate and is the location of the ostium of the
the meatus relatively avascular.45 An area anteriorly is supplied by a branch from the facial and part of the lateral
sphenoid sinus.
wall adjacent to the palate receives blood from the greater palatine. The internal carotid artery contribution is via
H I STOLOGY OF THE LATERAL WALL
the ethmoidal arteries which supply the superior lateral
The majority of the lateral wall is covered by respiratory ciliated columnar epithelium though there is a small variable area superiorly of olfactory epithelium spreading down from the cribriform plate. Areas of squamous metaplasia are often found on the lateral wall, particularly in areas subject to greatest airflow, such as the anterior inferior turbinate.
wall. There is considerable overlap between the internal and external carotid arterial systems on each side and between the right and left sides which may complicate attempts at arterial ligation in the management
of
epistaxis. 50 The vascular supply to the nose is well-developed and this is enhanced by cavernous plexus found in the lamina propria,
in
particular
on
the
inferior
and
middle
turbinates, which is controlled autonomically. The veins
B LOOD SU PPLY OF THE LATERAL WALL
of the plexus are between 0. 1 and 0.5 mm wide and
The external and internal carotid arteries supply the lateral wall (Figure 104.36) . The sphenopalatine artery (from the maxillary artery and thus external carotid artery) contributes the majo rity of the supply to the turbinates and meatus. It enters through the sphenopa latine foramen which lies just inferior to the horizontal
anastomose with each other. In addition, numerous
arteriovenous anastomoses are found in the deep mucosa and around the glands.57 Venous drainage is to the sphenopalatine veins via facial and ophthalmic vessels, intracranially via the ethmoidal veins to veins on the dura and to the superior sagittal sinus via the foramen caecum.
��I�����-tc=----
Posterior ethmoidal artery
Anterior ethmoidal -------I--+--+-.-m. artery
-....�:iIII� ... ��....�=--.::::
Facial artery ----l'-F-I-fi,�
--==;::;;ii;i.;��;a�+:��r:'t5iiJ.'.�
Branches of sphenopalatine artery supplying turbinates and meatus
Greate.r palatine artery Artery to inferior meatus
Figure 1 04.3 6
Blood supply to the latera l wa l l of the nose. Repri nted from Ref.
43
by cou rtesy of Georg Thieme Ve rl ag . !
.,. /
L \.
1 338 I
PART 1 3 TH E NOSE AND PARANASAL SI N U SES
and orbital branches of pterygopalatine ganglion. Lym
N ERVE S U PPLY OF THE IJHERAL WALL
Apart from the olfactory supply on the superior concha, the lateral wall receives ordinary sensation from the
phatics drain to the submandibular nodes anteriorly and retropharyngeal nodes posteriorly.
anterior ethmoidal nerve anterosuperiorly and from branches of the pterygopalatine ganglion and anterior palatine nerves posteriorly (Figure 104.37) . There is a
The sphenoid bo ne and si nuses
small area innervated by the infraorbital nerve anteriorly and an area of overlap between the ethmoidal and maxillary nerves. The anterior superior alveolar nerve sends a small branch to the anterior inferior meatus which may be damaged in inferior meatal surgery . af£ectmg dentaI sensatIOn. 58' 59 .
OSTEOLOGY
The sphenoid bone is the largest in the skull base and divides the anterior and middle cranial fossa ( Figure
104.38) . It is composed of a body (pneumatized to a variable degree) , two wings ( greater and lesser) and two inferior plates (lateral and medial pterygoid plates) . The jugum on the anterior superior surface of the body
LYM PHATIC DRAI NAG E OF TH E LATERAL WALL
The lateral wall drains with the external nose to the submandibular pharyngeal,
nodes
anteriorly
and
to
the
lateral
retropharyngeal and upper deep cervical
nodes posteriorly.
articulates with the cribriform plate. This surface bears the chiasmatic sulcus connecting the optic canals, the tuber culum sellae, sella turcica and dorsum sella with related anterior, middle and clinoid processes. The bone slopes away posterior to the dorsum sellae towards the clivus. The lateral surface of the body is grooved by the carotid sulcus
B LOOD. N ERVES A N D LYM PHATIC DRAI NAG E O F ETH M O I D S I N U SES
on each side as it traverses the cavernous sinus. The anterior face of the body bears a crest which articulates with the perpendicular plate of the ethmoid. O n
The vascular supply is derived from the sphenopalatine
either side, halfway u p the face, lie the ostia o f the sinuses.
and ethmoidal (anterior and posterior)
arteries and
These are large (5-8 mm in diameter) on a macerated
drains by corresponding veins. The ethmoid sinuses are
skull, but are partially overlapped and closed by the
innervated by the anterior and posterior ethmoidal nerves
sphenoidal concha and by mucous membrane in life. The
Olfactory
Anterior ethmoidal
Area of overlap of anterior ethmoidal and maxillary nerves
I nfraorbital
Figure
1 04.37
�������..���;.,=��...���-----=-
-
....����������������t----..
Nerve su pply to the latera l wa l l of the nose.
R eprinted
from Ref.
Branches of maxillary and pterygopalatine ganglion
Anterior superior alveolar
by cou rtesy of Georg Thieme Verlag.
43
I
Chapter 1 04 Anatomy of the nose and para n asal sinuses I 1 339 the orbit. The su perior orbital fissure separates it from the
lesser wing on each side; the inferior border contributes to the inferio r orbital fiss ure.
In additi o n , the bone is a number o f foramina. Th e foramen rotundum transmits the m axilla ry nerve, the foramen ovale the mandibular nerve, accessory m en in geal artery and sometimes the lesser petrosal nerve, and the middle
trave rsed
by
meningeal artery passes t hro u gh the fo ramen sp inosum
with a menin g e al branch of the mand ibu l ar n erve. In 40 pe rcent of skulls, an em issary venous sphenoi dal fo ramen is found , related to the fo ramen ovale. The poster i or margin of the greater wing contributes to t h e foramen
laceru m .
Each pterygoid p rocess consists of a lateral and med ial
plate which d iverge a round the pte rygo id
ca
n al wh i ch m ay invag inate the floor of the sp he n oid sinus. The lateral pterygoid muscle arises in part from the la ter al surface of the later al pterygoid plate, the m edi al pterygoid muscle from its med i al surface. Th e m edial pterygoid plate ends in a hamulus, around which the tendon of the tenso r veli p al atine hooks . Although the most p osterior et hmoidal cell is dosed by the sph eno i dal concha, t he sp heno i d sinus does not s imply lie behind. That portio n of th e sp hen oid is usually quite small with the most poste rio r ethmoid cell o ften running lateral to the s pheno id sinus and th us the latter may only be entered s a fe ly through the most inferior and medial po rtio n of the poste r io r ethmoid cell. The optic ne rve and in te rnal carot id artery produce variable p ro mi nen ces in t he late ral and p o sterio r walls of trans mits the pterygoi d nerve and artery and which
Figure 1 04.38
Sphenoid. (a) Superior view ; (b) posterior view. ch i asmatic sulcus; fo, foramen ova l e ; fr, fora men rotu n d u m : GW, g reater wing ; J, j u g u m ; I p , la tera l pte rygoid p l a te; LW, lesser w i n g ; m p, m edia l pterygoid plate ; 0, optic ca nal. Re pri nted from Ref. 43 by cou rtesy of Georg Th ieme Verl ag. CS,
the sinus, with an intervening deft which can be deep. The bone overlying - th ese structures is extremely thin or
sinuses open into the sphenoethmo idal recess , superior
a nd medial to the s u perior (and supreme) tUIbinate . The sinus
( intern al
carotid artery: 25 percent; o ptic nerve : 6
percent ) .
cavities are variable in size and sha pe .
Pneumatization
can
extend
in to
the
greater
w ing ,
pte r ygoid processes and rostrum and may encroach on th e basilar part of the occip ital bone. Four general forms
o f p n eum a t i za t i on are described:60 1.
dehiscent in a s ignificant propo rtion of the population
Conchal p n e um ati zati on ,
with o n ly a ru dim en ta r y
sinus (2-3 percent) .
2. PreseUar, in which t he sinus is pne um atized as far as th e an ter ior bony wall of the pituitary fossa ( 1 1 percent) . 3 . Sellar, in which pneumatization extends back beneath the pituitary fossa ( 59 p ercen t) . 4 . Mixed (27 p ercen t) . divided by a sep tum which is often paramedian, and there may be diverticula and incomp l ete septa. It is co m p l etely absent in a pp roximately 1 per cen t � of the po p ulati on . The inferior surface of the body bears the ros t ru m, which art i cula t es with the vomer. The grea ter wings
H I STO LOG Y
Th e goblet cell pop ula tion of the resp iratory epithelium
l inin g the sp h eno id sinuses is s imila r in number to th at
fo und in the ethrnoids ( 6200/mm2), tho ugh the sero
mucinous glan ds are le as t n umerous ( 0 .06 / mro2) .
42
BLOOD, N ERVES A N D LYM P H ATIC D RAI NAG E
The spheno i d sinuses
are suppl ied
by the poster ior
ethmoidal vessels an d nerves, with additional supp l y
from the orbital branches of the pterygopalatine ganglion. Lymphatics drain to the ret roph¥YTIgeal nodes .
The sinuses are
contribute to the middle cranial fossa and lateral wall o f
The fro ntal bone and sinuses OSTEO LOGY
The frontal bone forms the forehead and orbital roof a nd is
p neu m a tized to a variable degree
(Figure 104.39 ) .
It
I
j \
1 340 I
PART 1 3 TH E NOSE AN D PARANASAL S I N USES
forms the roof of the ethmoidal sinuses, which produce individual impressions upon the frontal bone, the
ethmoidales ossis frontalis.
The bone is relatively thick in
this region, and much thinner in the orbital roofS, where dehiscences may be present. The anterior
calvarium
increases in thickness from a mean of 4 mm in the newborn to 16 mm in the adult. The shape and size of the frontal sinuses vary from person to person. In 1 percent of the British population they are absent. When present, the sinus is usually '1: shaped,
composed
of a
horizontal
and
a
The maxi llary bone and s i n u s
fovea
vertical
OSTEOLOGY
The maxilla is the second largest facial bone, forming the majority of the roof of the mouth, the lateral wall and floor of the nasal cavity and the floor of the orbit 1 04.40 and
104.41).
(Figures
The body is usually described as a
quadrilateral pyramid, and contains the maxillary sinus. The bone has four processes: zygomatic, frontal, palatine and alveolar. It articulates with eight bones: the opposite
compartment but, in addition, diverticula, supernumer
maxilla, zygoma, frontal, p alatine, ethmoid, lacrimal,
tered. An intersinus septum is usually present, but may be
bears a number of elevations and depressions, related to
ary sinuses and incomplete septa are frequently encoun
paramedian and is partially dehiscent in 9 percent. The sinus
drains
into
the
frontal
recess,
usually by an
hourglass narrowing rather than by any definable 'duct'. Accessory channels
are fo und in
1 2 percent of the
population and there may be accessory connections to the
ethmoidal system.
Direct continuity of drainage
between the frontal and maxillary sinus may be found depending on the attachment of the uncinate process.
inferior concha and nasal bones. The anterior surface the dentition which may be named after the adjacent tooth, e.g. canine fossa. The infraorbital foramen is situated
above
the
canine
fossa
and transmits
the
infraorbital artery and nerve. The anterior surface is also characterized by the nasal notch and anterior nasal spine. The maxillary sinuses are relatively symmetrical and only rarely absent. The roof of the maxillary sinus forms most of the orbital floor. It is traversed by the infraorbital canal, which may be dehiscent. It is indented antero medially by the lacrimal notch which is related to the lacrimal sac. The posterior edge contributes to the inferior
H I STOLOGY
The frontal sinus respiratory epithelium has a small number of goblet cells (5900/mm2) and a few seromu cinous glands (O.08/mm2).
orbital fissure. Inferiorly, the floor of the sinus is generally thicker, but can be encroached upon by the roots of teeth, e.g. second premolar and all three molar teeth.
B LO O D, N ERVES AND LYM PHATI C D RA I NAG E
The supraorbital and anterior ethmoidal arteries supply the frontal sinuses. Venous drainage includes accompany ing veins, diploic veins draining into the sagittal and sphenoparietal sinuses and supraorbital
notch
an
anastomotic vein in the
connecting
the
supraorbital
and
superior ophthalmic vessels. The nerve supply is derived from the supraorbital nerve and the lymphatics drain to the submandibular gland.
F i gu re 1 04. 3 9
Frontal bone. inferior view. e, ethmoid roof; fs, frontal si nus; 0, orbita l roof. Reprinted from Ref. 43 by courtesy of Georg Th ieme Verlag.
Figu re 1 04.40 M axilla, a nterior view. a, a nterior nasa I spi n e ; A . a lveolar process; F. frontal process ; i o . infraorbita l fora m e n ; Z. zygomatic proeess. Repri nted from Ref. 43 by courtesy of Georg Th ieme Verlag.
/
Cha pter 1 04 Anatomy of the nose and pa ra n as a l sin uses I
1341
infrequent, but again more common in the maxillary
sinus and concentrated around the ostium.
RELATI O N S
Relations a r e a s follows: •
superior: infraorbital artery and nerve, orbit;
•
inferior: upper dentition and hard palate;
•
posterior: pterygopalatine and infratemporal fossae;
•
anterior: cheek with skin, fat and facial musculature.
B LO O D , N E RVES AN D LYM P H ATIC D RAI NAG E Fi g u re 104.41
Bony pal ate, i nferio r vi ew. p , p a l atine p rocess
of max i l l a ; h, horizo n ta l p rocess of pa latine bone.
The posterior, infratemporal surface o f the bone is convex and grooved by the posterior superior alveolar nerves. Inferiorly, it bears the maxill ary tuberosity from which
the
medial
pterygoid
muscle
takes
a
small
attachment. The medial nasal surface fo rms the flo or of the pyramid and contains a large defect, the maxillary hiatus. This is completed in life by a number of bones and mucous membrane leaving the natural maxillary ostium at the base of the ethmoidal infundibulum. Anterior to the maxillary hiatus is an oblique ethmoidal crest which articulates with the anterior edge of the middle turbinate and agger nasi. The lacrimal canal is created between the maxilla, the lacrimal bone and inferior concha, through which the nasolacrimal duct passes to the anterior part of the inferior meatus. Anterior to the lacrimal notch is the conchal crest to which the inferior concha is attach ed . Posteriorly, the greater palatine canal is formed b etween the p erpendicular plate of the palatine and maxilla . When the two maxill ae are articulated, the alveolar processes form the alveolar arch. The frontal process bears the anterio r lacrimal crest, to which the medial palpebral ligament is attached. The p alatine p rocess contributes a large portion of the nasal cavity flo or and roof of the mouth, articulating with
its opposite number in the
Small branches o f the facial, maxillary, infraorbital and greater palatine arteries and veins supply the maxilla. . Venous drainage is to the anterior facial vein and pterygOld
plexus. The maxillary division of the trigeminal nerve supplies sensation via the infraorbital, superior alveolar (anterior, middle and posterior) and greater palatine nerves. Near the midpoint of the infraorbital canal, a small branch, the anterior superior alveolar nerve, arises which p asses in
its own canal, the canalis sinosus, to the anterior wall of the maxilla.
It passes anterior to the inferior turbinate and in front of the incisive foramen. It supplies the anterior wall of the maxillary sinus, the pulps
reaches the nasal septum
of the canine and incisor teeth, the anteroinferior quadrant of the lateral nasal wall, the floor of the nose and a small portion of the anterior nasal septum. The posterior superior alveolar nerves arise from the maxillary nerve in the pterygopalatine fossa and enter the maxilla through the posterior wall to supply the adjacent mucosa and molar teeth. The middle superior alveolar nerve, when p resent, arises from the infraorbital nerve in
its canal and supplies the lateral wall of the sinus and upper p remolar teeth. The posteromedial wall of the sinus is supplied by the greater palatine nerve and the roof by perforating branches from the infraorbital nerve. Lymphatic
drainage
is
relatively
poor,
but
follows
predominantly into the pterygopalatine fossa and to the submandibular nodes.
midline and forming the incisive canal just posterior to the incisors. This transmits the greater palatine arteries
and nasopalatine nerves in separate channels to each side of the nose. Posteriorly, the palatine process articulates with the horizontal plate of the palatine bone to complete the hard palate. The inferior surface of the palatine process - is pitted by Sharpey's fibres from the palatal perio steum, by vascular fo ramina and indentations from small salivary glands. H J STO LO GY
The
maxillary
sinus
is
lined
by
ciliated
columnar
epithelium which contains the highest density of goblet cells compared to the other paranasal sinuses (median: 9700/mm2) .
The
seromucinous
glands
are
relatively
)
1 342 I
PART 13 TH E NOSE AN D PARANASAL S I N USES
1 6.
Dieul afe L. Morphology and embryology of the nasa l fossae of vertebrates. Annals o f Otology, Rhinology and
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Cave AJE, Wheeler H a i nes R. The para nasal sin uses of t h e anthropoid a pe. Journal of Anatomy. 1 93 9 ; 7 4 :
Deficienci es i n cu rre n t kn ow l ed g e a n d a reas fo r futu re resea rch �
Fu rther information on eth n ic va riation may assist i n surgery.
>
Fu rther i m p rovement in imaging may a l low better visu a l ization p re- and peroperatively though a re not a su bstitute for sound a natomica l knowledge.
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493 -523 . 1 8. 1 9. 20.
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21 .
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Otology. 1 992 ; 1 0 6 : 2 1 4-25. 24.
Bou rne GH. The chimpanzee. Base l : Ka rger, 1 9 7 2 : 1 53-92. Lu nd VJ . The maxi l la ry sinus in the h i g her primates. Acta
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Stuttga rt: Georg Thieme Verlag, 1 989 ; a-f: pp: 7, 1 5, 1 9, 20, 3 2 , 3 7. La ng J, Saka ls E. O ber den Recessus sphenoethmoid a l is, die Apertura nasa l is des Ductus nasolacri m a l is u nd den H iatus sem i l u n a ris. Anatomischer Anzeiger. 1 982 ; 1 5 2 :
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Lei pzi g : W. B rau m O l ler, 1 893. Schu ltz-Coulon HJ, Eckermeyer L. Zu m postnata len Wachstum der Nasenscheidewand. Acta Otolaryngologica.
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Pi rsig W. Septoplasty in children : i nfl uence on nasa l g rowth. Rhinology. 1 9 7 7 ; 1 5 : 1 93-204. Verwoerd CDA, U rbanus NAM, N ijdam DC. The effects of septa l su rgery on the g rowth of the nose a nd maxi l l a . Rhinology. 1 9 79 ; 2 7 : 53-63 .
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O nodi J. Das Verhi Htnis des Nervus opticus zu der Ke i l be i n h6hle und insbeson dere zu der hintersten Siebbeinzelle. Archiv f(ir Laryngologie. 1 903 ; XIV and 'IN. Ca una N. The fi ne structu res of the arteriovenous anastomosis and its nerve su pply in the h u man nasa l respiratory mucosa. Anatomical Record. 1 970 ; 1 68 : 9-22.
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105 Nasal endoscopy RODNEY J SCHLOSSER AND DAVID W KENNEDY
Introduction Anatomy Equipment Technique Clinical uses
1344
1344 1346 1347 1349
Key -points Best clinical practice Deficiencies in current knowledge and areas for future research References
1353 1353 1353 1353
The data in this chapter are supported by a Medline search using the key words endoscopy and paranasal sinus disease with focus on examination, diagnosis and treatment.
INTRODUCTION According to Draf,l Hirschmann performed the first attempts at nasal and sinus endoscopy in 1901 used a modified cystoscope. In 1925, Maltz2 used the term sinuscopy and described techniques for endoscopically examining the maxillary sinuses via both inferior meatal and canine fossa routes. He wisely noted the diagnostic capabilities of endoscopy and the limitations of relying solely on radiographic information. It was not until the middle of the twentieth century, when Professor HH Hopkins developed the rod optic telescope, that endoscopy of the upper airway made the next major advancement. 3 Endoscopes incorporating fibre optic light delivery and the rod optical system have markedly improved illumination and optical clarity, opening up the possibility of routine endoscopic examination of both the nasal cavity and the sinuses. This improved visualization of the sinonasal cavities was substantially responsible for a reconsideration of traditional concepts by Messerklinger and Proctor and for the development of new techniques for surgical management of paranasal sinus disease. Based on the experience and teaching of Messerklinger, Stamrnberger and Kennedy,3,4 the
diagnosis and treatment of inflammatory sinus disease continues to evolve. Nasal endoscopy allows a thorough evaluation of intranasal anatomy and identification of pathology that is impossible to see using standard techniques of anterior rhinoscopy and headlight or head mirror. It has proven more sensitive than computed tomography (CT) for the evaluation of accessible disease and provides valuable information regarding persistent asymptomatic disease postoperatively. This chapter outlines the pertinent intranasal anatomy. endoscopic equipment and technique and clinical uses of nasal endoscopy.
ANATOMY A comprehensive understanding of intranasal anatomy is required in order to obtain maximal benefit from an endoscopic examination. The initial structures typically encountered upon examining the nasal cavity include the septum, middle and inferior turbinates. The nasopharynx and Eustachian tubes lie posteriorly along the floor of the nose and (ian be visualized posterior to the posterior end of the inferior turbinate. The opening of the
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Chapter 105 Nasa I endoscopy I 1345
nasolacrimal duct (Hausner's valve) can usually be identified as a slit-like opening in the anterior third of the inferior meatus. The middle turbinate divides the superior part of the nasal cavity into the middle meatus laterally and the rima olfactoria m ecli ally. Medial to the middle and superior turbinates posteriorly, the sphenoethmoidal recess can be examined. The most critical site in a patient with inflammatory sinus disease is typically the ostiomeatal complex. The ostiomeatal
© Hodder Arnold I Scott-Brown 7E
Figure 105.1 Endoscopic view of left middle meatus in unoperated patient demonstrating the nasal septum (5), middle turbinate (M) and free edge of the uncinate process (arrows).
complex is the ·final common drainage pathway for the maxillary, frontal and anterior ethmoid sinuses. In the Wloperated patient, the uncinate process will usually be visible laterally in the anterior middle meatus and note should be made of any mucosal abnormalities, perforations, or displacement of the uncinate process (Figures 105.1 and 105.2). Immediately posterior to the uncinate process at its free border, the inferior portion of the hiatus semilunaris is usually visible. The ethmoidal infundibulum, the most frequently involved region in inflammatory sinus disease, lies lateral to the uncinate process and cannot be visualized directly. However, the uncinate process is frequently somewhat flexible and, when the infundibular mucosa is oedematous, it will herniate into the hiatus semilunaris in response to light pressure from the endoscope. The maxillary sinus ostium also lies behind the uncinate process and therefore any openings visualized into the maxillary sinus must be accessory ostia. It is OUI belief that these accessory ostia typically result from earlier infections, and therefore should be considered as evidence of prior disease, akin to tympanic membrane perforation or scarring. Accessory ostia into the ethmoidal infundibulum or marillary sinus also provide an indication of the condition of the infundibular mucosa or the status of the maxillary sinus. The superior meatus provides the drainage pathway for the posterior ethmoid and the sphenoethmoidal recess provides drainage for the sphenoid sinus. These areas are visible to varying degrees, depending upon the anatomy of the patient. Purulence or secretions draining from the superior meatus or sphenoethmoidal recess indicate disease within the posterior etht;noid or sphenoid sinuses, respectively. Within the nasopharynx, drainage from the
I~ Hodder PInold / Scott -E:rO\Nn 7E Figure 105.2 Endoscopic view of left middle meatus (a) in patient with silent sinus syndrome demonstrating an atelectatic' uncinate' process (U) and lateral displacement of the posterior fontanelle (arrows). Surgical correction of this condition requires a retrograde approach with a bali-tipped probe (b) to safely remove the uncinate process and avoid entry into the orbit.
\
1346 I
PART 13 THE NOSE AND PARANASAL SINUSES
I
Figure 105.3 Stream of mucus (arrows) drain ing from su perior to inferior across the left Eustachian tube into the nasopharynx.
© Hodder hnold I Scott-Brown 7E
Fig ure 105.5 Fail ure to completely remove the ri ght uncinate process (U) has led to mucus recirculation between the natural maxillary os and a posterior fontanelle antrostomy (arrow), anomalies may contribute to the pathogenesis of chronic rhino sinusitis, such as septal deviation, paradoxical middle turbinate, concha bullosa and large ethmoid bulla. In previously operated patients, additional note should be made of the patency of frontal, sphenoid and maxillary sinuses, presence and location of any synechiae (Figure 105.4) or polyps, and any osteitic appearing bone or granulation tissue. Particular attention should also be paid to the region of the maxillary sinus to ensure that the iatrogenic maxillary sinus opening does indeed communicate with the natural ostium of the sinus. Residual uncinate process may lead to persistent obstruction of the natural ostium of the maxillary sinus, despite the presence of a widely patent antrostomy more posteriorly. In some cases, this may lead to recirculation of mucus out of the maxillary sinus ostium and back into the sinus through an iatrogenic ostium (Figure 105.5). [**/*]
© Hodder hnold I Scott-Brown 7E
Fig ure 105.4 Synechiae between right inferior turbinate (In and na5al septum (5).
EQUIPMENT
superior meatus or sphenoethmoidal recess typically passes superior to the Eustachian tube, whereas drainage from the middle meatus typically passes inferior to the Eustachian tube (Figure 105.3). Finally, attention should be paid to the olfactory cleft, although visualization of this area is typically very limited because the width of this space is narrow from side to side. During the entire examination, note should be made of the condition of the sinonasal mucosa, presence and origin of purulence or secretions, ulcerations, and any abnormal masses or anatomic variants. Certain anatomic
The most commonly used endoscope for nasal examination is the 4.0 mm, 30° rigid scope. In adults with narrow nasal passages or in children, a 2.7 mm, 30° rigid endoscope or a flexible nasopharyngoscope may be better tolerated. Thirty degree scopes allow both direct line bf sight and angled visualization. The recent development of 45° scopes provides the examiner with - a similar advantage with direct line of sight, but an even wider angled view. Seventy degree scopes and flexible scopes are used occasionally to view more difficult areas of the maxillary -and frontal sinuses, especially in cases of turnour surveillance. Offset scopes have the light post
Chapter 105 Nasal endoscopy
attachment placed at 90 or 180 0 to the bevel of the angled scope. These are useful in moving the light cable and attachment, so that instruments can be passed below the scope without interference from the light cable and attachment. Regardless of the scope used, a high intensity light source and quality light cable are extremely useful in providing the maximum illumination for examination. Other useful equipment includes a variety of straight and curved suction tips, flexible metal cotton-tipped applicators, a basic collection of straight and upbiting forceps, topical decongestants and anaesthetic and antifog solution. Fine metal culture swabs or suction traps with malleable tips are necessary to perform direct culture from difficult to access regions under direct endoscopic visualization. Video and digital recording equipment, cameras, monitors and colour printers are useful in documenting the endoscopic examination and recording surgical procedures. [**/*]
TECHNIQUE Preparation Thorough nasal examination begins by taking a few moments to explain the procedure to the patient. 5,6 This _helps the patient to relax and cooperate with the examiner should any discomfort arise during the procedure. A nasal speculum and headlight or head mirror are then used to perform anterior rhinoscopy and assess the condition of the nasal mucosa, any secretions or ulcerations present and to spray topical decongestant and local anaesthetic. While waiting for the medications to take effect, the examiner can perform the rest of the otolaryngologic examination, as well as prepare the endoscope, the light source and camera, ensure other needed equipment is available and apply antifog solution. Nasal endoscopy can be performed with the patient in either the sitting or supine position, depending upon the preferences of the physician and the patient. The examiner should always use universal precautions, such as gloves and mask, when dealing with potential contact with secretions and blood.
General principles Once the patient is properly positioned and the equipment is prepared, the endoscopy is started. All attempts are made to be as atraumaticas possible. This minimizes patient discomfort and any bleeding that could impair the examination. . The telescope is held lightly in the left hand using the thumb and first two fingers and is introduced under direct vision. Direct visualization may be performed
I 1347
through the endoscope. This will assist the novice endoscopist in maintaining correct orientation during the examination. With more experience, cameras and/or beam splitters may be used to allow visualization on a colour monitor. This allows observers, students and ancillary staff to follow the endoscopic examination. Regardless of the technique used for visualization, the key to an atraumatic examination is the avoidance of forceful contact and abrasion of the nasal mucosa. Several clues can alert the examiner that excessive pressure and potential trauma is about to occur during the endoscopic examination. 6 First, progressive collection of mucus on the edge of the scope indicates the tip is embedding into adjacent mucous mem~rane. In the absence of significant secretions, the mucous membrane may blanch, indicating direct pressure from the scope tip, or excessive reflection from a scope tip that is about to make contact. Finally, when 2.7 mm endoscopes are bent excessively, they develop a grey or black meniscus along the periphery of the endoscopic view. When any of these clues are noted, the examiner should redirect or slightly withdraw the scope. This will prevent patient discomfort and equipment damage and allow the examiner to complete the endoscopy. In patients with sensitive or reactive nasal mucosa, discomfort, hypersecretion and sneezing may occur even without excessive mucosal contact. In this situation, the topical anaesthesia may be augmented by painting additional pontocaine or 4 percent cocaine onto the sensitive mucosal surfaces with small cotton-tipped Farrell applicators and allowing time for this additional anaesthesia to take effect. This is also helpful if the complete examination requires some degree of mucosal contact in order to enter a narrow region.
First pass / Three passes An organized nasal endoscopy can be accomplished in three passes that will facilitate a thorough, detailed examination. 5,6 The first pass is along the floor of the nose. An initial impression should be obtained regarding the health of the sinonasal mucosa, changes with decongestion and the overall anatomy of the sinonasal cavity. The inferior meatus is the first area to inspect. If the inferior turbinate is lateralized or the inferior meatus is too narrow, medialization of the inferior turbinate may be performed. This can be carried out after application of additional topical anaesthetic. Gentle, atraumatic application of a cotton-tipped applicator or Freer elevator can then be used to medialize the turbinate. Additionally, a 2.7 mm scope can be helpful. Once adequate access is established, the examiner will be able to see the nasolacrimal duct. Tears may be seen with gentle pressure over the lacrimal sac. An inferior nasal antral window will allow visualization into the maxillary sinus if present.
1348 I PART 13 THE NOSE AND PARANASAL SINUSES
After examination of the inferior meatus, the scope is advanced through the nasal cavity toward the nasopharynx. The Eustachian tube orifices, torus tubarius, adenoid pad (if present) and entire nasopharynx can be visualized by rotating a 30° endoscope. Secretions originating from the ostiomeatal complex will typically drain below the Eustachian tube orifice, while those coming from the posterior ethmoid or sphenoid sinuses will pass above the torus tubarius. The effects of the palatal musculature on the Eustachian tube orifice can also be visualized by having the patient swallow at this point in the examination.
Second pass The examination progresses superiorly as the endoscope is reinserted between the inferior and middle turbinates. While advancing in a posterior direction, the inferior portion of the middle turbinate (Figure 105.6) and middle meatus, the fontanelles and any accessory maxillary ostia are examined. The sphenoethmoidal recess is visualized by passing the scope medial to the posterior aspect of the middle turbinate and rotating it superiorly. The examiner will often be able to visualize the superior turbinate and the natural sphenoid os. Thorough examination of this narrow area may require multiple applications of topical decongestants and anaesthetics and may require the use of a 2.7 mm 45 or 70° endoscope.
laterally beneath the posterior aspect of the middle turbinate to gain access to the deeper areas of the middle meatus (Figure 105.7). Visualization of the bulla ethmoidalis, hiatus semilunaris and infundibular entrance is obtained, and as the scope is withdrawn even further, an excellent view of the uncinate process and its overlying mucosa is obtained. Similar to examination of the inferior meatus and its contents, examination of the middle meatus is dependent upon the anatomy and cooperation of the patient. As an alternative to examining the middle meatus from posterior to anterior, middle meatal examination can be performed from anterior, typically after displacing the middle turbinate medially. This is achieved by applying topical anaesthesia on cotton both to the site where pressure will be applied to the turbinate as well as to its anterior attachment. The turbinate is then gently displac~d medially using an anaesthetic-soaked cotton-tipped Farrell applicator or a Freer elevator. [*]
Third pass The final portion of the endoscopic examination occurs while withdrawing the endoscope. The scope is rotated
s © Hodder Nnold / Scott-Brown 7E
© Hodder Arnold / Scott-Brown 7E
Figure 105.6 Endoscopic view of septum (5) and right middle turbinate with an accessory os into a concha bullosa.
~
I
Figure 105.7 Endoscopic visualization of the middle meatus can be obtained by gently rolling the endoscope laterally in order to atraumatically displace the middle turbinate as demonstrated on these (a) saggital and (b) coronal diagrams.
Chapter 105 Nasa I endoscopy I 1349
CLINICAL USES Inflammatory disease OVERVIEW
Nasal endoscopy has changed the way otorhinolaryngologists evaluate and treat inflammatory diseases of the paranasal sinuses. 4 A meticulous endoscopic examination will detect subtle changes, such as mucosal hypertrophy, inflammation, erythema and pathologic secretions, long before such changes become apparent on radiographic
studies. Endoscopic examination of the ostiomeatal complex may help in determining the anatomic or mucosal abnormalities that can contribute to the development of chronic rhinosinusitis. Endoscopy is helpful in differentiating between inflammatory disease that may be due to allergies, autoimmune diseases and infectious aetiologies (Figures 105.8 and 105.9). In this age of bacterial resistance, endoscopically obtained cultures are essential to focused antimicrobial treatment and avoidance of routine broad-spectrum, empiric antibiotic usage (Figure 105.10). Cultures can be taken directly from the involved sinus using a sterile calcium alginate-tipped applicator (Hardwood Products Co., Guilford, Maine, USA). Care must be used to avoid touching the skin or mucosa of the nasal vestibule in order to minimize the risk of contamination. The swab is then immediately placed in culture medium and sent to
Figure 105.8 Endoscopy is essential to differentiate sarcoidosis in this patient from other inflammatory disorders.
© Hodder Arnold I Scott·Brown 7E
Figure 105.9 Endoscopic view of the right inferior turbinate and nasal septum (S) with severe nasal polyposis and eosinophilic mudn (arrow) extending down to the nasal floor.
(m
Endoscopic examination (and culture if needed) can help to differentiate a fungus ball (a) from a saprophytic fungal infection (b) that can occur on a crust. Figure 105.10
M
:1 _ _ \.
1350 I PART 13 THE NOSE AND PARANASAL SINUSES the microbiology laboratory. An alternative technique is to place a Lukins trap a short distance along the suction tubing. This technique can collect a larger volume of purulent secretions and increase the yield of the culture, provided the secretions do not get impeded in the tubing prior to entering the trap.
ENDOSCOPY AND CT
Nasal endoscopy and CT yield complementary information regarding diseases of the paranasal sinuses. The CT provides objective information about the condition of the sinuses, often in sites that are impossible to visualize endoscopically, especially in the unoperated patient. One of the disadvantages of CT is that it represents one data point in time. The clinical course of most chronic rhinosinusitis patients is a dynamic one with alternating periods of quiescence and exacerbations. It is impractical to obtrun frequent, serial scans that would be needed to properly document the course of the disease. Although CT provides information regarding mucosal hypertrophy and retained secretions, it does not provide information regarding mucosal hyperemia and provides limited information regarding mucosal atrophy and other changes that may be associated with chronic inflammation. Additionally, radiographic studies may not be able to differentiate between secretions, mucosal thickening, polyps or mass lesions as the cause of sinus opacification. Finally, CT provides little information regarding the type of inflammatory disease present, such as allergic fungal rhinosinusitis, invasive fungal rhinosinusitis, bacterial rhinosinusitis or nasal polyposis (Figure 105.11). Endoscopy is essential in order to provide serial examinations, differentiate among the various aetiologies of
inflammatory sinus disease and examine the condition of the mucosa in these patients. The complementary nature of endoscopy and CT was shown by Vining et aI.,7 who demonstrated that 9 percent of patients with normal CT scans had abnormal endoscopic examination. In patients with abnormal CT scans, they noted that 68 percent of patients had additional information gained by performing endoscopy. According to Vining's study, radiographic examination was more likely to miss synechiae, septal deformities/ deflections and subtle mucosal changes that can be detected using nasal endoscopy. In addition, differentiation between different types of inflammatory disease, as previously discussed, may not always be apparent on routine sinus CT scans, but can be seen relatively easily with endoscopy.
POSTOPERATIVE CARE AND EVALUATION
Meticulous postoperative care is essential to successful results after endoscopic sinus surgery. Postoperative endoscopic examination will allow the physician to detect early mucosal abnormalities and begin medical therapy before the patient becomes symptomatic and the inflammatory disease progresses to a severe degree that may require revision surgical intervention. Studies have shown that post-functional endoscopic sinus surgery (FESS) endoscopy provides prognostic information regarding the need for revision surgery and the potential for development of future episodes of sinusitis. Most patients with diffuse nasal polyposis demonstrate persistent mucosal abnormalities even after symptomatic improvement has occurred. 4 Senior et aI. 8 showed that patients whose cavities return to normal on endoscopic examination after FESS and postoperative care, were much less likely to require revision surgery. Endoscopic cleaning and removal of thick, tenacious allergic mucin is critical in removing the fungal and bacterial load in patients with allergic fungal rhinosinusitis and enhances the effectiveness of subsequent aggressive medical therapy. [Grade B]
Neoplastic disease
I
Figure 105.11
Recurrent nasal polyposis (P) in a patient who has had multiple surgeries. Note the nasal septum (S) and left inferior turbinate (IT).
;'
./
Nasal endoscopy clearly provides visualization and biopsy of intransasal neoplastic lesions with a degree of precision that was previously impossible. While a detailed discussion of endoscopic approaches to neoplasms of the sinonasal cavities is beyond the scope of this chapter, neoplasms of all paranasal sinuses) pituitary gland, anterior and lateral skull base and clivus can now also be treated with endoscopic or endoscopic-assisted approaches. Endoscopic resection of inverted papilloma has been wid~ly reported (Figure 105.12) and endoscopic approaches have also been used for tumours, such as
Chapter 105 Nasal endoscopy I
1351
© Hodder .A.rnold I Scott-Brown 7E Figure 105.12
Endoscopic examination is crucial to differentiate inflammatory disease from neoplasms, such as inverted papilloma (a
and b),
© Hodder Nnold I Scott-Brown 7E Figure 105.13
View after an endoscopic modified Lothrop through a patent nasal septectomy (a) looking into the left frontal (LF).
Note previously placed graft (G) over skull base defect and inverted papilloma in the left olfactory cleft (arrows), There is no apparent papilloma (b) in the right frontal (RF) in the vicinity of the graft (G),
juvenile angiofibromas, esthesioneuroblastomas, pituitary tumours and fibro-osseous lesions. 9 The endoscopic approach is not necessarily a less aggressive operation, it simply enhances the visualization and precision of the procedure while avoiding external incisions. In many cases, the use of the endoscope permits detection of the site of tumour origin, thus a more focused operation can be performed, with preservation of normal surrounding structures (Figure 105.13). Regardless of the technique used to resect lesions of the sinonasal cavities, endoscopic surveillance is critical to early detection of recurrent or persistent disease during the postoperative period. After healing has occurred in the early postoperative time frame, any suspicious
abnormalities can be biopsied in the clinic. Identification of such abnormalities allows the detection of recurrence well before the patient becomes symptomatic or radiographic evidence appears. [Grade B]
Skull base defects Solitary polyps, particularly those arising medial to the middle turbinate, should raise suspicion of the possibility of a meningocoele or meningoencephalocoele (Figure 105.14). In cases of gross CSF rhinorrhoea, nasal endoscopy without the use of intrathecal dye may allow identification of the leak site. However, in many cases, the
/
7
1352 I PART 13 THE NOSE AND PARANASAL SINUSES
Figu re 105.14
Solitary mucosal covered mass (arrows)
occurring between the nasal septum and the left middle turbinate. Further work-up demonstrated a men ingoen ce pha Iocoele.
use of an intrathecal dye may be required and a minor leak cannot be excluded without the use of both fluorescein and blue light endoscopy (Figure 105.15). Significant care is necessary when intravenous fluorescein is utilized intrathecally, because the dye is a neural irritant and can result in seizures or other complications if not administered carefully and in the correct dosage. One tenth of 1 cc of 10 percent fluorescein administered in 10 ccs of the patient's own CSF over a five-minute period is recommended. The patient can then be placed in a head down position for one to two hours to allow the fluorescein to circulate intracranially. Endoscopic examination is then performed, initially with a standard white light, and if this does not demonstrate a leak, with a blue light and blocking filter (Karl Storz Endoscopy, Tutlingen, Germany). Blue light endoscopy with a blocking filter is extremely sensitive for the presence of a CSF leak. Indeed, if the patient has had prior surgery, it is not uncommon to see an intracranial glow when the skull base is viewed in this fashion, as a result of CSF in the subarachnoid space. Endoscopic repair of CSF leaks and encephalocoeles is more successful than traditional intracranial approaches and has less morbidity.1O Intranasal endoscopic repair from below allows precise repair of these skull base defects with preservation of olfaction and avoidance of craniotomies. [Grade B]
© Hodder Arnold I Scott-Brown 7E
Figure 105.15
Intrathecal fluorescein is often visible using
native light (a) to localize skull base defects. A blue light filter
(b) can provide additional sensitivity in detecting fluorescein if needed.
can all be treated endoscopically (Figure 105.16). These procedures can now be performed without external incisions to a higher level of precision than was previously possible. Diagnostic nasal endoscopy in these situations is primarily indicated post-surgically, so as to ensure that herniated, decompressed fat does not obstruct the maxillary or frontal sinus ostia after an orbital decompression, or that synechiae do not lead to iatrogenic sinus obstruction after dacrocystorhinostomy. [Grade C]
Epistaxis Ophthalmologic procedures Orbital decompression, dacrocystorhinostomy, optic nerve decoD!pression and medial orbital wall blowouts
Nasal endoscopy is essential in the evaluation and treatment of the epistaxis patient. The time when blind packing of the nose was the treatment of choice should
/
/
Chapter 105 Nasa I endoscopy, • 1353
e' Iuation of patleUI
th\.' parana a1 inus . • Po t p~ratively. na a1 cnJo 't:0PY 'S$ It per i tent ymplom tic inflammatory d' 1 to be identified nd treated. Aggre sjw managenlent of u('h eli ea C' in the p() toperative period reduces the risk of ub cquent recurr nee of di e and r tiULCS th ' need tor rcvj ~ n surgery. •
A rc
~urillg
m nner anD g lero I topical
anae thetic will Uow a th >rough examination in most pali nt .
./ Nasal endoscopy is critical in the evaluation and treatment of patients with inflammatory, neoplastic or bleeding disorders. ./ Endoscopy and CT scan are complementary studies and should be frequently correlated during clinical evaluation and surgical treatment of paranasal sinus diseases.
© Hodder Arnold / Scott-Brown 7E
Figure 105.16 View into a widely patent left sphenoidotomy demonstrating access to the optic nerve (ON) and internal carotId artery (C).
now be passed, at least when management of the epistaxis is being performed by otolaryngologists. Repeated application of light packing soaked with topical decongestants and anaesthetic agents, and the. injection of local anaesthetic through the greater palatine foramen to obtain a sphenopalatine block, aid in optimizing conditions -for examination. The site of origin can then be determined and a neoplastic source of bleeding can be ruled out. Most cases of epistaxis can be treated with either localized cautery or the use of degradable haemostatic agents, such as Avitene or Gelfoam, thus avoiding the discomfort and morbidity of traditional nasal packing. Even when packing is utilized, the use of nasal endoscopy typically allows the bleeding site or region to be identified, enabling the overall amount of packing to be significantly reduced. In most cases, the nose does not need to be tightly packed, applying some generally light packing to the bleeding source is usually sufficient to maintain control. Occasional more severe cases may require either endoscopic ligation of the sphenopalatine or internal maxillary arteries or embolization. [Grade C/D J
Deficiencies in current knowledge and areas for future research
>>>-
REFERENCES 1.
KEY POINTS • A thorough undcrst'mJing of anatomy and its fetal ionsh ip to endosco pic and r diographic ex.amination rs critical in the evaluation of si nus disease. • Endoscopy should be performed in an o rganized manner to avoid missing 1 ' ions and routi ne nasal endoscopy should he pa r t
The degree to whic~ anatomical variations may predispose to recurrent and chronic rhinosinusitis is not well identified. Our hypothesis that accessory ostia are acquired from prior infections needs to be verified. Improved miniaturized optics may allow more detailed examination of the sinus mucosa and lead to a better understanding of the pathophysiology of i nfia mmatory si nus disease.
2. 3.
*
4.
Draf W. Endoscopy of the paronasal sinuses, New York: Spri nger-Verlag Inc, 1983. Maltz M. New instrument: the sinuscope. Laryngoscope. 1925; -35: 805-11. Messerklinger W. Endoscopy of the nose. Baltimore: Urban Et Schwa rzen berg, 1978. Kennedy DW. Prognostic factors, outcomes and staging in ethmoid sinus surgery. Laryngoscope. 1992; 102: 1-18. This article is one of the early landmark references that establishes the efficacy of functional endoscopic sinus surgery for chronic sinusitis.
I
-
\
J
\
1354 I PART 13 THE NOSE AND PARAI\JASAL SII\JUSES 5.
*
Bolger WE, Kennedy DW. Nasal endoscopy in the outpatient clinic. Otolaryngologic Clinics of North America. 1992; 25: 791-802. 6. Joe SA, Bolger WE, Kennedy DW. Nasal endoscopy: diagnosis and staging of inflammatory sinus disease. In: Kennedy DW, Bolger WE, Zinreich SJ (eds). Diseases of the sinuses: diagnosis and management. Hamilton, Ontario: BC Decker, Inc., 2001: 119-28. 7. Vining EM, Yanagisawa K, YanClgisawa E. The importance of preoperative nasal endoscopy in patients with sinonasal disease. Laryngoscope. 1993; 103: 512-9.
This article nicely demonstrates the complementary role of endoscopy and CT scan in the evaluation of patients with inflammatory disease of the paranasal sinuses.
*
8.
Senior BA, Kennedy DW, Tanabodee J, Kroger H, Hassab M, Lanza D. Long-term results of functional endoscopic sinus surgery. Laryngoscope. 1998; 108: 151-7. This article demonstrates the importance of postoperative endoscopy in treatment of persistent, asymptomatic inflammatory
disease in order to avoid revision sinus surgery. It also establishes the long-term clinical efficacy of functional endoscopic sinus surgery for chronic sinusitis. 9. Thaler ER, Kotapka lVI, Lanza DC, Kennedy DW. Endoscopically assisted anterior cranial skull base resection of sinonasal tumors. American Journal of Rhinology. 1999; 13: 303-10. 10. Lanza DC, O'Brien DA, Kennedy DW. Endoscopic repair of cerebrospinal fluid fistulae and encephaloceles. Laryngoscope. 1996; 106: 1119-25.
106 .
Physiology of the nose and paranasal Slrluses
ADRIAN DRAKE-LEE
Introduction
1355
The nose and the voice
Respiration
1355
Olfaction
1366
Heat excha n g e
1355
The vomeronasal orga n
1368
1366
H u m idification
1356
The paranasa l sin u ses
1368
Airflow
1357
Key poi nts
1369
Protection of the lower a i rway: mech a n ical and che mica l
1358
Deficiencies in curre nt know ledge a nd a reas for futu re
Protection of the lower airway: i mmunological
1361
N asa l vascu latu re a n d nerve supply
1362
Drugs acting on the vascu l ar tissue of the nose
1365
1369
research References
1369
the key words physiology and nose, nasal mucosa, sinuses animal physiological studies. Higher levels are more suitable for medical treatment, which is not addressed in this chap te r The data in this chapter are supported by a MedJine search using
and olfaction. The evidence base is level 1 as most information is gathered from human or
.
RESPIRATIO N
INTRODUCTION The
development
of
medical
sciences
has
led
to
The nose acts as an air conditioning unit and per forms
humidification, heat transfer and filtra
considerable overlap between physiology, biochemistry,
three functions:
microanatomy
tion. The functions of the nose are bypassed during
and
science of the
immunology.
normal function
Physiology
is
the
and phenomena of
living things and its parts. The nose contains the organ
exercise. Because of
its ability to transfer heat, the nose in temperature regulation than
may be more important
It warms, cleans and humidi
in respiration. The inspired gases contain pollutants,
fies the inspired air, and cools and removes water from
domestic dust particles and pollen, but also industrial
the expired air, it also adds quality to speech produc
products,
tion. The ENT surgeon should distinguish normal nasal
relative humidity and temperature vary widely.
of smell and respiration.
bacteria,
viruses
and
tobacco
smoke.
The
function from pathological symptoms to prevent un
a paired structure coronally into two chambers, it acts as a functional unit. The paranasal sinuses are mirror images of, each other and their importance is small. Deeper questioning reveals no single function. See Table 106.1 for necessary surgery. Although the nose is
divided
a brief summary
HEAT EXCHANGE The temperature of the inspired air can v ary from - 50 to 50°C. The nose has evolved
in different racial groups to
suit the local environment.
.
I j
...... ---"' � /, --"--- --'----- - -- -
i . .-
-
" \
1356 I
PART 13 THE
Table 106.1
NOS E A N D PARANASAl SIN USES
Physiolog ica l functions of the nose.
where Cp is the heat
of the gas in JIg per cC; YJ
ca pac ity
is the viscosity; an d KH is the thermal c onduct ivit y in
JIm per 0c. Gas in the nose and the arter i al blood may be con-
R e sp i r ati on Heat exchange
D i rection of b l ood flow Latent heat of evaporation Thermoreg u l ation
Hu m id ification
Anteri or serous g lands Mixed serous and mucus g l a nds Cap i l lary permeabi lity
sidered as two fluids that are in th ermal but not direct contact. Arterial blood flows forward from the spheno
palatine artery. Airflow is counter-current du ring in spir a tion and
is more e ffi c ient. Effi c iency is measured by
compar ing the temperature difference of the two 'fluids'
at one end, �Tl with the difference at the other end, �T2:
Other body flu i ds, e.g. tea rs Filtration
A irflow pattern: lam i n a r/turbu l ent
N asal resistance
Anatomica l , fixed N e u rovascular, variable
N asal fl u ids a nd cil iary fu nction
Mucus. m ucins Proteins including immunog lobul ins Ci l iary structu re and function
N asal neu rovascu l a r reflexes
Pa rasym pa th etic Sympath etic Sensory: axon reflexes Sneezing Centra I: nasopulmona ry reflexes Nasal cycle
Voice modification
Nasal escape
HUMIDIFICATION Vaporization cools th e surface and 10 perce nt of the body
heat is lost in this way. Inspiration Saturation follows the temperature rise rapidly. Energy is requi red
for tw o func tions : raising the temperature
of inspired air (lIS), and the latent heat of evaporation
(4/5).1 The amount of energy is dependent on ambient
Olfaction
Sti m u l u s
Th reshold and su prath reshold Adaptation, discri m i nation and cl assification
Pathways
Neurones i n contact with the exte rna l
Two n e u rone pe riphe r a l
Higher centres Pe rceived sme l l
envi ronment pathway Trige m ina l input
Pa in
Olfaction and behaviou r
Pheromones
temperature and relative humidi t y of insp ired air. Ten percent of the body h e at loss occurs through the nose in humans_ D e spit e variations in temperature of inspired air, air in the post - n as al space is approxima tel y 31°C and is 2 95 percent saturat e d.
Expiration The t emperatur e of the expire d air at the back of the nose is slightly below body core temperature and is s atu rated
.
As the temperature drops along the nose, some water
Cond u ction, convection and radiation Conduction occurs without flow when heat is transferred by inc reased molecular movement. A temperature gra dient leads to convection currents; this will affect airflow in the nose, causing turbulence. Flow results in forced
convection. The follow ing empirical formula describes
condenses onto the
mucosa. The t emperatu re in the the expirati on is 32°C and
anterior nose at the end of
ap proxim ate ly 30°C at the end of inspiration Approxi .
mat ely one-third of the wa ter required to humidify t h e
inspired air is recovered in this way. People who breathe in throu gh the nose and out through the mouth will dry the nasal mucosa.
this:
Water production where PH is the heat flux in JIm per s; Tf is the bulk temperat u re ; and h is the heat transfer coefficient in JIm per s per 0c.
Water comes from the serous glands, which are extensive
Prandtl number, the heat transfer coefficient expresses
vasculature.3 Capillary leakage occurs during inflamma
this as follows:
throughout the
nose.
Humidification is reduced by
at rop ine p roba bl y acting on
the glands rather t han the
tion. During the nasal cycle, secretions are lower on the more obstrutted side. Additional water comes from the expire d air, the nasolacrimal duct and th e oral cavity.
J
/
; , - � . . . -�, \ .....L:.:....��
Chapter 106 Physiology of the nose and paranasal sinuses
I 1357
AIRFLOW The airflow and the sensation of it are very different. Cold
receptors sense airflow. Most of the work of heat and mass
transport has been performed on simple structures with constant cross sections? The flow is turbulent, but is considered laminar at rest. The equations below describe flow, two for laminar and one for the transition to turbulent flow: Airflow : VA
=
constant
Bernoulli's equation: P Reynolds number: Re
+! P V2
=
constant
dVp = --
11
p is density (g m -1), Vis mean velocity (m sec -1); A is cross-sectional area ( m2); P is pressure (N m - 2); dis diameter (m); and 11 is viscosity (g sec - 1 m - 1 ) . where
Figure 106.1
The direction of inspiratory airflow.
Figure 106.2
The direction of expiratory airflow.
Gases flow faster through the choana. Proetz used
transparent models made from liquid latex cast at post mortem.4 Although there is considerable variety of nasal shape, the characteristics
of airflow were similar in
different noses. Cast wax has been developed to study the flow in both sides together.5 These studies do not take into account the variation
in the nasal lumen produced by
alterations within the nasal mucosa. Complex computer models have been developed recently. The cross-sectional flow is maximal at the centre and is zero at the edge. Energy overcoming the viscosity results in an irreversible drop in pressure so that the Bernoulli equation is not strictly applicable. The nose has a variable cross section and so the pressure and velocity will alter continuously within the system.
Because flow is turbulent in an
irregular tube, the resistance is inversely proportional to the square of the flow rate.6 Pressures vary during the respiratory cycle and the rate is between 10 and 18 cycles a minute
in adults at rest.
Inspiration The airflow is directed upwards and backwards from the
markedly and the walls are not smooth. The surface area is enlarged by the turbinates and the microanatomy of the epithelium.
nasal valve initially, mainly over the anterior part of the inferior turbinate. It then splits into two, below and over the middle turbinate, rejoining into the posterior choana. Air reaches the other parts of the nose to a lesser degree
(Figure 106.1). The velocity at the anterior valve is 12-18 m sec - 1 during quiet respiration.
Nasal resistance Differences exist between races. Negroes and Caucasians are similar, but it is difficult to obtain the sampling pressure for rhinomanometry in Japanese?,8 The nose accounts for up to half the total airway resistance. The
Expiration
nasal resistance is produced by two resistors in parallel and each cavity has a variable value produced by the nasal cycle. The resistance is made up of two elements; one
L
'
essentially
turbulent
(Figure 106.2). Extrapulmonary airflow is
attached muscles, and the other variable, the mucosa.
turbulent because the direction changes, the calibre varies
The nasal resistance is high in infants who initially are
fixed
comprising
the
bone,
cartilage
and
EXpiration lasts longer than inspiration and is more
/
1358 I
PART 13
TH E NOSE AN D PARAI\lASAL S I N USES
obligatory nose breathers. Adults breathe preferentially
mucosa. These are probably mediated directly on the
through the nose at rest even though there is a significant
blood vessels.
resistance. During expiration, the positive pressure is transmitted to the alveoli. Removal of this resistance by tracheostomy reduces the dead space but results in a degree of alveolar collapse. Reduced alveolar ventila tion gives a degree of right to left shunting of the pul monary blood.
Rhinomanometry and acoustic rhinometry The nasal airflow is usually measured as a volume flow and
plotted
against
pressure
(Figure 106.3). Quiet
respiration is studied and a sample point of the flow at 150 pascals pressure is the standard reference.IS The
The anterior nasal val ve
details of rhinomanometry are considered elsewhere.
This is the narrowest part of the nose and is less well
of reflection gives the cross-sectional area of the nose
defined physiologically than anatomically. As the nar rowest part of the airway and so the greatest resistor, it produces the most turbulent airflow.9 It is formed
P ulsed sound may be reflected (sonar) and the pattern which is the basis of acoustic rhinometry. It is more accurate nearer the nasal valve.
by the lower edge of the upper lateral cartilages, the anterior end of the inferior turbinate and the adjacent nasal septum, together with the surrounding soft tissues. Electromyography
shows
contraction
of
the
dilator
PROTECTION OF THE LOWER AIRWAY: MECHANICAL AND CHEMICAL
naris alone during inspiration,lO which increases during exercise and can be mimicked by voluntary dilatation.11
The nose protects the lower airway by removing particles
Alar collapse occurs after denervation, even in quiet
down to approximately 30 !lm, including most pollens
respiration.
from the inspired air. The shape and roughness of smaller particles may cause them to be deposited in the nose. Inspired air travels through 1800 and velocity drops markedly just after the nasal valve. Turbulence increases
Nasal cycl e
deposition of particles. Particles in motion will tend to
The cycle consists of alternate nasal blockage between passages. The cycle has been known by Yogis since antiquity although Kayser gave it its first physiological description in 1895.12 The changes are produced by vascular activity, particularly the volume of blood on the
carry on in the same direction: the larger the mass the
greater the tendency. Resistance to change in velocity is
greater in irregular particles because of the larger surface area and the number of facets. V ibrissae will only stop the largest particles.
venous sin usoids (capacitance vessels). Cyclical changes occur between four and 12 hours; they are constant for each person.
Litres/second
Normal 0.5
The nasal cycle can be demonstrated in over 80 percent of adults, but it is more difficult to demonstrate in children. It is present in early childhood.13 The physio logical significance is uncertain but, in addition to a
Obstructed
resistance and flow cycle, nasal secretions are also cyclical
Inspiration
with an increase in secretions in the side with the greatest airflow.3 Various factors may modify the nasal cycle and in clude allergy, infection, exercise, hormones, pregnancy, fear
and
emotions,
including
sexual
activity.
The
Expiration
autonomic nervous system controls the changes; vagal
Pa /
overactivity may cause nasal congestion. High levels
/
of CO2 in the inspired air produced by rebreathing may also reduce the nasal resistance. This reverses following hyperventilation.14 Drugs, which block the action of noradrenaline, cause nasal congestion. The anticholiner
0.5
gic effects of antihistamines can block the parasympa thetic activity and produce an increase of sympathetic tone, hence an improved airway. Times of hormonal
Figure 106.3
changes, such as puberty and pregnancy, affect the nasal
r es pi ra tion.
•
Pressure (Lis) flow (Pa) curve for q uiet nasa l
Chapter 106 PhysIology of the nose and paranasal sinuses I
Nasal secretions
vestibular
region.
These
produce
a
copious
1359
watery
secretion when stimulated. Sinuses have fewer goblet Nasal secretions are composed of two elements, mucus
cells and mixed glands.
and water. Glycoproteins are produced by the mucus glands and the water and ions are produced mainly from the serous glands and indirectly from transudation from the capillary network. There are also two secretory cell types in the mixed nasal glands, mucus and serous cells. Glycoproteins found in mucus are produced in two cell types, the goblet cells within the epithelium and the glandular mucus cells Glandular
(Figure 106.4).
mucus
and
goblet
cells
contain
large
electron-lucent secretory granules, containing acidic glyco proteins
(Figure 106.5).16
Serous cells contain discrete
electron dense granules. Granules may have a core of greater
density.
They
contain
neutral
glycoproteins,
enzymes such as lysozymes and lactoferrin as well as immunoglobulins of the 19A2 subclass. Submucosal glands
Com position of m u cu s The composition of mucus is outlined below: •
water and ions from transudation;
•
glycoproteins: sialomucins, fucomucins, sulphomucins;
•
enzymes: lysozymes, lactoferrin;
•
circulatory proteins: complement, cxrmacroglobulin,
•
protein;
C reactive; •
immunoglobulins: IgA, 19E, IgG, IgM, IgD;
•
cells: surface epithelium, basophils, eosinophils, leukocytes.
are mixed and are arranged around ducts. The anterior
Mucus is a complex non-Newtonian fluid. Both quality
part of the nose contains serous glands only in the
and quantity of the secretion are important and require an intact blood supply and nervous system. Mucins are packaged by the Golgi apparatus in 1-2 mm droplets. Droplets absorb water when secreted, enlarging rapidly over a three second period. Goblet cells respond directly
-"
-
and the exocrine glands secrete through parasympathetic 17 and M3.
stimulation via muscarinic receptors, Ml
Methacholine produces a watery and less viscous secre tion that is blocked by atropine. The action of the sympathetic nervous system is not clear. Dessiccation by the inspired air helps to develop a more viscous gel layer. Glycoproteins form approximately
80 percent of the dry weight of mucus. IS They consist of a single sugar side change and a polypeptide chain, which are •• Figure 106.4
Respiratory mucosa of the nose showing goblet
celis and epithelial celis.
linked
covalently.
These
units
are
polymerized
by disulphide linkages. Complexes in secretions may weigh up to 106 daltons. Mucins are random coils of carbohydrate up to 5)lm long and attached to protein cores by O-glycoside linkages, which produces a hydro philic gel with water. Mucin genes are expressed in the goblet cells and glandular tissue and are mainly the MUC2 and MUC5AC genes with some expression of MUCl, 4 and SB.I9 The amount of each depends on the cell type. The main site for MUC2 is on chromosome llp15. Glycoproteins are classified
as
acidic or neutraL The
acid is either sialic acid (sialomucins) or from a sulphate group
(sulphomucins). Neutral glycoproteins contain
fucose
(fucomucins).
Sialomucins can be subdivided
into those that are digested by sialidases and into those that are not. Hydroxaminoacids form up to 70 percent 20
of the amino acids and serine is the most common.
Secretory cells may contain a mixture of different mucins.
Rheol ogy of m u cus Figu're 106.5
Holocrine eel L The la rge arrow shows the
openIng where the granules are discharging. The small arrow
Glycoproteins
shows a tight junction.
measured properties, viscosity and elasticity. Viscosity
give
mucus
its
two
most
commonly
l
L
"&1 -------' ----------�--\....-� ..
1360 I and
PART 13 THE NOSE AND PARANASAL S I N USES
elasticity
are easier
to
measure,
but
adhesive
ness and fluidity may be more important. V iscosity is lowered by reducing the ionic content. The tempera ture of the nasal cavity is relatively constant and is lower than the tracheobronchial tree. Other compounds, such as immunoglobulins,
do not add to the flow
characteristics. Movement of the cilia produce shearing effects that the
COMPLEMENT
All components have been identified. C is produced 3 by the liver and locally by macrophages. It is activated by both nonspecific and specific immunological respon ses through the alternative and classical pathways. Its functions
include
the
lysis
of
microorganisms
and
enhancing neutrophil function as well as leukotaxis.
elasticity counteracts and if it is the right consistency, viscosity and elasticity complement each other and mucus moves. There is an optimum value for both of these properties but care must be taken when applying linear properties to a complex fluid. Two
in vitro techniques
LIPIDS
P hospholipids and triglycerides are present; their exact function is unknown.
are used to measure the rheology: microspherometry and controlled stress technique. Mucus viscosity can be measured most easily by drawing up mucus into a capillary tube under negative pressure and measuring the flow relative to the pressure. Recoil may be measured when the pressure is released.
IONS AND WATER
Na
+
and Cl - are hyperosmolar in mucus. Evaporation
may account for some of the hyperosmolarity but active ion transport also exists.21 This occurs mainly within the serous glands, which produce the major proportion of the fluid in nasal secretions.
Proteins in nasal secretion These are derived either from the circulation or are produced by the mucosa. Some compounds, such as lactoferrin, are present only in nasal secretions. Many proteins are involved in the immunological responses of the nose. A number of other plasma proteins and macromolecules are present because of capillary leakage.
IMMUNOGLOBULINS
All classes of immunoglobulins have been found in nasal secretions. Two immunoglobulins involved with mucosa defense, 19A
and 19E, are present in greater quantities 2 than serum. 19A accounts for 50 percent of the total protein content.
LACTOFERRIN
Lactoferrin is produced by the glandular epithelium,
Cilia
mainly the serous cells. Its action is to bind divalent metal ions - like transferrin in the circulation; transferrin is not found in secretions in any quantity. They both bind two divalent metal ions, particularly iron, and have a molecular weight of 76-77,000 daltons. By removing heavy metal ions, it prevents growth of certain bacteria, particularly staphylococcus and pseudomonas.
ULTRASTRUCTURE
Cilia are found on the surface of cells in the respiratory tract
and
their
function
here
is
to
propel
mucus
backwards in the nose towards the nasopharynx. All cilia have the same ultrastructure although nasal cilia are relatively short at 5 �m, with up to 2 00 per cell. A cilium has a surface membrane, which encloses an organized ultrastructure. Nine paired outer microtubules surround
LYSOZYMES
Lysozymes come from the serous glands and tears. They are also produced from leukocytes and macrophages, which are found in nasal secretions and mucosa. Their actions are nonspecific and act only on bacteria without capsules.
a single inner pair of microtubules. Outer-paired micro tubules are linked together by nexins and to the inner pair by central spokes. Outer pairs also have inner and outer dynein arms, which consist of an ATPase, which is lost in Kartagener's syndrome. Microtubules become the basal body in the cell; the outer pairs become triplets and the inner pair disappear. Three outer microtubules are similar to centrioles of mitotic cells and it has been suggested that
ANTIPROTEASES
centrioles migrate to the cell surface to form these
A number of different antiproteases have been demon
structures
strated and they
layers, one upper more viscous layer and a lower more
increase
with
infection;
their
role
(Figure 106.6). Nasal mucus film is in two
remains uncertain. They include C't-antitrypsin, C'tl-anti
watery layer in which cilia can move freely. Tips of the
chymotrypsin, C'tTmacroglobulin and other antiproteases
cilia on which there are small hooks enter the viscous
produced by leukocytes.
layer to move it.
Chapter 106 Physiology of the nose and pa ranasal si n uses I
1361
DRUGS
Acetylcholine increases the rate and adrenaline decreases the rate. The effects of
a
and
P
agonists and antagonists
are variable. High concentrations of
0:1
agonist, pheny
lephrine, decreases whereas lower doses increases CBP in
vitro.
Propranolol
(P
antagonist)
decreases ciliary
beat frequency and is dose dependent.23 Cocaine hydro
chloride causes immediate paralysis in solutions above
10 percent. Corticosteroids reduce the rate of saccharin
clearance following one week of therapy.25
Figu re 106.6
The n i ne plus two u Itrastructu re of normal ci I i a
are demonstrated. Some i n n e r a n d oute r dynein arms a nd ra d ial l i n ks are seen. The smal ler structures a re m icrovi l l i.
PROTECTION OF THE LOWER AIRWAY: IMMUNOLOGICAL Mucus contains a number of different compounds able to neutralize antigens, either by innate mechanisms or by learned or adaptive immunological responses. IgA and
CILIARY ACTION
Beat
frequency is between 7 and 16 Hz at body temperature.22 Beat frequency remains constant between and
32
40°C.
The
beat
consists
of a
rapid
pro
pulsive stroke and a slow recovery phase. During the propulsive phase, the cilium is straight and the tip points into the viscous layer of the mucus blanket; whereas in recovery the cilium is bent over in the aqueous layer. Energy is produced by conversion of ATP to ADP by the ATPase of the d ynein arms and the reaction is dependent of Mg2 + ions. Motion is produced
by the pair of outer microtubules
sliding
with respect to each other. ATP is generated by the
mitochondria near the cell surface next to the basal bodies
of the cilia.
T he mucus blanket is propelled backwards by meta
chronous movement of cilia, and only those at right
angles to the direction of flow are in phase.
All those in
IgE are mainly present on the surface, and IgM and IgG act if the mucosa is breached. Certain bacterial allergens are neutralized but several bacteria and viruses require the activation of the cell-mediated immune responses.
T lymphocytes are characterized by surface markers
into suppressor) helper and killer cells) respectively. T and
some B cells interact with macrophages, which have specific and nonspecific immunological properties. Anti
gens are often presented by macrophages or dendritic cells to T lymphocytes. Dendritic cells are important in the allergic response.26 Two groups of cytokines act on
CD4
+
T cells and gives rise to two main responses,
the Thl response and the
Th2 or allergic response. The
local lymphatic system can be subdivided into two, the mucosal-associated lymphoid tissue (MALT) - the tonsils,
adenoids and aggregations within the respirator y, and
lymph nodes
(Table 106.2).
the d irection of flow are slightly out of phase until the cycle is complete. Mucus flows from the front of the nose
Nonspecific immunity
the lateral wall, with most mucus going through the
Lactoferrin, lysozymes) complement, antiproteases
posteriorly. Mucus from the sinuses joins that flowing on middle meatus. Most passes around the Eustachian orifice
and it is then swallowed.
and
other macromolecules interact with a number of bacteria, particularly those without capsules, to give an innate nonspecific immunity. Polymorph leukocytes and macro
phages phagocytose and destroy foreign material. Many
FACTORS AFFECTING CILIARY ACTION
organisms
The nose is a remarkably constant environment and
and
viruses are resistant and
so
specific
reactions are required.
changes will affect ciliary function. Drying stops the cilia. Movement will cease below Isotonic
saline
lOoe and above 45°C. will preserve activity, but solutions
above 5 percent and below 0.2 percent will cause paralysis.
K
+
ions
do
not
affect
ciliary
function
nonphysiological levels.23 Similarly, cilia pH 6.4 and will function
except
at
will beat above
in slightly alkaline fluids of
Acquired immunity IgG (except IgG4 subgroup) activates complement result ing in cell lysis and phagocytosis. Viruses and myco
bacteria initiate cell-mediated immunity.
19A is divided 19A[ and 19A2' IgAJ is more frequent
pH 8.5 for long periods. Upper respiratory tract infec
into two subgroups:
away. Ciliary function may deteriorate with age.24
in nasal secretions and is a dimer. IgA accoWlts for up to
tion may damage the epithelium so that it sloughs
in the serum and is a monomer, IgA2 is more common
I
(
1362 I
PART 13 THE NOSE AND PARANASAL SINUSES
Table 106.2
constnctmg smooth muscle so changes in airway are
Nasal i mmune system.
produced by alterations in blood flow and pooling of
Nasal immune system
blood in resistance and capacitance vessels. The degree of development varies at different sites within the nose. It is
Surface properties
Mecha n ical
Innate immu nity
Bacteriocid a l a ctivity in mucus
Physical characteristics of mucus
most complex over the turbinates and part of the nasal septum (septal turbinate).
Protei ns: lactoferrin, Iyzomes D:2-macroglobulin, C reactive protein, complement system. Cellu l a r: polymorphs a n d macrophages Acquired immun ity
Surface IgA, Ig M, IgE and IgG Primed macrophages Submucosa m acrophages IgM, IgG, T and B Lymphocytes: mucosal associated lymphoid tissue
Distant sites
Adenoids, lymph nodes and spleen
Microanatomy
Figure 106.7 diagrammatically shows the blood vessels within
a
turbinate.
Arteries
and
arterioles
produce
resistance, and the venules and sinusoids, capacitance. Blood is shunted between the arteries and veins deep in the mucosa. It bypasses surface vessels and reduces the amount of blood within the system. Anastomotic arteries spiral upward through the cavernous plexus of veins
70 percent of the total protein in nasal secretions. IgA
dimer is transferred passively through interstitial fluid
and is actively taken up by the seromucinous glands and surface epithelium. In epithelium, a secretory piece is attached to IgA, which makes it stable in mucus. When it reacts with an antigen, it fonns an insoluble complex, which is swallowed and destroyed by stomach acid. IgA does not activate complement.
where most of the shunting occurs. Towards the surface, arteries branch into arterioles which lack an elastic lamina and end in capillaries, which run parallel and just below the surface epithelium (Figure 106.8). They also run around mucous glands?7 Capillaries drain into a superficial venous system. They are best developed just before the superficial veins drain into venous sinusoids,
a cavernous plexus of large
tortuous anastomotic veins without valves. Sinusoids
IGE This is the main immunoglobulin involved in allergic reactions. It was first identified by Ishizaka in 1967. It is
produced mainly in lymphoid aggregates such as the
tonsils and adenoids and within the submucosa. IgE is firmly attached to mast cells and basophils and two molecules of allergenic specific IgE have to sit on adjacent receptor sites on most cells to cause mast cell degranula tion. IgE does not activate complement. It is usually directed against intestinal parasites.
SU RFACE CELLS
Mucus contains epithelial cells, leukocytes, basophils, eosinophils, mast cells and macrophages.
Leukocytes
and macrophages are important in phagocytosis and may help prevent bacterial or viral invasion. Cytology of secretions may help in the diagnosis of allergy. Surface cells migrate through the interstitium from the blood.
------NASAL VASCULATURE AND NERVE SUPPLY G eneral considerations The
vascular
anatomy
was
described
extensively by
Burnham in 1935 and the microanatomy has been further
studied by Cauna?7 The nose is a rigid box devoid of a
/
Figu re 106.7
This is a schematic representation of the b l ood
supply of the turbinates. A. arteriole; V, venule; C, capillaries; G, interstitial g lan ds; p, venous plexus; S, venous sinusoi ds.
;'
Chapter 106 Physi olog y of the nose and paranasal sinuses
I 1363
2. Reduced arterial perfusion with no shunting
giving rise to venous congestion.
3. Ischemia. Both the autonomic nervous system and local inflamma tory reactions control flow and may sometimes be in dependent of each other.
Au tonomic nervous system The distribution may be seen schematically in Figure 106.9.
Motor nerves Figure 106.8
Confocal microscopy of subepithelial capillaries
running under the epithelium of the nasal mucosa of a normal
SYMPATHETIC NERVE SUPPLY
This is derived from the lateral horn of grey matter of the
inferior turbinate. Figure courtesy of S Ahmed.
spinal cord at the level of the first and second thoracic receive both arterial and venous blood. Blood flow is regulated by cushion or throttle veins which have a longitudinal muscle coat. They do not close the lumen completely
but
are
able
to
regulate
the
flow
into
bone through the deep venous plexus. Approximately 60 percent of blood flow is shunted through arteriove nous anastomosis in cats2S and the actual blood flow per
vertebrae. Preganglionic axons run through the anterior nerve roots,
anterior primary rami and white rami
communicates with the sympathetic chain. They synapse in the superior cervical ganglion. Postganglionic fibres hitchhike along the carotid to the deep petrosal and vidian nerves. They pass through the sphenopalatine ganglion and pass into the nasal cavity.
cubic millimetre is greater than muscle, brain or liver.29 The maxillary artery is the main feeding vessel and the flow is forward through the nose. The vascular arrange
PARASYMPATHETIC NERVE SUPPLY
ment within the turbinates is often called pseudoerectile
The pons contains the superior secretory nucleus and
because of the similarities to the blood supply of the pems.
preganglionic fibres have their cell bodies here. They proceed via the intermediate branch of the facial nerve to the geniculate ganglion through which they pass. After continuing along the greater superficial petrosal nerve,
Bl ood flow
the deep petrosal nerve and the nerve of the pterygoid
Measurement of nasal blood flow is difficult because instruments introduced into the nose will alter nasal
canal, they synapse in the sphenopalatine ganglion. Post ganglionic fibres then pass to the nasal mucosa.
resistance if the mucosa is touched. Blood flow may be inferred by: •
changes in colour;
•
photoelectric plethysmography;
•
temperature change (thermocouples);
•
laser Doppler.
Ganglia
Parasympathetic
Rhinometry may be used to assess blood flow indirectly.
Capillary leakage may be gauged by the appearance
ACh
of
labelled albumen in nasal secretion or the disappearance of xenon from venous blood.
A number of combinations of blood flow may exist venous shunting and venous pooling. Three main varia
1. Hyperaemia with both shunting and venous
congestion.
NA
====�===�;�(�' �===F==��� �(C
Sympathetic
-----�>====F�NA�� +
NPY
depending on the balance between arterial flow, arterio tions .are seen clinically:
Mucosa
Sensory
Figure 106.9
�
A
The autonomic nerve supply of the nose is
mediated by substance P (SP), acetylcholine (ACh), vasoactive intestinal polypeptide (VIP), noradrenaline (NA) an d neuropeptide Y (NPY). See text for details.
,.
� -
I
1364 I
PART 13 TH E NOSE AN D PARANASAL SIN USES
ganglion,
Sensory nerves
near
blood vessels and
under the surface
epithelium.35
Olfaction will be considered separately. The trigeminal nerve supplies sensation. The ophthalmic and maxillary nerves supply the nose. They arise in the trigeminal ganglion. It is uncertain what modalities the nasal mucosa appreciates but temperature, pain (or discomfort) and touch or irritation can be appreciated. There is some evidence that sensory nerve endings have HI receptors.30
Reflexes These may be mediated through the brainstem but axon reflexes may occur through sensory nerves alone.
Cold receptors sense airflow and there are more nerve
endings near the nasal vestibule.3 1 The rate of cooling is important. Receptors can be stimulated by the menthol, giving rise to an apparent increase in airflow.32
AXON REFLEXES
Substance P, a vasodilator, transmits the antidromic reflex.
Neu rotra nsmitters
and
initiated by
mechanical
irritation
P is also able to liberate histamine from mast cells. This
Parasympathetic and sympathetic nerve fibres supply the vasculature
It may be
or via histamine from mast cells. Once released, substance
glandular
epithelium.
Postganglionic
fibres have more than one neurotransmitter. Classical
amplifies the response. The concept of neurovascular reflexes and mast cell reactions being separate entities may need to be revised.
cholinergic antagonists do not block parasympathetic vasodilation completely.33 In addition to acetylcholine (ACh) and noradrenaline, neuropeptides are present in sympathetic, parasympa thetic and sensory nerves.34, 35 Detection is by immuno fluorescent techniques.
REFLEXES FROM NASAL STIMULI
Chemical irritation, temperature change and physical stimuli may cause widespread cardiovascular and respira tory responses. The degree depends on the intensity of stimulus and ranges from sneezing to cardiorespira tory arrest. Sneezing is associated with facial movements,
PARASYMPATHETIC
lacrimation, nasal secretions and vascular engorgement.
ACh is the main parasympathetic neurotransmitter but vasoactive intestinal polypeptide (V IP)
is present in
postganglionic fibres. There are specific V IP receptors on blood vessels but not within glandular epithelium. Transmitters probably act in combination. ACh acts on blood vessels and glands. ACh produces widespread vasodilation and increased glandular activity. If the rate of firing is low, then ACh probably acts alone on blood vessels. At higher rates, V IP causes atropine resistant vasodilation. ACh suppresses V IP release by negative
More usually, a change in respiratory rate with closure of the larynx and a variable cardiovascular response occurs. Sensory stimulation can result in intense vasocon striction of skin, muscles and visceral arteries. It is accompanied
by
lowered
cardiac
output.
This
is
a
modification of the submersion reflex, which diverts blood away from skin to the brain. When patients have an endotracheal tube passed through the nose, it may give rise to an unexplained bradycardia.
feedback.36 ACh is secretory motor for glandular tissue alone but V IP's effect on neighbouring blood vessels may indirectly affect secretion.
NASOPULMONARY REFLEXES
SYMPATHETIC
associated with increased ventilation of the homolateral
Increasing airflow through one side of the nose is
Noradrenaline is the main postsynaptic transmitter with ACh
acting at
neuropeptides,
the
postganglionic
synapses. Various
including neuropeptide Y
(NPY)
and
lung. Blowing air through the nose causes the bronchiole muscle to relax on the same side and increase respiratory activity.39
pancreatic polypeptide are also present. NPY is probably the more effective. It causes only arteriolar constriction.37 Avian pancreatic polypeptide is morphologically similar to substance P and shares its action of vasodilation.38
SENSORY
Some C fibre sensory neurones contain the neuropeptide, substance P. They are present in the sphenopalatine
REFLEXES ACTING ON THE NOSE
Exercise, emotion and stress may cause vasoconstriction. Sympathetic nerves increase tone and stellate ganglion block abolishes it. Nasal vasoconstriction occurs with increased arterial CO2, and is mediated by chemorecep tors. Hypoxia has the same effect. Hyperventilation will cause nasal congestion.
Chapter 106 Physiology of the nose and paranasal sinuses I
CUTANEOUS STIMULATION
Cocaine blocks the uptake of noradrenaline into the
Heating the skin of the feet, arm or neck will produce an increase in nasal resistance. Cooling results in vaso constriction. Adaptation is followed by rebound. Pressure to the axilla or lying on the dependent side will cause 4O nasal blockage.
nerve
endings
and
this
resuJts
in
vasoconstriction.
Drugs used for hypertension may give nasal obstruc tion by blocking sympathetic activity. Reserpine was the worst. Methyldopa and �-blockers may all cause nasal symptoms.
Parasympathomimetics and their antagonists
CENTRAL CONTROL
The hypothalamus controls cardiorespiratory respon ses. Stimulation causes marked nasal vasoconstriction. Exercise, fight and flight reflexes and reflexes following emotional change are coordinated by the hypothalamus. The relationship between the rhinencephalon and nasal function needs
1365
further evaluation.
Vagal overactivity
causes prolonged congestion and nasal obstruction in
Intravenous pilocarpine and carbachol cause nasal Con gestion, vasodilation and watery secretions. These actions are blocked by atropine and are a cholinergic effect. Atropine resistant vasodilation is mediated by VIP. Other mediators, such as histamine, are present in normal nasal secretions and may cause vasodilations.
some patients. Migraine may result in nasal symptoms, usually congestion and clear rhinorrhea.
Histamine and antihistamines
D RUGS ACTING ON THE VASCULAR TISSUE OF THE NOSE Four groups are important clinically
The pharmacology of histamine is complex and both HI and H2 receptors have been demonstrated in the nasal mucosa, with HI receptors being the predominant ones. H3 receptors are not present. Histamine vasodilates by
(Table 106.3):
relaxing vasculature musculature and shrinks capillary
1. sympathomimetics and antagonists;
endothelium. Plasma leaks from capillary walls. It irritates
2.
parasympathomimetics and antagonists;
the sensory nerve endings and sneezing results. Histamine
4.
local anaesthetics.
3. histamine and antihistamines;
is present only in the mast cells and basophils. Histamine, although not as powerful as other inflammatory media tors from mast cells, is present in the greatest amount. It accounts for some of the mast cell properties.
Sympathomimetics and their antagonists
Antihistamines are widely used in medicine and are a
T he naturally occurring sympathomimetics, noradrena line and adrenaline, act mainly through Cit-receptors, although
there
may
be
Cirreceptors
which
have
a
physiological role. Compounds acting on Cil-receptors cause vasoconstriction, whereas the agonists such as isoprenaline act on Ci2-receptors and cause vasodilation.
heterogeneous group of compounds. They have a number of properties,
which include blockage of Hl
recep
tors, anticholinergic activity, local anaesthesia and seda tion. Not all actions are present in each compound and second- and third-generation antihistamines have fewer central effects.
The main complications are rebound hyperaemia and occasional rhinorrhoea.
Local anaesthetics
Drugs acting on the nasal mucosa.
Local anaesthetics work by the action of an amide group. It blocks conduction through the transmembrane chan nels. Two main groups are lignocaine and its derivatives,
Sympathomimetics and their antagonists
Adrenaline and synthetic analogues Antihypertensives particularly � blockers
Parasympathomimetics and their antagonists Histamine and antihistamines
Atropine, pilocarpine Mainly H1 blockers
Loca I anaesthetics
Cocaine, lignocaine
Hormones
Sex hormones, thyroxine, corticosteroids
;
lary sphincters and so a vasoconstrictor is often combined with it. Both groups have systemic effects on the heart and central nervous system if given in high concentrations.
Antihistamines with this activity Sedative and nonsedative
......
and cocaine. Cocaine is both a local anaesthetic and a powerful vasoconstrictor. Lignocaine dilates the precapil
Hormones A close link exists between the anterior pituitary and the hypothalamus. A complex interrelationship is present between emotional states, the autonomic nervouS system
..
.. -----1-- --_ --=---___ _ __ �-:-___.____
_
1 366 I
PART 13 TH E N OSE AND PARANASAL S I NUSES
and the hormones of the body. In all animals, olfaction is
OLFACTION
part of sexual behaviour. Recent reviews cover the subject in more detaiL Olfaction
SEX H O R M O N ES
The
nasal
mucosa
rhoea
may
occur.
and modifies behaviour in m any
initiates
creatures. Man concentrates on audiovisual aspects, and is
susceptible
to
sex
hormones,
particularly oestrogens which it can concentrate. When oestrogen levels are
41, 42
high,
nasal obstruction with rhinor
Nasal
function
changes
during
menstruation, pregnancy and puberty in both sexes. High-dose oestrogen contraceptives were associated with rhinitis in some women.
yet
much
money is
spent
modifying
body
odour.
Olfactory compo unds need high water and lipid solubi lity. The solute in m ucus is presented to the sensory mucosa. Man discriminates a large number of different smells but the olfactory mucosa and pathway fatigues and subsequently recovers quickly. High levels of the cytochrome-P4S0 aid detoxification. Two tests are used clin ically, threshold and supra threshold. The latter is normally a fo rced choice test such as the University
THYROX I N E
of Pennsylvania smell identification test (UPSIT) . The
Hyperthyroidism may give rise t o rhinitis b u t the exact mechanism is unclear. Hypothyroidism is associated with nasal obstruction due to the deposition of mucopoly saccharides in the extracellular spaces of the submucosa.
best stimulus is produced by prolonged inspiration. Sniffing is not as effective. The
clinical importance
of testing is to distinguish patients who have
a
dis
order from those who malinger and seek compensation.
Table 1 06.4 classifies conditions that may be associated with disorders of the sense of smell and taste.
CO RTI eOSTEROI DS
Glucocorticosteroids affect nasal function indirectly by stabilizing cell membranes such as mast cells, lymphocytes and
vascular
endotheli um.
Ol factory area
Fluticasone may contract
smooth muscle of arterioles directly.
This varies between species, with dogs and rabbits having larger areas than man. Man has 200-400 mm2 with a density
o f apprOXImateIy 5
A D R E N A L M ED U LLA
.
x
1 04 receptor cells/mm2 . Receptor cells
Sympathomimetics p roduce a direct intense vasoconstric tion inside the nose.
conditions
Emotional states
Con genita l
Congenital craniofacial defects Tu rner's syndrome
Three different responses may be categorized.
Receptor expression Acq u i red
1. Fight or flight which causes vasoconstriction.
Tra um a
2. Sexual behaviour which p roduces a number of
Cri b riform and eth moid plate Cou n ter coup
different responses.
3. Stress causing vagal hypertonia.
I nfective
Post-neuropathic virus
N eoplastic
Mening ioma Olfactory neu roblastoma, other neopl asms
THE NOSE AND THE VOICE The nose adds quality -by allowing some air to escape through it. Sound resonates within the nose and mouth, if too little air escapes from the nose then rhinolalia
N e u rological
Epi lepsy
Degenerative
Age ing (physiolog ical) Alzhei mer's a n d Parkinso n 's d iseases Acids (e.g. H CI), a l ka l is (e.g. a m mon ia),
Toxic
org a n i c neurotoxins (e.g. phosgene), tobacco products
clausa occurs, if too much then rhinolalia aperta ensues.
The most effective resonance occurs at lower laryngeal frequencies. The sinuses have no effect on modifying voice. They may help with auditory feedback as trans mission of sound through the
facial skeleton helps
monitor voice quality. Many nasal
conditions
affect
the quality of the voice by blocking the p assage of air in expiration. Alterations are common in allergic rhinitis, the common cold and nasal polyps.
, /
Endocrine Psychiatric
,
Hypothyroid ism, Cushing's synd rome Psychosis
Iatrogenic Medica l
Cocaine - many others m ay be
S urgical
Surgery, accidental trauma, resections
im plicated I d iopath ic
/ /
./
Ch a pter 106 Physiol ogy of the n ose a n d pa ran asa l sinuses
I 1367
have modified cilia, which increase the surface area and
both increased and altered by hormones, particularly
project like normal cilia into the mucus. They are derived
the sex hormones.
from the basal cells, regenerating every month.
occur which are similar to colour blindness: a familial
In man, some genetic variations
lack of perception to certain odours is more common in males.
Stimulus Odours react with the lipid bilayer of the receptor cells at specific sites, which causes K + and CI - to flow out and thus depolarize the cells.43 After a latent period of up to
400 ms, a slow compound action potential, the electro olfactogram (EOG), is recorded from olfactory mucosa.44 The speed of the rising phase varies with intensity of stimulus. The recovery phase or falling phase is an exponential decay with a time constant of
0.9-1 .45 ms.
Discrimination Man is better at detecting the pleasantness of an odour rather than recognizing it. The pleasantness is largely cultural and therefore learnt. If two odours are mixed, the resulting intensity is always less than the sum of the two individually perceived intensities and is dominated by the stronger component.
Receptors Pathways Olfaction is mediated by G-protein coupled receptors in the cells which interact with a specific adenyl cyclase (type
Ill)
within
the
neuroepithelium.45
Adrenergic
and
There is
no
interaction
between
the
receptor cells.
Receptor cells are connected to the olfactory bulb by
muscarinic antagonists block some odour responses in
nonmyelinated nerve fibres prior to the cribriform plate.
olfactory receptor neurones whereas glutamine antago
These fibres synapse on olfactory glomeruli and approxi
nists do not, which suggests some degree of specificity.46
mately
Receptors are coded by between
acts as an integrator.
500 and 1 000 genes, but
25,000 fibres end on each glomerulus, which then Conduction time between the
receptor cells and the glomerulus is
each cell has one or two specific receptors.47
50 ms. Glomeruli fire
with an all or none response into mitral or tufted cells whose axons transport the signal through the lateral
Threshold
olfactory tract. Inhibition comes from feedback from high cortical centres.
Olfactory responses show both variations in thresholds and adaptation. Threshold concentrations can vary by
1 0 10 depending on the chemical nature of stimuli. The
threshold of perception is lower than identification: a smell is sensed before it is recognized. Threshold values vary widely between studies and reflect the nature of smell and different methods of detection. Thresholds depend on levels of inhibitory activity, which are generated by higher centres. Some animals, particularly dogs, have much lower thresholds.
Higher centres The
anterior
olfactory
nucleus
sends
impulses
to
the opposite bulb and to the ipsilateral forebrain through the anterior commissure. The primary olfactory cortex lies rostral· to the telencephalon and includes the . olfac tory
tubercle,
areas.
the
prepiriform
There are projections to
and
pre-amygdaloid
the thalamus where
they are integrated with taste fibres, and there are projections to the hypothalamus. Communication from
Ad aptation
the receptor cell to the brain ,stem occurs with only two
Olfactory responses show marked adaptation and thresh
synapses.
olds increase with exposure. Recovery of the EOG is rapid when
the
stimulus
is
withdrawn.
Adaptation
is
a
peripheral and central phenomenon. Cross adaptations are present between
odours at high
Trigeminal input
concentrations,
whereas cross facilitations occur near threshold values.
Most smell is independent of the trigeminal nerve, but at
Other factors affecting threshold
high
concentrations
irritation
occurs and
is
a factor in detecting the intensity of certain compounds, such as butyl acetate, and may account for
30 percent
of the odour intensity. 48 Patients who are anosmic Changes in nasal mucus and its pH will alter olfac
notice only sweet, sour, salt and bitter and irritation.
tory perception. Thresholds decrease with age and are
Irritation contributes to the nature of smell.
I
t
I
1 368 I
PART 13 TH E NOSE AN D PARANASAL S I N USES
septum in approximately
Classification of odours No satisfactory classification of odours exists but Amoore
has suggested that there are up to
20 percent of the population
and has no neurological connections with the central
30 primary odours for
nervous system. There is no correlation between its presence and human behaviour.
man, which he bases on the stereochemistry of com pounds.49
Spatiotemporal organization
is
important.
Man has difficulty in detecting and recognizing variation in intensity of more than
1 7 odours. Training is necessary
for scientific experiments and a 'good nose'. The science of
odours
requires
measurements
of
likenesses
and
differences. Wise and colleagues require three criteria: the resolution of small differences; scales of measure ments; and the avoidance of subjectivity.5o Most classi
THE PARANASAL SINUSES The physiological role of the paranasal sinuses is un certain. They are a contiriuation of the respiratory cavity and are lined by a respiratory mucosa. They share certain features with the nose but the responses are much less marked due to relatively poorly developed vasculature
fications are based on resemblance and odour profile.
and nerve supply. In man, their main interest relates to
Olfaction, ageing and behaviou r
age. While the ethmoids and maxillary sinuses are present
disease. Development of sinuses continues up to
Smell i s used in four main areas of behaviour: the detection and consumption of food; recognition; terri torial markings; and sexual behaviour. Perception de creases with age and neurodegenerative diseases, such
25 years of
rudimentarily at birth, the frontal sinuses develop after six but may be completely absent
( 1 0 percent). The
sphenoid sinus differs considerably in the degree of development. Whatever their physiological role is, it is of only minor importance.
as Alzheimer's and Parkinson's, have poor function that is not reversible. Since many elderly patients take medica tion, it is difficult to determine cause and effect.5 1 The most worrying problem is the association of cocaine and olfactory loss.
Mu cosa Respiratory mucosa runs in continuity from the nose. Goblet cells and cilia are less numerous in general but more frequent near the ostia and the blood supply is
EATING
Olfaction helps two aspects of eating: the recognition of food types and the initiation of digestion. Initiation of digestion is mediated via the lateral and ventromedial hypothalamus, causes salivation and increases output of
less well developed with no cavernous plexuses, which give the mucosa a pale colour. Since the nerve supply is less well developed, the sinus mucosa is able to give only a basic vasomotor response and increase mucus production with parasympathetic stimulation.
gastric acid and enzymes.
Drainage SEXUAL BEHAVIOUR
P heromones were first described in insects. They have been encountered widely in all animals. Three types of pheromone have been described: releaser pheromones;
Mucociliary clearance in the maxillary sinus is spiral and towards the natural ostium. 53 Drainage of the frontal and sphenoid sinuses is downwards and is aided by gravity, the blood supply is better developed in the frontal sinuses
primer pheromones; and imprinting pheromones. Bond ing occurs through neuroplasticity.52 The degree of
and the ostium is relatively large in the sphenoid sinus.
involvement in human behaviour is uncertain, but the
and may contribute to the total amount and effectiveness
influence of smell is probably underestimated since most of its activity occurs at the subconscious leveL
Secretions join the nasal mucus in the middle meatus of the nasal mucus.
Oxygen tension THE VOMERONASAL ORGAN This is a vestigial organ in man. It is important in reptiles
The P0 2 is lower in the maxillary sinuses than in the nose and it is lower still in the frontal sinuses. If the ostium
where molecules are presented by the tongue to it - hence
becomes blocked, the oxygen tension drops further.
the flicking tongue in snakes. It is an accessory organ of
Ciliary motion remains normal if the blood supply is
smell but differs from the olfactory area since it has no
adequate. If the blood supply is impaired, ciliary activity
pigment within the epithelium. Its function is more
is reduced and. stasis of secretions results. Levels of nitrous
related to taste. It can be found as a small pit on the nasal
oxide are higher in the sinuses than in the nasal cavity.
Chapter 1 06 Phys i o l ogy of t h e- n ose a nd pa ra n asa l sin uses
Osti u m size
I 1369
recognition and learning come late, prob ably after the age
in m an , but the sense is fully develope d
of two years Blockage of the natural sinus ostium results in a reduction
before the sinuses are .
o f ventilation and stasis of secretions. An ostium below " 2.5 mm predisposes to d Isease.
54
KEY POI NTS Pressu re changes Pressures in t h e maxill ary sinus vary
with resp iration but
l ag behind by 0.2 s. There is little fluctuation when the nose is p atent and the variation of pressure during quiet respiration is
+ / - 4 pascals, which reaches
1 7-20
m
a
pascals on exercise. If the nose is blocked, then pressure fluctuations are much more marked. Barotrauma is five
•
t imes less common than in the ear and is most frequently
m u( nc i l iary
tnJcrstand
m uc o s a .
seen in the maxillary sinuses and in divers.
•
Assess t he
dcara ncc. the aclion
sen e
)( u ru g
0(. Oldl and
on
t h nasal
t asl<.'.
Physiological fu nctions of the s i nu ses Th e functions of t h e sinuses are listed below: •
vocal resonance;
•
diminutio n of auditory feedback;
Defi ciencies in cu rrent knowled g e a nd areas for futu re research
•
air conditioning;
•
pressure damper;
•
red uction of skull weight;
two syste ms d i d not evolve independently. a n d
•
fl o t a tion of skull in water;
fu rth e r stu d ies a b o u t the e ffects o f the a uton o m i c
•
mechanical
•
he at insulation.
> Th e k n o w l ed g e of t h e i n te ract i o n betwee n the n e rvous and the i m m u n e systems is e l e m e ntary. These
rigidity;
transmitte rs a n d i m m u nomod u la tion are req u i red. Th e a i rway e q u iva l e n t of a p u re to n e a u d i og ra m i s re q u i red. Th e a p p l ication of so p h i sticated co m pu t e r tech no logy may so lve the p ro b l e m .
Comments
> Assess m e n t o f m u coci l i a ry fu nctio n i s l i m i ted a n d the va ri atio n s i n both h e a l t h and d i sease req u i re fu rth er
The vol u m e of the largest sinus is under 50 mL and so
rese a rch.
> The actions of med icat i o n s o n t h e nasa l m u cosa a re
contributes little t o air conditioning. A damper has to
h ave a l a rge volume to be effective. The reduction of skull
often not studied.
weight is small compared to the overall weight. Most of the
cranial activity is away from the sinuses so part in insulating the brain. Man h as long
little
they play ceased to
be an amph ibian. Apart from m ucus produ ction and
some strengthening of facial bones, the p ara n a sal si n uses
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*
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I 1371
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M su
t
th n s
Irw
RONALD ECCLES
Introduction Rh i nomanometry Acoustic rhinometry Peak nasal flow Other Subjective measurements
1372 1372 1375 1375 1375 1376
Key points Best clinical Deficiencies in current knowledge and areas for future research References
1377 1378 1378 1378
The data in this chapter are supported by a PubMed search the words rhino manometry, acoustic rhinometry and human. The data were supplemented by further searches and use of a personal database.
The nose acts as the entrance to the and its main function is as an airway. Measurements of the nasal airway function have mainly focused on nasal as this is a common problem associated with rhinitis. Measures of nasal obstruction usually involve measurement of nasal airflow or an assessment of the cross-sectional area of the The nasal can be considered as a simple tube, and measurement of the airflow through the tube and its pressure by means of can a measure of the resistance to nasal airflow or nasal conductance. The factor determining the resistance to airflow is the cross-sectional area of the nasal and this can be measured by means of acoustic rhinometry. Rhinomanome try provides a functional measure of the nasal airway resistance or conductance, whereas acoustic rhinometry an anatomical measurement of cross-sectional area or nasal volume. Rhinomanometry and acoustic rhinometry are the techniques used for measuring such as nasal the nasal airway but other spirometry and rhino stereometry, can also provide useful measures of nasal airflow.
Measurement of the nasal can be useful in the assessment of patients prior to any nasal surgery and nasal of measurements may also be used to assess the medical treatments of nasal congestion. This chapter will discuss the most commonly used and their relevance to measurements of the nasal research and clinical practice in rhinology.
RHINOMANOMETRY Nasal resistance to airflow is calculated from two measurements: nasal airflow and transnasal pressure. L 2 Both these are measured means of differential pressure transducers (manometers) and this is why the. study of nasal pressure and flow is termed (rhinomanometry, since manometry involves the measurement of pressure. Nasal airflow can be measured by means of a flow head that usually consists of a gauze resistance inside a cone-shaped tube. The pressure difference across the gauze by airflow the tube is used to measure airflow. Transnasal pressure can be measured by relating the pressure at the posterior u u .............u
Chapter 107 Measurement of the nasal airway
nares to that at the entrance of the nostril, which will normally be atmospheric pressure or nasal mask pressure. Active rhinomanometry involves the generation of nasal airflow and pressure with normal breathing. Passive rhino manometry involves the generation of nasal airflow and pressure from an external source, such as a fan or pump, to drive air into the nose. Active rhinomanometry can be divided into anterior and posterior methods according to the location of the pressure-sensing tube. In active anterior rhinomanometry, the pressure-sensing tube is normally taped to one nasal passage. The sealed nasal passage acts as an extension of the pressure-sensing tube to measure pressure in the posterior nares. With this method, nasal airflow is measured from one nostril at a time and the pressure-sensing tube is moved from one side of the nose to the other. Therefore, the nasal resistance is determined separately for each nasal passage and the total resistance is then calculated by summing the values as shown in. the formulae below. In active posterior rhino manometry as shown in Figure 107.1, the pressure-sensing tube· is held in the mouth and detects the posterior nares pressure when the soft palate allows an airway to the mouth. Total nasal airflow can be measured from both nasal passages simultaneously. The right and left nasal airflows can be measured separately by taping off one nostril at a time. Total nasal resistance can be determined directly from the total nasal airflow and trans nasal pressure with this method. A disadvantage of this method, when compared with the anterior method, is that not all subjects can obtain an airway around the soft palate into the mO}J-th. With some training of subjects it is possible to obtam satisfactory results from approximately 90 percent of subjects. Passive rhinomanometry involves the direction of an external flow of air through the nose and out of the
I 1373
mouth. The method may involve either measurement of a driving pressure at a constant flow or measurement of the flow at a constant pressure. Passive rhinomanometry is particularly useful if it is necessary to separate the upper and lower airways for experimental work. Active anterior rhino manometry, using surgical tape to seal a pressure-sensing tube into the nasal passage, is one of the most commonly used methods for clinical determination of nasal resistance. Nasal airway resistance can also be measured by use of a head-out body plethysmograph (displacement type) and, with this method, the flow head is located on the side of the body-box and the pressure-sensing tube is passed along the floor of the nasal cavity. This method has the advantage that the nose is unimpeded by any mask. 1 When making measurements of nasal airway resistance, it is important to take several measurements with repositioning of the mask between measurements. This is to control for air leaks around the mask which are a common source of error. A single measurement of nasal airway resistance is unreliable and a standard operating procedure should be implemented to prevent investigator bias when gathering data. 3.4 Nasal resistance to airflow may be calculated from the following equation: R = AP/V
where R =resistance to airflow, in cmH 2 0llitre per second or Pal cm 3 per second; 6P =transnasal pressure, in cmH 2 0 or Pa and V= nasal airflow, in litre/s or cm 3/s. This equation is a compromise that has been generally accepted by rhinologists and it does not take into consideration the separate components of laminar and turbulent airflow? A plot of the dynamic relations of transnasal pressure and flow on an xly plotter shows a curvilinear
~-----Face
mask
- -.....I----Flow head
Pressure sensing tube
Figure 107.1
The techn ique of posterior
rhinomanometry involves a pressure-sensing tube in the mouth that detects the changes in pressure in the posterior nares, and a flow head to measure nasal airflow.
,
I i
,-
j
1374 I PART 13 THE NOSE AND PARANASAL SINUSES relationship for the AP/V plot. Nasal airflow increases with increase of trans nasal pressure, but at higher pressures there is a limitation of flow due to the increased frictional effects of turbulent airflow. The flow-limiting effect of nasal alar collapse is only apparent during rapid or close to maximum inspiratory manoeuvres. The curvilinear relationship between transnasal pressure and flow means that one cannot simply determine nasal resistance from the slope of the graph, as would be the case with a straight-line relationship. The slope of the AP/V plot varies along its length and, therefore, it is not possible to describe the curve with a single numerical value for resistance. It is, however, possible to define the resistance at any given sample point along the curve and this has been the solution recommended for a standardized measurement of nasal resistance. 2 The positive or negative pressure at the posterior nares results in airflow through both nasal passages. The right and left nasal airflows are normally asymmetrical due to the nasal cycle and therefore a single pressure value may relate to two different airflows. It is, therefore, sensible to standardize nasal resistance by measuring both nasal airflows at the same sample pressure point rather than by measuring transnasal pressures at the same sample flow point. Unilateral nasal airflow measured at a sample pressure point of 150 Pa and bilateral nasal airflow measured at 75 Pa are recommended as universal standards. 2 However, the Asian population cannot always achieve these pressures during normal quiet breathing and the lower sample pressures of 100 and 50 Pa, respectively, are generally accepted for nasal resistance measurements in Japan. Total nasal resistance to airflow can be either determined directly using the posterior method of rhino manometry or it can be calculated by combining the two separate values of nasal resistance for the two nasal passages as shown in the formula below: 1
1
1
- - - = --- +--R (total) r (left) r (right)
The reciprocal of total resistance is equal to the sum of the reciprocals of left and right resistance. When quoting values for total nasal resistance it should be stated whether the value was obtained by measurement of total nasal airflow using posterior rhinomanometry, or whether the airflows of the nasal passages have been measured separately. The use of a sample pressure point to determine nasal resistance is a compromise, as the single numerical value calculated as nasal resistance only describes one point on the AP/V respiratory curve. It is possible to sample the curve at numerous points and obtain an average resistance value with the aid of a microprocessor, and this technique has particular
advantages when comparing the resistance values of different segments of the respiratory tract.
Normal nasal airflow In adult subjects free from signs of nasal disease, mean total resistance has been reported to be around 0.23Pacm 3 s with a range from 0.15 to 0.39Pacm 3 s. 3 As a routine screening procedure in our laboratory, we normally consider a total nasal resistance to airflow of 0.3 Pa cm 3 s as an upper limit of the normal range. Cole considers any total airway resistance greater than 0.25 Pa cm 3 as obstructed. 1 Nasal resistance is at a maximum in the infant at around 1.2 Pa cm 3 S5, 6 and declines to the adult value at around 16-18 years of age and then shows only a slow decline with increasing age. 7 In a study on healthy male volunteers, a relationship between age and nasal resistance was reported, with resistance declining with increasing age from 0.6Pacm 3 s (age 5-12 years) to 0.29Pacm 3 s (age 13-19 years) and 0.22Pacm 3 s (age >20 years) in males. 8 The relationship between age and nasal resistance was similar in females but, in general, nasal resistance was lower in females than males. 8 If the nose is decongested by exercise or application of a topical decongestant, then this eliminates any physiological variation in resistance and allows one to investigate the anatomical factors influencing resistance. Studies by Broms9 have provided a table of predictive values for height and nasal resistance in the decongested nose that are useful in assessing the extent of any deviation from normality in patients with nasal skeletal stenosis. Total nasal resistance gives an overall measure of nasal function, however, it is a very crude measurement as it provides no information about the separate nasal passages. Rhinologists have a dilemma when assessing nasal function as the nose consists of two separate dynamic airways. The ophthalmologist or audiologist would never consider using a bilateral measure of vision or hearing when assessing function as this measure could fail to detect blindness in one eye or deafness in one ear. Similarly, the measurement of total resistance may fail to detect unilateral nasal obstruction. However, it is not very informative to quote the mean of unilateral resistance when measured over several hours because this mean value will have a large standard deviation due to the instability of unilateral resistance. The range of unilateral nasal airway resistance in a group of healthy volunteers when recorded over a six to eight hour period has been shown to vary from 0.36 to 1.36 Pa cm 3 S10 and 0.28 to 0.63 Pa cm 3 S.ll This indicates that there is often' almost a four-fold change in unilateral resistance associated with the spontaneous congestion and decongestion of the nasal venous sinuses. One way to overcome the dilemma of spontaneous changes in unilateral nasal resistance is to decongest the nose prior to assessment. This solution is of use to the
Chapter 107 Measurement of the nasal airway
surgeon whose main interest may be in assessing the extent of any nasal anatomical problem. 9 However, decongestion of the nose is of no use in studying nasal physiology and pathophysiology as it is the spontaneous changes in unilateral resistance that are of interest to the physiologist and clinician. One solution is to quantify the extremes of unilateral resistance or the amplitude of the unilateral changes in resistance that occur over a period of several hours. This approach has been used to determine the unilateral changes in resistance and to assess the efficacy of nasal surgery.12 The disadvantage of unilateral nasal measurements is that in order to assess the amplitude of changes in unilateral nasal resistance it is necessary to make measurements over several hours. The advantage of unilateral measurements are that they provide a comprehensive assessment of the dynamic nose rather than the crude snapshot that is provided by a single measure of total resistance. [****]
I 1375
2
and this increases on decongestion to 0.9 cm 2 with a range from 0.5 to 1.3 cm2.14 The diagnostic value of acoustic rhinometry has been investigated by Lenders and Pirsig 17 who could distinguish various deviations of nasal structure, such as valve stenosis, septal deviation, turbinate hypertrophy and tumour masses. The accuracy of acoustic rhinometry like rhinomanometry is dependent on the interface between the equipment and the nose. For example, the cross-sectional area of the nasal vestibule is susceptible to distortion if a tube is inserted into the nose. Mispositioning of the nasal tube and air leaks are just as likely to give spurious measurements with acoustic rhinometry as face mask leaks with rhino manometry, but with care the technique of acoustic rhinometry provides reproducible data. The resolution of acoustic rhinometry is also limited by the speed of sound and this means that the maximum linear resolution of this device can only be around 7 mm. lS [****] 1.2 cm
ACOUSTIC RHINOMETRY Acoustic rhinometry has been developed from methods previously used to measure lower respiratory tract resistance. The method consists of generating an acoustic pulse from a spark source or speaker and the sound pulse is transmitted along a tube into the nose. The sound pulse is reflected back from inside the nose according to changes in the local acoustic impedance which are related to the cross-sectional area of the nasal cavity. The reflected sound is detected by a microphone, which transmits the sound signal to an amplifier and computer system for processing into an area distance graph. The cross-sectional area measurements obtained with acoustic rhinometry correlate extremely well with area measurements made by computed tomography scans, and nasal airway resistance measured by rhinomanometry, but the accuracy of acoustic rhinometry is unreliable in the posterior part of the nose, especially when the nasal passage is congested. 13, 14, 15 A major advantage of the technique of acoustic rhinometry is that it provides a measure of nasal crosssectional area along the length of the nasal passage, unlike rhino manometry which is limited to measuring the narrowest point of the nasal airway. The plot of crosssectional area against distance can also be expressed as nasal vol~e for given distances along the nasal passage. Technical specifications for standard operating procedures for acoustic rhinometry have been standardized as regards the accuracy and repeatability of measurements and the acquisition of data. 16
PEAK NASAL FLOW The peak inspiratory or expiratory airflow through the nose associated with maximal respiratory effort can be used as a measure of nasal conductance. The measurement is effort dependent and is less sensitive than rhino manometry or acoustic rhinometry in determining small changes in conductance. 19 Expiratory measurements are likely to cause expulsion of nasal secretions into the measuring instrument and inspiratory flow measurements are likely to cause nasal alar collapse and flow limitation. Simple peak flow instruments such as the Wright, miniWright and Youlten flow meters are often used to measure nasal peak flow with the use of a face mask. However, the use of more sensitive spirometers can improve the accuracy and reproducibility of nasal measurements. 20 Peak inspiratory flow (PIFR) and forced expiratory volume in one second FEV 1 have been proposed as the most reproducible spirometry measurements of nasal conductance. 2o Measurement of PIFR may be useful for the assessment of large changes in nasal conductance, such as those associated with nasal challenge and nasal decongestion,21 and for this type of work the measurement of peak nasal flow compares well with rhinomanometry for the assessment of nasal patency. [****]
OTHER TECHNIQUES Nasalance
Normal values for acoustic rhinometry The normal value for minimum cross-sectional area for a nasal passage is quoted as 0.7 cm 2 with a range from 0.3 to
Nasometry is an objective technique that is used for the assessment of the nasality of speech. It is based on a comparison of the acoustic output from the nose and the mouth for a given spoken word or phrase. Subjects with
I
I
( ~ .
6_
L
1376 I PART 13 THE NOSE AND PARANASAL SINUSES nasal obstruction tend to have hyponasal speech. Nasalance is the measure of the ratio of sound output from the nose compared with the sound output from the mouth, expressed as a percentage. There is an inverse relationship between nasalance and nasal airway resistance, and subjects with nasal obstruction will have a low measure of nasalance, whereas a subject with a patent nose, especially after decongestion, will have a high nasalance. 22, 23 Measurements are made using a pair of directional microphones mounted on either side of a hard plate that rests on the upper lip and acts as a sound separator. The measurement of nasalance is used to assess the quality of speech by speech therapists, and can also be used to study speech in patients with disorders of palatal function, such as cleft palate or following surgery of the palate. [****]
emptying of the nasal venous sinuses in the nasal epithelium24 that cause the tip of the turbinate to move in position by several millimetres. The changes in position of the turbinate can be plotted by directly observing the turbinate through a binocular microscope. The technique of measuring the position of the inferior turbinate by means of microscopy is termed rhino stereometry. The subjects head is fixed rigidly by the subject biting onto a tailor made tooth-splint fixed to the frame of the microscope stand. The changes in position of the turbinate can be measured in millimetres by means of a scale on the eye-piece of the microscope. Studies on the nasal cycle have demonstrated that the mucosal swelling causes the turbinate to change position by up to 3.5 mm. 27 Rhinostereometry has also been used to measure changes in the swelling of the inferior nasal turbinate associated with rhinitis medicamentosa. 28 [****]
Spirometry The airflow through the nasal passages is usually asymmetrical due to spontaneous congestion and decongestion of the venous sinuses in the nasal turbinates and septum. This phenomenon is usually termed a (nasal cycle' as the asymmetry of nasal airflow is not static but alternates over a period of several hours. 24 Most measurements of the nasal airways have been concerned with the measurement of resistance or conductance of airflow as nasal obstruction is a major symptom of rhinitis. However, measurements of resistance do not provide a direct measure of how the airflow is partitioned between the two nasal passages. With each breath the tidal volume is divided at the nose into two airstreams according to the relative resistance to airflow of each nasal passage. Deviation of the nasal septum is likely to cause an anatomical asymmetry of the nasal passages and influence the partitioning of nasal airflow. Measurement of the partitioning of nasal airflow can be made by measuring the volume of air expired from each side of the nose with a spirometer during a slow vital capacity manoeuvre. The introduction of small portable spirometers means that spirometry is not limited to the research laboratory and measurements can be easily made in the clinic. The partitioning ratio can be expressed on a scale from -1 to + 1 where 0 indicates equality of airflow through the nasal passages, -1 left side completely blocked, and + 1 right side completely blocked. Measurements of partitioning of nasal airflow have been used to monitor the physiological changes in airflow associated with the nasal cycle and after nasal decongestion they may be useful to assess the anatomical changes in airflow associated with nasal septal deviation, pre- and postoperatively.25,26 [****]
Rh inostereometry The inferior nasal turbinate exhibits spontaneous congestion and decongestion associated with the filling and
SUBJECTIVE MEASUREMENTS Objective measurements of the nasal airway, such as nasal airway resistance measured by rhino manometry, provide a functional measure of the nose as an airway but nasal sensations of airflow related to stimulation of trigeminal cold receptors are also of great importance. Nasal sensations are important in the study of nasal disease, as it is the patient's perception of nasal sensations (symptoms) that is of primary concern to the patient. However, in the assessment and treatment of nasal disease the clinician is mainly concerned with restoring normal nasal function to the nasal airway by reducing nasal obstruction by medical or surgical means. The clinician has various objective measures of nasal function, such as rhinomanometry and acoustic rhinometry, but the problem is that these objective measures of nasal function do not always correlate with the patient's own assessment of nasal sensations, such as the sensation of nasal airflow. 29 The reason for the lack of correlation between the perception of nasal airflow and nasal resistance, as measured by rhino manometry, may be because the resistance to nasal airflow is primarily determined by the nasal valve area, whereas the symptoms of nasal obstruction may be influenced by other areas of the nose as well as the nasal valve area, as illustrated in Figure 107.2. Congestion in the ethmoid region may cause contact of ethmoid surfaces and a sensation of pressure and obstruction that would have little or no effect on nasal airway resistance. Similarly, pressure changes in the middle ear and paranasal sinuses may cause a sensation of nasal obstruction without any effect on nasal airway resistance. Another factor that may explain the lack of correlation between objective and subjective measures of nasal obstruction is that the nasal airway consists of two parallel airways and the total nasal conductance' may be near normal even if one nasal passage is obstructed. Subjects with nasal obstruction
Chapter 107 Measurement of the nasal airway I 1377
Congestion of ethmoid area
Subjective-------
Sensation influenced by mood, air temperature, cold receptors and menthol
Objective
Congestion of eustachian tube
Nasal resistance mainly influenced by nasal valve region
Fig ure 107.2 Factors that influence the patient's perception of nasal airflow and relationship to objective and subjective measures of nasal obstruction. Objective measurements are mainly determined by the cross-sectional area of the nasal valve region at the tip of the inferior turbinate. Subjective measurements are influenced by the stimulation of cold receptors in the airway and the patient's perception of obstruction may be influenced by menthol and mood. Congestion in the ethmoid area, ostia of paranasal sinuses and Eustachian tube cause a perception of congestion and pressure that is unrelated to any change in nasal airway resistance as these areas are distant from the nasal valve.
15
10 Nasal congestion score
5
Nasal resistance
0
-5~-.----~---~---~---
Pretreatment
10
40 Post-treatment time minutes
80
Figure 107.3 The effects of ingestion of an 11 mg I-menthol lozenge on subjective sensation of nasal congestion and nasal resistance to airflow in human volunteers with common cold. The subjective sensation of nasal congestion, measured on a 100 mm visual analogue scale, was significantly reduced ten minutes after ingestion of the lozenge but nasal airway resistance as measured by rhinomanometry was unaffected. Shaded symbols represent the values for the menthol-treated group and the open symbols represent the mean values for the placebo-treated group. Results taken from Eccles et O/?l
associated with acute upper respiratory tract infection have a total nasal airway resistance that is close to normal yet they still complain of nasal obstruction because one nasaJ passage may be severely congested whilst the other is
patent. 10 Objective and unilateral measures of nasal obstruction have been shown to have a much better correlation than combined measures for the two nasal passages, indicating that the nose should be assessed as two separate organs rather than a single combined airway.3o Studies on the effects of menthol on nasal sensation of airflow clearly demonstrate the lack of any correlation between objective measures of nasal airway resistance and subjective measures of airflow. 31 In patients with nasal obstruction associated with common cold, ingestion of a menthol lozenge causes a great improvement in the sensation of nasal airflow without any change in nasal airway resistance, as shown in Figure 107.3. This is because the menthol vapour causes an increase in the sensitivity of cold receptors that detect nasal airflow, and a perception of nasal decongestion, without any objective change in nasal resistance. Subjective scores of nasal symptoms provide the main outcome criteria for clinical trials on new treatments for rhinitis, yet our knowledge of the factors influencing the perception of symptoms is still very superficial. [****1
KEY POINTS • Rhinom nometry is gen rally ccepted a.~ the 'gold standaPd' o r the m u re.tneht f u
• Th
I
/ h
'(
!
riP'
1378 I
PART 13 THE NOSE AND PARANASAL SINUSES
>-
>r/ Nasal surgery for the treatment of nasal obstruction should be guided by measurement of nasal airway resistance pre- and postoperatively.
Deficiencies in current knowledge and areas for future research
>-
>-
There is no generally accepted standard measurement to assess the degree of obstruction of the nasal airway. Rhinomanometry is generally accepted as the 'gold standard' for the assessment of nasal obstruction but this technique is only available in research centres and is not generally used in the clinic. Even when rhinomanometry is used, there is a choice between various techniques such as anterior and posterior, and various sample pressures (75 Pa for posterior and 150 Pa for anterior) that makes it difficult to compare results from different laboratories. Standardization of rhino manometry was attempted in 19842 but little progress has been made since then. The new recommendations for standardization of rhinomanometry and acoustic rhinometry add little more than mathematical modelling to the older standardization recommendations. 32 The introduction of acoustic rhinometry was initially proclaimed as a method that would replace rhinomanometry but this has not taken place as the technique is not quicker or more reproducible. A major problem in measuring the nasal airway is the spontaneous vasomotor activity associated with the nasal cycle 24 as this means that the airway is not stable and that unilateral nasal conductance is a moving target. Total nasal conductance or resistance gives an overall picture of the nasal airway but it provides no information about the spontaneous changes occurring in the separate nasal passages. New measures of minimum and maximum unilateral nasal conductance describe the amplitude of the spontaneous changes in nasal conductance and this type of nasal measurement has started to be used to
assess the efficacy of nasal surgery aimed at treating nasal obstruction. 12 Measurements of the nasal airway will be restricted to research laboratories unless a cheap and portable instrument is developed for use in the clinical setting. However, the variability in unilateral conductance associated with the nasal cycle means that nasal measurements will always be subject to much more variability than, for example, the widely used clinical measures of lower airway function. More research is needed on the subjective measures of nasal airflow and nasal symptoms as this area is extremely important for patient satisfaction when treating rhinitis, yet there is little knowledge on the pathophysiology of nasal symptoms.
REFERENCES
*
*
1. Cole P. Acoustic rhinometry and rhinomanometry. Rhinology. Supplement. 2000; 16: 29-34. Good review of subject area. 2. Clement PAR. Committee report on standardisation of rhinomanometry. Rhinology. 1984; 22: 151-5. 3. Morris S, Jawad M, Eccles R. Relationships between vital capacity, height and nasal airway resistance in asymptomatic volunteers. Rhinology. 1992; 30: 259-64. 4. Carney AS, Bateman NO, Jones NS. Reliable and reproducible anterior active rhinomanometry for the assessment of unilateral nasal resistance. Clinical Otolaryngology. 2000; 25: 499-503. Demonstrates importance of measurement of unilateral nasal resistance as opposed to total resistance. 5. Polgar G, Kong GP. The nasal resistance of newborn infants. Journal of Pediatrics. 1965; 67: 557-67. 6. Stocks J, Godfrey S. Nasal resistance during infancy. Respiration Physiology. 1978; 34: 233-46. 7. Syaballo NC, Bundgaard A. Entholm P, Schmidt A, Widicombe JG. Measurement and regulation of nasal ai rfIow resistance in man. Rhinology. 1986; 24: 87-101. 8. Vig PS, Zajac OJ. Age and gender effects on nasal respiratory function in normal subjects. Cleft PalateCraniofacial Journal. 1993; 30: 279-84. 9. Broms P. Rhinomanometry. III. Procedures and criteria for distinction between skeletal stenosis and mucosal swelling. Acta Oto-Laryngologica (Stockholm). 1982; 94: 361...,;70. 10. Eccles R, Reilly M, Eccles KSJ. Changes in the amplitude -of the nasal cycle associated with symptoms of acute upper respiratory tract infection. Acta Otolaryngologica. 1996; 116: 77-81, 11. Flanagan P, Eccles R. Spontaneous changes of unilateral nasal aipflow in man. A re-examination of the 'nasal cycle'. Acta Oto-Laryngologica (Stockholm). 1997; 11 7: 590-5.
Chapter 107 Measurement of the nasal airway I 1379
* 12.
13.
14.
15.
* 16. 17.
18.
19. 20.
21.
!
/
Quine SM, Aitken PM, Eccles R. Effect of submucosal diathermy to the inferior turbinates on unilateral and total nasal airflow in patients with rhinitis. Acta Oto-Laryngologica (Stockholm). 1999; 119: 911-5. Shows how it is important to take a time series of measurements of unilateral resistance in order to monitor spontaneous fluctuations in nasal resistance. Hilberg 0, Jackson AC, Swift DL, Pedersen OF. Acoustic rhinometry: evaluation of nasal cavity geometry by acoustic reflection. Journal of Applied Physiology. 1989; 66: 295-303. Grymer LF, Hlberg 0, Pedersen OF, Rasmussen TR. Acoustic rhinometry: values from adults with subjective normal nasal patency. Rhinology. 1991; 29: 35-47. I\lumminen J, Dastidar P, Heinonen T, Karhuketo T, Rautiainen M. Reliability of acoustic rhinometry. Respiratory Medicine. 2003; 97: 421-7. Hilberg 0, Pedersen OF. Acoustic rhinometry: recommendations for technical specifications and standard operating procedures. Rhinology. Supplement. 2000; 16: 3-17. Good review of subject area. Lenders H, Pirsig W. Diagnostic value of acoustic rhinometry: patients with allergic and vasomotor rhinitis compared with normal controls. Rhinology. 1990; 28: 5-16. Fisher EW, Daly NJ, Morris DP, Lund VJ. Experimental studies of the resolution of acoustic rhinometry in-vivo. Acta Oto-Laryngologica (Stockholm). 1994; 114: 647-50. Clarke RW, Jones AS. The limitations of peak nasal flow measurement. Clinical Otolaryngology. 1994; 19: 502-4. Harar RP, Kalan A, Kenyon GS. Assessing the reproducibility of nasal spirometry parameters in the measurement of nasal patency. Rhinology. 2001; 39: 211-4. Holmstrom M, Scaddil1g GK, Lund VJ, Darby yc. Assessment of nasal obstruction. A comparison between rhinomanometry and nasal inspiratory peak flow. Rhinology. 1990; 28: 191-6.
22.
*
Williams RG, Eccles R, Hutchings H. The relationship between nasalance and nasal resistance to airflow. Acta Oto-Laryngologica (Stockholm). 1990; 110: 443-9. 23. Parker AJ, Clarke PM, Dawes PJD, Maw AR. A comparison of active anterior rhinomanometry and nasometry in the objective assessment of nasal obstruction. Rhinology. 1990; 28: 47-53. 24. Eccles R. Nasal airflow in health and disease. Acta Oto-Laryngologica. 2000; 120: 580-95. 25. Hanif J, Eccles R, Jawad S. The use of a portable spirometer for studies on the nasal cycle. American Journal of Rhinology. 2001; 15: 303-6. 26. Hanif J, Jawad SS, Eccles R. A study to assess the usefulness of a portable spirometer to quantify the severity of nasa I septa I deviation. Rhinology. 2003; 41 : 11-5. 27. Hallen H, Geisler C, Haeggstrom A, Graf P. Variations in cOl1gestion of the nasal-mucosa in man. Clinical Otolaryngology. 1996; 21: 396-9. 28. Graf PM, Hallen H. One year follow-up of patients with rhinitis medicamentosa after vasoconstrictor withdrawal. American Journal of Rhinology. 1997; 11: 67-2. 29. Quine S, Eccles R. Nasal resistance from laboratory to clinic. Current Opinion in Otolaryngology and Head and Neck Surgery. 1999; 7: 20-5. Good review of subject area.· 30. Clarke JD, Hopkins ML, Eccles R. Evidence for correlation of objective and subjective measures of nasal airflow in patients with common cold. Clinical Otolaryngology. 2005; 30: 35-8. 31. Eccles R, Jawad MS, Morris S. The effects of ora I administration of (-)-menthol on nasal resistance to airflow and nasal sensation of airflow in subjects suffering from nasal congestion associated with the common cold. Journal of Pharmacy and Pharmacology. 1990; 42: 652-4. 32. Clement PA, Gordts F. Consensus report on acoustic rhinometry and rhinomanometry. Rhinology. 2005; 43: 169-79.
108 Classification and differential diagnosis of rhinosinusitis
IAN S MACKAY AND VALERIE J LUND
Definitions
1380
Differentia I diagnosis
1383
Allergic rhin itis
1381
Key points
1384
Infectious rhinosinusitis
1381
Deficiencies in current knowledge and areas for future
Clinical forms of infectious rhinosinusitis
1382
sinuses
The data
research
1384
References
Nonallergic, noninfectious inflammmation of nose and
1384
1382
in this chapter are supported by a Medline search usmg the key words rhinosinusitis, rhinitis, sinusitis,
classification and differential diagnosis.
DEFINITIONS
provide a framework which acts as an aide-memoire and
Rhinitis is defined as infl anunation of the lining of the
following chapter is largely based on expert opinion, i.e.
nose, characterized by one or more of the following
the lowest form of evidence-based medicine, though as
allows comparison of like with like. Consequently, the
symptoms: nasal congestion, rhinorrhoea, sneezing and itching.} The ciliated respiratory mucosal lining of the
Table 108.1
Classification of rhinosinusitis.
nose and paranasal sinuses are, however, contiguous and
Classjfication
it would be rare for one to be affected without the other. The tenn 'rhmosinusitis' encompasses this and to the above
symptoms
one
anosmia, facial pain and headache. No single classification of rhinosinusitis but it is intended to act as
will satisfy all,
Rhinosinusitis can usefully be considered under the following headings: allergic, infectious and 'other', or
(Table 108.1), while the differ
ential diagnosis will include: polyps, mechanical factors, tumours, granulomas and cerebrospinal fluid rhinorrhoea
(Table 108.2). Considerable time and effort has- been devoted to the classification and definitions of rhinosinusitis in recent years. However, it should be remembered that there are no right or wrong systems and the main purpose is simply to
/ /
Intermittent (seasonal) Persistent ( perennial)
2
Infectious
Acute Chronic
an aide-memoire for the
clinician to quickly consider when making the diagnosis.
nonallergic noninfective
Allergic
can therefore add hyposmia,
Specific Nonspecifi c
3
Other
Occupational Nares
nonallergic rhinitis with eosinophilia
Hormonal Drug-induced Irritants Food Emotional Atrophic Gastro-oesophagea I reflux Idiopathic
naniper
Chapter 108 Classification and differential diagnosis of rh inosin usitis
Table 108.2
Differential diagnosis.
Allergic rhinitis.
Table 108.3
Featur
Sympfoms Intermittent
,
Polyps
2
Mechanical factors
Deviated septum
Less than four days a week
(seasonal)
Hypertrophic turbinates
2
AND less than four weeks
Persistent (p�rennial)
Adenoidal hypertrophy
4
5
Tumours Granulomas
More than four days a week AND for more than four weeks
Obstruction ostiomeatal complex
3
I 1381
3
None of the following:
Mild
Foreign bodies
•
sleep disturbance
Choana I atresia
•
impairment of daily activity
Benign
•
impairment of school or work
Malignant
•
troublesome symptoms
Wegener's granulomatosis
4 Moderate-severe
Includes one or more of the following:
Sarcoid
•
sleep disturbance
Midline destructive granuloma
•
impairment of daily activity
Cerebrospina I rhinorrhoea
such should not be eschewed lightly as such expert opinion is usually the distillation of wide clinical experience and
•
impairment of school or work
•
troublesome symptoms
occur strictly in conjunction with the allergen season.
I I, 12
[**1*]
well-conducted clinical trials. A good example of this is t he recent World Health Organization (WHO) document on allergic rhinitis and its impact on asthma.2
INFECTIOUS RHINOSINUSITIS Infective rhinosinusitis is one of the most common disorders
ALLERGIC RHINITIS Allergic rhinitis is a common, global condition affecting
10-25 percent of the population2 and may also affect the sinuses as part of the general involvement of the upper respiratory tract infection. The prevalence would appear 3 to be increasing. Although often mild� it can significantly affect quality of life,4 academic achievement S and work prod uctivity. 6 Allergic rhinitis is frequently accompanied by asthma. Other conditions include conjunctivitis, sinusitis and otitis media. Symptoms tend to decline with advancing age but there have been some cases of late - onset allergic rhinitis.7
[***]
The WHO initiative, Allergic rhinitis and its impact on asthma
(ARlA)2
have suggested that the terms seasonal
and perennial allergic rhinitis should be abandoned in favour of intermittent and
persistent (Table 108.3).
The
reasons given are as follows. •
Pollens and moulds usually produce seasonal symptoms but
in some areas they are perennial
allergens. 8,9 •
Symptoms of perennial allergy need not be presen t
•
by
general
prac titioners
and
sinusi tis is part of the common cold and hence affects almost everyone . In the USA, it has been doc umented that the paranasal sinuses are involved in 87 percent of patients with colds and it has been estimated t ha t between 0.5
and 2 percent of viral
upper respiratory tract infections (URTIs) are complicated
bacterial infection . 14 Chronic rhinosinusitis affects 5-15 percen t of the urban populat ion. 1 5 , 1 6 The prev al ence of sinusitis (146/1000 population) has been
by an acute
reported to exceed that of any other chronic conditionI7 and is apparently on the increase. It is estimated that between 30 and 50 percent of all patients seen by the family B practitioner suffer from some fonn of rhinosinusitis.I [**] Infectious rhinitis may be acute or chronic. A wide range of viruses may cause
acute infectious rhinitis
although there may be sinus involvement with secondary bacterial infection. The most common bacterial patho gens are Streptococcus pneumoniae and
Haemophilus
-influenzae.19 Chronic infectious rhinitis may be caused by specific organisms such as tubercu losis (Mycobacterium tubercu losis), rhinoscleroma (Klebsiella rhinoscleromatis), leprosy
(M.
throughout the year. •
encountered
otorhinolaryngologists.13 The acute viral form of rhino
(T.
lepra e), syphilis (Treponema pall-idum), yaws
Perennial symptoms may present with seasonal
pertenue) or glanders (Loefflerella mallei). Nasal and sinus
exacerbations.
infection may be caused by a considerable number of
10
Owing to the priming affect on the nasal mucosa
fungal
'induced by low levels of pollen allergens
Dermatacious group and the Aspergillus genus.
and minimal
persistent inflammation of the nose in patients with symptom-free rhinitis, symp t oms need not necessarily
agents,
Chronic host
of which
infection
defence
the most
may
deficiency;
also
this
be
common the
may be
are the
result systemic,
a
of
e.g.
I
.....
j
1382 I PART 13 THE NOSE AND PARANASAl SINUSES pan-hypogammaglobulinaemia,
19A
or
have episodes of acute infection. The symptoms may
AIDS) or a local problem) e.g. primary ciliary dyskinesia
deficiency
clinically resemble acute rhinosinusitis and, even after
(PCD). Patients with PCD may develop sinusitis and
successful treatment of the acute episode, the chronic
bronchiectasis as the cilia fail to beat mucus from the
rhinosinusitis remains a problem or may have been
upper and lower respiratory tract. This condition is
aggravated.
similar to Young's
syndrome when,
despite
normal
ciliary activity, mucociliary clearance is inhibited because the
mucus
is
too
viscid.
Both
conditions
may
be
It is estimated that 75 percent of antibiotics prescribed for rhinosinusitis are for the condition.
chronic form of this
(**]
associated with subfertility, PCD because the sperms or
Acute rhinosinusitis is difficult to define) particularly
cilia lining the Fallopian tubes are immotile and Young's
with regard to the duration of symptoms) which can 8, 9, 10 range from one day to four weeks?' after which the
due to azospermia associated with blockage of the vas deferens.
symptoms have completely resolved. If a further episode
[**]
occurs during a 12-month period) the term acute recurrent rhinosinusitis is used. Chronic rhinosinusitis is even more difficult to define, relying largely on a
CLINICAL FORMS OF INFECTIOUS RHINOSINUSITIS
temporal criterion of symptoms greater than 12 weeks. There are few histological or microbiological parameters
There are four clinical forms of infectious rhinosinusitis:
to support this and one is left with an ill-defined interval
rhinosinusitis)
between acute and chronic which is sometimes referred to
chronic rhinosinusitis and acute exacerbations of chronic
as 'sub-acute: The international working party16 favoured
acute
rhinosinusitis,
rhinosinusitis
recurrent
acute
(Table 108.4).
Acute rhinosinusitis may be described as a condition in
additional support from imaging, though this presup poses that all patients will undergo this investigation
which the inflammation and infection are of limited
which is certainly not the case in many countries and
duration, which clear spontaneously or following appro
has been revised. Furthermore, the role of bacteria in
priate treatment. Although acute episodes can recur, the
chronic rhinosinusitis is unclear and the condition may
mucosa returns to normal between bouts. However)
represent a background of inflammation against which
chronic rhinosinusitis may present in several ways - for
acute exacerbations occur due to secondary bacterial
example rhinosinusitis is termed chronic when acute
inflammation.
[*]
rhinosinusitis fails to respond to treatment and persists. At times, however, chronic rhinosinusitis may develop when there has been no well-defined acute stage. Some patients with chronic rhinosinusitis may, in addition, Table 108.4
Infectious rhinosinusits.
Acute rhinosinusitis
Occupational Occupational rhinitis may result from allergy to airborne
Acute onset of symptoms Duration of symptoms
<
12 weeks
Symptoms resolve completely
2
Recurrent acute rh inosinusitis
> 1 to < 4 episodes of acute rhinosinusitis per year Complete recovery between attacks Symptom-free period of> 8 weeks between acute attacks in absence of medical treatment
3
Chronic rhinosinusitis
imaging > 4 weeks after starting appropriate medical therapy ( with no intervening acute episodes) Acute exacerbations of chronic rhinosinusitis
agents in the workplace. These will include laboratory animals - rats, mice, guinea-pigs, etc.; grain; agricultural workers; bakers; wood dusts - particularly hard woods; mahogany, oreoko, western red cedar, etc.; and latex. Nonallergic factors include low molecular weight sensi tizers; platinum salts, colophony fumes (electrical solder) acid anhydrides and isocyanates which are used with resins and paints.20
[**]
Duration of symptoms> 12 weeks Persistent inflammatory changes on
4
NONALLERGIC, NONINFECTIOUS INFLAMMMATION OF NOSE AND SINUSES
Worsening of existing symptoms or appearance of new symptoms Complete resolution of acute ( but not chronic) symptoms between episodes
Nonallergic rhinitis with eosinophilia syndrome Nonallergic
(NARES)21
rhinitis
with
eosinophilia
syndrome
is characterized by the presence of nasal
eosinophilia in subjects who are often middle-aged with perennial symptoms of sneezing paroxysms, nasal itching, rhinorrhoea and, occasionally, loss of sense of smell. However,
they
lack
evidence
of
allergic
disease
as
determined. by skin tests and IgE levels. Some may represent an early stage of aspirin idiosyncrasy?2 They
Chapter 108 Classification and differential diagnosis of rhinosinusitis
often
respond
particularly
intranasal corticosteroids.23
well
to
treatment
with
rhinitic symptoms and other mechanisms are invariably involved in these responses.30
[**]
I 1383
[**]
Emotional
Hormonal Inflammation of the nose (and sinuses) may occur with
Emotional factors, such as stress and sexual arousal, are
puberty, pregnancr4,25 and changes during the menstru
known to have an effect on the nose, probably due to
al cycle.26 It has been reported in specific endocrine
autonomic stimulation.
disorders,
such
as
hypothyroidism
and
Hormonal imbalance may also be responsible for the dryness of the nasal· mucosa experienced by some post menopausal
women.
A
persistent
[**]
acromegaly.
rhinosinusitis
Atrophic rhinitis
may
accompany the last trimester of pregnancy and its severity
Primary atrophic rhinitis is a condition where patients
parallels the blood oestrogen level. Symptoms usually
complain of nasal congestion, hyposmia and an unpleasant
resolve at delivery. Strangely, in women with persistent
smell
(perennial) rhinitis, symptoms may improve or deterio
with headache and chronic sinusitis?1 The condition is
rate during pregnancy.27
in
the
nose
(ozaena),
occasionally
associated
characterized by foul-smelling crusts filling the nasal
[**]
cavity, which itself usually appears capacious. Atrophic rhinitis has been attributed to infection from bacteria,
Drug-induced rhinitis
such as
Klebsiella ozaenae,32 but these are considered to
be secondary rather than primary pathogens. However,
Nsaids ACEI B-blockers OCP
Many medications may be associated with the develop
primary atrophic rhinitis should be distinguished from
ment
secondary
of
rhinitis.
These
include:
aspirin
and
other
atrophic
rhinitis,
which
may
result
from
nonsteroidal antiinflammatory drugs (NSAIDs), reser
chronic granulomatous infections, infectious rhinosinusitis,
pine, guanethidine, phentolomine, methyldopa, angio
irradiation, radical nasal surgery and trauma.
tensin-converting
enzyme
(ACE)
inhibitors,
adrenoceptor antagonists, intraocular ophthalmic pre parations,
e.g.
�-blockers,
chlorpromazine
and
[**]
\1. oral
Gastroesophageal reflux
contraceptives.2 Rhinitis medicamentosa may result from the overuse of nasal decongestants,28 while cocaine abuse can result in rhinorrhoea, hyposmia and septal perforation.29
Gastroesophageal reflux has been implicated as a cause of rhinitis in both adults and paediatric patients.33, 34
[**]
[**] Idiopathic
Irritants Having excluded allergic, infective and (other' causes for Many patients will blame pollution while others are sure
rhinitis, there remains a group of patients where no
that air-conditioning affects their rhinitis. Little informa
specific cause can be identified. These patients often
tion is available on the effects of air pollutants. Skier's
complain that their symptoms are affected by change in
nose (cold dry air) and gustatory rhinitis (hot spicy food)
temperature, atmospheric pressure or humidity. Idio
have been described as specific conditions, though it is
pathic rhinitis is probably a better term than (vasomotor
difficult to distinguish between a normal physiological
rhinitis' as the exact mechanism remains unknown.
response and a disease entity.2
[**]
Food
DIFFERENTIAL DIAGNOSIS Since other conditions may mimic the symptoms of
Food intolerance can produce rhinitis in a number of
rhinitis,
ways. Gustatory rhinorrhoea may occur when eating hot
diagnosis as listed in
and spicy foods, whilst specific allergic and hypersensivity
it is
important to consider
Table
the differential
108.2.
Polyps probably represent one end of a spectrum of
reactions may occur to foods themselves or to colourants
inflammation
and preservatives. Also, alcohol may produce a physio
rhinosinusitis. Polyps seen in children should immedi
logical vasodilatation and nasal congestion and may . provoke symptoms due to allergy and hypersensitivity to components contained in alcoholic drinks. True IgE mediated food allergy almost never provokes isolated
arising
from
many
of
the
causes
of
ately suggest the possibility of cystic fibrosis and patients should be referred for appropriate investigation. Unilateral polyps, indeed patients presenting with any unilateral
symptoms,
should
always be treated
with
/
,I / hal
I . "'\ .
1384 I
PART 13 THE NOSE AND PARANASAL SINUSES
suspicion and malignancy must be excluded. polyps should be removed without delay
Unilateral for histological
assessment after appropriate imaging. This is especially important in children to exclude a congenital meningo encephalocoele. In addition, in this age group, unilateral mucopurulent rhinorrhoea may be the presenting symp tom of a foreign body. Choanal atresia present
at
if bilateral will
birth, but a unilateral atresia can easily be
missed. Watery rhinorrhoea should suggest the possibility of a cerebrospinal fluid
(CSF)
leak, particularly
if this
is
unilateral. Wegener's gran�lomatosis) although usually a systemic
condition,
often presents with symptoms of rhinitis. The
differential diagnosis will also include sarcoid and midline destructive granulomas which are
most
often T cell
lymphomas. The diagnosis requires a careful history and examina tion. The diagnostic tests and investigations are summar
ized in Table
108.5. Only a number of these would be
Deficiencies in current knowledge and areas for future research
applicable for any individual patient, depending on the history and findings on examination.
All these conditions and investigations are considered in detail elsewhere.
> It is intuitive, but unproven. that allergic rhinitis also involves the paranasal sinuses - this needs to be confirmed by appropriate cytological and immu nohistochemical stud ies.
> The classification of infectious rhinosinusitis relies heavily on the duration of symptoms, which is History
entirely arbitrary, and more robust indicators for
General ENT examination Endoscopy Allergy tests
chronic rhinosinusitis are urgently required. Rigid
� The factors that predispose individuals to persistent
Flexible
inflammation in 'chronic rhinosinusitis', in particular
Skin prick tests (SPT)
genetic predisposition. needs clarification.
Serum specific IgE (RAST) Nasal swabs Nasal challenge
)0 The relationship of inflammation versus infection in
Smear for cytology
chronic rhinosinusitis needs further work and, in
Swabs for bacteriology
particular, the role of fungi in initiating this process
Allergen
evaluated.
Lysine aspirin Methacholine Radiology
CT sinuses MRI (CSF leak, soft tissue tumours. etc..) Plain x-rays CT and MRI chest
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1.
Nasal mucociliary clearance
management of rhinitis. International Rhinitis Management
(NMCC) Ciliary beat frequency (CBF) Electron microscopy for
Working Group. Allergy.
*
2.
Acoustic rhinometry Olfaction
on Asthma.
3.
[qualitative)
2000: 1-214.
Aberg N, Sundell J, Eriksson B, Hesselmar B, Aberg B. to family history, upper respiratory infections, and
(quantitative)
Nitric oxide measurement
19): 1-34.
Prevalence of allergic diseases in schoolchildren in relation
Olfactory threshold detection Smell identification tests
(Suppl.
Organization Initiative on Allergic Rhinitis and Its Impact
Nasal inspiratory peak flow (NIPF) Rh inomanometry
1994; 49
Bousquet J, Van Cauwenberge P, Khaltaev N, Gruber Tapsoba T. Annesi I. Bachert C et al. World Health
ultrastructure Nasal airway assessment
International Consensus Report on the diagnosis and
residential characteristics. Allergy.
4.
1996; 51: 278-83.
Bousquet J, Bullinger M, Fayol C, Marquis P, Valentin B, Burtin B Assesment of quality of life in patients with .•
perennial allergic rhinitis with the French version of the
Chapter 108 Classification and differential diagnosis of rhinosinusitis
SF-36 Health Status Questionnaire. Journal of Allergy and
other selected studies. Journal of Allergy and Clinical Immunology. 1992; 90: 457-62.
Clinical Immunology. 1994; 94: 182-8. 5.
Simons FE. Learning impairment and allergic rhintis.
20.
Allergy and Asthma Proceedings. 1996; 17: 185-9. 6.
7.
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and Neck Surgery. 1992; 106: 693-700. 21.
Immunology and Allergy Clinics of North America. 1987;
1999; 41: 948-53.
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Spector SL. Overview of comorbid associations of allergic
22.
rhinitis with eosinophila syndrome a precursor of
99: S773-80.
the triad nasal polyposis, intrinsic asthma, and
Bucholtz GA, Lockey RF, Wunderlin RP, Binford LR,
intolerance to aspirin. Annals of Allergy. 1990; 64: 513-18. 23.
rhinitis with eosinophila (NARES syndrome): clinical and
D'Amato G, Ruffilli A, Sacerdoti G, Bonini S. Parietaria
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Sibbald B, Rin_k E. Epidemiology of seasonal and perennial
Clinical Immunology. 1981; 67: 253-62. 24.
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Journal. 1986; 79: 965-71. Ellegard A, Karlsson G. Nasal congestion during pregnancy.
26.
Ellegard X, Karlson G. Nasal congestion during the
Clinical Otolaryngology. 1999; 24: 307-11.
exposure and placebo challenge on the nasal membrane.
menstrual cycle. Clinical Otolaryngology. 1994; 19:
Journal of Allergy. 1968; 41: 123-9.
400-3.
Ciprandi G, Buscaglia S Pesce G, Pronzato C, Ricca V,
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Parmiani S et al. Minimal persistent inflammation is rhinitis and mite allergy. Journal of Allergy and Clinical
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Graf P. Rhinitis medicamentosa: aspects of
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Schwartz RH, Estroff T, Fairbanks DN, Hoffmann NG. Nasal
pathophysiology and treatment. Allergy. 1997; 52: 28-34.
Stammberger H et al. Infectious rhinosinusitis in adults:
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Throat Journal. 1997; 76: 12. Kennedy DW. Overview. Otolaryngology and Head and Neck Surgery. 1990; 103: 847-54.
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Holmstrom M et al. European position paper on
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* 19.
Henrikson S, Gundersen W. The aetiology of azaena. Acta
Pathologica et Microbiologica Scan din avica. 1959; 47: 380-6. 33.
Wald ER. Epidemiology, pathophysiology and etiology of
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Zohar Y, Talmi YP, Strauss M, Finkelstein Y, Shvilli Y. Ozaena revisted. Journal of Otolaryngology. 1990; 19:
Fokkens W, Lund VJ, Bachert C, Clement P, Hellings P, rhinosinusitis and nasal polyps. EAACI Task Force.
Bousquet J, Metcalfe D, Warner J. Food allergy. Report of the Codex Alimentarius. ACllnternational. 1997; 9:
Gwaltney JM. Acute community-acquired sinusitis.
Clinical Infectious Diseases. 1996; 23: 1209-25. 16.
28.
Immunology. 1995; 96: 971-9. Lund VJ, Mann W, Gwaltney J, Ohnishi T, Baquero F,
Schatz M. Special considerations for the pregnant woman and senior citizen with airway disease. Journal of Allergy
present at mucosal level in patients with asymptomatic
* 13.
Mabry RL. Rhinitis of pregnancy. Southern Medical
25.
Connell J. Quantative intranasal pollen challenges. II. Effect of daily pollen challenge, environmental pollen
12.
Jacobs RL, Freedman PM, Boiswell RN. Non-allergic
Allergy. 1991; 67: 534-40. pollinosis: a review. Allergy. 1992; 47: 443-9.
11.
Moneret-Vautrin DA, Shieh V, Wayoff M. Nonallergic
rhinitis. Journal of Allergy and Clinical Immunology. 1997;
pollen survey of the Tampa Bay area, Florida. Annals of
10.
Jacobs RL. Non-allergic chronic rhinitis syndromes.
Journal of Occupational and Environmental Medicine.
Stabluin JJ, Serbousek D et al. A three-year aerobiologic
9.
Schiffman SS, Nagle HT. Effect of environmental pollutants on taste and smell. Otolaryngology and Head
Cockburn 1M, Bailit HL, Berndt ER, Finkelstein SN. Loss of work productivity due to illness and medical treatment.
I 1385
patients. Digestive Diseases. 1998; 16: 111-7. 34.
Halstead LA. Role of gastroesophageal reflux in paediatric
microbial etiology and antimicrobial therapy of adults
upper airway disorders. Otolaryngology and Head and
with acute community-acquired sinusitis: a fifteen-year
Neck Surgery. 1999; 120: 208-14.
experience at the University of Virginia and review of
I
rin' {wi
II
itis
GLENIS
AND
DURHAM
1 386 1386 1387 1387 1388 1388 1388 1388 1392 1392
Definition Prevalence Key point Risk factors
Co-morbidities Aetiology: pathophysiology Key points Clinica I presentation
The data in this ARlA
1393 1393 1 395 1396 1 400 1401 140 1
Key point Diagnosis Key points Treatment points Best clinical Special circumstances Deficiencies in current knowledge and areas
1402 1 402
for future research References
are supported by references in the personal collection of the author, and those taken from the the Cochrane database
a Medline search of recent data using the term
rhinitis' linked with
avoidance, pharmacotherapy, immunotherapy, surgery,
aetiology, pathophysiology, co-morbidities, sinusitis and otitis media with effusion.
studies show wide variations in prevalence Rhinitis is defined
by a combination of two or
more nasal symptoms: running, blocking, itching and rhinitis occurs when these
sneezing. are the result of
rhinitis as shown in
109.1. This
and defines treatment
classification is however, in the
additional retention of the
term (seasonal' rhinitis is advisable as it has both diagnostic and
International Study of Asthma and noted the
in Childhood
of rhinitis with itchy-
watery eyes, in six to seven year olds as 0.8 to 14.9 percent
inflammation
exposure to allergen. The recent ARIA documentl has classified
simple
'working definitions' in standardized questionnaires. The
Seaso
nal rhinitis can be intermittent or persistent.
and in 13-14 year olds from 1.4 to 39.7 percent in the world.
different countries
[***]
The UK
of rhinitis (Figure 109.2). The
had a high
overall correlation between the rhinitis in school children was
of asthma and 'HF.UH','-U��L
p
on Air Pollution and
Adults
9651
Diseases in adults
in
a
questionnaire, plus assessment of atopy by serum testing
PREVALENCE Allergic rhinitis is a
with Phadiatop and total serum IgE. Evidence of allergic
global
in prevalence.2,3
rhinitis (rhinitis symptoms associated with atopy) was health problem and is
[***] Recent multinational
13.5 percent (females 12.6 percent, males 14.3 percent,
p <0.05). [***] The ,-"
of
Phadiatop and
Chapter 109
Allergic rh initis I 1387
Imp Intermittent symptoms •
•
Persistent symptoms •
< 4 days per week Or<4 weeks
>4 days per week and >4 weeks
�-------.
x
�------�
Mild • • • •
Moderate-severe One or more items
Norm al sleep
•
Normal d ai l y activities
No rmal work and school
•
No troublesome symptoms
• •
•
>20%
• •
<10%
Abnormal s leep Impairment of dally activities,
sport, leisure
Problems caused at sc hoo l or
work
Tro ub lesome symptoms
Classification of rh i n itis accord i ng to the ARIA guidel ines. Red rawn with permission from Ref. 1.
Figure 109.1
10-20%
Figure 1 09.2 Preva lence of rhinitis worldwide, 13-14 yea r olds. Oata from the Internatio n a l Study of Asthma and Al lergies i n Ch ildhood ( ISAAC) . Reprinted from Ref. 4 , w ith permission.
skin prick tests (SPTs) decrease significantly with age with odds of 23, 21.1 and 21 percent, respectively, with every ten year increase in age. Smoking was found to increase total
serum
IgE,
but
was
associated
with
prevalence of symptomatic allergic rhinitis.
a
lower
RISK FACTORS Genetics and family history 5q, 11q, 12q, 13 There is undoubtedly a genetic component in allergic rhinitis, as in other allergic disease.6 The best established risk factor for allergic rhinitis is a family history of allergy, especially of allergic rhinitis.7 Seasonal allergic rhinitis increases the risk of asthma significantly on the basis of analysis of all individuals and
of discordant twin pairs.8
[***]
The genetics of rhinitis
has not been studied as much as that of asthma and atopy,
/
tinz
/
J.
.. :. :
/1
1388 I
PART 13 THE NOSE AND PARANASAL SINUSES
because there is difficulty in precise definition of the
•
allergic rhinitis phenotype. However, there are several genes which appear to be involved in atopy. These include an
Living in cl veloped countri pollutionl chmate int ra tinn and good hy iene' celn to be risk factors.
area on the 5q chromosome, where genes exist for
interleukin OL)-4 and IL-13, with markers associated with the presence of a high level of serum IgE. Other possible susceptibility loci exist on chromosome 11q, chromosome 13 in the Japanese population and chromo some 12q. This data requires further investigation in large multieentre population studies.9
QUALITY OF LIFE Although not a severe disorder, allergic rhinitis signifi cantly alters patients' social life, affects learning perfor mance at school and work productivity.18 The costs
incurred by rhinitis are substantial.
Environment The increase in prevalence of allergic rhinitis observed over the last 40 years is unlikely to be due to changes in the gene pooL Rhinitis is more common in developed countries and increases in prevalence are seen with urbanization of nonwesternized societies. Many possible factors have been suggested, such as lifestyle changes, increased exposure to allergen, pollution and irritants, dietary
modifications
responsible
for
diminution
of
protective nutrients, decrease in infections, leading to a reduction in Th1-type immune response (the hygiene hypothesislO) and stress. Pollution certainly increases symptomatic rhinitis and diesel exhaust particles may induce a Th2-like inflamma tion.l1
[**]
Although proof of an aetiological effect is
lacking, a recent Italian study suggests an interaction between pollution and climate,12 suggesting that ozone, which is a secondary pollutant formed from nitrogen oxide and oxygen, may be relevant.13
[***]
Several studies support the hygiene hypothesis. These include reduced seasonal allergic rhinitis and allergic
CO-MORBIDITIES Other conditions associated with allergic rhinitis are asthma, sinusitis, otitis media, sleep disorders, lower respiratory tract infection and dental occlusion. The costs for these conditions should be considered when assessing the socioeconomic impact of allergic rhinitis. 1 Rhinitis and asthma are hnked by epidemiological, pathophysiological characteristics and by a common therapeutic approach. Rhinitis is a risk factor for the development of subsequent asthma, is a frequent cause of asthma exacerbations and there is evidence that effective rhinitis treatment reduces asthma.19 Moreover, asthma costs are increased in patients with allergic rhinitis?O
[***]
Therefore, patients with persistent allergic rhinitis
should be evaluated for asthma; the converse is also true.
A strategy combining treatment of both upper and lower airway disease appears to be optimal in terms of both efficacy and safety.1
sensitization in farmers' children compared to their peers
. the same village m ' a nonlarnll c · ng £amily. 14 living In
[***]
Recent evidence suggests that early exposure to animals may reduce allergic sensitization. A role for endotoxin has been suggested. Several studies have noted an inverse relation between atopy, seasonal allergic rhinitis (and asthma) and sib-ship size and order.1s Early nursery attendance also reduces subsequent atopy.16
[***]
These
data could be explained by early exposure to bacterial
antigens favouring a Th1 response through a CD14dependent pathway. The CD14 gene maps to chromo
some 5q 31.1, a candidate region for loci regulating total serum IgE.17
[*_***]
AETIOLOGY: PATHOPHYSIOLOGY ihis is complex, involving cells, mediators, cytokines, chemokines, neuropetides and adhesion molecules which cooperate in a complex network to produce the specific symptoms of allergic rhinitis and the nonspecific hyper reactivity.1 The reaction can be considered in four phases (see Figure 109.3): 1. sensitization; 2. subsequent reaction to allergen - early phase; 3. late phase reaction; 4. systemic activation.
Sen sitizati on Allergens such as grass pollen, house dust mite, cat dander
are harmless molecules which do not elicit
symptoms in nonatopic individuals. In atopies, these molecules are' inhaled and presumably not completely cleared by the mucociliary system. They reach antigen-
• _ .
"'\')\.l....
Chapter 109 Allergic rhinitis
I 1389
(dJ Inflammation
(oJ Sensitization
(b) Allergic reaction Figure 1 09 . 3
The four phases o f the allergic reaction i n the nose.
presenting cells in the nose, the most important of which are dendritic cells called Langerhans cells. These CD 1positive cells containing Birbeck granules increase after allergen challenge and in patients with allergic rhinitis. Antigen presentation is a critical first step in activating local T lymphocytes. The dendritic cells form a network in the human respiratory mucosa which is at its highest in the epithelial surface of the upper airways?} [****] They capture antigen, process it and present it to naive T cells in the local lymph nodes. This requires T-cell receptor recognition of a peptide fragment associated with a major histocompatibility complex (MHC) molecule plus co stimulatory signals such as CD28 and B7 or CD40 and CD40 ligand. Resting Langerhans cells are well equipped for antigen binding and processing, but require matura tion in order to efficiently stimulate resting T cells. The maturation signal may involve some form of danger such as a virus, or adjuvant such as diesel exhaust particles. If no additional signal is present then a T-cell response will not ensue. This is probably the normal case as the airways are continuously bombarded by pathogens, allergens and other irritants. Airway mucosal dendritic cells play an important part in determining primary sensitization or tolerance to antigens. In atopic individuals, Th2 cells predominate at the sites of allergic response. There is some evidence that antigen presentation by airway
dendritic cells leads to the preferential development of a Th2 response, possibly by selective cytokine production.22 In the secondary immune response, any cell expressing surface MHC class 2 may serve as an antigen-presenting cell. This includes the activated nasal epithelium. Once they have recognized antigen and become activated, Th2 cells secrete cytokines, mainly IL-4, IL- 13 and IL-S. They also activate B lymphocytes in the local lymphoid tissues, encouraging them to proliferate, migrate to the nasal lining and produce antibody. The cytokine pattern leads to antibody production of the IgE class. B cells are found in the epithelium and lamina propria of the nasal mucosa, comprising approximately 20 percent of the total lymphocyte population in perennial allergic rhinitis patients. Local switching of immunoglobulin production to 19B in the nasal mucosa has been demonstrated?3 [***] Once produced, the IgE is very rapidly and avidly taken up by local cells possessing FcER 1, i.e. mainly mast cells. Thus armed, mast cells are able specifically to respond to subsequent allergen contact. The patient is thus sensitized. Skin prick-testing reveals that around 30 percent of the population are sensitized in this way with positive responses to allergens, such as grass pollen. However, not all these individuals respond clinically to grass pollen with hayfever, although
1-
1390 I PART
13
TH E N OSE AN D PARANASAL SI N USES
nonresponders do have a 50 percent chance of developing
proteins
hayfever in the future.
rhinorrhoea, sneezing, obstruction and pain and have
via
the
action
of
kininogen.
Kinins
cause
been noted in nasal secretions following allergen chal lenge.45,46
Subsequ e n t reaction to al l e rgen: early phase
[***]
Studies with the bradykinin B2 antago
nist icatibant given prior to allergen challenge have demonstrated reduction of the nasal obstruction seen
With Much has been learnt about the allergic response from
after house dust mite and a reduction in nasal eosinophil
extra
infiltration associated with decreased nasal hyperreactiv
seasonal
allergen
challenge
with
grass
pollen.
ity following grass pollen.47
Symptoms of sneezing, rhinorrhoea and itch occur within minutes and are associated with increase in mediators such as histamine, leukotriene C4 and prostaglandin D2 in the nasal mucus.24,25, 26
[***]
These appear to emanate
from mast cells which are encouraged to degranulate once
*
[***]
Mast cell degranulation also results in the release of several
cytokines
which
are
present
as
preformed
mediators. These include TH2 cytokines such as IL-4, IL-5, IL-13, and proinflammatory cytokines such as IL-6,
[***]
their cell-bound IgE has been cross-linked by allergen.
IL-8, IL-I0 and TNF-alpha.48,49,50,51,52
Some of the mediators are preformed in mast cell
have also been noted to release granulocyte macrophage
Mast cells
cytoplasmic granules, others such as the leukotrienes
colony-stimulating factor (GMCSF), monocyte chemo
and prostaglandins are manufactured from cell mem
tactic protein (MCP) 1, regulated on activation, normal T
brane arachidonic acid which is broken down initially by
expressed and secreted (RANTES), macrophage inflam
phospholipase A2 and then metabolized by either the
matory protein (MIP)I-alpha and CC chemokines. Mast
cyclo-oxygenase pathway to prostaglandins or the lipoxy
cells possess CCR3 receptors and respond to MCP3,
genase pathway to leukotrienes.27
MCP4, RANTES and eotaxins.
Histamine causes rhinorrhoea, sneezing, pruritis and nasal obstruction.28,29,30
[***]
However, its effects on
The release of Th2 cytokines by mast cells may well be important in regulation of the IgE response.53
[***]
The
nasal obstruction are not marked and require relatively
number of mast cells increased in the nasal mucosa of
high concentrations. The response is of short duration.
patients
Action on sensory nerves induces itching and sneezing,31
epithelium during seasonal allergen exposure.54
its action on endothelial cells and blood vessels results in
This may partly explain the priming nature of allergen
vasodilatation, plasma exudation and oedema.32,33
stimulation.
[***]
with
allergic
rhinitis,
mainly
in
the
nasal
[***]
Histamine also increases ipsilateral glandular secretion by a direct effect on mucus cells and vessels and contralateral secretion through neural reflexes.34
[***]
It is probably
the major mediator of the early phase reaction, but is also relevant in the late phase, when it probably emanates mainly from basophils. Histamine also possesses proinflammatory and im munomodulatory properties.35 These include upregula tion of adhesion molecules on vascular endothelial cells, increased production of cytokines IL-6 and IL-8 by endothelial cells and activation of epithelial cells with consequent ICAM 1 expression and cytokine production. Prostaglandin
D2
is
the
predominant
Late phase respo nse Following nasal allergen challenge, especially if high doses of allergen are used, a late phase response ensues in up to half the individuals tested. This is inflammatory in nature and involves the ingress of cells such as eosinophils, basophils, mast cells, T lymphocytes, neutrophils and macrophages into the local reaction site.55
[***]
The main
symptoms are nasal obstruction and hyperreactivity.56
[***]
prostanoid
released following mast cell degranulation. It induces a sustained nasal obstruction and is ten times more potent than histamine.36
EOSI I\lO PHILS These cells, first described by Ehrlich in 1879 in the blood
Leukotrienes belong to the family of eicosanoids
of a rhino, are associated with asthma, skin and parasitic
generated by the lipoxygenase pathways. The sulphido
diseases.
peptide or cysteinyl leukotrienes, formally known' as the
recognized. In the peripheral blood they represent
slow reacting substance of anaphylaxis (SRS-A), play an
percent of circulating cells, they migrate into the tissue
essential role in asthma and rhinitis. They induce vascular
upon an appropriate signal by a mechanism which
permeability and oedema in the nose and are also
involves cytokines, chemokines and adhesion molecules.
involved in eosinophil recruitment.37,38,39 triene B4 induces neutrophil recruitment.4o
[*] Leuko [***] Both
GMCSF
Their
and
proinflammatory
IL-5
enhance
role
eosinophil
is
now
well
<1
recruitment,
terminal maturation and the expression of their adhesion
LTC4 and LTB4 are found in nasal lavage fluid in both
molecules. Chemokines such as RANTES and eotaxin also
early and late phase reactions to allergen challenge and in
act on eosinophil recruitment and possibly activation.
seasonal and perennial rhinitis.41,42, 43
[***]
Kinins may also be involved in allergic rhinitis, in early and late phases.44 These are generated from plasma
* Histamine is preformed, leukotriene and PGs are manufactured from membrane arachidonic acid
Once in the tissue, eosinophils mature and remain alive for days or weeks, depending on survival signals from their
local
environment
which
retard
apoptosis
Chapter 109 Al lergic rh i nitis (programmed cell death). Mature eosinophils can be seen
I 1391
becomes anchored and is then encouraged to diapedese
easily
through the endothelium into the tissue where it follows
recognized by their bilobed nucleus and red granules.
a chemotactic gradient to the reaction site, becoming
in nasal
mucosa and in
secretions,
they
are
These contain major basic protein (MBP), eosinophil
more activated as it does so. In any inflammatory
cationic protein (ECP), eosinophil-derived neurotoxin
disease,
(EDN), eosinophil peroxidase and beta glucuronidase.
generated
They
and
also
possess
small
including arylsulphatase
enzyme-containing B which
is able
granules
to
inhibit
are
also
capable
of
synthesizing
and
releasing cytokines, such as IL-3, IL-5 and GMCSF plus
cytokines
the
molecules
and
upregulation and
hence
chemokines of
activation
determines
the
pattern and nature of the inflammatory cell infiltrate. infiltrating normally
cell.
However,
basophils
which
are
not
detected in nasal mucosa or secretions are
number of basophils correlates with the severity of the
•
chemokines;
•
IL-8 MIP I-alpha;
•
transforming growth factor (TGF) beta-l which is
cytokines such as IL-4 and IL-13. T lymphocytes (CD4 + and CD25
prostaglandin EI, thomboxane B2 and platelet activating factor (PAF); •
reactive oxygen intermediates (ROJ);
•
other enzymes including histaminase. 58 eosinophil
products
Infiltrating basophils are activated and
late phase response.56 They may also be able to produce
lipid mediators, such as cysteinyl leukotrienes,
activated,
[***1**]
disease.61
are thought to be the major source of histamine in the
involved in fibrosis;
Once
adhesion
of
found at these sites in allergic rhinitis patients. The
proinflammatory cytokines and:
•
pattern
determines
In allergic rhinitis, eosinophils are the predominant
. I Ieu kotnenes. ' 57 cystemy Eosinophils
the
+
) are found in
increased numbers in the submucosa and the epithelium of allergic rhinitis patients. In the late phase reaction there is a significant correlation between the CD4 + T cell 2
increase and the number of infiltrating eosinophils.6 increase
local
[***J
Increased expression of IL-4, IL-5, GMCSF
at
vascular permeability and mucus secretion and cause
mRNA levels was also noted. In perennial rhinitis, there
further inflammatory cell influx. Toxic products such as
was an increase in CD4 + T cells and B cells in the nasal
nasal surface epithelium. CT changes in rhinosinusitis
mucosa, again with a TH2 cytokine pattern.63 [***J An increase in intraepithelial gamma delta T cells has been
have been linked to the number of eosinophils present in
described in perennial allergic patients. These are able to
the mucosa. 59
induce B-cell IgE synthesis.
MBP, ECP, EDN and ROI may induce an alteration of the
[**]
A significant increase in macrophages has been found in the nasal mucosa in both seasonal and perennial rhinitis. These are not reduced by topical glucocorticos
ENDOTHELIAL CELLS
teroids, unlike Langerhans cells which appear to be
Infiltration by effector cells is crucial to the development
eliminated from the mucosa after two weeks topical
of allergic rhinitis and asthma. Structural cells, such as
therapy.64
endothelial
cells,
participate
in
the
recruitment
of
[***J
leukocytes to the site of the allergic response by releasing chemotactic factors and modulating adhesion molecules. Nasal
endothelial
cells express increased intercellular
adhesion molecule 1 (ICAM-l) and vascular cell adhesion
These of course have barrier and mucociliary clearance
molecule 1 (VCAM-1) in patients with perennial allergic
functions. They are also capable of a much wider range of
rhinitis compared to normal controls. VCAM-1 expres
activities including release of chemokines, cytokines,
[***I**J
sion is related to the number of infiltrating eosinophils
eicosanoids and endopeptidases.65
and T cells. Local cytokines such as IL-l , IL-4, IL-13 and
epithelial cells is noted in asthma and rhinitis where they
Activation of
chemokines such as eotaxin and RANTES enhance local
show increased expression of adhesion molecules, in
adhesion molecule expression.6 0
creased
Endothelial cells also act as an important source of
expression
and
production
of
inflammatory
mediators such as IL-6, IL-8, GMCSF and TNF-alpha,
cytokines and chemokines, such as RANTES and eotaxin.
increased release of RANTES, eotaxin, growth factors and
Like epithelial cells, they express the HI receptor and are
metalloproteinases.66 The growth factors include stem cell
activated after stimulation by histamine.
factor which influences growth and survival of mast cells
The trapping of circulating inflammatory cells occurs in two stages: initial elevation of selectins such as P
and GMCSF
which performs a similar function for
eosinophils.
selectin and L-selectin causes rolling of bypassing cells
In allergic individuals, epithelial cells appear to be
along the epithelium - subsequently, up regulation of
more sensitive to air pollutants such as diesel exhaust
[***]
adhesion molecules such as very late activation antigen 4
particles or nitrogen dioxide.67
(VLA4)
epithelial cells express MHC class II molecules and may be
on
the
eosinophil
elevated VCAM-I on the
..... l ....
EPITHELIAL CELLS
allows
combination with
endothelium
---------------�=-='--
and the cell
A proportion of
involved in secondary antigen presentation.
1392
I PART
1 3 THE NOSE AN D PARANASAL SIN USES
FIBROBLASTS The role of fibroblasts in rhinitis has not been well studied. However, cytokines
and
they appear capab le of producing
chemokines
such
as
GMCSF,
1L-8,
RANTES and eotaxill.
NEUTROPHILS These are normal constituents of nasal smears, but are upregulated in infection. There is also evidence for minor
upregulation in allergic reactions . Thus, the allergic nasal mucosa is oedematous, cellular
lA and prostaglandin
and contains many proinfl ammatory molecules. It is not surprising that it demonstrates increased reactivity not only
to
subsequent
allergen
contact,
but
also
rhinnorr •
Oth
•
Th I
to
non specific challenges such as cold, dry air or pollutants.
rcgtiJ in
if
. pruritis
D2 "ilUsing
and
Th_ yt ki ma b ti() 0 the 19E re po te ph c immune re p. �
proxim tely half
0
Il('czin
I ob tru -t' �
c.xP{
,
n.
.
e.
ns:
I
occurri P Ii nt
J •
the in re of ('n. 'J pi ils, ba phil, cd!.. 1 lymrhol"yle:s (l ItrorhiJs nJ ('foph ges into L )eal ti II , all of which
involv
System i c activatio n
rna 1 n
Al though allergic rhinitis appears to be a local phenom enon, there is evidence of upregulation of production and release of eosinophi l and basophil precursors from the bone marrow in response to aller gen contact in the nose
contribute to rhe intlamm tory ft'sponse
•
or lung. The resultant circulating precursors are attracted to the reaction site and to other parts of the respiratory tract by selectins and adhesion molecules and infiltrate the tissue, where they mature .
This process is also evident
in nasal polyposis and may be responsible for some of the
68 notable rhinitis/asthma link,
which presents Wi nasal ohstrm:tinn and hypcnea ,tivlty, Eosinophils have a prointlammalory role. (;M( :SF, 11.-5, RANTES 31 d l'otaxjll. released by mast cells, re all involved in eosinophil recruitment, maluration and al,tivat' m. [0 inophils 'ccretc a number of products whi hi -rea e va culaf p rntl.'ahility, mucuus creli: m nd C' u e further inflammatory cdI influx s el) as tnxk pr duct hi -h may alter urfi l.C n sal epithelium. Structural cnil Hal, Irs participate in the recnlitment u� leukocytes hy releasing ht:lUotauti.... ta'tors anti mo�.hilating acJht.'sion moleenl . I ike epithelial loCUS, they poss ss HI receptors which an: activated h� i.tamin�. fpit Hal t:cU as well as to ir b rri rand Ollh:odli fy d ran c fun"f , I (.) rel . �c ('hcmokin ,('ytokines. eku n ids nd endnpcpr'Ja 't. I�bro lasts also produce l.ytokines and ('h( IlU i ncs. N ftropniJs: there is evitlcn('c of minor upregulation in Ilergk rcacti,)n . Ant'gen slimul ti n in the nos or IUllg ('auses the rci('.c)se of esollophil precur )rs from the bone marrow which cirl.:uJate to hoth -ftcS. ,
Ig E-I N D EPEN D E NT R ESPONSES
•
Some allergens, such as house dust
mites, are capable of
elic iting responses similar to those described above via their enzymatic proteolytic ac tivity which directly acti vates cells .69 They can ind uce cytoki ne and chemokine release from epithelial cells and induce airway infl amma tion independent of 19E, Der p 1 (the major house dust
•
mite allergen) is able to alter epit helial tight junctions, therefore i ncreasing permeability. Mast cell degranulation can also result via non - lgE mediated mechanisms.
r
'
Certain drugs, e,g. morphine,
can act directly on the mast cell membrane causing degranulation. This can also happen with calcium ionophore, certain anti-IgE molecules and codeine and aspirin,
some lectins, e.g. str awberries .
•
•
•
,
CLINICAL PRESENTATION Immediate-type allergic symptoms of sneezing, rhinor l rhoea and itch are easily recognized. Their temporal
;
'
/ j
;
,- o,.{
--'--::---=.-"--'-----"-J -1.._�
Chapter 109 AllergiC rhinitis •
proximity to the stimulus often leads to its identification.
Table 109 . 1
However,
allergy diagnosis.
perennial
allergic
inflammation
is
mainly
Comparison of skin prick tests and blood tests in
expressed as nasal obstruction, hyperreactivity and often
SPT
concomitant poor sense of smell. The sinus lining is also usually involved so that the picture is one of a chronic inflammatory rhinosiQusitis. Immediate symptoms of
itching, running and sneezing are rare, although they may follow removal from the allergen for a week or two followed by re-exposure, such as occurs after a holiday. These patients are often not identified as allergic by themselves
or
by their doctors,
and
may undergo
unnecessary operations for septal deviation or turbinate
Ti me for resu Its
Immediate result
Days to weeks
Cost
Cheap
Expensive
Safety
Safe - inhalant only
Very safe
Sensitivity
Sensitive
Slightly less
Affected by therapy
Yes
No
Other requirements
Training for
sensitive
hypertrophy before the true nature of their problem is revealed by adequate history taking, assessment of atopy by skin prick or blood testing and/or nasal challenge.
1393
Trained operator
performance and
and interpreter
interpretation
required
Adapted from Scadding, GK and Lund. VJ 2003. Investigative Rhinology. London: Taylor and Francis, with permission.
hypothyroidism and rhinitis medicamentosa should all be taken into consideration.
KEY POINT
Examinat i o n The patient should b e looked a t generally t o assess any obvious external features, such as an allergic crease or
ntervention.
allergic salute. Atopic dermatitis or conjunctivitis should be sought and the patient's respiratory state noted. A full ENT examination should then be carried out with particular emphasis on the nose. Allergic nasal mucosa is usually bilaterally swollen) pale or bluish in
skin prik test
DIAGNOSIS
colour, oedematous and covered with watery secretions.
Most allergic rhinitis patients can be diagnosed by a combination of history, examination and SPT or radio allergoabsorbent tests (RAST) for specific IgE.! Occa sionally, other tests may be necessary
(Table 109.1).
History taking should be thorough and may be aided by the use of a questionnaire. Presenting symptoms, symptoms of co-morbidities and general medical history, past
history
and
family
history,
occupational
However, this is not always the case and some patients have a normal looking mucosa or a reddened nasal lining, particularly if using nasal sprays. Examination
of
the
chest
with
measurement
of
pulmonary function should be carried out where there is persistent rhinitis or any suspicion of asthma or other pulmonary disorder.l
and
environmental exposure, dietary history and drug use
all need to be taken into account. The patient should
A llergy diagnosis
always be asked which is his or her main symptom since treatment needs to be directed towards this. Rhinorrhoea and conjunctivitis is more common in seasonal allergic
SKIN PRICK TESTS
rhinitis, nasal obstruction is more common in perennial
Rationale
rhinitis.
Allergen introduced into the skin causes degranulation of
The frequency, severity, duration, persistence, inter mittence or seasonality of symptoms should be queried. The severity of symptoms and impact on quality of life needs to be noted. Possible allergens at work and school
IgE-sensitized
mast
cells
with
mediator
release and
formation of a wheal and flare. SPTs are simple,
cheap and safe
(provided food
allergens are not used and no intradermal testing is
should also be documented. Occasionally, nonallergic
undertaken). In Newcastle) there were three systemic
triggers may appear to cause symptoms because of nasal
reactions and no deaths over ten years when
hyperreactivity secondary to allergy.
prick tests were undertaken. Though systemic reactions
32,000
skin
There is an extensive differential diagnosis of allergic
are very rare, all skin prick tests must be undertaken with
rhinitis70 (see Chapter 110, Nonallergic perennial rhini
emergency equipment, including injectable adrenaline,
tis),
immediately available.71 Staff training in skin prick testing
and
problems
such
as
CSF
rhinorrhoea,
1394 I PART 13 TH E N OSE A N D PARAI\JASAL SIN USES should include resuscitation training. It is my practice that
all patients presenting to the
Rhinology
clinic
[*H]
However, determination of IgE in nasal secretions
has not proved satisfactory.74
[H*/H]
undergo testing for allergy as a routine since chronic
Skin prick testing with food allergens is less reliable
allergen exposure produces chronic nasal symptoms, the
and less safe than for inhalant allergens. False positive
allergic nature of which may be missed unless the patient
results are relatively common, false negative ones can also
and physician are alerted to the possibility of allergy by
occur because commercial extracts are heat-treated. If an
positive skin prick test results.
unexpected negative result occurs to a commercial food
Method
testing with the fresh fruit (e.g. apple in the birchlapple
A drop of a standardized allergen extract is placed on the
syndrome).
extract, it may be worthwhile undertaking prick to prick
volar aspect of the forearm and then pricked into the skin using a lancet.72 It is usual to test to a batch of allergens at the same time. A positive control (histamine) and a negative control (saline or diluent) should be included. A separate lancet is used for each test which is read as the mean wheal diameter at than
2 mm
15
in under fives and
minutes. Reactions greater
3 mm
in older subjects are
regarded as positive. Positive results should be at least
2 mm
ship is not linear. Tests in which the negative control gives a positive reaction are invalid, as are those in which there no
Rationale Stabilized allergen is incubated with the patient's serum, any specific IgE binds to allergen and is identified by a second incubation with labelled anti-IgE.
greater than the negative control. The wheal size
does relate to the amount of IgE, although the relation
is
BLOOD TESTS FOR ALLERGY
positive
reaction
to
histamine.
Under
these
circumstances RAST testing should be employed. A small battery of tests; such as negative control, house dust mite, cat, dog, grass pollen and positive control, will diagnose the majority of rhinitis patients. In the case of early hayfever, tree pollens may be necessary; a three-tree mix is available in the UK. However, relevant plant allergens vary in different parts of the world and so local sensitivity patterns need to be checked. Other possible
TOTAL IgE This is rarely helpful in uncomplicated rhinitis since
50
percent of patients have IgE levels within the normal range. A more satisfactory alternative is the P hadiatop test which involves the use of several common allergens in a single test. It is reported as either positive or negative and is more sensitive and specific in the identification of atopy than is total IgE. However, it does not give individualized results for specific allergens and is unhelpful in sugges tions for allergen avoidance?5
[H*]
allergens include animals to which the patient has been exposed, moulds and occupational allergens such as latex.
SPECIFIC IgE
Exclusion
This can be undertaken by RASTs or by fluorescent assays
Skin prick tests should not be performed if the patient is
and
on antihistamines, has severe eczema, has had previous
RAST involves allergen bound to a solid phase, this is
enzyme-linked
immunosorbent
assays
(ELISA).
life-threatening anaphylaxis or has dermagraphism. Oral
incubated with the patient's serum and IgE molecules
corticosteroids do not interfere except at very high
bind to the allergen. After detailed washing, radiolabelled
dosage, dermal corticosteroids may reduce reactivity. Sensitivity and specificity allergy unless supported by the relevant history. Positive
10-15
RAST in which the
allergen is coupled to a cellulose carrier and anti-IgE is
A positive skin prick test is not indicative of clinical skin prick tests occur in
anti-IgE is added and the radioactivity is measured. A recent improvement is the CAP
25-30
percent of adults, only
percent develop symptoms. The risk of clinical
enzyme-labelled with a fluorescent substrate acting as the developing agent. This system has a higher sensitivity and
specificity than other RAST tests.76
[*H]
The ELISA test is
similar although the allergen is in the fluid phase and the
allergy increases with the size of the skin reaction. Patients
IgE is enzyme-labelled. The substrate for the enzyme is
who have positive skin prick tests and no symptoms are
added
sensitized: approximately half of these will go on to
photometrically. RAST tests are more expensive, delayed,
develop clinical allergic disease. Conversely, skin prick
take longer and no more sensitive or specific than skin
and
the
resulted
colour
change
is
detected
tests remain positive after the resolution of clinical allergy
prick
in some patients.
contraindications to skin prick tests, where skin prick
tests.
They
should
be
used
where
there
are
False negative reactions can also occur when allergy is
tests are unavailable or difficult to interpret. There is
localized. Recently, patients with intrinsic rhinitis were
usually good correlation between RAST and skin prick
shown to have histological changes in inferior turbinates similar to those seen in allergy, and over
20
percent of
them reacted positively on nasal allergen challenge.73
test results. RAST results show some relation to IgE levels.
At very low levels of IgE ( <20 kU11), it is unlikely that an individual RAST will be positive; at very high IgE levels,
Chapter 109 Allergic rhinitis I
there may be false positives due to nonspecific binding of IgE. RAST are often graded as 0 to 6 where 0 shows no significant specific IgE, 1 is a borderline value and 2 to 6 demonstrates inneasing levels. Table 109.1 shows a comparison of SPT and RAST.
NASAL ALLERGEN CHALLENGE Rationale
1395
15 percent decrease after six minutes of running/ exercise; or - 10 percent a.m./p.m. variation in diurnal measurements (20 percent if taking a bronchodilator).
In rhinitis patients, history regarding lower respiratory tract symptoms should be taken, together with examina tion of the chest plus some fonn of objective measure ment (peak flow, spirometry). 1
Allergen is introduced into the nose and any reaction is measured and compared to placebo. This is the gold standard of allergy diagnosis, but is rarely necessary. Its place is where a positive history is accompanied by a negative SPT and prior to initiating immunotherapy if the history is doubtful in occupational allergy, where rhinitis usually precedes asthma. The relevant allergen needs to be obtained in a suitable fonn, i.e. not containing phenol or other irritants. A placebo, preferably the diluent of the allergen, should always be employed initially. The allergen should be applied in gradually increasing concentrations with careful monitoring of both upper and lower respiratory tract symptoms. Both subjective (symptom scores, visual analogue scales) and objective (sneeze count, nasal inspiratory peakflow, rhinomanometry, acoustic rhinometry, spirometry or pulmonary peakflow) need to be employed. It is also possible to collect nasal secretions and measure mediators, cytokines or cells such as eosinophils. Lysine aspirin can be used in this fashion as a test for aspirin sensitivity. Whereas with allergen the nasal reaction is immediate, occurring within 1 to 2 minutes and being maximal at around 15 to 20 minutes, with aspirin the reaction does not begin until about 45 minutes after nasal application and may persist for many hours. Nasal challenge testing is time-consuming, difficult and requires extensive laboratory facilities. Resuscitation equipment and trained staff are also necessary. Guide lines for nasal provocation tests have been published.77
[**1*]
Most asthmatics have rhinitis; approximately one-third of rhinitic patients have asthma. The key indicators for diagnosing asthma are as follows: •
•
• •
history of recurrent wheezing/cough/difficult breathing/chest tightness; occurring or worsening at night/or with exercise/viral colds/furry animals/dust mites/smoke/pollen! temperature changes/emotions /aerosols/ drugs such as aspirin/nonsteroid antiinflammatory drugs (NSAIDs) or beta-blockers; wheezing on chest examination; reversible and/or variable airflow limitation: -' 15 percent increase in PEFRlFEVl 15 to 20 minutes after inhalation of a short-acting beta agonist (salbutamol, terbutaline); or
/
.. . _'""' .. /�_�_
--'- __..__._.__ . ________�.==d.., ___
� _____
d-
1396 I PART
1 3 T H E NOSE AN D PARANASAL SINUSES
SECON DARY P R EVENTI ON Expos u re to allergens
TREATM ENT
Management of allergic rhinitis includes allergen avoid ance, phannacotherapy, education and possibly immu notherapy. Surgery is rarely needed. Treatment strategies should involve both the upper and lower airway where the latter is also affected.
Allergens represent major provoking factors in allergic rhinitis in atopic, exposed and sensitized individuals. Major indoor allergens include house dust mite, domestic pets, cockroach and moulds. Seasonal rhinitis results from exposure to pollens, which vary dependent on geography and time of year. In northern Europe, tree pollens are prevalent in March-May, grass pollens in May-July, weed pollen throughout the summer and mould spores during summer until late autumn. In sensitized symp tomatic individuals, allergen avoidance is desirable and should be regarded as complementary to usual pharmacotherapy with antihistamines and topical intranasal corticosteroids. However, allergen avoidance measures are frequently expensive, time-consuming, impracticable or, in the case of pollens, not feasible. Theoretical approaches to house dust mite avoidance/ reduction are summarized below: [Grade D] •
A l l e rg e n avo i d a n ce a n d envi ro n m e nta l co ntrol
Avoidance strategies can be divided into primary measures that may prevent disease and secondary measures that may ameliorate established disease.
P R I MARY P R EVENTI ON
Early use of antibiotics with alteration in the gut flora and increased vaccinations in early childhood have been implicated as possible causal factors in the increasing prevalence of allergic diseases. However, information is currently insufficient to make firm recommendations.78 Similarly, restriction of allergenic exposure to inhalant allergens and highly allergenic foods during early life have been suggested. However, these strategies, at best, have resulted in the delay of onset of atopic sensitization and further studies are required?9 [***] Recommendations concerning prolonged breastfeeding (for four months or longer) are also controversial, although breastfeeding can and should be endorsed on other grounds. Smoking during pregnancy and early life, particularly in mothers, is strongly associated with an increase in the prevalence of atopic sensitization, rhinitis, and asthma.80 [*** ] Several studies are currently investigating the role of environ mental control around birth and its effect on develop ment of atopic disorders in high-risk families. Preliminary data from one study have indicated that obsessional house dust mite avoidance measures are associated with improvement in lung function at three years, although, paradoxically, an increase in mite sensitization as determined by skin testing was observed.sl [***] It is too early to determine long-term effects on atopic senzitation and disease. Results of further studies are awaited.
•
•
•
•
•
•
•
•
encase mattress and pillows in plastic covers or special allergen-proof fabric; hot wash bedding (55°C) and damp wipe mite-proof covers every one to two weeks; remove objects that accumulate dust or place in a cabinet; store clothing in drawers and remove unused clothing from the bedroom; remove upholstered furniture and replace with leather, plastic or vinyl furniture; remove carpets, replace with washable rugs, install hardwood floors; treat carpets with acaricide, 3 percent tannic acid, vacuum regularly (ideally not patient); use washable curtains or venetian blinds, clean every two weeks; replace or wash air filters on air conditioners every month to remove debris.
However, a recent meta-analysis failed to show an overall significant improvement in symptoms in house dust mite-sensitive adult subjects with bronchial asthma.82 [Grade A] Moreover, two recent trials failed to demon strate efficacy in adult patients with perennial rhinitis,83 and with perennial asthma.84 However, both these studies involved the single intervention of bed and mattress encasings. Whether more aggressive 'global' measures may be effective remains to be determined. Also, strategies for house dust mite avoidance in children with a more limited spectrum of allergen sensitivities are more likely to be successfuL However, even in this age group a recent trial in monosensitized children was ineffective.85 These recent results question the current practice as recom mended in national and international guidelines of routine recommendation of house dust mite avoidance measures, particularly since these measures are expensive, time-consuming and inconvenient.1
Cha pter 1 09
Allergic rh initis I 1 397
Patients with allergic rhinitis with or without asthma
determined. Although evidence from controlled trials is
who are sensitive to cats and dogs should be advised to
lacking, avoidance of occupational allergens is clearly
remove the animals or, failing this, not to replace them.
indicated in sensitized, exPosed and symptomatic in
[Grade D] Even following removal of a family pet, several
dividuals. The alternative is likely to be progressive
months of vigorous vacuuming and cleaning are required
symptoms
in order to effectively reduce allergen levels in the home.
known to occur in patients with occupational asthma.
Other measures to reduce exposure to cat allergen are detailed below: [ Grade D ] •
remove cat, replace upholstered furniture and carpets,
allergy
almost
never
causes
changes, isolated
as
is
nas al
involvement including the mouth, upper and lower airways, gastrointestinal tract and skin. Provoking foods include peanuts, tree nuts, fish, shellfish and fruit. Milk
•
if refusal: keep cat out of bedroom and other
•
wash the cat weekly using
•
replace upholstered furniture with leather, vinyl or
and egg allergy are common in young children and
commonly used rooms;
usu ally resolve by four to eight years of age although may
1 L of water;
occasionally persist into adulthood. Diagnosis of food allergy depends on a history of an association between
plastic and wash weekly;
onset of symptoms and the suspected food(s), together
remove carpets, replace with washable rugs or
with objective confirmation of IgE sensitivity by either
hardwood floors, clean regularly;
positive immediate skin prick tests or detection of raised
•
vacuum rugs with HEPA-filter vacuum cleaner;
•
increase ventilation with fans, air-conditioning or by
•
use HEPA-type air cleaner in rooms where patient
opening windows;
serum
allergen-specific
IgE
concentrations.
IgE tests
should only be selected on the basis of the history. Random 'screening' by use o f a panel o f food allergens is strongly discouraged since misleading false positive tests
spends majority of time; •
ultimately irreversible
symptoms, although rhinitis may occur with other organ
steam clean walls;
•
Food
and
electrostatic filters may be considered but are likely to
to irrelevant foods may commonly occur.
have limited value. Avoidance of pollen is frequently not possible. Simple measures include keeping windows in cars and buildings tight shut. Cars may be fitted with a pollen filter. Patients should be recommended to avoid grassy open spaces. Paradoxically, pollen counts are highest
in the late
afternoon and evening when lower temperatures result in pollen counts falling to ground level. [ Grade D ] Recently, individual intranasal filters have demonstrated
P h a r m a coth erapy Medications available for use in allergic rhinitis and their effects upon symptoms are shown in Table
109.2.
[ Grade
A] The ARIA guidelines recommend that treatment be given according to severity and duration o f disease
(Figure 109.4).
efficacy.86 [Grade A] Certain
occupational
exposures,
well
known
for
provoking bronchial asthma in adults, may also result in rhinitis symptoms. Examples include exposure to flour
These rapidly relieve running, itching and sneezing, but
in ' bakers, laboratory animal workers and exposure to latex rubber, particularly within the health professions. A
have little or no effect on blockage87 although there are *** ] recent exceptions (desloratadine, levocetirizine).88 [
history of occupational exposure should always be sought.
First-generation antihistamines, such as chlorphenari
In p articular, patients should be asked whether nasal
mine and diphenhydramine, should be avoided because
symptoms are worse within the workplace or for several
of sedation,
hours
following work and whether their symptoms
impairment which probably occur because the drugs
improve at weekends or on holidays. Exposure to known
cross the blood-brain barrier and interact with central
sensitizers
histamine
Ta ble 1 09.2
within
_
the
workplace
should
also
be
Pharmacolog ica l treatments and their effects in allerg ic rhinitj � . ,_ �
Sod ium cromog lycate Ora l antih istamines I p ratropium bromide Topica l decongestants Topica l corticosteroids Ora r corticosteroids Antileukotrienes
Ii;..- _
ANTI H I STAM I N ES
psychomotor
receptors.89
+
+ + + + + +
+ + + + + + + + + + + + + +
+/+/+ + + + +
+ + +
+
Oral
+ + + + /-
and
learning
second-generation
-------_---.
_ _ _ _
+ + +
retardation
1398 I PART
13
TH E NOSE AN D PARANASAL S I N USES
Moderate severe
Mild intermittent
intermittent
Fig u re 1 09.4
Basic treatment p l an for allergic rhin itis according to severity and duration. Redrawn with permission fro m Ref. 1 . percent or more if combined with antihistamine.97, 98
antihistamines act within an hour, topical ones within 1 5 minutes.90 Some antihistamines
[ * * *1
( notably terfenadine,
astemizole, diphenhydramine, hydroxyzine) i nterfere with potassium reuptake channels, causing QTc and
cardiac
arrhythmias.9 1 , 92
[ * *]
prolongation
Others
SO D I U M CRO MOGLICATE
(ebastine,
mizolastine, loratadine) have the potential to do this
at
This
high doses92 so care m ust be taken not to overdose, nor to
spray
is
weakly
effective
all
against
rhinitis
symptoms, but needs to be used three to four times daily
combine them with other drugs metabolized by cytokine
and this limits compliance. Its safety means that it is
P45 0 , such as erythromycin, ketoconazole and grapefruit
useful for small children (less than four years) for whom a
juice, nor should they be used in patients on anti
topical corticosteroid is not available.99
arrhythmics, those with low potassium or a congenital prolonged QTc interval. Cetirizine, fexofenadine and desloratadine do not appear to block potassium channels
are safer to cardiac pts
even at supranormal doses.
Antihistamines
are now thought to act as inverse
agonists92 and to have some antiinflammatory effects.
topically,
these
reduce
nasal
obstruction,
but
days
can
resu1t
in
rhinitis
medicamentosa 1 00
with
abrogation of the normal response to alpha stimulation
than interrnitt�ntly93 and may reduce allergic progression children.94
Used
increase rhinorrhoea. Regular use for more than a few
They appear to be more effective if used regularly rather
in
D ECONG ESTANTS
by the sympathetic nervous system as well as to the drug. 1 0 1 Very short-term use, e.g. for flying, otitis media
[***1
with
effusion
and
rhinosinusitis
is
therefore
recommended.
TOPICAL GLUCOCORTI COSTEROIDS
Systemic decongestants are relatively ineffective and
These are the most effective treatment for rhinitis,95
have side effects such as hyperactivity and insomnia in 02, 1 03 [ ***] children and hypertension in adults. 1
especially if started prior to allergen exposure. Regular treatment is necessary. Side effects are minor and include ep istaxis and nasal irritation in 5-- 1 0 percent of patients. Nasal
steroids reduce
inflammation
and
consequent
IPRATROPIUM BRO M ID E
hyperreactivity, reduce nasal symptoms, eye symptoms
This atropine-like nasal spray i s useful against watery
and improve the sense of smell. Their onset of action is slow with some i mprovement after
rhinorrhoea and may, if regularly used, be curative. 104
6-1 2 hours and
[ **1
maximum effects occurring only after several days. There
is no difference in efficacy between the various prepara
alone.
tions, however steroid bioavailability does differ and the lowest
bioavailability
is
seen
with
fluticasone
Occasionally it is helpful in patients with allergic
rhinitis who do not respond to topical corticosterQids lO S
[ * ** J
Side effects can include worsening of
glaucoma or prostatism and dry mouth and eyes. 106
and
[* * ]
mometasone.96 This should be taken into consideration
in paediatric use and where steroid is also being used by
inhalation
or
topically on the
skin.
In
SYSTEM I C CORTICOSTEROI DS
three large
retrospective studies, topical corticosteroids reduced the relative risk of asthma exacerbationlhosp italization by 50
%
These can -be used to unblock the nose at the start of treatment or provided for very severe symptoms during
/
Chapter 1 09
the hayfever season.107 [ * * * ] Regular use is associated
with significant systemic side effects and therefore only occasional intermittent use for a few days at a time is sensible. They should be combined with topical corticos teroid and the usual precautions apply. Depot-injected preparations are not recommended because they are not removable if side effects occur.107 Injection of depot steroid into turbinates and polyps has been associated with blindness and is not recommended.
Al lergic rh initis I 1 399
EFFI CACY In selected patients,
immunotherapy may be highly
effective. [ Grade A]
In one study, patients with grass
50
pollen-induced rhinitis had a symptoms
and
80
an
percent
medication requirements.116
[ ** * ]
percent reduction in reduction
in
rescue
There was also
a
reduction in seasonal bronchial hyperresponsiveness and a marked improvement in quality of life scores. Treatment for three to four years resulted in sustained improvement for at least three years following discontinuation. 1 1 7 [ * * * ] [ Grade A ] I n a study o f children with seasonal rhinitis, immunotherapy for three years resulted in a two- to
ANTI LEU KOTR I E N ES Leukotriene
receptor
antagonists
have
recently been
licensed for use in rhinitis. They are effective against congestion and mucus production, with efficacy similar to that of loratadine,108 but less than topical corticoster
oids.109 [ * ** ] Combination of an antileukotriene plus an
antihistamine was superior to either alone in one study, 110 but in a second study did not show much clinically
three-fold reduction in the risk of developing bronchial asthma.118 [ * * * ] [Grade B] Studies in children have also suggested that immunotherapy for house dust mite and pollen allergy may prevent the onset of new allergic sensitizations.119 [ * * * ]
[ Grade C]
Thus, in contrast to
pharmacotherapy, immunotherapy offers the potential for long-term disease modification and prophylaxis.
significant added benefit. 111 [ * * * ] Antileukotrienes can also be helpful i n nasal polyposis. There is a wide range of individual responsiveness to these
S I D E EFFECTS
drugs so a defined period of use with symptomatic 2 monitoring is sensible.11 [ * * ]
Local reactions following immunotherapy injections are to be expected. In general, these are trivial and require no treatment other than simple reassurance. Systemic reac tions
may occur
in
up to
10
percent of patients,
particularly during the updosing phase.114 In general,
Nasal d ouch i n g
systemic reactions are mild and involve rhinitis or mild
I n rhino sinusitis, nasal douching improves quality o f life
bronchodilators.
asthma responding to antihistamines or simple inhaled
and endoscopic appearances.113 [ * * * ] Studies also suggest its efficacy in seasonal allergic rhinitis in children.
Occasionally,
more
severe
systemic
reactions involving general urticaria, more severe asthma and rarely anaphylaxis may occur and necessitate treat ment with intravenous antihistamine, corticosteroids and adrenaline by intramuscular injection. The large majority of
systemic
reactions
occur
within
30
minutes
of
injections. Occasional mild reactions may occur several
I m m u n oth erapy
hours later and require either no treatment or the use of
Allergen immunotherapy involves the repeated adminis
antihistamines or an inhaled beta-agonist.
tration of an allergen extract in order to induce a state of immunological tolerance, with a reduction in clinical symptoms
and
subsequent
requirements
natural
allergen
for
medication
exposure.114
during
[ Grade
A]
Allergen immunotherapy is indicated in those patients with allergic rhinitis with severe symptoms who fail to
A list of indications and contraindications for immu notherapy in allergic rhinitis are given in ployed.114
mines and topical nasal corticosteroids. A recent general
weekly injections for
many as 40 percent of patients with allergic rhinitis may be so-affected, although compliance was not assessed in detail. 115
[**]
Immunotherapy
is
more
effective
in
patients with a limited spectrum of allergies and is particularly effective in patients with seasonal hayfever. Objective
confirmation
of
IgE sensitivity should
be
obtained by skin. test and/or measurement of serum allergen-specific IgE to the relevant allergen.
Table 1 09.3.
Well-defined and validated protocols should be em
respond adequately to usual treatment with antihista practice-based study within the UK suggested that as
/ . (
PRACTICAL I M M U NOTH ERAPY
In
general,
the
8-16
'updosing'
phase
involves
weeks · followed by 'main
tenance' injections at four to eight weekly intervals for three to five years. Immunotherapy should only be performed in hospital-based clinics by trained staff and in the immediate presence of a physician. Standardized whole allergen extracts with documented clinical efficacy should be employed. Facilities for vaccine storage at +4°C are needed. Patients should be observed for at least minutes
following
injections
in
view
occurrence of systemic side effects.
of
the
60
rare
Staff should be
1400
I PART 1 3 TH E N OS E AN D PARANASAL SIN U SES
Table 1 09.3
Indications for immun otherapy i n allergic r h i n i tis.
Contraindications
Inclusion Criteria IgE-mediated disease (+SPT/RASn
Coexistent asthma
Inability to avoid allergen
Patients taking beta-blockers
Inadequacy of drug treatment
Other m ed i cal/i mmunologic disease
Li m ited spectrum of allergies (one or two)
Small children (less than five years)
Patients who und erstand risks and limitations of
Pregnancy (maintenance therapy may be continued in pregnancy)
treatm ent
familiar with the early recogmtIon and treatment of
length precludes IgE cross linking, thereby reducirtg the
systemic reactions, including an aphyl axis. There should
risks of IgE-mediated systemic reactions.
-
be immediate access to adrenaline and other resuscitation facilities. An out of hOll-rs contact number should be SU M MARY
available for patients.
Allergen immunotherapy, although highly effective, is restricted
M ECH A N I SM S OF I M M U NOTH E RAPY
to patients with severe
disease,
a limited
spectrum of allergies and in patients who fail to respond adequately to usual treatment. In view of the risks of
Immunotherapy results in a blunting of seasonal increases in allergen-specific IgE, an increase in (blocking) IgG
systemic side
antibodies and inhibition of recruitment and activation of
specialist
inflammatory cells to mucosal surfaces including mast
excluded from treatment in view of an increased risk of
underlying
effects,
centres.
the
Patients
treatment with
is
confined to
chronic
asthma
are
which
side effects. Sublingual approaches may represent a safe
orchestrate these changes are thought to involve modula
alternative) although more information concerning their
tion of T-lymphocyte functions. Thus immunotherapy
efficacy, compared to current usual treatment) is required In view of the disease modifying potential for immu
cells
and
basophils.
The
events
has been shown to induce immune deviation from a (Th2-type' T-lymph0 cyte response in favour of a 'protective) 'Thl -type response and also to induce a
.
notherapy,
novel
safer
strategies
are
currently
in
deVelopment.
distinct population of T regulatory cells which produce the inhibitory cytokines 1L- 1 O and TGF� both of which may downregulate Th2 responses to allergens l 2O 121 (*** .
]
,
Nasal surgery may be needed where there is a marked
NOVEL I M M U NOTH E RA PY STRATEG IES
septal deviation or bony turbinate enlargement which
In view of the side effects associated with subcutaneous immunotherapy, alternative strategies have been consid ered. 12 1 The sublingual route involves application of all ergen as drops or tablets under the tongue where they are retained for several minutes A recent meta analysis .
S u rg ery
-
confirmed the efficacy of this form of treatment. [Grade A] Although few controlled comparisons have been made,
makes topical nasal sprays usage difficult.
also be needed to relieve symptoms of rhino sinusitis (see Chapter 1 1 7, Surgical management of rhinosinusitis). [Grade
B]
efficacy appears modest when compared to the subcuta sympto ms and a 38 percent mean reduction in use of rescue medication was seen in a recent UK grass pollen sublingual immunotherapy trial ) with improvement on these values in the second year of treatment. 121 The product
is now licensed for use
vants such as bacterial
DNA
D]
possible) since after surgery the problem tends to recur within months. ( Grade C ] Endoscopic sinus surgery may
neous route. However a 30 percent mean reduction in
in Europe. Novel
immunotherapy approaches1 22 include the use of adju
(Grade
Mucosal hypertrophy is preferably dealt with medically if
sequences ( Cp G) which)
when co nj ugated to all ergen, induce preferential Th l
responses. Alternatively, the use of allergen peptides may
retain immunologic reactivity and the potential to induce 'protective ) T lymphocyte responses, whilst their short
;'
/
Cha pter 1 09
Allergic rhin itis I 1 40 1
./
f � l cm k side cffi cts, i m m u n(.:l t her y t rea t men l is confined to . e ' li �t cent res.
,
.I .I .I .I
./
.I
.I
.I
.I
.I
.I
, .I
.-
L
'
I
I�
�
I
'•
• •
J
t
Antihista m i n es a ppea r t o b e more effective if used reg u la rly a nd m ay reduce a l l ergic progression in chi ldren . ./ Topic a l g lucocorticoids a re the most effective treatment for rh initis, especia l ly if started prior to a l lergen exposu re . .I There is no difference in effica cy betwee n th e various topica l g l u cocorticoid preparations, but f1 uticasone a nd mometasone h ave the lowest bioava il a b i l i ty and therefore shou ld be considered i n paediatric practice or patients having i n h a led or cutaneous steroids. .I Topical corticosteroids reduce the risk of asthma exacerbation/hospita I ization.
� "t .
Advice for primary preven tion in h igh-risk fa m i l ies should be restricted at present. Avoida nce of parenta l smoki ng d uring pregna ncy a n d chi l dhood is im porta nt, particula rly for the mother. B reastfeed i n g is sti l l recomm ended. Prophylactic interve n tion with environmental a l lerg en con trol for h ig h-risk fam i l i es, a lthou g h att ractive, is not curren tly recom mended u nti l the resu lts of cu rre n t long-term trials a re re ported. 1 22 Althou gh a l lergen avoidance is desi rable, it is frequently expensive, time -co nsu m ing, i mpracticable or, i n the case of pol l ens, not feasib le. Recent tria ls and a meta-a na lysis have fai l ed to demonstrate efficacy of house d ust mite avoida nce or red uction methods i n a d u l t patients with pere n n i a l rhin itis and asth ma. Th is m ay b e more successful i n children with a more l i m ited spectru m o f a l l ergies. Pa tients with a l lerg ic rh initis a nd or asthma who a re demo nstra bly sensitive to cats and dogs sho u l d be advised to remove the a nimals or not replace them. Although evidence from c l i nica l trials is l acking, avoida nce of occu pational a l lergens is clea rly indica ted in sensitized, exposed and sym ptomatic i nd ividuals. Food a l lergy a l most never causes isola ted nasa l symptoms. Provoking foods incl ude pean uts, tree n uts, fish a nd fruit. M i lk and egg a l l ergy a re com mon in chil dren u nder fou r yea rs old, but most resolve spontaneously and a re replaced by i nhala n t sensitivity. Antihistami nes a l l rapidly re lieve itching a nd sneez i n g but on ly recent exceptions, e.g. desloratid i ne and levoceti rizi ne, have a n y i m pact on n asa l obstruction . Some a nti h ista m ines cause ca rdiac a rrhythm ias b u t cetirizine, fexofenadine a nd desloratadine do not, even at supra norma l doses. An tihista mines a re thought to act as inverse �gon ists a nd to h ave some a n tiinfl a mmatory properties.
SP ECIAL CI RCU MSTAN CES Pae d i atri c rhi n i tis Diagnosis of allergic rhinitis is difficult in small children who have between six and eight colds per year and whose skin prick tests tend to
lag behind their local nasal alle rgy.
Few treatments are available for small child ren and oral antihistamines tend to be used. Sedating antihista mines should be avoided because they i mpair tion.89 The only intranasal
cognitive func
formul ation
licensed
fo r
younger children is so dium cromoglicate; saline drops or spray may also be useful i n children under two. Top ica l co rticosteroid
nasal sprays differ in their lower age limit. is licensed fo r children from fou r
Fluticasone propionate
years, for others the age limit is five ( tl unisolide) or six (triamcinolone) beclomethasone or mometason e) j bude son ide
is
not
licensed
fo r
paediatric
use.
Systemic
absorption may occur after intranasal administration of steroids and growth suppression has b een reported in children after a year's treatment with budesonide 400 Jlg da ily or beclomethasone dipropionate 1 68 Jlg twice daily. Fluticasone propionate and mometasone fi.uoate have low systemic bioavailability and are associated with a lower risk. 96
Pregnancy Existing rhinitis may be exacerbated by pregnancy and rhinitis can occur high
circulating
de
novo
in pregnancy) probably due to
oestrogen
levels.
These
symptoms
disappear at delivery. There are no medications consid ered completely safe for treatment of allergic rh initis d uring pregnancy, however, by extrapolation from
the
continued use of inhaled corticosteroids in asthmatics) the least absorbed topical nasal corticostero ids would seem a sensible option for the treatment of existing rhinitis. Rhinitis of pregnancy is often resistant to
/
s '
1402 I PART
13
T H E NOSE AN D PARANASAL S I N USES
treatment. Occasional use of topical decongestants to aid
i nfection i n a l lergic individ ua ls. Preve ntion of these cou ld reduce the burden and cost of asthma. This needs i nvestigation. )0 R h i n itis treatment - i ntermittent or conti nuous? Most patients ta ke their rhi n itis treatment when they have sym ptoms and not otherw ise. There are stud ies su ggesti ng that m i n i m a l persistent i nfla m mation exists i n the rhi n itic nose and that reg u l a r treatment of this is beneficia l in red ucing not only rh i n itis but a l so co-morbidities such as asthma and sin usitis. Th is needs cla rification. � Pathophysiol ogy of rhinitis and asthma. Airways remodelling ta kes p lace in the l ower a i rways i n asthma, however there is l ittle evidence for t h i s i n rhin itis. T h e diffe rences u nderlying t h i s may be genetic and i m portant in understanding the pathophysiology of asthma.
sleep has been suggested, but there has been a report of foetal abdominal malformation, which may be associated.
Asth ma Since
most
asthmatics
have
concomitant
rhinitis,
a
treatment which relieves both conditions simultaneously would be optimal since there are problems with con cordance with inhaled and topical nasal corticosteroids. Oral corticosteroids are extremely effective, but have severe side effects and so are reserved for the most difficult end of the patient spectrum, being used either briefly in hay fever or very occasionally on a regular long-term basis in patients with aggressive polyposis and asthma. Leukotriene receptor antagonists have proved to have moderate effects in rhinitis and in asthma, with a spectrum of patient responsiveness. The most recent antihistamines (levocetir izine, desloratadine) have some effects on nasal obstruction and
desloratadine
improves
seasonal
asthma.
Their
possible use in asthma has been recently reviewed. 123 In
future, the use of anti-IgE and immunotherapy should . 124 . both conditlOns. prove ef£ectIve III .
REFEREN CES *
Deficien cies i n cu rre n t kn o w l ed g e a n d a reas for fu tu re resea rch
1.
2.
�
Natura l h istory of rhin itis and asthma. The accepted a l lergic 'march' in child hood starts with atopic dermatitis, with prog ression to subsequent asthma and then rhi n itis. However, many patients now appea r to develop rh initis as their first sym ptom , often i n childhood or ea rly adu lthood. T h i s t h e n prog resses to asth ma. Better epidemiologica l evidence is needed to understand the genetic backgrou nd and the natu re of this prog ression and whether prevention is possible. )0 Effect of rh i n itis treatment u pon asthma. This is a disputed a rea with the recent BTS/S I G N guideli nes denying that rh i n itis treatment has been shown to benefit asthma si nce there a re two large double-blind studies i n seasonal rh initis using the nonabsorbed top ica l corticosteroid fl uticasone propionate which a re negative. However, there are a nu mber of sma l ler stud ies i n the l iteratu re which demonstrate a benefi cia l effect, there are a lso three large retrospective studies suggesting that rhin itis treatment red uces emergency visits/hospita l ization for asthma. This needs cla rification. )0 I nfl uences of sinusitis and nasa l polyposis on asthma. Fu rther ca refu l ly designed prospective studies i n these areas are needed. )0 R h i n itis exacerbations. Most exacerbations of asth ma start with an exacerbation of rh i n itis, often rhi novirus
*
3.
* 4.
5.
6. 7. 8.
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27.
28.
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35.
* 36. 37.
38.
1404 I PART 1 3 TH E N OSE AN D PARANASAL SI N USES 39.
40.
41 .
42.
43.
44. 45.
46.
47.
48 .
49.
50.
51 .
Wenzel SE. I nflam mation, leukotrienes and the pathogenesis of the late asth matic response [editori a l ;com ment] . Clinical and Experimental Allergy. 1 999; 2 9 : 1 -3. Shaw RJ, Fitzharris P, Cromwell 0, Wa rd low AJ , Kay AB. Allergen-in duced release of su lphidopeptide leu kotrienes (SRS-A) and LTB4 in a l lergic rhinitis. Allergy. 1 985; 40 : 1 -6. Volovitz B, Osur SL, Bernstein J M , Og ra PL. Leu kotriene C4 release in u pper respiratory mucosa d u ring natural exposu re to ragweed in ragweed-sensitive chi ldren. Journal of Allergy a n d Clinical Immunology. 1 988; 82: 41 4-8. M iadonna A, Tedeschi A, Leggieri E, Lori n i M, Folco G, Sala A et 01. Behaviour and clin ica l releva nce of h ista m ine and leukotrienes C4 and B4 i n grass pollen-i nduced rhi n itis. American Review of Respiratory Disease. 1 987 ; 1 3 6 : 3 57-62. Kna n i J, Ca mpbell A, Enander I, Peterson CG, M ichel FB, Bousquet J. I n d i rect evidence of nasal inflammation assessed by titration of infl a m matory med iators and enu meration of cel l s in nasa l secrections of patients with chronic rh i n itis. Journal of Allergy and Clinical Immunology. 1 992 ; 90: 880-9. Proud D. The ki n i n system in rhi n itis and asthma. Clinical Reviews in Allergy and Immunology. 1 998; 1 6 : 3 5 1 -64. Proud D, Tog ias A, Naclerio RM, Crush SA, Norman PS, Lichtenstein LM. Kinins are generated in vivo fol lowing nasal a i rway cha l lenge of al lergic i ndivid u a ls with a l lergen. Journal of Clinical In vestigation. 1 983 ; 7 2 : 1 678-85. Ba umgarten CR, Tog ias AG, Naclerio RM, Lichtenstein LM, l\Iorman PS, Proud D. I nfl ux of ki ni nogens i nto nasa l secretions after antigen cha l lenge of a l lergic individua ls. Journal of Clinical Investigation. 1 985; 7 6 : 1 9 1 -7. Tu rner P, Dear J, Scadding G, Foreman JC. Role of kin ins in seasonal a l lergic rhinitis: icatibant, a bradyki n i n B2 receptor antagon ist. abol ishes the hyperresponsiveness and nasal eosi noph i l ia ind uced by antigen. Journal of Allergy and Clinical Immunology. 2001 ; 1 07 : 1 05- 1 3. B radding P, Feather I H , Wi lson S, Holgate ST, Howarth PH. Cytokine i m m u noreactivity in seasonal rh i n itis: reg u lation by a topical corticosteriod. American Journal of Respiratory and Critical Care Medicine. 1 995; 1 51 : 1 900-6. B radd ing P, Feather I H , Howarth PH, M u e l ler R, Roberts JA, B ritten K et 01. I nterleukin 4 is loca l ized to and rel eased by h u m a n mast cel ls. Journal of Experimental Medicine. 1 992 ; 1 76 : 1 38 1 -6. B radding P, Roberts JA, B ritten KM, Montefort S, Pju kanovic R, lVI uel ier R et 01. I nterl e u ki n-4, -5, and -6 and tumor necrosis factor-a lpha i n norm a l and asth matic a i rways: evidence for the h u m a n mast cel l as a sou rce of these cytoki nes. American Journal of Respiratory Cell and Molecular Biology. 1 994; 1 0: 471 -80. Gordon J R, Burd PR, Ga l l i SJ. Mast cel l s as a sou rce of m u l tifu n ctiona l cyto kines. Immunology Today. 1 990; 1 1 : 458-64.
52.
53.
54.
55.
56.
57.
58.
59.
60.
61 .
* 62.
63.
64.
65.
B radding P, Mediwake R, Feather I H , Madden J, Ch u rch M K, Hol gate ST et 01. TNF a l pha is loca l ized to nasa l mucosa l mast cel l s a n d is released i n acute a l lergic rhi n its. Clinical and Experimental Allergy. 1 995; 25: 406- 1 5. Pawa n kar R, Okuda M, Yssel H, Oku m u ra K, Ra C. Nasa l mast ce l ls in peren nial a l l erg ic rh i n itics exh ibit increased expression of the Fe epsiionRl, CD40L, I L-4, and I L- 1 3, and can ind uce I g E synthesis i n B cel ls. Journal of Clinical In vestigation. 1 997 ; 9 9 : 1 492-9. Enerback L, Pipkorn U, Olofsson A. I ntraep ithe l i a l migration o f mucosa l mast c e l l s i n h a y fever: u ltrastructural observations. International Archives of Allergy and Applied Immunology. 1 986; 8 1 : 289-97. Bascom R, Pipkorn U, Lichtenstein LM, Naclerio RM. The i nfl ux of infl a m matory cel l s i nto nasa l wash ings d u ri ng the late response to a l l ergen chal lenge. Effect of systemic steroid pre-treatment. American Review of Respiratory Disease. 1 988: 406- 1 2. Naclerio R M , Proud D, Togias AG, Ad kinson J r. 1\1 , lVIeyers DA, Kagey-Sobotka A et 01. I nfla m matory med iators in late antigen-i nd uced rhi n itis. Ne w England Journal of Medicine. 1 98 5 ; 3 1 3 : 65-70. Sil berstei n DS. Eosinophil fu nction i n hea lth and disease. Critical reviews in Oncology/Hematology. 1 995; 1 9 : 47-77. Ca pron M, Desre u maux P. I m m u nobiology of eosi noph i l s in a l lergy and infl a m mation. Research i n Immunology. 1 997 ; 1 48 : 29-33. Szucs E, Ravandi S, Goossens A, Beel M, Clement PA. Eosinoph i l ia in the ethmoid mucosa and its relationship to the severity of infl a m mation in chronic rh i nosi nusitis. American Journal of Rhinology. 2002; 1 6 : 1 3 1 -4. Sch leimer R P, Boch ner BS. The role of ad hesion molecu les i n a l l ergic infl a m mation and thei r suitabil ity as ta rgets of antia l lergic therapy. Clinical and Experimental Allergy. 1 998; 3 : 1 5-23. Sch roeder JT, Kagey-Sobotka A, Lichtenstei n LM. The ro le of the basoph i l i n a l l ergic infla mmation. Allergy. 1 99 5 ; 50: 463-72. Va rney VA, Jacobson M R , Sudderick RM, Robi nson DS, I ra n i AIVI, Schwa rtz LB et 01. I m m u noh istology of the nasa l mucosa fol lowi ng a l lergen-ind uced rh i n itis. Identification of activated T lym phocytes, eosi nophi ls, and neutroph i ls. American Review of Respiratory Disease. 1 992; 1 46 : 1 70-6. Va rga EM, Jacobson MR, Ti l l SJ, Masuya ma K, O' B rien F, Rak S et 01. Cel l u l ar infi ltration a nd cytokine m R NA expression in perennial al lergic rhi n itis. Allergy. 1 999 ; 54: 338-45. H o l m AF, Fokkens WJ , Godthe l p T, M u lder PG, Vroom TIVI, Rijntjes E. Effect of 3 months; nasa l steroid thera py on nasal T cel l s and La ngerhans cells in patients suffering from a l lergic rhi n itis. Allergy. 1 995; 50: 204-9. Cromwe l l 0, Hamid 0, Corrigan CJ , Ba rkans J, Meng 0, Col l i ns PD et 01. Expression and generation of interl e u kin8, I L-& a nd g ra n u l ocyte-macrophage colony-sti mu lating factor by bronchial epithe l i a l cells and enha ncement by
Chapter
66.
67 .
* 68.
69.
* 70.
71 .
72. * 73.
74.
7 5.
76.
77.
78. 79. 80.
I i �,
IL - 1 beta a nd tu mou r necrosis factor-al pha. Immunology. 1 992; 7 7 : 330-7. Ca non ica GW, Ci p ra ndi G, Pesce G P, B uscaglia S, Paolieri F, Bag nasco M. ICAM-l on epith e l i a l cel ls in a l lergic subjects: a ha l l m ark of al lergic infl amm ation. International Archives of Allergy and Immunology. 1 99 5 ; 1 07 : 99- 1 02. Deva l ia .lL, Bayra m H, Abdelaziz M M , Sa psford RJ , Davies RJ. Differences between cytokine release from bronch ial epithelial cel ls of asthmatic patients and non-asth matic subjects : effect of exposu re to diesel exha ust particl es. International Archives of Allergy and Immunology. 1 999; 1 1 8 : 43 7-9. Denburg JA. Bone ma rrow in atopy and asth m a : he matopoietic mechan isms in a l l erg ic inflamm ation. Immunology Today. 1 999 ; 20: 1 1 1 -3. Roche N, Chi net TC, H uchon GJ. All ergic and nona llerg ic interactions between house dust mite a l lergens and airway m ucosa. European Respiratory Journal. 1 997; 1 0 : 71 9-26. Scadding G K. Non-a l l e rg ic rhin itis : diagnosis and ma nagement. Current Opinion in Allergy and Clinical Immunology. 2001 ; 1 : 1 5-20. Demoly P, Michel F, Bousquet J. I n vivo methods for study of a l l ergy. Skin tests, tech niques and interpretation. I n : M idd l eton E, Reed C, El l is E, Ad ki nson N, Yu nginger J, B usse W (eds). Allergy, principles and practice, 5th ed n. St Louis: Mosby Co, 1 998: 530-9. Pepys J. Skin testing. British Journal of Hospital Medicine. 1 97 5 ; 1 4: 41 2. Powe DG, H uskisson RS, Ca rney AS, Jenkins 0, Jones NS. Evidence for an inflamm atory pathology in id iopathic rh in itis. Clinical and Experimental Allergy. 2001 ; 31 : 864-72. Deusch l H, Johansson SG. Specific I g E antibod ies in nasal secretion from patients with al lergic rh intis and with negative or wea kly positive RAST on the seru m. Clinical Allergy. 1 97 7 ; 7 : 1 95-202. Crobach MJ, Ka ptei n AA, Kram ps JA, H ermans J, Ridderikhoff J, M u lder J D. The Ph adiatop test com pared with RAST, with the CAP system ; proposa l for a th ird Phadiatop outcome: "i nconcl usive". Allergy. 1 994; 49 : 1 70-6. Bousquet J, Chanez P, Cha nal I, M ichel FB. Co mparison between RAST and Pharmacia CAP system : a new automated specific IgE assay. Journal of A llergy and Clinical Immunology. 1 990; 85 : 1 039-43. Ma i m L, Gerth-van-Wij k R, Bachert C. G u ideli nes for nasal provocations with aspects on nasal patency, airflow, and a i rfl ow resista nce. Rhinology. 1 999; 3 7 : 1 33-5. Gore C, Custovic A. Ca n we prevent a l lergy? Allergy. 2004; 59 : 1 51 -61 . Arshad SH, Matthews S, Gant C, Hide OW. Prevention of atopic disease i n ch i l d ren. Lancet. 1 992; 339 : 1 493-7. M u rray CS, Pipis SO, McArd l e EC, Lowe LA, Custovic A, Woodcock A. Lung fu nction at one month of age as a risk factor for infa nt respi ratory sym ptoms in a high risk population. Thorax. 2002 ; 57: 388-92.
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8 1 . Woodcock A, Lowe LA, M u rray CS, Sim pson B M , Pi pis SO, Kissen P et al. Ea rly life environ mental contro l : effect on sym ptoms, sensitization and l u ng fu nction at age 3 yea rs. American Journal of Respiratory a n d Critical Case
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89.
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91. 92.
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Medicine. 2004; 1 70 : 433-9. Gotzsche Pc. Ham marquist C. B u rr MHouse dust mite control measures i n the management of asth m a : metaana lysis. British Medical Journal. 1 998; 31 7 : 1 1 05 - 1 0. Terreehorst I , Hak E, Oosti ng AJ , Tem pels-Pavlica Z, de Monchy JG, B ruijnzeel-Koomen CA et al. Eva l u ation of im permea ble covers for bedd ing in patients with a l l ergic rh initis. Ne w England Journal of Medicine. 2003 ; 349 : 237-46. Woodcock A, Forster L, Matth ews E, Martin J, Letley L, Vickers M et al. A Control of exposure to mite a l lergen an� al lergen-i m permeable bed covers for adults with asth ma. Ne w England Journal of Medicine. 2003 ; 349 : 225-36. Sheikh A, H u rwitz B, Sibbald B, Ba rnes G, Howe M, Durham S. H ouse dust mite barrier bedd ing for ch i l d hood asth m a : ra ndom ised placebo controlled trial in pri m a ry ca re. BMC Family Practice. 2002 ; 3 : 1 2. O'Mea ra TJ, Sercombe J K, Morgan G, Reddel H K, Xuan W, Tovey ER. The red uction of rhin itis sym ptoms by nasal filters d u ring natural exposu re t o ra gweed a n d grass pollen. Allergy. 2005 ; 60: 529-32. Bousq uet J, Ca m pbell A, Michel F. Antia l l ergic activities of antih istamines. I n : Ch u rch M, Rihoux J (eds) . Therapeutic index of an tihistamines. Lewi nston, NY: Hog retfe and H u ber Publish ers, 1 992: 57-95. Horak F, Stu bner U P, Ziegelmayer R, I ng 0, H a rris AG. Effect of desloratadine versus placebo on nasa l a i rflow and subjective measures of nasal obstruction in patients with grass pol l en-ind uced a l lergic rhin itis in an a l lergenexposu re u nit. Journal of Allergy and Clinical Immunology. 2002 ; 1 09 : 956-61 . Timmerman H. Factors involved in the incidence of centra l nervous system side effects of H 1 blockers. I n : Ch urch M, Rihoux J (eds). Therapeutic index of antihistamines. Lewinston, NY: Hogrefe and H uber Publ ishers, 1 992 : 1 9-31 . Scadding G K. Clin ical assessment of antih istami nes in rh initis. Clinical and Experimental Allergy. 1 999 ; 29 : 77-8 1 . Woosl ey R L, Sa l e M . OT i nterva l : a measu re of dr�g action. American Journal of Cardiology. 1 993; 7 2 : 36B-43 B. Leu rs R, Ch u rch M K, Tag l ialatela M. Hl antih ista m i nes: inverse agonism, anti-inflamm atory actions and ca rdiac side effects. Clinical and Experimental Allergy. 2002 ; 32 : 489-98. Ci prandi G, Passa lacq ua G, Minca ri n i M, Ricca V, Ca non ica GW. Continuous versus on demand treatment with ceti rizine for a l lergic rhin itis. Annals of Allergy, Asthma and Immunology. 1 997 ; 79 : 507- 1 1 . ETAC R study-g rou p. Al l erg ic factors associated with the deve lopment of asth ma and the infl uence of cetrizine in a double-blind, ra ndom ised , p lacebo-control l ed tri a l : first results of ETAC R. Pediatric Allergy and Immunology. 1 998; 9: 1 1 6-24.
;
,
d(
1406 I PART 1 3 TH E NOSE AN D PARANASAL S I N USES Weiner J I\t1, Abra mson MJ , Puy RM. I ntranasa l corticosteroids versus ora l H 1 receptor antagon ists i n a l lergic rh i n itis: systematic review of ra ndomised contro l led trials. British Medical Journal. 1 998; 31 7 : 1 624-9. 96. Scadding G K. Safety of i ntranasa l steroids. Editorial in current opinion in ENT. London : RSM publ ications, 2002. * 97. Adams RJ, Fu h l brigge AL, Fin ke lstei n JA, Weiss ST. I ntranasa l steroids and the risk of emergency department visits for asthma. Journal of Allergy and Clinical Immunology. 2002 ; 1 09 : 636-42. * 98. Crysta l-Peters J, Nel usan C, Crown W H , Torres A. Treating a l lergic rh i n itis in patients with comorbid asthma : the risk of asthma-related emergency department visits. Journal of Allergy and Clinical Immunology. 2002 ; 1 09 : * 95.
99.
*1 00. 1 01 .
1 02.
1 03.
1 04.
1 05.
1 06.
57-62. Engstrom I, Oberger E, Blyckert A, Kraepel ien S. Disod i u m cromog lycate in the treatment of seasonal al lerg ic rh i noconjunctivitis i n children. Annals of Allergy. 1 971 ; 29: 505-9. Scadding G K. R h i n itis medicamentosa. Clinical and Experimental Allergy. 1 995; 2 5 : 391 -4. B radley JG. I\lon prescri ption d rugs and hypertension . Which ones affect blood pressure? Postgraduate Medical Journal. 1 99 1 ; 89 : 1 95-7, 201 -2. Joh nson DA, H ricik JG. The pha rmacology of a l phaadrenerg ic decongesta nts. Pharmacotherapy. 1 993 ; 1 3 : 1 1 0S-5S; d iscussion 43S-6S. Thomas SH, Clark KL, Al len R, Smith SE. A com pa rison of the cardiovascu l a r effects of phenyl propa nolamine and p henylep h rine conta i n i ng proprietary cold remedies. British Journal of Clinical Pharmacology. 1 99 1 ; 3 2 : 705- 1 1 . Kaiser HB, Fi ndlay SR, Georgitis JW, Grossman J, Ratner PH, Tinkel man DG et al. Long-term treatment of pere n n ia l rh i n itis with ipratropium bromide nasa l spray 0.06%. Journal of Allergy and Clinical Immunology. 1 99 5 ; 9 5 : 1 1 28-32. Dockhorn R, Aa ronson D, B ronsky E, Chervinsky P, Cohen R, Ehtessabian R et al. I pratropium bromide nasal spray 0.03% and beclomethasone nasal spray alone and i n combi nation for the treatment of rh inorrhea i n perennial rh i n itis. Annals of Allergy, Asthma and Immunology. 1 999 ; 82 : 349-59. G roth S, Di rksen H, l\t1yg ind 1\1. The absence of systemic side-effects from high doses of i p ratropium in the nose.
1 09.
1 1 0.
111.
1 1 2.
1 1 3.
* 1 1 4.
1 1 5.
1 1 6.
1 1 7.
* 1 1 8.
European Journal of Respiratory Diseases. Supplement.
1 983 ; 1 2 8 : 490-3. B rooks CD, Karl KJ , Fra ncom SF. O ra l methyl pred n isolone acetate (Med rol tabl ets) for seasonal rh i n itis: exa m i nation of dose and symptom response. Journal of Clinical Pharmacology. 1 993 ; 3 3 : 81 6-22. 1 08. Don ne l ly AL, G lass M, M i n kwitz MC, Casa le TB. The l e u kotriene D4-receptor antagonist, ICI 204,21 9, relieves sym ptoms of acute seasona l a l lergic rhin itis. American Journal of Respiratory and Critical Care Medicine. 1 99 5 ; 1 51 : 1 734-9. 1 07.
1 1 9.
*1 20.
Pu l lerts T, Pra ks L, Skoog h BE, Ani R, Lotva l l J . Randomized placebo-control led study com paring a l e u kotriene receptor antagon ist and a nasa l g l u cocorticoid in seasonal a l lergic rh i n itis. American Journal of Respiratory and Critical Care Medicine. 1 999 ; 1 59 : 1 8 1 4-8. Meltzer E, M a l mstrom K, Lu S, B renner B, Wei L, Wei nstein S et al. Concomitant monte l u kast and lorata d i ne as treatment for seasonal a l lergic rh i n itis: p lacebo-control led clin ica l trial. Journal of Allergy and Clinical Immunology. 2000 ; 1 05 : 9 1 7-22. Nayak AS, Ph i l i p G , Lu S, Malice M P, Reiss TF. Montel u kast Fal l investigator g roup. Efficacy and tolera b i l ity of montelu kast a lone or i n combi nation with loratadine in seasonal a l l erg ic rh initis: a muticenter, random ised, double-bl i nd, placebo-control led trial performed i n the fa l l. Annals of Allergy, Asthma and Immunology. 2002 ; 88: 592-600. Ragab S, Pa rikh A, Da rby YC, Scadding G K. An open audit of monte l u kast, a leukotriene receptor antagon ist, in nasal po lyposis associated with asthma. Clinical and Experimental Allergy. 2001 ; 31 : 1 38 5-9 1 . TacCa rie l lo M, Pa rikh PP, Da rby Y, Scadding G K. Nasa l douching i n ch ronic rh i nosi n usitis: a ra ndom ized, singleblind study com pa ring a l ka l i n e nasa l douche and steri le sea water. Rhinology. 1 999; 3 7 : 29-32. Bousquet J, Lockey R, M a i ling HJ, Alverez-Cuesta E, Ca non ica GW, Cha pman I\t1 D e t al. Al lergen i m m u nothera py: thera peutic vaccines for a l lergic diseases. Wo rl d Health Organization. Annals of Allergy, Asthma and Immunology. 1 99 8 ; 81 : 401 -5. Wh ite P, Smith H, Baker N, Davis W, Frew A. Sym ptom control i n patients with hay fever i n U K general practice: how we l l a re we doing and i s there a need fo r a l l ergen i m mu nothera py? Clinical and Experimental Allergy. 1 99 8 ; 2 8 : 266-70. Wa l ker SI\t1 , Paj no GB, Li ma MT, Wi lson DR, D u rham SR. G rass pol len i m m unothera py for seasonal rhin itis a n d asthma : a ra ndom ized, control led trial. Journal of Allergy and Clinical Imm unology. 2001 ; 1 07 : 87-93. D u rham SR, Wa l ker SM, Varga EM, Jacobson M R, O'Brien F, N o b l e W et al. Long-term clin ica l efficacy o f grass-po l len i m m u nothera py. Ne w England Journal o f Medicine. 1 999 ; 3 4 1 : 468-75. Moller C, Dreborg S, Ferdousi HA, H a l ken S, Host A, Jacobsen L et al. Pol l en i m m u nothera py reduces the development of asthma i n ch i l d ren with seasona l rhi noconju nctivitis (the PAT-study). Journal of Allergy and Clinical Immunology. 2002 ; 1 09 : 251 -6. Des Roches A, Pa radis L, Menardo J L, Bouges S, Da u res J P, Bousq u et J . I m m u notherapy with a sta ndardized Dermatophagoides pteronyssinus extract. VI. Specific i m m u notherapy prevents the onset of new sensitizations i n ch i l dren. Journal of Allergy and Clinical Immunology. 1 99 7 ; 9 9 : 450-3. Nou ri-Aria KT, Wachholz PA, Fra ncis I N , Jacobson M R, Wa l ker 51\t1, Wi lcock L K et al. G rass pollen i m m u nothera py ind uces mucosa l and peri phera l I L- 1 0 responses and
Chapter 1 09 Alle rgic rh in itis
blocki ng IgG activity. Journal of Immunology. 2004; 1 72 : 3252-9. 1 2 1 . Ti l l SJ, Fra n cis IN, Nou ri-Aria KT, D u rham SR. Mechan isms of a l le rgen i m m u nothera py. Journal of Allergy and Clinical Immunology. 2004; 1 1 3 : 1 02 5-34. 1 22. Sim pson A, Custovic A. A l l e rgen avoidance in the p rimary prevention of asthma. Current Opinion in Allergy and Clinical Immunology. 2004; 4: 45-51 .
1 23.
1 24.
I 1 407
Wi lson AM. Are antihista mines usefu l in managing asthma? Current Opinion in Allergy and Clinical Immunology. 2002 ; 2 : 53-9. G l oba l strategy for asth ma management and p revention. WHOI N H LBI workshop report: National Institutes of H ea lth, Nationa l Heart, Lung and Blood I nstitute Publication Nu mber 95-3659 ;1 995.
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BACHERT
I ntrod uction
1408
Conclusion
1412
Pathophysiologic.al c.onsiderations
1409
Key points
1412
Types of nonallergic rhinitis
1409
Best clinical
1413
Differential diagnosis
1411
Deficiencies in current knowledge and areas for future
Diagnosis as a step-wise approach
1412
Therapy for nonallergic. perennial rhinitis
1412
" ...-. ..... 1",
... 1-,,'/1
1413
vasomotor
by Medline and EMBASE searches
occupational
nonallergic
1413
research References
drug-induced
'!,>p·r'.>r,,,
chemical factors) food-induced
INTRODUCTION
emotion-
induced rhinitis, atrophic rhinitis).l, Although rhinitis is a cause of widespread morbidity, medical treatment costs, reduced work productivity and lost school
the disease is often trivialized. Non
infectious rhinitis can broadly be subdivided into two allergic and nonallergic rhinitis, depending on whether or not an UUl-'ll'''''O'� ....U.
investigated and the well
mechanisms are relatively
there is comparatively little information rhinitis'
rhinitis. The term applied to a diagnosis
is
nasal condition in
are identical to those seen in
which the
rhinitis but an allergic aetiology has been excluded. These UVH"-'-''-J.;Y'"'
•
ael:1010g.1C entities can broadly be classified as:
icliopathic rhinitis (also referred to as vasomotor
rhinitis,
or
nonallergic
noninfectious
Unlike allergic rhinitis there are no specific the basis of rhinitis symptoms in the absence of identifi able
Ninety-five
of normal subjects without rhinitis
complaints have recently been shown to sneeze up to four times a day and to blow their noses up to four times a day, as
an
that five
average over two weeks.:' This would
or more sneezes and/or nose blowing per day may possibly be indicative of nasal disease. Whilst it is difficult to rhinitis, it has been suggested rhinitis this
that in patients with condition
than nine months each year
two or more
and v_
for
....... ,.• v.L,
including hyper-
blockage. sneezing and
drip.
Although there are some studies of the of
•
nonallergic occ:u):lauonaJ
•
hormonal rhinitis;
48
drug-induced
•
other forms (nonallergic rhinitis with
(NARES),
(by allergy testing), structural abnormality, derlCH:ncy. sinus disease or other causes.
rhinitis (NANIPER));
syndrome
2
tests for nonallergic rhinitis, and diagnosis is made on
aetiology is
Whilst allergic rhinitis has been extensively
"L'-UIUl",
and surgery.
'�'J.HjlU"',
rhinitis
the rhinitic population.
variations (ranging from around 20-50 percent) and rhinitis due to
have been reported)4,5 t'>1"\�" T\r\nn
"1"'."1'''''.0'
due to difficulties in
definition and diagnosis of the disease. It is evident that the incidence of positive skin tests to inhalant
)
/
is
Chapter 110 Nonaliergic perennial rhinitis I
1409
far greater than the incidence of rhinitis symptoms
a consequence of abnormal nociceptor function, this has
in large cross-sectional epidemiological studies. This also
been shown not to be the case in NANIPER.II In a recent
implies that rhinitis symptoms in a patient with a positive
study, forced expiration through the nose was found to
skin test are not necessarily caused by the allergen,
significantly increase nasal airway resistance, but not
suggesting that the contribution of nonallergic rhinitis
mucous production or sneezing, within the first minute
to the total number of rhinitis patients may be sub
in NANIPER patients and not in nonrhinitic controls,
stantially greater than hitherto estimated. A recent survey
suggesting that mechanical stimulation may also be an
of nearly 1000 rhinitis patients seen in 18 allergy clinics
important mechanism in NANIPER patients.I2 However,
in the USA showed that 23 percent of the patients had
in view of the fact that sympathetic stimulation leads to
pure nonallergic rhinitis and, importantly, 34 percent
vasoconstriction and parasympathetic stimulation leads
of the patients were diagnosed with 'mixed' rhinitis (a
to nasal congestion, it is likely that the imbalance is biased
combination of allergic and nonallergic rhinitis), 6, 7 a
towards parasympathetic stimulation since rhinorrhoea is
group not considered in the other studies. Further
the predominant complaint in this condition.8
more, both nonallergic and mixed rhinitis occur more
Review of the limited data available for idiopathic
frequently in adults than in children, may be more
rhinitis, which comprises the largest group of patients
common in females and are more likely to be perennial
with nonallergic rhinitis, has indicated that several patho
than seasonaL More recently, the survey was extended to
logic mechanisms, including non-lgE-mediated inflam
include more than 22,000 practitioners, each of whom
matory responses, C-fibre stimulation, parasympathetic
contributed ten patients with rhinitis to the survey. The
hyperreactivity and/or sympathetic hyporeactivity, and
interim results of the survey indicated that as many as
glandular hyperreactivity, might play a role in these
70 percent of these patients have mixed rhinitis, with only
patients.13
9 percent having the nonallergic rhinitis component
mechanisms operate separately or in combination in
However,
it
is
not
clear
whether
these
alone. However, in rhinologic reference centres, approxi
the same patient, and whether these mechanisms may be
mately half of the rhinitis patients may suffer from
caused by different aetiological entities. Some attempts have been made to develop diagnostic
nonallergic rhinitis. [****/*** /**]
tools for this condition. Assessment of skin reactivity to a variety of vasomotor agents, including papaverine, metha choline, histamine and compound 48/40, has demonstrated that the
PATHOPHYSIOLOGICAL CONSIDERATIONS
frequency of
pathological
skin
reactivity
to
papaverine, but not the other three agents, is signifi Nonallergic rhinitis, allergic rhinitis and post-infectious
cantly increased in patients with perennial nonallergic
rhinitis have nasal hyperreactivity to various stimuli (for
rhinitis, compared with healthy subjects.I4 This suggests
example odours, position, temperature, histamine, etc.)
that papaverine-induced skin reactivity may be a useful
in common, which consequently does not allow dif
diagnostic tool for nonallergic rhinitis. A recent dose
ferentiation
response study has shown that histamine-induced total
between
allergic
and
nonallergic
causes.
Unlike patients from some subgroups of nonallergic
nasal
rhinitis
suggesting that it may be possible to classify nonspecific
(particularly
drug-induced,
hormone-induced
resistance
follows
a
model
exponential
curve,
and NARES) and patients with allergic rhinitis for whom
nasal hyperreactivity in allergic and nonallergic subjects as
the aetiology is well defined, the aetiology and patho
a function of the regression b coefficient of the empirical
physiology for the majority of patients with nonallergic
equation used in reactivity classes.IS Methacholine tests
noninfectious rhinitis are largely unknown. Although the
may be able to differentiate idiopathic rhinitis subjects from
term 'vasomotor' implies increased neuronal efferent
controls, but only in those suffering from rhinorrhoea as
traffic to the blood vessels supplying the nasal mucosa,
the main symptom. Recently, cold dry air (CDA) challenge
this has never been proved.1 Some mechanistic studies
has been suggested to differentiate best between controls
have
in
and idiopathic rhinitis patients.13 However, none of these
NANIPER may be associated with an imbalance between
tests is suitable to differentiate the nonallergic idiopathic
the sympathetic and parasympathetic nervous systems,
from other forms of rhinitis, nor has any been demon
which leads to an imbalance in neuronal control of the
strated to be superior to a simple case history. [****/***]
suggested
that
the
functional
abnormality
end organs in the nose.8 Indeed, nasal provocation with capsaicin, which specifically stimulates afferent nerve fibres, has been shown to result in a dose-dependent leukocyte influx, albumin leakage and glandular secretion in patients with allergic rhinitis9 and to be efficacious in the treatment of NANIPER.IO However, reports on
TYPES OF NONALLERGIC RHINITIS "
Idiopathic rhinitis
the underlying mechanisms are conflicting. Whilst some
/
studies have suggested that capsaicin induces neurogenic
Idiopathic rhinitis is characterized primarily by symp
inflammation in patients with allergic rhinitis, possibly as
toms
.5_.'.. ' --"'""-�-'-----.--.----.- --
of
nasal
blockage,
rhinorrhoea
and
sneezing,
/
I
1410 I
PART 13 THE NOSE AND PARAI\lASAL SINUSES
although the prevalence of sneezing, conjunctival symp
were smokers this was significantly increased with a
toms and pruritis is lower than that in allergic rhinitis.
relative risk enhancement of 69 percent.20 Neither asthma
Although the subjects have traditionally been classified as
nor rhinitis were, apparently, risk factors for pregnancy
either 'runners' (those with predominantly rhinorrhoea)
rhinitis.
or 'blockers' (those with predominantly nasal congestion
nonallergic rhinitis may be afflicted by rhinitis due to
and blockage), many patients suffer from more than one
hypothyroidism or acromegaly.21
In contrast,
only 2 percent of patients with
type of these symptoms, therefore making it difficult to
Oestrogens cause vascular engorgement, not only in
subdivide the patients into these groups. The aetiology is
the female genital tract, but also in the nose, leading
unknown in most cases and the disease is thought to be
to nasal obstruction and/or nasal hypersecretion. Beta
triggered mainly by irritants and changes in atmospheric conditions.16 Among patients with chronic symptoms,
oestradiol and progesterone have been shown to increase the expression of histamine HI receptors on human nasal
the percentage with a nonallergic aetiology increases
epithelial cells and mucosal microvascular endothelial
progressively with age and reaches > 60 percent beyond
cells,22
the age of 50 years, therefore suggesting that functional
degranulation,
abnormality in this condition may be associated with the 1 ageing process in the nasal mucosa. 6 [***/**]
which decreases eosinophil activation and viability.23
and
to
induce in
eosinophil
marked
migration
contrast
to
and/or
testosterone,
Compared with pregnancy rhinitis, the evidence linking hypothyroidism with nasal pathology is sparse,
and
the reported increase in nasal secretion associated with
Nonallergic occupational rhinitis
thyroid disease is anecdotal.1 [***/**]
Occupational rhinitis, as the term implies, may be defined as rhinitis caused by exposure to airborne agents present
Drug-induced rhinitis
in the work place. These agents elicit predominantly sneezing, nasal discharge and/or blockage and may act via both immunologic (IgE-mediated) and nonimmunologic mechanisms.
The nonimmunologic triggers are often
irritant or toxic small molecular weight compounds such as aldehydes,
isocyanates,
aircraft fuel and jet stream
exhaust, solvents, etc./' 8,17 or may be physical (long-term exposure to cold air). Whilst the specific mechanisms underlying the effects of these irritants and toxic agents have not been fully elucidated, it is possible that damage and/or stimulation of the epithelial cells and neurons by the irritants may lead to proinflammatory mediators and neuromediators, which may predispose the nasal mucosa to inflammation and infection, subsequently resulting in the symptoms of rhinitis. Indeed, a study investigating the effect of airborne exposure to the nonallergenic microbial agents endotoxin and beta(l,3)-glucan in compost work ers
has
reported
that
concentrations
(predominantly neutrophils),
of
total
cells
myeloperoxidase (MPO),
IL-8, nitric oxide (NO) and albumin were significantly higher in compost workers than in controls.18 Similarly, occupational exposure to vanadium pentoxide, a cons tituent of fuel oil ash and a known respiratory irritant, has been shown to significantly increase the number of polymorphonuclear
cells
in
nasal
lavage
of
boiler
makers.19 [****/***]
Hormonal rhinitis Hormonal rhinitis is often associated with pregnancy in particular, although puberty is also known to induce
Several commonly employed medications, such as aspirin, other nonsteroidal antiinflammatory drugs (NSAIDs), beta-blockers, angiotensin-converting enzyme (ACE) in hibitors, methyldopa, oral contraceptives, psychotropic agents and nasal topical decongestants (oxymetazoline, naphazoline, xylometazoline) may induce symptoms of rhinitis when they are administered either topically or systemically. The symptoms may be either predictable, as would be the case for known side effects of particular drugs, or unpredictable, based on individual hypersensi tivity to certain drugs,
in
particular
aspirin,
which
commonly exacerbates rhinitis and asthma. However, intolerance to aspirin and/or NSAIDs predominantly produces rhinorrhoea, which may be either isolated or part of a complex involving hyperplastic rhinosinusitis, nasal polyps and asthma.1 In contrast, intolerance to ACE inhibitors, methyldopa or oral contraceptives, which is less common than aspirin intolerance, leads predomi nantly to nasal blockage.1 Whilst persistent overuse of the topical nasal vasoconstrictors also leads to nasal decon gestion by a mechanism involving a rebound effect following withdrawal of these drugs,
excessive use of
these agents may also lead to nasal hyperreactivity and hypertrophy of the nasal mucosa, a condition known as , 'rhinitis medicamentosa .1,8 [****/***/**]
Other forms of rhinitis I\lARES
the symptoms of rhinitis.1,8 A large multicentre study
The term NARES was originally introduced by Mullarkey
has recently indicated that the cumulative incidence of
and colleagu�s, who characterized the condition on the
pregnancy rhinitis was 22 percent, and in women who
basis of a presence of greater than 20 percent eosinophils
Chapter 110 Nonaliergic perennial rhinitis
&
in nasal smears of symptomatic patients with perennial sneezing attacks, a profuse watery rhinorrhoea, nasal pruritis, incomplete nasal obstruction and occasional loss of smell. 1, 7, 8 In addition to these symptoms, a marked feature of the disease is the lack of evidence of allergy, as indicated by negative skin prick tests and/or absence of serum IgE antibodies to specific allergens. The prevalence of NARES has been shown to range between 13 and 33 percent in patients with nonallergic rhinitis?I,24 Although the specific aetiology of NARES is not clear, in view of the features shared by this syndrome and the triad (nasal polyposis, intrinsic asthma and intolerance to aspirin) and because NARES patients frequently develop nasal polyps and asthma later on in life, it has been suggested that NARES may be an early expression of the triad. 24 Indeed, in approximately 50 percent of NARES patients without a history of respiratory symptoms, bronchial responsiveness is associated with an increase in the number of sputum eosinophils, but not with an increase in the number of nasal eosinophils. 25 Some investigators have suggested that NARES is a variant of vasomotor rhinitis, and referred to the condition as 'perennial intrinsic rhinitis'. [***/**/*]
I 1411
EMOTIONALLY INDUCED RHINITIS
Although not studied extensively, emotional factors such as stress and sexual arousal have been documented to affect the nose, likely as a result of autonomic stimulation. 2,27 In patients suffering from post-coital rhinitis, anxiety appears to be a predominant feature, which leads to worsening of their disease. 27 [**/*]
ATROPHIC RHINITIS
Primary atrophic rhinitis is a condition that occurs predominantly in women and is characterized by progressive atrophy of the nasal mucosa and underlying bone of the turbinates. 1,2 This leads to the formation of thick crusts, which leave a constant foul smell (ozaena) in the nose. 1, 2 Furthermore, the nasal cavities are enlarged and there is the sensation of nasal congestion. Although the precise aetiology of this condition is not clear, it has been suggested that this may be a result of infection with Klebsiella ozaenae and other bacteria. However, primary atrophic rhinitis is distinct from secondary atrophic rhinitis, which develops directly as a result of granulomatous nasal infections, chronic rhinosinusitis, excessive nasal surgery, trauma and irradiation.
RHINITIS DUE TO PHYSICAL AND CHEMICAL FACTORS
Nasal symptoms similar to those of rhinitis can be induced by physical and chemical factors in individuals with sensitized nasal mucous membranes. 2 Cold, dry air has been shown to lead to a condition known as skier's nose, in which rhinorrhoea features prominently. Exposure to chemicals, particularly air pollutants derived ." from cigarette smoke and liquid petroleum fuels, have also been shown to directly exacerbate symptoms of rhinitis in nonallergic individuals,2 although their effects have generally been extensively investigated and well documented in the lower airways of allergic individuals. 26 Little information is available on the acute or chronic effects of air pollutants on the nasal mucosa. [***/**/*]
FOOD-INDUCED RHINITIS
Few studies have documented that certain foods and alcoholic beverages can induce nonallergic rhinitis, although the underlying mechanisms are largely unknown. Hot and spicy foods, in particular, which contain capsaicin lead to a watery rhinorrhoea termed 'gustatory rhinitis', probably as a result of the capsaicin stimulating the sensory nerves to release neuropeptides and tachykinins. I,2 In contrast, alcoholic beverages are thought to induce symptoms as a result of vasodilation. Dyes and preservatives, as well as sulphites, appear to playa role in a . very few cases, whereas some foods may contain clinically relevant concentrations of histamine or other biogenic amines. [*** /**1*]
.'/
!
DIFFERENTIAL DIAGNOSIS Allergic rhinitis is the major disease to differentiate from nonallergic rhinitis and may be excluded by appropriate allergy tests. However, the possibility of a local IgE production within the nasal mucosa may account for some cases where skin prick tests or IgE antibodies to common allergens are not positive. Several other conditions, including polyps, sinusitis, congenital and acquired anatomical abnormalities (e.g. nasal septal deviation, adenoid hypertrophy, hypertrophy of nasal turbinates, choanal atresia), b~nign and malignant tumours, granulomas, ciliary defects and cerebrospinal rhinorrhoea, 1,2 are known to mimic symptoms of nonallergic noninfectious rhinitis and therefore have to be excluded by careful examination in order to make the correct diagnosis. Anatomical nasal abnormalities block the flow of nasal secretions and lead to rhinorrhoea, postnasal drip and nasal blockage. In children, congenital choanal atresia can lead to reduced nasal airflow, resulting in nasal blockage. Tumours are not very common in the nasal passages, but when established and growing rapidly they often lead to unilateral nasal obstruction, bleeding and pain. Rhinorrhoea and nasal congestion, in the absence of pruritis, are also characteristic features of nasal mastocytosis, an extremely rare condition, in which eosinophils are absent and tests for IgE-mediated disease are negative.
1412 I
PART 13 THE NOSE AND PARANASAL SINUSES
DIAGNOSIS AS A STEP-WISE APPROACH
toxin
and
particularly
intranasal
CapSaICIn
may
be
beneficial. Studies in patients suffering from NANIPER In daily clinical practice. the diagnosis of nonallergic
have demonstrated that intranasal capsaicin leads to a
rhinitis and its subgroups is mainly based on a thorough
significant and long-term reduction in clinical VAS scores)
case history, followed by
the step-wise exclusion of
If the case history is suggestive of clinically relevant
•
also shown to significantly improve all symptoms and produce a larger vascular response throughout a six
noninfectious rhinitis: •
compared with placebo.lO In another study) treatment once daily for five weeks with intranasal capsaicin was
possible differential diagnoses) as follows.
check possible stimuli. severity and duration of disease; check drug use (systemic and topic) exposure at work place) hormonal status (pregnancy) hypothyroidism. acromegaly) and involvement of other organs (asthma, hormonal status);
•
exclude other nasal disease (rigid nasal endoscopy);
•
exclude allergy: skin prick test) serum 19E-antibodies to the most frequent inhalant allergens) and ultimately nasal provocation testing in selected cases;
•
exclude chronic rhinosinusitis (computed
•
perform nasal cytology (eosinophilia) and if shown
month follow-up period in patients suffering from severe chronic nonallergic rhinitis with nasal vasoconstrictor abuse.30 In cases where nasal obstruction is resistant to medical treatment and if the inferior turbinate is hyperplastic)
surgical intervention to reduce the size
of the turbinate by various procedures has been shown to be useful. Ethmoidal and vidian neurectomies have also been performed by excision. diathermy and cryotherapy) and have produced results with varying degrees and duration of success.
[****/***J
tomography (CT ) scan); to be positive then perform oral aspirin challenge.
CONCLUSION Despite increasing evidence for the various forms of nonallergic rhinitis) many of these conditions are often
THERAPY FOR NONALLERGIC PERENNIAL RHINITIS
underrated and trivialized) primarily due to the paucity of information on the causative factors) the underlying mechanisms and/or the absence of specific diagnostic
First) an evaluation of the severity of the disease should be
tests.
performed to confirm the need for therapy) in connection
amongst clinicians and researchers regarding classification
Furthermore)
there
are differences in opinion
with counselling on how to avoid nonspecific stimuli.
of disease and in conditions such as occupational rhinitis)
In
in particular) the situation is further compounded as
case
of
drug-induced)
food-induced
or
occupa
tional rhinitis) specific avoidance measures are employed
a
as first-line therapy.
implications) for both employers and employees alike.
consequence
of
legal
and
financial
compensatory
Several treatments (pharmaceutical, nonconventional
To date) no specific diagnostic test is available) and clinical
and surgery) have been employed for idiopathic non
diagnosis is based on case history and exclusion of other
allergic rhinitis?B Intranasal anticholinergics (ipratro
disease. Despite these difficulties) however) recent evi
pium bromide) may be useful in patients with nasal
dence suggests that relevant diagnostic tools and specific
secretion as the predominant symptom. whereas nasal
information regarding the mechanisms underlying some
decongestants should be avoided or limited to ten days.
of these conditions is more forthcoming and should
Topical steroids and antihistamines are the two main
therefore lead to a better overall understanding and
classes of drugs employed) of which only fluticasone
management of these conditions in the future.
propionate) budesonide) beclomethasone and azelastine) respectively) have been approved by the Food and Drug Administration (FDA). Azelastine nasal spray has been found to be more effective than placebo for control of rhinorrhoea) post-nasal drip) sneezing and nasal conges tion in most
patients.
although
its effect
on nasal
•
congestion was rather marginal. 29 T he efficacy of in tranasal steroids in patients with vasomotor rhinitis has
•
been inconsistent. Furthermore) whilst the topical nasal steroids are more frequently used for treatment of more
•
severe symptoms. they are mostly useful in patients in whom
an
.
inflammatory pathogenesis is a promi
nent feature of their
disease)
for
example NARES.
Recent evidence suggests that in patients who do not respond to treatment with nasal steroids, treatment with
Approximat I)' half of rhi Us patient may suffer from nonallergic rhinhis. There are no specific diagno tic test. for nonaU gic rhinitis. A thorough case hi ory is the best dtagno tic tooJ available and lould focus on drug intake, w0rk expo ure nd hormonal tatus to subdivide the onditi()n into ubgn�)Ups. 1\5 the, ymptoms are quite non�pecific, the differCHtial diagnoses have to be 6-xcluded.
•
nonconventional therapies such as silver nitrate) botulin
j
Chapter 110 Nonallergic perennial rhinitis
7.
I 1413
Settipane RA, Lieberman P. Update on nonallergic rhinitis. Annals of Allergy, Asthma and Immunology. 2001; 86:
.I Wherever possible, the treatment should take into account the aforementioned subgroups of nonallergic
*
494-507 . 8.
Rhinitis: the spectrum of the disease. In: Busse WW,
perennial rhinitis.
Holgate ST (eds). Asthma and rhinitis, 2nd edn. Oxford:
.I In idiopathic rhinitis, antihistamines and topical steroids are the two main classes of drugs for
Blackwell Science Ltd, 2000: 6-13. 9.
treatment. Topical steroids are to be preferred if an
human airway neurogenic inflammation. Journal of Allergy
.I Intranasal capsaicin treatment is still considered
.I Surgery is an option in patients with persistent nasal
Sanico A, Atsuta S, Proud D, Togias A. Dose-dependent effects of capsaicin nasal challenge: in vivo evidence of
inflammatory pathogenesis is suggested. experimental.
van Cauwenberge PB, Wang D-Y, Ingels KJAO, Bachert C.
and Clinical Immunology. 1997; 100: 632-41. 10.
Blom HM, van Rijswijk JB, Garrelds 1M, Mulder PGH, Timmermans T, Gerth van Wijk R. Intranasal capsaicin is
obstruction not improved by medication.
efficacious in nonallergic, non-infectious perennial rhinitis. A placebo-controlled study. Clinical and Experimental Allergy. 1997; 27: 796-801. 11.
Gerth van Wijk R, Fokkens WJ. The long-term effects of
Deficiencies in current knowledge and areas for future research
>-
capsaicin aqueous spray on the nasal mucosa. Clinical and Experimental Allergy. 1998; 28: 1351-8. 12.
There is a marked lack of diagnostic tools/procedures
nose is a stimulus for NANIPER but not for controls.
)- There is a marked lack of controlled trials for
>-
Epidemiological studies on prevalence of different
* 13.
Rhinology. 2000; 38: 172-6. Fokkens WJ. Thoughts on the pathophysiology of nonallergic rhinitis. Current Allergy and Asthma Reports.
types of nonallergic rhinitis are required. )- Research on mechanisms underlying these conditions
Braat JPM, Fokkens WJ, Mulder PG, Kianmaneshrad N, Rijntjes E, Gerth Van Wijk R. Forced expiration through the
for determining each type of these conditions. determining diagnosis.
Blom HM, Severijnen LA, van Rijswijk JB, Mulder PGH,
2002; 2: 203-9. 14.
is needed.
Milosevic DN, Janosevic UB, Janosevic SB. Intradermal tests with vasomotor agents in perennial nonallergic rhinitis. Acta Oto-Rhino-Laryngologica Belgica. 2000; 54: 465-71.
15.
Zambetti G, Moresi M, Romeo R, Luce M, Filiaci F. Nonspecific nasal provocation test with histamine. Analysis of
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1.
* 16.
Dykewicz MS, Fineman S, Skoner DP, Nicklas R, Lee R,
(NINAR); considerations on possible mechanisms.
Blessing-Moore J et al. Diagnosis and management of
American Journal of Rhinology. 1998; 12: 65-72.
rhinitis: complete guidelines of the Joint Task Force on
17.
PS, Ayres JG. Pulmonary function and respiratory
American Academy of Allergy, Asthma, and Immunology.
symptoms in a population of airport workers. Occupational
478-518. 2.
and Environmental Medicine. 1999; 56: 118-23. 18.
4.
Bousquet J, van Cauwenberge P, Khaltaev N, the ARIA
Steerenberg P, Doekes G et al. Upper airway inflammation assessed by nasal lavage in compost workers: A relation
asthma - ARIA Workshop Report. Journal of Allergy and
with bio-aerosol exposure. American Journal of Industrial
Hansen B, Mygind N. How often do- normal persons sneeze
Medicine. 2000; 37: 459-68. 19.
airway response in workers exposed to fuel oil ash: nasal
Mullarkey MF, Hill JS, Webb DR. Allergic and nonallergic
lavage analysis. Occupational and Environmental
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Medicine. 1995; 52:353-8. 20.
Clinical Immunology. 1980; 65: 122-6.
Ellegard E, Hellgren M, Toren K, Karlsson G. The incidence of pregnancy rhinitis. Gynecologic and Obstetric
Jessen M, Janzon L. Prevalence of nonallergic nasal complaints in urban and a rural population in Sweden.
6.
Hauser R, Elreedy S, Hoppin JA, Christiani DC. Upper
and blow the nose? Rhinology. 2002; 40: 10-2. rhinitis: their characterization with attention to the
5.
Douwes J, Wouters I, Dubbeld H, van Zweiten L,
Workshop Group. Allergic rhinitis and its impact on Clinical Immunology. 2001; 108: S147-333. 3.
Tunnicliffe WS, O'Hickey SP, Fletcher TJ, Miles TF, Burge
Practice Parameter in Allergy, Asthma and Immunology. Annals of Allergy, Asthma and Immunology. 1998; 81 :
*
the dose-response curve. Rhinology. 1999; 37: 168-74. Sanico A, Togias A. Noninfectious, nonallergic rhinitis
Investigation. 2000; 49: 98-101. 21.
Settipane GA, Klein DE. Non allergic rhinitis: demography
Allergy. 1989; 44: 582-7.
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1414 I PART 13 THE NOSE AND PARANASAL SINUSES Hamano N, Terada N, Maesako K, Ikeda T, Fukuda S, Wakita J et al. Expression of histamine receptors in nasal epithelial cells and endothelial cells - the effects of sex hormones. International Archives of Allergy and Immunology. 1998; 115: 220-7. 23. Hamano N, Terada N, Maesako K, Numata T, Konno A. Effect of sex hormones on eosinophilic inflammation in nasal mucosa. Allergy and Asthma Proceedings. 1998; 19: 263-9. 24. Moneret-Vautrin DA, Hsieh H, Wayoff M, Guyot JL, Mouton C, Maria Y. Nonallergic rhinitis with eosinophilia syndrome a precursor of the triad: nasal polyposis, intrinsic asthma, and intolerance to aspirin. Annals of Allergy. 1990; 64: 513-8. 25. Leone C, Teodoro C, Pelucchi A, Mastropasqua B, Cavigioli G, Marazzini L et al. Bronchial responsiveness and airway inflammation in patients with nonallergic rhinitis with 22.
26.
27. 28. 29.
30.
eosinophilia syndrome. Journal of Allergy and Clinical Immunology. 1997; 100: 775-80. Devalia JL, Rusznak C, Wang J, Khair OA, Abdelaziz M, Calderon MA et al. Air pollutants and respiratory hypersensitivity. Toxicology Letters. 1996; 86: 169-76. Shah A, Sircar M. Postcoital asthma and rhinitis. Chest. 1991; 100: 1039-41. Lieberman P. Treatment update: nonallergic rhinitis. Allergy and Asthma Proceedings. 2001; 22: 199-202. Banov CH, Lieberman P. Efficacy of azelastine nasal spray in the treatment of vasomotor (perennial nonallergic) rhinitis. Annals of Allergy, Asthma and Immunology. 2001 ; 86: 28-35. Lacroix JS, Buvelot JM, Polla BS, Lundberg JM. Improvement of symptoms of nonallergic chronic rhinitis by local treatment with capsaicin. Clinical and Experimental Allergy. 1991; 21: 595-600.
111 Occupational rhinitis HESHAM SALEH
Introduction Risk factors Pathogenesis High risk occupations Effects of air pollution Sick building syndrome Diagnosis
1415 1416 1416 1418 1419 1420
Management Key points Best clinical practice Deficiencies in current knowledge and areas for future research References
1421 1421 1422 1422 1422
1420
The data in this chapter are supported by Medline and Embase searches using the key words rhinitis, occupational rhinitis, rhinitis and occupation, air pollutants and occupational, occupational disease, occupational accident, occupational allergy, occupational exposure, occupational hazard, occupational health, occupational medicine, occupational safety, work environment, industrial medicine, industry, industry and industrial phenomena, work and disability.
INTRODUCTION Occupational rhinitis (OR) has been defined as the episodic work-related symptoms of rhinitis. I Symptoms usually manifest on weekdays and abate during weekends and holidays. When exposure has been prolonged, the condition may become irreversible and symptoms persist. 2 ,3 It frequently coexists with asthma and conjunctivitis, and it has been suggested that occupational rhinitis precedes the development of occupational asthma. I, 3 Although reports of occupational rhinitis turning into asthma are scarce, in one study most of the rhinitis patients were younger than those with asthma, suggesting that rhinitis is the first to develop.4 Occupational rhinitis is commoner than occupational asthma and most reports show that it tends to occur three times more frequently. 3 Occupational asthma rarely occurs as an' isolated disease without occupational rhinitis. lOne report· found that 92 percent of patients with
..
/
occupational asthma have occupational rhinitis and 72 percent had conjunctivitis. 5 [** /*] The prevalence of occupational rhinitis is unknown. Studies have dealt primarily with occupational asthma with less work on rhinitis. It has been estimated that 2-5 percent of all patients with asthma in the USA have workinduced asthma. I It is possible that the incidence of occupational rhinitis is underestimated due to failure to diagnose and because, unlike asthma, it is not a life-threatening condition. Workers may be reluctant to report symptoms for this reason and for fear of job loss, loss of seniority or fear of repercussions from coworkers. 6 Various cross-sectionaf studies of populations from diverse occupations exi~t but, because of the different methodology used, the interpretation of data is difficult. Furthermore, data from epidemiological studies are lacking. Information from the Finnish Institute of Health showed that 20 percent of all cases of rhinitis were occupational in origin. 7 It also showed that the number of
1416 I PART 13 THE NOSE AND PARANASAL SINUSES cases more than doubled between 1987 and 1991. Another study, utilizing the Finnish register, showed that the incidence of occupational rhinitis is higher in men than women (60 and 40 percent, respectively). Also, a gender difference exists for the age at which occupational rhinitis develops. Men have the highest incidence at the age range of 25-29 years, after which the incidence gradually declines. In women, the incidence of occupational rhinitis gradually increases and peaks between 40 and 44 years of age. 4 It has been suggested that this difference is related to the fact that men and women are engaged in different jobs and hence exposed to different kinds of causative agents. 8 [** /*] More than 200 chemicals and organic dusts have been implicated as a cause of occupational rhinitis and asthma. 1 The pathological effects of these are either due to an allergic reaction or irritation of the nasal mucosa. Welldocumented causative agents include laboratory animals, such as rats, mice and guinea pigs, grains (bakers), storage mite (agricultural workers), wood dust, particularly hard wood such as western red cedar (furniture manufacturers), guar gum (workers in the food processing and carpet industry), Bacillus subtilis enzymes (detergent manufacturing workers), latex and chemicals such as acid anhydrides, isocyanates, platinum salts, glues and solv~nts.I, 3, 6 Symptoms may develop after a latency period of two months to 18 years in the case of allergic occupational rhinitis. 1, 6 This observation does not apply to irritant occupational rhinitis which can develop on immediate exposure. [***/**]
Approximately 80 percent of those that have an AED of more than 9 !lm, 50 percent of those with 2-9!lm AED and 40 percent of material with less that 2 !lm stick to the nasal wall. Highly soluble materials, such as ammonia, sulphur dioxide and formaldehyde, also deposit in the upper airway. Smaller particles and less water-soluble gases generally pass to the lower airways. 8 According to the nature of the offending agent, occupational rhinitis may be allergic or irritant. [***]
Allergic occupational rhinitis Allergic occupational particles may trigger an IgEmediated (type 1) immune response. A late-phase response may also develop four to six hours after the initial reaction. 8 The causative agents are classified into high molecular weight compounds (HMWC), such as animal and vegetable proteins, and low molecular weight compounds (LMWC), such as isocyanates and anhydrides. An IgE-dependent mechanism, that can be assessed through skin prick test and radioallergosorbent test (RAST) , has been demonstrated with most HMWCs. 3 , 8 LMWCs can also produce specific IgE antibodies by acting as a hapten to form a hapten-protein conjugate. However, an IgE-mediated mechanism has been elicited only rarely with LMWC. Table 111.1 shows a number of HMWCs and Table 111.2 shows LMWCs implicated in allergic occupational rhinitis with the related occupations. 3 ,6,11 [**/*]
RISK FACTORS Irritant occupational rhinitis Risk factors for developing occupational rhinitis include exposure (intensity and duration), atopy and smoking. 6 Most reports on exposure have focussed on intensity, and associations have been confirmed in laboratory animal workers, wool textile mill workers and bakery workers amongst others. 3 Duration of exposure has seldom been studied. Other studies have shown an association between atopy and specific sensitization to high molecular weight agents in grain elevators, fish and seafood workers, bakers, workers exposed to latex, coffee and others. Although smoking is known to induce the release of inflammatory mediators and to cause mucosal changes, its impact on occupational rhinitis is yet to be shown. The current evidence on this matter is still inconclusive as some studies show higher risk of occupational rhinitis in smokers and some do not. 3 , 6, 9 [**]
PATHOGENESIS The nose is the first portal of entry and is exposed to a constant stream of air. Materials that accompany the air stream tend to impact on the mucus surface as a function of their aerodynamic equivalent diameter (AED) .10
Nonallergic, irritant chemicals may trigger the release of substance P and other inflammatory mediators from sensory C-fibres after binding to chemoreceptors on their surface. I2 This sequence, known as neurogenic inflammation, leads to vasodilatation, oedema and other manifestations of inflammation. The patients complain of burning, stinging or painful sensation in the nasal passages in addition to nasal congestion and rhinorrhoea. I Delayed response does not occur in cases of irritant rhinitis. 8 Although some existing evidence shows the release of substance P in the nose with exposures to nicotine, capsaicin, ether and formaldehyde, no such data are available for other chemicals. Chronic irritant rhinitis requires protracted exposure to one or more irritating chemicals. However, in reactive upper airways dysfunction syndrome (RUDS), rhinitis results from an acute exposure to high concentrations of a respiratory irritant and persists after the exposure. 12 Table 111.3 shows a number of agents implicated in irritant occupational rhinitis with the related occupations. 1, 6,11 [**/*] Corrosive reactions may also occur due to excessive concentrations of irritating and soluble chemical gases. Substances implicated in causing corrosion are ammonia,
Chapter 111 Occupational rhinitis
Animal proteins (rats, mice, guinea pigs, rabbits, hamsters) Other animal derived allergens (pig) Grain dust Flour; alpha amylase
Bacillus subtilis Enzymes (papain, trypsin, pancreatic extracts, lactase) Wool Insects (locust, fruit fly) Arthropods Mites (storage, red spider) Mould spores Latex Guar gum/vegetable gum Green coffee bean Tea Dried fruits Tobacco leaf Cayenne peppers Pollens Sunflower pollen Soy bean dust Saffron flower Cocoa Garlic Milk proteins (alpha lactalbumin, casein) Fish, prawn, crab Bird proteins Raw poultry Cow dander
Table 111.2
Laboratory animal workers, pet shop owners, veterinarians, farmers Swine confinement workers Grain elevators Bakery workers Detergent workers Pharmaceuticals Wool textile workers Laboratory workers Laboratory workers Bakers, farmers, grain elevators, food processors Librarians Health care workers Food processors, carpet workers, printing Coffee production Tea workers Dried fruit workers Tobacco workers Hot pepper workers Gardeners, greenhouse workers Bakers, agricultural workers Farmers, food processors Saffron workers Packers Food workers Chocolate manufacturing, tannery Food processors Poultry breeders, farmers Food processors Dairy farms
Low molecular weight compounds (LMWC) causing allergic occu
Diisocyanates (toluene diisocyanates, diphenyl-methane diisocyanates) Anhydrides (trimellitic anhydride, methyl tetrahydrophtalic anhydride, pyrotomellitic anhydride) Wood dust (western red cedar, several other woods) Colophony Metals (platinum, nickel, chromium) Drugs (psyllium, senna, spiramycin) Chemicals (reactive dyes, carmine, polyamide, polyester, para-amide) Cotton Persulphates Solvents and organic dust Azo dyes Chlorine
..
/
Painters, urethane mould workers Epoxy resin production, plastics, electric condenser workers, chemical workers Furniture making, carpentry Electronics, welders Platinum refinery, metal processing or plating Health care workers, bulk laxatives factory workers, pharmaceuticals Reactive dye products, synthetic fibre Cotton mills Persulphate products, hairdressers Shoe manufacturing Textile dying Pulp and paper production
I 1417
1418 I PART 13
THE NOSE AND PARANASAL SINUSES
Ammonia, nitrogen dioxide, hydrogen sulphide Smoke Cooking vapour Glutaraldehyde, formaldehyde Inorganic acid vapours Sulphur dioxide Solvent vapours Zinc chloride smoke Chlorine, chlorine dioxide, hydrogen sulphide Oxides of nitrogen, ozone, diesel exhaust Asphalt vapours, polycyclic aromatic hydrocarbons Metallic oxide fumes Talc
Agricultural workers Firefighters Food service workers Health care workers Laboratory workers Power plant, oil refinery workers Printers, painters Military personnel Pulp mill workers Traffic wardens, lorry drivers, railroad workers Roofers, pavers Welders Pharmaceuticals workers, cosmetics manufacturers
hypochloric acid, vinyl chloride, organic sulphur containing compounds, acrylamide, cyanide, nitriles and organophosphoside compounds. 1 Disorders of olfaction may occur as a result of rhinitis or as a direct effect of irritants on the olfactory receptors and their central connections. 13 Anosmia and hyposmia have been reported after single high-dose exposure to sulphuric acid, hydrogen selenide, phosphorous oxychloride and a mixture of pepper and cresoL S Other case reports of olfactory disorders present workers chronically exposed to low levels of chemicals such as benzene, benzol, cadmium, carbon disulphide, ethyl acetate, formaldehyde, hydrazine, menthol, solvents and oil of peppermint. s, 14 However, olfactory disorders in occupational rhinitis are otherwise underinvestigated. [**/*] Similar to other patients with allergic and nonallergic rhinitis, patients with occupational rhinitis may manifest nasal hyperreactivity to nonspecific environmental agents such as changes in temperature and humidity, exposure to tobacco smoke and strong odours. 1 The prevalence of this entity is, however, unknown. [*]
The prevalence of occupational rhinitis in farmers is unknown. However, a variety of agricultural exposures have been associated with rhinitis. These include grain farming and handling, livestock breeding, feed manufacture and handling, dairy farming, tea farming, cotton, flax and hemp processing and organophosphorous pesticides. 15 Storage mites, present in storage hay, have been described as a cause of barn allergy. A number of reports on grain elevator workers showed prevalence of sensitization in 9-28 percent? [**]
HIGH RISK OCCUPATIONS
Food-processing workers
Data from the Finnish Register of Occupational Diseases identified furriers, who are exposed to different kinds of animal epithelium, as the highest risk group for developing occupational rhinitis. Livestock breeders and bakers were the occupations following in rank. 4 Other commonly reported occupations include farmers, food-processing workers, wood workers, detergents manufacturers, animal laboratory workers and healthcare workers. [**]
It has been suggested that the food industry accounts for
Bakers A large number of cross-sectional studies show that workrelated symptoms of rhinitis and sensitization are
common among bakery workers. Work-related rhinitis has been shown in 18-29 percent of workers and specific sensitization in 10-38 percent. 3 The offending agents are wheat and cereal flours, cereal amylases, fungal amylases, storage mites contaminating wheat flour and others such as baking additives. [**]
Farmers
the largest number of cases of occupational rhinitis.12 Cases of occupational rhinitis due to guar gum are well documented. It is obtained from the seeds of the tree Cyamopsis tetragonoloba, and used as a food additive as well as a laxative and a colour fixing in agent in the carpet industry. The prevalence of symptoms in workers is, however, less well documented. Symptoms related to other plant-related allergens, such as soybean, coffee bean, garlic, cinnamon and hot peppers, have also been reported. 3 , 12 Occupational rhinitis has also been correlated to fish and seafood proteins. 3 Prevalence of symptoms ill' 5-25 percent of fish factory workers has been reported. 3 [**/*]
Chapter 111 Occupational rhinitis
Wood manufacturers Hard woods, often of tropical ongm, are well-known factors in causing work-related symptoms. Plicatic acid, found in western red cedar, has been suggested as the causative agent of rhinitis in carpenters and furnituremanufacturing workers. 3,16 Symptom prevalence figures are less well documented. Oak, beech and pine have also been implicated. 16 Soft woods, used in joiner shops, have been less reported in relation to rhinitis.16 [**/*]
Detergent manufacturers Biological enzymes are used extensively in the detergent industry as weli as the pharmaceutical and food industry. Bacillus subtilis enzymes and lactase have been commonly implicated in occupational rhinitis. 1, 3, 6 Prevalence rates of occupational rhinitis from 7 to 16 percent have been reported in workers. Specific sensitization ranged from 22 to 52 percent. 3 [**]
Animal laboratory workers Laboratory workers are one of the groups most commonly affected with occupational rhinitis.9 It has been suggested that proteins from virtually any mammalian species may induce an allergic response in human beings. 1 Rats are the most commonly implicated but mice, guinea pigs, rabbits and hamsters are also known to cause occupational rhinitis. 3, 9 Immunological substances implicated include saliva, urine, dander and serum. Reports demonstrate symptom prevalences of 10 to 33 percent and specific IgE antibodies to animal protein in 6-46 percent of workers. 3 [**]
Health care workers
.
Concern about latex allergy in health care workers and patients has risen due to the extensive use of latex gloves. Rubber latex is a naturally occurring cytoplasmic exudate obtained from the tree HeveaBrasiliensis. 1? It is used extensively in the manufacture of surgical gloves and other medical devices (drains, ambu bags, mouth gags and bandages are some) .18 Aerosolized particles of latex proteins are carried in the cornstarch used to powder the gloves and may remain airborne for hours. 18, 19 Significant quantities of airborne latex have been measured in areas using powdered latex gloves. 19 These proteins have been implicated in causing rhinitis, asthma and anaphylaxis. 1?, 18, 19 Exposed personnel may also develop contact dermatitis as a reaction to the chemical accelerators and preservatives that are added to latex to improve its physical property. 18 Anaphylaxis most often affects
/
( ~
I 1419
patients during open surgery due to mucosal absorption and has been reported in those who have had multiple surgical procedures and in patients with spina bifida. 1? However, anaphylactic reactions were also reported during gloving and inhaling latex in the workplace. I? Health care workers with regular latex exposure have been reported to have symptom prevalence rates of 3-17 percent. 20 Specific skin tests have been shown to be positive in 5-20 percent in contrast to prevalence in the general population of less than 1 percent. I? [**] Other substances that may cause occupational rhinitis in health care workers include formaldehyde and drugs such as psyllium, senna and spiramycin.3 Formaldehyde is also used widely in industry in addition to its use as a sterilizing agent in medicine. It is toxic at high doses and can induce irritant reaction. It has also been suggested that it can act as hapten and cause an IgE mediated reaction. 21 [**/*]
Other occupations Workers reported to have occupational rhinitis in other occupations are detailed in Tables 111.1, 111.2 and 111.3. [**/*]
EFFECTS OF AIR POLLUTION In the first half of the twentieth century, dramatic episodes of severe pollution caused by sulphur dioxide (S02) derived from coal combustion occurred in the western world. Regulations to decrease the use of coal in homes and industry were set and other fuels, such as petrol and gas, substituted coal. The bypro ducts of petrol consumption in transport and industry, however, have replaced the decline of coal-associated pollution. Exhaust fumes consist of oxides of nitrogen, namely nitric oxide (NO) and nitric dioxide (N0 2), ozone (0 3), particulate matter (PM) and volatile organic compounds (VOCS).22 Much of the research carried out on pollution has been on its effects on the lower airway. However, epidemiological studies suggest an association between pollution and rhinitis.23 Laboratory studies have shown that exposures to NO, 0 3 and diesel exhaust particles result in the release of inflammatory mediators in the nasal mucosa. 24 A link between high levels of environmental pollutants and 25 increased prevalence of allergy has also been suggested. Whether this would have an impact on allergic occupational rhinitis remains to be examined. [***/**] Certain occupations, such as tt:affic wardens, railroad workers and lorry drivers, may be exposed to high levels of pollution. Epidemiological studies in this area are almost nonexistent. One study from Thailand showed a high prevalence of symptoms of rhinitis of traffic 26 policemen compared to the general population. Further research is needed in this area. [**]
I
.l1f~)jZkl . i.
1420 I PART 13 THE NOSE AND PARANASAL SINUSES
SICK BUILDING SYNDROME Sick building syndrome (SBS) is described as the high prevalence of eye, nose and throat irritation, fatigue and headache among office workers temporally associated with time at work and is characterized by an absence of abnormal physical findings and laboratory results. 8 It is a diagnosis of exclusion as multiple causative agent have been implicated. More than 300 VOCs were identified as indoor pollutants causing SBS. They originate from building materials, combustion fumes, cleaning compounds, paints and stains, in addition to tobacco smoke. It has been suggested that the type of ventilation is important in the causation of SBS. 27 One study showed that workers in buildings with mechanical ventilation and air conditioning have a higher risk of SBS symptoms than workers in naturally ventilated buildings. 28 [**/*]
DIAGNOSIS Diagnosing occupational rhinitis can be difficult. A combination of history, examination and investigation will aid the diagnosis. Nasal challenge with the suspected agent is particularly central to secure the diagnosis. [** /*]
first -degree relatives. 1, 2 An enquiry about problems of the sense of smell and taste should also be made. [**/*] A detailed occupational history includes the patient's account of a typical working day, the nature of chemicals, duration and intensity of daily exposure and use of protective masks. 8 Substance information sheet or an engineer's report may also be required, particularly in medicolegal cases. Other work factors such as type and efficiency of ventilation, history of accidents and spills, and effects on co-workers should also be considered. 26 A site visit has been recommended if the history of work conditions is unhelpful. 1 [*]
~Examination The physical findings in occupational rhinitis are nonspecific. Nasal examination should include description of mucosal changes, nature of secretions, crusting, epistaxis, ulceration and perforation. These are particularly important in medicolegal cases. 1 Crusting and epistaxis are more common in irritant rhinitis. Eye inspection for conjunctivitis and oral cavity/oropharynx examination for ulceration should also be carried out. Chest examination for signs of asthma is important as well as inspection for dermatitis, which occurs in latex allergy. [*]
History Investigations The patients present with a variable number of symptoms including nasal obstruction, anterior rhinorrhoea, postnasal discharge, crusting, disturbed sense of smell and taste and epistaxis? A detailed history of the patient's complaint in addition to occupational history is essential to aid the diagnosis. Development of symptoms during the working week with improvement at weekends and holidays provide the clue for diagnosis. However, history in itself is not sufficient for diagnosis and could be feigned by workers claiming compensation. The history can be further compounded by the presence of symptoms of rhinitis due to atopy in allergic patients. In patients with protracted exposure, the symptoms may continue during absence from work, further complicating matters. 1 1 The difference in presentation between allergic and irritant occupational rhinitics should also be borne in mind. In allergic patients, rhinitis may take longer to develop and may be manifested by a delayed response a few hours after exposure. On the other hand, patients with irritant rhinitis may develop the symptoms instandy on exposure and do not have a delayed response. 1 A history of eye, throat, skin and chest symptoms should be elicited. It is important to enquire about smoking and drug history including overthe-counter decongestants, substance abuse and other drugs known to cause nasal symptoms such as aspirin, alpha-blockers, beta-blockers, antidepressants and angiotensin-converting enzyme (ACE) inhibitors. Enquiries should be made on history of atopy in the patient and
The skin prick test is useful in allergic occupational rhinitis if an appropriate antigen exists. It is also helpful in diagnosing suspected atopy. Some occupational antigens are available commercially, such as in the case of latex. However, sensitization to an occupational agent is not sufficient to diagnose occupational rhinitis, because it only indicates an immunological response and not necessarily a clinical syndrome. 3 Skin prick tests have been used extensively in cross-sectional studies to assess sensitization to a specific agent. Sensitivity and specificity have been evaluated with differing results. 3 Measuring serum specific IgE RAST has also been used in a number of studies. The sensitivity and specificity is probably less than that of the skin prick test. It has been suggested that a combination of both tests may enhance sensitivity and specificity.6 [***/**] A secure diagnosis cannot be made without an attempt to nasal challenge. 1, 6 This is more conclusive when performed in controlled conditions in the laboratory with known agents. Carefully graded exposure to increasing doses of the suspected agent in specialized ventilated environmental chambers is the best method. Difficulties arise when dealing with unknown or multiple agents?' l3 On these occasions, a work place challenge may be an option. 3 ,15 Unfortunately, no standardized method for nasal challenge is yet recommended and the test is time consuming.-The test must be accompanied by an objective measure of the nasal response, such as acoustic
Chapter 111 Occupational rhinitis
rhinometry. It is suitable for rapid and repeated measurement and its portability makes it ideal for assessment in the work place. 4 Nasal inspiratory flow (NIPF) rate measurement is also useful with nasal challenge. It can also be used by the patient to measure fluctuations of the nasal airway during the working week. 3 Other measures, such as collecting nasal lavage for analysis of cells and inflammatory markers, rhino manometry and brush biopsies, have been used with nasal challenge. They are generally more suitable for research situations and have been used extensively in various trials. 3 [***/**] When an olfactory disorder is suspected and in medicolegal cases, olfaction should be tested using one of the commercially available tests, such as the University of Pennsylvania Smell Identification Test (UPSIT).2 [*]
MANAGEMENT The best management approach for occupational rhinitis is prevention. In established cases avoidance methods should be instituted and medical therapy may be tried. Immunotherapy may have a part to play in treating severe cases of allergic occupational rhinitis. [Grade C]
Prevention It has been suggested that applicants for high risk jobs
should be screened for atopy by history taking and a skin prick test. However, in a study on laboratory animal workers, this method was shown to be inefficient. Rejecting workers who were atopic by history and skin prick test leads to an avoidance of 44 percent of workers who develop rhinitis and asthma and only 23 percent of those who develop rhinitis alone. Eliminating those with a positive skin test only removes 13 percent of those who develop rhinitis.29 Prevention in the work place may be effective and should always be considered. 9 Environmental control measures are undertaken by recognizing potentially sensitizing allergens and controlling the point source of any mucosal irritant. Masks, gloves and protective clothing should be used and ventilation improved. 1, 6, 9 [Grade C] In workers with established diagnosis, certain avoidance measures may be effective. For example, laboratory workers who become sensitive to rats generally react to rat urinary protein rather than epithelium. It has been suggested that it may be possible for them to perform surgery on rats, if the cage containing the rats - which is soaked with urine - is kept out of the laboratory.9 In health care workers sensitive to latex, the use of powderfree gloves by all co-workers has been shown to reduce symptoms and allow allergic patients to continue their work. 17 Low protein latex gloves have also been suggested but studies confirming their effectiveness are needed. I7 Nonlatex gloves are becoming available and may be used as an alternative for sensitive individuals. In some
I 1421
occupations where preventive measures are ineffective, relocation of the worker or even changing jobs may be recommended. [Grade C]
Medical therapy Medical therapy of occupational rhinitis is similar to that of other types of rhinitis. Antihistamines, sodium cromoglycate, topical corticosteroids, anticholinergic spray and saline douches have all been used. 1,6,9 Systemic steroids have also been suggested in severe cases. 6 Treatment may be most effective in allergic occupational rhinitis. 6 However, no studies on the efficacy of these medications in occupational rhinitis are available at present. The choice of agent is often based on trial and error according to efficacy and frequency of side effects. Sedating antihistamines affect work productivity adversely and second-generation antihistamines are preferred. Patients may use them regularly when they have chronic symptoms or periodically before an expected exposure to an allergen. 9 [Grade D]
Immunotherapy Limited information is available on the efficacy of immunotherapy in allergic occupational rhinitis. Fear of severe reactions with continued exposure to the offending antigen at the same time of the administration of immunotherapy have precluded its use. 1 Furthermore, many of the offending antigens are not available for treatment. 9 A recent study showed that latex immunotherapy led to significant improvement in rhinitis symptoms but several adverse effects occurred in the study group.30 However, where alternative jobs are not a consideration, the risks of treatment should be balanced against the benefits.1 [Grade C]
1422 I
PART 13 THE NOSE AND PARANASAL SINUSES
current knowledge of the epidemiology of occupational rhinitis. 4. ,/ When occupational rhinitis is suspected, a detailed
Mutanen P, Toikkanen J. The risk of occupational rhinitis.
history of the patient's complaint in addition to
International Archives of Occupational and Environmental
occupational history is essential to aid the diagnosis.
Health. 1997; 69: 487-90.
,/ In addition to nasal examination, inspection for
5.
dermatitis and chest examination for asthma are
occupational asthma. European Respiratory Journal. 1997;
,/ Every patient with suspected occupational rhinitis ,/ Nasal challenge is the main diagnostic test.
*
10: 1513-5. 6.
Puchner TC, Fink IN. Occupational rhinitis. Immunology and Allergy Clinics of North America. 2000; 20: 303-22. A
,/ Prevention in the work place should start early. ,/ In patients with occupational rhinitis, only
Malo JL, Lemiere C, Desjadins A, Cartier A. Prevalence and intensity of rhinoconjunctivitis in subjects with
mandatory. must have an allergy test.
Hytonen M, Kanerva L, Malmberg H, Martikainen R,
comprehensive review on occupational rhinitis. 7.
nonsedating antihistamines should be used.
Kanerva L, Vaheri E. Occupational allergic rhinitis in Finland. International Archives of Occupational and Environmental Health. 1993; 64: 565-8.
8.
Epling CA. Upper respiratory problems. Occupational and
9.
Slavin RG. Occupational rhinitis. Annals of Allergy, Asthma
Environmental Medicine. 2000; 27: 997-1007.
Deficiencies in current knowledge and areas for future research
and Immunology. 1999; 83: 579-601. 10. Andersen I, Lundqvist GR, Proctor DF, Swift DL. Human response to controlled levels of inert dust. American Review of Respiratory Diseases. 1979; 119: 619-27.
.. Most available data on occupational rhinitis originate from cross-sectional studies that used different
11.
methodologies making interpretation difficult.
disorders. Seminars in Respiratory and Critical Care Medicine. 1999; 20: 569-80.
Evidence on the prevalence and natural history of the condition is insufficient. Diagnostic methods have not
Balkissoon R, Shusterman DJ. Occupational upper airway
12.
Meggs WJ. RADS and RUDS - The toxin induction of
been standardized and no studies have been carried
asthma and rhinitis. Clinical Toxicology. 1994; 32:
out on the efficacy of treatment. Furthermore, the
487-501.
impact of occupational rhinitis on quality of life has
13.
not been documented.
possible mechanisms of pathogenesis. Journal of
.. Epidemiological studies are needed to detect incidence and prevalence in various populations.
Laryngology and Otology. 1995; 109: 104-7.
14.
.. The impact of occupational rhinitis on the quality of
Emmett EA. Parosmia and hyposmia induced by solvent exposure. British Journal of Internal Medicine. 1976; 33:
.. Longitudinal studies should be conducted to document the natural history of the condition.
Welch AR, Birchall JP, Stafford FW. Occupational rhinitis -
196-8 . 15. Schenker MB, Christiani D, Cormier Y, Dimich-Ward H,
life of affected workers needs to be studied.
Doekes G, Dosman J et al. Respiratory health hazards in
)- Agreed diagnostic tests such as nasal challenge
agriculture. American Journal of Respiratory and Critical Care Medicine. 1998; 158: 51-76.
should be standardized. )- Randomized controlled trials should be designed to
16.
identify the best possible therapy.
De Zotti R, Gubian
F. Asthma and rhinitis in wooding
workers. Allergy and Asthma Proceedings. 1996; 17:
199-203. 17.
Sussman GL, Beezhold DH. Latex Allergy - A clinical perspective. Journal of Long-Term Effects of Medical Implants. 1994; 4: 95-101.
REFERENCES
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Deacock S. Latex allergy. CPD Bulletin of Immunology and Allergy. 2001; 2: 8-11.
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*
2.
Bardana EJ. Octupational asthma and related respiratory
19.
MA, Reed CE. Quantification of occupational latex
Drake-Lee A, Ruckley R, Parker A. Occupational rhinitis: a
aeroallergens in a medical center. Journal of Allergy and Clinical Immunology. 1994; 94: 445-51.
poorly diagnosed condition. Journal of Laryngology and Otology. 2002; 116: 580-5. A useful guide on the
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Swanson MC, Buback ME, Hunt LW, Yunginger JW, Warner
disorders. Disease-a-Month. 1995; 41: 143-99.
20.
Charous B, Hamilton R, Yunginger J. Occupational latex
medicolegal aspects of occupational rhinitis.
exposure: characteristics of contact and systemic
Siracusa A, Desrosiers M, Marabini A. Epidemiology of
reactions in 47 workers. Journal of Allergy and Clinical Immunology. 1994; 94: 18-21.
occupational rhinitis: prevalence, aetiology and determinants. Clinical and Experimental Allergy.
2000; 30: 1519-34. A valuable guide on the state of the
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Bous~uet J, Michel FB. Allergy to formaldehyde and
ethylene oxide. Clinical Reviews in Allergy. 1991; 9: 357-70.
Chapter 111 Occupational rhinitis I 1423 22. 23.
Saleh HA, Lund VJ. The nose as a target of air pollution.
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pollution, including sick building syndrome. Current
Kopp MV, Ulmer C, Ihorst G, Seydewitz HH, Frischer T,
Opinion in Otolaryngology Head and Neck Surgery. 1996; 4: 44-9.
Forster J et al. Upper airway inflammation in children exposed to ambient ozone and potential signs of adaptation.
European Respiratory Journal. 1999; 14: 854-61.
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Bascom R, Naclerio RM, Fitzgerald TK, Kagey-Sobotka A, Proud D. Effect of ozone inhalation on the response to nasal
28. Jaakkola JJ, Miettinen P. Type of ventilation system in office buildings and sick building syndrome. American Journal of Epidemiology. 1995; 141: 755-65. 29. Platts-Mills TA, Longbottom J, Edwards J, Cockroft A,
challenge with antigen of allergic subjects. American
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Wilkins S. Occupational asthma and rhinitis related to
Review ofRespiratory Diseases. 1990; 142: 594-601.
laboratory rats: serum IgE and IgE antibodies to the rat
Davies RJ, Rusznak C, Devalia JL. Why is allergy
urinary allergen. Journal of Allergy and Clinical
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increasing? - Environmental factors. Clinical and
Experimental Allergy. 1998; 28: 8-14.
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Wnogsurakiat P, Maranetra KN, Nana A, Naruman C,
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Leynadier F, Herman D, Vervloet D, Andre C. Specific immunotherapy with a standardized latex
Aksornint M, Chalermsanyakorn T. Respiratory symptoms
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and pulmonary function of traffic policemen in Thonburi.
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Clerico DM. Sources and effects of indoor air
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f
Ln
'<:'''st'
112 Food allergy and intolerance CARSTEN BINDSLEV-JENSEN AND MORTEN OSTERBALLE
Introduction Defi nitions Sensitization Primary prevention of food allergy Allergens and food additives Prevalence Diagnosis of food hypersensitivity
1424 1424 1425 1426 1426 1427 1427
Treatment Key points Best clinical practice Deficiencies in current knowledge and areas for future research References
1431 1431 1431 1432 1432
The data in this chapter are supported by a Medline search using the key words food allergy/hypersensitivity, allergens, additives, oral challenge, prevalence, respiratory symptoms including asthma, rhinitis and conjunctivitis.
INTRODUCTION Perceived adverse reactions to foods are very common in adults, but only in a few cases can such reactions be verified - on the other hand, food allergy is a common disease in infancy and childhood, as well as in patients with pollinosis. 1, 2, 3
DEFINITIONS Adverse reactions to foods may be classified either as food allergy (mediated by immunoglobulin E or, in a small proportion of cases by non-IgE-mediated mechanisms), or as nonallergic food intolerance caused by pharmacological, metabolic or toxic reactions to foods. In contrast, food aversion refers to symptoms, which are often nonspecific and unconfirmed by double-blind placebo-controlled food challenge (DBPCFC) (Figure 112.1 and Table 112.1).1 A true food allergy is a disorder where ingestion of a small amount of food elicits an abnormal immunologically mediated clinical response. Food may cause allergic reactions by several mechanisms. The classical type I,
IgE-mediated reaction is the most thoroughly studied and potentially important in view of the risk of life-threatening reactions in a proportion of individuals. However, evidence is increasing for an important role for delayed reactions (classical type IV-mediated reactions). Examples include exacerbation of eczema by milk ingestion in children. 4 A small percentage of severely affected adults with contact dermatitis due to nickel may react to the content of nickel in the diet. Nonallergic food intolerance may be due to pharmacological causes (anaphalactoid reactions), flushing, hypotension, urticaria in foods with high histamine content (e.g. scromboid poisoning due to ingestion of brown oily fish (mackerel, tuna, etc.) which has gone off). Tyramine in cheese or red wine may provoke/exacerbate migraine. Nonallergic food intolerance due to a metabolic cause includes abdominal symptoms and chronic diarrhoea following ingestion of milk in young children with lactase deficiency. Toxic reactions to foods may be due to contamination of food by chemicals, bacterial toxins, etc. The harmless, nonimmunologically mediated immediate perioral .flare reaction (nonimmunological contact urticaria (NICU))5 to, for example, benzoic acid from
Chapter 112 Food allergy and intolerance
Figure 112.1
Table 112.1
I 1425
Adverse reactions to foods. Redrawn from Ref. 29, with permission.
Type of adverse reactions to foods.
Food allergy due to IgE-mediated mechanism (type I)
Traditional food allergy, most often seen in children. The patient most often presents with concomitant symptoms and signs from two or more organ systems. This group also contains the pollen allergic patients reacting to fruits and vegetables due to immunological crossreactions.
Food allergy not involving IgE,
Data are emerging pointing towards a possible importance of delayed type reactions (Coomb's
where other immunological
type IV) in children with atopic dermatitis and positive patch testings to, for example, cow's
mechanisms implicated (e.g.
milk or house dust mite.
type IV) Nonallergic food intolerance (e.g.
May be due to sulphites in wine eliciting asthma in susceptible individuals, or to
pharmocological, metabolic or
pharmacologically active substances in foods such as tyramine. Upper respiratory reactions
toxic reactions to foods)
to monosodium glutamate (MSG) or other additives also belong to this group, although its actual existence has been disputed.
(lg E-mediated)
Baker's asthma: Asthma and rhinitis by inhalation of flour (amylase), also seen with egg and
Contact urticaria (immunological)
Contact urticaria in persons handling foods (e.g. cooks)
Contact urticaria
Nonimmunological contact urticaria is especially seen in infants as a perioral rash after intake
other foods.
(nonimmunological)
of citrus. The phenomenon is harmless and is caused by the presence of acids in the fruit
Contact dermatitis
Contact eczema in persons handling foods (e.g. cooks)
Food aversion. Symptoms often
This group represent a large and heterogeneous group of all kinds of symptoms and signs
nonspecific and unconfirmed
ranging from hyperkinetic children over multiple chemical sensitivities and the chronic
by blind food challenge.
fatigue syndrome to reactions to sugar or C-vitamins.
citrus fruits in children (especially those with atopic eczema dermatitis syndrome (AEDS)), which many parents and doctors may misinterpret as an allergy with unnecessary avoidance of citrus fruits in the child, is much overlooked. Reactions to food additives and colourings most often elicit acute flare up reactions or urticaria. Additives include benzoates, salicylates, sulphites and tartrazine and other colourings. [*]
SENSITIZATION At least three routes of sensitization exist. The classical route, by ingestion, is by far the most common in infants and may apparently occur in close relation to childbirth. In
a cohort study on 1749 newborns, only the infants who were fed cow's milk formula in the maternity ward and thereafter breastfed for a period of weeks to months developed cow's milk allergy, whereas this was not the case in either the group who were exclusively breastfed or in the group who were fed cow's milk formula in the maternity ward and thereafter continued on formula. 6 Intrauterine sensitization occurs rarely, as does sensitization to cow's milk protein present in undigested forms in human milk'? The exact mode of sensitization is at present unknown, as is the exact place in the human body (mouth, intestine, respiratory tract) where the sensitization takes place. [***] Sensitization by inhalation can occur in two different ways. First, inhaled allergens sensitize the body in the same classical way as any other inhalant allergen, in the nose or
1426 I
PART 13 THE NOSE AND PARANASAL SINUSES
in the lungs. This is most typically seen in baker's asthma, where inhaled proteins from flour will result in asthma (and rhinitis) in up to 20 percent of bakers after 15-20 years of exposure. 8 Sensitization by inhalation also occurs in the very common oral allergy syndrome (OAS), where the food allergy is due to allergenic cross-reaction between epitopes in pollen (to which the patient is sensitized by inhalation) and various fruits and vegetables. 9, 10 The third route of sensitization is via the skin, where younger women especially develop a type IV sensitivity to nickel and, in some cases thereafter, also react with exacerbation of their eczema after oral intake of higher amounts of nickel containing foods. 11
PRIMARY PREVENTION OF FOOD ALLERGY Primary prevention through a hypo allergenic diet may reduce the prevalence of food allergy and associated comorbidity, such as eczema and urticaria. Breastfeeding has many advantages and should be recommended for all children. Those with a history of atopy in the immediate family are at a higher risk and maternal diet during lactation, avoiding highly allergenic foods, may enhance the benefit. Cow's milk should be strictly avoided, and supplements, if required, should be with a hypoallergenic formula. Delayed introduction of egg, nuts, wheat and fish has also been suggested. Dietary restriction may have nutritional consequences for the mother and child. Maternal diet during pregnancy is not advisable as the benefit is minimal and there may be adverse effects on the foetal nutrition. In high risk infants, a combined approach, where breastfeeding with maternal avoidance of highly allergenic foods, supplemented by extensively hydrolyzed formula during the first six months of life, in addition to the delayed introduction of solid foods, may in selected cases reduce the development of food allergy in infants. 1, 2 The combination of atopic eczema dermatitis syndrome (AEDS) and food allergy at 12 months has been demonstrated to be the strongest risk factor in a high risk cohort for the development of asthma -like disease at 24 months of age. 3 Furthermore, early sensitization to foods constitutes a high relative risk (RR) of subsequent development of airway diseases, a factor which is three times greater than the relative risk induced by early AEDS without sensitization (RR 9.5 versus RR 3.4).4 Prevention of food allergy early in life may thus also have beneficial consequences later in childhood, although the food allergy itself may be outgrown. [*]
in the USA peanut. 12 This reflects both the fact that these are foods commonly eaten in high quantities by adults and infants and that they contain allergenic glycoproteins, characterized by being heat- and acid-stable and thus not degraded in the stomach. Pollen cross-reacting foods contain proteins sharing epitopes with the pollen. In contrast to what was previously believed, where the oral allergy syndrome was thought to be elicited by lectins in the food crossbinding IgE-molecules on the surface of mast cells in the mouth and throat, it has now been demonstrated in several of the cross-reacting food items, including hazelnut, apple and kiwi, that these reactions are due to common epitopes of approximately 18 kDa in size in the pollen allergen and for example in hazelnut. 13 The pollen cross-reacting proteins are seldom heat- and acid-stable, and are therefore usually destroyed by heat or by stomach acid, thus in the majority of cases only giving rise to symptoms when eaten raw and fresh. Examples of crossreaction food items are shown in Table 112.2. [****] The most common allergens giving rise to type IV reactions are nickel and cobalt.ll Sensitization to nickel requires binding of the hapten to a carrier protein prior to presentation to the Langerhans' cell in the skin; the events giving rise to reactivation of the eczema following the ingestion of nickel are unknown.
Table 112.2
Examples of cross-reaction food items.
Cow's milk
Mare's milk, goat's milk, sheep's milk
Hen's egg
Eggs from other birds
Cod
Mackerel, herring, plaice, tuna, salmon,
Shrimp
Other crustaceans, house dust mite
Peanut
Soy, green bean, lima bean, green pea
Soy
See above
trout, eel, etc.
Wheat
Other grains, most often rye
Additives
Mostly unknown (both synthetic and naturally occurring)
Cross reacting foods in pollen allergic patients without clinical significance (serological cross-reaction) Birch pollen
Latex, seed-fruit, stone-fruit, banana, kiwi, Iychee, mango, orange, raw carrot, raw potato, celery, soya, raw tomato, aniseed, curry, red pepper, pepper, caraway, coriander, nuts
Grass pollen
Seed-fruit, stone-fruit, kiwi, melon, celery, raw tomato, onion, flour, rice,
ALLERGENS AND FOOD ADDITIVES
latex Mugwort pollen
Allergens
Seed-fruit, stone-fruit, kiwi, mango, pea, raw carrot, celery, raw tomato, aniseed, curry, dill, red pepper,
The allergens which most often give rise to an IgEmediated reaction are milk, egg, cod fish, wheat, soy and
pepper, caraway, coriander, peanut, nuts, latex
Chapter 112 Food allergy and intolerance
I 1427
Food add itives
PREVALENCE
The mode of action of food additives (preservatives and colourants) is also unknown. A clinically significant crosssensitization between aspirin (which is not found in nature) and the preservative salicylate, which may also occur naturally in high quantities in certain foods, has still not been demonstrated convincingly. The same is true for the alleged connection between aspirin and the colourant tartrazine. Stevenson et al. 14 challenged 80 aspirin-sensitive asthmatics with large quantities of tartrazine without any positive reactions. Also, in a survey of respiratory reactions to monosodium glutamate, Schwartzstein 1S was unable to find more than one report of a positive reaction in doubleblind, placebo-controlled food challenge in the medical literature from 1966 to 1991. Contrary to these findings, a proportion of patients with bronchial asthma will experience dyspnoea upon oral intake of sulphite 16 - data on rhinitis provoked by sulphite have not been published. Food additives are generally believed to be harmful by the public; a fact that has not been supported in trials using double-blind, placebo-controlled food challenges. As an example, the artificial sweetener aspartame (Nutrasweet) was investigated for a period of several years in the USA without finding a single patient whose symptoms could be attributed to aspartame,17 although the product was banned by ecological organizations in many countries because of its alleged allergic potentiaL [*]
The prevalence or incidence of adverse reactions to food or food additives varies immensely depending on the method used. By using a questionnaire, the prevalence of cow's milk allergy in infants exceeds 25 percent, whereas if a double-blind, placebo-controlled food challenge is used in the same population, a prevalence of 2.2 percent is obtained. 6 In a prospective study by Bock, the cumulative prevalence of adverse reactions to food during the first three years of life was found to be 5.2 percent using open and double-blind challenges. 19 Interestingly, in Bock's study, a large proportion of the children (11.7 percent) reacted to the sugars in fruit or juices (enzyme deficiency). Such reactions are not hypersensitivity reaction and should not be included in prevalence studies. Jansen et al. 20 found the self-reported food allergy/ intolerance to be 10 percent in adults, but the true prevalence was estimated to be 2.4 percent and was confirmed by oral challenge. The incidence of adverse reactions to food additives has been widely overestimated. By using double-blind, placebo-controlled food challenges, Fuglsang et al. 21 estimated the prevalence of reactions in school children to a maximum value of less than 2 percent. Although the validity of that study is hampered by the lack of data on the frequency of reactions to placebo in the food challenges, the results are supported by Rosenhall's results in 504 patients with a history of asthma or rhinitis elicited by food additives. 22 At present, no data exist on the prevalence of nickel-sensitive patients reacting to nickel in food, but Veien l l has estimated the number to be 10 percent of the severe cases at the most. Depending on the allergen, many patients will develop tolerance to the food in question. In Host and Halken's study, 6 more than 90 percent of the children who had confirmed allergy to cow's milk in the first year of life had outgrown their clinical allergy by the age of three years. Skin tests and RASTs may be positive for a period of time after clinical tolerance has evolved. It is therefore important to regularly rechallenge the patients with an established diagnosis of cow's milk allergy. Patients with other food allergies, especially cod fish, will develop tolerance less frequently. [***/**]
Immunological and clinical cross-reactivity It is important to discriminate between immunological
and clinical cross-reactivity. In the first case, the crossreactivity is demonstrated in the laboratory by sophisticated immunochemical techniques. However, such a crossreactivity does not imply clinical cross-reactivity as demonstrated by the fact that up to 65 percent of grasspollen allergic patients with specific IgE to grass pollen epitopes will demonstrate specific IgE to wheat in one or more of the new and very sensitive tests for specific IgE (radioallergosorbent tests (RASTs)) without ever having reacted upon ingestion of white bread (Poulsen and Bindslev-Jensen, unpublished results). Another example applies to immunological cross-reactivity between the peanut and various other vegetables (Table 112.2), where Bernhisel-Broadbent et al. could elicit a clinical response to the other vegetables in only two of 41 children allergic to peanut, verified by double-blind, placebo-controlled food challenge. 18 Thus, the clinical significance of crossreactivity must be evaluated for each and every allergen in every patient if the management is to be correct. As a rule, probability of clinical reaction reflects the heat- and acid-stability of the food, but also normal preparation of a given food is important, for example those allergic to grass pollen would probably react clinically to wheat if they ingested raw, fresh and unprocessed wheat. [***/**/*]
.""=-'='""'(-"~~~-~~--- .
DIAGNOSIS OF FOOD HYPERSENSITIVITY In its most simple form, a diagnosis of food hypersensitivity is based on the following steps (Figure 112.2). [Grade B]
Case history Most patients will describe a close connection between intake of a food and development of symptoms. Especially
1428 I
PART 13 THE NOSE AND PARANASAL SINUSES
The patient's case history should point towards a close relationship between intake of a specific food or additive and initiation of symptoms.
The symptomatology described by the patient should be of the 'classical' atopic type i.e. immediate allergic symptoms, most often from two or more organs.
Case history Type I food allergy
Classical allergic symptoms, most
Food intolerance
As above - additives: Cutaneous
Pollen cross reaction
OAS
Contact urticaria
Urticaria by skin contact, not by
Protei n dermatitis
Eczema by skin contact
Type IV reactions
Excacerbations of eczema by oral
often in combination
Symptoms
symptoms, rarely rhinitis
May be in vivo or in vitro. Skin prick test, specific IgE, basophil histamine Release Patch testing
Allergy testing
ingestion - allergic or NICU
ingestion (e.g. nickel) Symptoms should disappear, or at least be significantly reduced, by a restricted, tailormade diet.
Diagnostic diet
The original symptomatology should reappear during challenge. An initial positive open challenge should be confirmed by DBPCFC (open challenge in children:::; 3 years of age).
Challenge
Figure 112.2
A simplified guide for diagnosing food
hypersensitivity.
in infants, symptoms will usually appear shortly after a new food has been introduced. A history of other atopies - inhalant or food - will support the history. The time course is of utmost importance, in most cases symptoms and signs appear within minutes to a few hours after intake, whereas late symptoms appearing days after intake without an immediate reaction can only rarely be verified.
Symptoms The symptomatology depends on the type of adverse reaction to a rood, see Table 112.3. The typical symptoms and signs appearing in type 1 food allergy are very characteristic. In more than 90 percent of cases of DBPCFC-proven food allergy, the patient present with concomitant symptoms and signs from two or more organ systems: asthma and/or rhinitis from the respiratory system, vomiting and/or diarrhoea from the gastrointestinal system and urticaria or angioedema and/or excacerbation of AEDS (usually a late reaction preceded by other symptoms and signs shortly after challenge). A very characteristic symptom, usually preceding more serious reactions, is the oral allergy syndrome (OAS), where the patient experiences itching and tingling in the mouth and pharynx immediately after the offending food comes into contact with the mucosal lining of the mouth. The reaction may be due to a local release of histamine in the mouth. 23 OAS is very common in pollen allergy where more than 80 percent of birch pollen allergics will react to intake of fresh hazelnuts, kiwi fruit or green apples, but it
is also very characteristic in classical, IgE-mediated food hypersensitivity. OAS is most common in patients with birch rhinitis, where 50-80 percent will demonstrate this symptom upon ingestion of fresh fruits and vegetables (Table 112.2). Only rarely are clinical symptoms of OAS associated with grass pollen rhinitis, whereas serological cross reactions are frequent between grass and, for example, wheat or peanut. 24 Cross reactions in mugwort rhinitis are less frequent but often more severe, probably due to the heat stable nature of the celery allergens. 25 It is important to realize that the symptomatology of pollen cross reactions vary depending on geographical variations - in Scandinavian countries, symptoms are almost exclusively confined to local symptoms in the mouth and throat, whereas systemic allergic reactions due to birch pollen cross reaction to hazelnut are rare. 26 In contrast, this it not the case in the Mediterranean area where systemic reactions to hazelnut occurs frequently, and where, furthermore, one of the most frequent and severe food allergies is actually allergy to celery (tuber and/or root).27 The diagnosis of intolerance to additives should, in selected cases, be suspected in patients who develop symptoms on exposure to preservative-containing foods. Here, there are no diagnostic tests. Diagnosis depends on suspicion and the use of elimination diets and/or blinded challenges with preservative-containing capsules and placebo capsules. [Grade C] Type IV reactions to foods only give rise to cutaneous reactions. [****]
Diagnostic tests The allergen extracts used in inhalant allergy are, in many cases, standardized and have been shown to correlate well to clinical disease in numerous studies. In contrast, no standardized extracts are available for use in the diagnosis of food hypersensitivity and therefore variable and often poor correlations are seen. The commercial extracts used in skin prick tests (SPT) are generally of poor quality and
Chapter 112 Food allergy and intolerance
should be used with caution. In many cases, it is better and more convenient to use fresh foods for SPT, by placing a drop of liquid food on the forearm and pricking through it, or, in the case of solid food, by placing a piece of the food on the forearm and pricking through it (the prick-prick method).28 It is extremely important to realize that every single allergen is a unique system and must be validated by itself. None can deduct anything on how a test will perform in, for example, milk allergy, from knowledge on how the test performs in, for example, cod allergy. Knowledge of immunological cross reactions and their potential clinical value are also important when using RAST for diagnosis. As an example, more than 60 percent of grass pollen allergic patients will show positive values of specific IgE against wheat in the CAP-system - this immunological cross-reactivity is not reflected clinically. Similar results have been obtained with SPT to peanut and peanut-cross-reacting foods. The performance (sensitivity and specificity) of a given test should always be calculated in comparison to the outcome of DBPCFC. 1 [****]
Diet Usually, a very restricted diet is not necessary, the amino acid based elimination diets are expensive and have a low compliance. The case history supported by the diagnostic tests should point towards a few possible offending foods or groups of foods, otherwise the indication for the diagnostic diet period should be re-evaluated. In most cases, a diet period of two weeks is sufficient but the period may be prolonged, especially in the case of atopic eczema dermatitis syndrome. [Grade C] Care should always be taken in ensuring sufficient nutrition to the patient during the period. The help of a clinical dietitian is often needed.
Challenge By tradition, allergists most often base the diagnosis of a specific allergy on the patient's medical history, supplemented with specific allergy testing before initiating proper treatment. This procedure has proven valid in many cases of inhalant allergy including allergic rhinitis, whereas this is only in very clear cases the fact in food hypersensitivity, for example a medical history of anaphylaxis in an atopic patient immediately after intake of peanuts, where the SPT is positive. In most other cases, the diagnosis must be verified or ruled out by DBPCFC. In children and infants up to three years of age, open controlled challenge is most often sufficient, l but should be controlled by competent staff and not by the parents. Several attempts have been made in order to facilitate the diagnostic procedures in patients with food
I 1429
hypersensitivity but so far only the DBPCFC fullfills the criteria for a suitable diagnostic tool, 'the gold standard'. [Grade B] A statistical model for evaluation of DBPCFC has been published and should be applied. Several parameters are important to evaluate and control prior to challenge for correct performance ofDBPCFC (Table 112.4). The items can be divided into parameters which are patient related and parameters related to the challenge procedure. A manual for standardized challenge has recently been published and should be followed. 29
FOOD HYPERSENSITIVITY AND RESPIRATORY SYMPTOMS
Asthma symptoms are more frequently elicited during oral challenge than rhinitis and conjunctivitis. A Medline survey yielded 560 clinical trials distributed on 186 open controlled food challenges (OCFC), 29 single-blind challenges and 345 double-blind placebo controlled food challenges, totally 6917 patients (Table 112.5).
Based on these data, the elicitation of asthma was estimated to be 8 percent during oral challenges, 2 percent rhinitis and 0.5 percent conjunctivitis. The most common foods eliciting asthma were the classical allergenic foods (peanuts, fish, soy, cow's milk and egg). Rhinitis symptoms are less frequent and most often in combination with other symptoms. Host and Halken6 reported respiratory symptoms in 33 percent of the children with cow's milk allergy, and rhinitis appeared in 80 percent of the cases in combination with asthma. However, the opposite was not the case as asthma appeared in combination with other symptoms in only 50 percent of the cases. Rhinitis may often be in combination with conjunctivitis. All the egg-allergic patients in the study by Norgaard and Bindslev-Jensen developed rhino-conjunctivitis in combination. 60 In conclusion, asthma symptoms in food hypersensitivity are common, whereas rhinitis mostly develops in combination with asthma. [***/**]
Table 112.4
Parameters to evaluate and control prior to rmance of DBPCFC.
Nature of reaction
Source of food
Age of patient
Starting dose
Food in question
Increment Timing Top dose Blinding procedure Settings Requirements
1430 I PART 13 THE NOSE AND PARANASAL SINUSES Table 112.5
Results of Medline clinical trial on food hypersensitivity and respiratory systems.
Preservatives
16/0/30
338
6
3
0
Dyes
7/1/32
298
2
6
0
Taste enhancers Apple Barley Beef Carrot Cashew Celery Cherry Chestnut Chocolate Corn flour Cow's milk
2/4/5 7/1/3 1/0/3 2/1/4 5/0/2 0/0/2 4/0/2 2/0/1 1/0/0 2/0/2 3/0/3 19/1/57
39 161 20 30 15 6 33 34
0 1 6 2 0 0 2 0 0
4 26 2028
Crab Egg
2/0/0 12/1/43
Fenugreek Fish
149
0 59
0 1 0 0 1 0 3 0 0 0 0 12
4 1655
0 86
16
0 5
0/0/1 3/1/20
2 203
2 37
0 3
0 0
Garlic Goat's milk Hazelnut Lettuce Melon Mustard Orange Pea Peach Peanut
2/0/1 0/1/1 3/1/4 1/0/1 1/0/1 0/2/0 4/0/3 2/1/3 5/0/2 12/1/17
3 29 137 1 18 64 50 47 47 651
0 7 3
1 7 1 0
0 0 0 0
1 2 14
5 0
81
16
5 0 0 0 2
Pork Potato Rye Sesame
4/1/1 4/0/3 1/0/6 0/1/1
26 23 9 6
0 4 1
0 0 0 0
0 0 0
4 4 0 0 5 2 1 0
30,31,32,33,34,35,36,37,38,39,40,41, 42,43,44,45,46,47,48,49,50, 51, 52 19,31,32,33,34,35,36,37,40,41,42,43, 44,45,46,47,48,49,51, 53, 54, 55 26,32,33,38,41,42,44,46, 56, 57 5~ 5~ 6Q 61, 6~ 63, 6~ 6~ 6~ 67, 68 69, 70, 71, 72 64, 71, 73, 74, 75, 76, 77 60, 62, 78, 79, 80, 81 73, 82 62, 80, 83, 84, 85, 86 62, 87, 88 89 20, 86, 90, 91 61, 72, 81,92, 93 6,9,19,20,46,61,64,68,70,71,73,74,75, 82,90,91,92,93,94,95,96,97,98,99, 100, 101, 102, 103, 104, 105, 106, 107, 108,109,110,111,112,113,114,115,116, 117, 118, 119,120,121,122,123,124, 125,126,127,128,129,130,131,132, 133,134,135,136,137,138,139,140, 141, 142, 143, 144, 145, 146 64, 79 18,39,46,61,64,70,71,73,74,75,76,78, 79,82,85,86,90,91,92,95,96,98,99, 100,101,102,104,107,117,118,120, 122, 124, 125, 126, 127, 128, 132, 135, 137,138,140,141, 146,147,148,149, 150,151,152,153,154,155,156,157, 158 159 64, 70, 73, 74, 75, 76, 86, 91, 92, 95, 100,102,107,118,120,138,157,160, 161, 162, 163 80,86, 130 5,64 62, 64, 86, 100, 130, 157, 164, 165 84 62, 166 64, 167 60,61,62,71,95, 140 64,75,76,81,100,147 60, 62, 65, 80, 88, 168 60, 61, 62, 64, 75, 76, 78, 79, 80, 82, 85,86, 91,95,99,100,102,117,122,138,141, 169,170, 171, 172, 173, 174, 175 21,64,71,74,81,176 62,74,81,91,130,140,177 69, 72, 75, 86, 91, 96, 100 64, 178
(Continued over)
Chapter 112 Food allergy and intolerance.
Table 112.5
1431
Results of Medline clinical trial on food hypersensitivity and respiratory systems (continued).
Shrimp Soy
2/1/6 7/1/23
37 282
4 62
2 5
1 0
Tomato Wheat
5/0/4 12/1/30
25 285
2 60
3 5
0 0
Othersd
29/8/24
280
0
0
0
Total
186/29/345
6917
546
148
32
21, 64, 68, 73, 78, 79, 85, 100, 179 46,61,64,70,71,73,74,76,82,86,91,95, 99, 100, 102, 107, 117, 118, 126, 127, 132, 135, 137, 138, 140, 147, 180; 181, 182 20, 60, 62, 71, 80, 130, 140, 183 46, 60, 61, 62, 69, 70, 71, 72, 73, 74, 75, 76, 80,85,90,91,92,95,96,100,101,104, 117, 118, 126, 127, 130, 135, 137, 138, 140, 184, 185, 186, 187, 188 20,35,60,61,62,64,65,68,69,70,71,72, 74, 78, 79, 80, 81, 88, 90, 91, 97, 100, 102, 130, 163, 189, 190
aType of challenge and numbers of studies. Open food challenge (OC), single blind food challenge (5B) and double blind food challenge (DB). bTotal number (No.) of patients. cNumber of patients reacting with asthma, rhinitis or conjunctivitis (Conjunc.) symptoms during challenge. dAlmond, apricot, avocado, banana, bean, beer, chicken, citrus, coconut, fennel, kiwi, lamb, lentil, lupine flour, oat, onion, pear, plum, rabbit, rice, strawberry, sunflower, turkey, vanilla, walnut, yeast, zucchini.
TREATMENT The only suitable treatment of adverse reactions to foods is avoidance. [Grade B] In cases of anaphylaxis, early administration of adrenaline (epinephrine) is life saving. Antihistamines only serve as adjuvant treatment and should be used with caution since these drugs may mask the early warning signs (OAS) of a systemic reaction. Specific allergy vaccination of pollen rhinitis has proven extremely effective in alienating the symptoms from l~l~ nose and eyes, but will only rarely have a significant effect on the symptoms elicited from the mouth by crossreacting foods (OAS).
I
I
I
1 .*."<_<1.1IIIIIioi_........_ _.-..L~__
./ Double-blind, placebo-controlled food challenge is the gold standard for the diagnosis of food allergies. However, patients with histories of life-threatening anaphylaxis should undergo food challenges (in an intensive care unit-like setting) only when the history and laboratory testing cannot determine the causative antigen . ./ For preventative reasons, 'high-risk' infants should be exclusively breastfed, supplemented, if necessary, with a highly hydrolyzed formula, and lactating mothers . should avoid peanuts and nuts. Introduction of egg, nuts, wheat and fish after the age of three has been suggested . ./ Strict elimination of offending foods is the only proven therapy of food allergy. Patients and their families should be instructed not only to avoid ingesting food allergens accidentally, but also to recognize the symptoms of an allergic reaction and to act appropriately in case of an anaphylactic reaction (i.e. administration of adrenaline/epinephrine).
<_ _ _ <__
~
~=='-------
_ _
'PI -, - * ' <>,
1432 I PART 13
THE NOSE AND PARANASAL SINUSES
and commercial food extracts) and RAST in 100 patients
Deficiencies in current knowledge and areas for future research
>
Immunology. 1989; 83: 683-90. 10. Amiot PL, Kemeny DM, Zachary C, Parkes P, Lessof MH.
Diagnosis: Currently, fresh fruits and vegetables must
Oral allergy syndrome (OAS): symptoms of IgE-mediated
be used for skin prick tests because commercially
hypersensitivity to foods. Clinical Allergy. 1987; 17:
available fruit and vegetable extracts are very
33-42.
unreliable and often yield false-negative results. The same problem applies for the extracts used for radioallergosorbent tests. In the future, recombinant food allergens may prove to be more reliable diagnostic tools than natural food extracts
>
with oral allergy syndrome. Journal of Allergy and Clinical
Treatment: Currently, the only proven 'therapy' of food allergy is elimination of the offending foods. Anti-lgE and novel forms of immunotherapy are currently being explored for the treatment of IgE-
11. Veien NK. Systemically induced eczema in adults. Acta Dermato-venereologica (Supplement (Stockh)). 1989; 147: 1-58. 12. American Academy of Allergy and Immunology Committee on Adverse Reactions to Foods. Adverse reactions to foods. Bethesda: National Institutes of Health. 1984. NIH Publ. No. 84-2442. 13. Hirschwehr R, Valenta R, Ebner C, Ferreira F, Sperr WR, Valent P et al. Identification of common allergenic
mediated food allergy.
>-
structures in hazel pollen and hazelnuts: a possible
Immunophathological mechanisms: Our understanding
explanation for sensitivity to hazelnuts in patients allergic
of basic immunological mechanisms underlying food
to tree pollen. Journal of Allergy and Clinical Immunology.
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1992; 90: 927-36. 14.
Adverse reactions to tartrazine. Journal of Allergy and
the pathogenesis of these disorders and will hopefully lead to the development of new and better forms of therapy.
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165. Cavataio F, Iacono G, Montalto G, Soresi M, Tumminello M, Campagna P et al. Gastroesophageal reflux associated with cow's milk allergy in infants: which diagnostic examinations are useful? American Journal of
Gastroenterology. 1996; 91: 1215-20. 166. Vatn MH, Grimstad lA, Thorsen L, Kittang E, Refnin I, Malt U et al. Adverse reaction to food: assessment by double-
Allergy. 1994; 73: 301-8.
blind placebo-controlled food challenge and clinical,
Roesler TA, Barry PC, Bock SA. Factitious food allergy and
psychosomatic and immunologic analysis. Digestion.
failure to thrive. Archives of Pediatrics and Adolescent
153.
Pastorello EA, Ortolani C, Farioli L, Pravettoni V, Ispano M,
Hashimoto K. Food-dependent exercise-induced
898-900.
152.
Martin ME, Guthrie LA, Bock SA. Serum complement
Medicine. 1994; 148: 1150-5. Bentley SJ, Pearson DJ, Rix KJ. Food hypersensitivity in irritable bowel syndrome. Lancet. 1983; 2: 295-7.
1995; 56: 421-8. 167. Caffarelli C, Cavagni G, Giordano S, Stapane I, Rossi C. Relationship between oral challenges with previously uningested egg and egg-specific IgE antibodies and skin
154. Schrander JJ, van den Bogart JP, Forget PP, Schrander-
prick tests in infants with food allergy. Journal of Allergy
Stumpel CT, Kuijten RH, Kester AD. Cow's milk protein
and Clinical Immunology. 1995; 95: 1215-20. 168. Vila L, Sanz ML, Sanchez-Lopez G, Garcia-Aviles C, Dieguez I. Variations of serum eosinophil cationic protein
intolerance in infants under 1 year of age: a prospective epidemiological study. European Journal of Pediatrics.
155.
1993; 152: 640-4.
and tryptase, measured in serum and saliva, during the
Burks AW, Williams LW, Casteel HB, Fiedorek SC,
course of immediate allergic reactions to foods. Allergy.
2001; 56: 568-72.
Connaughton CA. Antibody response to milk proteins in patients with milk-protein intolerance documented by
156. 157.
169.
Pacor ML, Di Lorenzo G, Corrocher R. Efficacy of
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leukotriene receptor antagonist in chronic urticaria. A
1990; 85: 921-7.
double-blind, placebo-controlled comparison of treatment
Baker H, Luyt D, Stern M. Open challenge to nuts in
with montelukast and cetirizine in patients with chronic
children. Allergy. 1999; 54: 79-80.
urticaria with intolerance to food additive and/or
De Swert LF, Cadot P, Ceuppens JL. Allergy to cooked white
acetylsalicylic acid. Clinical and Experimental Allergy.
potatoes in infants and young children: A cause of severe, dironic allergic disease. Journal of Allergy and Clinical
2001; 31: 1607-14. 170. Gibson A, Clancy R. Management of chronic idiopathic
Immunology. 2002; 110: 524-35.
urticaria by the identification and exclusion of dietary
158.
Kanny G, Chenuel B, Moneret-Vautrin DA. Chronic
factors. Clinical Allergy. 1980; 10: 699-704.
159.
Lucarelli S, Corrado G, Pelliccia A, D'Ambrini G, Cavaliere M,
urticaria to wheat. Allergy. 2001; 56: 356-7. Barbato M et al. Cyclic vomiting syndrome and food allergy/intolerance in seven children: a possible association.
160.
171. Sampson HA. Role of immediate food hypersensitivity in the pathogenesis of atopic dermatitis. Journal of Allergy and Clinical Immunology. 1983: 473-80. 172. Bernstein M, Day JH, Welsh A. Double-blind food
European Journal of Pediatrics. 2000; 159: 360-3.
challenge in the diagnosis of food sensitivity in the adult.
Fuglsang G, Madsen C, Saval P, Osterballe O. Prevalence of
Journal of Allergy and Clinical Immunology. 1982; 70: 205-10.
intolerance to food additives among Danish school
1438 I 173.
PART 13 THE NOSE AND PARANASAL SINUSES
Niggemann B. Beyer K. Wahn U. The role of eosinophils
182.
and eosinophil cationic protein in monitoring oral challenge tests in children with food-sensitive atopic
183.
dermatitis. Journal of Allergy and Clinical Immunology. 174.
1994; 94: 963-71.
in chronic: and recurrent urticaria and recurrent angioedema. Clinical and Experimental Allergy. 1989;
leukocyte distribution during double-blind. placebo-
19: 539-43. 184.
dermatitis and suspected food allergy. International 110-5.
Childhood. 1991; 66: 93-9. 185.
Kanny G. Food specific IgE antibodies: a comparative study
not CD8+ • T cells expressing interferon-gamma is related
of AlaSTAT and Pharmacia RAST Phadebas CAP systems in
to cow's milk allergy in infancy. Pediatric Allergy and
49 patients with food allergies. Annals of Allergy. 1993;
Doeglas HM. Reactions to aspirin and food additives in
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testing enhances identification of food allergy in infants
urticarias. British Journal of Dermatology. 1975; 93:
with atopic dermatitis. Journal of Allergy and Clinical
Jones SM. Magnolfi CF. Cooke SK, Sampson HA.
Immunology. 1996; 97: 9-15. 187.
Immunologic cross-reactivity among cereal grains
Outcome of double-blind. placebo-controlled food challenge tests in 107 children with atopic dermatitis.
341-51.
Clinical and Experimental Allergy. 1999; 29: 91-6. 188.
(APT) - a useful tool for the diagnosis of food allergy
dermatitis with a strict elimination diet. Clinical Allergy.
in children with atopic dermatitis. Allergy. 2000; 55:
Eigenmann PA, Ca!za AM. Diagnosis of IgE-mediated food
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allergy among Swiss children with atopic dermatitis. Wuthrich B. Adverse reactions to food additives. Annals of
Simon RA. Additive-induced urticaria: experience with monosodium glutamate (MSG). Journal of Nutrition. 2000;
Pediatric Allergy and Immunology. 2000; 11: 95-100.
181.
Niggemann B. Reibel S. Wahn U. The atopy patch test
Juto p. Engberg S. Winberg J. Treatment of infantile atopic 1978; 8: 493-500.
180.
Niggemann B. Sielaff B. Beyer K. Binder C. Wahn U.
and grasses in children with food hypersensitivity. Journal of Allergy and Clinical Immunology. 1995; 96:
179.
Isolauri E. Turjanmaa K. Combined skin prick and patch
patients with chronic urticaria. including the physical 135-44.
178.
Moneret-Vautrin DA. Halpern GM. Brignon JJ. Nicolas JP.
Osterlund p. Suomalainen H. Low frequency of CD4+ • but
Immunology. 2002; 13: 262-8.
177.
Devlin J. David TJ. Stanton RH. Elemental diet for refractory atopic eczema. Archives of Disease in
Archives of Allergy and Applied Immunology. 1998; 116:
176.
Malanin G. Kalimo K. The results of skin testing with food additives and the effect of an elimination diet
Beyer K. Renz H. Wahn U. Niggemann B. Changes in blood controlled food challenges in children with atopic
175.
Gall H. Steinert M. Peter RU. Exercise-induced anaphylaxis to wheat flour. Allergy. 2000; 55: 1096-7.
130: 1063S-6. 190.
Fukutomi O. Kondo N. Agata H. Shinoda S. Kuwabara N.
Allergy. 1993; 71: 379-84.
Shinbara M et al. Timing of onset of allergic symptoms as
Chandra RK. Five-year follow-up of high-risk infants
a response to a double-blind. placebo-controlled food
with family history of allergy who were exclusively
challenge in patients with food allergy combined with a
breast-fed or fed partial whey hydrolysate. soy. and
radioallergosorbent test and the evaluation of proliferative
conventional cow's milk formulas. Journal of
lymphocyte responses. International Archives of Allergy
Pediatric Gastroenterology and Nutrition. 1997; 24: 380-8.
and Applied Immunology. 1994; 104: 352-7.
113 Rh i nasi n usitis
MICHAEL S BENNINGER
1439 144{) 1442 1443 1443
Defi niti0 ns Pathophysiology Diagnosis Natural history Prevalence of rhinos/nus'ltis
The economic and quality of life impact of rhinosinusitis Key points Best clinical practice Deficiencies in knowledge and areas for future research References
1444 1447 1447 1447 1447
The data in this chapter are supported by a MedJine search using the key words sinusitis, rhinosin usitis, bacterial, sinusitis, actute sinusit is, chronic sinusitis, fungal sinusitis an d rh initis.
t emporal differences in the pr esentatio n and, in some on the c li nic al presentation. T here are also
DEFINITIONS
cases, a group of disorders
differences in the histopathology and the bacteriology of
characterized by inflammation of the mucosa of the
acute and chronic rhinosinusitis. Although somewhat
Be cause the inflammatio n
accepted that
arbitrary, consensus ha s been reac h ed to define these three distinct but related clinical enti ties based on duration of symptoms an d defining clinical fac tors that
describe this inflammation of the nose and para nasal
would suggest rhinosinusitis.2
The tenn <sinusitis' refers to paranasal sinuses
.
[****/**/*]
ne arl y always also involves the nose, it is now generally
number of factors that pl ay a role in the development of rhinosinusitis, in cludi ng both host and environmental factors. Because of the c omp lexity of the factors that are associated with r hinosinusiti s, there has been significant debate and confusion related to the developrp.ent of definitions. A widely a ccept ed set of classifications or definitions was developed by the sinuses. There are a
Acute bacterial rhinosinusitis has been defined sudden
in onset and
weeks.2 Since many cases of rhinosinusitis oc cur foll owing a viral upper respirat or y tract infection and since upper Table 113.1
Classification of rhinosinusitis.
Duration
Rhinosinusitis Task Force of the American Academy of Oto l aryngology Head and Neck Surger� and reported by -
r (Table 113.1).
Lanza and Kenned
based
in
These criteria are
large part on temporal time
distinctions between acute rhino sinusitis acute
rhinosinusitis
(SRS),
chronic
(RARS),
,/
The
subacute
rhinosinusitis
rhinosinusitis (CRS) and acute exacerba (AECRS) are based on the
tion of chronic rhinosinusitis
h '
frames.
(ARS), r ecurrent
as
with a duration of less than four
Acute (ARS)
7
Subacute
4- 12 weeks
Recurrent acute
;::: 4 episodes of ARS per year
days to::;;; 4 weeks
Chronic (CRS)
:c: 12 weeks
Acute exacerbation of
Sudden worsening of CRS with return
chronic
to baseline after
/
1440 I
PART 13
THE NOSE AND PARANASAL SINUSES
respiratory infection (URI) symptoms may mimic those of an episode of rhinosinusitis, a minimal duration of symptoms is generally recommended prior to the determination of an acute bacterial rhinosinusitis, t ypically five to seven days. Recurrent acute infections are defined by four or more episodes per year, with each lasting greater than seven to ten days and an absence of intervening signs or symptoms that would suggest an ongoing or chronic rhinosinusitis.2 Chronic rhinosinusi tis occurs when the duration of symptoms is greater than 12 weeks in duration. There may be occasional acute worsening of symptoms in individuals with chronic rhinosinusitis, suggestive of an acute exacerbation of the chronic condition. With treatment of the acute symp toms, they return to the baseline chronic rhinosinusitis. This entity is referred to as 'acute exacerbation of chronic rhinosinusitis'. Since individuals with acute rhinosinusitis have symptoms for less than four weeks and those with chronic rhinosinusitis have symptoms for greater than 12 weeks, those who have symptoms from four to 12 weeks are considered to have a subacute infection, or 'subacute rhinosinusitis'. Some of these will resolve within that time frame and others will progress to chronic rhinosinusitis.2 Although all cases of rhinosinusitis involve inflamma tion of the mucosal linings, in the practice setting, the focus is on those patients in whom this inflammation leads to symptoms. Because of this important relationship to symptoms, the Rhinosinusitis Task Force's definitions include a group of symptoms to be applied to these conditions to allow for clinical diagnosis (Table 113.2). In addition, since in acute infections viral infections are almost always self-limited, the most interest has been in th�se with a bacterial disease. Furthermore, although the symptoms noted in Table 113.2 are valuable in the diagnosis of acute bacterial rhinosinusitis (ABRS), they are more difficult to apply to subacute and chronic rhinosinusitis. Definitions for CRS have been particularly difficult to establish due to the wide variety of conditions that have been found to be associated with CRS. Furthermore, although the role of bacteria in ARS is also well recognized, the role of bacteria in CRS is also not well
Rhinosinusitis symptoms/signs (requires two major factors, or one major and two minor).
Table 113.2
------�-------------
Major
symptoms
Minor symptoms
5 Facial pain/pressure 6 Facial congestion/fullness 1 Nasal obstruction/blockage 2 Nasal discharge/purulence/discoloured
Headache Fever (nonacute) Halitosis Fatigue
posterior drainage
3 Hyposmia/anosmia 4 Purulence on nasal examination 7 Fever (acute RS only)
Dental pain Cough Ear pain/pressure/ fullness
Back
established, except perhaps for those with AECRS. Therefore, the symptom-based diagnosis used to define ARS is not likely to be insufficient to define CRS. To delineate the role of inflammation better, newer definitions have been applied to rhinosinusitis. The newer definitions are: Rhinosinusitis is a group of disorders characterized by inflammation of the mucosa of the nose and paranasal sinuses. Chronic rhinosinusitis is rhino sinusitis of at least 12 consecutive weeks' duration. Therefore, chronic rhinosinusitis is a group of disorders characterized by inflammation of the mucosa of the nose and paranasal sinuses of at least 12 consecutive weeks' duration.' 3
PATHOPHYSIOLOGY An inflammatory response is an expected sequela of an infectious process. Inflammation in the nose and sinuses from a variety of causes can result in sinus ostia obstruction and predispose to the development of an infection. Many factors have been described as playing a role in the development of ABRs.2, 3, 4 These include factors related to the host: genetic factors such as immotile cilia syndrome or cystic fibrosis; anatomic abnormalities such as a concha bullosa, septal spur or paradoxical turbinate; certain systemic diseases or med- . ical treatments that predispose individuals to infections; neoplasms; and allergic or immune disorders. Rhino sinusitis may also develop in relationship to environ mental factors: bacterial, viral, or fungal infections, or inflammation that occurs secondary to fungal or bacterial colonization3,5 trauma; primary or secondary tobacco smoke exposure,6 chronic or acute irritants or noxious chemicals; or iatrogenic factors including surgery, med ications, nasal packing or nasogastric tube placement. There is growing evidence that individuals with allergies have a higher incidence of developing both acute and chronic rhinosinusitis and an association of acute bacterial rhinosinusitis with asthma has also been suggested, although this may also relate to the presence of allergic rhinitis. 7, 8, 9 [***/**/*] 10 The pathophysiology of ABRS has been postulated.4, Typically, acute rhinosinusitis develops in conjunction with an acute viral upper respiratory tract infection. This may occur more commonly in predisposed individuals, as mentioned previously. The infection results in mucosal swelling with occlusion or obstruction of the sinus ostia. A reduction in oxygen tension occurs which can reduce mucociliary transport and transudation of fluid into the sinuses.4 The inflammation also results in changes in the mucous that become more viscous and alterations in cilia beat frequency often occurs. These changes in the nasal-sinus environment lead to mucostasis and bacterial colonization. If the sinuses remain obstructed or the mucociliary. transport system does not return to normal, a bacterial infection can ensue. The predisposing factors
Chapter 113
listed above
will play a role
in whether or not this URI
develops into an acute sinus infection.
Rhinosinusitis I 1441
4%
The role of
allergies in the development of rhinosinusitis has been strongly suggested but not proven. Antigen-antibody reactions result in the release of histamine and other
mediators
in
changes
of
inflammation.
vascular
These
mediators
permeability,
cause
destabilization
of
lysosomal membranes and other reactions that produce
0-9%
inflammation, mucosal swelling and ostia obstruction.4
Although infectious agents can be primary causes of sinus inflammation,
they may also represent a secondary
infection. There has been growing recent interest in the
3-9%
host response and how it relates to the disease process and
progression. Many cells and proteins that are involved
with inflammator y response have been implicated and are being
investigated
to
their
roles
in
rhinosinusitis,
particularly CRS. These include, but are not limited to, eosinophils,
neutrophils,
mast
cells,
T and
B
celis,
immunoglobulins, interleukins, tumour necrosis factor, major basic protein and a nwnber of other mediators of
inflammation. Whether any specific inflammatory med
iator is present is difficult to determine and may vary based on what is the inciting factor in the inflamma tion.3,4, 11 Other factors have also been identified that may play a role
in the development or perpetuation of
CRS, including biofilms, superantigens and osteitis.3,-4
When viewed histopathologically, acute rhinosinusitis shows a predominance of
n eutroph
il s
,
An
exUdative
process is identified and there are visible areas of necrosis, hemorrhage
and
ulceration.2,12
Histopathologically,
chronic rhino sinusitis is somewhat distinct from acute rhinosinusitis. In the acute setting, there is a predomi nance
of
neutrophils
and
hemorrhage,
ulcerations,
necrosis and exudate are present.2,12 In chronic rhino sinusitis, a proliferative process is pr es ent
with lympho
cytes, plasma celis and eosinophils being present. In most cases, an eosinophilic infiltration may be seen either in the mucosa or in the sinus cavities themselves. There is evidence of fibrosis of the lamina propria. Fungi and
bacteria may be seen.2, 3, 4,
5, 11
Bacteriologically, these two
temporally different stages of rhinosinusitis are also found
to differ. Streptococcus pneumoniae
(20-45 percent) and
Haemophilus inj7.uenzae (22-35 percent) are the predo minant organisms in acute bacterial rhinosinusitis
in (Figure 113.1), while Streptococcus pneumoniae (30-43 percent), Haemophilus inj7.uenzae (20-28 percent) and Morexella catarrhalis (20-28 percen t) are the
adults
predominant organisms in acute bacterial rhino sinusitis
in children
(Figure 113.2).2,14,15 Although previously
22-35%
• •
Streptococcus pneumoniae Haemophilus infJuenzae Strep species
• •
Anaerobes
• •
Staphylococcus aureas
Moraxella catarrha/is
Other
Figure 113.1 Microbiology of acute bacterial rhinosinusitis in adults. Redrawn from Otolaryngology and Head and Neck Surgery 123 5uppl 1, Si nus a nd Allergy Health Partnership. Antimicrobial treatment guidelines for acute bacterial rhinosinusitis, 5 1-532, @ 2000 with permission from the American Academy of Otolaryngology - Head and Neck Surgery Foundation.13
associated organisms. As mentioned above, it is becoming more dear that CRS is an inflammatory disease, and it mayor may not involve pathogenic microbes. Therefore, bacteria, fungi or viruses may be involved in some cases but there may be cases with no identifiable pathogenic organism. In those patients with CRS who do have potential pathogenic bacteria, the most common organ isms are Staphylococcus species (55 percent) and Staphy 1 lococcus aureus (20 percent).2, 6 Some studies have shown a high prevalence of Enterobacteriaceae organisms,16, 17 l1 anaerobes,Is Gram-negative bacteria19 artd fungi.
Emerging antimicrobial resistance 3 mechanisms
thought to be a contaminmt, Staphylococcus aureus is now being considered a real pathogen
in ABRS, and since
common pathogens
to treat.
appears to be largely related to the use of antibiotics. In
Staphylococcus aureus may be a more important bacteria . Since the pathogenesis of chronic rhinosinusitis is not
well
defined
and
there
may
be
multiple
potential
associated or aetiologic factors, it is difficult to identify
•
Antimicrobial resistance appears to be increasing for the
Morexella catarrhalis is largely a self-limited pathogen,
in rhino sinusitis, particularly for H.
inj7.uenzae and S. pneumoniae. This increasing resistance
parts of the world, particularly rates
of
the Far East, resistance 50 percent are not uncommon for both
macrolides and the beta-Iactams. Resistartce mechanisms
1442 I
PART 13
THE NOSE AND PARANASAL SINUSES lower, then clinical criteria including symptoms and physical findings are preferred.20,21 The diagnosis for research should usually include more objective informa tion. Most recommend a maxilla ry sinus tap with culture, to identify specific pathogens for research. At this time, a maxillary sinus tap with cultures revealing pathogenic organisms remains the gold standard for the diagnosis of ABRS, although there is increasing interest in the role of
5-7%
endoscopic-guided middle meatal cultures, in lieu of maxillary sinus taps.16.22 It has even been suggested that endoscopically guided cultures may be a preferred culture technique to maxilla ry sinus taps, as they can identify patients with 20-28%
• •
ethmoid infection
and may be more
sensitive to identifying pathogens. Middle meatal cultures are also less traumatic to patients and can allow for more frequent cultures, which can aid in surveillance, improve
S. pneumoniae
culture-specific therapy and identify early failures.22 If
H. influenzae
one is to make the diagnosis of bacterial rhinosinusitis,
M. catarrhalis
the current accepted reference standard for culture is
• Anaerobes
more than 1.0
S.pyogenes
sinus
Microbiology of acute bacterial rhinosinusitis in children. Redrawn from Otolaryngology and Head and Neck Surgery 123 5uppl 1, Sinus and Allergy Health Partnership. Antimicrobial treatment guidelines for acute bacterial rhinosinusitis, 51-532, @ 2000 with permission from the American Academy of Otolaryngology - Head and Neck Surgery Foundation.13 Figure 113.2
are beyond the scope of this chapter, but fall primarily into three different mechanisms:
x
104 colony forming units (CFU)/mL in
aspirate.23
Lower
colony
concentrations
could
potentially represent early infection.
.
In CRS and in SRS, definitive methods for diagnosis
have not yet been determined. The stratification of disease by symptoms, as established by the Rhinosinusitis Task Force, may not apply well to these conditions and other diagnostic tools may be necessary. The recommended time frames of greater than
12 weeks for CRS
and
between four and 12 weeks for SRS have been commonly adopted. Therefore, in most cases, an identification of the length of time from the onset of symptoms or first physical findings will clarify what type of rhinosinusitis
L antibiotic deactivating enzymes;
should be considered. Then, appropriate history, physical
2. alterations in the target site of the antibiotic; 3. changes in the influx/efflux procesS.14
examinations and testing will confirm the diagnosis.
This emerging resistance has had significant implications
establishing the diagnosis of rhinosinusitis, but these are
in the antimicrobial treatment of rhinosinusitis and has
prompted the modification of traditional antibiotics and the development of new antibiotics to combat these resistant organisms. Appropriate prescribing behaviours may
serve
to
reduce
this
rapid
rate
of
resistance
development.
There are a number of tests that are important in often more important in chronic rather than acute rhinosinusitis. Nasal endoscopes are valuable to assess the
nasal
anatomy,
confirm
drainage
and
evaluate
treatment response.24 Radiographs have been used for all types of rhinosinusitis. Plain sinus radiographs were commonly used for diagnosis but are not of much value. The
Agency
(AHCPR)
for
Health
Care
Policy
and Research
report suggests that plain radiographs are not
cost-effective in the diagnosis of ABRS20, 21 and, given the
DIAGNOSIS
poor specificity and sensitivity, do not add much in
There are many possible methods to make a diagnosis of
subacute or chronic. The use of plain radiographs is
rhinosinusitis, but there is much debate related to the best
suspect except in specific circumstances.
It has become increasingly clear that
At this time, the preferred radiologic test is a sinus
the diagnosis of ABRS is best made on clinical grounds
computed tomography (CT) scan. Although CT scans
and criteria (Table 113.2). An evidence-based report from
cannot distinguish between inflammation and infection,
method.
[****1***]
the Agency on Health Care Policy and Research in the
they do seem to correlate fairly well with the extent of
USA suggested that the most cost-effective method for
disease. Studies using CT or magnetic resonance imaging
diagnosis differs at different prevalence rates. In general,
(MRl) have reported sinus mucosal abnonnalities in
the diagnosis can be made on an empiric basis and
15-49 percent of patients without symptoms suggestive
symptoms if the prevalence rates are high, such as in
of
specialty practices. In areas where prevalence rates are
those findings remains unclear?O
rhinosirwsits
and
the
clinical
;'
/
CT
correlations
of
scans are not
Chapter 113
recommended in the evaluation of ABRS, as they are not cost-effective for this indication.2o, 21 There is also good evidence that a CT scan may be abnormal following an acute viral respiratory tract infection or a viral rhino sinusitis.25 The role of CT scanning in ABRS is mostly for evaluation of suspected or impending complications, such as orbital or intracranial involvement. CT scans have been very helpful in assessing severity of disease or response to treatment in CRS. In an effort to standardize the CT scan evaluation, there have been a number of attempts to establish staging systems to assess the severity of rhinosinusitis. One staging system that is commonly used was recommended by Lund and Mackay in 1993.26 CT scans have now become the radiologic workhorse for both clinical care and research in rhinosinusitis. MR imagings have been limited in their application, primarily because they may be too sensitive for routine clinical use and the lack of bony detail needed for surgical intervention. It has been recently recom mended that either a CT scan or endoscopic evaluation of the nose (preferably with photo or video documentation) should be a part of any prospective clinical trial in CRS.3 Although there have been some that have advocated ultrasonography, this test has limited usefulness in the clinical setting, particularly in ABRS.20
NATURAL HISTORY The natural history of rhinosinusitis varies depending on the classification. For the most part, ABRS tends to be a self-limited disease. Studies comparing antibiotics to placebo have not shown a dramatic difference in cure rates between the two groups.20, 21 It is clear, however, that antibiotics play an important role in reducing symptoms and speeding the time to recovery.20, 21 Because of this more rapid improvement, most cases of clinically diagnosed acute bacterial rhinosinusitis are best treated with antibiotics. The natural history of CRS is much more variable and is dependent on a number of factors including those of both the host and external factors. [HH/H*/H] Complications of ABRS are rare. The primary serious complications of bacterial rhinosinusitis are local exten sions of the infection into the intracranial cavity or orbit and metastatic spread to the central nervous system with subsequent brain abscess, meningitis and cavernous sinus thrombosis. Major complications related to ABRS are exceedingly rare and reliable data for their frequency are not available. As reported in the AHCPR report, an estimated one in 10,000 general hospital admissions are for brain abscess and, in different geographic locations, there is wide variation in the estimated percentage (0.5 percent in China and 15-25 percent in northern Europe) that are secondary to rhinosinusitis.14, 27 In 1995, the number of US hospital discharges for brain abscesses (ICD-9 code 324.0) was 5000.28 Using the highest
-...
i ;
Rhinosinusitis I 1443
estimated percentage of brain abscess secondary to rhinosinusitis (25 percent), approximately 1250 cases are likely to occur from among 118,255,000 discharges recorded for that year (approximately 1:95,000 admis sions). Estimates of complications related to CRS are even more difficult given the heterogeneity of the disease and the general lack of definitions.
PREVALENCE OF RHINOSINUSITIS It is difficult to make good estimates of the disease prevalence of rhinosinusitis. Differences in prevalence rates may vary in part from differences in definitions of the disease and from differences in the populations in which the prevalence is assessed. [*H*/H*/H] One way to estimate prevalence in common conditions is by assessing insurance claims. Rhinosinusitis, as estimated through insurance reimbursement claims and population statistics (e.g. National Ambulatory Medical Care Survey), is one of the most common health complaints in the US.29 In order to make such determinations, assumptions can be made using estimates of the average number of acute respira tory illnesses per year. It is estimated that children have between six and eight URI per year and adults average two to three.3 0 If an assumption is made that 90 percent of patients with colds have sinusitis (bacterial or viral), then it can be estimated that in the US there are over a billion cases of viral and bacterial rhinosinusitis annually (260 million people x four episodes per person approximately one billion cases).20 Acute bacterial rhinosinusitis affects three in every 1000 people in the US each year, with some individuals having multiple episodes. Up to 18 million visits to health care profes sionals also occur each year for chronic rhinosinusitis. The frequency of ABRS appears to be higher in children with the peak age group for acute bacterial rhinosinusitis occurring between three and six years. This age range also corresponds to the peak ages where the incidence of community-acquired upper-respiratory infections is highest. Children in this age group may experience an average of six to eight respiratory infections per year. As stated in a recent United States' Agency on Health Care Policy and Research Evidence Based Report on Acute Rhinosinusits, 'Recent outpatient data from the 1995 National Ambulatory Medical Care Survey (NAMCS) estimated that the roughly 700 million visits to non federally employed physicians in office-based practices included about three million cases of acute sinusitis (ICD-9-CM-461). The NAMCS data from 1990 to 1995 (National Center for Health Statistics, 1990-1995) show an increasing trend in the prevalence of this diagnosis.. .. It is not clear whether this trend represents an actual increase in disease prevalence, potential changes in reporting (e.g. disease definition, billing practices), or changes in patients seeking or accessing medical care. The National Hospital Discharge Survey documented 61,000 =
I
1444 I
PART 13
THE NOSE AND PARANASAL SINUSES
hospital discharges for patients with diagnoses (primary or other) of acute sinusitis (ICD-9-CM-461) for 1993; 66,000 for 1994; and 84,000 for 1995 (National Center for , Health Statistics, 1993; 1994; 1995). 20 It is generally accepted that rhinosinusitis is a common entity, although given the wide range of clinical presentations, the multiple potential types and the varied aetiologic and associated factors, this diagnosis often includes several pathophysiologic conditions. In order to better define the incidence and prevalence, more specific criteria should be applied. Although the Rhinosinusitis Task Force has added some clarity to acute rhinosinusitis by applying both time frame and symptom criteria, there has been no standardization in relation to chronic rhinosinusitis. To these ends, there have been no antimicrobial products approved in the US with an indication for chronic rhino sinusitis and no formal clinical trials comparing two antimicrobials for this entity. Estimating the prevalence of various sinusitis subgroups (e.g. ABRS) requires using more specific diagnostic criteria in research studies. Even if the same definition were used, there could still be important selection biases that could result in different incidence and prevalence assumptions for the general population as opposed to patients in specific clinical settings. This might be even more substantial for patients enrolled in studies or clinical trials where other certain specific selection criteria are applied. These prevalence rates have also been found to vary substantially depending on the type of provider and method used for diagnosis. For children seen in a primary care setting with symptoms of an acute upper respiratory tract infection, 9-17 percent will have an acute bacterial rhinosinusitis. This number increases to 38 percent for patients presenting to a general medical clinic with URI symptoms and increases dramatically in an otolaryngol ogy clinic where up to 83 percent of patients presenting with an 'acute URI have acute bacterial rhinosinusitis.20, 21 In adults, rhinosinusitis rates may be higher among women and in people living in the southern parts of the country. According to the US National Center for Health Statistics, chronic and acute rhinosinuisitis are diagnosed more frequently than all of the other respiratory diseases in adults and may affect as many as 32 million Americans, which is approximately 14 percent of the population.31
THE ECONOMIC AN D QUALITY OF LIFE IMPACT OF RHINOSINUSITIS Since it is fairly well accepted that rhinosinusitis is one of the most common reasons for an individual seeking medical care, rhinosinusitis results in high direct medical costs. [***/**] These include the costs of an office visit; any diagnostic tests performed, such as cultures, labora tory or radiologic costs; antibiotics or other pharmaceu ticals; procedures or surgery; hospitalizations; and the
treatment of any complications. Chronic rhinosinusitis results in 13-18 million office visits to a physician in the US each year. Americans make 645,000 emergency room visits for rhinosinusitis annually.31 A careful analysis of the 1985, 1989 and 1992 NAMCS data reveals not only an increasing trend of office visits for sinusitis, but also an increasing rate for antibiotic prescriptions, representing 7, 9 and 12 percent of prescriptions over those three years, respectively. By 1992, rhinosinusitis was the fifth most common diagnosis where an antibiotic was prescribed.32 As prescribing patterns have moved to newer generation antibiotics, and as more physicians move towards longer-duration therapy, antifungal or systemic antibiotic treatment for CRS, the cost of antimicrobial therapy would be expected to be escalating. It was estimated that Americans spent approximately $200 million on prescription cold medications for sinusitis in 1992, which was a $50 million increase over 1989.33 It is also estimated that they spend more than $2 billion annually on over-the-counter medications for nasal and sinus disorders (AHCPR)?O If all direct health care expenditures are measured, the primary diagnosis of sinusitis leads to approximately $3.39 billion in the US.34 Total costs have been estimated at $5.8 billion.34 In recent years, there has also been a trend for patients to use more vitamin, homeopathic and naturopathic remedies for their upper respiratory tract infections. These costs have not been estimated but are likely to be substantive, driving up the direct costs of medical care. The direct costs of rhinosinusitis do not include other important costs to the individual, the community and society. There are losses in time away from work or school with the associated decrease in productivity. There are also the costs related to decreased productivity of individuals who do not miss work but are less effective because of their illness. If all the costs were measured, rhinosinusitis costs in the billions of dollars each year in the US alone. Such costs worldwide are higher than the gross national products of many of the world's nations. In the Far East, antibiotic resistance has developed rapidly for penicillins and macrolides and is beginning to be seen even in the fluoroquinolones. More expensive antibiotics are needed to manage these infections. One immeasurable result of any disease such as rhinosinusitis is the impact on quality of life. Recent efforts to evaluate the impact of disease on quality of life and the outcome of disease have clarified the importance of such impacts. Glicklich et al.35 have shown that rhinosinusitis has a significant quality of life impact, even in comparison to chronic debilitating diseases such as diabetes and congestive heart failure. We have compared a variety of acute and chronic nasal and sinus conditions using the Rhinosinusitis Disability Index (RSDI) (Figure 113.3). The RSDI is a validated instrument that measures the physical, functional and emotional impact of rhinosinusitis on a person's quality of life. Although
Chapter 113
•
Rhinosinusitis I 1445
•
RHINOSINUSITIS DISABILITY INDEX (RSDI)
The purpose of this scale is to identify difficulties that you may be experiencing because of your nose or sinus problems. Please answer: Never, Almost Never, Sometimes, Almost Always, or Always to each item. Answer each item as it pertains to your nose and sinus problem only. Never
Almost Sometimes Almost Never
Always
Always
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
F5. Because of my problem I feel fatigued.
0
0
0
0
0
F6. Because of my problem I don't sleep well.
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
E16. Because of my problem I avoid being around people.
0
0
0
0
0
E17. Because of my problem I am frequently angry.
0
0
0
0
0
E18. Because of my problem I do not like to socialize.
0
0
0
0
0
E19. Because of my problem I frequently feel tense.
0
0
0
0
0
P20. Food does not taste good because of my change in smell.
0
0
0
0
0
E21. Because of my problem I frequently feel irritable.
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
F1. Because of my problem
I feel handicapped.
F2. Because of my problem I feel restricted in performance of my routine daily activities. F3. Because of my problem I restrict my recreational activities. F4. Because of my problem
F7.
I feel frustrated.
I have difficulty with exertion due to my nasal obstruction.
P8. I am inconvenienced by my chronic runny nose. P9. The pain or pressure in my face makes it difficult to me to concentrate. P10. The pain in my eyes makes it difficult for me to read. P11.
I have difficulty stooping over to lift objects due to face pressure.
E12. Because of my problem I feel stressed in relationships with friends and family. F13. Because of my problem I avoid traveling. E14. Because of my problem I feel confused. E15. Because of my problem
I have difficulty paying attention.
P22. Because of my problem I have difficulty with strenuous yardwork and housework. F23. Because of my problem I miss work or social activities.
5093
�
• ' Figure 113.3
•
Rhinosinusitis disability index (RSDI) (continued over).
;'
1446 I
PART 13
THE NOSE AND PARANASAL SINUSES
•
Never
Almost Sometimes Almost Never
• Always
Always
P24. My frequent sniffling is irritating to my friends and family.
0
0
0
0
0
P25. Straining increases or worsens my problem.
0
0
0
0
0
E26. Because of my problem I am depressed.
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
E27. My problem places stress on my relationships with members of my family or friends. F28. My outlook on the world is affected by my problem. F29. Because of my problem I find it difficult to focus my attention away from my problem and on other things. P30. My sexual activity is affected by my problem.
Please evaluate the overall severity of your nasal-sinus problem. Moderate
Normal
P Scale
Severe
1
2
3
4
5
6
7
0
0
0
0
0
0
0
F Scale
E Scale
[0[0[0
Total Scale
I I I I
[0 [0 - [0 I I I I I I I I I I I I II I I I I I I I I I I I I I I I I I � [0-[0-[0 I I I I I I I I I UJ Todays Date:
First Name:
-
Last Name:
Birth Date:
MRN:
o Male
o Female
Provider:
Date of Operation:
I I I I I I I I I I I I I I I I I I I I I 1[0-[0-[0 Type of Visit: 0 New Visit
o Retu rn Visit Diagnosis:
o Pre-Treatment
o Pre-Surgical Treatment
o Post Medical Treatment
o Post Surgical Treatment
0 1. Allergic Rhinitis
o 5. Anatomic Obstruction (septum/turbinates)
o 2. Non-allergic Rhinitis
o 6. Nasal mass/tumor
o 3. Acute Rhinosinusitis
o 7. Other (describe)
o 4. Chronic Rhinosinusitis o 4a. Chronic Rhinosinusitis w/o polyps o 4b. Chronic Rhinosinusitis with polyps o 4c. Chronic Rhinosinustis / polyps / asthma o 4d. ASA - Hypersensitivity triad 5093
� .
• Figure 113.3
Rhinosinusitis disability index (RSDI) (continued).
Chapter 113
originally validated for rhinosinusitis, the RSDI has also
Rhinosinusitis I 1447
methods for diagnosis and treatment are, therefore, difficult to determine at this time. ,/ Antibiotic therapy is usually not needed until seven to ten days after the onset of symptoms in an upper respiratory tract infection. ,/ Resistant organisms are more likely to be the cause of ABR5 jf a patient has had recent antibiotic therapy.
been found to be valid in other acute and chronic nasal sinus disorders including allergic and nonaUergic rhinitis and anatomic obstructive disorders. Using the RSDI, we have shown that ABRS has a greater impact on the general quali ty of life of pa ti ents than other disorders, such as allergic and nonallergic rhinitis or anatomic obstruc 3 tion.36, 7 Since the RSDI measures not only the physical symptoms but also the emotional and functional impact of the disorder, it can be seen that rhino sinusitis has a broader impact than that ascribed to the local symptoms
alone When we consider the quality of life impact from the .
Deficiencies in knowledge and areas for future research
rhinosinusitis-related symptoms and the associated emo tional and functional impairments, it can be assumed that rhinosinusitis has a dramatic impact on patients' lives.
>-
This, in turn, will affect their overall sense of weU-being, which can" ultimately effect work productivity and life satisfaction.
It is possible that the direct costs of
)-
rhinosinusitis are less than the indirect costs related to reduced productivity in the workforce.
)-
KEY POINTS ..
llinu. inu:;itis is a group of J" order c;haraderiz('d hy intlamrnation of the
)mucC1 a
)-
REFERENCES
•
*
(lis
,/
Good definitions for rhinosinusitis other than acute bacterial rh inosi nusitis, particularry chron ic rh inosinusitis. Since many pharmaceutical trials and federal agencies rely on maxillary sinus taps for assessing the bacteriology, supporting the role of middle meatal cultures in comparison to maxillary taps should improve surveillance, reduce morbidity and improve enrollment in further trials. Further work must be carried out on the roles of inflammatory cells and mediatiors in relationship to the pathogenesis of rhinosinusitis. Research in these areas is critical to our understanding of the disease and designing treatments. Since ultimately quality of life may be the most important measure of the disease state and response to treatment, future research should include further outcomes investigations in rhinosinusitis .
. 'gn
fie
nt
imp
"t
on
direct and inc.Jire�t quality of liti...
co t
are rarc.
an
The diagnosis of acute rhinosinusitis is best made on clinical grounds with little role for imaging. ',/ Chronic rhinosinusitis is a heterogeneous group of disorders characterized by chronic inflammation of the nose and paranasal sinuses. The preferred
*
1. Report of the Rhinosinusitis Task Force Committee Meeting. Otolaryngology and Head and Neck Surgery. 1997; 117: 51-68. 2. Lanza DC, Kennedy DW. Adult rhinosinusitis defined. Otolaryngology and Head and Neck Surgery. 1997; 117: 51-7. 3. Benninger M5, Ferguson BJ, Hadley JA, Hamilos DJ, Jacobs M, Kennedy DW et 01. Adult chronic rhinosinusitis: Definitions, diagnosis. epidemiology and pathophysiology. Otolaryngology and Head and Neck Surgery. 2003; 129: 51-32. 4. Benninger M5, Anon J, Mabry RL. The medical management of rhinosinusitis. Otolaryngology and Head and Neck Surgery. 1997; 117: 541-9. 5. Meltzer EO, Hamilos OJ, Hadley JA, Lanza DC, Marple BF, Nicklas RA et 01. Rhinosinusitis: Establishing definitions for clinical -research and patient care. Otolaryngology and Head and Neck Surgery. 2 004; 114: 51-62. I
I
,- �---�... "
! ..J,'
1448 I
PART
13 THE NOSE AND PARAI\JASAL SINUSES
6. Benninger MS. The impact of cigarette smoking and environmental tobacco smoke on nasal and sinus disease. American Journal of Rhinology. 1999; 13: 435-8. 7. Benninger MS. Rhinitis, sinusitis, and their relationship to allergies. American Journal of Rhinology. 1992; 6: 37-43. 8. Slavin R. Sinusitis in adults and its relationship to allergic rhinitis, asthma and nasal polyps. Journal of Allergy and Clinical Immunology. 1985; 82: 950-5. 9. Kaliner MA, Osguthorpe JD, Fireman P, Anon J, Georgitis J, Davis ML et al. Sinusits: Bench to bedside. Current findings, future directions. Otolaryngology and Head and Neck Surgery. 1997; 116: Sl-20. 10. Kennedy DW, Zinreich SJ, Rosenbaum AE, Johns ME. Functional endoscopic sinus surgery: theory and diagnostic evaluation. Archives of Otolaryngology. 1985; 111: 576-82. 11. Ponikau JU, Sherris DA, Kern EB, Homburger HA, Frigas E, ' Gaffey TA et al. The diagnosis and incidence of allergic fungal sinusitis. Mayo Clinic Proceedings. 1999; 74: 877-84. 12. Coltran RS, Kumar V, Robbins SL (eds). Robbins pathologic basis of disease, 5th edn. Philadelphia: WB Saunders, 1994: 55-83. 13. Sinus and Allergy Health Partnership. Antimicrobial treatment guidelines for acute bacterial rhinosinusitis. Otolaryngology and Head and Neck Surgery. 2000; 123: Sl-32. * 14. Sinus and Allergy Health Partnership. Antimicrobial treatment guidelines for acute bacterial rhinosinusitis. Otolaryngology and Head and Neck Surgery. 2004; 130: Sl-45. 15. Gwaltney JM, Scheid WM, Sande MA, Sydor A. The microbial etiology and antimicrobial therapy of adults with acute community-acquired sinusitis: a fifteen-year experience at the University of Virginia and review of other selected studies. Journal of Allergy and Clinical Immunology. 1992; 90: 457-62. 16. Benninger MS, Appelbaum PC, Denneny JC, Osguthorpe DJ, Stankiewicz JA. Maxillary sinus puncture and culture in the diagnosis of acute rhinosinusitis: The case for pursuing alternative culture methods. Otolaryngology and Head and Neck Surgery. 2002; 127: 7-12. 17. Rombaux P, Gigi J, Hamoir M, Eloy P, Bertrand B. Bacteriology of chronic sinusitis: the bulla ethmoidalis content. Rhinology. 2002; 40: 18-23. 18. Erkan M, Asian T, Ozcan M, Koc N. Bacteriology of antrum in adults with chronic maxillary sinusitis. Laryngoscope. 1994; 104: 321-4. 19. Bolger WE. Gram negative sinusitis: An emerging clinical entity? American Journal of Rhinology. 1994; 8: 279-84. 20. Agency on Health Care Policy and Research. Diagnosis and Treatment of Acute Bacterial Rhinosinusitis. AHCPR Publications Clearinghouse, Publication No. 99-E016, 1999. * 21. Benninger MS, Holzer SE, Lau J. Diagnosis and treatment of uncomplicated acute bacterial rhinosinusitis: Summary of the Agency on Health Care Policy and Research Evidence Based Report. Otolaryngology and Head and Neck Surgery. 2000; 122: 1-7.
*
22.
23.
24. *
25.
*
26. 27.
28.
29. 30.
31.
32.
33.
34.
35.
36.
37.
Benninger MS, Payne SC, Ferguson BJ, Ahmad N, Hadley J. Endoscopically directed middle meatal cultures versus maxillary sinus taps in acute bacterial rhinosinusitis: A meta-analysis. Otolaryngology and Head and Neck Surgery. 2006; 134: 1-7. Turner BW, Cail WS, Hendley JO, Haydon FG, Doyle WJ, Sorrentino N. Physiologic abnormalities in the paranasal sinuses during experimental rhinovirus colds. Journal of Allergy and Clinical Immunology. 1992; 90: 474-8. Benninger MS. l\Jasal endoscopy: Its role in office diagnosis. American Journal of Rhinology. 1997; 11: 177-80. Gwaltney JW, Phililips CD, Miller RD, Riker DK. Computed tomography of the common cold. New England Journal of Medicine. 1994; 330: 25-30. Lund VJ, Mackay IS. Staging in rhinosinusitis. Rhinology. 1993; 107: 183-4. Wispelwey B, Scheid WM. Brain abcess. In: Mandell GL, Douglas RG, Bennett JE, Dolin R (eds). Principles and practice of infectious diseases, 4th edn. l\Jew York: Churchill Livingston, 1995: 887-98. United States National Center for Health Statistics, 1995. Cited September 14, 1999. Available from: http:// www.cdc.gov.nchs. Gwaltney .1M. Acute community acquired sinusitis. Clinical Infectious Diseases. 1996; 23: 1209-23. Dowell SF, Schwartz B, Phillips WR. Appropriate use of antibiotics for URI's in children: Part I. Otitis media and acute sinusitis. The Pediatric Consensus Team. American Family Physician. 1998; 58: 1113-8. Chronic Sinusitis Statistics by National Center for Health Statistics, Center for Disease Control, US, 2000. http:// www.cdc.gov/nchs/data/hus/hus05.pdf. McCaig LF, Hughs .1M. Trends in antimicrobial drug prescribing among office-based physicians in the United States. Journal of the American Medical Association. 1995·; 273: 214-9. Kennedy DW, Gwaltney JM, Jones JG. Medical management of sinusitis: educational goals and management guidelines. The International Conference on Sinus Disease. Annals of Otology, Rhinology, and Laryngology. 1995; 167 Suppl.: 22-30. Ray NF, Baraniuk .IN, Thamer M, Rinehart CS, Gergen PJ, Kaliner M et al. Healthcare expenditures for sinusitis in 1996: contributions of asthma, rhinitis and other airway disorders. Journal of Allergy and Clinical Immunology. 1999; 103: 408-14. Glicklich RE, Metson R. The health imnpact of chronic sinusitis in patients seeking otolaryngologic care. Otolaryngology and Head and Neck Surgery. 1995; 113: 104-9. Benninger MS, Senior BA. The development of the rhinosinusitis disability index. Archives of Otolaryngologyogy and Head and Neck Surgery. 1997; 123: 1175-9. Senior BA, Benninger MS, Glaze C. The use of the Rhino�inusitis Disability Index (RSDI) in rhinologic disease. American Journal of Rhinology. 2001; 15: 21-5.
114 Funga'i rhinosinusitis
JEAN MICHEL KLOSSEK
Introduction
1449
Best clinical practice
Noninvasive fungal sinusitis or rhinosinusitis
1452
Deficiencies in current, knowledge and areas for future
Invasive fungal rhinosinusitis
1454
Key points
1455
The data
allergy.
research
1456
References
1456
in the chapter are supported by a Medline search using the key words fungal
some
sinusitis, rh ino sinusitis and
fungus
control subjects while standard cultures were positive in 7 s percent and Hend olin et aI. improved this finding with a
INTRODUCTION For
1455
years,
fungal
rhinosinusitis
has
become
procedure based on panfungal
PCR
and multiplex liquid
increasingly recognized although the classification and
hybridization. Nevertheless, in spite of these interesting
treatment ar e
and more sensitive techniques and despite the lack of
still
and much remains-to be
under debate
learnt about its optimal management.
1. 2, 3
The role, of fungi in the nose and sinus cavities is
fungi
correlation between the presence of
fungi
in the nose in
control patients and patients with chronic rh inosinusitis,
be
the role of fungal agents in the pathogenesis of sinus
as
distinguish noninvasive and invasive fungal rhino sinusitis
pathogens or simply a part of normal flora? Several
based on the presence or not of fungi in sinus mucosa
unclear, even
if in some healthy individuals
can
cultured from nasal secretions.4, 5, 6 However, there poor
understanding
of when
fungi
are
present
is
a
collection techniques have been performed in control
subjects
and
their
results
vary
dependent ,on
the
disease
remains
unclear. - However,
it
is
possible
(submucosa, vessels or bone). A range of acute chronic
manifestations
is
described.
Several
to
and
fungal
techniques of identification. The technique of sampling
organisms may be involved in these various pathologies,
(swab, irrigation, aspiration)
such as Aspergillus, Scedosporium, Alternaria, CurvuIaria
or identification (histo
pathology, culture, polymerase chain reacti on explains the large differences found in studies,s.
7,8,9
everywhere
(PCR)) the different
Nevertheless, as fungi are normally found
in nat ure as spores, it is reasonable to suggest
that most people have fungal colonization in the nasal
cavity.
Using sample collection with irrigation and, cultures, S Ponikau et aI, d isc overe d that over 90 percent of controls
subjects have
PCR,
fungi
present in the nasal mucosa. Using
9 Catten et al. detected 42 perce nt of fungal DNA in
and
Mucor.
The
most
accepted
is
classification
represented by the system proposed by deShazo et al.
1
(Table 114.1). Terminology is also a subject of confu si on (Table 114.2) as many terms are used to d efine similar
pathologies in the medical literature; for example, the common fungus ball is still referred to as mycetomas or previously as aspergillosis, both now abandoned. Further
more, the patient's state o f immunocompetence is o f importance in predicting the aggressiveness of the fungal
organism.
[H]
I
i-
f'
Table 114.1
Classification of fungal disease in the nose and sinuses.
Syndrome Allergic fungal
Common cause
Geographic distribution
Characteristics of host
Associated conditions
Bipolaris species,
Humid areas, especially
Immunocompetent.
Chronic rhinosinusitis,
rhinos!nusitis
c,
Curvulan'a lunata
coastal United
and Aspergillus
States
frequently atopic
nasa I polyps
fum;gatus
Sinus fungal ball
A. fumigotus and
A
(mycetoma)
fJovus
scepdosporium
Histopathological findings Sparse fungal elements in
Clinical presentation Chronic pansinusitis.
PrOlp[Osis
Treatment
Prognosis
Debridment. aeration,
dense, eosinophil-rich,
nasal polyps,
oral and topical
mucoid material
expanded
corticosteroids,
('allergic mucin')
opacities on
and
containing rare
computed
immunotherapy
hyphae;
tomography,
Iymphoplasmocytic
proptOSis or eye -
and eosinophilic
muscle
response in adjacent
entrapment
mucosa
children
(7)
allergen
in
Rhinosinusitis (often
Debridment. aeration;
coastal United
fungal elements in a
unilateral) nasal
antifungal agents
States
mucoid matrix forming
obstruction,
not required
an expansile mass;
green-brown nasal
Humid areas, especially
Immunocompetent
Chronic rhinosinusitis
Dense accumulation of
low-grade chonic
discharge.
inflammatory response
calcification in
in adjacent mucosa
Recurrent( common
Excellent
sinus on computed tomography
Acute (fulminant) invasive
Fungi of the order Mucorales and
fungal rhinosinusitis
No specific geographic location
Aspergillus
Chronic invasive fungal
A fumigatus
Immunocompromised;
Diabetes mellitus,
Fever. cough. crusting
± Radical
debridment
Fair when disease is
malignant
mucosa, submucosa,
of nasal mucosa,
until
immunocompetent
conditions,
blood vessels or bone.
epistaxis.
histopathologically
poor with
immunosuppres
with extensive tissue
headache, mental
normal tissue is
intracranial
sive therapy
necrosis and
status change
evident. antifungal
involvement
limited to sinus;
neutrophilic
agents. treatment
inflammation
of underlying conditions
No specific geographic
Immunocompetent
Diabetes mellitus
Necrosis of mucosa. submucosa, bone and
location
rhi nosinusitis
Fungal elements in
rarely
Orbital apex syndrome. nerve palsy
± Radical antifungal
blood vessels, with
Variable. long-term
debridement,
survey required
agents
low-grade ,-
Granulomatous invasive
A ffovus
inflammation Predominantly North
I mmu nocompetent
Africa
fungal rhinosinusitis
None
Granuloma with
f:· ( � 'f �-;
©
1997 Massachusetts Medical Society. All rights reserved.
Debridement, aeration, and antifungal
cells and palisading
agents
histiocytes
Adapted from deShazo et 01.1
Unilateral proptosis
multinucleated giant
Good, but disease can recur
Table 114.2
Fungal rhinosinusitis and diagnostic criteria. CIi{1ical
da
Radiologjtal data
:1
Immunology Immu ocompetent
� .. Sap rophyt i c
colo n ization
Fungus ball
Asympto m atic Post nasal discharge
Opacity of the
��'agy
�erum
11{
my
pnh
Yes
nl
No
No
No
Yes
Aerocontamination
Yes
nl
No
No
Rare
Yes
Aspergillus Scedosporium
Elevate d
No
No
Yes eosinophiles
Yes
Dematiaceous + + Aspergillus
Yes
M iscella neo us (Aspergillus)
±
Yes
sinus cavity involved.
Headache
Maxillary
Asymptomatic
Sphenoid
Young adults
Opacity
(commonly) Ethmoid Allergic fungal
Yes (atopic)
Elevated (skin test
rhinosinusitis Nasal obstruction
B o ne erosion
Bilateral or
Bone deformation
u ni l ate ra l
Asthma Invasive chronic fungal rhin osinusiti s
rhinosi nusitis
Nasal discharge
crystals
Adults
Opacity
Pain, proptosis
Tissue infiltration
Fever
Mucorales
Aspergillus
Tissue inti Itration Ophthalmic
d iso rders
nl, normal; NR, not relevant
Charcot Leyden
�50%
Neurological Invasive acutefungal
Heterog eneous
Nasal polyps
+)
Yes
NR
No (AIDS, diabetes)
NR
NR
Yes ±
gran uloma
±
Bone erosion Opacity
Yes
necrosis
Yes
Rare
th rom bosi s
1452
I PART 13 THE NOSE AND PARANASAL SINUSES
N ON INVASIVE FUNGAL SINUSITIS OR RHIN OSINUSITIS Fungus ball Previously frequently referred to incorrectly as myceto mas, the fungus ball is now well defined
as
the presence of
tangled mats of hyphae in one or more sinus cavi ties It .
occurs in immunocompetent patients without invasion of
the mucous membrane on histopathologyl, 2,10 and must be distinguished from saprophytic
fungal infestation
which corresponds to fungal spores found on crusts and
mucus in the n os e [***] In all the publications in English, only adults with a .
female predominan ce
are affected and no paediatric cases
have been reported.!i According to the available publica tions, the incidence seems to correlate with geographic
CT scan showing fungus ball of the right
Figure 114.1 maxillary sinus.
1 factors suc h as humidity.2, 0 The maxillary sinus followed
by the sphenoid sinus are the main 10cations,12 though any sinuses may be involved alone or in association with others.
Persistent symptoms such as post-nasal discharge and cacosmia are the most common clinical presentation, but the patient may also be asymp toma tic. Acute presentation with fever, proptosis or blurred vision are extremely uncommon. Nonspecific changes are seen with nas al endoscopy as the actual fungus ball is rarely observed in the nose. Sinus computed tomography (CT) is the most reliable radiological examination to identify a fungus ball.13 Heterogeneous opacification is the most common ap
pearance, associated with bony thicke ning or sclerosis of the sinus walls involved (Figure 114.1). Calcification corresponding to dense hyphae is frequently observed but is not specific to a fungus ball.14 Furthermore, bone
Fungus ball of the left ethmoid with bone
Figure 114.2 inflammation.
erosion may be observed especially when there is a significant inflammatory reaction of the mucous mem brane (Figure 114.2).
Allergic fungal rhinosinusitis
Diagnosis is confirmed by histopathology. No mucosal invasion is
fOW1d, as it is
an
extramucosal disease.
Haematoxylin and eosin stains are used routinely to reveal
fungi but sometimes special fungal stains such as Gomori' methenamine silver are recommended. Cultures may lead to identification of the fungal agent but in the largest published series fungal growth was observed in only 20--50 percent of cases. Failure of the fungus to grow is attributed to the lack of viability of the fungi . A spergillus is the most common agent involved in this pathology, especially Aspergillus fumigatus, but A. flavus or Scedosponum may also be found. Treatment consists of the surgical removal
of the fungus ball by an endon asal approach under endoscopic guidance after enlargement of the natural
2 ostium of the infected sinus(es). ,10 The fungus ball is
aspirated away from the underlying mucous membrane. No medical treatment is required and recurrence or
relapse is exceptional, usually due to residual debris.ls
Allergic fungal rhinosinusitis (AFRS), in th e strictest sense, is defined as an immunocompetent patient with allergy to fu ngus .
[**J*]
an
6,17
Since initial publications,1
approximately 7 percent of all chronic rhinosinusitis cases requiring surgery have been diagnosed as AFRS, especially 2 in the United States. The fungi which are the cause of the hypersensitivity reside in the mucin and provide con tinued stimulation. It is suggested that it has a similar aetiology
to
allergic
bronchopulmonary
aspergillosis
Ascribed
(ABPA) , for which several stages have b
depending on the presence of major or minor criteria for diagnosis.
This
pulmonary pathology
concerns
only
AFRS, the most common fungi reported are dematiaceous species (Bipolaris, Curvularia, Alternaria) and more rarely Aspergillus al th oug h it was originally reported in the first cases.16 Some countries,
Aspergillus although for
and even some geographic areas, are more commonly
j
Cha pter 114 Fungal rhinosinusitis I
1453
represented especially where the climate is warm and
present in the nose associated with complete opacification
humid, but warm dry climates can also be associated with
of the sinus cavities on CT scan associated frequently with
this pathology. Recently, a prospective study in some centres in the United States was performed and, although
lesions are common and highly suggestive of fungus, no
the technique to identify fungal agent was not described, '
direct invasion of the dura or periorbita is seen (Figure
bone
expansion,
although
expanding
inflammatory
it appeared that cases of AFRS occur more frequently in
114.3). The presence of hyphae in the mucin associated
the southern central United States.2 In contrast, mould
with eosinophils is one of the main criteria for the
counts did not seem to correlate with the incidence of
diagnosis. Culture is necessary to identify the actual fungal agent but no growth is frequently observed. Type I
AFRS in this analysis.
hypersensitivity (radioallergosorbent test (RAST) or skin
The pathophysiology of the condition remains subject to considerable discussion
as
several factors are probably
test) appears to be the minimal allergy test to perform for the diagnosis. Other investigations, such as total eosino
necessary for the development of this disease. One of the
hypotheses is represented by the inhalation of ubiquitous
phil count, total serum IgE, antigen specific IgE or IgG (if
fungi which in cases of atopic patients provokes an
available), are suggested to reinforce the diagnosis.2, 25, 26
antigenic stimulus and an inflammatory response of the
IgE levels are frequently higher than in the normal
mucous membrane.5 The resulting oedema is associated with the production of an (allergic mucin', defined
a
as
thick green to grey lamellate of dense inflammatory cells, mostly eosinophils, in various stages of degranulation, Charcot-Leyden crystals and fungal hyphae.ls Never theless, the term (allergic mucin' is inappropriate accord ing to recent studies analysing the presence of these criteria in patients suffering from chronic rhino sinusitis with an abundant thick mucin. According to these results the term (eosinophilic mucin with or without fungus' seems
to
be
more
appropriate. 19
Recently,
a
new
hypothesis has been suggested concerning the presence and production of microbial T cell superantigen,20 but this theory, in keeping with others, requires further studies and analysis to be definitively accepted. The criteria for diagnosis21 are still under debate
(Table 114.3), as several authors have proposed their own rules. Nevertheless, the presence of allergy manifested as a type
I
hypersensitivity
diagnosis.22, 23, 24
is
increasingly
Clinically,
most
essential
patients
are
for
in
a
younger age group (approximately 30 years of age), either
Figur� 114.3
male or female. Bilateral, but also unilateral, polyps are
Heterogeneous opacity with bone expansion.
Table 114.3
:
Unilateral left allergic fungal rhinosinusitis.
Diagnostic criteria for allergic fungal rhinosinusitis.
Endoscopic finding
Dia9nOSTS crite�ia
Stage 0
No mucosal oedema or allergic mucin
Type I hypersensitivity confirmed by history,
Stage 1
Mucosal oedema with or without allergic mucin
Nasal polyposis
Stage 2
Polypoid oedema with or without allergic mucin
St.ag
skin tests or serology Characteristics CT scan signs Positive fungal stain or culture Asthma Stage 3
Sinus polyps with fungal debris or allergic mucin
Eosinophilic mucus with fungal elements and no tissue invas·lon Unilateral predominance Radiographic bone erosion Charcot-Leyden crystals Peripheral eosinophilia
This table was published in
580-8_ © Elsevier
...
(1994).
Otolaryngology and Head and Neck Surgery, 111, Bent 3rd JP, Kuhn FA, Diagnosis of allergic fungal sinusitis,
_
.
.. .
__
_
__ _
.
_
_
_ --l..__ ____
!
---........ .. - -?-� -�--
1454
I PART 13 THE NOSE AND PARANASAL SINUSES
population. Allergic rhinitis, when studied, is generally more frequently found in cases of AFRS.
Treatment is controversial. Even though the removal of
all the mucin is recommended by almost all authors,
sinus seems to be the major site. Nasal endoscopy reveals nasal congestion or polypoid mucosa and sometimes a soft tissue mass covered by a normal or ulcerated mucosa. Radiological appearances usually show opacification with
recurrences are quite common which leads to combina
bone erosion extending to the orbit and/or skull base.
tion with medical therapy, an area still under debate. An
Magnetic resonance imaging (MRI) is helpful to confirm
evaluate the postoperative management. 24 Prednisone is
only generous biopsies, usually taken under general
the oral steroid most commonly given in this period.
anaesthesia, are required when the diagnosis is suspected.
endoscopic mucosal staging system has been suggested to
Nevertheless, length and dosage are not clearly defined.
Simultaneously, topical intranasal steroid is prescribed for at least one year. Topical
and
systemic
antifungal
therapy
are
not
actually considered as sufficiently efficacious in this condition. Immunotherapy was studied by Mabry
et
the extension in the soft tissue
(Figure 114.4). In all cases
Histopathology reveals fungal invasion of the tissue: bone, mucous membrane, vessels. Mycologic cultures lead to identification of the species and several causative fungal species have been reported. Treatment is not totally evaluated, according to the few reported cases. Most patients have been 'treated with a
al.,27 with a small group of patients in a nonrandomized
combination of surgery and antifungal chemotherapy. No
study. In this protocol, immunotherapy was started after
one surgical procedure is recommended and a wide range
complete removal of the allergic mucin and conservation of the underlying mucosa. Fungal antigens and positive nonfungal antigens were injected weekly during the first
year up to a maximum tolerated dose. Although no data
are available on the length of the treatment, injections were continued for at least three years with an increased interval between treatment (two to three weeks). With this treatment, the authors observed that immunotherapy reduces the necessity for systemic and nasal corticosteroid
of techniques has been suggested ranging from biopsy to total exenteration of diseased tissue. While DeShazo
et al.1
are in favour of surgery alone, Washburn31 suggests the need for a prolonged course of antifungal agents, the duration of which is still under debate. In our experience, antifungals seem to be necessary in association with a large,
but
not
New antifungal
total,
removal
of
agents are more
the
granulomas.32
effective
and
lead
to a reduction in the need for extensive and aggressive
and it also limits recurrences.28, 29 To confirm these results
surgery.32 A long-term clinical and radiological follow up
in a limited number of patients, a multicentre study is
is required to identify and treat recurrent disease.
ongoing. Nevertheless, some problems remain and this therapy is totally ineffective in some individuals. T his approach is promising but is limited by the lack of availability of all fungal antigen and the necessity for accurate identification with cultures in all clinical cases.
Acute fulminant fungal rhinosinusitis T his is characterized by a mycotic infiltration of the mucous membrane of the nasal cavity and/or paranasal
INVASIVE FUNGAL RHINOSINUSITIS Chronic or indolent invasive fungal rhinosi nusitis Invasive fungal rhinosinusitis is probably one of the less frequent forms of fungal rhinosinusitis, most of them being reported in northern Africa and Asia.30 [**/*] Two fonns are usually described: granulomatous and non granulomatous, based on the presence or absence of granulomas within tissue.1 It occurs in healthy indivi
duals, sometimes after
a
previous history of chronic
rhinosinusitis. However, even if not all cases have been analysed, it appears that most patients are immunologi cally competent. T he pathophysiology remains unknown as
no
specific
factors
have
been
identified.
It
is
characterized by a clinical presentation where pain is the main symptom.
An
asymptomatic period frequently
occurs, symptoms appearing only when the orbit or skull base are involved.
Chronic headache, proptosis
and
cranial nerve deficits have been reported. T he maxillary /
Figure 114.4 maxillary sinus.
Invasive indolent fungaI rhinosinusitis of the left
Chapter 114 Fungal rhinosinusitis I
[**1*] ( A I DS,
sinuses.
patients mellitus)
It
in
occurs
immunocompromised
1 diabetes
haematologic diseases, type
with
a
fatal
1455
outcome
the
in
absence
of
treatment. 33 An early detection of the disease is essential, especially
when
CD4
the
cell
counts
are
notably
depressed. The initial symptoms are often subtle, even in at-risk patients. Fever of unknown origin or rhinorrhoea are the most common first symptoms. Later, proptosis, ophtal moplegia and focal neurological signs occur. Meticulous nasal endoscopy is the crux of the diagnosis to identify discolouration (often a black necrotic turbinate), gran
crusts in the nose. The most
ulation, ulceration or frequent
sites
turbinate,
the
of involvement, are
near
the
middle
septum and more rarely
the
inferior
turbinate.34 A full cranial nerve evaluation and examina tion of the oral cavity and oropharynx complete the
examination. A presumptive diagnosis can be made histologically with haematoxylin and eosin tissue starns, Gomori methenamine silver or periodic acid-Schiff and Gridley. The inflammatory tissue reaction reflects the host's
immunologic
status.
Fungi
show
a
marked
with direct invasion
predilection for vascular invasion
of the walls of large and small arteries and sometimes
Mucoraceae and Aspergillus are CT scan is the most commonly
veins, causing thrombosis. frequently isolated. A
used imaging modality for evaluating invasion but MRI is superior to
CT in delineating intracranial extent
Nevertheless, MRI a nd the CT scan may be normal in limited cases, especially
've fun al rhin inu 'li
at the beginning of the infection,
which reinforces the necessity for a careful endoscopic nasal
evaluation
and
biopsy
in
'at
risk'
patients.
Treatment is a combination of antifungal antibiotics, aggressive
surgical
debridement
and
reversal,
when
possible, of the underlying immunocompromising con dition.
If
especially
amphotericin for
is the
mucormycosis,35
conventional new
capsofugine) are now proposed with a efficacy
for
other
fungal
species,
the
therapy,
drugs
high
(awles, degree of
choice
being
modified by the result of culture. However, control of the primary disorder is the most important determinant of survival as is
an
early diagnosis. Despite this, fatalities
.
of 25 to 100 percent have been reported.
' \
I
!.
I
•
•
I '. :
�
I
\
•
Fungus ball ./ Surgical removal of the fungal ball is required for
t rea tment. No antifungal treatment is necessary. [Grade A]
Allergic fungal rhinosinusitis ./ Treatment includes surgical removal of eosinophilic mucin and oral steroid. [Grade BJ
Chronic or indolent invasive fungal
rhinosinusitis
./ Treatment includes.a combination of surgery and antifungal therapy. [Grade B]
I
L-_ ,.-
• • _____ 01 ___ _
.
-
. ..
_.
_
---
_ ._ ..
----'-----'-
-
/
1456 I
PART 13 THE NOSE AND PARANASAL SINUSES
Acute fulminant fungal rhinosinusitis
tissue specimens. Journal of Clinical Microbiology. 2000;
t! Nasal examination, especially with an endoscope, is
38: 4186-92.
essential to perform sampling and biopsy. [***]
9.
t! CT scan and MRI are helpful to analyse the extension.
polymerase chain reaction. Laryngoscope. 2001; 111:
[***]
t! Combination of surgery and antifungal therapy and reestablishment of immunity are required to control
Catten MD, Murr AH, Goldstein JA, Mhatre AN, Lalwani AK. Detection of fungi in the nasal mucosa using 399-403.
10.
Klossek JM, Serrano E, Peloquin L, Percodani J, Fontanel JP, Pessey JJ. Functional endoscopic sinus surgery and 109
the pathology. [Grade B]
mycetomas of paranasal sinuses. Laryngoscope. 1997; 107: 112-7. 11.
Dufour X, Kauffmann-Lacroix C, Ferrie SC, Goujon .1M, Rodier MM, Klossek .1M. Paranasal sinus fungus ball: epidemiology, clinical features and diagnosis. A
Deficiencies in current knowledge and areas for future research
retrospective analysis of 173 cases from a single medical center in France 1989-2002. Medical Mycology. 2006; 44: 61-7.
)- Doubts remain concerning the nature and the role of saprophytic fungal agents in the nose and sinus
12.
Aspergillomas of the sphenoid sinus: a series of 10 cases
cavities.
treated by endoscopic sinus surgery. Rhinology. 1996; 34:
)- The exact criteria for the diagnosis of allergic fungal
179-83.
rhinosinusitis remains to be determined, as does optimum treatment.
13.
Lund VJ, Lloyd G, Savy L, Howard D. Fungal rhinosinusitis. Journal of Laryngology and Otology. 2000; 114: 76-80.
)- Randomized studies to evaluate the treatment in allergic fungal rhinosinusitis and standardization of
Klossek JIVI, Peloquin L, Fourcroy P J, Ferrie JC, Fontanel JP.
14.
Braun JJ, Bourjat P. CT imaging of fungal and nonfungal
the method to collect the nasal mucin to evaluate
caseous sinusitis. A report of 50 cases. Journal de
the normal fungus flora in the nose are strongly
Radiologie. 2000; 8 1: 227-31.
recommended.
15.
Dufour X, Kauffmann-Lacroix C, Ferrie JC, Goujon JM, Rodier IVIH, Karkas A et al. Paranasal sinus fungus ball and surgery: a review of 175 cases. Rhinology. 2005; 43: 34-9.
16.
Katzenstein AL, Sale SR, Greenberger PA. Allergic Aspergillus sinusitis: a newly recognized form of sinusitis.
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Journal of Allergy and Clinical Immunology. 1983; 72: 89-93.
*
1.
deShazo RD, Chapin K, Swain RE. Fungal sinusitis. New
17.
2.
Ferguson BJ. Definitions of fungal rhinosinusitis. Otolaryngologic Clinics of North America. 2000; 33:
of a new clinical entity. Laryngoscope. 1987; 97: 261-6. 18.
Klossek JM, Serrano E. Les mycoses en ORL. Paris: l'Europeenne d'Edition, 2003.
4.
ry. 1998; 124: 1179-80.
* 19.
Lackner A, Stammberger H, Buzina W, Freudenschuss K,
5.
799-813. 20.
pathogenesis of chronic hypertrophic rhinosinusitis,
Ponikau JU, Sherris DA, Kern EB, Homburger HA, Frigas E,
allergic fungal sinusitis, and related disorders. Annals of
Gaffey TA et al. The diagnosis and incidence of allergic
Allergy, Asthma and Immunology. 2001; 87: 181-8. 21.
Otolaryngology and Head and Neck Surgery. 1994; 111:
Lackner A, Freudenschuss K, Buzina W, Stammberger H,
580-8. 22.
be identified in nasal mucus of humans?]. Klossek JM, Kauffmann-Lacroix XD. Sinusites fongiques:
Mabry RL. Allergic and infective rhinosinusitis: differential diqgnosis and interrelationship. Otolaryngology and Head and Neck Surgery. 1994; 111: 335-9.
Laryngorhinootologie. 2004; 83: 117-21. 23.
classification, methodes diagnostiques et prise en charge. 8.
Bent 3rd JP, Kuhn FA. Diagnosis of allergic fungal sinusitis.
877-84.
Panzitt T, Schosteritsch S et al. [From when on can fungi
7.
Schubert MS. A superantigen hypothesis for the
19: 125-9.
fungal sinusitis. Mayo Clinic Proceedings. 1999; 74: 6.
Ferg sson BJ. Eosinophilic mucin rhinosinusitis: a distinct S clini opathological entity. Laryngoscope. 2000; 110:
Panzitt T, Schosteritsch S et al. Fungi: a normal content of human nasal mucus. American Journal of Rhinology. 2005;
Kuhn FA, Javer AR. Allergic fungal rhinosinusitis: our experience. Archives of Otolaryngology - Head and Neck
227-35. 3.
Waxman .IE, Spector JG, Sale SR, Katzenstein AL. Allergic Aspergillus sinusitis: concepts in diagnosis and treatment
England Journal of Medicine. 1997; 337: 254-9.
Mabry RL, Marple BF, Mabry CS. Mold testing by RAST and skin test methods in patients with allergic fungal sinusitis.
Journal de Mycologie Medicale. 2001; 11: 216-21.
Otolaryngology and Head and Neck Surgery. 1999; 121:
Hendolin PH, Paulin L, Koukila-Kahkola P, Anttila VJ,
252-4.
Malmberg H, Richardson M et al. Panfungal PCR and multiplex liquid hybridization for detection of fungi in
24.
Ferguspn BJ, Barnes L, Bernstein JM, Brown D, Clark CE, Cook PR et al. Geographic variation in allergic fungal
114 Fungal rhinosinusitis III
25.
nervous system
2001; 44: 141-5.
Corey JP, Delsupehe KG, Ferguson BJ. Allergic
31.
sinusitis: allergic, infectious, or both? Otolaryngology and Head and Neck
* 26.
1995; 113: 110-9.
32.
Mabry RL, Manning S. Radioallergosorbent microscreen
Otolaryngology and Head and Neck
rhinosinusitis: two new cases and review of the literature. American Journal of Rhinology. 2004; 18: 221-6. 33.
30.
Hunt SM, Miyamoto RC, Cornelius RS, Tami TA. Invasive fungal sinusitis in the
for allergic fungal sinusitis: three
syndrome. Otolaryngologic Clinics of North America.
Otolaryngology and Head and Neck Surgery. 1998; 119:
29.
immunodeficiency
2000; 33: 335-47.
* 34.
Gillespie MB, O'Malley BW. An algorithmic approach to
Bassicbis BA, Marple BF, Mabry RL, l'Jewcomer MT,
the
Schwade NO. Use of immunotherapy in previously treated
rhinosinusitis in the immunocompromised patient.
and management of invasive
patients with allergic fungal sinusitis. Otolaryngology and
Otolaryngologic Clinics of North America. 2000; 33:
Head and Neck Surgery. 2001; 125: 487-90.
323-34.
Marple BF. Allergic
rhinosinusitis: current theories
in
Dufour X, Kauffmann-Lacroix C, Roblot F, Goujon JM,
Mabry RL, Marple BF, Folker RJ, Mabry CS. Immunotherapy
648-51. 28.
Washburn RG. Fungal sinusitis. Current Clinical
Breux JP, Ferrie JC et al. Chronic invasive
1995; 113:
721-3.
in south India. Mycoses.
Infectious Diseases. 1998; 18: 60-74.
and total immunoglobulin E in allergic fungal sinusitis.
27.
�cr.prrllll(,<:i<:
rhinosinusitis. Otolaryngologic Clinics of North America. 2000; 33: 441-9.
1457
35.
Sungkanuparph S, Sathapatayavongs B, Kunachak S,
and management strategies. Laryngoscope. 2001; 111:
Luxameechanporn T, Cheewaruangroj W. Treatment of
1006-19.
invasive
Murthy JM, Sundaram C, Prasad VS, Purohit AK, Rammurti
report of four cases. Journal of the Medical Association of
S, Laxmi V. Sinocranial aspergillosis: a form of central
Thailand. 2001; 84: 593-601.
sinusitis with liposomal
B: a
115 Sp.ecific chronic infections
S BAHAD U R AN D A THAKAR
Introduction
1458
Best clinical practice
1465
Nasal tubercu losis
1458
Atrophic rhinitis
1465
Best clinical practice
1460
Best clinical practice
1466
Syphilis
1460
Rhinitis sicca
1466
Best clinical practice
1462
Key points
1466
Scleroma
1462
Deficiencies in current knowledge and areas for future
Best clinical practice
1463
Leprosy
1463
The data and recommendations
1467
research
1467
References
in this chapter are supported by a Medline search using the key words nasal tuberculosis,
syphilis, rhinoscleroma, leprosy nose and atrophic rhinitis.
�
INTRODUCTION
tuberculosis or it may occur by haematogenous dissemi nation of a primary infection elsewhere. Recent work has
Most
of
these
conditions
have
become
increasingly
demonstrated the frequent contamination of the nasal fossae by
Mycobacterium tuberculosis
in cases with smear
been a resurgence in some in the past two decades, fuelled
positive
pulmonary tuberculosis.l
Clinical
primarily
by
drug
however, extremely rare and, in the head and neck,
resistance
and
These
tuberculous involvement of the cervical lymph nodes,
uncommon
in the western world. There has, however, the
AIDS
epidemic,
increasing
increasing international travel.
factors would presumably also have led to an enlargement
larynx,
in the infective reservoir, thus leading on to further transmission and infection. [**]
involvement of the nose.
This
chapter
discusses
the
nasal
and
paranasal
manifestations of tuberculosis, syphilis, scleroma, leprosy and atrophic
pharynx
and
ear
are
more
disease is,
common
than
[***/**]
Clinical features
rhinitis. Fungal diseases are dealt with in
Chapter 114, Fungal rrunosinusitis.
Three fonns are recognized. The nodular and ulcerative forms are seen in the nose and another form is primarily localized to
the paranasal sinuses.
NASAL TUBERCULOSIS The causative organism in the nose is almost invariably
Mycobacterium
tuberculosis.
Nasal
infection
may
be
LUPUS VULGARIS (NODULAR FORM) This form usually begins in the vestibule and then extends
consequent to direct inoculation either by nose picking
to the adjoining skin and mucosa
It is
a
and
consequence of direct inoculation into the dennis in
a
finger
nail
trauma,
,or
by
open
pulmonar y
(Figure 115.1).
/
/
/
,_-:'1',
Chapter 115 Specific chronic infections.
Figure 115.2
1459
Lupus vulgaris (late stage) causing destruction
and deformity of the nasal tip.
from syphilis. Clinically, this form may be confused with Wegener's granulomatosis and with malignancy. [**]
SINUS GRANULOMA
Figure 115.1
Lupus vulgaris demonstrating the characteristic
well-demarcated and nodular lesion in the nasal vestibule.
patient who otherWise has strong immunity to the infection, usually due to a previous exposure. It presents with glistening reddish-brown or skin-coloured papules or nodules (apple jelly nodules). Blanching maneouvres (by pressure with a glass slide for skin lesions, and by the application of adrenaline or cocaine for mucosal lesions) makes them increasingly prominent as the surrounding areas blanch while the nodules remain relatively unaffected. Pain is unusual. The nodules may coalesce and break down to form characteristic ulcers with a pale granular base and undermined edges. The disease is usually very slowly progressive - untreated it can lead to progressive scarring and deformity (Figure 115.2). Malignant transformation of the scar is well documented. [**]
ULCERATIVE FORM
This usually involves the cartilaginous nasal septum or the inferior turbinate, and presents with nasal obstruction, crusting, discharge and epistaxis. It may be unilateral or bilateraL The lesion may progress to septal perforation, but dorsal saddling does not usually occur. The bony septum is not involved, a feature which differentiates it
b
i
Isolated sinus involvement may occur without any signs or symptoms in the nose. In previous years, this form usually presented with a diffuse soft tissue swelling and multiple discharging sinuses in the supraorbital region secondary to osteomyelitic involvement of the frontal bone. With improvements in imaging, however, minimally symptomatic proliferative lesions are being picked up before such significant bone destruction is evident (Figure 115.3). The computed tomography (CT) and magnetic resonance imaging (MRI) characteristics are nonspecific and demonstrate a soft tissue mass with or without bone destruction. 2 Involvement of the orbit and its nerves may occur. The diagnosis is established by an external or endoscopic biopsy. [**]
Diagnosis The diagnosis is usually established by a tissue biopsy, histopathological examination of which demonstrates the characteristic epitheloid cell granulomas. Additional features of caseation and the presence of acid-fast bacilli (AFE), though characteristic, are not always present. [**] Microbiologic diagnosis by direct demonstration or culture of the organism is ideal and is the only confirmatory test for infection with Mycobacterium tuberculosis. It is obviously specific but lacks sensitivity,3 and culture results by the traditional technique on the Lowenstein-Jensen slope may take as long as six to eight weeks to become available. Recent techniques of DNA amplification by polymerase chain reaction (PCR) have greatly improved the sensitivity of microbiological
1460 I PART 13
THE NOSE AND PARANASAL SINUSES
rifampicin, ethambutol and pyrazinamide) for two months followed by two drugs ( isoniazid and rifampicin) for an additional four months. 3 Multidrug resistant tuberculosis (MDRTB) is, however, an increasing global problems,6 and should the response to treatment be unsatisfactory, recourse to second-line therapy is called for. Second-line therapy is based on culture-sensitivity patterns and is probably best undertaken by an internist/ infectious disease specialist. [*** /**]
./ Molecular techniques of PCR and BACTEC should be applied to the diagnosis of Mycobacterium tuberculosis infection as they have greatly improved the sensitivity of detection and have also reduced the time period for culture and sensitivity studies to be available . ./ MDRTB is increasing and antitubercular therapy should be closely monitored so as to detect resistant cases early.
SYPHILIS
Figure 115.3 Sino-nasal tuberculosis. (a) and (b) CT appearances demonstrating a sino-nasal mass with surrounding infiltration and bone destruction.
detection. Also, culture can now be accelerated by the use of recent technology, such as BACTEC, so as to be available in less than a week. 4 [***/**] In cases where the microbiology and histology are indicative but not entirely confirmatory for tuberculosis, skin testing for delayed hypersensitivity by the purified protein derivative (Manteaux test) may help to corroborate the diagnosis. Alternatively, a therapeutic trial with antituberculous therapy may be initiated. [*] Associated pulmonary tuberculosis is more common than is generally believed3 and should always be excluded by a chest x-ray. [***]
Treatment The recommended first-line treatment for extra-pulmonary tuberculosis is an initial four drug regime (isoniazid,
The involvement of the nose secondary to syphilis can occur at any age group, from the neonate to the elderly. The disease is rare today and the diagnosis may be difficult in the early stages, particularly if the patient has already received antibiotics. The causative organism is a spirochaete, Treponema pallidum. Contact with an infectious sexual partner is associated with a moderate risk of transmission. [**** /***] The organisms usually reside and multiply in the perivascular lymphatics of the blood vessel wall. The local host reaction results in an infiltration by polymorphs, activated lymphocytes (CD4+ and CDS+), plasma cells and histiocytes which are typical of syphilis. The resultant endarteritis of small blood vessels with secondary hypertrophic changes in the endothelium, may lead to endarteritis obliterans and luminal obliteration. 7 [****]
Clinical features and diagnosis The infection may present in various forms that have been classified as primary, secondary, tertiary and the congenital forms. The disease is infectious in its primary and secondary forms, but the infectivity decreases considerably in its late phase. [**]
PRIMARY SYPHILIS
A sore or. chancre develops at the site of inoculation 10-90 days (average 21 days) following infection and is
Chapter 115 Specific chronic infections
usually accompanied by regional lymphadenitis. Most chancres are genital (90-95 percent). Primary chancre at the nose is unusual but may occur on the external nose or inside the vestibule. It presents as a hard, nonpainful, ulcerated papule that is often associated with enlarged rubbery nontender nodes, and a transient malaise and pyrexia. The lesion is usually self-limiting and disappears spontaneously in six to ten weeks. It has to be differentiated from malignant neoplasms and furunculosis. Malignant lesions are progressive and occur in later age groups, while furunculosis is painful and is followed by suppuration. [**] The diagnosis is confirmed by the following laboratory tests. • Smears from the ulcer or the node examined by darkground illumination or after staining show the spirochaete, Treponema pallidum. [****] • Serological tests for syphilis may be positive, except in the earliest cases, or in those cases already receiving antibiotics. The serological tests in current use include: - Venereal Disease Reference Laboratory (VDRL) titres; - T. pallidum haemagglutination test (TPHA); - fluorescent treponemal antibody test (FTA-ABS). The VDRL is a nontreponemal test and is relatively nonspecific but becomes positive early (four to five weeks) and correlates well with disease activity. Titres decrease after treatment and also in the late phases of the disease. TPHA and FTA-ABS, by contrast, are treponemal antibody tests which are quite specific and titres persist in the late and tertiary phase of the disease. [**] • A biopsy may be performed in doubtful cases; the histological appearances are characteristic. [***]
SECONDARY SYPHILIS
The secondary stage of syphilis is the most infectious. It usually manifests by six to ten weeks after inoculation, but may be delayed for up to nine months. It is a systemic disease in which a high index of clinical suspicion is essentiaL The most common manifestation in the nose is a simple catarrhal rhinitis. Clinically, this does not show any special characteristics, except in its persistence. There may be crusting and fissuring of the nasal vestibule. [**] Secondary syphilis is rarely recognized in the nose, as mucous patches hardly ever occur on such a thin, attenuated mucous membrane. The diagnosis is usually suggested by the appearance of other secondary lesions, particularly the development of mucous patches in the pharynx, a roseolar or papular rash, pyrexia and the shorty enlargement of many lymph nodes. The scar of the primary le$ion in the genitals or elsewhere may be visible. [**/*] . Secondary syphilis is best confirmed by serological tests, which by this stage are almost universally positive. 8
.
/
,.
I 1461
Dark-field examination of moist or intentionally abraided dry lesions may demonstrate the organism. Lymph node aspirates or tissue specimens (lymph nodes, liver, skin or mucous membrane) may also be examined by silver stains or immunofluorescence for detection of spirochaetes. 9 [****/**] TERTIARY SYPHILIS
Even though serological evidence of infection, as indicated by the FTA-ABS test, persists indefinitely in almost all cases, only approximately one-third of cases with secondary syphilis progress to show clinical manifestations of tertiary syphilis. The morbidity and mortality of syphilis in adults is principally caused by its late manifestations in the skin, bones, central nervous system or viscera - particularly the heart and great vessels. Late lesions are chronic and destructive. lO [**] This is the stage most commonly encountered in the nose. It usually occurs nearly two years after the initial inoculation. The pathological lesion is a gumma, which begins as a subcutaneous nodule, progresses to involve the overlying skin, and then breaks down to form a punched out destructive ulcer (Figure 115.4). The bony portion of the septum is the site most commonly involved. More rarely, the lateral nasal wall, frontal sinus, nasal bones or floor of the nose are invaded. The early symptoms include pain (which is always worse at night), swelling and obstruction. The swelling may be diffuse or localized and offensive discharge, bleeding and crusting and anosmia follow. Tenderness over the nasal bridge is a characteristic sign. In neglected cases, perforation of the affected nasal wall and collapse of the bony support of the nose may occur. Ultimately, there may be severe scarring and secondary atrophic rhinitis. [**] Diagnosis of tertiary syphilis may be made from a combination of characteristic organ involvement, the histopathological picture, reactive nontreponemal and treponemal serological tests and response to adequate
Figure 115.4
Tertiary syphilis with an ulcerated gumma and
cicatrization of the bony nasal dorsum .
1462 I PART 13 THE NOSE AND PARANASAL SINUSES
antibiotic therapy.9 Persisting sequelae, such as dorsal collapse or atrophic rhinitis, are not always associated with active disease and the VDRL test may be negative. The FTA-ABS and TPHA tests, however, continue to be positive. In addition, a past history of a genital sore or lesions suggestive of secondary syphilis or inadequately treated early syphilis may aid the diagnosis. [**] The differential diagnosis of a gumma includes a variety of disease pathology such as tuberculosis, lupus vulgaris, sarcoidosis, yaws, atrophic rhinitis, leprosy, scleroma, chronic glanders, leishmaniasis and benign and malignant neoplasms. [*]
ephedrine solution or simple normal saline, and by hyperextending the head before feeding. In the tertiary forms, simple nasal toilet by syringing with isotonic alkaline douche solution will remove the crusts and discharge, and yellow mercuric oxide ointment may be applied frequently to the nasal vestibules. [**] In both forms, antisyphilitic treatment is essential and rapidly arrests the disease, but destruction and deformity remain. [**]
Treatment
Parenteral penicillin remains the preferred drug for treatment of all stages of syphilis in patients who are not otherwise allergic to it. Local treatment consists of clearance of crusts and regular cleansing of the nasal passages by copious alkaline douches one to three times a day. Yellow mercury oxide ointment may be applied locally. Gummas respond rapidly to general antisyphilitic treatment but atrophic rhinitis and deformity may persist after the disease is cured and this may need further surgery. [**]
,/ Primary and secondary syphilis are infective and require adequate precautions on patient examination, but are unlikely to present with nasal manifestations. ./' Nasal manifestations are usual with tertiary and congenital syphilis and may be diagnosed by the characteristic clinical findings and other stigmata of syphilis. The relevant serological tests in this situation are the TPHA and the FfA-ABS test. ./' Treatment is with penicillin unless the patient is sensitive to it.
Hereditary or congenital syphilis In congenital syphilis, any of the lesions of the secondary and tertiary forms of syphilis of the nose may occur. In the infant, 'snuffles' is the most common lesion. This begins at around the third week to three months after birth. At first it appears as a simple catarrhal rhinitis. In a short time it becomes purulent, with secondary fissuring and excoriation of the nasal vestibule and upper lip. The obstruction may be so severe as to seriously interfere with suckling and nutrition. [**] Gummatous and destructive lesions occur most commonly at puberty. Mucous membrane, periosteum and bone may all be affected. The resulting ulceration and destruction ultimately lead to features of secondary atrophic rhinitis and sinking of the nasal bridge, producing the saddle nose deformity. Other stigmata of syphilis, particularly Hutchinson's incisors and Moon's molars, interstitial keratitis, corneal opacities and sensorineural deafuess may be present, and there may be a family history of syphilis, miscarriages and still births. [**] Serological tests for syphilis of the patient and the parent are positive. The biopsy confirms the diagnosis. [***/**]
TREATMENT
In snuffles, the airWay must be restored for suckling. The nasal discharge is removed by gentle suction and irrigation and the use of local drops of 0.5 percent
SCLEROMA Respiratory scleroma or rhinoscleroma is a progressive granulomatous disease commencing in the nose and later extending into the nasopharynx and oropharynx, the larynx and sometimes the trachea and bronchi. 11 Laryngeal involvement may occur in almost half the cases l l and the disease is perhaps better designated as respiratory scleroma, rather than rhinoscleroma. 12 It may occur at any age and in either sex, but is more common in females and in the middle aged. It is seen mainly in central and south-eastern Europe, North Africa, the Indian subcontinent, Indonesia and Central and South America. [**]
Pathology The disease is caused by the Gram-negative bacillus, Klebsiella rhinoscleroma tis, also known as Frisch bacillus. The organism predominantly resides intracellularly and can be difficult to isolate in the laboratory. The characteristic histological features include granulomatous tissue infiltrates in the submucosa, characterized by the presence of plasma cells, lymphocytes and eosinophils. Besides, there are scattered large foam cells (Mikulicz cells) which have a central nucleus and a vacuolated cytoplasm cpntaining bacilli and Russel bodies. The Mikulicz cells are transformed macro phages which have
Chapter 115 Specific chronic infections I
ingested the bacillus, but the bacillus being resistant to digestion by the macrophage persists intracellularly. The Russel bodies resemble plasma cells with an eccentric nucleus and deep eosin staining cytoplasm. Ultrastructure studies have supported the theory of an intracellular formation of Russel bodies. 13, 14, 15 Histochemical studies have indicated a high content of mucopolysaccharides around the walls of the bacillus 16 and it is hypothesized that this may be responsible for the protection afforded to the organism from antibiotics and the hosts antibodies. [**]
Clinical features The disease has been noted to progress following the three stages described below: 1. The atrophic stage: The features resemble that of atrophic rhinitis, including crust formation and a foul smelling discharge. 2. Granulomatous or proliferative (or nodular) stage: Nonulcerative nodules develop which are at first bluish red and rubbery and later become paler and harder. These nodules never break down but fibrose and progressively decrease in size. Regional lymph node involvement is extremely infrequent. 3. Cicatrizing stage: Adhesions and stenosis distort the normal anatomy. The disease may extend to involve the nasopharynx, hard palate, trachea and main bronchi. Bone involvement has also been reported. I? Occasionally, malignant change has been reported. IS [**]
1463
been confirmed by biopsy, treatment must be intense and prolonged. Bactericidal antibiotics in large doses are given for a minimum of four to six weeks and are continued until two consecutive cultures from biopsy material are proven negative. 22 Initial surgical debridement prior to chemotherapy is reported to be useful in the granulomatous stage. 11, 23 The traditional antibiotics used are streptomycin and tetracycline, but the lengthy nature of the treatment can lead to problems with adverse effects and compliance. Recent reports have emphasized the good results achieved with oral therapy with rifampicin, sulphamethoxazole-trimethoprim combination, and ciprofloxacin. 12,23 [**] Local application of 2 percent acriflavin for a period of eight weeks has been noted to be both efficacious and nontoxic?4 Locally applied rifampicin has been used with success. 25 Irradiation to a total dose of 3000-3500 Gy over three weeks destroys scleroma26 but, with the currently available antimicrobials, is unlikely to be required. [** /*] In late cases where disease has been eradicated, further plastic reconstructive surgery may be required. This may be carried out by nasal endoscopy and laser, if appropriate. [*]
./ The diagnosis of scleroma is suspected on clinical grounds and confirmed by histology. ./ Treatment is prolonged for at least six weeks and must continue until at least two consecutive cultures from biopsied tissue are negative. ./ Oral treatment with ciprofioxacin, rifampicin, cotrimoxazole and tetracycline is better tolerated and less toxic than paraentral streptomycin, and should probably be used as first-line therapy.
Diagnosis Diagnosis in the atrophic stage is extremely difficult and the disease is usually recognized only in the granulomatous or cicatrizing stage. MRI in the hypertrophic stage shows a soft tissue mass with mild to marked high signal intensity in both Tl- and T2-weighted images. 19 The diagnosis may be further aided by a complement fixation test20 ,21 or by microbiological demonstration of the organism, but it is usually established by a biopsy demonstrating the characteristic histological features. [**]
Treatment Though the disease follows a protracted but usually selflimiting course of its own accord ending in the cicatrizing stage, the organism can nevertheless be extremely difficult to eradicate by antimicrobials. Once the diagnosis has
.,./
LEPROSY Leprosy is a chronic granulomatous disease caused by Mycobacterium leprae, an acid-fast bacillus morphologically similar to M. tuberculosis. Although M. leprae cannot yet be cultured on an artificial medium, it can nevertheless be inoculated into experimental animals, particularly immunologically deficient mice, to produce a disease similar to that in man. Worldwide, 12-15 million people suffer from this disease. Five countries (Brazil, India, Indonesia, Myanmar and Nigeria) account for 82 percent of all leprosy patients. The disease most commonly initially manifests between the ages of 10 and 20. [**] The seventh WHO Expert Committee on Leprosr? defined one or more of the following parameters for the
i,;
+~r.;
1464 I PART
13 THE NOSE AND PARANASAL SINUSES
disease: hypopigmented or reddish skin lesion(s) with definite loss of sensations; involvement of peripheral nerves (as demonstrated by nerve thickening and loss of sensations); and skin smear positive for acid-fast bacilli. In endemic areas there is widespread subclinical transmission of M. leprae and a large number of people are exposed, but only a very few actually develop the disease?8 Dissemination from infected cases is primarily via the nasal secretions. 28 The route of entry into susceptible hosts is via the upper respiratory tract or the skin. The bacillus has a special propensity to invade the nerves and reside in the schwann cells. Two distinct forms are recognized, based on the host's immunological status and clinical, histological and microbiological features. The tuberculoid type (tuberculoid pole) is associated with strong host resistance, is noninfective and localized. The lepromatous type (lepromatous pole) has poor host resistance, is infective and systemic, with widespread involvement of the skin, nerves, upper respiratory tract, eyes and testis. There are intermediate forms between these poles. In the spectrum of these disease manifestations from tuberculoid to intermediate to lepromatous, the number of lepra bacilli in the involved tissues are maximal in the lepromatous type and progressively decrease towards the tuberculoid pole. 29 The polar forms of tuberculoid leprosy and lepromatous leprosy are stable, while the intermediate (borderline) forms are unstable and tend to downgrade if left untreated. [**]
Clinical features The clinical features in the nose depend on the type of leprosy.3o
TUBERCULOID LEPROSY
There are solitary lesions causing anaesthetic cutaneous patches with involvement of sensory or motor nerves with possible paralysis of muscles. Isolated cranial nerve palsies (e.g. Vth and VIIth) may occur. There is no mucosal involvement but the skin of the nasal vestibule can be involved.
LEPROMATOUS LEPROSY
There is diffuse infiltration of skin, nerves and mucosal surfaces. Nasal mucosal involvement occurs early and is seen in the majority of patients. Histologically damaged and infiltrated nasal mucosa may appear relatively normal on clinical evaluation. 31 Clinical features include nasal obstruction, crust formation and blood-stained discharge, the latter containing infectious bacilli. Atrophic rhinitis, septal perforation and dorsal saddling suggest late disease.
Hyposmia may be demonstrated patients. 32
III
40 percent of
BORDERLINE LEPROSY
Patients with borderline leprosy may convert to lepromatous or tuberculoid leprosy depending upon their immunological status. In the pure borderline type there is no mucosal involvement of nose, mouth, pharynx and larynx. [**]
Diagnosis Diagnosis of leprosy is usually made on the clinical findings of anaesthesia on the skin, thickened peripheral nerves and skin lesions, and is supplemented by bacteriological examination. Early diagnosis is essential since nasal discharge is the principal route of transmission of the disease. Diagnosis is confirmed by demonstration of M. leprae on microscopy of the nasal discharge or scrapings of nasal mucosa, or histopathology of nasal mucosa. In tuberculoid or intermediate leprosy, a skin biopsy may be required to demonstrate the bacillus. [****/***]
Treatment Treatment is best undertaken by a specialist familiar with the illness and its treatment, and often has to continue for several years. Dapsone remains the standard and safe drug and will reduce the bacterial count of nasal discharge to zero or near zero within two months. When used as a single drug, M. leprae tend to develop resistance to the drug. Rifampicin and clofazimine act more rapidly and reduce the count to zero in ten days; their cost, however, has precluded their general use in developing countries. Triple therapy with all three, if available, reduces the relapse rate and helps in preventing drug resistance. The usual regimen is rifampicin 600 mg on the first two days of each month taken before breakfast, clofazimine 100 mg on alternate days three times a week, and dapsone 100 mg daily. [**] Direct intranasal administration of rifampicin has been noted to reduce the M. leprae load in the nose much faster than when the drug was given by the oral route. 33 Local treatment to the nose with Betnovate (one part) in unguentum (two parts) has been used to prevent external deformity of advanced lepromatous leprosy. In cases of septal perforation and atrophic rhinitis, careful crust removal is important. 32 [**/*] In established cases of nasal deformity, corrective surgery improves cosmesis and may also contribute to restoring the self-esteem and the injured psyche of these patients. [*]
Chapter 115 Specific chronic infections
./ The nasal secretions in cases of lepromatous leprosy contain bacilli and are the principal source of transmission of infection. ./ Early institution of treatment with dapsone,
I 1465
natives of equatorial Africa. An autoimmune aetiology has also been proposed. In vitro studies have indicated altered cellular reactivitl 8 and it is hypothesized that local virus infections, malnutrition and/or immunodeficiency may result in the release of nasal mucosal antigen into the systemic circulation and so trigger an autoimmune reaction. [**/*]
rifampicin and c10fazamine renders these patients rapidly noninfective . ./ Single drug treatment with dapsone may lead to the development of resistance and should be avoided.
ATROPHIC RHINITIS Atrophic rhinitis is a chronic nasal disease characterized by progressive atrophy of the mucosa and the underlying bone of the turbinates. It is associated with viscid secretions which dry resulting in crust formation with a characteristic foul odour, sometimes called ozaena. There is abnormal patency of the nasal passages. [**/*]
Aetiology The precise aetiology is still unknown. Cases wherein no specific aetiologic factor can be identified are designated primary atrophic rhinitis. Cases wherein a specific aetiologic factor can be implicated are designated secondary atrophic rhinitis. Aetiologic factors include chronic sinusitis, chronic granulomatous lesions, such as tuberculosis, syphilis and leprosy, and excessive destruction of nasal tissues caused by surgery. A wide range of bacterial flora have been reported from the nasal secretions of these patients, namely, coccobacillus foetidus ozaena, diptheroid bacilli and Klebsiella ozaenae. 34 Recent studies have identified Bordetella bronchoseptica and Pasteurella multocida,35 and have suggested that inoculation o( these organisms into animals has produced changes similar to atrophic rhinitis. Biochemical studies of the nasal aspirate in atrophic rhinitis have noted a significant decrease in the total phospholipids and also a change in the phospholipid profile. 36 This suggests a possible role for surfactant deficiency in the aetiopathogenesis. Primary atrophic rhinitis usually commences at puberty and is much more common in females, suggesting that endocrine imbalance may have some role to play. The disease is more common in people of low socioeconomic background and has been associated with poor nutrition and iron-deficiency.37. Heredity is an important factor and there also appears to be a racial influence. It is more common in yellow and Latin races and American blacks are more susceptible as compared to
.r·
/
1
Pathology There are patches of metaplasia in the epithelium, with a transition from the usual ciliated columnar epithelium to nonkeratinized or keratinized squamous epithelium. The lamina propria shows chronic cellular infiltration, granulation tissue and fibrosis. 39 The mucous glands are decreased in size and number. Vascular changes have been demonstrated in the form of decreased vascularity, periarteritis and endarteritis of the terminal arterioles. Taylor and Young40 were, however, unable to demonstrate such endarteritis and periarteritis of terminal arterioles, and suggested a possible other type of atrophic rhinitis in which there was vasodilatation of the capillaries. [** /*]
Clinical features The cases present with nasal crusting which is brown black or dark green in colour and is accompanied by a thick purulent discharge and a foul smelL The foul smell is due to the anerobic flora in the nasal cavity. Anosmia is also a feature, and the patients themselves may at times not be unduly troubled by the foul smell from their nose. Other features include headache, epistaxis and nasal obstruction. The latter is attributed to the presence of crusts producing mechanical obstruction, and also to the blunting of sensory nerve endings, thus resulting in a diminished sensation of air flow. At times, the symptoms are mainly pharyngeal and are caused by pharyngitis sicca which often accompanies the condition. Clinical examination confirms the presence of fetor in all but the earliest cases. Changes in the nasal passages include atrophy of turbinates resulting in widening of the cavity, presence of green crusts and thick purulent discharge. Occasionally, the condition may be complicated by maggot infestation in the nose. [**/*]
INVESTIGATIONS It is advisable to exclude the presence of sepsis in the
paranasal sinuses by radiology and, if necessary, by proof puncture or sinus endoscopy. Swabs from nasal secretions may be cultured, but the results are unlikely to be helpfuL Serological tests to exclude syphilis are essential as syphilis is the most likely condition to be confused with atrophic
1466 I
PART 13 THE NOSE AND PARANASAL SINUSES
rhinitis. The haemogram, serum proteins and iIon should
also be checked.
(*] .I Chronic rhinosinusitis and syphilis must be excluded in all cases presenting with a presumably primary
Treatment
atrophic rhinitis.
.I Failure of adequate relief or noncompliance with conservative treatment by nasal irrigations and
MEDICAL TREATMENT
Regular
nasal
cleansing
treatment in atrophic rhinitis. The patient should be
instructed to
douche
glucose in glycerine drops are indications for surgical
is the basis of conservative
the
nose
twice
daily
with
a
treatment.
.I Partial vestibular closure, either by a modified Young's operation or by vestibuloplasty, allows for recovery of
hypertonic and alkaline solution41 which has traditionally
the nasal mucosa and symptomatic relief without the
been prepared by dissolving a teaspoonful of a mixture of sodium
bicarbonate,
sodium
chloride (in proportions of
mL)
diborate
and
in half a pint
1:1:2)
morbidity of complete nasal obstruction.
sodium
(280
of warm water. Following the alkaline nasal douche,
a solution of 25 percent glucose in glycerine may be applied, so as to inhibit the proteolytic organisms in the
RHINITIS SICCA
been administered both systemically and locally (sub
Rhinitis sicca is a condition which is similar to mild
improvement,42 but are unlikely to be used currently due
picture. This is a widespread condition, frequent in those
homologous
caused by a variety of other factors such
nasal cavity. Injections of human placental extract have
mucosal intranasal) and have been noted to result in an to
the
concerns
of
sources.
virus
transmission
Rifampicin
from
such
600 mg orally once
daily for 12 weeks has been used with reportedly good
results.43
[** /*]
atrophic rhinitis without progressing to its
full clinical
engaged in dry, hot and dusty occupations, and is also as
alcoholism,
anaemia, nutritional and constitutional diseases.
,
[*]
There is deficiency and inactivity of the seromucinous
glands, metaplasia of the columnar ciliated epithelium to cuboidal or squamous epithelium and deficiency of the
mucous
SURGICAL TREATMENT
Numerous attempts to relieve the condition surgically
have been made in the past. These include submucous
injections of paraffin and procedures placing
materials, glycerine,
the
lateral
nasal
walls
aimed at dis
medially.
such as teflon strips, powdered
plastipore,
bone
and
cartilage,
Various
teflon
have
in
been
inserted submucosally after raising flaps of mucoper
ichondrium from the septum or mucoperiosteum from
the floor and lateral nasal wall.
The most conunonly used operation, however, remains
the one described by Young.44 The procedure involves
raising flaps of skin from the medial and lateral walls of
the nasal vestibule and suturing them together so as to
completely close the nasal passages. The nasal cavities are then re-opened after periods varying from several months
blanket.
However,
clinical
measurement
in differentiating these patients from normals.46
[H]
The patients complain of discomfort, irritation and
sometimes epistaxis and crusting, but the crusts are thin
and
dry and usually do not
extend to the posterior part of
nasal cavities as in atrophic rhinitis. The charactedstic fetor of atrophic rhinitis is also absent. Clinical examina
tion reveals a dry, whitish or glazed mucous membrane,
sometimes accompanied by crusting or complicated by a
septal perforation. The patient should be investigated to exclude nutritional deficiencies or local infection. Treatment consists of removal of
[*] all possible causes and
supplementing iron and vitamins. Douching of the nose
with isotonic salt water solution or
with the solution
described for treatment of atrophic rhinitis is useful.46
to several years, usually to reveal normal nasal mucosa
and absence of crusting. Presumably, the absence of the drying effects of air flow results in regeneration of healthy
nasal mucosa. However, there are obvious disadvantages of complete bilateral
nasal
closure,
and a
KEY POINTS
modified
operation with partial nostril closure leaving a 3 rom
•
tolerated.42
Ghosh45
described
an
alternative
surgical technique of vestibuloplasty, wherein a poster
iorly based skin flap is raised in the lateral wall of the
nasal vestibule and sutured on itself, thus decreasing the lateral flow of air into the nasal cavity.
[**/*]
Tubercular di e e arc increasing in the world nd extra.puhnonary I'nanitestalion are bccomin-g more common. Drug r sistance poe' a significant pOOHc healt h prohlem. SyphHi in the nose is mainlr recognized in and cnn nital sta es. The th
Wc&tc-rn
hole has been found to give similar results and to be
better
of
mucociliary transport has not been noted to be useful
•
as
[*J
Chapter 115 Specific chronic infections
I 1467
2001; 344: 1294-303. Eye opener with regard to the problem of MDRTB. 6.
Djuretic T, Herbert J, Drobniewski F, Yates M, Smith EG, Magee JG et al. Antibiotic resistant tuberculosis in the United Kingdom: 1993-1999. Thorax. 2002; 57: 477-82.
7.
Siddappa K, Ravindra K. Syphilis and non-venereal trepnonematosis. In: Valia RG (ed.). Text book and atlas of dermatology, 2nd edn. Bombay, India: Bhalani Publishing
House, 2001: 1390-417. 8.
Thin RN. Early syphilis in adult. In: Holmes KK, Mardh PA, Sparling PF, Weisner PS (eds). Sexually transmitted diseases, 2nd edn. New York: McGraw-Hili, 1990: 221-30.
9.
Sanchez M, luger AFH. Syphilis. In: Fitzpatrick TB, Eisen Al, Wolf K, Freedberg 1M, Asten FK (eds). Dermatology in general medicine, 4th edn. New York: McGraw-Hili, 1993:
2703-43. 10.
Sparling PF. Natural history of syphilis. In: Holmes KK, Mardh PA, Sparling PF, Weisner PS (eds). Sexually transmitted diseases, 2nd edn. New York: McGraw-Hili,
Deficiencies in current knowledge and areas for future research
1990: 213-9. 11.
Soni NK. Scleroma of the larynx. Journal of Laryngology and Otology. 1997; 111: 438-40.
). In the current era wherein sectional imaging for
12.
Badia l, lund VJ. A case of rhinoscleroma treated with
paranasal sinus lesions is almost invariable, there is
ciprofloxacin. Journal of Laryngology and Otology. 2001;
little information on the radiological characteristics of
115: 220-2.
these infections.
13.
). The immune mechanisms countering these intracellular pathogens remain unclear. ). Recommended optimum treatment strategies are
Friedmann I. Electron microscopy of rare diseases of the nose. Transactions of the American Academy of Ophthalmoscopy and Otolaryngology. 1963; 67: 261-80.
14.
Toppozada H, Riad H, Michaels l, Gaffar H, Sid-Ahmad K.
currently based on expert opinion and a robust
The epithelium and chronic inflammatory cells in
evidence base validating these strategies is currently
scleroma. Journal of Laryngology and Otology. 1981; 95:
unavailable.
1049-57. 15.
Firdousi FA, Sadiq S, Kadar AA. Rhinoscleroma. Journal of Pakistan Medical Association. 2000; 50: 276-7.
16.
Gonzalez-Angulo A, Marques-Monter H, Greenberg SO, Cerbon J. Ultrastructure of nasal scleroma. Annals of
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Badraway R. Affection of bone in rhinoscleroma. Journal
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*
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*
Williams RG, Jones TO. Mycobacterium marches back. Journal of Laryngology and Otology. 1995; 109: 5-13.
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13 THE NOSE AND PARANASAL SINUSES
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38.
Ramprasad P, Fernando A, Madhale S, Rao JR, Edward VK,
rhinitis. Journal of Laryngology and Otology. 1980; 94: 507-14. 39.
Sharma VK. Leprosy: Classification and clinical features.
tropical environment. Chennai, India: MERF Publications,
In: Valia RG (ed.). Text book and atlas of dermatology, 2nd
1999: 119-32.
edn. Bombay, India: Bhalani Publishing House, 2001:
40.
Taylor M, Young A. Studies on atrophic rhinitis. Journal of
41.
Tomooka LF, Murphy C, Davidson TM. Clinical study and
Laryngology and Otology. 1961; 75: 574-90.
1578-603. Barton RPE, Davey TF. Early leprosy of nose and throat.
literature review of nasal irrigation. Laryngoscope. 2000;
Journal of Laryngology and Otology. 1976; 90: 953-61. 31.
110: 1189-93.
Fokken WJ, Nolst Trenite GJ, Virmond M, KleinJan A, Andrade V, Van Baar NG. Immunohistochemistry of
32.
* 42.
of 273 cases of atrophic rhinitis and its management.
Mycobacterial Diseases. 1998; 66: 328-39.
Journal of Laryngology and Otology. 1977; 91: 591-600. Recommended. Qizilbash AAH, Daif M. Atrophic rhinitis revisited. Pakistan Journal of Otolaryngology. 1992; 8: 197-9. Young A. Closure of nostrils in atrophic rhinitis. Journal of Laryngology and Otology. 1967; 81 : 515-24.
Barton RPE. Ear nose and throat involvement in leprosy. In: 43.
Livingstone, 1985: 243-52. Mamidi NV, Prabhakar MC, Krishna DR. Disposition of
44.
rifampicin following intranasal and oral administration.
Indian Journal of Leprosy. 1996; 68: 149-53. 34.
45.
Ghosh P. Vestibuloplasty. A new one stage operation for atrophic rhinitis. Journal of Laryngology and Otology.
Henriksen SO, Gundersen WB. The etiology of ozaena. Acta
Pathologica and Microbiologica Scandinavica. 1959; 47: 380-6. 35.
Sinha SM, Sardana OS, Rajvanshi VS. A nine years review
leprosy. International Journal of Leprosy and Other
Hastings RC (ed.). Leprosy. Edinburgh: Churchill 33.
Chaturvedi VN. Atrophic rhinitis and nasal myiasis. In: Kameswaran S, Kameswaran M (eds). ENT disorders in a
Review. 1997; 68: 301-15.
30.
Fouad H, Afifi N, Fatt-Hi A, EI-Sheeny N, Iskander I, Abon Sail MN. Altered cell mediated immunity in atrophic
Samson PO et al. Transmission and protection in leprosy: Indications of the role of mucosal immunity. Leprosy 29.
Bernat J. Ozaena, a manifestation of iron deficiency. Oxford: Pergamon Press, 1965.
Technical Report Series No. 874, 1998; 24. 28.
Sayed RH, Abon-Elhamad KE, Abdel KM, Saleem TH. Study of surfactant level in cases of primary atrophic
1987; 101: 905-9. 46.
Keerl
R.
Weber R, Draf W, Dohambazov K. Tolerance,
Chen KS. Animal models of rhinitis. In: Raeburn 0,
subjective complaints and mucociliary clearance in rhinitis
Giembycz WB (eds). Rhinitis: Immunopathology and
sicca before and after nasal irrigation.
pharmacology. Basel: Birkhauser Verlag, 1996: 207-32.
Laryngorhinootologica. 1999; 77: 196-200.
M di
m
n
t
m
r
In
usitis
SI
GLENIS SCADDING
1474
DiagnosIs
1469
Predisposing factors
1469
Best clinical practice
Medical therapy
1470
Deficiencies in current knowledge and areas for future
1471
Long-term prophylaxis
1474
of medical approach to chronic rhinosinusitis
points
1474 1475
research
1475
References
The data in this chapter are supported by a medicine search using the key words chronic rhinosinusitis, together with the tenns medical treatment, antibiotics, antileukotrienes, corticosteroids, nasal douching, saline, decongestants, bacterial vaccines. The
gammaglobulin,
Cochrane reviews and the ARIA document (Allergic Rhinitis and its Impact on Asthma) have also been searched.
DIAGNOSIS
PREDISPOSING FACTORS
The European Position Paper on Rhinosinusitis and Nasal Polypsl the criteria for diagnosis of chronic
These include
rhinosinusitis in adults as 12 or more weeks of symptoms
and
Rhinosinusitis
with
no
complete
-n""�(,H·T"" •.,1"
resolution.
(including nasal polyps) is defined as
inflammation of the nose and the
sinuses
characterized by two or more of the following symptoms:
rhinitis, nonallergic rhinitis and
immune deficiency (innate or acquired).
[**]
Structural abnormalities, such as conchae etc., are no more common in
Haller (infraorbital)
chromc rhinosinusitis than
are in a control group, deviation?
with the
Anatomical abnormalities are not responsible for chronic rhinosinusitis, which is a mucosal disease. The inflam-
..
anterior/posterior (discoloured);
mation
may be predominantly
polyps)
.. reduction or loss of
UU.'-
plus either:
or neutrophilic
.... '.HJ'.�'
(immune
chronic
fibrosis). )
polyps in
including
systemic
Serious
sensitive
granulomatosis, Churg-Strauss disease and sarCO],Qo,SlS,
enc:1miCOplc signs of:
chromc
rhinosinusitis.
- polyps;
may
- mucopurulent discharge from middle meatus;
evidence of adhesions, contact bleeding and
-: or oedema/mucosal obstruction primarily in
with
aggressive prompt
middle meatus;
blood
and/or: ..
(allergic
nasal polyps, especially
.. facial pain/pressure;
polyposis the
requiring
relevant
count
oral
investigations erythrocyte
steroids including
sedimentation
rate
eosinophil count, angiotensin-converting enzyme tomography (CT)
....u ...,-'--'- ;;;, ,_...,.
- mucosal changes within ostiomeatal complex and/ or sinuses.
(ACE),
antinuclear
antibody
(ANA),
cytoplasmic antibodies (ANCA) and consideration of nasal biopsy.
) I J
1470 I PART 13
THE NOSE AND PARANASAL SINUSES
Allergic fungal rhinosinusitis usually presents in patients with nasal polyposis and previous surgery with tenacious mucus, which is intensely eosinophilic and contains very few fungal hyphae on silver staining. Characteristically, the CT shows evidence of hyperdense regions due to chelation of metals. Genetic factors are probably relevant in nasal poly posis, where affected parents give a high relative risk to their offspring. There is also evidence for overrepresenta tion of heterozygotes for cystic fibrosis in the chronic rhinosinusitis population. [**]
MEDICAL THERAPY
Since the pathophysiology and microbiology of chronic rhinosinusitis remain a source of debate,4 it is not surprising that many avenues of medical treatment exist and that treatments tend to be combined. Medical treatment used in chronic rhinosinusitis include: • • • • • • • • • •
allergen and/or irritant avoidance; douching; corticosteroids; decongestants; antibiotics; antifungals; antileukotrienes; aspirin; immunotherapy; other therapies.
Aim of treatment
Medical treatment of chronic rhinosinusitis is intended to reduce symptom and signs, improve patients' quality of life and prevent disease progression and/or recurrence.
Efficacy compared to surgery A recent randomized prospective studl [****] has shown
that medical treatment of chronic rhinosinusitis is as effective as endoscopic sinus surgery combined with topical nasal steroids, both in polypoid and nonpolypoid chronic rhinosinusitis. Both treatments improve asthma; however, medical treatment is superior in this respect in patients with nasal polyposis.
Allergen avoidance
There is no evidence that this is effective in chronic rhinosinusitis. However, since allergic rhinitis, especially when perennial, leads to mucosal inflammation and hypertrophy, thus possibly blocking the ostiomeatal
complex, it is usually employed in patients with allergic history together with relevant positive skin prick tests. Irritant avoidance
Irritants can increase nasal symptoms, therefore avoid ance of smoke, pollution and occupational irritants is usually advised. Nasal douching
This reduces nasal symptoms and increase quality of life,6,7 but has not been shown to have any effect on the nasal airway, nor on mucociliary clearance. [****] Corticosteroids
Systemic corticosteroids (oral, intramuscular) can reduce the size of nasal polyps to an extent that is comparable with surgery.8 [****/***/**] Topical corticosteroids reduce the recurrence of nasal polyps9,10,11,12,13,14 and should be used routinely in the long term, preferably employing a. molecule with low systemic absorption in drop form in the head upside down position;15,16,17 50 percent of postsurgical patients unresponsive to topical steroid sprays respond to fluticasone propionate nasules. In nonpolypoid chronic rhino sinusitis, topical corti costeroid shows modest efficacy in reducing symptoms during acute exacerbations when combined with anti 1 1 biotics. 8, 9,20,21,22,23 [***] Budesonide alone gave some symptom and airway improvement,24 a combination of dexamethasone and tramazoline (a decongestant) im proved discharge, obstruction and facial pain with improvements measured in x-rays, nasal airways resis tance and mucociliary clearance.22 In a small study, prophylactic use over the winter was no more effective than placebo spray.25 There is no evidence to suggest that topical intranasal corticosteroids worsen nose and sinus infection. Decongestants
In theory, these could be useful and in practice, a topical steroid/decongestant spray is widely used in initial therapy. However, there is no evidence to support this. Two double-blind, placebo-controlled paediatric studies have proved negative.26,27 [****] Antibiotics
Since the· majority of exacerbations of chronic rhino sinusitus are probably viral or inflammatory, rather than
Chapter 116
bacterial, the routine use of antibiotics for increased symptoms, especially in children, is not recommended.28 Treatment of the common cold is still problematical, though there is some evidence in favour of zinc, especially if not chelated by the addition of vitamin e.29 Antibiotics are needed for acute severe bacterial sinusitis; their place in the chronic form is controversial. Two routes are available: topical and oral.
Medical management of chronic rhinosinusitis I
exceeds the minimal inhibitory concentration (MIC) of the pathogen. Knowledge of this for individual antibiotics can determine frequency of use and hence efficacy. Drug A is over the MIC for over 75 percent of the dosing interval, whereas drug B is present over the MIC at < 50 percent of the dosing interval (see Figure 116.1a). With concentration-dependent killing, the goal is to maximize concentration and obtain the highest possible concentra tion of antimicrobial at the site of infection. With this form of killing, prolonged post-antibiotic activity occurs even when concentrations are below .NIle. This is characteristic of aminoglycosides, quinolones, azalides (azithromycin), ketolides and vancomycin. The major pharmacodynamic parameters that correlate with efficacy are the 24-hour area under the curve (AVC) serum drug concentration to MIC ratio (see Figure 116.1b).
Topical - this avenue is underexplored.30 [****/***] The use of the combination of betamethasone drops with neomycin was largely abandoned because of occasional resulting hyposmia. Two studies of topical antibiotics showed possible benefits in paediatric upper airways infections. The use of tobramycin instilled into maxillary sinuses in cystic fibrosis is helpful. 2. Oral short course - used in the treatment of acute exacerbations of chronic rhinosinusitis with or without the guidance of middle meatal swabs (which do reflect the sinus microbial population).31 1.
LONG-TERM PROPHYLAXIS
The observation that long-term erythromycin therapy reduced the mortality from diffuse pan-bronchiolitis (an
However, the relevance of bacteria present to disease exacerbation is not always certain. Common bacteria found in chronic rhinosinusitis include: • • • • •
Time-dependent killing
Haemophilus inJluenzae (nontypeable); Streptococcus pneumoniae; Staphylococcus aureus; Moraxella catarrhalis; Pseudomonas aeruginosa (in cystic fibrosis).
Drug A
c o
�
C Q) o c o o o
.. _ .
Drug B
� :.0
The bacteria found in chronic rhinosinusitis are the same as those causing the acute form, with the addition of occasional Gram-negative bacteria and organisms of low virulence, such as streptococcus viridans. These last are of doubtful significance. Many of the infecting organisms have virulence factors, such as carbohydrate capsules, which decrease phagacytosis, beta-lactamase which can hydrolyze penicillins and molecules which disrupt or damage ciliary beating. There are recent important observations about anti biotic pharmacokinetics and pharmacodynamics with some drugs killing in a time-dependent manner, whilst others are concentration dependent. 32 [***] The anti biotic used and the dose employed should be based on knowledge of this and of local patterns of antibiotic resistarice.33 Time-dependent killing refers to the time it takes for a pathogen to be killed by exposure to an antimicrobial. The goal is to optimize the duration of exposure. With time-dependent killing, post-antibiotic effects (i.e. persistence of antimicrobial action after the antimicrobial is removed) are minimal. This form of killing is characteristic of �-lactam antibiotics, macrolides and clindamycin. The major pharmacokinetic/pharmaco dynamic parameter that correlates with the efiicacy of these drugs is the time for which the serum concentration
----., ... ---- ... --.��=-�-'-
1471
�
«
�-----n----'r--+-- MIC
-------A-----� Time
Dose
[a)
Dose
Concentration-dependent killing ---- Peak concentration c o
� C
Q) o c o o o
�
:0
� «
MIC
Dose
Dose
[b) Figure 116.1
Patterns of antimicrobial activity:
dependent killing;
._ ..... _ . .
(b)
�------....... �-=---'-'"�
_ _ �
(a)
time-
concentration-dependent killing.
/
III!I ·.. . ..I111 ?...-:""�--IIIIiI--'
1472 I
PART 13 THE NOSE AND PARANASAL SINUSES
intractable aetiology),
chronic respiratory infection of unknown and
improved
sinus
symptoms
in
those
patients with concomitant rhinosinusitis,34 led to the treatment of chronic rhinosinusitis with long-term, low dose erythromycin.
[***]
This was found to be effective,
and the other 14-membered ring macrolides clarithro
mycin and roxithromycin were also effective, even when the
bacterial
Josithromycin,
pathogen which
identified
has a
was
not
sensitive.
16-membered ring,
Antifungals ? role
was
relatively ineffective. These observations have now been
extended to nasal polyps where roxithromycin in eight
Allergic fungal rrunosinusitis
(AFRS) has precise diag all inspissated secretion plus medical treatment with corti
nostic criteria and treatment is by surgical removal of costeroids
(topical
and
oral)
together
with
allergy
management, and possibly also with oral antifungals.37 Recently, however, Ponikau et aI.38 have suggested that practically all nasal polyposis and chronic rhinosinusitis is of fungal aetiology.
[***]
This theory is based on the
finding of fungi associated with degranulating eosinophils
weeks treatment in an open study decreased polyp size in
in nasal mucus. However, fungi can be isolated from all
resulted in 68 percent improving; the difference was not
between pa tien ts
52 percent of 20 patients.35 Additional oral azelastine
significant. The improvement appeared to increase with
t ime, with smaller polyps responding better than larger
ones.
The
improvement
with
long-term
antibiotics
appears to be better in those patients with a normal IgE and is inversely proportional to the eosinophil count in bloods, smears and mucosa. It is not proportional to the CT score nor to the number of interferon-positive,
IL-4-
positive cells nor to the neutrophil counts in smears or mucosa.36 The mechanism of effect of macrolides could be due to a variety of factors. Macrolides have anti inflammatory as well as antibiotic e ffe cts
animals. The improvement in ciliary beat frequency was months
rhinosinusitis patients given three
of antibiotic
included molecules other than
macrolides, used in response to sensitivity of organisms cultured from sinus swabs. Long-term low-dose antibiotic treatment is associated with the development of resistance and this therapy should probably be restricted to patients who have failed to respond to other forms of medical treatment.
Two open trials of antifungal douching therapy have shown benefit in patients with nasal polyps,40 but a multi centre,
randomized,
116.1
Mechanism of macrolide activity.
Mechal'lfSm of aetjv�ty
placebo-controlled
better than using a matched placebo.41 Open studies of oral antifungal itraconawle have noted benefit, but a recent
double-blind
study
with
terbinafine
proved
negative.42
[***]
Antihistamines/antileukotrienes There is little evidence of the efficacy of antihistamines in chronic rhinosinusitis, presumably because the majority have little or no effect on nasal blockage, though one trial suggests that the addition of loratadine to standard therapy with antibiotics and oral corticosteroids con ferred benefit compared to placebo.43 Antileukotrienes have been
[***]
tested in nasal polyposis in
open studies and recently in a positive double-blind Approximately
percent
50
of
nasal
polyps
respond to some degree.4S,4Q In a small study, there was no
difference
between
aspirin-sensitive
and
aspirin
tolerant patients.47 Asthmatic symptoms also improved in responders, usually to a greater degree than those of the
Anti-agent
W w
double-blind,
study demonstrated that amphotericin douching was no
study.44
Table
with classical allergic fungal rhinosinu
sitis and those with eosinophilic mucin rhinosinusitis.
(Table 116.1).
Most of those noted are from open studies, some in noted in chronic
noses and Ferguson39 has noted significant differences
Adhesion [pseudomonas/moraxelia)
nose.
No
identified.
factor
predicting
responsiveness
could
be
[***]
Virulence Inhibit toxi n/dye production Destruction of biofilm
Aspirin
On host Modulation of defence mechanisms l'
Monocyte
-7
macrophage
Aspirin sensitivity
is
usually
associated
an
nasal
intense
eosinophilic inflammation which responds poorly to
Inhibit cytoki ne production
surgery, with rapid and frequent relapse.
I nh ibit neutrophil function
Zeiss and Lockey48 noted that in patients with aspirin
Decrease mucus production
sensitive asthma and nasal polyposis, following a response
Inhibit chloride channels Decrease glycoconjugate secretion Increase ciliary beat frequency Increase steroid receptors
to aspirin there was a refractory period which aspirin
could again be taken without
ill effects. This phenomenon
has been put to use by regular administration of aspirin
either orally or topically in the nose.
-.
with
polyposis and asthma (Samter's triad). There is
�,/
/
Chapter 116 Medical management of chronic rhinosinusitis I
1473
deficiency (varying from frank hypogammoglobulinae
ORAL
The patient is given a small initial dose and the dose is then gradually increased until several hundred milligrams per day are tolerated. Used in this fashion, there is evidence of significant improvement in many parameters affecting both nose and chest
(Table 116.2).48,49
The use
of oral aspirin in addition to other treatments is beneficial in patients with Samtees triad, but side effects are high with gastrointestinal problems (mainly bleeding) occurring.45,49,50
Recently, smaller doses, i.e. 100 mg per day, have also
mia (IgG < 3 giL) to IgA andlor IgG subclass deficien
cies).55
It
might
be
expected
that
replacement
of
antibodies would prove beneficial in some subjects. There are no formal double-blind, placebo-controlled studies, but open studies do suggest benefit that is not confined to
individuals
who
demonstrate
poor
tetanus and pneumococcal vaccines.
responses
[***J
to
However, the
use of blood products is only indicated for very seriously affected
individuals,
since
transfer
of
prions
is
a
possibility.
shown efficacy.51 BACTERIAL VACCINES
These were previously widely used, but lost favour in the
NASAL
Lysine aspirin, the only truly soluble from of aspirin, is used for diagnosis of aspirin sensitivity by nasal or bronchial challenge and also for topical nasal desensitiza
UK once double-blind, placebo-controlled studies de
monstrated
them
to
be
ineffective.
vaccines are still available in Europe.
Some
bacterial
[***I**J
tion. Patriarca et aI.52 noted prolongation of the polyp free interval in both aspirin-sensitive and aspirin-tolerant patients. In an open study, this has been confirmed in aspirin-tolerant patients.53 In a double-blind, placebo controlled crossover study, it was shown that topical lysine aspirin was associated with a reduction on cysteinyl leukotriene receptors which are upregulated in the nasal mucosa of aspirin-sensitive individuals.54
[****]
However,
there was no significant clinical effect. Addition of topical lysine aspirin to other therapies in patients with persistent symptoms improves the nasal airway.
[***]
Other therapies
? role
DIET
Many nasal polyposis patients note an exacerbation after drinking
alcoho1.56
Some
also
react
to
E-numbers,
preservatives and high salicylate foods. Avoidance diets are difficult, but may reduce exacerbations. There has been no double-blind, placebo-controlled study.
[**J
Milk is regarded by many as a mucus promoter, although the effect is also seen with
all liquids of similar
viscosity. Certain patients adopt largely dairy-free diets
Immunotherapy
with subjective benefit. Objective proof is lacking and care should be taken that calcium deficiency does not
Various forms of immunotherapy have been attempted in
occur.
chronic rhinosinusitis. DIURETICS IMMUNOGLOBULIN REPLACEMENT THERAPY
If pt.
Since approximately 5 percent of chronic rhinosinusitis patients seen in specialist clinics have humoral immune
Table 116.2
Oral aspirin desensitization in 65 aspirin-sensitive
patients treated daily for one to six years (mean 3.5 years) .
Median values
.J,.J,.J,-
Sinus infections
6
Hospital ization
0.2
Use of systemic
10.2
l' .J,-
Olfaction
0
Sinus/polyp operations
.J,-,
Nasal corticosteroids
-7 -7 -7
found to reduce the response to nasal allergen challenge and to reduce recUrrence of polyps if administered nasally to post-polypectomy patients over a prolonged period.57 Amiloride, which is used in cystic fibrosis, has also been suggested as a topical therapy for nasal polyps.
NITRIC OXIDE DONORS
2
0
The sodium channel-blocking diuretic frusemide has been
p < 0.0001
2.5 mg
Nitric oxide (NO) is manufactured in the paranasal
sinuses
where bactericidal
levels
of 20/25
ppm
are
reached. Arginine is the substrate and the relevant NO
corticosteroids
synthase has the characteristics of an inducible form, but
2
0.2
-7 -7
0
p< 0.004
and the bronchial mucosa, inducible NO synthase is
137
-7
106
p< 0.01
occurs. In chronic rhinosinusitis, and especially in nasal
per year
No change in: emergency department use; inhaled corticosteroids. Reproduced from Ref. 51, with permission from Georg Thieme Verlag.
appears to be constitutive. In the remainder of the nasal found and NO levels are raised when inflammation polyposis, NO levels measured in the nose tend to be low,
probably
secondary
to
ostiomeatal
complex
/ ...
1474
I
PART
13 THE NOSE AND PARANASAL SINUSES
- trial of antileukotriene for nasal polyposis;
obstruction. Successful therapy is associated with a rise in 8 This correlates with an improvement in
- antibiotics for infective rhinosinusitis and possibly
NO levelS.5 nasal
mucociliary 8 Improvements. 5
clearance
and
with
symptomatic
for nasal polyposis; - aspirin (topical or oral for nasal polyposis).
·
In primary ciliary dyskinesia, even when an ultra
•
inducible nitric oxide synthase (iNOS) levels of nasal NO.59 [***] NO donors
might
be useful
57
cotrimoxazole.
and very low •
in improving nasal
mucociliary clearance. To date, the use of arginine in primary ciliary dyskinesia has temporarily improved 60 ciliary beat frequency. [***] As yet, there is no suitable
Specific therapy, e.g. for Wegener's granulomatosis: cyclophosphamide azathiaprine and/or
structural defect cannot be identified, there is a lack of
Gammaglobulin replacement therapy for significant immune deficiency.
for eg• If no
improvement after three to six months,
consider surgical intervention.
molecule for long-term human use.
SUMMARY OF MEDICAL APPROACH TO CHRONIC RHINOSINUSITIS
popuL
li
m
Diagnosis •
Chronic rhinosinusitis (symptoms, signs, endoscopy)
•
Polypoid or nonpolypoid
•
Eosinophilic or neutrophilic
•
Consider underlying causes: - allergy (skin prick tests/RAST ); - immune deficiency (immunoglobulins/lgG subclasses); - autoimmune disease; - vasculitis
(ACE, ANA, ANCA, FBC,
ESR);
- aspirin sensitivity (nasal lysine aspirin challenge);
•
- allergic fungal sinusitis (skin prick tests, aspergillus precipitins, CT changes, silver stains on histological specimen).
Initial management •
benefits
accompanying asthma.
Decrease any known predisposing factors.
Improve ostiomeatal complex drainage medically
\'
.
�•
I
:I
'I . .
,
•
Decongestants (brief use of topical formulations).
•
Nasal douching.
intended to reduce symptoms and signs, improve
•
Topical corticosteroids (preferably drop formulation,
patients' quality of life and prevent disease
•
Review at six weeks;
nonsystemically bioavailable).
if no improvement CT scan to
exclude sinister underlying disease and to act as possible road map if surgical intervention required.
.I Medical treatment of chronic rhinosinusitis is
progression and/or recurrence.
./ Medical treatment of chronic rhinosinusitis is as effective as endoscopic sinus surgery combined with topical nasal steroids, both in polypoid and non polypoid chronic rh inosin usitis .
.I Since the majority of exacerbations of chronic
Further medical therapy
rhinosinusitis are probably viral or inflammatory rather than bacterial, the routine use of antibiotics
•
Consider
for increased symptoms, especially in children, is not
- oral corticosteroids (few days) plus nonabsorbed
recommended.
drops (long term) for nasal polyposis;
./
61.62
..
,
Chapter 116 Medical management of chronic rhinosinusi ti s I
10.
Deficiencies in current knowledge and areas for future research
1475
Drettner B, Ebbesen A, Nilsson M. Prophylactic treatment with flunisolide after polypectomy. Rhinology. 1982; 20: 149-58.
11.
> In the majority of patients, no obvious cause for
Dingsor G, Kramer J, Olsholt R, Soderstrom T. Flunisolide nasal spray 0.025% in the prophylactic treatment of nasal
chronic rhinosi nusiti s is found. Prospective trials of
polyposis after polypectomy. A randomized, double blind,
different forms of medical i ntervention need to be
parallel, placebo controlled study. Rhinology. 1985; 23:
undertaken using well-characterized groups of
49-58.
patients and including symptoms, objective measures
12.
and quality of life i nstruments in the analysis.
Karlsson G. Fluticasone propionate aqueous nasal spray in
> Further trials involving randomi zation to further
the treatment of nasal polyposis. Annals of Allergy,
medical and surgical treatment in those failing initial medical therapy need to be undertaken i n order to
Holmberg K, Juliusson S, Balder B, Smith DL, Richards DH,
Asthma and Immunology. 1997; 78: 270- 6.
13.
Hartwig S, Linden M, Laurent C, Vargo AK, Lindqvist N.
determine which patients are most likely to benefit
Budesonide nasal spray as prophylacti c treatment after
from surgery.
polypectomy (a double blind clinical trial). Journal of
> The observation that raised levels of NO indicates patent ostiomeatal complexes needs confirmation, as
Laryngology and Otology.
14.
this may reduce the need for CT scans.
Ruhno J, Andersson B, Denbury J, Anerson M, Hitch D, Lapp P et al. budesonide with placebo for nasal polyposis. Journal of Allergy and Clinical Immunology. 1990; 86: 946-53.
15.
Chalton R, Mackay I, Wilson R, Cole P. Double-blind, placebo-controlled trial of betamethasone nasal drops for
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1.
European Academy of Allergology and Clinical
nasal polyposis. British Medical Journal (Clinical Research 16.
Immunology. European position paper on rhinosinusitis 2.
and tolerability of fluticasone propionate nasal drops 400
and nasal polyps. Rhinology. Supplement. 2005; 18: 1-87.
mgs once daily compared with placebo for the treatment
Lloyd GAS, Lund VJ, Scadding GK. CT of the paranasal
of bilateral polyposis in adults. Clinical and Experimental Allergy. 2000; 30: 1460-8.
sinuses and functional endoscopic surgery - A critical analysis of 100 symptomatic patients. Journal of 3.
4.
17.
Dose-related efficacy and tolerabi lity of fluticasone
Bachert C, Van Cauwenberge PB. Inflammatory
propionate nasal drops 400 rng once daily and twice daily
mechanisms in chroni c sinusitis. Acta Oto-rhino
in the treatment of bilateral nasal polyposis: a placebo
laryngologica Belgica.
controlled, randomised study in adult patients. Clinical
Ramadan HH. What is the bacteriology of chronic sinusitis
and Experimental Allergy. 2000; 30: 94-102.
18.
Ragab SM, Lund VJ, Scadding G. Evaluation of the medical and surgical treatment of chroni c rhinosinusitis: a
6.
sinusitis. Rhinology. 1992; 30: 103- 12. 19.
prosp.ective, randomised,
Guerrier Y. Efficacy of endonasal neomycin-toxocortol pivalate irri gation in the treatment of chronic allergic and
Taccariello M, Parikh P, Darby Y, Scadding GK. l\Jasal
bacterial sinusitis. ORL; Journal for Oto-rhino-Iaryngology
blind study comparing alkaline nasal douche and sterile
and its Related Specialties.
20.
sea water. Rhinology. 1999; 37: 29-32.
9.
Meltzer EO, Orgel HA, Backhaus JW, Busse WW, Druce HM, Metzger WJ et al.
Tomooka LT, Murphy C, Davidson TM. Clinical study and
adjunct to oral antibi otic therapy for sinusitis. Journal of
literature review of nasal irrigation. Laryngoscope.
Allergy and Clinical Immunology.
110: 1189-93. 8.
Cuenant G, Stipon JP, Plante-Longchamp G, Baudoin C,
2004; 114: 923-30. douching in chroni c rhinosinusitis: a randomised, single
7.
Qvarnberg Y, Kantola 0, Salo J, Toivanen H, Vuori E. Influence of topical steroid treatment on maxillary
303-6.
*
Penttila M, Poulsen P P, Hollingworth K, Holmstrom M.
Laryngology and Otology. 1991; 105: 181-5.
in adults? American Journal of Otolaryngology. 5.
edition). ' Keith P, Nieminen J, Hollingworth K, Kolovich J. Efficacy
21.
Dolor RJ, Witsell DL, Hellkamp AS, Williams Jr JW, Califf
Lildholdt T, Runderantz H, Bende M, Larsen K.
RM, Simel DL et al.
Glucocorticoid treatment for nasal polyps: the use of
without intranasal fluticasone for the treatment of
topical Budesonide powder, intramuscular betamethasone
rhinosinusitis. The CAFFS Tri al: a randomised controlled
and surgical treatment. Archives of Otolaryngology -
trial. Journal of the American Medical Association.
Head and Neck Surgery. 1997; 123: 595-600.
286: 3097-105.
Holopanien E, Grahne B, Malmberg H, Makinein J,
22.
Sykes DA, Wilson R, Chan K, MacKay I, Cole P. Relative
Lindqvist N. Budesonide in the treatment of nasal
impQrtance of antibi otics and i mproved clearance in
polyposis. European Journal of Respiratory Di seases.
topical treatment of chronic muco purulent rhinosinusitis.
Supplement. 1982; 122: 221-8.
A controlled study. Lancet. 1986; 2: 359-60.
19
1476 I PART 13 23.
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Meltzer EO, Charous BL, Busse WW, Zinreich SJ, Lorber RR,
Archives of Otolaryngology - Head and Neck Surgery.
2000; 126: 690.
Danzig MR. Added relief in the treatment of acute recurrent sinusitis with adjunctive mometasone furoate
37.
sinusitis. Annals of Allergy, Asthma and Immunology.
nasal spray. The I\lasonex Sinusitis Group. Journal of
2000; 85: 90-7.
Allergy and Clinical Immunology. 2000; 106:
38.
630-7. 24.
Efficacy and tolerability of budesonide aqueous nasal
fungal sinusitis. Mayo Clinic Proceedings.
spray in chronic rhinosinusitis patients. Rhinology. 2004;
877-84.
* 39.
Otolaryngologic Clinics of North America.
{:orticosteroids in chronic rhinosinusitis: a randomized,
227-35. 40.
propionate aqueous nasal spray. Rhinology. 2001; 39: 75-9.
on nasal polyposis. Journal of Laryngology and Otology. 2002; 116: 261-3.
McCormick DP, John SD, Swischuk LE, Uchinda T. A
* 41.
Hellings PW et 01. Amphotericin B nasal lavages: not a
Clinical Pediatrics (Philadelphia).
solution for patients suffering from chronic rhinosinusitis.
Otten FW, Grote JJ. Otitis media with effusion and chronic
Journal of Allergy and Clinical Immunology. 2006; 118:
42.
Poole MD, Jacobs MR, Anon JB, Marchant CD, Hoberman
high-dose oral terbinafine: a double blind, placebo
A, Harrison CJ. Antimicrobial guidelines for the treatment
controlled study. Laryngoscope.
of acute bacterial rhinosinusitis in immunocompetent
43.
Cougnard J et 01. Adjunct effect of loratadine in the
Otorhinolaryngology. 2002; 63: 1-13.
treatment of acute sinusitis in patients with allergic rhinitis. Allergy. 1997; 52: 650-5.
Prasad AS, Fitzgerald JT, Bao BB, Beck FW, Chandrasekar PH. 44.
oxide in objective evaluation of chronic rhinosinusitis
A randomized, double-blind, placebo-controlled trial.
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Phenomenology, pathogenesis, diagnosis and treatment of
antimicrobial agents. Laryngoscope.
aspirin sensitive rhinosinusitis. Acta Oto-rhino
Biel MA, Brown CA, Levinson RM, Gavis GE, Paisner HM,
therapy for the relief of sinus symptoms in aspirin triad disease. Ear, Nose and Throat Journal.
Jacobs MR. Optimization of antimicrobial therapy using
608, 613. 47.
of montelukast, a leukotriene receptor antagonist, in nasal
Hickner JM, Bartlett JG, Besser RE, Gonzales R, Hoffman
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Experimental Allergy. 2001; 31: 1385-91.
48.
of Internal Medicine. 2001; 136: 708-9.
Kudoh S, Azuma A, Yamamoto M, Izumi
Zeiss CR, Lockey RF. Refractory period to aspirin in a patient with aspirin-induced asthma. Journal of Allergy
1.
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Ando M.
Improvement of survival in patients with diffuse
49.
Berges-Gimeno MP, Simon RA, Stevenson DD. Long-term
panbronchiolitis treated with low-dose erythromycin.
treatment with aspirin desensitisation in asthmatic
American Journal of Respiratory and Critical Care
patients with aspirin-exacerbated respiratory disease.
Medicine.
1998; 157: 1829-32. Journal of Allergy and Clinical Immunology. 2003; 111:
Ichimura K, Shimazaki Y, Ishibashi T, Higho R. Effect of new macrolide roxithromycin upon nasal polyps
36.
Ragab S, Parikh A, Darby YC, Scadding GK. An open audit
Clinical Microbiology and Infection.
JR, Sande IViA et 01. Principles of appropriate antibiotic use
35.
Ulualp SO, Sterman BM, Toohill RJ. Antileukotriene
Laryngology. 1998; 107: 942-5.
pharmacokinetic and pharmacodynamic parameters.
2000; 1
laryngologica Belgica.
46.
maxillary sinusitis. Annals of Otology, Rhinology, and
34.
Schapowal AG, Simon HU, Schmitz-Schumann M.
Goh YH, Goode RL. Current status of topical nasal
Sigel ME et 01. Evaluation of the microbiology of chronic
* 33.
Ragab SM, Lund VJ, Saleh HA, Scadding G. Nasal nitric
patients with the common cold treated with zinc acetate Annals of Internal Medicine.
* 32.
Braun JJ, Alabert JP, Michel FB, Quiniou M, Rat C,
children. International Journal of Pediatric
Duration of symptoms and plasma cytokine levels in
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Kennedy DW, Kuhn FA, Hamilos DL, Zinreich SJ, Butler D, Warsi G et 01. Treatment of chronic rhinosinusitis with
100: 627.
* 30.
19
1149-56.
upper respiratory tract infection in children: a randomised,
29.
Ebbens FA, Scadding G, Badia L, Bachert C, van Zele T,
antihistamine for the treatment of sinusitis in children.
placebo-controlled clinical study. Laryngoscope.
* 28.
Ricchetti A, Landis BN, Maffioli A, Giger R, Zeng C, Lacroix JS. Effect of anti-fungal nasal lavage with amphotericin B
double-blind, placebo-controlled trial of decongestant
27.
Ferguson BJ. Definitions of fungal rhinosinusitis.
Parikh A, Scadding GK, Darby YC, Baker RC. Topical double blind, placebo controlled trial using fluticasone
26.
Ponikau JU, Sheris DA, Kern EB, Homburger HA, Frigas E, Garffey TA et 01. The diagnosis and incidence of allergic
Lund VJ, Black JH, Szabo LZ, Schrewelius C, Akerlund A.
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Schubert MS. Medical treatment of allergic fungal
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Stevenson DD, Hankammer MA, Mathison DA,
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Christiansen SC, Somon RA. Aspirin desensitisation
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treatment of aspirin-sensitive patients with rhinosinusitis
Suzuki H, Ikeda K, Honma R, Gotoh S, Oshima 1. Furukawa
asthma.: long-term outcomes. Journal of Allergy and
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Chapter 116 51.
52.
Gosepath J, Schafer 0, Mann WJ. Analgetika-Intoleranz:
inhalation from of furosemide to prevent postsurgical relapses of rhinosinusal polyposis. Journal for Oto-rhino
100 mg aspirin. Laryngo-rhino-otologie.
laryngology and its Related Specialties.
Patriarca G, Nucera E, DiRienzo V, Schiavino 0, Pellegrino
307-10. Mostafa BE, Abdel Hay H, Mohammed HE, Yamani M. Role of leukotriene inhibitors in the postoperative management
Allergy. 1991; 67: 60-2.
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Scadding GK, Hassab M, Darby YC, Lund VJ, Freeman A.
20:
Related Specialies.
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Wodehouse T. Ciliary aspects of chronic sino-pulmonary disease. PhD thesis, University College, London
561-3.
(2002) .
Sousa A, Parikh A, Scadding GK, Corrigan CC, Lee TH. Downregulation of cysteinyl leukotriene receptor by
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Loukides S, Kharitonov S, Wodehouse T, Cole P J. Effect of
intranasal lysine aspirin in aspirin sensitive nasal
arginine on mucociliary function in primary ciliary
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dyskinesia. Lancet. 1998; 352: 371-2. 61.
1524-6.
Clement PA, Bluestone CD, Gordts F, Lusk RP, Otten FW,
Scadding GK, Lund VJ, Darby YC, Navas-Romero J,
Goossens H et al.
Seymour N, Turner MW. IgG subclass levels in chronic
children. International Journal of Pediatric
rhinosinusitis. Rhinology. 1994; 56.
58.
acetylsalicylate in aspirin sensitive patients. Annals of
Clinical Otolaryngology. 1995;
55.
Passali 0, Mezzedimi C, Passali GC, Bellussi L. Efficacy of
Desaktivierung mit einer taglichen Erhaltungsdosis von
Intranasal lysine aspirin in recurrent nasal polyposis.
* 54.
1477
Langzeitergebnisse bis zu 3 Jahren bei adaptiver
S, Fais G. l\Jasal provocation test with lysine
53.
57.
Medical management of chronic rhinosinusitis I
32:
Otorhinolaryngology. 1999; 5: 49.
15-9.
Mathison DA, Stevenson DO, Simon RA. Precipitating factors in asthma. Aspirin, sulfites and other drugs and
62.
Jones NS. Acute and chronic sinusitis in children. Current Opinion in Pulmonary Medicine.
chemicaIs. Chest. 1985; 87 ( Suppl. ) : 50S-54S.
r
/
117 Su rg ica I management of rh inosin usitis
VALERIE J LUND AND JULIAN ROWE-JONES
I ntr od uction
1 478
K ey p oi nt s
1 496
D ia gnosis
1478
Best c l in ica l pra ct ic e
1496
S ur gica l appr oac h es
1 480
D ef iciencies i n current kn owled ge a nd a reas f or f ut ur e
S ur gica l pr oced ur es R hi nosi nusit is i n c hi ld ren
1481 1 495
R ef er enc es
Conc lusi ons
1 496
1 49 6
r esear ch
1496
The data in this chapter are supported by a Medline search as
using the key words rhino sinusitis, sinusitis and surgery, as well data taken from the authors' personal collection of literature.
INTRODUCTION
has been adopted intern ationally in recent yea rs , l, 2 in recognition of the physiology and pathophysiology within the nose and sinuses, where it is impossible to make an absolute distinction between where one starts and the other ends. An increasing recognition of the importance of the lateral wall of the nose and in par ticular the ostiomeatal complex has reinforced the use of this terminology, although clearly one anatomical area may be more obviously affected than another. None theless imaging studies on the common cold3 clearly demonstrated that even a viral rhinitis produced inflam matory c hanges in over 80 percent of the adjacent sinus. In a preantibiotic era, surgical drainage of the sinuses was a necessity in cases that had failed to resolve spontaneously and were often potentially li fe threatening The indications for surgery have changed somewhat with a host of effective medical therapies now avail able, but despite these a cohort of patients remain in whom surgery will be required. Nonetheless, adequa te trial of medical therapy is a prerequisite in most cir cumstances, as we recognize that many patients will
continue to need medical therapy even when surgery is undertaken (Figure 117.1).
The term 'rhinosinusitis'
-
DIAGNOSIS While a careful clinical history of
remains the cornerstone diagnosis and all patients will undergo a general
.
Surgery Figure 11 7.1
.Algori thm of ma na gem en t of pat ient s wit h
c hr on ic rhi nosi nusi tis.
Cha pter 11 7 Sur gi cal m anageme nt of rh inosi nu si ti s I
otorhinolaryngological examination, the emphasis has moved towards endoscopy supported by appropriate imaging to confirm the diagnosis, define the extent of pathology and demonstrate relevant anatomy. A
number of international consensus groups and task
1479
However, the diagnostic role of endoscopy cannot be too strongly emphasized and it should be available for routine clinical use both in outpatients and in the operating theatre.
forces on behalf of organizations -with a clinical interest in
this
area
have
considered
the
classification
and
diagnosis of rhinosinusitis. 1, 2, 3, 4, 5 In recent years in the absence of firm pathophysiological criteria, clinical
definitions have relied upon duration and symptom complexes of varying severity ideally corroborated by
endoscopy and imaging.
[**/*]
Radiology The role of plain sinus x-rays has been the subject of considerable discussion as false-positives and false negatives
can
occur, particularly in infants and children.12
Neither is it possible adequately to visualize the ostio meatal area
(Figure 117.2),
identify anatomical variants
or judge important surgical features, such as prominent or
Endoscopy
dehiscent optic or carotid canals.
Endoscopy was first performed by Hirschmann6 in
1903
using a modified Nitze cystoscope which he used in the nasal cavity and in the maxillary sinus via a tooth socket. This cystoscope had a diameter of
5 mm and an electric bulb deflected 90° by a distal prism with 180° rotation. Reichere in 1902, Sargon8 in 1908 and Imhofer9 in 1910 all used similar instruments and even attempted removal of foreign bodies. In
1922, SpeilberglO was the first to
Zinreich et al.13 popularized a protocol for computer
assisted tomography (CT) using sections taken in the coronal plane -with <wide'
window settings to show
optimally fine bone detail
(2000-4000 HU). A wide
range of protocols is recommended in the literature
(Table 117.1).14
The newer technology has reduced
the scan duration and radiation dose, whilst improving visualization, and the surgery may be assisted by
3D
introduce an endoscope into the maxillary sinus via the inferior meatus, but it was in
1925 that Maltzll
commissioned Wolf to make a dedicated endoscope and who introduced the term 'sinoscopy. These endoscopes using a series of small lenses continued in use until Hopkins, Professor of Optics at Reading, invented a far superior system in the
1950s, based on solid glass rods,
which is now universally in use. The technique is described in Chapter lOS, Nasal endoscopy, but a few specific points should be made: •
A careful endoscopic examination will reveal disease not visualized by conventional anterior or posterior , rhinoscopy, but it is not always possible to enter the
•
middle meatus, either anteriorly or medially. Even when the middle meatus is readily examined, only the
•
disease. Particularly -with the wide-angled lenses, there is a
Figure 117.2
flattening effect on the mucosal surface.
i n the re g ion of the infundi bulum .
Table 1 1 7.1
Cor ona l sec ti on thr ou gh an adu lt m id facial bl ock
Protoc ols f or CT sca n ni ng i n chr onic rhi nosi n usiti s.14 RNTN:EH'4
Zlnreich et al. �3
Pl a ne
Dire ct cor onal
Direc t c or ona l
D irec t cor on al
S lice th ick ne ss
4mm
2mm
I nc reme n ts
Smm
Scan im ages
3mm 20-25
5mm (2. 5mm thr ough the OMC) Conti g u ous, i.e . 5mm ( 2.5 mm thr ough the OMC)
10 + 2 a xial
18-20
Wi ndow
2000 H ou nsfi eld u ni ts
2000 Hounsfield uni ts
Wi dth, 4000; le vel + 350
Radi ation
125 kV, 450 m As
120 kV, 200 m As
1 20 kV, 1 00 mAs
OMC. ostiomeatal complex.
....
/
1480
I PART 13 THE NOS E AN D PARANASAL SINU SES
in selected cases.
imaging and navigational techniques
Reconstructed coronals derived from fine cut axials on
the newer scanners may obviate the need for direct
coronal sections in which the patient must hyperextend the head. However, as the coronal plane approximates
closest to the surgical field and best demonstrates the
ostiomeatal complex and skull base, coronal cuts of
the
highest
possible
resolution
are
always
required
(Figure 117.3a). However, when pathology is present in
the posterior ethmoids and sphenoids, axial views are also
required to optimally show the optic nerve and carotid artery
(Figure 117.3b). This may obviate the need for
direct coronal
sections
in which
the
patient
must
hyperextend the head, but the coronal plane approximates
closest to the surgical field and best demonstrates the osteomeatal complex and the base of the skull. However,
the posterior ethmoids axial views are also required to optimally show the optic nerve and carotid artery. Reconstructed when pathology is present in
and sphenoid,
sagittals can be of considerable assistance in evaluating the frontal recess
(Figure 117.3c). [**]
Magnetic resonance imaging (MRI) provides excellent
soft tissue detail, but only offers bone detail as a signal void, whilst tending to 'overdiagnose' clinically relevant
inflammatory changes in the sinuses. Thus CT remains
the primary imaging modality and is generally reserved for patients who have failed appropriate medical therapy and are being considered for surgery
in uncomplicated
rhinosinusitis. The timing of the scan should take into
account the effect of the common cold which produces
87
sinus opacification in up to
percent of sinuses3 and
the persistence of changes on imaging many weeks after
S
bacterial infection despite clinical resolution.I
SU RGICAL APP ROACHES Historical aspects The first clear indication of the existence of the paranasal
sinuses was provided by Berenger del Carpi, anatomist and surgeon at Bologna in the early sixteenth century. In
1600,
16
FaJlopius17 referred to the maxillary sinus and
suggested that the sinuses were absent in children until
they reached maturity. Apart from the quotation, 'In person having a painful spot
a
in the head, with intense
headaches, pus or fluid running from the nose removes
the disease'
(Hippocrates,
5BC)IB which may be in
ferred as describing a sinus infection, the maxillary
sinus
and associated suppuration were not
tely described until
1651
adequa
when they were reported by
Nathaniel Highmorel9 and for some time the sinus was
Figure 117.3
CT scan: (a) coronal plane,
s.agittal plane. Figure courtes.y of
(b)
axial plane,
(c)
T Beale.
referred to by his eponym.
The treatment of the maxillary sinusitis by opening
and irrigating the sinus via a variety of routes has a long and varied history. Highmore himself advocated
decompression by thrusting a silver bodkin through
an empty tooth socket. Many of the earliest writers,
such as Cowper20 in
1707
and Meibomius21 in
, I
/ .J
171 B,
Chapter 117 Sur gical ma na ge ment
recommended
of rhi nosinusitis I 1481
irrigation through the alveolar tooth 22 margin after molar tooth extraction, while Lamorier 23 in 1798 preferred the canine in 1743 and Desault 24 fossa approach. In 1835, John Hunter was one of
whereas
the first proponents of the intranasal approach and in 25 1893 , Zuckerkandl initially advocated perforation of
concluded that while theoretically easy, this operation
the middle meatus, but later abandoned the technique
the
Lynch-Howarth
external
frontoethmoi
dectomy was favoured in the UK. 40 In 1913, Mosher is credited with the first description of
an
intranasal
ethmoidectomy,
but
by
1929
he
had in practice, proven to be one of the easiest operations
with which to kill the patient!
because of the potential for orbital damage. It is of
Endoscopic surgery was traditionally divided into
interest that sporadic interest continued in middle meatal
two schools, though in practice the distinction is far less
antrostomy, predating the introduction of endoscopic 26 visualization.
approach,
The first description of the inferior meatal antrostomy 27 but routine puncture of
was probably by Gooch in 1770,
the inferior meatus was not common until advocated by 28 29 30 Krause in 1887, Mickulicz in 1887 and Lichtwitz in
definite. The primary objective of the 'Messerklinger' 41 42 43 44 championed by Stammberger , , is the removal of pathology in the ostiomeatal complex, sufficient to achieve ventilation and drainage, thereby addressing the underlying pathophysiology by a con
began the first attempts at diagnosis by proof puncture
servative technique; hence the term 'functional' endorsed 45 by Kennedy. A more radical extirp ation of disease has 6 47 been proposed by Dra� and Wigand particularly
followed by irrigation. In 1890, Lichtwitz invented the
related to polyposis, in which an absence of surgical
cannula which accompanied the perforating needle.
landmarks and profuse pathology determines a 'back
1890, using needle, trocar and stylette, respectively. Thus
Mickulicz understood the anatomical and physiologi
to-front' approach. The title, FESS (functional endoscopic
cal pitfalls of the inferior meatal antrostomy, including
sinus surgery) is therefore only appropriate when per
its propensity to closure. Shortly after its introduction,
forming limited surgery with preservation of existing
it was largely superseded by the more radical canine 31 32 fossa approach described by Caldwe1l in 1893, Spicer 33 in 1894 and LUC in 1897. This differed from that already
structures and should not be used for the many surgical
described by Lamorier and Desault in that
large number of acronyms have since appeared MESS
a nasal
indications for which the endoscope may now be utilized, e.g. orbital decompression, dacrocystorhinostomy, etc. A
counteropening was included. The Caldwell-Luc ap
(microscopic endonasal sinus surgery), MISS (minimally
proach was the primary operation during the first part
invasive sinus surgery), TSS (transitional space surgery)
of the twentieth century, but there began an increasing
to name but a few, but these have not substantially altered
trend . towards
practice and are largely variations on a theme.
lavage,
followed
by
inferior
meatal
antrostomy with Caldwell-Luc reserved for any failures. This situation pertained up to the early 1980s in the UK when endoscopic surgery first made its appearance. From the outset, operations on the frontoethmoid 34 complex fell into two groups, those designed to enhance drainage while preserving facial contour and those aimed
SURG ICAL P ROCE DURES The operations on the paranasal sinuses for treating chro
nic rhinosinusitis are listed in Table 117.2 [Grade BIC].
at eradicating diseased mucosa disregarding cosmesis. As with the maxillary sinus, initial surgical treatment of the infection concentrated on opening and draining 35 A more extreme of the frontal sinus by trephination. 36 procedure was described by Riedel in 1898 in which inferior and anterior walls were removed leading to severe cosmetic deformity. To overcome some of these problems, in 1903 Killian
37
proposed removal of the anterior and inferior walls, but with preservation of the supraorbital rims. Later, he extended dissection to include the frontal process of the maXilla to facilitate drainage through the anterior ethmoidal cells and this procedure remained popular during the beginning of the twentieth century. In 1921, it 38 amongst others,
was, however, criticized by Howarth
for leaving a 'dead space', for closure of the frontonasal recess. Howarth proposed an alternative operation which 39 n was synchronously described by Lynch i 1921 in the USA in which all diseased frontal sinus mucosa was removed and the sinus drained via an ethmoidectomy. This operation gained considerable popular in the USA ,
Endoscopic sinus surgery
INDICATIONS Whilst originally designed for the treatment of rhinosinu sitis and nasal polyposis, endoscopic sinus surgery (ESS) has been extended to a wide range of other conditions: • • • • • • • • • • • •
chronic rhinosinusitis; acute recurrent rhinosinusitis; nasal polyposis; mucocoeles; allergic fungal sinusitis and mycetoma; repair of cerebrospinal fluid (CSF) leaks; orbital and optic nerve decompression; repair of blow-out fractures; dacrocystorhinostomy; choanal atresia; hypophysectomy; septal and turbinate surgery;
i I
I
Ie
1482
I PART 13 TH E N OSE AN D P ARAN ASAL S I N U SE S
Oper atio ns on the p ar an as al si nuse s for c hr onic rhin osir) usi tis .
Table'117.2
Radical
C a Idwell -Luc
Antr a I wash out
Maxillar y si nu s
I ntr a n as a I an trost omy Mi ddle me at al (e ndo sc o pic) Fr on toe th m osph en 0 i d
I nferi or mea tal
Dr af I -I I I e ndon asal dr ain age46 Treph i n at ion of the f ront al sinu s or sphen oi d wash out
Extern a I fr on toeth mosphen oi de ctomy
I ntr a nasal e th moi de ctomy
Mi dline se ptect omy ( Lothr op: rhin ofr onta I
E ndosc opic u nci ne ct om y, e th moi dect omy, cle ar an ce of the
sin use pt otom y) Oste opl astic fl ap ( wi th or with out
( Lyn ch -Howar th , Patters on)
obii ter ati on)
fr ontal reces s, ope ni ng of the sphe noid ostium ( fu ncti on al e nd osc op ic sin us sur ger y)
Cr a ni alization of the fr ontal si nu s
Tr an santr a I e th moi de ctomy ( Ja nse n-Hor ga n)
• • •
m an agem en t of epistaxis;
antrum h as bec ome compartmentalized by 'scar tissue'.
dr ain age of peri orbi t al abscess;
Under these circumstances access may be facilitated by a
some benign a nd mali gn ant tumours.
Only
the
treatment
of chronic
small anterior
and acute
recurrent
rhi nosi nusit is c oul d be regar de d as ex ercising a 'func tional' approach, i.e. attempting to reverse pathophy siological processes by co nse rv ative surgery in define d
areas dictated by disease. It should only be offere d after an
adequate trial of medi cal treatment and, wherever
possible, treatment of any un derlyi ng factors. If such
pre disposing con di t ions exist , they will require long- term management and this is also true of conditions such
as
an trostomy.
Similarly, endonasal access to
th e frontal sinus can be t echnicall y difficult and this may
be facilitated by a combined approach through a small
opening in the anterior wall of the sinus throu gh which
angled en doscopes can be introduced. P at h ology localized in the lateral
fro ntal sin us may n ot be techn ica ll y
accessible and ma y require external approaches, but the
trauma in fr ontal recess thereby avoi din g stents and many of the
addition of endonasal endoscopy will minimize the
problems previously a ssocia ted with externa l approaches .
nasal polyposis. Nasal polyposis, in partic ular, represents
a considerable spectrum of disease, from a small area of localized oedema, where mucosal surfac e s touch, to
ANAESTHESIA
diffuse change throughout the nose and sinuses, in their
Endoscopic surge ry can be per formed under local or
mos t
general
aggress i ve form wh en
aspirin sensitivity or to
perform
associated
wjth asthma,
cystic fibrosis. It may be possible
conservative
surgery
within
the
middle
meatus, but it was for th e more extensive disease which had already undergone repeated surgery, with loss of
a naesthesia. Stamm ber ger48 and
Ke n nedy et
al.49
originally declare d a preference for loc al anaesthesia,
believing that it was
safer and
associated with less
bleeding, while Anand and Panje50 state that 'effici en cy,
reduced pain, controlled ventilation, especially for asth avoidance of aspir ation
are our primary
surgical landmarks that Wigand advocated defining the
matics and
skull base in the sphenoid an d workin g from posterior 47 to anterior. The amount of tissue removed will be
to refute the s u ggestion that local anaesthesia is safer,
determined by the surgeon's own philosophy, the extent of disease and
pa ti ent
factors.
Repres en tative
tissue
should always be sent for histology and speci mens for
microbiology may also be required.
consider
intracra ni al complica tio n
though generally complications are more likely to occur
in those pati ents with more advanced pathology, such as nasal polyposis, and it is this group which is more likely to be selected for general anaesthesi a . Local
an aest hesia
is carr i ed out in a similar m anner
to that for antral lavage, except that further injections
CONTRAIN D I CATION S Most surgeo ns
reasons for the choice of general anaesthesia'. It is difficult
that in the presence of of acute
infection,
an
such as
menin giti s, subperiosteal or epi du ral abscess, cavernous
sinus thrombosis or with any visu al loss, an endoscopic appr oac h is contrai ndi c a te d.
Access to t h e lateral wall
and floor of the maxillary sinus can also be difficult,
partic u la rly in cert ain cases of revision surgery where the
-�
../
may be ma de
with 2 percen t lignocaine (with 1:80,000)
into the un cin ate process, greater palatine foramen and middle turbinate (up to
4 mL). Al tern atively,
vasocon
striction can be achie ved with ribbon gauze soaked in
1: 1000 adrenalin packe d around the middle meat us and
su rgical
cavity.
With gener al anaesthesia , Moffatt ' s sol u tion Sl is in
stille d in the anaesthetic room
(2 mL of 2 percent sodi um
/
i
Chapter bicarbonate, 2 rnL of
1:1000
10
percent cocaine and 1
mL of
1 1 7 Surgical management of rhinosinusitis •
1483
Hopkins rod telescope should be used for most of the
adrenalin» half in each nostril. The patient's head
surgery, as it is easy to become disorientated with angled
10 minutes before transfer to the
endoscopes, though the latter are necessary for inspecting
main operating room where the patient is placed on the
recesses and performing middle meatal antrostomy or
operating table in the supine position.
operating
is left hyperextended for
If the surgeon
An
prefers to sit, the table is kept low and horizontal. If the
in the frontonasal recess (Figure 117.4a-d).
infundibulotomy is performed by incising the a
surgeon wishes to stand, the left elbow can be supported
anterior attachment of the uncinate process with
on a Loewy support placed towards the head of the
knife or Freer's elevator. The elevator can be used to lift
sickle
table and the patient put in a head-up position which
the uncinate process medially to display the infundibu
aids haemostasis. In either case, the patients are usually
lum and it is then grasped with forceps, the upper and
kept in hospital overnight and discharged the follOwing
lower attachments cut with fine scissors and the process
day (usually less than 24-hour hospital stay). Packing is
detached with a twisting motion. Care is taken with the
avoided
site of incision. If this is made too far anteriorly, the bone
if possible, though sometimes a small temporary
is hard overlying the nasolacrimal duct. Any residual rim
Telfar or Merocel pack is placed in the surgical cavity. The authors' preference is for general anaesthesia, except in
can be removed secondarily with backbiting forceps, again
those cases with minimal pathology, when the patient has
with care to avoid damage to the nasolacrimal duct. An
particularly requested a local anaesthetic or occasionally
inferior uncinectomy can be perfonned with the Ostrom
when their general state of health is so poor that general
backbiter alone, but with care as above.
anaesthesia is contraindicated.
The ethmoidal bulla is opened with a fine straight Blakesley-Wilde forceps and removed piecemeal. T he lamina papyracea is extremely
SURGICAL TECHNIQUE
yellow orbital fat
can
thin, through which the
often be discerned. Slight pressure
will demonstrate whether the lamina is
The CT scan should always be available in theatre and the
on the globe
eyes left uncovered throughout the procedure. A
dehiscent. Behind the bulla, a variable space is entered,
Figure recess.
1 1 7 .4
(b)
(a)
0° 4-mm
Parasagittal view of the lateral wall with middle turbinate lifted to show uncinate process, bulla and retrobulla
Lateral wall of the nose after removal of middle turbinate, uncinate process and opening of the bulla.
posterior ethmoids via the basal lamella of the middle turbinate.
(d)
(e)
Opening of the
Closer view of the lateral wall to demonstrate the position of the
nasal lacrimal duct anterior to the attachment of the uncinate process.
"L
,l \
I
1484 I
PART 13 TH E NOSE AND PARANASAL SI NUSES
the retrobullar recess (previously called the 'lateral sinus'),
artery. If the ostium cannot be found, the posterior
which extends above the bulla as the suprabullar recess.
fontanelle can be perforated just above the attachment of
Superiorly, the skull base may be visible and the anterior
the inferior turbinate, but failure to incorporate the
ethmoidal artery may be identified running posterior to
natural ostium can again lead to recirculation of mucus
the frontal recess.
and infection.
In many cases, this may be all that is required surgically and the decision as to whether to continue to open the
Conservation
of mucosa
in the
frontal
recess
is
generally advisable, particularly in the absence of frontal
maxillary antrum, explore the frontal recess, the posterior
sinus infection so
ethmoids and sphenoid will depend upon the extent
instilled postoperatively can often effect improvement
as to
avoid scarring. Medication
of disease as evidenced by the CT scan and operative
even when inflammation is present. To avoid bleeding
findings. The posterior ethmoids are entered by piercing
running into the operative field, it is best to reserve
the basal lamella, 3-4 mm above the horizontal attach
surgery in this area to the end of the operation. When the
ment of the turbinate adjacent to the vertical attachment
uncinate process attaches laterally on to the lamina
of the turbinate. The posterior cells are generally larger
papyracea, the infundibulum leads into the blind-ending,
and
be
terminal recess. When the uncinate process attaches
prominent in the lateral wall and the overlying bone
superiorly or rarely medially to the middle turbinate, it
extremely thin. This is
is possible to visualize the frontal recess directly with a 30
pyramidal
in
shape.
The
optic
nerve
can
particularly noticeable
in
a
sphenoethmoidal cell (Onodi) cell which is a posterior
or 40°
ethmoidal cell extending lateral and superior to the
instruments and curettes have been devised for surgery
sphenoid ( see
in this area, which is certainly the most challenging
Figure 132.2 in Chapter 132, Orbital and
scope
in most
cases.
A number
of angled
optic nerve decompression). The sphenoid can be opened
surgically. The frontal recess is usually an hourglass
from the posterior ethmoid, by entering it as inferiorly
restriction rather than a 'duct' and is often found situated
and medially as possible from the last cell. However,
medial to an opening of a suprabullar ethmoidal cell
mucociliary clearance occurs into the sphenoethmoidal
which extends over the orbital roof. Removal of this cell,
recess and it is more logical and safer to enlarge the
so-called 'uncapping' the egg will open access to the
natural ostium of the sinus rather than use the posterior
frontal sinus, ideally avoiding any circumferential removal
ethmoid approach. The ostium in the bone of the
of mucosa. Care should always be taken when operating
sphenoid varies in size, but is usually 3-4 mm in diameter
in this area to avoid damage to the anterior ethmoidal
and can usually be found by blunt probing approximately
artery and entry into the anterior cranial fossa where the
1 cm up on the anterior face of the sphenoid, adjacent to
artery traverses the medial superior ethmoidal cavity.
the septum. Identification may be aided in some cases by
The
use
of powered instrumentation
has
gained
excising a small inferior portion of superior turbinate.
considerable popularity in recent years, particularly in
This should be done with cutting instruments to avoid
the management of polypoid disease. They undoubtedly
tearing the olfactory epithelium and risking a possible
speed up the procedure and allow precise atraumatic
CSF leak. Great care must be exercised in the sphenoid
removal of soft tissue. However, the same considerations
sinus which is variable in size and shape and intimately
must be observed as with ordinary instrumentation, i.e.
related to the carotid artery and optic nerve. It is also
always know exactly where the tip of the instrument is to
worth checking the superior meatus and clearing any local
avoid complications and submit representative tissue for
pathology so that there is free access into the posterior ' ethmoidal system.
histology. The latter may be taken independently or from
Middle meatal antrostomy is not necessary if the
a tissue trap attached to the machine.
52 53 Similarly, computer-assisted surgery ( CAs) , using
natural maxillary ostium is found to be patent after
a variety of navigational systems has provoked increasing
uncinectomy. If an accessory ostium is present, it should
interest. There are a variety of systems available and each
be joined to the natural ostium to avoid abnormal
have their proponents. Clearly, CAS has a role in teaching,
recirculation of mucus. The ostium may be enlarged into
particularly in difficult areas, such as the frontal recess,
either of the respective fontanelles, but it should be
especially in revision cases. However, some issues remain,
remembered that any damage will lead to disruption of
related to cost, radiation doses from additional narrow
mucus clearance, particularly over the posterior ostial
axial slice scanning and, above all,
edge. If the ostium is not readily visible after uncinect
problems are likely to be resolved in due course.
accuracy. These
omy, palpation of the lateral wall with a blunt probe, 'J' curette or curved sucker will usually identify its position, or a few bubbles of air or mucus may be seen. Once identified, the ostium can be enlarged posteriorly with
POSTOPERATIVE MANAGEM ENT
fine forward-biting Grunwald forceps ('chompers') and
A significant component in the success of endoscopic
anteriorly and inferiorly with Stammberger Ostrom-type
surgery is postoperative care, including cleaning of the
backbiting and/or downbiting punches, again taking care
surgical cav.ity
to avoid the nasolacrimal duct and lateral sphenopalatine
important commitment on the part of the surgeon. It is
(Figure 117.Sa,b). This represents an
...i���/_�-� I,
Chapter 117 Surgical management of rhi no si nusitis I
the authors' practice to give all patients prophylactic broad-spectrum antibiotics for two weeks postoperatively, combined with alkaline nasal douche and an intranasal steroid preparation. Most patients with diffuse polyposis
1485
receive a course of oral steroids in reducing dosage (prednisolone 30 mg/20 mg/10 mg/day each for one week), if there are no contraindications. In severe cases, a similar course is given preoperatively and all patients remain on intranasal steroids prior to surgery. The patients are usually seen seven to ten days after the surgery and then as often as necessary, usually on a two-weekly basis until the cavities are well healed. For the purposes of audit, the patients are seen at least at 3, 6, 12 and 24 months postoperatively. On each visit the cavity is cleaned under endoscopic control, sometimes after application of t op ical local anaesthetic, though this is rarely required. Any adhesions are divided, debris removed, further polypoid mucosa removed and addi tional medication prescribed.
COMPLICATIONS
Figure 117.5
with
Postoperative cavity: (a) well-healed
g ra nulat i o ns
Table
117.3
54 Stankiewicz 55 Stankiewicz Stammberger
Such is the excellent visualization provided by an endoscopic approach that a false sense of security may lead the unwary into problems. In the hands of the experienced clinician, reported complications are surpris ingly few and similar to those reported by other approaches (Table 117.3). In a series of over 4000 cases, Stammberger and Wolf56 reported only two cases of CSF rhinorrhoea, no intracranial complications and no ophthalmic problems. Wigand47 reporting on 220 patients undergoing complete ethmoidectomy mainly for polyposis, reported a CSF leak in two (0.9 percent) and one case of an orbital haematoma (0.5 percent). Stankiewicz55 suggested that the complication rate decreases with increasing experience, reporting a rate of 29 percent in the first 90 cases which he performed compared with only 2.2 percent in the subsequent 90. Most of the cases were minor, such as adhesions, but there were two cases of CSF rhinorrhoea and one case of temporary blindness. (Conventional' surgery is not immune from these problems and Maniglia63 reported seven cases of blindness, four cases of CSF rhinorrhoea and two deaths following intranasal ethmoidectomy,
a nd (b)
a nd adhesions.
Complications following sinus surgery.
a nd WolfsS
Schaefer et al.57 58 Levine
59 Wigand and Hoseman 60 Freedman and Kern Watson and Griffiths61 s2 Lund
Operation
No. Rat'ients
FESS
INE
90 90 4000+ 100 250 1000 1000 105
EE
320
FESS FESS FESS FESS FESS
INE
CSF leak
Intracranial
infectipn
Orbital
Haemornage
Oe-ath
2
1 2 3
10
2 12
INE, intranasal ethmoidectomy; EE. external frontoethmoidectomy.
I I
hti/
j
1486 I
PART 1 3 TH E N OSE AN D P ARAN ASAL S IN USES
while a 2.8 percent complication rate was reported for this operation by Freedman and Kern.60 In a group 0f 650 consecutIve patI. ents,64 one patI. ent developed a CSF leak on the third postoperative day, after he sneezed. This was managed endoscopically with a free mucoperichondrial graft from the opposite side of the septum. One further case required an external ethmoi dectomy at the time of the surgery, due to an orbital haematoma resulting from bleeding from the anterior ethmoidal artery which retracted into the orbit. Both cases underwent satisfactory and uneventful postoperative recovery. There have been no cases of diplopia, blindness, meningitis or death. In a survey of British otolaryngologists,65 a question naire sent to 653 members of the British Association of Otolaryngologists, received a 57 percent response, of
degloving and craniofacial resection appear to have no detrimental effect in the long term.69 Indeed, the animal experiments which led to these concerns70 have been repeated71 and the route of access to the lateral wall has been shown to be the main cause of facial distortion rather than the (endoscopic' procedure itself. The patency of the middle meatal antrostomy appears more reliable than that of the inferior meatus despite its smaller size.72 This is probably related to it being a natural physiological fistula made predominantly in membrane rather than bone and the fact that it is generally not enlarged circumferentially.73
whom 38 percent were reportedly routinely undertaking functional endoscopic sinus surgery. The estimated complication rate was 0.24 percent, predominantly CSF leaks, followed by problems related to bleeding. All occurred in patients with diffuse polyposis. A recent audit undertaken by the Clinical Effectiveness Unit of the Royal College of Surgeons of England considered 3 128 patients with chronic rhinosinusitis/nasal polyposis in whom the majority underwent endoscopic sinus surgery. Of these, 0.2 percent developed periorbital haematoma, but there were no long-term visual problems.66 A working party of The Royal College of Surgeons of Edinburgh67 was set up to consider ways of reducing
An internet search using PubMed and the key words sinusitis and surgery, limited to publications in English with abstracts, from 1996 (when the sixth edition of Scott Brown's Otorhinolaryngology, head and neck surgery was prepared), and including all publication types produced 828 references. When the publication types were re stricted, 60 clinical trials were available of which 29 were randomized controlled trials [****] the remainder being level 2b or 3 [***1**]. The majority of the randomized controlled trials assessed adjuvant medical therapies. Two meta-analyses were available. Of these only one addressed surgery for sinusitis?4 The authors included eight published articles (832 patients) plus unpublished data from 50 patients at their own institution. The (positive' outcome rates for published, unpublished and combined data with an average follow up of 3.7 years were 88.4, 92 and 88.7 percent, respectively. The population studied was children undergoing functional endoscopic sinus surgery. In 2001, Lund75 critically reviewed outcomes of surgery for chronic rhinosinusitis and assessed the levels of evidence available at that time. Fourteen studies on the outcome of endoscopic sinus surgery were analysed. A mean of 89 percent of patients reported surgery as successfuL [**] Five papers quoted a mean of 1 1 percent of patients feeling unchanged or worse after surgery. These papers represent a range of endoscopic procedures, using a range of techniques for a range of inHammatory pathologies. In 2000, Havas and Lowinger76 provided an
.
complications associated with endoscopic sinus surgery. Among the various conclusions it included the following suggestions. •
•
•
•
•
The operator should have experience of at least a 100 diagnostic endoscopic procedures before attempting surgery. The surgeon should attend and participate in a course or workshop that allows hands-on experience. Where possible a proctor system should be encouraged with an experienced surgeon attending initial operations. Follow-up and assessment clinics should, wherever possible, be separate from the general clinics and should be used for training and audit purposes. CT scan facilities should be available.
RESULTS
Although some of these recommendations have been sub sumed in normal training programmes, the underlying tenets remain.
example of how different approaches and philosophies may exist under the single, generic heading of endoscopic sinus surgery. They carried out a randomized controlled
Concerns have been raised regarding the long-term effects of such surgery, for example as to whether surgery in the frontal recess might lead to frontoethmoidal mucocoele formation in the future and in particular the effects of endoscopic surgery on facial growth in children. This has not been supported by longitudinal clinical studies68 and indeed disruption of facial growth is unlikely given that major sinus procedures such as external ethmoidectomy, lateral rhinotomy, midfacial
trial related to removal (509 patients) or preservation (597 patients) of the middle turbinate during endoscopic sinus surgery. [***] They concluded removal was beneficial in more severe cases of rhinosinusitis. In 1996, Metson77 demonstrated in a randomized, prospec tive, single-blind study that symptom improvement was similarly significantly improved with and without use of the Holmium Yag laser. Haemostasis was less, but mucosal oedema more in the laser group. Rowe-Jones and
Chapter 117
Mackal8 looked at the outcome of endoscopic sinus surgery in a pathological subgroup, namely patients with cystic fibrosis and found they had a 50 percent chance of requiring further surgery 18 months after the index
procedure. [**] Lawson79 reported his experience of 1077 nonendo scopic ethmoidectomies: 825 were performed with sphenoidotomies, 89.5 percent were intranasal, 2.3 percent transantral and 9.5 percent performed using an external approach. The overall success rate was 73 percent
(level 3). Friedman and Katsantonis80 reported on 1 168 primary, nonendoscopic sphenoethmoidectomies of which 135 were performed transantrally. They quoted a 15.5 percent recurrence rate for hyperplastic disease. [**] Sogg81 reported on 346 consecutive nonendoscopic intranasal ethmoidectomies: 51-82 percent of patients were described as recurrence free, depending on disease groups. [**] Eiche182 similarly described findings follow ing 236 procedures. [**] 'Control rates' for varying patient groups ranged from 83 to 92 percent. These studies represent 2845 procedures on 1492 patients. There have been relatively few comparative trials of the surgical options in chronic rhinosinusitis and their methodology has been criticized by Lund.75 Studies comparing endoscopic sinus surgery with inferior meatal antrostomy or a Caldwell-Luc procedure have been performed.83,84 In Pentilla's study, a marked difference was observed in favour of endoscopic sinus surgery over the Caldwell-Luc procedure with regard to symptoms and procedure morbidity.85 Arnes et ai. found no difference between inferior meatal antrostomy and middle meatal antrostomy, although no indication of follow-up time was given.83 If a historical comparison is made between two prospective groups of chronic rhinosinusitis (65 under going inferior meatal antrostoml6 and 650 undergoing functional endoscopic sinus surgerl4) similar overall rates of subjective improvement are obtained (84 versus 87 percent, respectively). However, when the percentage of symptoms which are the same or worse following the surgery are compared, the functional endoscopic sinus surgery patients do significantly better in all cases. Once the cavity has healed well, it generally remains healthy. The main criticism of these comparative studies is that they do not compare like with like, with regard to patient population and disease. Since Lund's evidence-based review in 2001, ten clinical trials on the outcome of endoscopic sinus surgery have been published, excluding six papers on surgical techniques for frontal sinusitis, one on the treatment of maxillary sinus lesions and one on children with cystic fibrosis and polyps. Two of the ten papers provide level 2
evidence. [***] Kuehnemund et ai.87 in a multicentre study compared the extended approach with the limited
approach endoscopic sinus surgery involving 65 patients. Surgical results and symptomatology were similar in both groups of patients. Venkatachalam and Jain88 compared functional endoscopic sinus surgery with conventional
Su rgical management of rhinosinusitis I 1487
surgery and reported that 92 percent of patients improved in the former group and 76 percent in the latter group. Of the remaining eight studies, two used quality of life scores and both found significant score improvements
following endoscopic sinus surgery.89,90 [**] Ramadan in two papers described a mean of 8 1 percent success in relation to symptom questionnaire scores in children undergoing endoscopic sinus surgeryl, 92 and Jiang and Hsu93 found no difference in outcome related to age
whether child, adult or adult over 65 years. Wang et ai.94 described a mean 24-month follow up on 13 patients undergoing potassium titanyl phosphate (KTP) laser clear-out endoscopic sinus surgery for recurrent poly posis. All patients reported symptom improvement, although two patients had polyp recurrence. Jiang and Hsu95 also reported on revision endoscopic sinus surgery. In 147 patients, 65 percent were improved following surgery. Wreesmann et ai.96 reported retrospectively on 82 patients who had failed to improve with endoscopic sinus surgery. Denker's procedure was performed and 84 percent of patients reported significant symptom improvement. All these studies variously demonstrate the difficulties of assessing and comparing reported outcomes of surgery for chronic rhino sinusitis. As with any surgical procedure there can be no placebo for controL 'Functional endoscopic sinus surgery' may be used as a term representing a potential range of procedures, determined by disease extent or may be used by some as a term representing extensive marsupialization and exenteration of all sinuses regardless of disease extent. The pathological case-mix may vary widely inter- and intrastudy with as yet no clear classification based on aetiology, immuno logy, molecular biology or natural history. No prognostic staging system exists to describe disease. CoeXistent systemic disease, such as asthma, may influence prog nosis,97 but is not always included in population descriptions. Indications for surgery may vary as may postoperative medical therapy regimens. The latter may not even be included with outcomes being erroneously attributed to surgery alone. Outcome measures may also vary between studies as may follow-up times. Some may be surgeon based, such as examination, and some patient based, such as symptom scores and, more recently, quality of life scores. Outcome data may also be biased, C(ollected by parties such as the surgeon who has a vested interest in recording good results. In an attempt to overcome some of these problems, an objective assessment was conducted by Lund and Scadding98 on 200 patients with chronic rhinosinusitis, with between one and four years' follow up [***]. Symptoms were assessed by visual analogue scoring (VAS), mucociliary function by ciliary beat frequency (CBF), olfaction by quantitative olfactometry (University of Pennsylvania smell identification test, UPSIT) and olfactory threshold assessment (Olfacto-Labs, EI-Cerrito, CA, USA; pm-carbinol), nasal airway by nasal forced
1 488
I PART 1 3
TH E NOSE AND PARANASAL SI NUSES
inspiratory peak: flow, anterior rhinomanometry and in selected cases acoustic rhinometry, which provides topographical information 0 n the nasal cavity. All tests were performed
pre-
and
postoperatively when
around
three
months.
There
was
a
significant
improvement in all symptom VAS. in CBF and both olfactory tests . As expected, neither nasal inspiratory peak flow nor airway resistance altered. The acoustic rhino metry allowed some quantification of the surgical cavities created.
9 Rowe-Jones and Mackay have also looked prospec
tively at the five-year outcome of functional endoscopic sinus surgery for 109 consecutive patients
[ ***] .
Our
indications for FESS with regard to symptoms in patients with chronic rhinosinusitis with sinonasal polyps were intolerable nasal obstruction or two or more of the
following symptoms: ( 1 ) anosmia/hyposmia; (2) nasal obstruction/congestion; (3) anterior or posterior rhinor r hoea;
(4)
headachelfacial pain. Our indications for FESS
in patients with chronic rhinosinusitis (CRSS) without
polyposis were: ( 1) anosmia/hyposmia; (2) nasal block
age/congestion; (3) posterior rhinorrhoea; (4) headache/ facial pain, for more than one hour on most days, for two
months or more. All patients had failed to improve with topical steroids and antibiotics as necessary. Subjective
and
objective
outcome
measures
were
employed, including visual analogue scores and endo scopic scores, nasal mucociliary clearance times. olfactory detection thresholds and total nasal volumes measured with acoustic rhinometry. Rescue medication courses of one week of prednisolone (30. 30. 25. 20, I S , 1 0 and
5 mg)
and co-amoxiclav 625 mg eight-hourly were prescribed when symptoms postoperatively deteriorated to their p reoperative level. If a patient required one rescue course a
month
for
two
consecutive
months,
they
were
considered to have failed surgery. The number of rescue medication
courses
was
recorded
and
failure
was
described using a Kaplan-Meier plot. Six weeks after surgery. patients were randomly allocated to fluticasone propionate aqueous nasal spray (FPANS) 200 Ilg twice daily (55
patients)
or
placebo
spray
Demog raphic data on 109 consecutive patients undergoing endoscopic sinus su rgery.
the
surgical cavities were healed as much as possible, usually at
Ta b l e 1 1 7.4
(54 patients) .
Allocation was double-blind and stratified on the extent 1 00 Patient demographics are of disease on CT scan . [** * *]
Average age (years) Male Smoker Atopic CT g roup 1 CT g rou p 2 Ch ron ic rhinosi nusitis Grade 1 polyps Grade 2 polyps Grade 3 polyps Asthma ASA Idiopathic bronch iectasis Cystic fi b rosis Major Ig deficiency Primary ci l i a ry dyskinesia Sjog ren's synd rome You ng's synd rome Previous fess
FPANS
P�acebo
40 32 13
34 16
66 29
60.6 26
27
26 18
Total
'%
42
53 34
48.6
37
16 38
75
69
16 13
16
32
29
16
29
26
16
11
27
10 18
11 16
21 34
25 19
5
0
5
4.6
2
0
2
1.8
2 2
0
2
1.8
0
2 3
2 0
31
31
1 .8 2.8 0.9 0.9
0 7
10
11
4
FPANS, fluticasone propionate a q u eous nasal spray; CT g roup 1 , Lu nd and
Mackay score of 5 or less; CT g ro u p 2, score of 6 or mo re ; ASA, asp i ri n sensitive asthma; Ig. i m m u noglobulin. perm i ssi o n .
Re pri nted from Ref.
100 with
Ta ble 1 1 7.5
Changes in outcome measures for 72 patients attending for assessment five years after endoscopic sinus surgery. Ou(come measure
I m proved %
Overall VAS 88.9 Total VAS 95.8 Endoscopic d ischarge score 87. 5 Endoscopic oedema score 93. 1 85.2 Endoscopic polyp score O DT 29.7 NMCC 65.7 Total nasal volu me 81.2
Same %
Worse om
8. 3
2.8
2.8 11 . 1
1.4
6.9 13
0
38.9
23.6 0
33.3 0
1.4 1 .9
1 8.8
VAS, vi sual analogue score; ODT, olfactory detection threshold; NMCC, nasal mucoci l iary cle a ra n ce . Repri n ted from Ref. 1 00, w ith permission.
listed in Table 1 17.4. Ninety-five patients attended for
follow-up at year I , 87 at year 2, 77 at year 3, 73 at year 4
and 72 (66 percent) at year 5. Wilcoxon signed rank
analysis was used to compare each patient's p reoperative
score
with their postop erative score at six weeks and a l
Table 117.5 shows the change in relation to preoperative scores for the 72 patients attending at five years. Twenty six of these 72 patients had required rescue medication. O ver the period of the study, 3 8 p ati en ts r e quired a to tal
88
one, two, three, four and five years. At each time period
of
the mean change in visual analogue score representing
required further surgery. Table 1 17.6 shows the failures
courses of rescue medication and six: patients
how the patients felt overall had significantly improved as
over five years and Figure 117.6 the Kaplan-Meier plot.
had that for the sum of all the visual analogue scores. the
The p ostoperative five-year survival rate for not failing
endoscopic polyp, oedema and discharge scores, the nasal
was 84 percent. The
mucociliary clearance times and increase in total nasal
group demonstrated similarly significant improvements
volume. The olfactory detection thresholds were signifi cantly improved only at six weeks. one and two years.
in outcome ,measures to the placebo and FPANS groups combined.
54
patients in the placebo treatment
Chapter
1 1 7 Surg lca I ma nage ment of rhinosi n usitis I
1489
Mann-Whitney U testing was employed to assess the
antibiotics ( erythromycin or c1arithromycin) or endo
impact of postoperative FPANS on outcome. The change
scopic sinus surgery following a six-week run-in with
I , 3,
in outcome measure for each patient at each time p erio d
topical treatment. Patients were assessed at
was compared with the value recorded for them six weeks
months using a visual analogue score, quality o f life
SNOT-20) ,
6 and 1 2
after surgery. The mean change in the FPANS group was
instruments ( SF-36 and
compared with the mean change in the placeb o group. In
levels in respiratory gases, acoustic rhinometry, nasomu
each treatment group, the last value recorded before
co ciliary clearance time and nasal endoscopy. At the end
failing or being lost to follow-up was carried forward to
of three months there was improvement in all subjective
(p < 0.0 1 )
expired nitric oxide
be included in each subsequent time period analysis.
and objective parameters
Outcomes for overall visual analogue score, endoscopic
no difference between the medical and surgical groups
overall, but there was
polyp score and total nasal volume were significantly
(p < 0 . 5 ) ,
b etter in the FPANS group at five years. Three patients
surgical group as measured by aco ustic rhinometry. These
percent) in the FPANS gro up and 1 1 (20 p ercent) in
levels of improvement were maintained at one year with
the placebo group failed. This difference is significant at
no significant difference between the 3- and 1 2 - month
(5.5
0.05
the
level and represents five-year survival rates of
93
and 74 percent, respectively.99 In a recent randomized, prospective trial comparing
findings.
except that total nasal volume was larger in the
This
further serves to emphasize the importance
of undertaking an adequate course of medical therapy before embarking on surgery. I O I
medical and surgical treatment of patients with chronic rhinosinusitis/nasal polyposis, a cohort of 90 patients was
randomized to either a three-month course of macrolide
Sta g i n g of rh i n os i n u s itis I n an
Ta b l e 1 1 7 . 6
Th e num ber of patients by nasal diagnosis, failing
No. of patients (%)
Time of failure (months)
Crss Grade Grade Grade
some
of t h e problems
b een addressed by several authors 1 02, 1
0 3, 1 04 but many
systems suffer from a complexity which has precluded their
entering routine
approach was devised 1
18 36 33 27
2 (6) 2 (6.8) 2 (7) 8 (1 4) 1 4 (1 2.8)
1 polyps 2 polyps 3 polyps
overcome
on trying to stage the extent of inflammation. This has
endoscopic surgery over a five-year fol low- up.
N'a��1 diagnosis
attempt t o
encountered in result assessment, interest has focused
clinical
practice.
A simplified
00 which produces a numerical
score for four aspects of the condition and this has been used
average
in
a
number
of outcome
studies
in
chronic
rhinosinusitis ( Tables 1 1 7.7, 1 1 7.8, 1 17.9 and l S, 6 1 17. 1 0 ) . O 1 0 However, the development of any staging
28.5
system is an evolutionary process and the simplicity of the above may be criticized for overdiagnosing disease extent
Rep ri n ted from Ref. 1 00, with permission.
when secretion, rather than mucosal change, produces sinus opacification or for the difficulties in interpreting
Survival function
1 . 02
change due to previous surgery. Imaging represents a snapshot in time and these problems are common to all staging or scoring systems dependent on this modality.
CT
1 .00
changes are known to correlate po orly with patient
symptoms and staging has proved of variable utility in (tj
0.98
predicting outcome. In addition, CT poses ethical and
0.96
Tab l e
>
.� ::! CJJ
� � "'S E ::! ()
1 1 7.7
The Lund and M a ckay staging syste m : radiolog i c
stagi ng .
0.94
left
0.92
Right
Max i l l a ry (0/1 /2) Anterior ethmoids
0.90
Posterior ethmoids
(0/1 /2) (0/1 /2)
[6X2=12]X2=24
Sphe noid
0.88
0
10
20
30
40
50
60
Frontal
70
Time when failed in months
Figure
1 1 7.6
Ka p la n-Meier plot of fai l ures following e ndoscopic
sinus surgery. Redrawn from Ref.
..,
1 00,
wi th permission.
(0/1 /2) (0/1 /2)
Ostiometal com plex
(0
or
2
only) 3
Total points
O. no abnormalities; 1, partical opacifica tion; 2, total opacification. a D, not occluded ; 2, occl uded. Repri n ted from Ref. 1 00, with perm i ss i o n.
- ·L- � -;;-)h( f ___
_ ..: -:-:-:-:. _ •..J
1490
I PART 1 3 TH E NOSE AN D PARANASAL SIN U SES
cost
considerations.
a
As
po sto p er ati ve
evalu ator
of
success it does provide inclusion criteria fo r stu di es i n a
condition where symptoms are Wlreliable p redictors of
Ta b l e 1 1 7.8
pathology and consequ ently con tin ues to be one of the few 'objective' i nvestigations.
[**1*]
Antral lava g e
The Lund and M a c kay staging system: surgery
score.
Right
Antral lavage has been used b oth in th e diagnosis of and
treatment of rhinosinusitis though its previ o u s diagnostic
Anterior ethmoidectomy Fronta l recess surgery
role
7X2=14
Middle meatal antrostomy
the
treatment
of
a cute
maxillary sinu sitis whlch has
failed to respond to conservative medication and
a djun c tive
Sphenoidectomy Uncinectomy
Antral puncture is usually performed thro ugh the and in the past was often performed
Tota I points each side Total points both sides
inferior meatus
0, no procedure ca rried out; 1 , surgery carried out. Maxim um 0 to 14 (0 to 7 each side) . Reprinted from Ref. 100, with perm i ssion.
Score as follows:
several times before proceeding to formal inferior
meatal
fenestration. One alternative to repeat ed p uncture was the
The Lund and Mackay staging system : symptom score.
1:.Sl/rnl�tum (score by
ana ague method)
vimal
Facial pain or pressure Headache
is
plain sinus x-ray by proof puncture
as an p r ocedu re to external drainage for acute o rb i t al co mpl icatio n s .
Reduction of middle turbi nate
Tab l e 1 1 7.9
to clarify
obsolete. Therapeutically, it is still sometimes used in
Posterior ethmoidectomy
score is
I N D I CATIONS
BaselillJ
3 months
6 months
1
year
2
yea
s
( 1- 10)
(1-10)
Nasal blockage or congestion
(1- 10)
Nasal discharge
( 1- 10) Olfactory disturbance (1-10) Overall discomfort ( 1- 10)
5X10=60
Total points eac h visit
0,
symptom n ot present;
Ta ble 1 1 7 . 1 0
0- 1 0.
deg ree of symptom severity, w i th
10
i n d i cating greatest severity. Repri n ted from Ref.
1 00,
w i th perm ission.
The Lund and Mackay staging syste m : endosco p i c app earance score.
Baseline
3 months
1
6 month
year
(0, 1, 2, 3) (0, 1 , 2, 3) Oedema, left (0, 1, 2) Oedema, right (0, 1, 2) Discharge, left (0, 1, 2) Discharge, rig ht (0, 1, 2) Polyp, left
Poly p, right
Posto perative scores t o b e used for outco me assessment only Searring, left
(0, 1, 2) (0, 1, 2) left (0, 1, 2) rig ht (0, 1 , 2)
Scarring, rig ht Crusting , Crusting,
Total points Polyps:
0,
absence of polyps;
1,
polyps i n m i d d l e meatus only; 2, polyps beyond the m i d d l e m ea t us, but not completely obstructing the nose ; 3 , polyps
com pl e te ly obstru cting the nose.
0, a bsent; 1 , m i l d ; 2, severe. 0, no d ischa rge ; 1 , c l ear, th in discharg e ; Sca rri n g : 0, a bse n t ; 1 , m i l d ; 2 , severe. Crustin g : 0, a bsent; 1, m i l d ; 2, severe. Repri n ted from Ref. 1 00, with perm ission. Oedema :
Discharge :
2 , thick purulent disc.harge.
.I
Cha pter
117
Su rgical management of rh i n osin usitis I 1491
insertion of an indwelling catheter through which daily
vasoconstricting agents, such as 25 percent cocaine paste,
irrigation
performed
which can be spread in the surgical field with a cotton
which antral washout is performed will vary between
wool bud, under electrocardiogram (ECG) monitoring. S1 can be instilled by the Alternatively, Moffatt's solution
surgeons, with many now rarely employing the technique
anaesthetist.
could
be
until the quantity 107 The frequency with and quality of secretion improves.
and preferring a definitive endoscopic middle meatal approach
to
enlarge
the natural
ostium.
Aspiration
devices, for example Sinujet, have been developed to provide
microbiological
culture.
Perforation
of the
SURGI CAL TECHNIQUE
With the patient seated comfortably, the wool carriers
anterior wall through the canine fossa may also be
or
performed for lavage or for sinoscopy.
visualized
pledgets
are
using
removed a
and
Thudicum
the
inferior
speculum
or
meatus a
rigid
endoscope. A Tilley-Lichtwiz trocar and cannula are used for the puncture and it is advisable to check that the
CONTRAIN D I CATIONS
instruments match, engaging smoothly and with a sharp
The proximity of the orbital floor and the teeth in the
trocar end protruding 3 mm from the cannial. This is
small maxillary sinus of a child under the age of three
passed under the attachment of the inferior turbinate up to the genu where it will naturally come to rest. The
years makes antral puncture hazardous and is, therefore, rarely performed. Similarly, in the hypoplastic maxilla
instruments are held with the body of the trocar in the
with thick bony walls, puncture may be technically
palm of the hand and the index finger running along the
difficult. In the presence of trauma which may have
shaft so movement is controlled. Holding the patient's
disrupted the orbital floor, antral washout is contra
head steady, the trocar is directed towards the tragus of
indicated and if drainage of a haematoma is deemed
the ipsilateral ear. Moderate pressure accompanied by a gentle boring
necessary, a formal antrostomy is safer.
action is usually sufficient to perforate the inferior meatal wall at its thinnest point. The trocar is advanced until it
ANAESTH ESIA
abuts the opposite antral wall and then is withdrawn several millimetres
anaesthetic.
removed. The patient now leans forwards, holding a
Local anaesthesia
instructed to breathe through the mouth and to mention
bowl beneath the chin to collect the washings and is
The nasal cavities are first sprayed with
1 0 percent
cocaine and 1 : 1000 adrenalin solution and left for three
any discomfort as the lavage proceeds. The washout is performed using a Higginson syringe and sterile normal
to four minutes, or cophenylcaine forte. This leads to
saline or water at 3 7°C. As fluid is flushed into the
shrinkage of the mucosa and facilitates insertion of cotton
sinus, the majority returns via the anterior nares, but
wool into the inferior meatus and drainage from the
any running posteriorly readily runs out of the mouth
middle meatus through the natural ostium. Pledgets
into the bowl. Washings can be sent for bacteriological
of cotton wool soaked in 10 percent cocaine and 1 : 1000 adrenaine solution can be placed along the inferior meatus and left for a further four minutes. Alternatively
25 percent cocaine paste on malleable silver wire
wool carriers or Tumarki wires can be placed ideally
and cytological examination though it may be preferable to aspirate with an empty syringe before attachment of the Higginson apparatus to obtain an undiluted specimen. If the procedure is performed under general anaes
close to
thesia, the patient" is placed in the tonsil position, with a
the sphenopalatine ganglion at the posterior end of the
Boyle-Davis gag in place or in reverse Trendelenberg
at the genu of the inferior turbinate
and
middle meatus.
position with 1 5 ° of head flexion and a throat pack. In
been some recent discussion concerning the safety of its
either case, lavage is achieved with an ordinary hypo dermic syringe containing 5-1 0 mL of fluid which is
Cocaine can cause adverse side effects and there has use in combination with adrenalin. Gastric absorption is
introduced and
more rapid than that from the nasal mucosa so excessive
overflow in the nasopharynx. If the natural ostium is
cocaine
occluded, drainage may be facilitated by the introduction
trickling
down
the
nasopharynx
should
be
avoided. The maximal dose of cocaine for an adult is
usually between 1 00 and 200 mg or up to 3 mg/kg.
L�d
with
children
avoid
unnecessary
of a second cannula alongside the first. Excessive pressure should never be used. Care should also be taken not to
:
has been described.
This is rarely required for antral washouts alone unless dealing
then aspirated to
introduce air during the procedure as fatal air embolus
Genera l anaesthesia
I
(Figure 117.7). The trocar is then
Antral washout can be performed under local or general
or
anxious
adults.
A
cuffed
oral endotracheal tube is employed and haemostasis acce� facilimted by addl onru locru anaesilietic
If a purulent washout is obtained, lavage is co ntinued
until it is clear. If the washout is initially clear, in stillation should continue as mucoid material may require some
loosening. Following adequate lavage, the cannula is
J
!
-' -
,_ .. --- - - .-
- . - -- -- - - - - . - -- -
4
1492 I
PART 1 3 TH E N OSE AND PARANASAL S I N USES
I nfer ior meata l antrostomy I N D I CATIONS
This
op era t i on
has
tradition ally
been used in the
treatment o f acute, recurrent and chronic
maxillary
sin usitis which has failed to respond to conservative managemen t .
p erform ed
In 1 986, it was the B ritish
by
most common operation
otolaryngologists
for
chronic
s i nu siti s, but it has been sup ersede d by mi ddle meatal 65 It relies upon gr avitation al drainage and su rgery,
aeration to effect improvement may therefore be theoretiCally of and
primary
in sinus mucosa and benefit in cystic fibrosis
dyski nesia,
ciliary
tho ugh
em ployed under these circumstances.
it
is
rarely
AN AESTH ESIA
Altho ugh the operation can be performed under local anaesthesia, general anaesthesia with a cuffed oral endotracheal tub e or laryng eal mask and pharyngeal pack is preferable. The use of topical anaesthetic agents such as Moffatt 's solution
are
mucosa prior to sur g ery.
useful in preparing
the
n asal
SURG I CAL TECH N I QU E Fi g u re 1 1 7.7
line of in troduct ion of trochar and cannula i n to
maxillary sinus in a n tral washout.
The surgical techniqu e
(Figure 1 17,8) involves the patient
being prep ared and towelled with 1 5 ° of head flexion, in a reverse Trendelenberg position. A headli ght, illuminated
removed and t he pa t ient warned that fl uid may continue to d rain fro m the nose over t he next few ho urs.
Killi an speculum, microscope or rigid end oscope can be used for illumination. The inferio r turbinate is elevated with a
Hill elevator. This i ns t r ument is then used to
perforate the inferior meatus at the highest point under the genu o f the turbinate where the bone is thi nnest.
COM PLICATIO NS
Mild haemo rrhage may occur fro m the pun cture site which can be sto pp ed with a temporary nasal pack d uring
Enlargement is then perform ed
in all directions using a
variety of instruments, e.g. posteriorly with Gru nwald
nasal turbinate forceps and superiorly and inferiorly with
in hospi t al . I ncorrect positioning of the cannula should not occur if the techn i que described is followed. However, t he a n terior wall can be breached leadin g to pain and swelling of the cheek. This is rapi dly noticed in the conscious pat ient but, under general anaesthesia, requires observation and palpation . Similarly, perforation
antrostomies and it is, there fo re, not surprising that they
o f the orbital floor leads to immediate pain. Under
but, ideally,
general ana esthesia, bulging of the orbital contents may
long-term patency is
which time the p atien t must remain
be observed and for this reason the eyes must always be left:
u ntaped and the upper lids gently elevated by
an assistant. In the presence of a deruscent infraorbital canal,
even
a correctly placed cannula can
this
complication.
the
cannula can lead to - penetration
Excessive zeal
prod uce
on introduction of the
or posterolateral wall, but this is rare.
In
of
lateral
all these
circumstances, the proced ure should be abandoned and antibiotics given .
a Hayek antrum punch forceps, either up- or down cutting . s6 The Ostrom forceps which are frequently used to cut anteriorly, were designed to perform middle mea t al
freq uently break when incorrectly used on the hard bone
of the inferior meatus.
108
Anatomical constraints limit the size of the ant rostomy
at least 2
x
1
em
windows are fashioned if
d es i red . Care shou ld be t aken to
lower the inferior edge as much as possible to minimize
the inevit able sump whi ch results between the £J oor of the nasal cavity and that of the maxillary sinus. The ,inferior edge may be covered with a m u cosal flap . While discrete polyps can be
blind ly recommended. A
removed via the antrosto my,
curett in g with a Mackie curette is not
rigid endoscope may, however, be inserted to inspect
directly the, antru m and pa tho l o gy removed und er d irec t
v i sion .
/
;'
Cha pter 1 1 7 S u rg ical management of rhinosinusitis
After
I 1 493
in itial fash i oning, all inferior meatal antros
tomies undergo so me circumferential closure due to heali ng, on average
0.4 cm. However, complete closure
may be anticipated if the antrostomy is made 1 cm or less 86 in diameter.
Caldwe l l-Luc procedure I N D I CATI O NS
The operation
was
designed
to
remove
'irreversibly'
damaged mucosa of the maxillary sinus and to facilitate gravitational drainage and aeration via an inferior meatal antrostomy. It has p redominantly been used for persistent chronic rhinosinusitis when medication, lavage and inferior meatal antrostomy has failed . However, it is not normal ciliated respiratory epithelium which
replaces d iseased
mucosa and the cavity becomes partially obliterated by fibrous tissue which may of
retention
cysts.
be
The
associated with the formation numbers
of
thls
procedure
perfonned in the UK have gradually fallen and although the following list gives the range of potential indications, in reality it is principally utilized as a route of access: • •
• • •
• •
chronic maxillary sinusitis; removal of foreign bodies, such as a dental root or amalgam; closure of
an
or antr al fistula;
dental cysts involving the antrum; access to the p terygomaxillary fissure and pterygopalatine fossa; removal of recurrent antrochoanal polyps; access to the orbital floor for elevation and
in 'imploding' antra (see 1 32, Orbital and optic nerve decompression)
stabilization for fractures or Chapter
or removal of the floor fo r orbital decompression. It is not recommended as Fig u re 1 1 7.8
Photog raph of inferior meatal an trostomy.
a
route for biopsy of antral
malignancy as it po tentiaUy opens a h itherto unaffected area to contamination.
The i nferior turbinate should be repositioned at the end of the procedure and a pack may be placed in the nasal cavity overnight. S uction cleaning and do uching
CONTRAI N DICA TIO NS
It is rarely performed in children as damage to the
may be used postoperatively.
secondary dentition
can
result.
COM PLiCATI O N S
If the antrostomy is extended too far posterio rly, the
ANAESTH ESIA
inferior meatal branch of the lateral sphenopalatine artery
Whilst the operation may be performed under local
is encountered, resulting in significant haemorrhage.
anaesthesia
Anterior extension
may damage branches
of the
(using
a
maxillary
nerve
block)
commonly carried out under general anaesthesia
it
is
with a
anterior superior alveo lar nerve pl exus leading to altered
cuffed endotracheal tube or laryngeal mask and phar
dental
yngeal pack. The use of topical local anaesthesia within
sensation,
underestimated
the
incidence
of
which
has
been
in the past. Damage to the nasolacrimal
the inferior meatus and injection of
1 : 2,000,000 ad rena
duct orifice is fortunately rare due to its position and the
line into the gingivolabial sulcus and soft tissue of the
thickness of the surrounding bone.
canine fossa is recommended .
/
"'1
l
1494
I PART 1 3 THE NOSE AN D PARANASAL SINU SES
SURGICA L TECH N I QU E
The headlight or illuminated speculum is used with the patient positioned in a reverse Trendelenberg position with 1 5 0 of head flexion. An incision is made down to the
bone in the gum margin, 3 mm above and p arallel to the gingivolabial fold from the posterior edge of the lateral incisor to the first or second molar tooth ( 3-4 cm) . It is
advisable that the incision does not directly overlie the
opening in the anterior face o f the maxilla so as to lessen
(Figure 1 17.9). The mucoperiosteal flap is then dissected s up eriorly
the risk of a fistula
with a p eriosteal elevator to expose the anterior wall of the sinus, taking care to avoid damage to the infraorbital nerve arising from its foramen just below the orbital rim, either directly or indirectly from retraction. The anterior wall is opened in the canine fossa where the bone is relatively thin (see
Figure 1 17.9) with a 5-mm Jenkins
gouge or more precisely with a drill. The opening can be enlarged with Hayek or Kerrison punch forceps to produce a hole sufficiently large to provide access, for
branches of the sphenopalatine artery. Bleeding from the bony edge can be controlled by crushing the bone with p u nch forceps or by diathermy, but this usually settles once the mucosa is removed. As originally described, the entire lining of the sinus is
dissected and removed as the success of the operation in chronic rhinosinusitis was thought to
depend
upon
complete extirpation of the mucosa. This can be difficult to achieve in the inferolateral angle and roof. A large inferior meatal
antrostomy
(2
x
1 cm) is
fashioned as previously described. Packing of the nasal
cavity and occasionally of the antrum via the antrostomy is sometimes required. Suturing of the buccal incision is recommended with absorbable sutUre material to decrease the risk of fistula formation, but should be sufficiently loose to allow drainage of blood. The patient should be advised against overenthusiastic blowing of the nose for at least a week and should replace
upper dentures within 24 ho urs to avoid obliteration of
the labioalveolar sulcus.
example to allow removal of the sinus mucosa (approxi mately 1- 1 . 5 cm diameter) or introduction of an endo scope and instruments. Inferior extension may lead to damage to the teeth and their nerve supply and laterally bleeding may be enco untered from the anterolateral
C O M P LI CATI O N S
Pain and soft tissue sweJJing are minimized b y attention to surgical technique. Haemorrhage can occur from the anterior wall or inferior meatal antrostomy, but is rarely a problem. Paraesthesia due to damage of the infraorbital nerve may be temporary or permanent and has been reported in
21 percent of cases.8S
It may be minimized by careful
dissection and retraction. In the long term, patients may complain of significant neuralgia in the distribution of the infraorbital nerve. Damage to the teeth and their innervation can lead to alteration in dental sensation and occasionally devitalization and discolouration of the teeth. An oroantral fistula occasionally occurs, particularly if care is not taken with siting of the incision. The fistula may be temporary or p ermanent, requiring subsequent surgical intervention. The mucosa which regrows in the maxillary sinus is abnormal b oth histologically and functionally. 109 In
addition, retention cysts, sufficiently large to fill and expand the sinus have been described, particularly in the Japanese literature. 1 10
I ntra n a sa l eth moidectomy I N D I CATI O N S
The principal indication for this procedure has been chronic rhinosinusitis associated with nasal polyposis.
Fig u re
1 1 7.9
a ppr oa c h
.
S i te of a nteri or a n t r ostomy in m ini-Caldwell-Luc
As originally describep and performed with headlight
illumination, it provides an inadequate approach for complete exenteration of the ethmoid complex.
j
Cha pter 117 S u rgical m a na ge ment of rh inosin usitis
I 1 495
CONTRAI N D I CATIONS
CONTRAI N D I CATIONS
The procedure has largely been superseded by an endoscopic approach to this area, as without adequate visualization it is particularly hazardous.
The inadequate approach afforded to the ethmoids has significantly limited its use.
SU RGI CAL TECHNIQU E SURG I CAL TECHNI QU E
The operation is generally performed under general anaesthesia with topical vasoconstrictors to improve haemostasis and in a reverse Trendelenberg position with 15° of head flexion with the eyes uncovered. Essentially, the ethmoidal labyrinth is cleared between vertical attachment of the middle turbinate medially and the lamina papyracea laterally using small Tilley-Henckel forceps. Care is taken not to open these towards the lamina. The ethmoids may be cleared superiorly until the hard white bone of the fovea ethmoidalis is seen. Ine posterior system may be entered by traversing the basal lamella of the middle turbinate and the turbinate should be preserved as a surgical landmark for this or future procedures. The sphenoid may also be entered, though taking care to do so as inferiorly and medially as possible from the posterior ethmoid system. All material removed should be examined for the presence of orbital fat which will float in water.
COM PLi CATIONS
Injury to the lamina papyracea may lead to haemorrhage which can produce a periorbital haematoma, erroneously considered by some as the hallmark of a successful operation. Posterior tracking of the haematoma leads to proptosis and risks visual loss, necessitating removal of packing and orbital decompression via an external approach. I l l Direct injury to the orbital periosteum can lead to prolapse of fat into the surgical field, followed by direct damage to the medial rectus muscle and optic nerve. Dural injury via the medial ethmoidal roof can result in a cerebrospinal fluid leak which can be repaired in a number of ways. Thus both blindness and meningitis are possible sequelae of this surgery and careful monitoring of the patient must be instituted postoperatively.
Tra nsa ntra l eth moidectomy - J a n sen Horg a n proced u re IND I CATI ONS
Transantral ethmoidectomy (Jansen-Horgan pro cedure1 12, 1 13) combines a Caldwell-Luc approach with access to the ethmoids and was originally described for chronic antroethmoiditis. It has also been used as a route for orbital decompression.
bs
After performing a routine Caldwell-Luc approach, the posterior ethmoid cells are opened through the antrum by pushing a closed Tilley-Henckel forceps upwards, medially and posteriorly at the upper and inner angle of the antrum, in the direction of the opposite parietal eminence. Those cells which can be safely reached are cleared though the angle of approach will inevitably limit access. It may be combined with an intransal ethmoi dectomy to clear the anterior cells more effectively. COM PLiCATIONS
Complications are as for intranasal ethmoidectomy and Caldwell-Luc procedures.
R H I N OSI N USITIS I N CH I LDREN The management of children with recurrent or chronic sinus infection (see Chapter 83, Paediatric rhinosinusitis) has always been a source of debate. Radical surgery is generally avoided because of concerns regarding the long term effects on dentition. In most cases when medical treatment failed, antral washout, combined with adeno tosillectomy was the mainstay of surgical management on the basis that the tonsils and adenoids acted as reservoirs of infection, with inferior meatal antrostomy reserved for recalcitrant cases. It should always be remembered, however, that congenital abnormalities of immune and mucociliary function may present in the upper respira tory tract at a young age and these should be considered in any individual who does not improve with conservative therapy. In addition, there is evidence that allergy may contribute to the development of infection 1 14 and should always be adequately treated. Endoscopic sinus surgery in the paediatric population has raised a number of concerns related to the necessity for imaging, potential complications, the possible need for subsequent general anaesthetics to perform postoperative cleaning arid suggestions that in the long term this surgery may create frontoethmoidal mucocoeles or affect facial growth. Luskl 15 was at the forefront of introducing functional endoscopic sinus surgery in children and has emphasized the need for great care in both patient selection and surgical conservatism. There does not appear to be any evidence of abnormal midfacial growth in children under going radical ethmoidal surgery such as lateral rhinotomy or craniofacial resection for benign neoplasia, and subsequent longitudinal studies in endoscopic sinus surgery have not shown any significant clinical problems (see Endoscopic sinus surgery). However, caution is
f'
1496 I
PART
1 3 TH E NOSE AN D PARANASAL S I N USES
certainly required in advo cating this surgery and should
Defi ci e n ci es i n cu r r e n t kn ow l ed g e a n d a rea s fo r futu re resea rch
only be undertaken by experienced surgeons familiar both with the technique and p aediatric anatomy. [***]
>- Novel m edical thera pies may reduce the number of
CO N CLU S I O N S
patients who req u i re su rgery and should be tested in randomized control trials.
A range o f operations exists for the treatment o f acute and chromc rhinosinusitis. The choice
>- The uti l i ty, accuracy a nd cost of computer-assisted
will be determined by
surgery requires further development and assessment.
the experience and philosophical attitude of the surgeon.
>- Robust longitudinal studies of patients undergoing
The importance of the ostiomeatal region in the develop ! ment of infection has b een recognized for a centu and
both med ica l and surgical treatment of rh inosinusitis
rY
are required.
the diagnostic role of the endoscope and CT scan is well established. An endoscopic approach offers many advan tages
over
more
'conventional'
op erations,
but
also
requires specific training; however, endoscopic surgery is not applicable to
all cases of sinus inflammation and with an external frontoeth
infection. Indeed, experience
moidectomy approach is a prerequisite for under taking endoscopic surgery in case an acute orbital haematoma develops
during
importance
is
the
the
operation.
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1 992; 6: 5-1 2.
Ke n n edy OW. Prog n ostic factors, outcom es a n d sta g i n g i n eth moid s i n u s s u rg e ry. Laryngoscope.
rh i n osi n usitis-specific o u tco me measu re. Rhinology.
91.
G a s k i ns RE. A surgica l sta g i n g system for chro n i c sin usitis. American Journal of Rhinology.
1 03.
Fa h m y FF, M cCo m b e A, McKi e rn a n DC. Si n o n asa l assessment q uesti o n n a i re, a patie nt-focused,
90.
I 1499
1 1 5.
1 992 ; 3 : 1 01 -5.
Lusk R. Pediatric Sinusitis. New Yo rk: Raven Press,
1 992.
/.
_
_." __
a _ - _ ___ ------
...... -_....-.... - · ..... *'--1
_ _ _____
h
S
SI
WOLFGANG DRAF
problems
1524
Conclusion
Introduction, comprehensive anatomy and specific
1500
Key points
1524 1525
Embryological and pathophysiologic considerations
1500
Best clinical
Clinical cllagnc)sls
1501
Deficiencies in current knowledge and areas for future
Clinical
1502
n�thl'\l,nn\J
1525
research
Trauma of the frontal sinus
1505
Acknowledgements
Inflammatory diseases of the frontal sinus
1507
References
Tumours
1520
The data in this
a search of PubMed
are
the
words frontal sinus
1525
frontal sinus
frontal sinus surgery and frontal sinus neoplasm. In
frontal sinus
malformation, frontal sinus
1525
the reader with some
addition, leading textbooks and relevant publications are included in the list of references to historical background as a basis for further research.
INTRODUCTION. COMPREHENSIVE ANATOMY AND SPECIFIC PROBLEMS
becomes chronic. In addition, frontal cells the frontal sinus, when he
The frontal sinus varies
In
and
of its
the
(Figure 118.1)
can mislead the surgeon into thinking that he is in
in
still in a frontal cell.
Since the renaissance of endonasal surgery via
visual
such as the
and
Killian's infundibulum. The infundibulum opens with
endoscope,4> 5, 6, 7, 8 it has been established that preexisting
its lowest
frontal sinus disease has not always healed
into the frontonasal recess, which ends in
and
the anterosuperior area of the ethmoidal infundibulum in the middle meatus with the frontal ostium.1 As the rt1l"�11"" "
NO
of the frontal sinus is downwards, acute sinusitis
usually heals fast and chronic frontal sinusitis is less
that an initially clear
frontal sinus shows evidence of inflammatory reaction after
sinus surgery. For this reason, the frontal 10,11
sinus has been the topic of much discussion.9,
than, for example, maxillary sinusitis because of the high position of the in less favourable
sinus
�V�i�A,'"
The width and course of the frontonasal recess, be it straight or curved, depends on the size and number of the anterior ethmoidal cells, some of which develop into the frontal sinus and are then called 'frontal cells'l or 'frontal bulla',2 The more the frontonasal recess is of curved configurat�Qn and the more frontal cells have developed into the frontal
the easier
an
acute frontal sinusitis
AND CONSIDERATIONS The frontal sinus is absent at birth and only becomes obvious at 6-12 months of age. It ae,relcms: •
by direct extension of the whole frontal receSSj
•
from one or more of the anterior ethmoid cells;
Chapter
118
The frontal sinus I
1501
PALPATION
Painful percussion of the anterior wall is an extremely reliable sign of acute frontal sinusitis or a pyocoele. In the case
of
anterior
wall
bulging,
a
sharp
margin
of
percussion is suspicious for frontal bone osteomyelitis and indicates the extent of disease. In patients with acute sinusitis, the area which is painful to percussion is more diffuse. In the case of painless percussion in a patient with a bulging anterior wall, diagnosis of a mucocoele, a tumour or a pneumatosinus dilatans of the frontal sinus should be considered. Another useful test is thumb pressure on the frontal sinus floor. Pain strongly indicates a diagnosis of acute frontal sinusitis. Care must be taken to press the floor Figure 11 8.1
Frontal sin us view from above after corona I
osteoplastic revision. Several frontal cells of different sizes narrow the drainage into the nose (* marks the cells). •
occasionally from the ventral extremity of the
clearly behind the supraorbital rim and not at the area of the supratrochlear or the supraorbital foramen, where pain with pressure means irritation of the different branches of the supraorbital nerve or the first branch of the trigeminal nerve .
ethmoidal infundibulum.
'The embryological origin of the sinus is responsible for the mucous patterns which may recirculate in the frontal recess along its medial wall.12 There
is no doubt that minor or more extended in the middle
anatomical and pathophysiological changes meatus,
such
as
malformation,
trawna,
infl ammatory
disease, as well as tumour may cause retention of mucus and mucocoele, not only in the maxillary sinus and ethmoid
but also in the frontal sinus. 13,
14
In the
case
of predisposing
anatomical factors, frontal sinus pathology may not respond
to conservative therapy and
will require surgery.
ANTERIOR RHINOSCOPY AND ENDOSCOPY
Classical anterior rhinoscopy using a mirror or electric headlight is not very efficient for examining the nasal cavity and the middle meatus to the area into which the frontal sinus drains. It is better to examine the inside of the nose using a microscope, which provides excellent illumination and magnification. To answer specific questions regarding the frontal sinus.,
nasal endoscopy is essential. In the outpatient clinic, a flexible rhinopharyngoscope provides
an
excellent view of
in the nose and paranasal sinuses, as long as there are openings through which a 3.8-mm
all the relevant regions
flexible scope may pass. Using this, even small children can
CLINICAL DIAGNOSIS
be examined without local anaesthesia. However, the best possible results are achieved with the rigid telescope
History
is recommended, since during unexpected movements the
A carefully taken patient history is still of considerable
importance despite
surgery. An important question, for example, is whether the symptoms have changed since the last operation and,
if so, how long has it been since these changes took place. When the patient reports improvement after the last operation, there is a reasonable likelihood of a positive outcome after revision surgery.
C linical examination
Imaging PLAIN X-RAY
Plain sinus x-rays are nowadays only acceptable for rough orientation in patients
with signs of acute bacterial
rhinosinusitis. An occipitofrontal sinus plain x-ray enables a template of the frontal sinus projection to be cut, which 1s is of benefit for transfrontal osteoplastic opening.
INSPECTION
ULTRASOUND
Inspection of the anterior frontal sinus wall for redness of
Although ultrasound examination provides useful infor
the skjn and bulging, combined with percussion, may give important information on more acute or chronic changes.
./
patient may feel considerable pain.
all the modern, sophisticated, diag
nostic tools. TIlls is even more valid before any revision
its {
with
different angles. To use this approach, topical anaesthesia
mation in the outpatient clinic in the A- and more
recently
in the B-mode,16 it is not
in routine use for
I -
1502 I PART 13
THE NOSE AND PARANASAL SI NUSES
paranasal sinus diagnosis as computerized tomography (CT)
is the gold standard for detailed assessment.
COM PUTED TOMOGRAPHY In virtually
all cases of sinus disease and in particular (CT) is the
frontal sinus disease, computed tomography
first choice of radiologic imaging. Zinreich et al.17 have
developed a protocol for evaluation of the nasal cavity and the paranasal sinuses. For a surgical approach to the frontal sinus, axial and coronal slices are required 'With
additional sagittal cuts in certain situations to provide the surgeon with three-dimensional
(3D)
orientation. The
latest CT machines allow a complete set of axial slices to be made within a few seconds, from which other projections
can
be reconstructed at the same quality,
excluding dental artifacts
(Figure 118.2). In the majority
of patients, for example those undergoing first surgery as unproblematic cases,
CT examination alone gives
the necessary diagnostic and anatomical information. [Grade
B]
MAGNETIC RESONANCE IMAGING If there is a need to differentiate between polyps, tumour and
mucus,
magnetic
resonance
imaging
(MRI) is
indicated.1B It is recommended that in the cases of unilateral sinus disease, CT and routinely,
MRI be performed
since frequently a tumour is part of the
unilateral opacification. In a high percentage, a tumour, for example an inverted papilloma, can be diagnosed preoperatively and the patient can give his informed consent for whatever additional surgical measures may prove necessary
(Figure l1S.3). MRI allows the diagnosis
of a tumour and also raises the specific suspicion of fungal disease, angiofibroma19 and/or inverted papillo ma.18 [Grade
B]
Figure
118.2
(a)
Axial and (b) coronal CT scans of a frontal
sinus osteoma based at the lamina papyracea. This is a borderline case for endonasal resection with which the
SCINTIGRAPHY
operation should start. If complete resection is not possible,
Technetium-99 bone scintigraphy is mdicated in the cases
surgery can be extended to the o�teoplastic flap procedure.
of frontal bone osteomyelitis to confirm the clinical diagnosis, to show the extent of the disease and most importantly for follow up.
FISTULAS
AND CYSTS
The simplest cleft malformation in the frontobasal region is the dermal sinus which may be accompanied by
CLINICAL PATHOLOGY
dennoid cysts. This group includes a large proportion of the congenital nasal fistulas and dermoid cysts of the
Frontobasal malformations The frontal sinus can rarely be involved
nose and frontal area, which are infrequently seen by -the
ear, nose and throat surgeon?!' 22,23 These fistulas may
in frontobasal
dysraphic anomalies or in various types of craniofacial
syn- or dysostosis.
Closure defects of the skull and frontobasal dysraphic
anomalies are classified either by the site of herniation
(Table 118.1) or by its contents (Table 118.2).20
--j
/
extend from the skin to the frontal bone
(Figure 118.4a),
leading to pressure atrophy and narrovving of a frontal sinus if it is developed. They may extend through the
in an extra (�igure l1S.4b). Nasal fistulas can also pass through the dUIa ending in a subarachnoidal, intradural' skull base into the cranial cavity ending dural cyst
i /
I
.'
Chapter 118 Table 118.1
The fronta l sinus I 1503
Classification of frontobasa l dysraphic a nomal ies by
site of occurrence.
1. Nasa I fistu la 2. Nasal fistu la w. ith cyst 3. Encephalocoele 3.1 Frontoeth moidal
a. Nasofrontal b. Nasoethmoidal c. Nasoorbital
3.2 Sphenoorbita l 3.3 Sphenomaxil l a ry 3 . 4 Nasopharyngeal
Modified from Ref. 20,
a. Transethmoidal b. Sph enoeth moidal c. Sphenopharyngeal
with permission.
Table 118.2
Classification of frontobasa l dysraphic anoma l ies by the contents of the sac. maJy 1.
Dermal s inus Dermal sinus with dermal cyst 3. Encephalocoe les 2.
3.1 Meningocoele Meningoencephalocoele 3.3 Ence phalocystocoele 3.4 Encephalocystomeningocoele 3.2
Modified from Ref. 20,
with permission.
(Figure 118.4c). The external opening in the skin be inconspici o us and masked by a pigm ent ed spot, so the condition remains undia gnosed until a subcuta neous fistulitis supervenes, poss ibly accompanied by i n tr acran ial complications, e.g. menin gi tis or encephalitis. The fis tula opening is most commonly located on the nasal dorsum, rarely at the columella.24 With a subdural epidermoid cyst, a supervening inflammatory complica t i on can pro du ce symptoms of men in git is brain abscess or brain tum our ; the possibility of such an a nomaly should be cons i dered whenever unexplained meningitis appears. [Grade D] An uninflamed, tumo ur l ike lesion at the root of the nose in the midline is rare, but should raise suspicion of a glioma, which could be an isolated m alformati on or OCCllI in conju n ction with a menin go or encephalocoele (Figure 118.5). Frontoethmoidal enceph al oco eles result from congenital o penings in the midline region of the skull, o ften at the junction of the chondro-" and desmocranium, which pe r m its m eninges brain substance or both to herniate from the cranial cavity?S The hernial opening of the nasofrontal encephalocoele (Figure 118.6) is located in t he midline over the root of the nose. cyst
'
may
,
Figure 118.3
CT and MRI scans in the case of a bilatera l inverted papil loma. (a) Coronal CT scan with opacification of both ethmoids and fronta l sinuses. Differentiation between tumour and secret retention is not possi ble. (b) Sag ittal reconstruction clarifies a major destruction of the posterior frontal sinus wall and the anterior ethmoid roof giving the suspicion of mal i gnant transformation. (c:) MRI scan shows the typica l streaky del ineation of inverted papilloma and additiona l ly allows for d ifferentiation between tumou r and mucus retention [m �rked by *).
'hi
J , J
-
-
,
1504 I
PART 13 THE NOSE AND PARANASAL SINUSES
Cerebrum Dura mater--I-.J-JL...ur-
Nasal fistu
with Cyst
_��dl�ig���
Sphenoid sinus Ethmoid cells
(0)
(b)
Figure 118.4
Nasal fistulas and cysts
(a)
Nasal fistula
and cyst anterior to the frontal hone. The anterior wall of the frontal sinus is thinned out and the lumen narrowed.
(b)
Nasal fistula extending through the skull base into the
cranial cavity, where it communicates with an extradural cyst.
(c)
(e)
Nasal fistula with an associated intradural cyst.
Redrawn from Ref.
A meningocoele is a cerebrospinaLfluid-filled hernial sac that is lined and covered by meninges. A sac that additionally contains brain tissue or other glial matter is referred to as a meningoencephalocoele (Figure 118.5). A review of the pattern of frontal sinus development26 was carried out on ten. patients with a frontoethmoidal meningoencephaio·��ele, who had been operated on at the age of 12 or above, when the frontal sinus would normally already be developed. Eighty-five percent of the frontal sinuses were either absent or rudimentary. This is in marked contrast to the approximately 20 percent seen in the normal population. It should be taken into account that, depending on the age of the patient at operation, structural interference to the development of the frontal sinus may result. Aesthetic forehead and supraorbital ridge reconstruction requires attention to augmentation of the glabella. __
23,
courtesy of Springer.
Occult and manifest malformations
Differentiation of fronto- or rhinobasaf7 malformations, both occult and manifest, has proved to be practical for clinical use (Table 118.3).9) 10 Whereas in manifest malformations the cause of an intracranial complication is easily recognized, this can be difficult in occult skull base defects. This means in clinical practice that in every meningitis of unknown o r i gin a precise and detailed examination with the most up-to-date imaging techni ques, such as CT and MRI, is required. It is necessary to consider the whole skull base since sometimes multi locular defects occur. [Grade C] Diagnosis
The treatment of nasal fistulas and cysts should be preceded by a selective diagnostic evaluation, even in
!
.I
Chapter
118
The fronta l sinus I 1505
Frontal bone
Hernial opening
Encephalocoele
Ethmoid ceUs
Sphenoid sinus
Figure 118.5 Nasofrontal encepha locoel e in touch with the frontal sinus. Redrawn from Ref. 23, courtesy of Spring er.
patients with small fistulas. The work up must include endoscopy, CT and MRI.
A
contrast study of a fistula is
not sufficiently reliable to be recommended for routine use.
Operative principles It is most important that nasal fistulas and cysts are removed 'completely,
the
short
ones
endoscopically,
the larger via an external approach. Extra- and intra dural
extension
surgeons
demands
(Figure 118.7),
cooperation
with
neuro
In these cases the surgical
approach traverses the frontal sinus and a decision has to be made as to whether it can be preserved as a cavity. If 8 in doubt, it is safer to obliterate or to cranialize2 the frontal
sinus.
Constantinidis
et
az.29 have recently [**J
reported indications, technique and results.
Meningo- and encephalocoeles need to be resected as they are potential sources of intracranial compli cations and the externally visible ones need aesthetic improvement. locoeles
of
Most
the
of
the
anterior
time,
skull
base
meningoencepha hidden
in
the
nasal cavity can be treated using an endonasal micro endoscopic approach for resection and duraplasty.3o,31
[**J
For
large,
obvious
meningoencephalocoeles,
Figure 118.6 Combined g lioma and meningocoele. Duraplasty was necessary. (a) Patient with swe l l ing over the nasa l dorsu m; (b) axial CT scan showing the bony defect (arrows).
an external approach, preferably via a coronal incision, without
shaving
the
hair
for
aesthetic
reasons,
is
preferred.
TRAUMA OF THE FRONTAL SINUS Fractures
Prognosis If surgical correction is undertaken, the prognosis is excellent and the success rate high with around primary persistent closure of the dura mater.
95 percent
The
frontal
sinuses,
paranasal sinuses,
as
the most
are very
superiorly located
frequently involved in a
fronto- or rhinobasal trauma. The term
1506 I PART 13 Table 11 B.3
THE NOSE AND PARANASAL SINUSES
Occult and manifest malformations of the skull
sinus fractures and maxillofacial trauma has been given by Stanley,33 based on personal experience in more than
base.
160 OCCULT
MANIFEST
Outwardly invisible
Outwardly visible
Clinically obvious because of
Often disfigured
also a fracture of the posterior wall including a lesion of the dura mater and, quite frequently, varying degrees of
Occasionally dysfunctional
systematic CT and MR imaging Surgical indication not easy to
[**]
these patients often suffer not only soft tissue trauma, but
complications (e.g. meningitis) Establishment of the diagnosis by
cases.
With the exception of localized anterior table fractures,
brain injury. These patients obviously need interdisci plinary diagnosis and treatment.
Possible complications;
1. Inflammatory
accept by the patient
2.
IMAGING
Adjacent distortion
Besides precise clinical examination, CT imaging gives the
Patient requests:
1. 2.
necessary information about the extent of the trauma.
Aesthetic correction Avoidance of malfunction
Reprinted from Ref. 10, with permission.
Comminuted fracture of the posterior wall of the frontal sinus
is
highly
suspicious
for
a
dural
laceration,
confirmed by the presence of intradural air. Magnetic resonance imaging may clearly show a dural leakage.
SURGICAL PRINCIPLES Here, only a few basic principles can be given. •
If a severely fractured frontal sinus is not treated adequately in the primary setting, sinus complications, such as mucopyocoeles, as a consequence of frontal sinus outflow obstruction are to be expected earlier or even years later. In addition, there is great danger of intracranial complications in the case of a dural defect. Experience shows that the spontaneously resulting scar of the dura is not sufficient to prevent ascending infections.3D. 31 The paranasal sinuses are not sterile and are therefore permanently a potential source of ascending intracranial infection. Therefore, a wait-and-see policy in these cases is not acceptable. Late complications may arise between
•
1
and
48
years after trauma.3D,31
(
In severe fractures of the frontal sinus, an approach via a coronal incision allows excellent exposure of the frontal sinus, including its surroundings such as the anterior skull base and the roof of the orbit. In
Figure 11 B.7 fistula;
(2)
Extra-intradural nasa I fistula and cyst
mucus retention in the frontal sinus;
(3)
(1)
addition, it is possible to obtain bone grafts from the
Nasal
temporal fossa to reconstruct defects of the anterior
intradural
wall of the frontal sinus. There is nO need to shave
cyst. Rhinoneurosurgical removal as one stage procedure
hair and a good aesthetic result may be obtained. If
removing the pathology in one piece via the subfrontal
there are large lacerations of the frontal soft tissue,
approach. The frontal sinus was cranialized after complete
these might exceptionally be used for the surgical
removal of mucosa and posterior wall.
approach. The advantages of the coronal incision versus the classic infra-eyebrow incision or the
defined by Wullstein27 as the part of the anterior skull
bilateral eyeglass incision are that the supratrochlear
base in direct contact with the pneumatization of the
and supraorbital nerves as branches of the first
facial skeleton. This means that the otorhinolaryngologist
trigeminal main branch, the ophthalmic nerve, are
must be part of the surgical team treating these patients. In
119
preserved under direct visual control. Thus hypo- or
patients at the Marburg University ENT
anaesthesia and also the more rare severe neuralgic
Department with fractures of the anterior table of the frontal sinus,
41.5
percent showed involvement of the
anterior skull base.32
A view
of the management of frontal
pain, can be safely avoided. •
Some 40 years ago, Riedel's operation,34 which meant
radical resection of the whole anterior frontal sinus
Chapter 118 The
•
wall including all frontal sinus mucosa, was the surgical standard. Besides the fact that this operation was not easy to perform and the rate of postoperative mucopyocoeles was high, aesthetic deformation often led to severe psychological impairment. Matzker35,36 was probably the first to abandon the Riedel approach when antibiotics became generally available. He successfully reconstructed the anterior frontal sinus wall piece by piece with wire osteosynthesis. He also underlined the importance of a wide drainage of the frontal sinus via the exenterated ethmoid cell system and the need for duraplasty. Nowadays, three options for frontal sinus treatment in the cases of trauma are used according to the 2 individual situation.21, 22, 3 - In cases of fracture of the anterior and/or posterior wall, but a more or less intact Killian's infundibulum, reconstruction of the anterior and posterior wall is undertaken leaving the outlet undisturbed. For reconstruction of the anterior wall, sutures with resorb able or nonresorbable material or wire may be used. For reconstruction with many bone fragments, one of the new plating systems is advisable. The fragments can be put together away from the surgical site and then placed into the site as a whole and fixed. Care has to be taken to use nonmagnetic material to maintain the facility of magnetic resonance imaging.37 Modern metallic materials have good tissue compatibility and can be left in situ as long as there are no signs of inflammatory reaction. Perhaps in the future biodegradable miniplates will play a major role for osteosynthesis. Until now, clinical experience is still limited.38 - In cases of a severely comminuted posterior wall, reconstruction of the anterior and complete resection of the posterior wall is undertaken. This must be followed by delicate removal of all frontal sinus mucosa using both a microscope and an endoscope in niches and recesses using a cutting drill; however, in dangerous areas the diamond burr should be used. This type of surgery is called cranialization of the frontal sinus.28 Finally, the dead space between the frontal dura and the anterior frontal sinus wall is obliterated by cubes of fresh abdominal fat after any connection between the nasal cavity and the frontal sinus has been closed, e.g. with preserved dura, fascia or galea periosteum. If there is a larger gap into the nasal cavity, pinna cartilage has proved to be effective. - Fractures of the orbital roof are, to a varying degree, part of the frontal sinus floor trauma, depending on the pneumatization. They may lead to entrapment of the superior oblique or/and rectus muscle. If this is the case, careful preoperative assessment is required by a forced duction test,39 as well as neurologic examination,
frontal sinus I 1507
to differentiate between a simple muscle disturbance and a lesion of the superior branch of the oculomotor nerve, which causes at its most severe, a complete ptosis. If this nerve seems to be intact, gentle reduction of the fragments is necessary, to avoid irritation of this delicate structure. Lesions of the periorbita may be reconstructed by galeal periosteum, autogenic temporalis fascia or a preserved fascia. It is also important to search for dural defects next to the orbital roof fracture, otherwise a pclsating swollen cerebrospinal fluid (CSF)-filled upper lid may appear later as a rare complication. An efficient surgical solution is important in avoiding late 21, 22, 23 inflammatory orbital complications. It is recommended to have CT and MRI two to three months after surgery to assess the bony and soft tissue as a baseline for further complications. [**] [Grade C]
DURAL LESION
Since CSF rhinorrhoea is discussed in detail in Chapter 129, Cerebrospinal t1uid rhinorrhoea, only some basic clinical recommendations with regard to the dural defect in the posterior frontal sinus wall will be discussed here. [Grade B] •
•
Stabile dural reconstruction is important, otherwise a traumatic meningocoele or arachnoidal cyst may develop. There are three techniques of dural reconstruc tion.21, 22, 23 - The underlay technique between brain and dura for which fresh abdominal fat is the most suitable and adaptable. Fascia, galea periosteum or preserved fascia may also be used. - The underlay technique between dura and bone. This works after careful exposure of the whole dural defect by removing the surrounding bone and mobilizing the dura for a few millimetres laterally to the midline. Near the midline dura, mobilization may be impossible without damaging the olfactory fibres, which should be avoided. - The onlay technique on to the posterior wall of the frontal sinus after careful removal of mucosal lining.
Fibrin glue to assist primary fixation is useful, but not indispensable. Often different techniques of duraplasty are combined for safety reasons. [**]
IN FLAMMATORY DISEASES OF THE FRONTAL SINUS Frontal sinus drainage Most of the time, frontal sinusitis is more or less ex tended panrhinosinusitis. Anatomical variations of the /
I
!
i
1508 I PART 13
THE NOSE AND PARANASAL SINUSES
purulent frontal sinusitis. Frontal sinus endoscop�3,54 frontonasal recess may play an important role aetiologi cally.40 In 92 of 359 cases (26 percent), the nasofrontal is a modification of trephination using endoscopes for recess was found to be radiologically abnormaL In 18 i.e. inspection and for smaller interventions. It replaced blind patients (5 percent) it was narrowed and in 74 ( 2 1 or frontal sinus puncture and irrigation for treatment of acute sinusitis.55 Recently, external frontal sinus puncture percent) obstructed. Frontal sinusitis was noted in 78 (85 in combination with irrigation has been used to ease the percent) of the m 92 cases of frontonasal recess variation, suggesting a strong correlation between abnormalities of location of the frontal sinus during endonasal frontal . . · . smus operatIOn WIth a mICroscope and an endoscope.56,57 the frontonasal recess and frontal sinusitis. Agger nasi cells contribute to nasofrontal recess obstruction and chronic Operative princi p l es frontal sinus disease. Sagittal reformatted CT images are more capable than coronal images of demonstrating agger If this operation is needed at all, a l-cm incision is nasi cell encroachment on the nasofrontal recess, as well as made just above the medial end of the eyebrow and with a mucosal disease in this area.41 O.5-cm drill hole the anterior wall of the frontal sinus is Frontal sinus inflammation heals either with medical opened. Under endoscopic control, irrigation and inspec treatment (see Chapter 1 16, Medical management of tion of the frontal sinus is possible. Irrigation should be chronic rhino sinusitis) or after improvement of drainage undertaken with great care if a defect of the orbital roof following surgery, which does not interfere with the has been seen at CT. In these cases the fluid may enter the frontal sinus itself. A compromise approach is endosco orbit and lead to visual decrease or even loss of vision.46 pically guided instillation of beclomethasone for refrac Preoperative CT will show the extent of the frontal sinus tory frontal sinus/frontal recess mucosal oedema and and help avoid injury to the dura. [**/*] polyposis.42 Often, limited pathology entities in the middle nasal EXTERNAL FRONTOETH MOIDECTOMY meatus cause a localized frontal sinusitis, which can be treated without problems.13,14,43,44,45 [**] Operative princi p l es
Surgical approaches to the frontal sinus The development of frontal sinus surgery clearly reflects how difficult it is to achieve the goals of a cosmetically satisfactory appearance and the prevention of recurrent or chronic infection in a single operation.46,47 As a general rule, surgery should be as extensive as necessary, but as limited as possible. On the other hand, the number of surgical interventions needed for the best available result has to be as low as possible. In other words, the patient might be happier with a more extended operation avoiding further interventions, rather than with several smaller operations resulting in a limited success rate. From a technical point of view, the frontal sinus surgeon needs a thorough knowledge and understanding of the underlying pathologic anatomy and special surgical skills, usmg · a mICroscope · . l· and endoscope as Vlsua alds.48 ' 49 Computer-assisted surgery with a navigation system may improve operative security and surgical training.50, 51 There is an obvious need to critically evaluate safety and long term reliability, as well as complications. [**] Different procedures are in use today, but remarkable differences exist between different institutions in relation to the indications.
FRONTAL SINUS TREPH INATION AN D FRONTAL SINUS EN DOSCOPY
2 Frontal sinus trephination5 is the oldest external intervention and was indicated primarily for acute
External frontoethmoidectom�8, 59,60,61 starts with a slightly curved medial and concave incision towards the medial canthus of the eye straight down to the bone. The incision divides the distance between the nasal dorsum and the medial canthus in the middle. The frontal sinus is reached by mostly osteoclastic resection of the lacrimal bone, part of the frontal process of the maxilla and the frontal sinus floor. The ethmoid cell system is delicately resected resulting in one open cavity and a wide approach between nasal cavity, the ethmoid and the frontal sinus. Details of this operation are described in many surgical . 46 62 . bone resectIOn/' manu a1s. A temporary osteop1astlc probably reduces the shrinkage of the postoperative) soft tissue and the danger of mucopyocoele. Resu lts
Apart from the danger of supraorbital- and supratro chlear nerve injury, this operation has a basic conceptual problem. Almost two-thirds of the bony margins of the frontal sinus drainage is resected and is replaced by a soft tissue scar. This is associated with a high risk of contracture and a resultant mucocoele. There have been many attempts to overcome this problem, most recently with different types of silicone sheeting63 or combining external and endoscopic frontal sinusotomy with addi tional stent placement.64 The percentage of revisions because of stenosis depends on how long these patients are observed. In 123 cases reported by Goodale,65 30.8 percent had to be reoperated and in 22.2 percent he found mucocoeles. Amble et al.66 observed 157 patients on average for �lmost four years. The stent was left in place for six to eight weeks and sometimes for several months.
Ch apter 118
Eighteen percent of the initial cases needed reVISIOns. Sixty-two patients64 showed a patency rate of 79 percent during a mean follow up time of one year and duration of stent placement of five weeks. The best technique would be the one which gives the same or even better results without the need for stenting; however, this always leads to some sort of foreign body reaction. Another problem is ocular motility disturbance with double vision. In 160 patients at the University of Marburg,66,67 postoperative double vision was found in 3 1.9 percent, of which 23.S percent was transient, S.1 percent persistent. This group of patients included not only inflammatory disease, but also trauma and tumour. In the latter two, mobilization of the trochlea as the main cause of double vision was the more frequent. Because of these severe disadvantages, the Fulda group have not recommended this operation for chronic frontal sinusitis since more reliable alternative techniques have been developed.68,69 [**1*] ENDONASAL SURGERY OF THE FRONTAL SINUS: THE FULDA CONCEPT
Apart from a couple of earlier reports, endonasal surgery of the paranasal sinuses began some hundred 1 years ago?O,7 ,72, 73,74 Only a few skilled surgeons have been able to perform endonasal ethmoidectomy, as well as adequate drainage of the frontal sinus, using just a headlight and the naked eye, whereas others created serious· complications such as CSF leak, meningitis, brain abscess and encephalitis which generally resulted in the pre-antibiotic era with the death of the patient. For this reason, until the 1970s endonasal sinus surgery was not accepted in most of the leading institutions. The renaissance of endonasal surgery was due to several facts: (1) new optical aids such as the microscope and endoscope; (2) improved understanding of the physiology and pathophysiology of the nasal and para nasal sinus mucosa; (3) patients no longer accepting the sometimes serious sequelae of external operations in addition to an unsatisfactory outcome; and (4) remark able progress in anaesthesiology providing the endonasal surgeon with an almost bloodless field. Since 19S4, an endonasal surgical approach with different degrees of frontal sinus opening has been established and intensively tested before being pub lished.9,IO With increasing experience, it became clear that not all problems could be solved using the endonasal route and the osteoplastic obliterative frontal sinus operation75 was included in order to cover all the various frontal sinus problems. In difficult revision cases, the endonasal operation must be combined with the 10 1 9 , 5 osteoplastIc, · most1y 0bl·Iterative · procedure.' 10, For type I-III frontal sinus drainage,9, 15,76,77 general anaesthesia is required. In addition, topical decongestion helps to provide a dry field. Surgery on the frontal recess is usually preceded at least by an
/
The frontal si nus • 1509
anterior, more often than not by a complete ethmoidect omy. Exceptions are those cases where a complete ethmoidectomy has already been performed. It is important to remove agger nasi cells and to visualize the attachment of the middle turbinate medially, the lamina papyracea laterally and the anterior skull base with the anterior ethmoidal artery superiorly. Type I: Sim ple drainage
Simple drainage (Figure IIS.Sa) is established by ethmoidectomy including the cell septa in the region of 1 the frontal recess. The inferior part of Killian's infundi bulum and its mucosa is not touched. This approach is indicated when there is only minor pathology in the frontal sinus and the patient does not suffer from risk factors, such as aspirin intolerance and asthma, which are associated with poor quality of mucosa and possible problems in outcome (Table 11S.4). In the majority of cases, the frontal sinus heals because of the improved drainage via the ethmoid cavity. Type I I : Extended drainage
Extended drainage (Figure 11S.Sb, Figure 11S.9) is achieved by resecting the floor of the frontal sinus between the lamina papyracea and the middle turbinate (type IIa) or the nasal septum (type lIb) anterior to the ventral margin of the olfactory fossa. In May and Schaitkin's classification, 78 type IIa corresponds to NFA (nasofrontal approach) II and type lIb with NFA III. In a detailed anatomical study, Hosemann et az.79,80 showed that the maximum diameter of a neo-ostium of the frontal sinus (type IIa), which could be gained using a spoon or a curette, was 11 mm with an average of 5.6 mm. They also presented an excellent critical evaluation and results.79 Where a larger drainage opening is required as in type lIb, one has to use a drill because of the increasing thickness of the bone going more medially towards the nasal septum. During drilling with the diamond burr, bone dust fogs the endoscope which requires repeated cleaning. At this point the microscope is useful and allows the surgeon to work with both hands, while an assistant holds a simple self retracting speculum.81 The endoscopic four-hand techni que, introduced by May, is also a useful alternative, allowing the surgeon to work with both hands, while an assistant holds the endoscope. In revision cases after incomplete ethmoidectomy, it is recommended that a wide approach to the ethmoid is created using a microscope and drill or punch when possible. Punches and through-cutting instruments82 help to preserve the mucosa, whereas the drill is more destructive in this respect. The wide approach to the ethmoid is obtained by exposing the lacrimal bone and reducing it, as well as parts of the agger nasi and part of the frontal process of the maxilla, until the lamina papyracea is clearly seen with the microscope. This facilitates better visualization of the frontal recess to
j
.
L
1510 I
PART 13
THE
NOSE AND PARANASAL SINUSES
(b]
(0)
Figure 118.8
9 Types I-III frontal sinus drainage. .
10
For a detailed
description, see the text.
Table 118.4
I ndications
--
---
for endonasal frontal sinus drainage types 1_111.1o.l1
--------�
Type I drainage
Acute rhi osinusiti5
Chronic
Type III drainag�
Serious complications of acute
Difficult revision surgery
rh' nosinusi tis
Failure of conservative surgery
First time surgery
Orbital and endocranial
No risk factors (aspirin
complications
Type II drainage
/
rhinosinusitis
)
intolerance, asth rna, triad Revision after incomplete ethm oidectomy
Primarily in patients with risk
Medial mucopyocoele
factors and severe polyposis
Tumour surgery
particu larly patie nts with:
Good quality mucosa
Samter's triad Mucoviscidosis (cystic fibrosis
)
Kartagener's syndrome Ciliary primary dyskinesia
allow further work on the frontal sinus floor, but also
anterior et hmoidal cells are resected. During surgery, CT scans will establish the presence of so-called
makes the postoperative treatment less painful. As soon
repeated
the frontal recess is identified using the middle turbinate
frontal cells/ which can develop far into the frontal sinus
and, where identifiable, the anterior ethmoidal artery as
giving the s!lrgeon the erroneous impression that the
landmarks, the frontal infundibulum is exposed and
frontal sinus has been properly opened. Sagittal
the
CT slices
�- ':.. -_-
-� i � ---..J.�_·l
Chapter
1 1 8 The frontal sinus I 1511
Figure 1 1 8.9 Recently, type II d rainage has been further differentiated. Type Iia (a) is the opening from the lamina papyracea up to the middle turbinate and type lib (b) up to the nasal septum in front of the olfactory fossa.
and navigation may be helpful in difficult situations. In the case of frontal cells (Figure 118.1), a procedure called 8
8 86, 87, 88 advocated the use of soft, Some authors 5, flexible silicone stents in cases of a frontal sinus neo ostium of less than 5 mm in diameter, since more rigid 8 silicone tubes have not given good results. 9, 90 So far, the techniques using soft silicone drainage devices showed promising results, although long-term observation is still lacking. [**/*] Type III: Endonasal median drainage
The extended lIb opening is enlarged by resecting portions of the superior nasal septum in the area of the frontal sinus floor (Figure 118.8e). The diameter of this opening should be about 1.5 cm. This is followed by resection of the frontal sinus septum or septa, if there is more than one. Starting on one side of the patient, the midline is crossed until the contralateral lamina papyracea is reached. To achieve the maximum possible opening of the frontal sinus, it is helpful to identify the first olfactory fibres on both sides: the middle turbinate is exposed and cut from anterior to posterior along its origin at the skull base. After about 5 mm, the first olfactory fibre is observed coming out of a small bony hole. This is repeated on the contralateral side until, finally, the so-called
I
....'
. _
__
I
:/
1512
I PART 1 3 TH E NOSE AN D PARANASAL SI N U SES
Important to understand
Fig ure 1 1 8. 1 0
Fron ta I si n u s resc ue
p roce d u re (a) In d ica tion is fro n t a l s i n u s obstruction by a l a te ra l ly retracted m i d d l e tu rbin ate.
(b)
Aft e r resect i o n of the sca r,
th e an terior re m n a n t of t h e m i d d l e turbinate cove red m e d i a l ly a n d l a tera l ly by m u cosa beco mes visibl e . (e) The med i a l osse ous a n d m u cosal l a me l l a of the m i dd le tu rbi n a te, i nc l u d i n g the m u cosa cove r i n g the sku l l base a re resected , t h e l a tera l m ucosa l l a m e l l a i s p reserved .
(d)
Co nseq u e n tly, the l a teral m u cosa l la mel la is turned media l ly cove ri n g t h e s ku l l base.
Th e fro nta l s i n u s neost i u m is e p i t h e l ized. Redra w n from Ref. 84, with pe rm i ss i o n .
the ethmoidectomy on the left side is completed in the same way as on
the right.
Performing the type III drainage in the technically
most efficient way, it
is necessary to alternate between the
endoscope and the microscope. Alternatively, this proce dure can be done with the endoscope alone, although it is more time consuming. Finally, a rubber finger stall is
The endonasal median drainage co rresponds with the
NFA
IV78
and
the
modified
Lothrop
procedure.92
Lothrop93 . 94 himself warned aga i nst using t he endo nasal ro ute, ju dging i t as too dange ro us during his time and performed median drainage via an external approach. The principle difference between t he endonasal median fronta l sinus drainage and the classic external
p laced into each frontal sinus and two more are put in the
Jansen, Lothrop, Ritter, Lynch and Howarth operation is th at the
ethmoid cavity on each side This packing is left for seven
bony borders around the frontal
days under prophylactic antibiotic treatment. The rubber
preserved. This makes it more stable in the long term and
.
sinus
drai nage are
finger stalls do not stick to the surrounding tissue and are
reduces the likelihood of reelosure by scarring, which may
therefore easily and painlessly removed In the interim , a
lead to recurrent frontal sinusitis or a mucocoele, as well
.
m aj or p art of the
surgical
cavity has re-epithelized,
making postoperative treatment simple.
as the avoidance of external scarr ing. Endonasal med ian drainage (type
In difficult revision cases, type III drainage can begin prima rily from two points, either from the lateral side as
III ) is i ndicated after
one or several previous sinus operations have not resolved the fro ntal sinus p roblem including an external
fronto
already described or from the medial side. The p rimary
ethmoidecto my. It is a lso j usti fied as a primary procedure
la teral approach
in patients with severe polyposis and other risk factors
is recommended if the previous ethmoi
dal work was incomplete and the middle turbinate is still
affecting outcome, such as aspirin intolerance, asthma,
present as a landmark. One should adopt the primary
Sam ter's
triade
medial approach if the ethmoid has been cleared andlor
allergy) ,
Kartagenees
if the middle turbinate is absent. The medial appro ach
( aspirin
asthma
an d
m ucovisci dosis
and
hyp ersensitivity,
syndrome,
ciliary dyskinesia syndrome
(Table 1 18.4) . Its use in
begins with the pa r tia l resection of the perpend icular
pa tients with severe polyposis wi thout these risk fa ctors
first olfactory fibre on
seems tha t patients with generalized polyposis, but who
plate of the nasal septum , followed by identi fication of the
each side
as
/
already des c ribed
.
has not been determined and should be evaluated. It
Cha pter 1 1 8
have air on coronal CT ( 'halo sign' ) in the periphery sinuses, have a comparatively better p rogn osi s than those without, and can be managed by a more c onservative technique.
The fronta l si nus I 1 5 13
still
of th e
Improvement 45.2% (1 9)
Resu lts of endonasal frontal s inus su rgery
Judging the results of endonasal frontal sinus surgery re quires a p o stoperative follow up of ten or more years.95, 96 The failure rate of Neel et al.9s with a modified Lynch procedure grew from 7 percent at a mean follow up of 3.7 years to 30 p ercent at seven years . Kikawada et al. 97 presented a retrospective review of 22 consecutive cases of extended frontal sinus surgery (Draf type III) in patients with obstructive frontal sinusitis caused by p o stop erative scarring with a fo ll ow up time of at least 12 months after surgery. Of the 16 p atients who underwent th e type III procedure, in 14 ( 8 8 p er cent ) the p atency of the newly created fro ntal sinus draina ge and an aerated sinus were co nfirm ed . Of 1 2 sides in nine patients who underwent Draf type II procedure, five sides (42 percent) were also confirmed as cured. In the opinion of the authors, the me dian drainage o perat i o n (Draf type III) on th e frontal sinus showed excellent long-term results compared with the type II procedure. Draf et al. IS and Weber et al.86• 87 carried out two stud ies . In the first retro spe ctive study, p atients who underwent endonasal frontal sinus dra i na ge (47 1 type I drainages, 125 type II drainages and 52 type III drainages) between 1 979 and 1992 were evaluated. From these groups, rand o m patients were examined: 42 p ati ents with type I draina ge , 43 with type II drainage and 47 with type III drainage were included in the study. In each patient the indication was chronic polypoid rhinosinusi tis, except in five cases with type III drai na g e in whi ch an o rb ital comp li cat i on presented associated with acute sinusitis. The follo w- up p eri od was between one and 12 years with a me d i an of five years. The subjective estimatio n of operative results by th e pa t ients is shown in Figure 1l8�1 1 . Ap p lying subjective and objective criteria to evaluate the success of end onasal frontal sinus drainage (grade 1, endoscopically no rm al mu co s a, in dependent of th e subj ective complaints; grade 2, subj ectively fr e e of symptoms, but with end o scop i cally visible inflammatory mucosal changes; grade 3, no subje ct ive improvement and pathologic m ucosa, therefore failure) , it was possible to achieve a success rate of 83.4 per cent with type I drainage, 83.7 pe rcent with type II drainage and 89.4 p er cent with type III drai na ge . This means that, despite the choice of p rogn osti c ally un favourable cases, type III drainages appeared to show the best results though this was not statistically signifi cant among the three gro ups . In a second study,86. 87 endoscopic and CT examina tions were systematically carried out (Figures 118.12 and 1 18. 13), After between 1 2 and 9 8 months follow-up of p atients with type II drainage, 5 8 percent of 83 fro ntal sinuses were venti l ated and normal. A ventilated
Unchanged 9.5% (4)
10] Improvement 32.6% (1 74)
Free 51 .2% (22)
Worse 4 .7% (2)
(b)
worse ......
( e)
2. 1 % (1)
Figure 11 8 . 1 1
Subjective judgement of results of frontal sinus surgery. 1 to 1 2 years after surgery. (a) Type I dra i nage ; (b) type I I drainage; (c) ty pe I II dra inage.
Ventilated
�
frontal sinus
Normal 58% 48
1 2% Completely opacified scars 1 4% Figure 11 8 . 1 2
following type
II
Completely opacified polyps 1 6%
Synopsis of CT and endoscopy 1 2 to 98 months drainage. Redrawn from Ref. 98, with permission.
i
j
1 5 1 4 I PART 1 3 TH E
NOSE AN D PARANASAL S I N USES
�
S u rgical techniq u e
Normal
59%
The surgical technique consists of eight steps:
Ventilated frontal sinus
one reading
1.
48
the external approach according to Jansen-Ritter; resection of frontal sinus pathology; total resection of the frontal intersinus septum; partial endonasal resection of the nasal sep tu m; bilateral subtotal resection of the free dependent part of the middle turbinate; 6. bilateral endoscopic ethmoidectomy; 7 . maximal enlargement of the isthmus area between both frontal sinuses and nasal cavities. including the anterior ethrno ids; 8. complete epithelization of the neo communication with free mucosal grafts and closure of the Jansen-Ritter approach.
2. 3. 4. 5. Thickened 1 7%
Completely opacified
polyps 1 6%
Completely opacified scars 7%
Fig u re
11 8. 1 3
Synopsis of CT and endoscopy
1 2 to 98
mon ths
following ty p e I I I drainage. Redrawn from Ref. 98, w i th permission.
frontal sinus with hyperplastic mucosa was seen in 1 2 percent. Scar tissue occlusion with total opacification on CT was evident in 15 percent. In 16 percent, total opacification was due to recurrent polyposis. Patients were free of symptoms or had only minor problems in 79 percent. Twelve to 89 months following type III drainage, 59 percent of 8 1 frontal sinuses were ventilated and normal. A ventilated frontal sinus with hyperplastic mucosa was seen in 17 percent. Scar tissue occlusion with total opacification on CT was obvious in 7 percent and in 16 percent there was total opacification due to recurrent polyposis. The patients were free of symptoms or had only minor problems in 95 percent. This first series of re-evaluation of long-term results demo nstrates the value of endonasal frontal sinus surgery. In a retrospective study, Mertens et al. 99 compared the results of 236 patients operated on between 1 985 and 1993 using different techniques. Only 8 percent of p atients needed revision at follow up of between three and ten years. The lowest revision rate was seen after the endonasal technique according Draf's classi fication ( 5 .9 percent) , compared with the osteoclastic techniques of Jansen-Ritter (Lynch) and Riedel ( 1 0.6 percent) . [**I*J
THE RHINOFRONTAL S I NUSEPTOTOMY: A COM BIN ED INTRA-EXTRANASAL APPROACH
As a solution for very difficult inflammatory frontal sinus disease, usually after several previous operations, Sten nert lOO developed a combined intra-extranasal approach, rhinofrontal sinusep totomy (RFS ) , which is similar to the combined external and intranasal technique of Lothrop,94 but includes immediate re-epithelization of the fro ntal sinus drainage a rea with free mucosal grafts. This operation is somewhere between the endonasal median drainage and the osteoplastic flap obliteration with regard to the extent of surgery.
/
Results
After a mean follow up of 62 months, 40 of 4 1 patients (98 percent) had a widely patent epithelized naso frontal communication. Ninety-one percent of the patients with chronic frontal sinusitis or mucocoeles noted complete relief of their frontal discomfort within one week. No patient has so far required revision surgery of the naso fro ntal outflow tract. Only one major complication, a cerebrosp i nal fluid leak, was observed. [**1
THE OSTEOPLASTIC B O N E FLAP PROCEDU RE
Today, most inflammatory frontal sinus disease requiring surgical treatment can be successfully treated endona sally. 9 , 1 0, 1 5 , 46. 1 0 1 , 102. 1 03 About 5 percent of all frontal sinus operations are external. The osteoplastic frontal sinus approach is regarded by some as the preferred approach, particularly if a so-called 'problem frontal sinus' o ccurs. This approach permits an optimal view encompassing the entire frontal sinus and allows complete micro-endoscopic removal of mucosa and obliteration of the sinus with abdominal fat as described by Tato and Bergaglio, as far back as 1 949. 75 Indications are as follows: • •
•
• • •
•
•
failure of correctly performed type III drainage; problem frontal sinus, sometimes in combination with complete endonasal ethmoidectomy; type III drainage technically not possible (anteriorposterior diameter less than 8 mm); laterally located m ucopyocoele; major destruction of posterior wall; inflammatory complications after trauma (e.g. alioplastic material) ; aesthetic correction of pneuma to sinus dilatans frontalis ( mostly without obliteration) ; major benign tumo urs ( e.g. osteoma) without or with obliteration.
/ / /
)
Chapter
Operative tec h n i q u e This operation (Figure 118. 14) demands great effort and precision and may be time consuming depending on the extent of pathology and the degree of pneumatization. This is the reason why it is no longer universally popular. Its success depends on numerous operative details as o utlined below. D uring preoperative preparation, a few points are important. In addition to high-resolution CT with primary
1 1 8 The fronta l sin us I
1515
axial slices (maximum thickness o f 2 mm ) and reconstruc tion in the coronal plane, together in special cases with sagittal cuts, an occipito-frontal x-ray is necessary. From this image, the contours of the frontal sinus are cut out as a template which is preserved in a disinfectant solution. For aesthetic purposes, shaving of the hair should be avoided, as generally the coronal incision is used. The evening before the operation, the hair should be washed with disinfectant solution to avoid infection.
(b)
(0)
(d] Fi g u re
1 1 8.1 4 Tech nique of the osteoplastic fronta l sinus operation. (a) The x-ray template is placed a n d the periosta l i n'cision is ma rked ; the supraorbital nerves a re preserved after scalping flap elevation. (b) Formation of the bone flap with a saw correspondi n g to the lim its of the frontal sinus. The periosteum is elevated from the a rea of bone incision. (c) An oblique i ncision th rough the bone enlarges the area for replacement of the bony flap. (d) Th en the a nterior wall of the frontal sinus is elevated with two broad chisels. This ends in a fracture of the frontal sinus' floor just posteriorly of the supraorbital ridge (continued over).
b
/ -
\
1516 I
PART 1 3
TH E
NOSE AND PARANASAL S INUSES
Figure 1 1 8 . 1 4
Technique of the osteoplastic frontal sinus operation (continued). (e) Appeara nces after down fracturing of a nterior wall of frontal si nus. (f) The m ucosa is compl ete ly removed and us i n g the operation m icroscope, the i nternal table dri l l ed w ith the burr. (g) After blockage of the ostium, fronta l sinus drainage by i nverting the mucosa, covering the carti lage with preserved fascia or galea periosteum and fixing with fi brin g l ue, the frontal sinus is filled with pi eces of fat These are made to cohere with fibri n g lue. Finally, the bony flap is replaced and closure of the wound begins. (h) Situation at the end of the operation: ( 1 ) Elevated galea-periosteu m ; (2) patholog ica l ly a l tered mucosa frontal sinus; (3) dri l l holes; (4) bony fl a p h inged o n periosteu m (anterior w a l l o f the frontal sinus) ; (5) preserved fascia ; (6) cartilage; (7) transplanted fat w ith fibrin g lue ; (8) fibrin g lue ; (9) resorbable sponge; ( 1 0) rubber finger packs. Redrawn from Ref. 46, with permission. Surgery requires general anaesthesia, with orotracheal
inCIsIOn.
The
great
advantage
is
intubation and the insertion of a pharyngeal pack to
immediately after surgery. In patients
an
invisible
scar
with male pattern
avoid aspiration. The preferred incision for uni - and
baldness,
bilateral osteoplastic frontal sinus op eration in indivi
corona. Inj�ction with local anaesthetic and s up rarenin
full head of hair is the bitemporal coronal
1 : 200 , 000 or better 1 : 1 20 , 000, 1 5 minutes before making
duals with a
the incision is located in the hair-bearing
�.�- r ,
-'--'-.----=--''--',: -l. - -:- ----..r.o.;::;
Chapter
the incision reduces bleeding. Special scalp clamps stop the remaining bleeding. The incision goes down as far as the periosteum. Using partly blunt, partly sharp dissec tion extending to the supraorbital ridge and over the root of the nose, the scalp flap is pulled caudally on both sides, leaving behind the periosteum and the bone, thus preserving the supraorbital and supratrochlear vascular nerve bundles. Next, the template of the frontal sinus that was excised from the occipito-frontal x-ray is carefully positioned on the root of the nose so that the borders of the frontal sinus can be marked on the periosteum. The periosteum is incised 1 . 5 cm outside the template and elevated slightly outside the marking on the bone. Then, the osteotomy is made in the bone, from which the periosteum has been elevated, a few millimetres inside the marked line. The oscillating saw is angled at 30° towards the frontal sinus, allowing a surface that is as wide as possible to be created for the later replacement of the bony lid. The bony incision reaches the supraorbital ridge on both sides. When opening the frontal sinus bilaterally, the intersinus septum must be separated from the anterior frontal sinus wall with an angled chiseL The fracture and elevation of the bony lid is undertaken with a wide osteotome. The supraorbital ridge slightly anterior to the controlled fracture in the region of the frontal sinus floor is preserved and the bony lid hinges on the periosteal flap. The diseased tissue is then removed according to the pathological-anatomical findings. Frac tures must be exposed to their full extent, repositioned and, if necessary, a dural lesion should be treated with duraplasty. In cases secondary to trauma or osteoma, where there is healthy frontal sinus mucosa, it must be decided whether the mucosa around the infundibulum is sufficiently healthy to preserve the frontal sinus or whether obliteration should be carried out. Where the sinus is preserved, a type III median drainage can be performed easily from above with optimum exposure. Javer et al. 1 04 have called this the 'frontal sinus unobliteration procedure'. If obliteration is indicated, the frontal sinus mucosa can be removed using a microscope and/or endoscope. The inner layer of the bony walls must be drilled away with a burr using a microscope and/or endoscope, as only by doing so can the mucosa be completely removed. In a high percentage of cases, simply macroscopically stripping off the mucosa leads to inflammatory recurrences and mucocoeles.1 05 At the inner table of the anterior and posterior frontal sinus wall, as well as for the medial and lateral orbital roof, the cutting drill is the instrument of choice. It allows total removal of the mucosa leaving the bony vascular channels open, which facilitates the revascularization of fat, used for obliteration. In dangerous areas such as exposed dura and the central roof of the orbit, the frontal sinus mucosa is safely removed with a diamond drill under microscopic control, which in experienced hands is not a contra indication for the obliterative frontal sinus operation. As a general rule, the larger the drill, the less the danger. The
•
1 1 8 The frontal sinus I 1517
mucosa in the region of the frontonasal ostium is inverted nasally and the drainage opening is blocked with bone or cartilage splints fixed with fibrin glue. The bone can be taken from the calvarium, or more easily pinna conchal cartilage can be used. The bone or cartilage can be tightly sealed with fascia held with fibrin glue. Through this three-layered closure, the frontal sinus is securely isolated from the nasal cavity, and growth of mucosa into the sinus with the associated risk of mucocoele formation prevented. Next, abdominal fat is harvested either via a pre-existing scar or an incision around the naveL The abdominal fat is temporarily placed in isotonic saline solution and is then placed into the frontal sinus with pieces held together by fibrin glue, until the sinus cavity is completely filled. The periosteal bone lid is replaced and wedged closed with a tap of the mallet and then the periosteum is sutured. If the bone lid fractures during elevation, these bony fragments should be fixed together either with absorbable threads, wire sutures or miniplates. Finally, the scalp flap is flipped back into place, two suction drainages are inserted and the coronal incision closed with single stitch sutures. The tube drains are removed no later than two days after surgery, otherwise removal is difficult and more painful. Results
Weber et al.98 evaluated 82 operative records of patients who had undergone obliterative osteoplastic frontal sinus surgery, of which 59 were followed for 1-12 years after surgery. Eighty-six MRl scans in 5 1 patients were available for analysis. The most frequent intraoperative complications were exposure of orbital fat ( 19.5 percent), unintentional fracture of the anterior wall ( 1 9.5 percent), incorrect placement of the anterior wall ( 1 7 percent) and dural injury (9.8 percent). Persistent changes of the frontal contour (embossment, depression) occurred in 10.2 percent and the aesthetic result was unfavourable in 5 . 1 percent of the cases. Mucocoeles could be detected in five of 5 1 cases (9.8 percent). The amount of adipose tissue detectable in the last scan was less than 20 percent in the majority of cases (53 percent) and more than 60 percent in only 18 percent of cases and decreased significantly with time. The median half-life was 1 5.4 months. Weber et al. came to the conclusion that osteoplastic frontal sinus surgery with fat obliteration is very useful and successful in patients in whom the frontal sinus cannot be treated definitively via an endonasal approach. MRI is judged to be currently the most valuable tool to evaluate the frontal sinus after obliteration with adipose tissue. They admit that this method has some limitations with regard to detection of small recurrent mucocoeles and differentiating vital adipose tissue from fat necrosis in the form of oil cysts. In these difficult cases, long-term follow up is necessary. In an earlier prospective MRl study of 13 patients, Loevner et al. 1 0 6 came to the conclusion that this examination technique is of limited utility in differentiation of inflammatory complications of
1518 I PART 1 3 TH E NOSE A N D PARAI'JASAL SI N USES symptomatic patients and postoperative scarring in the frontal sinus in asymptomatic patients. Bottermann, and Berghaus, 1 0 7 in a similar study of only ten cases, came to the opinion that MRI did not correlate with the clinical symptoms and does not help with postoperative control. 1 , , I l l , 1 1 2, Looking at previous major analyses/08, 09 1 1 0 1 1 3, 1 1 4, 1 15 it becomes obvious that the obliterative osteoplastic frontal sinus operation via a coronal incision should be the ultimate solution if endonasal procedures fail. The classic frontoorbital operation (Jansen-Ritter, Lynch, Howarth) no longer seems to be an acceptable alternative.68, 69, 70 [ **]
CRANIALIZATION O F TH E FRO NTAL SI NUS
The success of obliteration of the frontal sinus may be undermined by a comminuted fracture of the frontal sinus or when the frontal sinus mucosa is incompletely removed. Sometimes a severe post-traumatic oedema of the frontal lobe or an intracranial foreign body is present. In other cases, variable destruction of the posterior frontal sinus wall caused by inflammation or a neoplastic process presents an additional problem. For these special types of frontal sinus diseases, Donald and Bernstein 1 1 6 have published the cranialization of the frontal sinus as a safe and reliable modification of the osteoplastic flap proce dure, 21 cases of which Donald reviewed in 1982.28 Operative techniq u e
The initial part of the operation corresponds with the technique of the osteoplastic frontal sinus procedure. In the case of a comminuted fracture, the bone fragments have to be removed for later reconstruction of the anterior wall, sometimes with an additional bone graft from the temporal area. It is important to remove the mucosa completely from the bone fragments using the operating microscope before replacement, osteosynthesis and obliteration. After careful mobilization of the dura and eventual duraplasty, the remnants of the posterior wall of the frontal sinus are completely removed using a microscope and sometimes the endoscope, as well as punches and a diamond burr. After that, the mucosa of the floor of the frontal sinus is completely removed or inverted into the nose. Depending on the anterior posterior diameter of the frontal sinus, the connection to the nose is obliterated with conchal cartilage or a galea periostal flap if the sinus is small. A large dead space between the anterior wall and the dura can be obliterated immediately by fresh abdominal fat. Constantinidis et al.29 supported this approach, whereas Donald and Ettin 1 0 5 considered this to be dangerous because of reduced vascularization and possible necrosis of fatty tissue and the development of a mucopyocoele. However, the latter should not happen if removal of mucosa is complete. Infection and fat necrosis may occur, if, after a severe midfacial fracture, both maxillary arteries have
been destroyed. Only in these rare cases are free fat grafts not the first choice of material. Instead of fat, other materials have been recommended for frontal sinus obliteration. Shumrick and Smith, 1 1 7 for example, used cancellous bone from the iliac crest with good results as far as the obliteration was concerned, but with some pain at the donor site. Alloplastic material, such as hydroxyapatite, has also been used, 1 18 but autogenous fat is the tissue of choice because of its excellent biocompatibility and minimal donor-site morbidity. Results
Constantinidis et al.29 reported eight cases of different pathology, three with severe trauma, four with pyocoeles and destruction of the posterior wall of the frontal sinus, two of which had methylmetacrylate reconstruction of the skull with direct contact of the implant to the frontal sinus mucosa, which almost always leads to inflammatory complications. One patient had been operated on six times via a Howarth operation, despite which he developed a large mucocoele. Another patient had a large osteoma with a wide base on the posterior wall of the frontal sinus. The mean follow up was 1.8 years with a range of 1 1 months and eight years. None of these patients had any recurrence of inflammatory disease or tumour, nor a late complication such as a mucocoele and the aesthetic results have been excellent. More recently, Ameline et al. 1 1 9 published their experience with 19 cases over a 13-year period, including frontal sinus fractures, infections, mucocoeles and tumours. In the cases of sinusitis or mucocoele, cranialization was indicated after failure of endoscopic sinus surgery. The morbidity of the operation was low, although in the author's opinion, the presence of a neurosurgeon was required. [**]
Guidelines for surgical therapy of frontal sinus infl am m atory diseases not responding to conservative measures The following situations are the sources of continued discussion: [ Grade BID] 1. How should frontal sinusitis be treated which has not responded to conservative measures nor been operated on before? Depending on the individual situation, in most cases endonasal type I or type II drainage will be sufficient, whereas in severe polyposis with Samter's triad or other risk factors, a primary type III operation may be indicated. 2. Chronic postoperative frontal sinusitis after one or even several previous operations otherwise referred to as 'iatrogenic' sinusitis.83, 85, 96 This term suggests that previous surgeons have made mistakes. Since many other factors may have
Chapter
3.
4.
5.
.
! .I
" I.
contributed to an unsatisfactory surgical outcome of treatment such as a particular anatomical situation, it seems more appropriate to use the term 'postoperative sinusitis' indicating that such a patient has already undergone surgery, an important fact in further decision making. In many patients one can prove with CT that the ethmoidectomy was incomplete. Inflamed residual anterior ethmoid cells often cause symptoms of chronic frontal sinusitis, whereas the more posteriorly located, well-drained parts of the sinus system are aerated. In this situation, completion of the ethmoidectomy in combination with a type lIa/b is indicated. In the case of Samter's triad and other risk factors, type III drainage is the best choice. If the patient had numerous operations before and this is to be his 'last' sinus operation, the choice is between type III drainage and the osteoplastic flap procedure with obliteration. If the frontal sinus is large and has an anterior posterior diameter of at least 0.8 mm, type III drainage may be tried. If the frontal sinus has a smaller diameter, frontal sinus fat obliteration is the safer technique although more extensive. How radical should extended primary surgery be in patients with extensive polyposis in the frontal sinus? In this situation, particularly in the presence of aspirin hypersensitivity and/or asthma, experience has shown that the primary type III drainage is most likely to lead to success. In the case of recurrence and severe frontal sinus symptoms, an osteoplastic operation is indicated. Should patients with so-called spontaneous or postoperative mucocoeles of the frontal sinus be operated on endonasally or via an external approach? As long as the endonasal route using type II or type III provides sufficient drainage and not a bottleneck situation, endonasal marsupialization is possible. However, if the medial border of the mucocoele is laterally to a vertical line through the lamina papyracea, the endonasal approach is rarely possible. This is also the case if, usually after several previous operations, multiple mucocoeles are diagnosed. In this situation the frontal sinus obliteration is usually indicated. The final decision has to be made on the basis of a multiplanar CT, often in combination with MRI, since MRI gives the best proof of a mucopyocoele. A previous Jansen Ritter, Howarth or Lynch operation is not per se a contraindication to endonasal drainage. Is a Pott's puffy tumour always an indication for an external procedure? If the anterior posterior diameter of the frontal sinus is 0.8 mm or greater, the likelihood of a successful type III drainage is high enough to be tried. Long-term postoperative antibiotic therapy is mandatory.
1 1 8 The fronta l sinus I 15 19
However, these general guidelines cannot replace personal experience.
Frontal pneum osinus dil atans DEFI NITI ON
Pneumatization of the paranasal sinuses varies between individuals to a considerable extent. Well-pneumatized sinuses are usually lined by normal mucosa, but some times paranasal sinuses may be hyperpneumatized on one or both sides. Occasionally, pneumatization extends beyond the confines of the frontal bone and leads to an unaesthetic swelling or pneumosinus dilatans frontalis. 120 In this situation, the bony frontal sinus walls are still intact. If not, a frontal pneumocoele has developed.121 Approximately 13 percent of pneumosinus dilatans cases are associated with arachnoid cysts, or occasionally with other conditions such as meningioma, fibrous dysplasia, acromegaly and craniocerebral hemiatrophy (Dyke-Da vidoff-Masson syndrome). 122 Therefore, magnetic reso nance imaging is indicated where CT is suspicious for an intracranial lesion.
CLINICAL SYM PTOMS
frontal sinus most common
Clinically, many patients do not suffer anything more than the psychological impact of the deformity. Some have problems with frontal pain associated with baro traumas (e.g. flying, scuba diving) or sneezing. The majority of patients are men in their third decade. Other sinuses may be affected alone or in addition to the frontal, e.g. the sphenoid sinus.123, 124 The dilated sphenoid sinus may be associated by uni- or bilateral visual decrease including blindness, which may improve after anterior wall resection to produce optic nerve decompression.
AETIOLOGY AN D PATHOGEN ESIS
The aetiology is unclear, but suggestions include a spontaneously discharging frontal sinus mucocoele, 125 though this is not convincing, since they usually develop into the orbit. In other cases, a valve mechanism has been discussed, due to a large anterior ethmoid cell and mucosal swelling of the frontonasal recess.121, 126 Some researchers have found increased pressure in the frontal sinus, 127 others have found negative pressure which is difficult to explain.128 The stimulation of paranasal sinus pneumatiza tion by growth and sexual hormones regulating the activity of osteoblasts and osteoclasts has also been proposed.126
DIFFERENTIAL D IAG NOSIS
The differential diagnosis includes the deformities found in acromegaly, fibrous dysplasia, Sturge-Weber syndrome
!
!
I
1520 I PART 1 3 TH E NOSE AND PARANASAL SI NUSES and
the p neumocoele.
Computerized
tomography is
essential to establish the diagnosis and as
a
TU MOURS
preoperative
assessment.
Introd u cti on a nd the role of i ma ging
SU RGICAL TH ERAPY
More
: The therapy of choice for the b ulging of the anterior wall \of the frontal sinus is its reduction and plastic reconstruc l tion and eradication of any frontal sinus patholo gy, either 129, 130, 1 3 1 I . n . or 0 bliteratlOn. b Y Improvement 0 f dramage ' Draf's technique, the anterior wall of the frontal sinus is elevated via a coronal incision in the same way
as in the
osteoplastic flap operation
If frontal
(Figure 1 1 8.14a-d).
sinus obliteration is necessary, the process described in
Figure 118. 1 4e--h should be followed. si nus wall osteoplasty, horizontal
For anterior frontal
full thickness bone strips
are removed after the anterior wall has been elevated, whilst still being attached by galea-periosteum. If oblitera tion is required, first the mucosa is removed delicately using the microscope, if not, the mucosa is left on the i n ner table. To resect the bone strips, the
full thickness
resection should be commenced at the inner table. The width and the number of bone strips depend o n the degree of bulging
(Figure 1 1 8. 15).
bony swelling and reconstruction to the desired degree. Comp licated reassembly and plating is not necessary. observation
of
endonasal
microAendoscopic
surgery
has gained increasing importance fo r removal of tumouIS in the nasal cavity, paranasal sinuses, as well
as
the
anterior and central skull base around the clivus. In this regard, the frontal sinus is a very specific and difficult area from the technical point of view of the tumour excision itself. In the frontal sinus, imaging plays a useful role i n obtaining reliable information on the type of tumour, whether it is likely to be
benign or malignant, the point of
origin, extent and any concomitant inflamm atory reac tion.
I maging helps to differentiate osseous and fibro
osseous lesions from soft tissue tumours, although in many cases
a
more specific pathologic-anatomic diag
is not possible. The best information is achieved through a combination of CT and MRI, starting with CT, which is always needed to demonstrate individual surgical anatomy. [ Grade D] nosis
Replacing the fragments of
the anterior wall includes automatic reduction of the
Long-term
recently,
up
to
eight
years has l3 2 [**]
Ind i cati ons for endonasa l tu m our su rgery of the fronta l sinus
shown satisfactory results witho ut complications.
In general, it is preferable to remove a frontal sinus
[Grade
tumo ur in the most minimally invasive way avoiding
D]
Fi g u re 1 1 8. 1 5 Anterior frontal sinus wal l osteoplasty for pneumatosinus frontalis dilatans. (a) Frontal sinus with bulg i ng of the anterior wal l (sag ittal view). Blue markings show the bone stri pes to be resected. The galea-periosteu m is left intact. (b) Th e intraoperative situation after elevation of the bone flap a n d resection of bone stri pes using a diamond burr. (c) Postoperative si tuation (sagittal vi ew) : bone frag ments are adapted in a stabi le position because of the intact periosteu m, bu lging is corrected . Redrawn from Ref. 1 3 1 , with permission.
/
/
i
Ch a pter 1 1 8 Th e fro nta l s i n u s I 1 5 2 1
visible scars . For most frontoethmoidal tu mo urs, the following stepwise approaches may be valid : 1 32 1.
the endonasal;
2. the midfacial degloving; and
3. the subcranial according to Raveh et al. 133 In the author's opin ion, the 'classic' lateral rhi noto my is only if an o rbi tal exenteration
nowadays justified necessary at
is
the same time.
The indication for endonasal tu mour surgery depe nds
on the type, location, extension and origin of the lesion, as well as the skill of the inclivi dual surgeo n . The degree of pneumatization of the frontal sinus is another imp o rtan t factor. The better the pnewnatizati on, the wider the
radius of action for the endonasal surgeon and this is at least as important as the skill of the surgeon. Vast experience in dealing with infla mmato ry diseases and also endonasal duraplasty is . manda tory
,
together with ex
pertise in head and neck surgery, in cludin g the differen t external approaches in this area. If the surgeon l acks
neurosurgical traini ng him self, close cooperation with neurosurgeons
major
in
intra�tracranial
cases
is
mandatory. This becomes of partic ular i mp ortan ce when d eciding if an endonasal or a more extended approach, fo r example that advocated by Raveh et
al. 1 33 is required.
Genera l cl i n ica l reco m m endati o n s fo r su rgery of be n i g n fro nta l s i n us neo p la s m s Some general guidelirIes fo r op era t i n g on neop lasms of the frontal sinus may be of help. 1. Tumours
no t
extending more laterally
benign
than a
vertical pla ne through the lamina papyracea
(Figure 1 18.16a)
may be operated on t h rough
the nose. 2. Lesions whose point of origin or fixation is in the
lower third of the posterior sinus are most often
an
wall of the frontal
ind ic a tion for the
endonasal micro endo s copic p roce d u re
(Figure 1 1 8. 16b). Fixation at th e anterior wall of the fr ontal sinus is often a contraindication for thi s -
technique.
(b)
Tu m o u rs o ri g i na t i n g from the i nferi o r th i rd of
the posterior fro nta l si n us wa l l may be resected t h ro u g h the nose if the a n terior- poste rior d i ameter i s su fficiently w i d e , w h e reas t u m o u rs g row i n g from t he a n te rior wa l l n eed a n osteo p l a stic fla p a p p roach.
136
than the sinus from which they originate . Age o f present atio n is most co mmonly the second to fifth decade, with a male: female ratio o f approximately 3: 1 . Some have sugges ted an ethnic variatio n . 1 3 7 sinus, rather
rather it depends o n the degree and the
surgeon. [*] [Grade C]
OSTEOMA
Paranasal sinus osteomas are most frequently discov
ered incid en tally
on radiographs
or m ay enlarge, produ
I ntroducti on. defin itio n and eli n ical symptoms
cing symptoms such as swelling, or rare comp l ication s
Crani ofacial osteomas are
such
ing
in the paranasal
benign tumours often originat 1 34 , The frontal sinus is the
sinuses.
most frequen t location, followed by the eth moid, m axill ary sinus
/
th rou g h t h e l a m i n a papyracea c a n u s u a lly be removed e n d on asa i ly.
uncertain. Traditionally, they are named after the affected
contraindication to the endonasal approach;
S f
La n d m a rks for indication of e n d o n a sa l su rgery
originate on the sinus wall, but their aetiology is still
3 . Intracranial extension by itself is no t a
experience of the
Fig u re 1 1 8 . 1 6
of t u m o u rs. (a) Tu mours m edial to a virtua l vertica l p l a n e
and
sph enoid
sinus,
respectively. l 3S
Osteomas
as
visual impairment and intracranial neu rological ,
complications such as meningitis or pneum oencephalus with seizure, referable to thei r locatio n near to the orbit 1 39 or anterior cranial base . 1 38•
.M ·
1522 I
PA RT
1 3 TH E NOSE AN D PARANASAL S I N USES
Differential diagnosis of paranasal sinus osteomas includes other fibroosseous lesions, such as fibrous dysplasia or ossifying fibromas. These lesions may have a similar radiological appearance, but their borders are 4 usually less well defined than those of osteomas. 1 0 Speci fi c surgical techniq ue
The indications for the endonasal versus osteoplastic flap approach have been discussed above (see Guidelines for surgical therapy of frontal sinus inflammatory diseases not responding to conservative measures above) . During the endonasal procedure, mucosa should be preserved as much as possible. Small osteomas with a small origin may be removed in one piece. If the neoplasm has a wide base, attaches to the skull base, particularly next to the olfactory fossa or is of a larger size, it is strongly recommended to perform a pie<:emeal resection. The drill plays an important role, allowing debulking o f the lesion from inside until the shell is thin enough to be gently fractured and removed under direct vision avoiding damage of the dura, olfactory fibres or orbital contents. In the case of larger osteomas, a through and through cut is necessary to divide the tumour into two or more pieces. This needs to be done as long as the tumour is still immobile, which eases the procedure remarkably allowing larger tumours to be removed through the small nostrils. It depends on the size of the frontal sinus and of the tumour as to whether a type II or a type III drainage results. Results
For about ten years, the endonasal approach has been found to be suitable to treat tumours of the nose, paranasal sinuses and anterior skull base, 1 4 1 , 1 42 , 143, 144 4 4 amongst which are osteomas.7 6, 1 3, 1 5, 146 Schick et al.1 34 presented a retrospective study of 34 frontoethmoidal osteomas (23 frontal and 1 1 ethmoidal osteomas) treated at a tertiary care facility between 1990 and 1999. Clinical indications for surgery are listed in Table 1 1 8.5. Twenty-three osteomas (68 p ercent) were resected endonasally. Three endonasally resected tumours were not completely removed, two of which had under gone successful endonasal revision. The third small residual osteoma is under observation. If endonasal Ta b l e 118.5
Clin ical indications for surgery of frontoethmoidal
osteomas.
Osteoma adjacent to the frontal recess Ma nagement of chronic rhinosinusitis Chronic headache Frontal protuberance Mening itis Displacement of eye ball
n = 34.
16 6 7 3
removal is not possible) the osteoplastic flap procedure via a coronal incision allows for complete tumour resection with the best aesthetic result. The hair is not shaved to avoid any surgical stigma for the patient. It depends on how far the mucosa has been preserved during tumour removal whether the sinus may be left alone or whether obliteration is needed. [**1*1
FI B R O U S DYS P LASIA
I ntroduction, defi nition and clinical sym pto ms
4 Fibrous dysplasia is a tumour-like lesion of the bone. 1 7 It is self-limiting) is not encapsulated and is characterized by replacement of normal bone with cellular fibrous connective tissue, which contains irregular trabecles of immature, nonlamellar, metaplastic bone. The aetiology is unknown, but different hypotheses have been dis cussed. 1 48 The disease may develop at an early age, progress actively during childhood and stabilize in adulthood. 1 49 In the majority of cases, fibrous dysplasia is diagnosed before the second decade of life, rarely after the fifth. This disease is much more frequent in white populations than black 1 47 and the monostotic form is found more often in females than in males. Clinically, three types of fibrous dysplasia are differentiated: 1 . monostotic; 2. polyostotic; 3. McCune-Albright syndrome, which presents as a combination of polyostotic fibrous dysplasia, skin hyperpigmentation and endocrine dysfunction. It occurs in one of 30-40 cases of fibrous dysplasia.
The skull is involved in about only 15 percent with the majority being monostotic. One-third of cases are located in the maxilla or mandible, 150 sometimes the frontal or sphenoid sinus is obliterated by the disease. A mucocoele only develops if fibrous dysplasia involves an already existing frontal sinus, which is seldom, because of the early age onset. The ethmoid as a starting point has been reported in single case publications. l S I There are only a few clinical symptoms of fibro us dysplasia. In three-quarters of cases, palpable or visible swelling of the involved bone is found at initial presentation, with pain being a rare complaint. Deformity and compression of functio nally important structures create the main symptomatology. Where the frontal, ethmoidal or sphenoid bones are involved in this disease, visual decrease due to optic nerve compression and resulting atrophy may occur. Since this process is very indolent, this important symptom may manifest late. Rarely, extended monostotic frontoorbital fibrous dyspla sia leads to thinning of the dura with consequent destruction. of the posterior frontal sinus wall, signs of meningitis and encephalitis resulting in convulsion. 15 2
/
/
": : t!.· -
'- / �\.�
Cha pter
The monostotic type does not usually progress after puberty, although episodic growth is described into the fourth decade of life. IS3 Using CT and MRI, suspicion of fibrous dysplasia can be raised by imaging in the majority of cases. The differential diagnoses include ossifying fibroma, histiocytosis X, Paget's disease, en plaque meningioma, aneurysmal bone cyst, giant cell tumour and the brown tumour of hyperparathyroidism. 1s4 Ossifying fibroma is the most difficult to distinguish from fibrous dysplasia. Compared with fibrous dysplasia, it is a better demarcated expansile lesion with smooth margins and tends to be more aggressively encroaching on the nasal fossae, orbits and paranasal sinuses. 1 ss If in doubt, a biopsy should be undertaken. Specific su rgical tech niq ue. incl uding navigation
Surgery may target complete removal of this space occupying lesion as long it is not too extensive and allowing resection without too many risks. The defect created in the forehead needs to be reconstructed to avoid an unaesthetic deformity. Healthy autogenic bone, for example from the temporal region, is an excellent material.1S6 Coronal incision and temporary elevation of the temporal muscle allows a full thickness calvarial bone to be taken from which, after splitting, the inner table may be used to cover the donor site, whereas the outer layer is ideal for forehead reconstruction. As long as the forehead defect is not connected to the sinuses or the nasal cavity, some artificial material for bone replacement may work well. Complete resection means a minimal chance of recurrence. When fibrous dysplasia cannot be resected completely, surgery for contouring or, in special situations decom 2 pression of the optic nerve are important options. 1 , 22, 23 For optic nerve decompression, the patient needs to be informed that the visual decrease already acquired will not usually improve, but stopping further visual loss is a possibility. For removing major osseous lesions in difficult locations next to functionally important vascular and nerve structures, the use of navigation systems is helpful and may reduce the length of surgery. [*]
I NVERTED PAPI LLOMA I ntroduction. defi n ition and cl i n ical sym ptoms
Inverted papilloma is a benign, epithelial neoplasm originating from the Schneiderian membrane of the nose and paranasal sinuses. It usually arises from the lateral nasal wall, in the middle meatus, often extending to the ethmoid and maxillary sinuses. In advanced cases, extension into all of the ipsilateral paranasal sinuses may occur, whereas intracranial growth and dura penetration are rare. 1S7 Histologically, the inverted papilloma is a tumour in which there is inversion of the neoplastic . epithelium into the underlying stroma rather than proliferation outwards.
1 1 8 The fronta l si nus I 1523
The pathogenesis of this lesion still remains unclear, although allergy, chronic sinusitis and viral infection have been suggested as possible causes.1S8 Inverted papilloma has been reported to arise in all age groups with an incidence varying from 0.5 to 4 percent of all primary nasal tumours. The most common presenting symptom is unilateral nasal obstruction, often combined with rhinorrhoea and epistaxis. Appropriate imaging combining CT and MRI is of utmost importance in any unilateral space-occupying lesion of the nose and paranasal sinuses. Often MRI shows an image with streaky delineation, typical, or at least highly suspicious, of inverted papilloma, I S9 allowing for informed discussion with the patient about the possibility of more extended surgery, particularly when inverted papilloma is also associated with carcinoma. Sometimes, in cases without bone destruction, neither CT nor MRI is helpful in the qualitative diagnosis, but they at least provide the suspicion of a neoplasm. 19 MRI is the first imaging modality to perform in the follow up after removal of inverted papillomas. 160 Specific surg i ca l indication a n d tech niq ue
Inverted papilloma has been associated with a high rate of recurrence between 0 and 78 percent, malignant transfor mation, residual disease and a tendency towards multi centricity. 'Recurrence' actually represents residual disease in most cases, so the basic problem facing the clinician is to determine adequate treatment. Besides the more extended approaches of midfacial degloving, the subcranial ap proach and more rarely, lateral rhinotomy, the endonasal operation using both microscope and endoscope have grown in importance since the early 1990s.161, 162 In the case of frontal sinus involvement, the endonasal route is appropriate as long as there are no signs of major bone destruction caused by the tumour and as long there is no significant extension of the neoplasm lateral to a sagittal, vertical plane through the lamina papyracea (Figure 118.16a) . It is mandatory to resect not only the tumour, but also to remove the mucoperiosteum in areas from which the tumour originates using the drill. Intraoperative histologic control by frozen section is strongly recommended. Because of the small but definite association with carcinoma « 2 percent) , one should separate the specimens according to their different sites of origin to obtain the most detailed mapping of the tumout. It depends on the pneumatization which type of frontal sinus drainage is recommended. In well pneumatized cases a type II drainage is recommended, while in minor pneumatized patients a type III drainage provides a sufficient connection between the frontal sinus and the nasal and ethmoidal cavity, which is important to avoid subsequent mucocoele formation. Statistics a n d results
There is no statistical evaluation of results after surgery of inverted papillomas of the nasal cavity and paranasal
I
1524 1
PART 1 3 THE NOSE AND PARANASAL S I NUSES
sinuses with regard to frontal sinus involvement. Early diagnosis and precise identification of lesions by modern
imaging techniques has led to an increasing tendency for using
the
more
functional
and
minimally
invasive
endonasal approach with both microscope and endo
scope. Waitz and Wigan d 1 6 1 reported one of the largest
and earliest series on
patients, who underwent surgery
35
by an intranasal endoscopic approach, with a
17
percent
recurrence rate at nearly two years follow up. Compara
tively, extranasal approaches in relapse rate of
19
16 patients resulted
in a
percent. Endoscopic surgery seems to be
Malignant tumours of the
destruction and are j ust reaching the frontal sinus, may be
operated on via the endonasal route.
More extensive tumo u rs of this type, or pri mary
malignant frontal sinus tumours, may be approached by
the subcranial technique, according to Raveh et al. , 133 through a coronal incision, without shaving the hair,
sometimes in combination with midfacial degloving,
also allows man agement of malignancies with skull base
or even intradural invo lvement.
sphenoid sinus. Plinkert et al. 1 63 recommend that the
techniques:
endonasal approach is reliable fo r processes restricted to the middle nasal meatus and the anterior ethmoidal cells.
if
the lower sinuses a re involved. The subcranial approach
successful even in the treatment of large lesions affecting the posterior ethmoidal cells, the nasofrontal recess or the
nasal cavity and other
paranasal sinuses, which have not led to maj or bone
To su m mcuize , there is a stepladder of three surgical
( 1)
endonasal;
(2)
midfacial degloving;
(3)
subcranial approach , 1 33 which has proved t o b e very efficient when deal ing with malignant tumours of the
In more recent studies, Stankiewicz and Girgis, l64 McCary
nasal cavity and the paranasal sinuses, including the
et al. 1 68 and Cooter et al. 169 have do cumented similar
advantage o f all these approaches is the avoidance o f
et
aI., 1 65 Peter and Grossenbacher, l 66 Tsue
et
success using the same technique. Brors et a large series o f
al., 167 Homer
al. l 44 reported 33 received
patients, of whom
37
endonasal treatment. The follow-up period ranged from
12
months to 1 0 years,
with a mean of 3.4 years. The 16.2 percent (six of 37) and
overall recurrence rate was
revision surgery was necessary in six cases between o ne and
three years
after
the first operation.
Malignant
changes were histologically diagnosed in three cases. Between January
1992
and September
et al. 1 70 collected a series of
pap ill omas
undergoing
47
2000, Tomenzoli
p atients with inverted
endoscopic resection.
Massive
skull base erosion, intradural and intraorbital extensio n ,
extensive involvement of the frontal sinus, abundant scar
frontal sin us and
the anterior sku ll base.
The great
visible scars, a fact much appreciated b y t h e patients. The lateral rhinotomy is generally reserved the orbit is needed simultaneously. 1 32
if [*]
exenteration of
CO NCLUSION Surgery of the frontal sinus has changed remarkably during the last decade mainly for treatment of inflam
matory diseases, but also fo r removal of tumours, despite various opinions in different countries. 17l Different degrees of endonasal frontal sinus drainage , leaving
the
bony borders
o f the
outlet
intact
and
tissue due to previous surgery and concomitant presence
preserving the mucosa as much as possible, offer better
contraindications for a purely endoscop ic approach. Up
external approach .
of squamous cell carcinoma were considered absolute to September
2000,
mean follow up of
no recurrences were observed with a
39
months ( range,
24-1 3 0
months ) .
The literature and the author's o wn experi ence suggest
that inverted papilloma of the nose and paranasal sin uses can be successfully treated with endonasal approaches,
where appropriately selected.
[**1*1
results and less morbid i ty compared with the classical
If endonasal frontal sinus surgery is
not expected to lead to a satisfying, long-term result or
endonasal revision is not successsful, the osteoplastic frontal sinus op eration via a coronal approach, without shaving the hair, is the ultimate) and percent of cases a definite, solution .
in more than 90 In cases of chronic
i n flammatory disease) obliteration of the frontal sinus is frequently necessary, whereas after removal of benign
tumours with preservation o f frontal sinus mucosa this may not be needed.
I n d i cation and strategy for malignant tum our resection Primary malignant tumours o f the frontal si nus are very rare. Generally, malignant tumours of the nasal cavity or
the other sinuses h ave extended into the frontal sinus and
•
the combination of CT and MRI helps to analyse this
special situation preoperatively, with confirmation by frozen sections intraoperatively. [ Grade Cj
Complete resection of the neoplasm is the absolute
priority. However, another principle should be surgery as extensive as necessary, b ut as minimally traumatic as possible, requiring a great deal of experience. / /
/
Ch a pter 11 8
The frontal si nus I 1 525
>-
Th e most appropriate pri mary treatment of the frontal sinus in cases of severe polyposis. in Samter's triad, Kartagener's syndrome and mucoviscidosis needs to be determined. Should treatment be more conservative or should immediate type I I I drainage be undertaken? >- A prospective study using one or other surgical option a l ternately would be of g reat benefit. >- The principle of preservation or major resection of the m iddle tu rbinate in severe polyposis is a nother a rea of intensive discussion where better evidence is requ i red. A prospective study comparing the 101'\g term results after alternative application of one or other method in simi lar cases would be of major benefit.
tGr
./ Nasal fistulas and cysts require careful radiologic evaluation to plan surg ery precisely and to decide whether or not interd isciplinary cooperation is needed for complete resection. ./ For fractures of the frontal sinus. facial skeleton and anterior skull base. adequate prima ry care is essentia l includ ing reconstruction o f a possible dural defect to avoid late post-tr�umatic complications. ./ Riedel's radical frontal sinus resection to treat the complex frontal sinus trauma is no longer acceptable. Best possible prima ry reconstruction of a l l tissues involved may give superior functional a n d aesthetic results. ./ First choice of surgical treatment for acute or chronic fronta l sinus disease, resistant to medical the rapy, is the endonasa l technique usi ng the microscope and/or endoscope as visual a i ds. .; In case endonasal frontal sinus surgery does not give the desired result, osteoplastic fronta l sinus obl iteration is the technique of choice to obtain a definite solution . ./ The 'classic' external frontoorbital frontal sinus operation (Ja nsen, Ritter, Howarth, and Lynch) seems, in the author's opinion, to be the wrong concept to ach ieve this goal. ./ Endonasal micro-endoscopic resection has to be considered more and more as a minimal ly traumatizing way for complete resection of many appropriately sized ben ig n a nd also some malignant tumours of the nose, ' paranasal sinuses a n d a nterior skull base.
ACKNOWLEDG EM ENTS The author thanks the former Director and Vice Director of the D epartment of Radiology, Fulda Hospital, Prof Dr
IP Haas and Dr Gabriele Kahle, as well
as
Prof Dr med
Erich Hofmann, Director of the D epartment of Interven tional Neuroradiology, Fulda Hospital, for the continuous excellent cooperation and the radiolo gic imaging
in this
chapter.
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Recommendations for best clinical practice of fronta l sinus problems are based on retrospective stud ies and expert opinion. >- Prospective long -term studies (ten years or more) a re necessary to achieve more information a bout the long-term resu lts and late surgical complications, e.g. mucocoeles. >- Recent research demonstrates the important role of fungi in chronic eosinoph i l i c fu ngal rh inosinusitis. I n the future. i t would b e interesting to see i f the combination of specific med ica l and surg ical treatment will lead to better results.
* 6. *
7.
8. * 9.
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1 526 I PART 1 3 TH E NOSE AN D PARANASAL SINUSES
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1 1 8 The f ronta l sinus 1 1 527
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-- - ---
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_ __ _
1 528 I PART 1 3 THE NOSE AND PARANASAL SIN USES
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*1 02.
1 03.
1 04.
1 05.
1 06.
... ! ' \
�
Chapter
1 07.
1 08. 1 09.
1 1 0.
111.
1 1 2.
1 1 3.
1 1 4.
1 1 5.
-j
1 1 6.
1 1 7.
1 1 8.
1 1 9.
1 20. 1 21 .
1 22.
1 23.
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!
.,
! -. -- - . �
-. --
. . -�---�- -.- -- -
/
..-
1 1 8 The fronta l sinus I 1 529
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!
•
%'
1 530 I PART 1 3 TH E NOSE AND PARANASAL S I N USES zugaenge). European Archives of Otorhinolaryngology. Su pplement 1 993 ; I : 1 05-203. 1 42. Anderhuber W, Sta mmberger H, Walch CH, Fock CH, Rega uer S, Luxenberger W et al. Rigid endoscopy i n m i n i ma l ly i nvasive thera py o f tumors o f t h e para nasal sin uses a nd sku l l base. Minimally Invasive Therapy and Allied Technologies. 1 999 ; 8: 25-32. 1 43 . Hosema n n W. Die endonasa le Chiru rg ie der Nasen nebenhoeh len - konzepte, tech n i ken, ergebnisse, komplikationen, revisionseing riffe (endonasal surgery of para nasal sin uses - concepts, techniques, resu lts, com plications, revision surgery). I n : D raf W (ed.) . Aktuelle
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1 999 ; 7 : 33-8. Som PM, D i l lon WP, Sze G, Lidov M, B i l ler H F, Lawson W. Benign and ma l ig n a nt sinonasa l lesions with i ntracra nial extension : Differentiation with M R imagi ng. Radiology. 1 989 ; 1 7 2 : 763-6. Petit P, Viva rrat-Perrin L, Cha m psa u r P, J u h a n V, Chagnaud C, Vidal V et al. Radiological fol low-u p of i nverted papil loma. European Radiology. 2000 ; 1 0 : 1 1 84-9. Waitz G, Wigand M E. Results of endoscopic sinus su rgery for the treatment of i nverted pa pi l lomas. Laryngoscope. 1 99 2 ; 1 02 : 9 1 7-22. Ka mel R. Conservative endoscopic surgery in i nverted pa p i l loma. Archives of Otolaryngology - Head and Neck Surgery. 1 99 2 ; 1 1 8 : 649-53. P l i n kert PK, Ruck P, Bauma n n I , Scheffl e r B. I nverted pa pil loma of the nose and pa ra nasal sin uses : Diagnosis, operative procedure a n d ana lysis of the cytokeratin profi le. Laryngo- Rhino- Otologie. 1 997; 76: 2 1 6-27. Sta n kiewicz JA, Girgis SJ. Endoscopic surgical treatment of nasal and pa ra nasal sinus i nverted pa pil loma. Otolaryngology a n d Head a n d Neck Surgery. 1 993 ; 1 09 : 988-95. McCa ry WS, Gross CW, Reibel J F, Ca ntre l l RW. Pre l i m i n a ry report : Endoscopic versus external surgery i n the ma nagement of i nverted pa pil loma. Laryngoscope. 1 994; 1 04 : 41 5-9. Peter B, Grossenbacher R. The i nverted pa p i l l oma of the nose and para nasa l sin uses. Laryngo- Rhino- Otologie. 1 99 7 ; 7 6 : 1 4-8. Tsue TI, Bai let JW, Ba rlow DW, Makielski KH. Bilatera l sinonasa l pa pil lomas in a p lastic maxi l lary sin uses. American Journal of Otolaryngology. 1 997 ; 1 8 : 263-8. Homer JJ, Jones NS, Bradley PJ. The role of endoscopy in the ma nagement of nasal neoplasia. American Journal of Rhinology. 1 997 ; 1 1 : 41 -7. Cooter MS, Cha rlton SA, Lafren iere D, Spi ro J. Endoscopic ma nagement of i nverted nasal pa p i l loma i n a ch ild. Otolaryngology and Head and Neck Surgery. 1 998 ; 1 1 8 : 876-9. Tomenzol i D, Caste l n u ovo P, Pagel la F, Berlucchi M, Pia nti L, Delu G et al. Different endoscopic surgica l strategies in the ma nagement of i nverted pa p i l loma. Experience with 47 patients. Laryngoscope. 2004; 1 1 4 : 1 93-200. Molony N C, Ah-See K, Rach m a n idou A, Draf W. A su rvey of contempora ry manag ement of fronta l si nus d isease in the U n ited Ki ngdom. European Archives of Otorhinolaryngology. 2000 ; 2 5 7 : 247-50.
119 Mucocoeles VALERIE J LUND
Definition Site Aetiology Clinical features Imaging Treatment Results
1531 1531 1531 1532 1533 1535 1535
1535 1537 1537 1537
Complications Mucocoeles in children Key points Best clinical practice Deficiencies in current knowledge and areas for future
1537 1537
research References
The data in this chapter are supported by a Medline search using the key words mucocoeles, paranasal sinuses, frontoethmoidal, maxillary and sphenoid.
DEFINITION A mucocoele is an epithelial-lined, mucus-containing sac completely filling the sinus and capable of expansion.! This is in contradistinction to a blocked sinus cavity which simply contains mucus. 2
SITE The fronto-ethmoidal region is by far the most commonly affected overall and the maxillary sinus the least, but a proportion of sphenoidal mucocoeles present to neurosurgeons and the number is therefore probably more common than in this personal series (Table 119.1). It is possible that the frontoethmoidal area is more susceptible to mucocoele formation due to the complexity of its drainage, as compared to the sphenoid and maxillary sinusus. [**]
(Table 119.2).3 Fewer than 5 percent are bilateral and/or multiloculated. There may be a considerable time lag between the initiating factor and the clinical presentation with the mucocoele. In the case of surgery or trauma this is an average of 23 years, whereas following an acute infective episode the mean time to presentation is 22 months. 3 [**] Mucocoeles are thought to arise as a consequence of obstruction plus inflammation. Three main theories of pathogenesis are found in the literature: 1. pressure erosion; 2. cystic degeneration of glandular tissue; 3. active bone resorption and regeneration. Table 119.1
Distribution of site of mucocoeles.
Frontoeth moid
AETIOLOGY Mucocoeles are relatively uncommon and occur in at least a third of cases without an obvious predisposing factor
89
Ethmoid
8
Sphenoid
2
Maxilla
n = 166 patients.
1532 I
PART 13 THE NOSE AND PARANASAl SINUSES
Aetiological factors in frontoethmoidal mucocoeles.
Table 119.2
Percentage None
37
Infection
23
Polyps
21
Trauma
11
Other n
=
8
45 patients. Repri nted from Ref. 3, with permission.
Although raised pressure
within the mucocoele has been
reported, the histological appearances of the mucocoele lining are against this, being composed of pseudo strati fied, pseudocolumnar epithelium with some squamous
Figure 119.1
Photomicrograph showing positive staining for
IL-l in the epithelial cells of a frontal mucocoele.
metaplasia, goblet cell hyperplasia and a cellular infiltrate reflecting both acute and/or chronic inflammation.4 Thus neutrophils, macrophages, monocytes and T cells may be found with a variable degree of fibroblastic activity.
Infection?
[***]
Cystic degeneration of glandular tissue may account for some of the 'mucocoeles' reported following Cald well-Luc
operations
Japan,
in
structure is not found
but
a
double-walled
in the classical mucocoele.s [**]
Using the analogy of the odontogenic cyst, a number of bone-resorbing factors have been found in mucocoele
Cytokines (IL-1 TNFa)
mucosa, including prostaglandins such as PGE2, leuko
,
trienes, HETES and a range of cytokines.6 In a study comparing
mucocoele
increased levels of
factor
C1
lining
with
IL-IO'.., IL-l�
were found
together
<normal'
Fibro blast
with upregulation of
vascular adhesion molecules, e-selectin and Not only were these absent
\
controls
and tumour necrosis
I-CA.l\Il.7
in the normal controls but
they were minimally expressed in chronic rhinosinusitis
PG�
and absent in the lining from a simply obstructed sinus.
Thus, although obstruction is clearly important, some
other events are necessary to initiate the production of bone-resorbing cytokines and a cascade of inflammation resulting
in
formation
(Figures 119.1
both
bone
resorption and
In the normal situation, balanced by osteolysis.
and
new
bone
Osteoclastic bone resorption
119.2). [***] new
bone
formation is
In chronic rhinosinusitis
the
Figure 119.2
A schematic diagram showing possible
balance is tipped in favour of osteogenesis and sclerosis,
pathogenesis for mucocoeles.
bone resorption leading to spread of infection. In the
abnormalities on a preoperative ophthalmic assessment of
whereas in acute complicated sinusitis there is significant mucocoele,
the balance
is just
tipped
in
favour
of
osteolysis, facilitating expansion of the lesion unless acute
infection supervenes with pyocoele
formation
(Figure 119.3).
120 patients are shown in
Table 119.3.
Endoscopic examination may reveal the expanded mass presenting in the nasal cavity and acute infection,
and/or attempts at drainage may result
in fistulas through
the upper lid. The mucocoeles in the maxillary sinus may expand into the nasal cavity producing nasal obstruction or erode the anterior wall producing swelling of the cheek. In addition) the floor of the orbit may be lifted up,
CLINICAL FEATURES
again resulting in displacement of the globe. Typically, patients with mucocoeles in the frontoethmoi
dal region are referred to ophthalmic surgeons in the first
instance d�e to orbital displacement
. /
(Figure 119.4).
The
In the sphenoid) the intimate relation of the sinus to the orbital apex and cavernous sinus may lead to
an
acute
presentation with visual disturbance, including diplopia
/
J
Chapter 119 Mucocoeles
Normal
Osteogenesis
I 1533
Osteolysis
Chronic rhinosinusitis
L Mucocoele ----r-----JI ~ ~ Figure 119.3
Diagram representing bone dynamics in
sinonasal disease.
Figure 119.5
Coronal CT scan showing frontal mucocoele in
the patient in Figure 119.4.
Figure 119.4
Patient with frontal mucocoele displacing the
eye anteriorly, laterally and inferiorly with some mild associated preseptal inflammation.
Proptosis (1-17 mm) Lateral displacement (2-13 mm) Inferior displacement (1-8 mm) Diplopia (vertical) Limited ocular mobility Visual acuity reduced
91 55 59 95 55 9
and blindness. The patient may also complain of headache which is typically referred to the occipitoparietal region. [**]
IMAGING Computed tomography (CT) scanning is the optimum method of demonstrating a mucocoele, using the following protocol8 and may also show contributory
Figure 119.6
Axial CT showing biloculated ethmoid
mucocoele.
factors such as Paget's disease (Figures 119.5, 119.6, 119.7, 119.8 and 119.9). The appearances of the mucocoele contents on magnetic resonance imaging (MRI) vary considerably from low to high signal depending upon the constituents of the mucocoele and
1534 I PART 13 THE NOSE AND PARANASAL SINUSES are generally not very helpful (Figures 119.10 and 119.11). [**] The differential diagnosis is shown below: • • • •
fungal disease; cholesterol granuloma; odontogenic cyst (maxilla); neoplasia: - benign; - malignant.
Figure 119.9 mucocoeles.
Figure 119.7
Coronal CT scan showing bilateral frontal
Coronal CT scan showing sphenoid mucocoele.
Figure 119.8 Coronal CT scan showing frontal mucocoele with sclerosis in frontonasal recess, rendering an entirely endoscopic approach difficult.
Figure 119.10 Coronal Tl-weighted MRI scan with gadolinium, sh9wing ethmoidal mucocoele with enhancing contents.
Chapter 119 Mucocoeles
I 1535
stenting and subsequent circumferential scarring is avoided. Whatever approach is used, there is absolutely no necessity to reconstruct areas of bone resorption even when there is widespread dehiscence of the skull base. As long as the mucosal lining is intact, restitution of contour occurs very rapidly and in younger patients may even reossify.
RESULTS
Figure 119.11
Axial MRI scan post-gadolinium showing
maxillary sinus mucocoele (nonenhancing).
TREATMENT In the majority of cases an endonasal endoscopic · d .'9 10, 11 , 12, 13"14 15 When approapproach may b e utnlze priately selected, the advantages of the endoscopic approach are the lack of external scar, no disturbance of the trochlea and no supraorbital paresthesia. Although there will be significant reduction in the orbital displacement, a residuum of expanded bone may take some weeks or months to remodeL Patients should therefore be warned that the final cosmetic result may not be apparent for several months. However, this also has the advantage of minimizing any double vision secondary to the decompression. [Grade C] An endoscopic approach is ideal in those mucocoeles which can be accessed and widely marsupialized. Thus, virtually all ethmoidal, maxillary and sphenoidal mucocoeles may be managed by an entirely endoscopic approach. However, in a number of more complicated cases, particularly in the presence of significant pathology and/ or previous surgery, a combined endoscopic and external approach may be necessary in the frontal region. In a recent cohort of 48 patients, 20 were treated by an entirely endoscopic approach, but a combined endoscopic and small external incision was required in 28. 16 The external approaches include a Lynch-Howarth frontoethmoidectomy or an osteoplastic flap, the latter being particularly popular in the United States. [Grade B] In a classical Lynch-Howarth approach, the entire lateral support of the frontonasal recess is removed allowing medialization of the orbital contents which in turn leads to the high recurrence rates reported for this approach. When an exclusively endonasal approach is not possible, the external and endoscopic approaches may be combined, allowing a very limited amount of bone to be removed in this region. Thus, the need for artificial
In a series of 48 patients of similar demography and followup, the recurrence rate was 0 percent in the endoscopic group and 11 percent in the combined endoscopic and external group.16 However, when the aetiological factors leading to the mucocoele formation are compared, it is clear that the combined group were by far the most complex, the majority suffering widespread nasal polyposis/ chronic rhinosinusitis for which they had undergone multiple previous procedures (Tables 119.4 and 119.5). [**] In the vast majority of patients with frontoethmoidal mucocoeles, there is a significant improvement in their orbital status following surgery (Table 119.6). [**]
COMPLICATIONS The complications of endoscopic surgery are minimaL There is a potential risk of haemorrhage, a cerebrospinal fluid (CSF) leak and/ or orbital damage, though in practice this has not been reported. The complications associated with external frontoethmoidectomy and osteoplastic flap (with and without obliteration) are shown in Table 119.7. When visual loss has occurred, most often associated with an acute pyocoele of the sphenoid, rapid surgical decompression may result in restitution of vision, though the window of opportunity is estimated to be only a matter of hours. [**] Table 119.4
Results of endoscopic versus combined endoscopic
and external approaches for mucocoeles.
n
20
Age range
4-89 43
Mean
28 25-83 59 28
Follow-up range
12 6 2 7-61 months
Mean
34 months
44 months
Recurrence rate
0 0/0
110f0
Site frontoethmoid Ethmoid Sphenoid
Repri nted from Ref. 16, with permission.
10-76 months
1536 I PART 13 THE NOSE AND PARANASAL SINUSES
Table 119.5
Comparison of surgical treatment of frontoethmoidal mucocoeles. No.
Kennedy et oJ.9
Endoscopic, frontoethmoidectomy
Harrison and Lund17
External frontoethmoidectomy
Lund
Endoscopic drainage
8
Hardy and Montgomery1
Table 119.6
Osteoplastic flap
15
o
2-42 months
100
4
3-27 years
50
2
6- 132 months
116
6
3-19 years
Post-operative ophthalmic assessment
Proptosis
Resolved
75
Improved
25 100
L ateral displacement
Resolved
Inferior displacement
Resolved
90
Diplopia
Resolved
67
Persisted
33
Reprinted from Ref. 19, with permission.
Table 119.7
Complications of surgical treatment of mucocoeles reported in the literature. ef :renc-e
Patients �-
----
�.
--
%
External fro ntoeth moidectomy infec.ti on Primary operation site
Canalis et 01.20
1/112
Natvig and Larsen'
2/20
10.0
CSF leak
Canalis et 01.20
1/20
5.0
Webbing
Rubin et oe'
4/60
6.0
Diplopia
Lund and Rolfe19
7/22
32.0
0.9
Osteoplastic flap Cosmesis, frontal bossing, depression of bone
Sessions et 01.22 Ward and Bauknight23
3
Schenck24 Hardy and Montgomery18 1 Hardy and Montgomery 8
13/250
5.2
7/250
2.8
Primary operation site
1 Hardy and Montgomery 8
14/250
5.6
Fat
Sessions et oe2
13/250
5.2
7/250
2.8
'2/250
0.8
CSF leak I nfecti o n
Schenck24 Sessions et 01.22 Abdominal wound Laceration of dura Nasal skin necrosis
Schenck24
Hardy and Montgomery'8
Schenck24
1 Hardy and Montgomery 8
Hardy and Montgomery18
Chapter 119 Mucocoeles I 1537
MUCOCOELES IN CHILDREN Mucocoeles in children are exceptionally rare. In one of the largest series, seven have been described primarily affecting the anterior ethmoid and all following an acute infective episode. 25 In this personal series of seven patients, the anterior ethmoid sinuses were primarily affected, following an acute infective episode. Virtually all mucocoeles in children can be managed by an entirely endoscopic approach, thus avoiding an external facial incision. 26 [**]
REFERENCES
*
1.
2.
* *
3. 4.
5.
*
6.
7.
8.
9.
10.
11.
12. ./' CT scanning is the best investigative tool and an endonasal endoscopic approach is the first line of treatment, as long as the mucocoele can be accessed and widely marsupialized. ./' When required, a combined external and endoscopic approach avoids the need for artificial stenting. ./' A pyocoele with acute orbital symptoms requires emergency surgery.
13.
14.
15.
16.
Deficiencies in current knowledge and areas for future research 17. Further work is needed to identify why some individuals -are susceptible to this condition, whereas the majority are not.
I
ttlIt·
* 18.
Natvig K, Larsen TE. Mucocoele of the paranasal sinuses. Journal of Laryngology and Otology. 1978; 92: 1075-982. Schenck NL, Rauchbach E, Ogura JH. Frontal sinus disease. II. Development of the frontal sinus model: Occlusion of the nasofrontal duct. Laryngoscope. 1974; 84: 1233-47. Lund VJ. Anatomical considerations in the aetiology of fronto-ethmoidal mucoceles. Rhinology. 1987; 25: 83-8. Lund VJ, Milroy CM. Fronto-ethmoidal mucocoeles: A histopathological analysis. Journal of Laryngology and Otology. 1991; 105: 921-3. Moriyama H, Nakajima T, Honda Y. Studies on mucoceles of the ethmoid and sphenoid sinuses: Analysis of 47 cases. Journal of Laryngology and Otology. 1992; 106: 23-7. Lund VJ, Harvey W, Meghji S, Harris M. Prostaglandin synthesis in the pathogenesis of fronto-ethmoidal mucoceles. Acta Otolaryngologica. 1988; 106: 145-51. Lund VJ, Henderson B, Yu Song. Involvement of cytokines and vascular adhesion receptors in the pathology of fronto-ethmoidal mucocoeles. Acta Otolaryngologica. 1993; 113: 540-6. Lloyd G, Lund VJ, Savy L, Howard D. Optimum imaging for mucoceles. Journal of Laryngology and Otology. 2000; 114: 233-6. Kennedy OW, Josephson JS, Zinreich SJ, Mattox DE, Goldsmith MM. Endoscopic sinus surgery for mucoceles. Laryngoscope. 1989; 99: 885-95. Li J, Stankiewicz JA. The endoscopic approach to the lateral accessory sphenoid sinus. Otolaryngology Head and Neck Surgery. 1991; 105: 608-12. Naudo P, Gilain L, Coste A, Lelievre G, Peynegre R. Chirurgie fonctionnelle endoscopique des mucoceles sinusiennes. Annales d'Otolaryngologie et de Chirurgie Cervico Faciale. 1994; 111: 23-7. Beasley NJP, Jones NS. Paranasal sinus mucoceles, modern management. American Journal of Rhinology. 1995; 9: 251-6. Benninger MS, Marks S. The endoscopic management of sphenoid and ethmoid mucoceles with orbital and intranasal extension. Rhinology. 1995; 33: 157-61. Yardeni E. Les mucoceles sinusiennes: Place de la chirurgie endoscopique endonasle: A propos de 33 cas. These Universite Paul Sabatier, Toulouse III Facultes de Medecine, 1995. Makeieff M, Gardiner 0, Mondain M, Crampette L. Maxillary sinus mucoceles - 10 cases - 8 treated endoscopically. Rhinology. 1998; 36: 192-5. Lund VJ. Endoscopic management of paranasal sinus mucoceles. Journal of Laryngology and Otology. 1998; 112: 36-40. Harrison DFN, Lund VJ. Conditions simulating neoplasia. In: Harrison 0, Lund VJ (eds). Tumours of the upper jaw. Edinburgh: Churchill-Livingstone, 1991: 54-62. Hardy JM, Montgomery WW. Osteoplastic frontal sinusotomy. Annals of Otology. 1976; 85: 523-32.
1538 I PART 13 THE 19.
NOSE AND PARANASAL SINUSES
Lund VJ, Rolfe ME. Ophthalmic considerations in fronto-
23.
Head and Neck Surgery. 1973; 98: 389-90.
1989; 103: 667-9. 20.
Canalis JG, Zajtchuk JT, Jenkins HA. Ethmoidal mucoceles.
24.
Archives of Otolaryngology. 1978; 104: 268-91.
21.
and Neck Surgery. 1986; 112: 434-6.
22.
Sessions RB, Alford BR, Stratton C, Ainsworth JZ, Shill O. Current concepts of frontal sinus surgery: an appraisal of the osteoplastic flap-fat obliteration operation.
Laryngoscope. 1972; 82: 918-30.
Schenck NL. Frontal sinus disease: III, Experimental and clinical factors in failure of the frontal osteoplastic operation. Laryngoscope. 1975; 85: 76-82.
Rubin JS, Lund VJ, Salmon B. Frontoethmoidectomy in the treatment of mucoceles. Archives of Otolaryngology Head
Ward PH, Bauknight S. A serious cosmetic complication of the osteoplastic frontal flap. Archives of Otolaryngology
ethmoidal mucoceles. Journal of Laryngology and Otology.
25.
Hartley BE, Lund VJ. Endonasal drainage of paediatric paranasal sinus mucoceles. International Journal of
Pediatric Otorhinolaryngology. 1999; 50: 109-11. 26. Zrada SE, Issacson Gc. Endoscopic treatment of pediatric ethmoid mucoceles. American Journal of Otolaryngology. 1996; 17: 197-201.
120 Complications of rhinosinusitis
ROBERT SLACK AND RICHARD SIM
1539
Definition Classification Clinical presentation Investigati ons Treatment Prognosis
The data
1539 1540 1542 1543 1545
1546
Key points Best clinical practice Deficiencies in current knowledge and areas for future research References Further reading
1546 1547 1547 1548
in this chapter are supported by a PubMed search using the terms rhinosinusitis or sinogenic and complications, all
and focussing on orbital, intracranial) diagnosis, bacteriology and treatment. With the exception of Refs1, 2,3 and Re f. 4, evidence is based on case series analysis and expert opinion.
DEFINITION
vessel, such as the infraorbital canal, or the diploeic veins of the frontal and sphenoid bones. The absence of valves
A complication of rhinosinusitis may be defined as any adverse progression of chronic or acute bacterial infection beyond the paranasal sinuses, or compromise in function of any part of the body due to local or distant effects of the condition.
in the veins between the orbit and the sinuses facili t a t es
retrograde venous spread of infection. The second first molar dental root canals also provide a direct route of spread, although it is more common for dental problems to cause rhinosinusitis, rather than being the result of rhinosinusitis, with the exception of premolar and
uncomplicated dentalgia.
CLASSIFICATION
Local progression of disease in the sinuses will give
Table 120.1
effects that are usually specific for the
individual sinuses
and migh t be best considered relating to the individual
Acute
sinus groups.
Acute complications of rhinosinusitis can be divided into those that are due to local progression of the disease, and
sys temic presumed haematogenous spread. ,
Frontal Sinus A subperiosteal abscess may result from an acute episode of frontal rhinosinusitis if the local progression of the disease is through the outer table of the skull. This condition is still frequently referred to
LOCAL Local progression is via areas wh ere the surrounding bone is
thin, such
as
the lamina papyracea, or where there is a
direct anatomical connection by way of
i
•
I
a
nerve or blood
as
pou's puffy
tumour, following its description by Sir Percival Pott
1760. If the progress is inward, there may be
an
in
acute
intracranial complication, such as intracranial abscess or
meningitis.
j
/
1540 I PART
13 THE NOSE AND PARANASAL SINUSES
Ethmoid
The most important and frequent acute complication of ethmoid rhinosinusitis is orbital cellulitis, which can vary in degree and severity. A convenient, clinical classification of five stages5 (Figure 120.1) helps to determine the overall management of the patient (Table 120.1). [**] These stages are:
Preseptal cellulitis. Inflammation does not extend beyond the orbital septum (the site at which the medial orbital periosteal reflection attaches to the medial eyelid at the tarsal plate). 2. Postseptal cellulitis or orbital cellulitis without abscess. Inflammation extends into the tissues of the orbit. 3. Subperiosteal abscess. There is abscess formation deep to the periosteum of the orbital bones, usually the lamina papyracea. 4. Orbital abscess. There is abscess formation within the orbit which has breached the periosteum. 5. Cavernous sinus thrombosis/abscess. The inflammatory process has extended through the optic foramen into the cavernous sinus which thromboses and possibly progresses to abscess formation. 1.
Maxillary
Isolated maxillary rhinosinusitis rarely gives rise to acute local complications. Patients with acute swelling of the cheek are almost invariably suffering from a complication of primary dental disease rather than sinus infection, although there might be an associated maxillary rhino sinusitis secondary to the dental disease. Sphenoid
Acute local complications of sphenoid rhinosinusitis are rare, as indeed is sphenoid rhinosinusitis itself, but can result in cavernous sinus thrombosis by direct spread? Additionally, intracranial complications can occur as a result of a base of skull fracture through the sphenoid sinus. [**]
Chronic
Chronic complications of rhinosinusitis will usually be the result of chronic rhinosinusitis and are invariably local. As with acute complications, the nature of the complication depends on the particular sinus or group of sinuses involved. Mucocoeles are chronic, slowly expanding lesions in any of the sinuses that may result in bony erosion and subsequent extension beyond the sinus. If the mucocoele becomes secondarily infected and the contents purulent, it is described as a pyocoele (see Chapter 119, Mucocoeles). Although the role of chronic rhinosinusitis as the cause of a mucocoele is debatable, 25 percent of patients with a frontoethmoidal mucocoele have a history of rhinosinu sitis or surgery for rhinosinusitis.8 [**] In the maxillary sinus due to the proximity of the dental roots, which may even protrude into the maxillary antrum, the teeth may be affected by maxillary rhinosinusitis. However, this is rare and any dental effect other than pain is much more likely to be due to malignant rather than inflammatory disease of the maxillary sinuses. It is unusual for chronic rhinosinusitis to cause orbital cellulitis or intracranial complications unless there is an acute exacerbation. CLINICAL PRESENTATION
Any of the complications described above may present with a good history of preceding rhinosinusitis and/or obvious coexisting signs of rhinosinusitis. However, it is not uncommon for the rhinosinusitis itself to be 'occult' or asymptomatic. Indeed, in children it is much more likely that there will be no prior history of rhinosinusitis, with the complication presenting ab initio.
Orbital cellulitis
DISTANT Brain abscess
As already described, this would most commonly occur as a complication of local spread, but haematogenous spread may occur and has been described secondary to maxillary rhinosinusitis associated with dental disease. Septicaemia
As in any infective condition, progression to septicaemia and its sequelae may occur. Toxic shock syndrome
This has been described on at least one occasion; in any patient with systemic septic condition, the sinuses must be remembered as being a possible primary source.
The history here will usually be one of a mild upper respiratory tract infection accompanied or followed by swelling around the eye. It is far more common in children (50 percent under six years) 9 and young adults (76-85 percent under 20).1,10 Visual problems may be present if the problem is stage three (subperiosteal abscess) or beyond, and specific enquiries should be made regarding visual acuity and colour vision, problems which might indicate a compromise of optic nerve function. At stage five (cavernous sinus thrombosis) , as well as chemosis, periorbital oedema and proptosis, there will be a progressive opthalmoplegia (lateral gaze may be affected first) and visual impairment (possibly resulting in total blindness) due to direct cranial nerve involvement, together with other symptoms including headache and
Chapter 120
Complications of rhinosinusitis I 1541
Fig u r e 120.1 Various orbital complications on axial projection: (a) preseptal inflammation: (b) orbital cellulitis; (c) orbital cellulitis with subperiosteal (extra periosteal) abscess; (d) orbital cellulitis with intraperiosteal abscess. Red and yellow shading indicate inflammation/cellulitis, and green shading indicates pus. Redrawn from Ref. 6, with permission (continued over).
Table
120.1
Complications of rhinosin usitis.
BACK Intracra tal
Bony
Chronic
Presepta I cellulitis
Meningitis
Osteomyelitis (Pott's puffy tumour)
Mucocoele/pyocoele
Postseptal cellulitis or orbital cellulitis without abscess Subperiosteal abscess Or�ital or intraperiosteal abscess Cavernous sinus thrombosis
Epidura I abscess Subdura I abscess Intracerebral abscess Cavernous or sagittal sinus thrombosis
1542 I
PART 13 THE NOSE AND PARANASAL SINUSES
In the case of orbital cellulitis, a formal assessment of the
full range of eye movements, degree of proptosis,
relative afferent pupillary defect, visual acuity (using a Snellen chart), colour vision (using Ishihara plates) and inspection
of the
optic
disc
should
be
made.
Where possible this should be carried out by opt hal mologists. This assessment
should be repeated daily
where clinically appropriate. Where there is increasing concern, six-hourly monitoring
of the full range of
eye movements, visual acuity and colour vision should be undertaken in conjunction with regular temperature and pulse measurements. For intracranial complications, clinical examination of the cranial nerves and central nervous system should be undertaken. The possibility of occult intracranial com plications should always be considered, even in a patient with a normal neurological examination. If intracranial complications are found, hourly neurological monitoring is likely to be appropriate.
Figure
1 20.1
Various orbital
c omp l ic a tions on axial projection
(continued): (e) cavernous sinus thrombosis.
INVESTIGATIONS
trigeminal parasthesia.ll These are often bilateral, espe
Radiological
cially proptosis. Animal experiments have demonstrated that visual loss may be irreversible time exceeds 100 minutes.2
[**1***]
if retinal ischaemic
may be involved in the
complications of sinus disease.
The aim of these investigations is to:
Again, there may or may not be a history of acute bacterial rhinosinusitis or upper respiratory tract infection. In most reported case series, adolescent and young adult males 13
possibly due to the
•
confirm the diagnosis of the complication;
•
define the extent and site of the complication;
•
help planning of any treatment;
•
confirm that there is no other covert complication present.
vascularity of the diploeic system in this age group. A study
is currently a wide range of techniques available for
imaging the sinuses and surrounding structures, which
Intracranial complications
are more commonly affected,12.
There
of 74 patients admitted with orbital complications
secondary to rhinosinusitis identified an incidence of
24 percent for concomitant intracranial complications
ORBITAL COMPLICATIONS
in patients aged seven or older (mean age
In
15 years
11 months) who required surgical intervention for their
orbital complications.14 The presenting history may range from mild confusion or mood change
if there is a
well-defined intracranial abscess, to the acute pain and possible
loss of consciousness associated with acute
meningitis. Whenever there is a history suggestive of intracranial pathology, specific enquiries should be made to elicit symptoms and signs of rhinosmusitis as a primary
cause of the presenting problem. Some would advocate scanning of all patients with acute frontal rhinosinusitis or orbital cellulitis to exclude such serious complications, which may initially be clinically' silent'.n.
15
[U]
Examination Clinical endoscopic examination of the nose should be performed to help determine the site and extent of clisease.
the
case
of orbital
cellulitis,
the
main
aim
of
radiological investigation will be to define the extent and site of the disease. The diagnosis from the clinical appearance.
will be apparent full ocular
If there is
movement and normal vision (including colour vision), no immediate
radiological
investigation is indicated,
unless there are concerns about an intracranial problem also being present. Appropriate investigations should be undertaken to confirm the presence,
and
site of, a
suspected surgically treatable abscess prior to drainage. Plain x-rays have no role here, as they are unable to define anything but the grossest orbital abnormalities. The investigation of choice is a high definition computed tomography (CT) scan taken in both coronal and axial
planes. This approach
will give the greatest chance of
picking up small abnormalities, which might be missed
with scans .carried out magnetic
resonance
in only one plane. Although
imaging
r i I
(MRI)
will
define
Chapter 120 Complications of rhinosinusitis
abnormalities in the orbit, there is no evidence that it is more accurate than CT.16 Additionally, the lack of bone definition makes it of limited value, as the bony surgical landmarks important for planning surgery will not be shown. Similarly, although ultrasound imaging may pick up orbital abnormalities, it will not demonstrate the important surgical anatomy. Radioisotope scanning has similar limitations. [**]
INTRACRANIAL COMPLICATIONS
The place of imaging in the management of intracranial complications of sinus disease is perhaps more impor tantly diagnostic rather than for the purposes of surgical planning (although the two might well be able to be combined). MRI scanning has been demonstrated to be superior to CT in the diagnosis of intracranial complica tions and is the investigation of choice for the diagnosis of suspected intracranial extension.12, 16, 17 As soon as an intracranial complication is detected, joint manage ment of the case with neurological or neurosurgical colleagues is mandatory. For the treatment of the intracranial complication, MRI may be all that is needed for the surgeon to be able to plan a safe surgical approach for drainage. If synchronous sinus surgery were going to be undertaken, a CT scan, with its ability to define the bony anatomy, would be desirable, if any delay incurred in obtaining such a scan were compatible with the patient's clinical condition. It should not be forgotten that intracranial complications may be relatively 'silent' and a high level of suspicion should be maintained. [**]
Haematological investigations
The place of haematological investigations is three-fold: 1. to help ensure there is no serious underlying disease process such as a leukaemia; 2. to act as an assessment of fitness for surgery; 3. to monitor the patient's response to treatment.
To these ends, on suspicion of a complication of rhinosinusitis, a full blood count should be performed. Subsequently, this is one of the indices that should be measured to monitor the patient's response during and after treatment.
Other investigations
As in any infective condition, it is important, if possible, to establish the nature of the infecting organism and its antimicrobial sensitivities. Accordingly, it will often be helpful to set up blood cultures as soon as possible, preferably prior to, but not at the expense of, anti-
I 1543
biotic treatment. Similarly, the culture of any purulent material found in the nose on clinical examination at the time of surgery in the sinuses or from an abscess is important. In patients with a diagnosed complication of rhino sinusitis, urinalysis should be undertaken to detect diabetes mellitus, which might have led to immuno compromise. For ongoing monitoring of treatment, the simple regular measurement of temperature should not be forgotten, as any persisting infection may manifest itself as sustained or 'spiking' pyrexia. Such a situation would indicate further radiological investigation.
TREATMENT Medical
Unless an abscess is demonstrated by radiological or other investigation, nonsurgical management of rhinosinusitis complications would usually be the first choice. The exception to this would be when vision was affected by pressure on the optic nerve resulting from surrounding inflammation without abscess formation. The aim of medical management is two-fold: (1) to control and eliminate the disease process directly relating to the complication; and (2) to control and eliminate the primary rhinosinusitis. Although antimicrobials will form the mainstay of medical treatment, many clinicians would advocate specific treatment for nasal decongestion with the aim of facilitating resolution of the underlying rhinosinusitis. A typical decongestant regime would be the intranasal administration of ephedrine 0.5 percent drops, two drops six-hourly to the affected side of the nose. However, there is little evidence to support this as an addition to treatment. The selection of antibiotics will usually be made before any information regarding the infecting organism or its sensitivity to antimicrobials is available. The choice of antibiotics, therefore, needs to be of a broad enough spectrum to cover the likely infecting organisms, but at the same time be reasonably selective in order to minimize the development of microbe resistance. The likely infecting organisms are Streptococcus pneumoniae and other Streptococcus spp., Staphylococcus aureus, Moraxella catarrhalis, Haemophilus inJluenzae and anae robes.10, 13,15, 18,19,20 Polymicrobial and anaerobic isolates are more common in patients greater than 15 years of age and in intracranial complications. 19,21 Accordingly, a regime of intravenous cephalosporin with metroni dazole would be an appropriate first choice. Rectal metronidazole takes considerably longer to reach blood concentration levels that will cross the blood-brain barrier, so should not be used as initial treatment in this
/
'c
?,;
1544 I PART
13 THE NOSE AND PARANASAL SINUSES
situation. In patients with antibiotic sensitivities, other appropriate antibiotics should be selected in accordance with local microbiology policies. It should be noted that the incidence of bacterial species isolated is not wholly consistent across series reports and it is possible that the major pathogens vary geographically. This may be due to differences in the use of antibiotics and subsequent selective pressures on pathogenic bacteria (although equally it may represent sensitivities of culture techni ques and the influence of the relatively small numbers of cases) . It is possible that the current trend away from routine prescription of antibiotics for upper respiratory tract infections will lead to a relative increase in the incidence of complicated rhinosinusitis. Fungal rhinosinusitis is dealt with in Chapter 114, Fungal rhinosinusitis. [**] Systemic steroid administration is sometimes recom mended to accelerate the resolution of the inflammatory process, but there is no evidence to support this treatment.3 Although the risk of direct pressure effects of inflammation may be reduced, the immunosuppressive action of the steroids may mask other complications of the infective process, as well as having their own side effects. It could be argued that if there were such an urgent need to reduce pressure effects that surgical intervention would be more appropriate. [****] Initially, medical management should be planned for 24 hours, with frequent monitoring of the patient over this period as described above. If there is not a significant clinical improvement in the first 24 hours of medical treatment, surgical intervention should be considered. Additionally, if there is clinical deteriora tion, then emergency surgical intervention is likely to be appropriate. For orbital complications, intravenous antibiotic administration should continue until clinical improve ment is well established and only then should oral treatment be substituted. A good indication of established improvement is the absence of pyrexia for a period of 24 hours combined with a general clinical improvement. There is little good evidence as to how long oral antibiotics should be continued, but a period of 7-14 days would usually be effective. With intracranial complications, a prolonged (four- to eight-week) course of intravenous antibiotics may be necessary, as serum levels achieved with oral antibiotics may not be sufficient to cross the blood-brain barrier efficiently.4 In the case of cavernous sinus thrombosis, the addition of anticoagulation to antibiotic therapy and appropriate surgical drainage of any collection may be beneficial in preventing mortality, but not morbidity. The haemor rhagic sequelae of cavernous sinus thrombosis should be excluded radiologically prior to anticoagulation (Jones NS, personal communication) . In all instances, the importance of working with and cons:ulting other clinical colleagues should not
be overlooked. An appropriate combination of ear, nose and throat (ENT) surgeons, paediatricians, ophthal mologists and neurologists should be involved in the management from the time the patient is admitted to hospital.
Surgical
The surgical treatment of patients with complications of rhinosinusitis can be conveniently divided into that necessary for the treatment of the rhinosinusitis and that necessary for the treatment of the complication. These are likely to be carried out at the same time, but may involve more than one team of surgeons.
SURGERY FOR RHINOSINUSITIS
The type of surgery needed for the treatment of acute rhinosinusitis with complications is essentially no differ ent from that needed without complications. The principles of draining any pus and establishing ventilation of the sinuses remain exactly the same and are described elsewhere. Where the complication has arisen from acute rhinosinusitis, it is likely that the operative field will be very haemorrhagic, making endoscopic surgery much more difficult than in the presence of chronic rhinosinu sitis alone. Contraindications for an endoscopic approach include any intracranial complication, osteomyelitis of the frontal bone or orbital complications with an acute visual problem.22 [*]
ORBITAL CELLULITIS
A study of 240 patients divided into three clinical groups suggests that infections with cellulitis alone are likely to settle with conservative treatment, whereas patients with proptosis but normal eye movements and visual acuity are likely to require surgery.l In addition, patients older than 15 years would appear to be more likely to develop complications requiring surgical inter vention.21 [**/***] Orbital cellulitis is almost always secondary to ethmoid rhinosinusitis, but may occur with frontal rhinosinusitis. The position of any abscess is likely to be medial to the globe with ethmoid rhinosinusitis, but may be more superior when the frontal sinus is the main source of the complication (Figure 120.2). Some surgeons suggest that endoscopic ethmoidectomy together with removal of the lamina papyracea and perinasal drainage of the orbital abscess is sufficient treatment. However, unless the surgeon is extremely familiar with endoscopic nasal surgery, it is probably easier and wiser to use an external approach. This has the advantage of allowing an assistant to help keep the operative field clear. If an external approach is used, the conventional Lynch-Howarth
Chapter 120
Complications of (hinosinusitis I 1545
or exter nally through the medial canthal incision. The former, endonasal, siting is likely to result in l ess cosmetic
deformi ty than
leaving
simpl e dr ainage of
an
an
external
drain. Although
orbital abscess without any ethmoid
surgery (relying on medical treat ment to deal with the rhinosinusitis) may be effective, it is probably better
to perform both definitive surgery for the rhino sinusitis, as well as surgery for the orbital abscess at the same time
(Figure 120.3). INTRACRANIAL COMPLICATIONS The
surgical treatment of intracranial complications will
ine vitably involve neurosurgical expertise . As far as the otorhinolaryngologist is concerned, discussion needs to take place as to whether the neurosurgical approach is going to be done at the same time as any sinus surgery. There is little evidence to help decide whether these should be done
as
separate procedures, but as with orbital
cellulitis, it is probably better to undertake the surgery for the complication at the same time as undertaking surgical treatment
for
the
underlying rhinosinusitis.
However, intr acran ial complications are most likely to
arise from frontal rhinosinusitis rather than disease of the other paranasal sinuses, and definitive surgery on the frontal sinus is difficult at the best of times. In these
circumstances,
it is
probably better
to undertake a
temporary drainage procedure at the time of surgery for the intracranial complication, rather than attempt a formal sinus reventilation procedure or obliteration. A frontal si nus
trephine procedure with placement of
an external drain is likely to give the best immediate result, leaving the decision about any definitive surgical procedure until the patient has fully recovered from treatment of the complication.23
[**}
OTHER COMPLICATIONS Osteomyelitis of the frontal bone ( P ott s puffy tumour) '
requires abscess drainage and removal of infected bone , Figure 120.2
Patient suffering from frontal rhinosinusitis with associated orbital cellulitis: (a) and (b) clinical photographs; (c) and (d) CT scans.
combined with antibiotic treatment. Other concurrent
complications of rhinosinusitis should be excluded prior to theatre. Following surgery, a prolonged course (six weeks) of culture-directed antibiotic therapy should be
given.24 [**}
appr oach for an external ethmoidectomy will allow the surgeon to drain the subperiosteal abscess 'on the way' to
carrying out the definitive ethmoidectomy. Occasionally the
orbital
abscess
will
lie
away
from
the
lamina
papyracea, especially if there is a frontal rhino sinusitis.
PROGNOSIS
Orbital complications
Since the abscess may lie in the roof of the orbit or even further
laterally, it is essential to obtain a CT scan
If
p rompt treatment is carried out with adequate
preoperatively to define the p os ition of any c ollection
monitoring of patients du ring treatment, the prognosis
and thus direct exploration. Drainage of the abscess
for the return of normal vision is excellent
can be established using dr ainage tubes placed to drain
there is a small, but significant risk of diplopia follo
either into the nasal cavity (fixing to the septum)
wing surgery.18 It is likely,
.
However,
provided there is good
I
/
I
.
\
1546 I
PART 13 THE
NOSE AND PARANASAL SINUSES
Admit all (except minor preseptal inflammation)
!
ENT/endoscopy/ophthalmic opinion Visual assessment every 30 mins in first 24 hours
!
IV antibiotics +
_______ Bilateral visual and neurological
�
decongestant drops, analgesics
VISual a
L
Visual
tY
!
!
CT if possible
!
t IV ASS + Staph cover
Surgical drainage
I
,
'-----------�-��
!
CTwithin 24 hours
!
within 1-2 hours
to save eye
Antral washout/
!
-+---
Improves
!
Does not improve or localized abscess
external or
No visual loss
No significant proptosis
!
Emergency 100 mins
Emergency CT
�
significant proptosis
!
thrombOSiS
cuity
reasonable but
and/or fixed globe
Cavernous sinus
f
Colour vision
Failing or gone
Signs/symptoms?
______
Oral antibiotics
endoscopic Note: Further CT brai n 6-8weeks later if headaches persist or any suggestion of frontal lobe abscess. Figure 120.3
Algorithm showing the management of orbital complications (Lund, personal communication).
communication
and teamwork between opthalmolo
gists, paediatricians and otorhinolaryngologists ensuring prompt surgical intervention if nonsurgical management
fails, that full recovery of eye function will occur.
Intracranial complications Although
the
advent
[**]
Recently mortality 15% morbidity 30%
of CT with
associated
earlier
diagnosis and treatment has undoubtedly had a bene ficial effect on the outcome of intracranial complica tions,25 the mortality rate is still reported at up to 12 26 27 ' 25 percen. t " However, some retrospectIve stu d'Ies quoted include
.
data from more than 40 years ago
and often have low patient numbers. A more recent study of 219 patients showed an overall mortality rate
of 16 percent.lS Mortality varies according to the specific
complication,
but
increases with
age and 1 , level of consciousness on admission. 5
decreased Residual
morbidity including hemiparesis, chronic seizures, altered cognitive function and cranial nerve defects following intracranial complications 62
..
is reported to be between 0 f complica-
. , 7,28Ear1y recogmtIOn 19 and40 percent2
tions and subsequent treatment is essential to optimal
outcome.
[**]
.I
Radiological investigations of choice are CT and MRL If intracranial complications are suspected, radiological investigations should be performed prior to a lumbar puncture. .I Broad-spectrum antibiotics, including anaerobic: cover, form the mainstay of medical treatment. .I StaphylJJcoccus aureus should not be dismissed as a contaminant if cultured. .I
j
Chapter 120 Complications of rhinosinusitis
./ Surgical treatment is normal l y required for resol ution
3.
in patients with abscess formation.
I 1547
No aUthors given. Steroid therapy of acute ENT infections: Rarely indicated. Prescrire International. 2001; 10: 185-7.
./ A multidisciplinary approach is essential to optimal
4.
Thea D, Barza M. Use of antibacterial agents in infections of the central nervous system. Infectious Disease Clinics of
outcome.
North America. 1989; 3: 553-70.
*
5.
Chandler JR, Langenbrunner DJ, Stevens ER. The pathogenesis of orbital complications in acute rhinosinusitis. Laryngoscope. 1970; 80: 1414-28.
Deficiencies in current knowledge and areas for future research
6.
Lusk RP. Pediatric sinusitis. !\Jew York: Raven Press, 1992:
7.
Lew D, Southwick FS, Montgomery WW, Weber AL, Baker
127-46. AS. Sphenoid rhinosinusitis. A review of 30 cases. New
» The numbers of patients presenting with complications of rhinosinusitis is very smal l , and the symptomatology often very varied. This makes it very difficult to design studies in any particular area that would result in l evel 1 or 2 evidence. The evidence
England Journal of Medicine. 1983; 309: 1149-54. 8.
fronto-ethmoidal mucoceles. Rhinology. 1987; 25: 83-8. 9.
of the widely quoted series cover periods that must
Pediatrics. 1977; 16: 464-71. 10.
now be considered the medical past, particularly with
However, much of the data they provide with regard
orbital cel l ul itis due to rhinosinusitis. Journal of Laryngology and Otology Suppl. 1987; 12: 1-18. 11.
(Baltimore). 1986; 65: 82-106. 12.
in adults and children. Archives of Otolaryngology - Head
for orbital abscess complications is best undertaken centre, perhaps in a country where the condition is
and Neck Surgery. 1989; 115: 1424-9. 13.
children: 12-year review. Clinical Infectious Diseases.
investigate this. However, extrapolation of results to surgery would, as ever, be difficult.
1994; 18: 750-4. 14.
children. International Journal of Pediatric
individual s shoul d develop compl icated sinus disease with uncomplicated disease. Further investigation of
Otorhinolaryngology. 2004; 68: 619-25.
* 15.
techniques such as pol ymerase chain reaction for the
Otology. 1995; 109: 945-50. 16.
Younis RT, Anand VK, Davidson B. The role of computed tomography and magnetic resonance imaging in patients
detection of bacterial sequences may be helpful in
with rhinosinusitis with compl ications. Laryngoscope.
gaining more information on otherwise culture negative specimens.
Singh B, Van Dellen J, Ramjettan S, Maharaj TJ. Sinogenic intracranial compl ications. Journal of Laryngology and
factors, including host and bacterial genetics, may suggest potential reasons. In addition, the use of
Herrmann BW, Forsen Jr. JW. Simultaneous intracranial and orbital complications of acute rhinosinusitis in
» There is also little information to suggest why some when similar organisms are isolated from patients
Rosenfeld EA, Rowley AH. Infectious intracranial compl ications of rhinosinusitis, other than meningitis, in
seen more frequently, would be the optimal setting to other centres with varying experience of endoscopic
Maniglia AJ, Goodwin WJ, Arnol d JE, Ganz E. Intracranial abscesses secondary to nasal, sinus, and orbital infections
» There is continued controversy as to whether surgery endoscopically or by an external approach. A large
Southwick FS, Richardson Jr. EP, Swartz MN. Septic thrombosis of the dural venous sinuses. Medicine
to populations at risk, organisms isolated and prognosis for outcome are stil l general l y comparable 1 15 with modern series. •
Moloney JR, Badham NJ, McRae A. The acute orbit. Preseptal (periorbital) cel l ul itis, subperiosteal abscess and
regard to the development and widespread availability of imaging techniques and therefore diagnosis.
Hawkins DB, Clark RW. Orbital invol vement in acute rhinosinusitis. Lessons from 24 childhood patients. Clinical
presented here is, therefore, mostl y based on the results of retrospective case series reviews. A number
Lund VJ. Anatomical considerations in the aetiology of
2002; 112: 224-9. 17.
Smith RR. Neuroradiology of intracranial infection.
18.
Swift AC, Charlton G. Rhinosinusitis and the acute orbit in
Pediatric Neurosurgery. -1992; 18: 92-104. children. Journal of Laryngology and Otology. 1990; 104: 213-6.
REFERENCES
19.
Brook I. Bacteriology of intracranial abscess in children. Journal of Neurosurgery. 1981; 54: 484-8.
*
1.
Singh B. The management of sinogenic orbital
20.
complications. Journal of Laryngology and Otology. 1995;
acute and complicated rhinosinusitis. Journal of
109: 300-3. -2.
Hayreh SS, Kolder HE, Weingeist TA. Central retinal artery
Mortimore S, Wormal d PJ, Oliver S. Antibiotic choice in Laryngology and Otology. 1998; 112: 264-8.
21.
Harris GJ. Subperiosteal abscess of the orbit. Age as a
occlusion and retinal tol erance time. Ophthalmology.
factor in the bacteriology and response to treatment.
1980; 87: 75-8.
Ophthalmology. 1994; 101: 585-95.
/ {
I
1548 I 22.
23.
24.
PART 13 THE NOSE AND PARANASAL SINUSES
Stammberger H. The Messerklinger technique. In:
* 27.
Jones NS, Walker JL, Bassi S, Jones T, Punt J. The
Stammberger H (ed.). Functional endoscopic sinus surgery.
intracranial compl ications of rhinosinusitis: Can they be
Philadel phia: B.C. Dekker, 1991: 276.
prevented? Laryngoscope. 2002; 112: 59-63.
Lang EE, Curran Al, Patil N, Walsh RM, Rawluk D, Walsh
28.
Cl ayman GL, Adams GL, Paugh DR, Koopmann Jr CF.
MA. Intracranial compl ications of acute frontal
Intracranial complications of paranasal rhinosinusitis: A
rhinosinusitis. Clinical Otolaryngology. 2001; 26:
combined institutional review. Laryngoscope. 1991; 101:
452-7.
234-9.
Marshal l AH, Jones NS. Osteomyelitis of the frontal bone secondary to frontal rhinosinusitis. Journal of Laryngology and Otology. 2000; 114: 944-6.
25.
26.
FURTHER READING
Rosenblum ML, Hoff JT, Norman D, Weinstein PR, Pitts L. Decreased mortality from brain abscesses since advent of
Herrmann BW, Forsen Jr Jw. Simultaneous intracranial and
computerized tomography. Journal of Neurosurgery. 1978;
orbital complications of acute rhinosinusitis in children.
49: 658-68.
International Journal of Pediatric Otorhinolaryngology. 2004;
Bradley PJ, Manning KP, Shaw IVID. Brain abscess secondary to paranasal rhinosinusitis. Journal of Laryngology and Otology. 19 84 ; 98: 719-25.
68: 619-25. Reid JR. Compl ications of pediatric paranasal sinusitis. Pediatric Radiology. December, 2004; 34: 933-42.
I
/
121 Nasal polyposis
NIELS MYGIND AND VALERIE J LUND
Introduction
1549
Treatment
1554
Definition and characteristics
1549
Summary
1556
Epidemiology
1550
Key poin ts
1556
Aetiology and associated diseases
1550
Best clinical practice
1556
Pathology and pathogenesis
1551
Deficiencies in current knowledge and areas for future
Clinical presentation
1552
Diagnosis and staging
1553
research
1556
References
1557
The data in this chapter are supported by a PubMed search using the key words nasal polyps, intranasal corticosteroids, systemic corticosteroids and surgery.
DEFIN ITION AND CHARACTER IST ICS
INT RODUCTION surgeon may consider
A polyp presents in the nasal cavity with a grape-like
nasal polyps to be a trivial disease, as the diagnosis is easy
appearance, having a 'body' and a 'stalk'. The surface is
to make by endoscopy and the treatment consists of
smooth and the colour is more yellow than the pink
The ear, nose and throat
(ENT)
corticosteroids and surgery. The patient will experience
mucous membrane. Nasal polyps originate in the upper
nasal polyps to be an unpleasant disease, which severely
of life. 1 The scientist will find
part of the nose around the openings to the ethmoidal
interferes with the quality
sinuses. The polyps protrude into the nasal cavity from
nasal polyps to be a challenge because the aetiology, in the
the middle and superior meatus,
large majority of cases, is unknown and because the
blockage and abolishing airflow to the olfactory region.
pathogenesis Why
do
of polyp formation is poorly understood.
polyps
often
develop
in
some
types
of
inflammatory airway diseases and not in others? Why
resulting in nasal
Nasal polyposis, consisting of multiple, bilateral polyps, is part of an inflammatory reaction involving the mucous membrane of the nose, the paranasal sinuses and often
do polyps only develop in a few square centimetres of a
the
generally inflamed airway mucous membrane?
histological and immunological studies and an increasing 2 number of publications have appeared in recent years. • 3
Even the name is problematic. Polyp is derived from
Greek, meaning many footed
airways.
Polyps
are
easily
accessible
for
footed),
The relationship between nasal polyposis and chronic
but a polyp has only one 'foot' (stalk). Finally, a disease
rhino sinusitis is much debated but in its broadest sense
polyposis and, strictly speaking, it
of chronic inflammation in the nose and sinuses, i.e. part
(poly,
many;
lower
pous,
characterized by the occurrence of multiple polyps is most
correctly named nasal
is not a nasal but a sinonasal disease.
nasal polyposis should probably be regarded as one form of the spectrum of chronic rhinosinusitis.4
I
t·1
1550 I PART
13 THE NOSE AND
PARANASAL
SINUSES
EPIDEMIOLOGY
NSAID intolerance is typically associated with polyp
The prevalence rate of nasal polyposis is about
formation.
formation, intake of NSAIDs is not the cause of polyp
2 percent.s It increases with age, reaching a peak in those aged 50 years and older. The male:female ratio is about 2:1. Nasal polyposis occurs with a high frequency in groups of patients having specific airway diseases
[****]
Allergic fungal sinusitis
(Table 121.1).
It is noteworthy that nasal polyps are very rare in allergic
Nasal polyps occur in almost all patients with allergic
children in contrast to children with cystic fibrosis and
fungal rhinosinusitis (see Chapter
that the disease is more frequent in nonallergic than in
nusitis).
allergic adult patients with rhinitis and asthma.
typically eosinophil-dominated,9 as in the aspirin triad.
Although the disease, nasal polyposis, is rare, isolated nasal polyps occur in one third of examined nasoethmoi
dal blocks from cadavers.6
There are few studies of the natural history of nasal
In
this
disease,
the
114,
tissue
Fungal rhinosi inflammation
is
[****] Allergy?
polyposis. In a follow up of patients in an otology practice, the median time from the first to the second
As most polyps are characterized by tissue eosinophilia, it
polypectomy was six years, indicating that many cases of
has been the belief for decades that allergy is a significant
percent of
cause of nasal polyposis. However, this view has been
patients referred to a hospital ENT clinic for nasal
nasal polyposis are mild.7 In another study,
challenged because most studies have failed to show a
polyposis had visible polyps
higher
20
85
years after the first visit,
showing that nasal polyposis is a chronic disease.s The polyp recurrence rate depends upon the type of
occurrence
of
positive
disease. It is low in cystic fibrosis and high in patients
a high prevalence of polyposis
with nonsteroidal antiinflammatory drug (NSAID) intol
on IgE-mediated allergy.
erance and asthma.
skin
tests
to
inhaled
allergens in patients with polyps than in the general 0, , 2 population.s, 1 11 1 In addition, diseases associated with
(Table 121.1) are not based
In striking contrast to nasal polyposis, which is a
[***]
disease of middle-aged people, allergic rhinitis occurs with its highest prevalence in children and young adults. Children with perennial allergic rhinitis, who can have
AETIOLOGY AND ASSOCIATED DISEASES
markedly swollen nasal mucous membranes, almost never develop polyps
The as piri n triad A triad of nasal polyposis, asthma and aspirin (acetyl salicylic acid) intolerance was described many years ago and represents the most aggressive form of the disease. It is a nonallergic entity and the intolerance is not confined to acetylsalicylic acid, as the patients react to other NSAIDs,
Table
acting
121.1
as
cyclooxygenase
inhibitors.
While
Frequency of nasal polyps in various diseases. GrQUll
Allergic rhinitis Nonallergic rhinitis Asthma in adults intolerance NSAIO intolerance and asthma Allergic fungal rhinosinusitis Churg-Strauss syndrome Cystic fibrosis
In children In adults
Adapted from ReF. 2.
0.1 1.5 5
Allergic Nonallergic
NSAI D
Primary ciliary dyskinesia
(Table 121.1).
Even the pathogenic contribution of allergic reactions
5
13 36-72 SO >SO 50
In children In adults
10 40 40
in patients with coincidental occurrence of the two conditions can be questioned. Keith and coworkers13 were unable to show any deterioration of nasal symptoms or eosinophilia during the pollen season in polyp patients having a positive skin test to pollen. Thus, it appears that allergy is not a well-documented cause or aggravating factor in nasal polyposis.
Cystic
[**]
fibrosis
Nasal endoscopy demonstrated polyps in
45
percent of
adults with cystic fibrosis (CF).14 In the majority of patients, the disease was staged as mild and the polyps did middle turbinate. 15 Mucosal
not extend beyond the
abnormalities in the sinuses consistent with polypoid hyperplasia are demonstrated on computed tomography (CT) scans in almost all patients with CF.15
[****]
Histology results of CF polyps are controversiaL Three studies, comparing polyps from children with CF and adults with non -CF polyps, showed a strikingly lower number of eosinophils in the CF pOlyps.16, 17,
IS
However,
in a study of adult patients, there was a considerable overlap in ,the number of eosinophils between the two groupS.19
_'.L / , -'----"----:: _ _ � _ J: _\� .. _____ -"'
Chapter 121 Nasal polyposis
Primary ciliary dyskinesia (Kartagener's syndrome)
I 1551
Surface epithelium TYPE OF EPITHELIUM
Absent mucociliary clearance and recurrent bacterial infections result in nasal polyposis in about 40 percent of the patients.2o The recurrence rate is low after surgery. [****]
The major part of the polyp surface is covered by a ciliated pseudostratified epithelium, but, in addition, transitional and squamous epithelia are found, especially in anterior polyps, influenced by the inhaled air currents.25
Young's syndrome EPITHELIAL DEFECTS
The cause of this syndrome is unknown. It consists of recurrent respiratory disease with chronic rhinosinusitis, nasal polyps, bronchiectasis and azoospermia. [***] As we are reluctant to expose our ignorance to patients, some physicians still call nasal polyps 'allergic'. This is misleading and may result in futile attempts at identifying a causative allergen in air, food or beverages. It is more correct to tell the patient that polyps are caused by an 'allergy-like' inflammation, but that the cause is unknown. [**] Chronic urticaria is a non allergic disease, having many similarities to allergy. It was recently shown that, in a number of cases, it is caused by IgG autoantibodies to the receptor for IgE on mast cells. Although tempting to hypothesize, a similar process has not been identified in nasal polyposis.
?
There is experimental evidence that cytotoxic proteins from eosinophils can damage the respiratory epithelium and induce bronchial hyperreactivity in asthma. Epithelial defects have also been described in nasal polyps.26 However, this may be due to cutting artefacts during processing, as the polyp epithelium appears well pre served without defects when polyps are removed carefully, and gentle methods are used for fixation, dehydration and cutting.
ROLE IN INFLAMMATION
There is increasing evidence that the airway epithelium may play an important role in airway inflammation, as disturbance of the epithelium, such as may occur on exposure to chemical, physical and immunological stimuli, can lead to the release of proinflammatory cytokines.
PATHOLOGY AND PATHOGENESIS Site of polyp f ormation
Innervation
Nasal endoscopy of a large number of patients with nasal polyposis21 and a detailed anatomic examination of . autopsy speCImens22 have shown that nasal polyps are mainly situated in the middle meatus and that they originate from the mucous membrane of the outlets (ostia, clefts, recesses) from the paranasal sinuses. This area, so critical for sinus pathology, is also referred to as the ostiomeatal complex. It is remarkable that polyps exclusively develop from a few square centimetres of an airway mucous membrane which often is universally inflamed. The reason for this is unknown and one can only speculate about the nature of a 'localization factor'. One possibility is that 'touching mucous membranes' in the narrow ostiomeatal complex results in the release of proinflammatory cytokines from epithelial cells. Another possibility is an influence of special airflow, air current and pressure in the upper part of the nose. Finally, it may be of significance that the nerve endings near the borderline between the nose and paranasal sinuses are thin23 and may easily become damaged by cytotoxic proteins, released by eosinophils.24 [****]
Sensory nerves, autonomic secretory and vasomotor nerves, invariably found in normal and abnormal nasal mucosa, cannot be identified within the stroma of polyps.23 It is assumed, therefore, that denervation of nasal polyps causes a decrease in secretory activity of the glands and induces an abnormal vascular permeability, leading to tissue oedema. As mentioned, nasal polyps develop in areas where the lining of the nasal cavity joins that of the sinuses, and these marginal zones contain thin nerve fascicles,23 which may have increased sensitivity to damaging factors. While the exact cause and mechanism of the denerva tion of the nasal polyps is unknown, there is little doubt that the complete loss of autonomic innervation is an important pathogenetic factor in the formation of polyps.24
--
.\
Goblet cells The number of goblet cells in polyps vary considerably between and within polyps. However, the average density is much lower than in the nasal mucous membrane.25
J
1552 I
PART 13 THE NOSE AND PARANASAL SINUSES
Submucosal glands The glands of nasal polyps differ markedly from normal nasal glands. While nasal mucosa glands are small branched tubuloalveolar glands, those in the polyps are long, tubular and of varying shape, size and type. The nasal glands are evenly distributed over the mucous membrane, while the glands in the polyps are very unevenly distributed. Their density is more than ten times less than in the nasal mucosa.27 All glands in the polyps are abnormal, showing signs of cystic degeneration with . . h'In the d'Istended tubuIes. 1 6 ,27 stagnatIOn 0 f mucus WIt
lymphocytes predominate over B cells and there are more T supressor (CDS + ) than T-helper cells (CD4 + ) , the number of which are reduced by corticosteroid treatment. 31
EOSINOPHILS
Eosinophils comprise the most prevalent inflammatory cell in most types of nasal polyps. They show signs of activation and have markedly prolonged survivaL
ADHESION MOLECULES AND CYTOKINES
Blood vessels. plasma exudation and oedema formation The vascularity of polyps is minimal as compared to normal nasal mucosa and neither venous sinusoids nor arteriovenous anastomoses are found.23 The venules of the polyps show unusual organization with respect to their endothelial cell junctions and the basement membrane. Many cell junctions have the appearance of a web of villous processes and are incompletely sealed, while others are wide open,23 promoting oedema formation.
Inflammation Nasal polyposis is the ultimate form of inflammation of the upper airways, which, for unknown reasons, prefer entially develops in subtypes of inflammatory diseases. Although IgE-mediated allergy is not an important aetiological factor, recent data indicate that both mast cells and histamine are involved in the inflammation and in the pathogenesis of polyps.
MAST CELLS AND HISTAMINE
There is an increased number of epithelial mast cells in nasal polyps.28 Electron microscopic studies have shown marked and widespread mast cell degranulation in all polyps studied.29 It is in accordance with the ultrastructural changes that total histamine levels in polyps are far higher than in other tissues (l00-1000 times that of plasma) .3 o The release of histamine may be an important factor in causing plasma exudation. This is highly characteristic of polyps, which are 'oedema-filled sacks'.
LYMPHOCYTES
There is accumulating evidence that the inflammatory reaction in nasal polyposis is at least in part driven by T lymphocytes and their humoral products, the cytokines. T
Eosinophil infiltration and activation is caused by cytokines, chemokines and adhesion molecules. Polyp epithelial cells produce IL-l, IL-3, IL-4 and TNFa, and these cytokines can up regulate the adhesion molecule, VCAM -1 in endothelial cells.32 , 33 The interaction be tween VCAM -1 and VLA-4 plays an important role for extravasation of eosinophils into polyps. In addition, the chemokines, eotaxin and RANTES are probably involved . h'l as eOSInOp I attractan ts. 32 The finding of high amounts of IL-5 in the majority of nasal polyp specimens, but in none of the normal control or sinusitis samples, indicates that IL-5 plays a key role in the pathophysiology of eosinophil-dominated polyps.34 As activated eosinophils generate IL-5, which promote further eosinophil accumulation and activation, nasal polyps can be considered as a 'self-perpetuating eosino phil-dominated inflammation'.35
CLINICAL P RESENTATION Rhinosinusitis Patients, as a rule, have suffered from perennial nonallergic rhinitis (idiopathic rhinitis) with profuse watery rhinorrhea for some years, then nasal blockage gradually develops and becomes persistent. Simulta neously, secretions become more viscous and are removed by noisy sniffing as 'postnasal drip'. Involvement of the paranasal sinuses, the mucosa of which has many goblet cells but few seromucous glands, contributes to the viscosity of the discharge. It is most important that impaired airflow in the upper part of the nose is followed by a reduced or abolished sense of smell, and with that 'taste'. This symptom is very annoying as it mars the pleasure of eating and drinking. The disease can vary in severity from a single episode of nasal blockage, relieved by a short course of treatment, to a life-long disease, requiring continuous and combined treatment. Patients. often believe that they are allergic because inhaled irritants, certain food and alcoholic beverages can
",.--
Chapter 121
Nasal polyposis I 1553
provoke symptoms. They should be told that these factors are not the cause of the disease, although they can provoke symptoms from an irritable mucous membrane. Nasal polyps are always associated with paranasal sinus pathology. There is hyperplasia of the maxillary mucous membrane and the ethmoidal cells are filled with polypoid mucous membraqe. This pathology may not necessarily result in symptoms, but it can cause a feeling of congestion and may also increase the tendency to bacterial infection, especially following a common cold. When polyps develop in children, it can cause widening of the ethmoidal cells, and flattening and broadening of the nasal bridge Cfrog nose').
While a plain x-ray examination is not very helpful, a CT scan of the nose and paranasal sinuses gives an excellent demonstration of the anatomy and pathology. It is indicated when there is a suspicion of malignancy or meningocoele, and also in all cases before endoscopic surgery. In addition, it is used for staging of the disease (Table 121.3).
Asthma and NSAID intolerance
Other examinations
Patients with severe nasal polyposis and blood eosino philia often have, or will develop, asthma (30 percent) and/or NSAID intolerance (15 percent). These three disease manifestations usually start Within months or a few years in 40- to 50-year-old patients. Most patients develop asthma before polyps. Asthma patients have polyps which are sensitive to corticosteroid treatment, but they usually require continuous intranasal therapy and surgery as well. As a rule, the asthma is chronic, severe and persistent, requiring continuous inhaled corticoster oid treatment. Questioning about adverse reactions to acetylsalicylic acid is obligatory in patients with nasal polyps. When ingestion of an NSAID within minutes to a few hours has resulted in rhinitis, asthma, skin itching or urticaria, then the diagnosis is made. In case of doubt, a challenge test with acetylsalicylic acid may be necessary. It starts with a low dosage (10 mg) and it must be performed by a specialist in a hospital setting. It is important to inform NSAID intolerant patients that they must avoid not only acetylsalicylic acid, but all NSAIDs, for life. Usually, patients tolerate paracetamol and salicylic acid.
Any child with nasal polyps needs an evaluation for cystic fibrosis. In general, allergy testing is not indicated but it is often expected by the patient.
DIAGNOS IS AND STAGING Rhinoscopy. endoscopy
Large polyps can be identified by simple rhinoscopy. In contrast to a hyperplastic turbinate, a polyp can be made to move by touching with a probe. Endoscopy with a rigid scope is the preferred examination, as it can diagnose small polyps in the middle meatus and give a superior assessment of the extent of the disease and of anatomical abnormalities. The examination is performed after simple spraying of the nose with a local anaesthetic and a vasoconstrictor. Endoscopy is useful, not only for the diagnosis, but also for follow-up examination after
medical and surgical treatment, and for staging of the disease (Table 121.2).
Imaging
Differential diagnosis
Nasal polyps are typically multiple and bilateral. Nasal bleeding, pain and unilateral polyps should alert the physician to other conditions, such as malignant tumours, inverted papillomata and, in a child, meningo coeles, all of which may masquerade as simple polyps. For that reason, microscopy is always necessary when polyps are removed for the first time) and when polyps are unilateral.
Table
121.2
Endoscopic staging of nasal polyposis.
Endoscopic app aranc.t
Score
No polyps Restricted to middle meatus Below middle turbinate Massive polyposis
o 1 2 3
Reprinted from Ref. 36, with permission.
Table
121.3
CT scan staging of nasal polyposis.
Maxillary Anterior ethmoid Posteriod ethmoid Sphenoid Frontal Ostiomeatal complex Total
R.ight
left
0-2
0-2
0-2
0-2
0-2
0-2
0-2
0-2
0-2
0-2
0/2
0/2
0-12
0-12
O. no opacity; 1, some opacity; 2, total opacity. Reprinted from Ref. 37, with permission.
;.
1554 I
PART 13 THE NOSE AND PARANASAL SINUSES
A single choanal polyp, ansmg from the maxillary sinus, can present in the nose. The aetiology is unknown and treatment consists of surgical removal, which cures the disease. Thus, it is not part of nasal polyposis. 3
T REATMENT Treatment can be either medical and/or surgical. Medical treatment consists of intranasal and systemic corticoster oids. Possibly, leukotriene antagonists may have an additional effect in selected patients.
� o
c75
2
Intranasal corticostero ids Intranasal corticosteroids are by far the best documented **** 0 1 8 type of treatment for nasal polyposis? , 39, 4 , 4 , 42 [ ] There are at least 16 placebo�controlled studies and they have all shown a significant clinical effect. [Grade A] RESPONSIVENESS TO NASAL CORTICOSTEROIDS
Apparently, some patients do not respond to topical steroids. This may be due to inadequate intranasal distribution of the spray in a very blocked nose. Responsiveness can then be achieved after a short course of systemic steroids. There is a close connection between eosinophilia and steroid responsiveness, and it is dubious whether nasal steroids are of value in primary ciliary dyskinesia and CF, although a small placebo-controlled study has shown efficacy in CF. 43 POLYP SIZE
Intranasal steroids will not eliminate polyps, but the treat 8 ment clearly reduces their size (Figure 121.1) .44, 45, 46, 47,4 On the other hand, an effect on polyps in the middle meatus cannot be expected as only a small fraction of the spray reaches the middle meatus.49
Entry
2
3 Months
D
Budesonide aerosol
•
Budesonide aqua
•
Placebo
Figure 121.1
Mean score for polyp size in patients before and
after three months of treatment with budesonide aerosol 400llg!day (white bars), budesonide aqua 400llg!day (pale blue bars) or placebo (dark blue bars). Redrawn from Ref. 44.
because many patients predominantly suffer from blockage with little sneezing and rhinorrhoea. The overall symptom reduction is about 50 percent (Figure 121.2) .44, 54, 55 An open, one-year study has shown that the anti rhinitis effect is maintained and that symptoms only slowly recur when the treatment is discontinued. 5 6 Although steroids do not cure the disease, long-term therapy may break vicious circles and have a long-lasting efficacy, especially in mild cases.
NASAL AIRWAY PATENCY
Nasal breathing is a required outcome from therapy and studies have clearly shown a significant effect of topical treatment on blockage symptom scores and on objective 5 8 50 51 5 5 measures of nasal patency.44 , 4 , 4 , , , 2 , 53 , 4 However, a patent nasal airway is not necessarily a normal airway. Pressure from polyps may have changed the normal slit like cavity to a wide tube in the lower part of the nose, at the same time as there may be considerable pathology and blockage in the upper part of the nose.
SENSE OF SMELL
Loss of the sense of smell, and with that 'taste', caused by polyp obstruction of the upper part of the nasal cavity, is a very annoying symptom for most patients. Clinical experience indicates that the effect of topical steroids, in 5 contrast to systemic administration, is poor.4 , 46, 47, 48, 57 This is probably because a spray will not reach the olfactory epithelium due to airway obstruction by polyps. RECURRENCE OF POLYPS
RHINITIS SYMPTOMS
While all studies have shown an effect on nasal blockage, the effect on sneezing and secretion has varied, probably
Controlled studies have shown that topical steroids can delay the �ecurrence of polyps after surgery and with that 0 58 postpone the need for new surgery. , 59, 6 However, the
Chapter
121
Nasal polyposis I 1555
for 30 years without any report of serious adverse events.40
2
1.5 Q)
� 1.0
Systemic corticosteroids
0.5
2
o
3
4
5
[a)
6
7
8
9
10 11 12
8
9
10 11 12
8
9
10 11 12
Weeks 2
1.5 �
8
(fJ
1.0
0.5
o
2
3
4
5
(b)
6
7
Weeks 2
1.5 �
8
(fJ
1.0-
0.5
o
2
3
4
5
6
7
Weeks
(el ....----...
0------0
o------a
Placebo Budesonide aerosol
Surgical treatment
Budesonide aqua
Figure 121.2 Effect of nasal steroid (budesonide) as the only treatment in patients treated with budesonide aerosol 400 )lg/day (open circles), budesonide aqua 400 )lg/day (open squares) or placebo (filled c'ircles). (a) Blocked nose, (b) runny nose, (c) sneezing. Redrawn from Ref. 44.
effect is merely partial, in particular pronounced inflammatory activity. SINUS
Systemic steroids can be given as tablets (prednisolone) and as a depot-injection, probably having similar therapeutic indices. The total glucocorticoid dose in a depot-injection corresponds to about 100 mg predniso lone. When treatment is given orally, a higher total dose is probably necessary, e.g. 25 mg prednisolone daily for 10-14 days. However, controlled dose-effect studies are not available. [Grade B) Although systemic steroid treatment has not yet been studied in placebo-controlled trials, there is no doubt that within a few days it can reduce all nasal symptoms considerably, including the sense of smell. 57, 61 A depot injection releases glucocorticoid for two to three weeks and oral treatment is often given for a similar period of time. Clinical experience confirms that the beneficial effect, in many cases, will outlast the medication for a variable period. A short course of systemic steroid is equally effective as simple polypectomy with a snare57 and it may serve as a 'medical polypectomy'. In severe disease, requiring endoscopic surgery, preoperative use of a systemic steroid will considerably facilitate surgery. Only a Single, two- to three-week course of systemic steroids has been given in the few published studies. However, it seems likely that some patients with severe recurrent polyposis may benefit from repeated use of short-term systemic steroids. Adverse effects from this therapy cannot be expected to be severe and may be outweighed by increased quality of life in patients with severe disease and abolished olfaction. [***]
m
cases of
PATHOLOGY
There is no reason to believe that intranasal steroids have any effect on sinus pathology.58 SAFElY
One should emphasize that intranasal steroids are the best studied fonn of nasal treatment, extensively used
Due to the nature of nasal polyposis as an inflammatory disease of the mucous membrane, surgery cannot be expected to cure the disease. However, in some mild cases presenting for the first time with large polyps, poly pectomy can have a long-lasting effect. In more severe cases with persistent symptoms, surgery is added to medical treatment in order to reduce the amount of inflammatory tissue, open up the nasal airway and improve ventilation of the paranasal sinuses. [Grade C] A few large polyps can be removed under local anaesthesia by a snare. While simple polypectomy was fonnerly perfonned repeatedly in severe cases, such patients are nowadays referred to a rhinosurgeon for endoscopic sinonasal surgery, preceded by a CT scan examination. Recently, Blomqvist and coworkers62 performed a controlled study by taking advantage of the bilateral
/-
z6
,,_
1556 I
PART 13
THE NOSE AND PARANASAl SINUSES
nature of the disease. Following intranasal corticosteroid
and together with systemic steroids andlor surgery in
treatment for one month and orally for ten days, patients
severe cases. Systemic steroids for two to three weeks have
had a unilateral endoscopic surgery performed. Compar
an effect on all types of symptoms and pathology, can
ison of the two sides post-operatively showed that surgery
including the sense of smell. This type of treatment
had an additional effect on nasal blockage and on polyp
serve as (medical polypectomy'. When blockage is a
score, but not on the sense of smell. Twenty-five percent
problem
of
further
recommended. Simple polypectomy is still performed,
operation on the unoperated side at the end of the study.
but in the more severe and persistent cases, endoscopic
The
surgery is recommended.
the
patients
authors
were
willing to
concluded
that
undergo
medical
a
treatment
is
in
spite
of
medical
treatment,
surgery
sufficient to treat most cases of nasal polyposis. If nasal obstruction
remains
a
main
problem
after
medical
treatment then surgical treatment is indicated. The choice of surgical approach will depend upon the individual surgeon's experience. Whether a more con servative or more radical approach offers the better long 63 term results remains to be determiIied. [***1**]
SUMMARY Nasal polyposis, occurring in about 2 percent of the general population, is the ultimate form of inflammation of the upper airways. For unknown reasons, polyps preferentially
develop
in
subtypes
of
inflammatory
diseases and they are associated with perennial nonallergic rhinitis, asthma and intolerance to acetylsalicylic acid (NSAIDs), allergic fungal rhinosinusitis, cystic fibrosis and primary ciliary dyskinesia. In contrast to common belief, IgE-mediated allergy does not seem to play an aetiological role. The polyps originate from the mucosa around the ostiomeatal complex. The factors determining the loca lization of the disease to a few square centimetres of the airways are not known. Polyps are oedematous sacks covered by a normal airway epithelium and containing very few nerves, blood vessels and glands which have undergone cystic degeneration. Polyps contain degranu
,/ Primary treatment consists of intranasal
lated mast cells and they have a very high concentration of
corticosteroids in the majority of cases. ,/ A short course of systemic corticosteroid treatment can serve as 'medical polypectomy' and it can improve olfaction. ,/ In more severe cases, surgery is required. In moderate cases, this is Simple polypectomy, and in more severe cases intranasal endoscopic surgery, preceded by a CT scan examination of the nose and paranasal sinuses.
histamine.
Polyps are characteristically
infiltrated by
eosinophils, which accumulate due to release of cytokines (in
particular
molecules
IL-5)
and
upregulation
of
adhesion
(VCAM-1). As eosinophils generate IL-5,
attracting more eosinophils, nasal polyps can be con sidered as self-perpetuating inflammatory processes. Preceded by some years with rhinitis symptoms, nasal blockage becomes severe and persistent and, typically, the sens�. of smell is seriously impaired, when polyps develop. The
diagnosis is
based on
anterior
rhinoscopy,
or
preferably, endoscopy. A CT scan is necessary when malignancy
is
suspected
(bleeding,
pain,
unilateral
polyps) and before endoscopic surgery. Treatment consists of corticosteroids and in severe
Deficiencies in current knowledge and areas for future research
cases surgery. Intranasal corticosteroids reduce rhinitis symptoms, improve nasal breathing, reduce the size of polyps and prevent, in part, their recurrence, but it has little effect on the sense of smell. Intranasal steroids
can,
as basic long-term therapy, be used alone in mild cases,
Nasal polyposis resembles an autoimmune disease and this possibility needs further examination. >- The su.ggestion that environmental fungi may be an initiating factor needs further investigation. >-
,/
is
Chapter 1 2 1 Nasal polyposis
� At present, the immune inflammatory process is
10.
11.
Laryngology and Otology 1984; 98: 783-93.
� It is worth studying whether intranasal corticosteroids 12.
Braun JJ, Haas F, Conraux C. Polyposis of the nasal sinuses. Epidemiology and clinical aspects of 350 cases. Treatment
drops.
and results with a follow-up over 5 years on 93 cases.
� The effect of systemic corticosteroid treatment needs
Annales d'Otolaryngologie et de Chirurgie Cervico Faciale.
to be investigated in placebo-controlled, dose-response studies.
� The possibility that a long-term treatment with a low
Drake-Lee AB, Lowe D, Swanston A, Grace A. Clinical profile and recurrence of nasal polyps. Journal of
antibodies can be a future treatment. can be given in a more efficient way, e.g. as nose
Caplin I, Haynes TJ, Spahn J. Are nasal polyps an allergic phenomenon? Annals of Allergy 1971; 29: 631-4.
undergoing detailed analysis, which is needed in order to study whether, for example, treatment with IL-5
I 1557
1992; 109: 189-99. 13.
Keith PK, Conway M, Evans 5, Wong 5, Jordana G, Pengelly
dose of systemic corticosteroid in selected patients
D et al. Nasal polyps: effects of seasonal allergen
has a beneficial effect which outweighs the risk of
exposure. Journal of Allergy and Clinical Immunology
1994; 93: 567-74.
side effects needs a thorough investigation.
� It is possible that leukotriene antagonists can have a
14.
nasal polyps in adults with cystic fibrosis. Clinical
beneficial effect in subgroups of polyp patient, for
Otolaryngology 2000; 25: 19-22.
example in those who are intolerant to NsAlDs.
� Controlled studies of surgery are required.
Hadfield PJ, Rowe-Jones JM, Mackay IS. The prevalence of
15.
� It is necessary in long-term controlled studies to
Brihaye P, Clement PAR, Dab I, Desprechin B. Pathological changes of the lateral nasal wall in patients with cystic fibrosis. International Journal of Pediatric
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Otorhinolaryngology 1994; 28: 141-7.
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s�)rensen H, Mygind N, Tygstrup I, Flensborg EW. Histology of nasal polyps of different etiology. Rhinology. 1977; 15: 121-8.
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Oppenheimer EA, Rosenstein BJ. Differential pathology of nasal polyps in cystic fibrosis and atopy. Laboratory
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I I
.-..--.<�- .-- ......
/ \
122 The relationship between the upper and lower respiratory tract JEAN BOUSQUET AND ANTONIO M VIGNOLAt Introduction Epidemiological evidence Key points Nasal and sinusal inflammation in asthma and chronic obstructive pulmonary disease Bronchial inflammation in rhinitis Key points Quality of life in asthma and rhinitis Key points
1560 1560 1561 1561 1562 1563 1564 1564
Therapeutic consequences Best clinical practice Costs Rhinitis and asthma: a continuum of disease? Best clinical practice Deficiencies in current knowledge and areas for future research References
1564 1565 1565 1565 1565 1566 1566
A Medline search was carried out using the key words rhinitis-asthma-epidemiology; rhinitis-nonspecific bronchial hyperreactivity; rhinitis-asthma-occupational; rhinitis-asthma-allergens; rhinitis-asthma-nasal mucosa; rhinitis-asthmabronchial mucosa; rhinitis-asthma-biospsies; asthma-sinus-CT scans; rhinitis-remodelling; rhinitis-bronchial challenge (endobronchial); asthma-nasal challenge; allergy-systemic; virus-nasal-bronchial; quality-of-life-asthma; quality-of-liferhinitis; (all drugs) rhinitis-asthma; immunotherapy-rhinitis-asthma; anti-IgE (omalizumab)-rhinitis or asthma.
INTRODUCTION Asthma and allergies, including rhino conjunctivitis and atopic dermatitis, are common throughout the world, with a high burden of morbidity and cost. Nasal and bronchial mucosa present similarities and most patients with asthma also have rhinitisl suggesting the concept of 'one airway, one disease'. However, not all patients with rhinitis present with asthma and there are some differences between rhinitis and asthma.
EPIDEMIOLOGICAL EVIDENCE Epidemiologic relationship between rhinitis and asthma Epidemiologic studies have consistently shown that asthma and rhinitis often coexist in the same patients. 2
The maJonty of patients with asthma present with seasonal or perennial allergic rhinitis symptoms. However, it has been shown that perennial rhinitis is a factor independent of allergy in the risk for asthma. Rhinitis usually happens in over 65 percent of patients with allergic asthma and in over 80 percent of patients with nonallergic asthma (for review, see Ree). However, in many instances, symptoms predominate in one organ and may be hidden in the other although they exist. The Copenhagen Allergy Study 3 investigated the frequency of asthma and rhinitis related to exposure to pollens, animal dander or mites. Between 42 and 52 percent of patients with rhinitis had asthma and more than 99 percent of subjects with allergic asthma also had allergic rhinitis. The risk of asthma among subjects with allergic rhinitis was calculated to be up to 300 times that among subjects without aller£ic rhinitis. However, the results observed in developing countries may differ from those in western
Chapter 122 The relationship between the upper and lower respiratory tract. 1561
populations. A recent study showed that allergic rhinitis is far less common among asthmatic subjects in rural China than in asthmatic subjects in industrialized countries with 4 a western lifestyle. [****] The age of onset of atopy may be an important confounding factor for the development of asthma and rhinitis or rhinitis alone. In an Australian study, it was found that atopy acquired at an early age (before the age of six years) is an important predictive factor for asthma continuing into late childhood, whereas atopy acquired later was only strongly associated with seasonal allergic rhinitis.5, 6
Rhinitis and nonspecific bronchial hyperreactivity Many patients with allergic rhinitis have a unique physiologic behaviour separating them from patients with asthma or normal subjects. They have increased bronchial sensitivity to methacholine or histamine/ especially during and slightly after the pollen season, 8 but there are large differences in the magnitude of airway reactivity between asthmatics and rhinitics which are not explained by the allergen type or degree of reactivity. [****]
Causative agents in rhinitis and asthma Among the causative agents inducing asthma and rhinitis, some (e.g. allergens and aspirin9 ) are well known to affect both the nose and the bronchi. Most inhaled allergens are associated with nasal lO and bronchial symptoms, but in epidemiologic studies differences have been observed. Although there have been some recent concerns, the prevalence of immunoglobulin (Ig)E sensitization to indoor allergens (house dust mites and cat allergens) is positively correlated with both the frequency of asthma and its severity. Alternaria and insect dusts have also been found to be linked to asthma, however, pollen sensitivity has not been found to be associated with asthma in epidemiological studies. 1 [****] Occupational disease represents an interesting model to study the relationships between rhinitis and asthma. All of the most common triggers of occupational asthma can induce occupational rhinitis. Subjects with occupational asthma may often report symptoms of rhinoconjunctivitis. Rhinitis is less pronounced than asthma with low molecular weight agents. On the other hand, rhinitis more often appears before asthma in the case of high molecular weight agents such as small mammals. 1 In addition, rhinitis caused by some occupational agents often develops into occupational asthma, highlighting the importance of cessation of allergen exposure in occupational allergic rhinitis, in order to prevent asthma. [****]
/
It)
Allergic rhinitis as a risk factor for asthma Asthma develops more commonly in patients with perennial rhinitis. The Children's Respiratory Studyll showed that the presence of physician-diagnosed allergic rhinitis in infancy was independently associated with a doubling of the risk of developing asthma by 11 years of age. In adults, allergic rhinitis as a risk factor for asthma was shown in a 23-year follow-up of college students. 12 Significantly more (10.5 percent) of the students originally diagnosed with allergic rhinitis went on to develop asthma compared with 3.6 percent of those who did not have rhinitis. This study was recently confirmed by two other studies in Sweden 13 and the USA.14 In both studies the onset of asthma was associated with allergic rhinitis, and in the US study, after stratification, rhinitis increased the risk of development of asthma by about three times both among atopic and nonatopic patients and by more than five times among patients in the highest IgE tertile. Patients with rhinitis with persistent and severe nasal symptoms and a personal history of physician-confirmed sinusitis had an additional increased risk of asthma development. The authors concluded that rhinitis is a significant risk factor for adult -onset asthma in both atopic and nonatopic subjects. [****] It is, however, not clear whether allergic rhinitis represents an earlier clinical manifestation of allergic disease in atopic subjects who will later go on to develop asthma or if the nasal disease itself is causative for asthma.
NASAL AND SINUSAL INFLAMMATION IN ASTHMA AND CHRONIC OBSTRUCTIVE PULMONARY DISEASE Similarities and differences between nasal and bronchial inflammation in asthma In normal subjects, the structure of the airways mucosa presents similarities between the nose and the bronchi.
1562 I PART 13 THE NOSE AND PARANASAL SINUSES Both nasal and bronchial mucosa are characterized by a pseudo stratified epithelium with columnar, ciliated cells resting on a basement membrane. Underneath the epithelium, in the submucosa, vessels and mucous glands are present with structural cells (fibroblasts), some inflammatory cells (essentially monocytic cells, lymphocytes and mast cells) and nerves. [****] There are also differences between the nose and the bronchi. In the nose, there is a large supply of subepithelial capillary and arterial system and venous cavernous sinusoids. The high degree of vascularization is a key feature of the nasal mucosa and changes in the vasculature may lead to severe nasal obstruction. On the other hand, smooth muscle is present from the trachea to the bronchioles explaining bronchoconstriction in asthma. The recent progress achieved in the cellular and molecular biology of airways diseases has clearly documented that inflammation plays a critical role in the pathogenesis of asthma and rhinitis. The same inflammatory cells appear to be present in the nasal and bronchial mucosa. A growing number of studies show that the inflammation of nasal and bronchial mucosa is sustained by a similar inflammatory infiltrate, which is represented by eosinophils, mast cells, T lymphocytes and cells of the monocytic lineage. The same proinflammatory mediators (histamine, CysLT), T helper (Th)2 cytokines (interleukin (IL)-4, IL-5, IL-13 and granulocytemacrophage colony-stimulating factor), chemokines (RANTES and eotaxin) and adhesion molecules appear to be involved in nasal and bronchial inflammation of patients with rhinitis and asthma. [***] However, there are major differences between both sites. Although the nasal and bronchial mucosa are exposed to the same noxious environment (and even more so the nose), epithelial shedding is more pronounced in the bronchi than in the nose of the same patients suffering from asthma and rhinitis. 15 The magnitude of inflammation may not be identical. In patients with moderate-severe asthma, eosinophilic inflammation is more pronounced in the bronchi than in the nose,15 whereas in patients with mild asthma inflammation appears to be similar in both sites. Moreover, eosinophilic inflammation of the nose exists in asthmatics with or without nasal symptoms. 16 On the other hand, features of airways remodelling appear to be less extensive in the nasal mucosa than in the bronchial mucosa. [****]
Sinus involvement in asthma For more than 70 years, the coexistence of asthma and rhinosinusitis has been noted in the medical literature. 17 The debate still remains as to whether rhinosinusitis is a precipitating factor for bronchial asthma. In the light of current knowledge, it seems that rhinosinusitis and
asthma are linked by a common process that is mainly inflammatory, and central to the pathogenesis is the role of eosinophils and airway epithelium. Chronic rhinosinusitis associated with asthma and allergy appears to be restricted to the asthmatic population with an extensive sinonasal disease and the presence of peripheral eosinophilia in patients with rhinosinusitis indicates a high likelihood of extensive disease. 18 In a study comparing mild-moderate asthmatics with corticodependent asthmatics, the proportion of patients with symptoms of rhinosinusitis was similar in both groups (74 percent in corticosteroid-dependent asthma and 70 percent in mild-moderate asthma).19 All corticosteroid-dependent asthmatics versus 88 percent of the mild-moderate asthmatics had abnormal computed tomography (CT) scans. The clinical and CT scan scores were higher in the corticosteroid-dependent asthmatics. In both groups, the CT scan scores were correlated to the clinical scores and the absolute number of blood eosinophils. 19 [****]
Nasal and sinus inflammation in chronic obstructive pulmonary disease In order to determine whether nasal inflammation in asthma was related to asthma or was found commonly in other bronchial diseases, nasal inflammation and sinus involvement were studied in patients with chronic obstructive pulmonary disease (COPD). Less than 10 percent of patients with COPD have nasal symptoms. Nasal inflammation assessed by nasal mucosal biopsies differs from that of patients with asthma, but similarities can be observed between nasal and bronchial mucosa in COPD patients. In particular, there is a common epithelial metaplasia, and the presence of CD8 and elastase-positive cells. Computed tomography scans show few abnormalities in COPD. Thus, sinonasal inflammation seen in asthmatics is related to asthma and is not a feature of all bronchial diseases. [****]
BRONCHIAL INFLAMMATION IN RHINITIS Bronchial inflammation and remodelling in rhinitis Some studies have examined the bronchial mucosa in atopic nonasthmatic patients or in patients with allergic rhinitis. They all combined to indicate that there was a slight increase of the basement membrane size20 and a moderate eosinophilic inflammation. 21 Natural exposure to pollen during the season provokes an increase in airway responsiveness in nonasthmatic subjects with seasonal allergic rhinitis and also induces inflammatory cell recruitment and IL-5 expression, leading to bronchial inflammation. 22
Chapter 122 The relationship between the upper and lower respiratory tract
Bronchial challenge of rhinitis patients leads to bronchial symptoms and inflammation Endobronchial allergen challenge was carried out in patients with seasonal rhinitis who had never presented with asthma before. These patients developed a bronchoconstriction, and lavage carried out serially after challenge demonstrated the occurrence of pro inflammatory mediators and cytokines, as well as the recruitment of inflammatory cells. 23 [****] Pulmonary inflammation after segmental ragweed challenge was examined in allergic asthmatic and . sub'Jects. 24 A total of 46 ragweed-allergic nonasth matlC subjects took part in these studies. Subjects had normal or nearly normal pulmonary function, were on no chronic medication, and were characterized as to their skin sensitivity to intradermal ragweed injection, their nonspecific responsiveness to methacholine, and the presence (or absence) of a late asthmatic response after whole-lung antigen challenge. In both groups, a marked inflammatory response measured in bronchoalveolar lavage fluid (total cells per millilitre, macro phages per millilitre, lymphocytes per millilitre, eosinophils per millilitre, neutrophils per millilitre, total protein, albumin, urea or eosinophil cationic protein) 24 hours after challenge was seen only in the subgroup of subjects who demonstrated a late airway reaction after whole-lung antigen challenge, regardless of disease classification. These studies combine to indicate that although patients with nasal symptoms can only react if the allergen is properly administered into the airways, it may be argued that the doses of allergen inducing these bronchial reactions are far greater than those naturally happening during allergen exposure. This situation seems to exist in thunderstorm-induced asthma 25 which has been associated with grass pollen allergy.26 The aerodynamic size of pollen grains ranges from 10 to 100 Jlm and only a fraction of them can be deposited into the bronchi, thus most patients only present rhinitis without asthma. However, when exposed to water, pollen allergens are released in submicronic particles, the starch granules, which can reach the lower airways and induce asthma. 27
Bronchial challenge of rhinitis patients leads to nasal inflammation
I 1563
et al. 29 found that nasal challenge increased eosinophils in the bronchial mucosa. [***]
Allergy as a systemic disease In patients with allergic diseases, allergen provocation can activate a systemic response that provokes inflammatory cell production by the bone marrow. 30 After release and differentiation of progenitor cells, eosinophils, basophils and mast cells are typically recruited to tissues in atopic individuals. An understanding at the molecular level of the signalling process that leads to these systemic responses between the target organ, especially the airways, and the bone marrow may open up new avenues of therapy for allergic inflammatory disease. 31 Studies that support the critical involvement of the bone marrow in the development of eosinophilic inflammation of the airways point to the systemic nature of these conditions. A second important mechanism may be involved in the systemic origin of airway inflammation. 'In situ . . ,32 d epend s on the production of haemohaemopOlesls poietic cytokines by inflamed tissues from patients with . rh'" . 34 which, generating a11erglC mItIs 33 an d nasaI po IYPOSIS, a particular local 'microenvironment', promote the differentiation and maturation of eosinophil progenitors that populate the nasal or the bronchial mucosa. 35 It is therefore likely that a truly 'systemic' response to the application of inflammatory stimuli to the nasal (or bronchial) mucosa should be associated with an activation of the aforementioned mechanisms. [****]
Viral infection of the nose induces asthma and bronchial inflammation A large number of asthma exacerbations are due to nasal viral infections both in children and adults. Rhinoviruses are the major cause of the common cold and a trigger of acute asthma exacerbations. 36 Experimental rhinovirus upper respiratory infection increases airway hyperreactivity and late asthmatic reactions following allergen challenge. However, rhinoviruses can also infect the lower airways during natural and experimental exposure raising the possibility that asthma exacerbations may be induced through direct enhancement of lower airway inflammation. [****]
In a recent study, endobronchial allergen challenge induced nasal and bronchial symptoms as well as reductions in pulmonary and nasal function. 28 In this study, the number of eosinophils increased in the challenged bronchial mucosa, in the blood and in the nasal mucosa 24 hours after bronchial challenge. Moreover, eotaxin-positive cells in the nasal lamina propria and enhanced expression of IL-5 in the nasal epithelium were found 24 hours after bronchial challenge. Braunstahl
! ~~_ _L -_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _~"HL~'*~, ·~;.S~,:_·~
__ _
~-~.------ ...- -
_..
•.
1564 I PART 13 THE NOSE AND PARANASAL SINUSES cromoglycate or nedocromil, are not absorbed when given orally and are only effective when administered locally. In patients suffering from asthma and rhinitis, local administration of drugs requires that they are given both nasally and bronchially and this may decrease compliance to treatment which is low in asthma and rhinitis.
Drugs administered topically'
QUALITY OF LIFE IN ASTHMA AND RHINITIS Quality oflife (QOL) has been found to be impaired both in patients with asthma and in patients with allergic rhinitis, and the relative burden of these diseases has been recently studied using the generic SF-36 questionnaire in the European Community Respiratory Health Survey (ECRHS), a population-based study of young adults?7 Patients with both asthma and allergic rhinitis experienced more physical limitations than patients with allergic rhinitis alone, but no difference was found between these two groups for concepts related to social/ mental health. Subjects with asthma without rhinitis could not be studied since their number was too low. However, it seems that impairment in social life in asthmatics may be attributable to nasal symptoms. [****]
Glucocorticosteroids are the most effective drugs when used topically in the nose and the bronchi for the treatment of rhinitis and asthma. The intranasal treatment of rhinitis using glucocorticosteroids was found to improve asthma, at best, moderately in some but not all studies. 38 Symptoms and pulmonary function tests were improved. 39 These data suggest that treating nasal inflammation may help to control asthma. However, a number of aspects, such as the extent to which the pathophysiology of the two diseases overlaps and whether treating one will affect the other, still remain to be clarified. Less is known about the effects on nasal disease by inhaled (intrabronchial) treatment with glucocorticosteroids. One study examined effects on nasal allergic disease of inhaled budesonide (avoiding nasal deposition of the drug) in patients with seasonal allergic rhinitis, but without asthma. 40 During the birch pollen season, budesonide reduced the seasonal eosinophilia both in the circulation and in the nose along with an attenuation of seasonal nasal symptoms. Nasal and systemic antieosinophil actions are produced at commonly employed dose levels of orally inhaled budesonide.
Drugs administered orally
THERAPEUTIC CONSEQUENCES Although asthma and allergic rhinitis commonly appear together, treatments for one condition could potentially alleviate the coexisting condition. Medications for asthma and rhinitis can be administered via local (intranasal, intraocular or inhaled (intrabronchial)), oral and parenteral routes. There are advantages (and some drawbacks) to administering the drug directly into the target organ. 1 Moreover, some drugs, such as
Drugs administered by the oral route may have an effect on both nasal and bronchial symptoms. Oral HI-antihistamines represent the first-line treatment of allergic rhinitis and although some studies have found a modest effect on asthma symptoms, these drugs are not recommended for the treatment of asthma.41 The association of oral HI-antihistamines and decongestants was found to be more effective on asthma symptoms. 42 Leukotriene modifiers were shown to be effective in controlling symptoms of mild to moderate asthma and seasonal allergic rhinitis.43 Oral glucocorticosteroids are highly effective in the treatment of rhinitis and asthma but side effects after long-term use are common.
Specific immunotherapy The indications of specific immunotherapy in allergic asthma and rhinitis have been separated in some guidelines. This aptificial separation has led to unresolved issues possibly because the allergen-induced IgE-mediated
Chapter 122 The relationship between the upper and lower respiratory tract
reaction has not been considered to be a multiorgan disease. It is therefore important to consider specific immunotherapy based on the allergen sensitization rather than on the disease itself since most patients with allergic asthma also present rhinitis or rhino conjunctivitis. 1 Immunotherapy can also alter the atopic phenotype by restoring the normal equilibrium between Thl and Th2 lymphocytes. This form of therapy is currently under investigation in subjects with allergic rhinitis as a means of prevention of secondary asthma, and initial results are . 44 encouragmg.
I 1565
if Intrabronchial corticosteroids are effective in rhinitis
(single study). [Grade A] if Oral leukotriene receptor antagonists are often
effective in rhinitis. [Grade A] if Allergen-specific immunotherapy is effective in both
rhinitis and asthma. [Grade A] if Anti-lgE monoclonal antibody is effective in both
rhinitis and asthma. [Grade A]
COSTS Anti-immunoglobulin E monoclonal antibody The anti-IgE antibody, omalizumab,45 has been shown to be safe and effective in separate populations of patients with seasonal and perennial allergic rhinitis, and in children and adults with moderate-severe allergic asthma. Studies are ongoing to assess its effectiveness in patients with comorbid allergic airways disease, and to investigate whether a course of treatment could reduce the risk of developing asthma. Its systemic activity and ability to reduce levels of IgE regardless of allergen specificity may be especially advantageous in these respects.
Treatment of rhinitis reduces asthma severity Two very recent studies showed that treating allergic rhinitis reduces health care utilization for comorbid asthma. In a first study, a retrospective cohort study was carried out in 4944 patients with both allergic rhinitis and asthma, aged 12 to 60 years, who were continuously enrolled and had no evidence of COPD. 46 The risk of an asthma-related event (hospitalization and emergency department visit) for the treated group was about half that for the untreated group. In another retrospective cohort study carried out in 13,844 asthmatics of a managed care organization aged greater than five years,47 patients who received intranasal corticosteroids had a reduced risk for emergency department visits by comparison with those who did not receive this treatment.
Rhinitis inceases the costs of asthma and it was found in a large population that yearly medical care charges were on average 46 percent higher for those with asthma and concomitant allergic rhinitis than for persons with asthma alone. 48
RHINITIS AND ASTHMA: A CONTINUUM OF DISEASE? There are similarities and differences between the nasal and bronchial mucosa in rhinitis and asthma. It appears that most asthmatics present rhinitis, whereas only a fraction of rhinitis patients present clinically demonstrable asthma even though a greater number of patients has nonspecific bronchial hyperreactivity. It seems that the epithelial-mesenchymal trophic unit exists from the nose to the bronchiolar-alveolar junction and that the same inflammatory cells are present throughout the airways suggesting a continuum of disease. However, there are differences in terms of exposure to allergens and noxious agents, the nose being more exposed than the lower airways. There are also major structural differences between the nasal and the bronchial mucosa since in the former there is a large vascular supply whereras in the latter there is smooth muscle. Airway smooth muscle is of paramount importance in asthma due to its contractile properties,but in addition, it may contribute to the pathogenesis of the disease by increased proliferation and the expression and secretion of pro inflammatory mediators and cytokines. It is therefore possible that the difference between rhinitis and asthma is that in the fomer there is an epithelial-mesenchymal trophic unit,49 whereas in the latter there is an epithelial-mesenchymal-muscular trophic unit.
if Oral H1-antihistamines are effective in rhinitis.
[Grade A] if Oral H1-antihistamines are poorly effective in
asthma. [Grade A] if Intranasal corticosteroids are inconstantly effective in
asthma. [Grade A] if Intranasal corticosteroids reduce asthma
exacerbations. [Grade B]
These studies strongly support the 1999 World Health Organization workshop 'Allergic rhinitis and its impact on asthma" which recommended that:
i
:fir
tie (
1566 I PART 13
THE NOSE AND PARANASAL SINUSES
t! patients with persistent allergic rhinitis should be
2.
evaluated for asthma by history, chest examination
Leynaert B, Bousquet J, Neukirch C, Liard R, Neukirch F. Perennial rhinitis: An independent risk factor for asthma in
and, if possible and when necessary, assessment of
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airflow obstruction before and after bronchodilator;
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t! history and examination of the upper respiratory tract
Immunology. 1999; 104: 301-4.
for allergic rhinitis is performed in patients with
3.
Linneberg A, Nielsen NH, Madsen F, Frolund L, Dirksen A, Jorgensen T. Secular trends of allergic asthma in Danish
asthma;
t! proposal of a strategy combining the treatment of
adults. The Copenhagen Allergy Study. Respiratory
Medicine. 2001; 95: 258-64.
both the upper and lower airway disease in terms of efficacy and safety.
4.
Celedon JC, Palmer U, Weiss ST, Wang B, Fang Z, Xu X. Asthma, rhinitis, and skin test reactivity to aeroallergens in families of asthmatic subjects in Anqing, China.
American Journal of Respiratory and CritiCal Care Medicine. 2001; 163: 1108-12.
Deficiencies in current knowledge and areas for future research
5.
Peat JK, Salome CM, Woolcock AJ. Longitudinal changes in atopy during a 4-year period: relation to bronchial hyperresponsiveness and respiratory symptoms in a
)- More prospective studies should assess the
population sample of Australian schoolchildren. Journal of Allergy and Clinical Immunology. 1990; 85: 65-74.
relationship between rhinitis and asthma and confirm that rhinitis is a risk factor for asthma.
6.
)- In occupational diseases, the recognition of rhinitis
Increasing prevalence of hay fever and atopy among
may detect patients early during the course of the
children in Leipzig, East Germany. Lancet. 1998; 351:
disease in order to prevent the onset and progression of persistent asthma in subjects exposed to known
*
862-6. 7.
risk factors.
than in men? A population-based study. American Journal
bronchial inflammation in patients with asthma and
of Respiratory and Critical Care Medicine. 1997; 156:
COPD.
1413-20. The first large epidemiologic survey showing an association between rhinitis and asthma. Moreover, this study is the first to show that nonallergic rhinitis is strongly associated with asthma.
)- Nasal remodelling is poorly understood. )- Mechanistic studies are needed. More studies are needed to appreciate the relationships between the upper and lower airways
»
8.
increase of carbachol airway responsiveness in patients
Lar~e pivotal clinical trials should be started to assess
allergic to grass pollen. Reversal by corticosteroids.
whether the treatment of one target organ may
American Review of Respiratory Disease. 1984; 130:
These studies should be carried out in persistent and
56-8. 9.
intermittent diseases. 10.
measures of the entire airway.
Sibbald B, Rink E. Epidemiology of seasonal and perennial rhinitis: clinical presentation and medical history. Thorax.
Prospective studies should confirm the protective role of nasal treatment on asthma exacerbations and
Szczeklik A, Stevenson DO. Aspirin-induced asthma: advances in pathogenesis and management. Journal of Allergy and Clinical Immunology. 1999; 104: 5-13.
Large pivotal trials should be started to show that oral or systemic treatments improve outcome
»
Sotomayor H, Badier M, Vervloet 0, Orehek J. Seasonal
and the systemic nature of allergic diseases.
improve outcome measures of the other target organ.
»
Leynaert B, Bousquet J, Henry C, Liard R, Neukirch F. Is bronchial hyperresponsiveness more frequent in women
)- More studies are needed to assess nasal and
»
von Mutius E, Weiland SK, Fritzsch C, Duhme H, Keil U.
1991; 46: 895-901. 11.
emergency department visits.
Wright AL, Holberg CJ, Martinez FD, Halonen M, Morgan W, Taussig LM. Epidemiology of physician-diagnosed allergic rhinitis in childhood. Pediatrics. 1994; 94: 895-901.
12.
Settipane RJ, Hagy GW, Settipane GA. Long-term risk factors for developing asthma and allergic rhinitis: a 23year follow-up study Of college students. Allergy
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123 The septum ADRIAAN F VAN OLPHEN
Introduction The development and growth of the septum The septum in nasal function Pathology Symptoms and signs related to the septal pathology Diagnosis Indications for septoplasty
1569 1569 1570 1570 1575 1575 1576
1577 1580 1580
Septoplasty Key points Best clinical practice Deficiencies in current knowledge and areas for future
1580 1580
research References
The data in this chapter are supported by the author's personal collection of references and a search in PubMed and Medline using combinations of key words abscess, air, flow, bone, cartilage, deviation, embryology, fracture, growth, implants, haematoma, obstruction, perforation, septum, trauma, newborn, rhinomanometry, acoustic rhinometry and twins.
INTRODUCTION The main functions of the nose (olfaction, heating, humidification and defence) require good interaction between the inspired air and the mucous membranes or the sensory cells of the olfactory system. This is achieved by complicated aerodynamics that depend on the geometry of the internal nose. The septum helps to preserve this geometry. The septum also supports the dorsum, columella and the tip of the nose and as such it contributes to cosmesis. The success of functional nasal surgery, as well as cosmetic nasal surgery, depends heavily on the correction of the septum. This explains why nasal surgery almost always involves both function and aesthetics as pointed out by Maurice Cottle in the 1960s. 1 The nose is the most prominent part of the face and as such vulnerable. Usually this is of no consequence because due to its flexibility it can withstand limited mechanical impact. Nevertheless, from life in utero onwards there are many risks of nasal trauma in which the septum is involved. Therefore, in adulthood a straight septum is more the exception than the rule.
,
'tt
Furthermore, the septum plays a key role in the development and growth of the nose, the mid face and maxilla. 2 , 3, 4, 5, 6, 7, 8 A number of internal diseases are manifest at an early stage at the septum. 9 [H/*]
THE DEVELOPMENT AND GROWTH OF THE SEPTUM Animal experiments and clinical observations, particularly in identical twins, have demonstrated that lesions of the nasal cartilages can disturb the growth of the nose, the mid-third of the face and the maxilla. These lesions not only disturb the growth of the cartilage involved, but also the growth of the bones related to this cartilage. 2, 3, 4, 5, 6, 7,8 Trauma is rarely symmetrical and can therefore result in asymmetrical growth of the nose and the face. Trauma can occur in utero, during birth and at all ages after birth. The effects of trauma in early childhood are often first noticed during the growth spurt in puberty. Examination of the development of the nose and the face can give a fair
.)
1570 I
PART 13 THE NOSE AND PARANASAL SINUSES
indication of the age at which the trauma of the nasal cartilage took place. The septum develops from the frontonasal process. Initially) it is entirely cartilaginous and together with the triangular cartilages forms a cartilaginous structure that supports the nose from the crista galli to the lower third of the nose (Figure 123.1). The cephalic part of the septum ossifies from the perpendicular plate of the ethmoidal bone. The vomer develops in the tissues covering the posteroinferior part of the septal cartilage as two bony plates with the cartilage between. The latter will subsequently be resorbed after ossification is complete. The perpendicular plate forms the cephalic part of the skeleton of the septum, the vomer the posterocaudal part and the quadrilateral cartilage the anterior part. The septum sits anteriorly via the quadrilateral cartilage on the anterior nasal spine and the premaxilla. More posteriorly, it lies on the anterior part of the maxillary crest. Again, more posteriorly the vomer slides between the maxillary crest and the quadrilateral cartilage. Near the choana, the vomer sits on the palatine crest (Figure 123.2). [**1*]
THE SEPTUM IN NASAL FUNCTION The nasal vestibule distributes the air through the nose. The valve has the smallest cross-sectional surface of the upper respiratory tract. As a consequence the airflow is accelerated. After passing through the valve, the air enters the relatively wide nasal cavity. Due to the deceleration, vortices ,-
are created) which are necessary to bring the inspired air in contact with the mucous membranes. The mucous membranes heat and humidify the air. Particles over 5 !lm are captured in the mucus and transported to the nasopharynx by ciliary movements. During expiration, moisture is regained in the relatively cool vestibule (Figure 123.3). Thus, it is obvious that good function of the nose depends on healthy mucous membranes that will need a great deal of moisture and energy in the form of heat. This requires a rich blood supply (Figure 123.4). [**1*]
PATHOLOGY Developmental disorders Although developmental disorders of the septum are rare, the posterior part of the septum can be involved in a choanal atresia. Choanal atresia is a relatively rare condition, which is seen in one in 10,000 births. Approximately 50 percent of cases are bilateraL It should be noted that complete neonatal nasal obstruction can result in intermittent hypoxia, apnoea and failure to thrive and therefore constitutes a life-threatening emergency. Furthermore, the septum may be involved in rare congenital conditions, such as congenital midline nasal masses, teratomas or frontonasal dysplasia and bifid noses. Cleft lip and palate are two of the most common congenital conditions in which the septum is involved, not only because the basal support of the septum is missing, but also because surgical closure at a very young
Parietal bone Frontal bone
Squama of OCCipital bone
.........+---,1--
Nasal bone
Maxilla
Cart septum Alisphenoid
Mandible Meckel's cartilage Malleus Incus Stapes
Figure 123.1 Styloid process
The cartilaginous
nasal skeleton in the newborn.
/
/
Chapter 123 The septum.
1571
Figure 123.2
The skeleton of the nasal septum.
Figure 123.3
The airflow through the nose
with vortices.
age causes scar formation that inhibits further development of the surrounding structures (Figure 123.5). In the l3.5--20-mm human embryo) the primitive nasal cavities are formed as a vault in the roof of the primitive mouth) the stomatodaeum. At the same time, the palatine process can be seen. The maxillary and palatine processes form the palate and fuse in the midline with the septum. Failure of this process will result in a cleft palate. If only one side does not develop) the other side may still fuse with the septum. Consequently) in surgery a cleft can be found to the right or to the left of the septum. When there
.*__,.'. . _-'-__-__ _ _ !
is insufficient growth of the palatine and maxillary processes from both sides) the inferior part of the septum will be free. When the maxillary process does not reach the frontonasal process) this will result in a cleft lip which can be unilateral or bilateral.
Septal trauma Septal trauma is very common. It may occur at any stage of life. Often a septal defonnity is the only sign of trauma,
-?
I
r
1572 I PART 13 THE NOSE AND PARANASAL SINUSES
Kiesselbach's /plexus
Superior labial artery
Figure 123.4 The vascular supply of the nasal septum and locus Kiesselbach's plexus.
Primitive palate Franto-nasal process Medial nasal fold
Naso-Iacrimal furrow
Maxillary process
Eye Primitive posterior naris
Palatal progess of maxillary mesoderm
which previously went unnoticed or was forgotten. Nevertheless, all nasal trauma deserve careful physical examination even when there are no serious signs, such as nose bleeding, in which case one should be aware of the possibility of a septal haematoma .
Figure 123.5 The roof of the stomatodeum in a , 3.S-mm human embryo.
frequently overlooked because of lack of symptoms that arouse any suspicion. A septal haematoma should be drained to avoid an abscess developing. If an incision in the mucosa is made to drain a haematoma, it should be a horizontal incision to avoid disruption of the mucociliary transport.
Septal haematoma Septal abscess Internal nasal bleeding that cannot escape through the mucous membranes or skin will result in a haematoma. These haematomas can be found in the septum or around the triangular cartilages. It is a serious condition that is
The most common cause of a septal abscess is a septal haematoma. Three to five days after the trauma that caused the haematoma, a fever and nasal blockage may
/
-f_.', ~"":': ' -:":"" ' -
,
..
Chapter 123 The septum I 1573 occur which, at that time, will not be associated with the trauma and frequently is interpreted as flu. In fact, the septal haematoma has developed into a septal abscess and it is at this point that the patient seeks help, by which time there is already severe damage to the septal skeleton. Since this condition usually occurs in children, severe growth impainnent is unavoidable, although good medical and surgical care can diminish the consequences to some extent. The treatment consists of drainage of the abscess and antibiotics. Reconstruction of the defect in the acu te phase will reduce growth impairment.
Septal fractures The type of fracture in nasal trauma depends on the side and magnitude of the impact. Frontal trauma will frequently result in vertical fractures, whereas lateral trauma can give horizontal fractures. The tension that is normally present in the septal cartilage can make a dislocation worse and difficult to reposition. At the side of the fracture the mucosa may tear. In vertical fractures in particular, the consequent scar can impede mucociliary transport. Incomplete fractures can lead to bending of the cartilage because the balance of the stresses in the cartilaginous fibres is lost, or because of scar retraction in fibrous tissue filling up the incomplete fracture. In the former case, there is a bending away from the incomplete fracture, while in the latter the convexity is on the same side of the incomplete fracture. Although perichondrium is able to fonn cartilage, in general the conditions under which this can occur do not exist in fractured cartilage. Consequently, connective tissue binds the edges of the fracture after healing. In vertical fractures, there may be a luxation or subluxation of the caudal part of the quadrilateraJ cartilage. In case of a luxation, the caudal rim of the cartilage can be seen to the left or to the right of the columella. In case of a subluxation, this is only seen after the tip of the nose is lifted.
Mucosal trauma The significance of mucosal trauma is frequently overlooked. Surgery is probably the most conunon cause of mucosal trauma. In the septum, mucosa and perichondrium or periosteum are closely related to each other. Therefore the lining of the septum is called mucoperichondrium or mucoperiosteum. The blood vessels of the mucoperichondrium lie close to the cartilage and damage during surgery can lead to severe atrophy of the mucosa (Figure 123.6). Since the mucosa is the effector 'organ' of the nose, this has a major impact on its function which may result in atrophic rhinitis with symptoms such as foetor, crusting, congestion, epistaxis and headache. Too vigorous surgery of the inferior turbinate can change the
_ tp
I .
f. '
Figure 123.6
Cross-section through the mucoperichondrium
of the septum.
aerodynamics of the nose in such a way that serious trauma of the mucosa may result. 10
Septal perforation Septal perforations are either the result of trauma or systemic disease. A mucosal laceration over a sound skeleton has a strong healing capacity. When there is no skeleton to prevent drying of the back of the mucosa opposite to the mucosal laceration, the mucosa on both sides of the septum will disappear and this leads to a perforation. This explains why perforations are seen in deep trawna of the septum, which not only involve the mucosa but aJso the underlying skeleton. Examples are cautery for nose bleeding, nose picking and cocaine abuse. In submucosal skeleton resections, such as the Killian procedure, a septum perforation is a common complication, because in the case of a mucosal defect the inner surface of the opposite mucosa is not protected against dehydration by the skeleton. In the end, the mucosa on .both sides will be lost The result will be a perforation. It is
i
/
iw '
1574 I PART 13 THE NOSE AND PARANASAL SINUSES one of the reasons why at present the skeleton of the septum is carefully reconstructed in a septoplasty. Although septal perforations can be asymptomatic, they may present to the surgeon with debilitating symptoms such as nasal blockage, atrophy of the mucosa, dryness, crusting, nose bleeding, whistling and headache. The nose blockage and whistling are related to abnormal aerodynamics. The other symptoms are the result of the poor condition of the mucosa, which is worse around the perforation. Perforations in the anterior part of the septum present more symptoms than perforations in the posterior part. Small perforations have a stronger tendency to produce sounds than larger ones. In large perforations, the patient's complaints can be mild. Closure of a septal perforation is difficult due to lack of material to reconstruct the skeleton and the mucosa and because of the poor condition of the tissues around the perforation" a larger part of the septum has to be reconstructed than the size of the perforation suggests. There are many techniques to close a septal perforation, which indicates that none of them presents the ultimate solution. Basically, they are all the same. Vital tissues are brought into the perforation to reconstruct the skeleton and the lining of the septum and to replace the atrophic tissues around the perforation. For the mucosa, pedicled flaps are used. Anatomical limitations mean that these transplants only marginally meet the requirements of the vascularization for these types of reconstruction. The necessary mucosa can be found locally, on the turbinates or at the inside of the upper lip. The required parts of the skeleton can be harvested from the septum itself. In their absence ear or rib cartilage are alternatives. It is difficult to get good access to the surgical field, especially to lay the necessary sutures in the often very delicate edges of the perforation. The ~ndonasal approach is the first choice to limit surgical trauma. The open approach is advocated to improve access to the surgical field. When closure of a perforation is difficult, conservative treatment might be an alternative. Crusting and infection can be reduced by douching the nose with saline. A silas tic button may have a positive effect by improving the aerodynamics and protecting the edges of the perforation, although the button itself can be the cause of crusting. More information can be found in Chapter 124, Nasal septum perforations.
Septum luxation in the newborn There is a great deal of literature on nasal trauma during delivery. This raises the question as to whether septal trauma at birth should be treated in the acute phase. ? Repositioning the caudal septum with a forceps covered with silastic or rubber tubes has been advocated. There is insufficient evidence that correction of a birth trauma of the septum has a positive effect in the long term.
Vascular and bleeding disorders The function of the nose requires an extensive blood supply. The abundance of blood vessels and their relatively superficial position in the nasal septum result in epistaxis following mucosal trauma, inflammation, tumours, vascular diseases or bleeding dyscrasias. Nose bleeding due to septal deviations has been mentioned in the literature. It is conceivable that septal surgery influences nose bleeding by altering the vascularization. However, there is insufficient evidence for a causal relationship between nasal bleeding and septal deviations. Nevertheless, there might be an indication for a septoplasty to make the site of the bleeding more accessible for local treatment. The ophthalmic artery leads off the anterior and posterior ethmoidal arteries. They enter the nose through the cribriform plate of the ethmoid bone. Branches of the anterior ethmoidal artery are divided over the anterior part of the septum. The posterior ethmoidal artery provides blood to the superior posterior part of the septum. The sphenopalatine branch of the maxillary artery enters the nose through the sphenopalatine foramen and supplies the posterior inferior part of the septum. In the region of the anterior nasal spine, it forms anastomoses with terminal branches off the greater palatine artery and the labial branch of the facial artery. Above the incisive foramen along the inferior mucocutaneous junction, capillary vessels run to the surface. This area is known as Kiesselbach's area. Especially in children, this is a place where nose bleeding is seen (Figure 123.4). Clipping the main arteries to the nasal septum can be helpful in severe nose bleeding. For the anterior and posterior ethmoidal arteries, this can be done through a transorbital access. The maxillary artery can be found in the pterygopalatine fossa by a trans antral or endoscopic approach. See Chapter 126, Epistaxis. Embolization of the arteries that supply the bleeding area, guided by radiology, can be an alternative. Hereditary haemorrhagic telangiectasia or OslerWeber-Rendu disease is an autosomal dominant condition. There is a deficiency of the muscle or elastic tissue in the wall of the blood vessels. Therefore, they cannot contract when severed. This can lead to telangectasia in the skin, the lips, nail beds, the mouth tongue and the nose. The gastrointestinal tract and the lungs can also be involved. The manifestations on the septum can cause nose bleeds that are difficult to controL
Septum deformities The most common clinical findings are deviations, perforations, (sub)luxation of the caudal septum, crests due to fracttlres, spurs and spines. A straight septum is the exception rather than the rule. Almost all deformities
Chapter 123 The septum I 1575
are caused by developmental disturbances, trauma, impaired growth after trauma or systemic diseases. Whether or not a deformity deserves surgical attention depends on its impact on function and cosmesis. Septal pathology can manifest itself in the external nose and face in the form of a cartilaginous hump or saddle, deviations of the cartilaginous p)'Tamid, lack of tip projection, all kinds of deformities of the columella and nares and underdevelopment of the nose and the mid face. Atrophy, congestion, scars and metaplasia are frequent findings in the mucosa. Congestion of the septal swell bodies can erroneously be mistaken as a septal deviation. Sometimes there is a pit at the inferior part of the septum anterior of the vomer. It is a remnant ofJacobson's organ, a small-paired organ. It is innervated by a special branch of the olfactory nerve, the vomero-nasal nerve. It is prominent in foetal life, but may disappear completely in adults.
Septal disease in systemic disorders Many systemic diseases manifest themselves at the nasal septum (Table 123.1). The septum is often the first site in which they can be found. Common symptoms are nasal blockage, foetor, discharge, crusting and nose bleeding. The findings at physical examinations are congestion, ulceration, septal perforations, crusting, pus, vascular abnormalities, bleeding and tumour growth. The lesions can destroy the septlU11 to such an extent that support of the external nose is lost, resulting in a saddle and retracted columella with the accompanying functional complaints, due to changes in the geometry of the valve. Early diagnosis and treatment can minimize damage to the nose. As this site is accessible for nasendoscopy, biopsies can be taken, which can be helpful in establishing the diagnosis. Cleaning the crusts by nasal lavage reduces symptoms and prevents the sequelae of infection. In autoimmune diseases, local steroids are often beneficial. In arteriosclerosis, Osler-Weber-Rendu disease and juvenile angiofibroma, nasal bleeding can be difficult to control. After treatment, reconstructive surgery of the nose should be considered. [**1*]
Table 123.1 septum.
Systemic diseases that manifest in the nasal
Vascu'lar -diseases
Arte ri oscl eros is Osler-Weber-Rendu
Infectious diseases
Autoi mmu ~~ ,
Syphilis Tuberculosis Lepra Diphtheria
Sa rcoidosis Lu pus erythematosus Ta kayasu disease Wegener's gran ul omatosis
~..;"
miscellane~_?~
SYMPTOMS AND SIGNS RELATED TO THE SEPTAL PATHOLOGY The symptoms and signs accompanying septal pathology may be nasal blockage, dryness, crusting, bleeding, itching, rhinorrhoea, anosmia, headache and cosmetic complaints. The underlying pathology is either a septal deformity or mucosal pathology. Nasal blockage is nonspecific and often misinterpreted as a sign indicating airflow obstruction. In fact, it is a rather nonspecific finding associated with disturbed function and not necessarily caused by mechanical obstruction to airflow. As such, it is frequently seen in cases where the nasal cavity is too wide, as in atrophic rhinitis. It is not well understood which sensory modalities are responsible for a feeling of nasal blockage. It is interesting that drugs like menthol give a feeling of opening the nose without in fact reducing congestion of the mucosa. Anosmia of the conductive type, in which the air cannot reach the olfactory epithelium, can result from congestion of the mucosa, a septal deviation, tumour or crusting. ["""1*]
DIAGNOSIS Physical examination of the nose begins with an inspection of the external nose in relation to the face. The objective is to see if the dimensions of the nose are in harmony with the face and to establish developmental disturbances. As a rule of thumb, the length of the nose should be approximately a third of the distance between the hairline above the forehead and the lower border of the chin. Furthermore, attention must be paid to the projection and protection of the tip. The projection is the distance between the tip and the face. The protection is the resistance against deformation of the tip. The latter gives an impression of the support of the tip by the septal cartilage and special attention should be paid to the development of the maxilla and dentition, since this can be related to pathology of the nose. A retrograde position of the mandible can accentuate the projection of the nose. Nasal trauma in childhood manifests itself in a small and infantile nose or a deviation. Frequently these signs become evident during the growth spurt at puberty. A cartilaginous saddle nose and a retracted columella are signs of poor support of the nasal pyramid by the septum, often caused by missing cartilage and scar retraction in the septum. A deviated nose or a luxation or subluxation of the caudal septal cartilage is always found with a septal deviation. The shape of the nostrils and the tip projection are closely related to the geometry of the vestibule and the dimensions of the valve area and as such are signs related to functional problems. Inspection of the internal nose begins with the nostrils, ve~tibule and valve area. At this stage, no specula should
1576 • PART 13 THE NOSE AND PARANASAL SINUSES
be inserted, as this would lateralize the ala making it impossible to judge the internal dimensions of the nares, the vestibule and the valve. Inspection of the nasal cavity can be undertaken with the naked eye, although Hopkin's optics may be very helpful in providing an optimal illumination and some magnification. First, the mucosa is inspected for swelling, vulnerable blood vessels, secretions, pus, crusts, atrophy and dysplasia. Congestion of the mucosa can mask or accentuate pathology related to the skeleton, such as septal deviations, spurs and crests. In order to observe these properly, decongestion by adrenaline or similar is strongly recommended. Although some of the findings are clearly related to symptoms, there is a twilight zone between normal and pathological irregularities in the septum. The complexity of the aerodynamics of the nose makes it difficult to relate a bent spur or crest to an abnormal airflow, while the patient's symptoms offer little help in this respect. As mentioned before, nasal blockage does not indicate the nature of the changes in the physiology of the nose. Photography, rhino manometry, acoustic rhinometry and olfactometry are the standardized objective investigations to evaluate septal pathology. They are helpful to evaluate the result of the treatment and are sometimes valuable for medicolegal purposes. In cases where growth may be influenced and cosmetic changes are anticipated, preoperative photography is indicated. This is particularly important in children, in cases of cosmetic surgery and in septal surgery which influences the support of the nasal dorsum, the tip and the columella or in corrections of cartilaginous deviations of the nasal pyramid. A minimum of four photographs is taken according to a standard protocol showing not only the nose, but also the face as a whole. The standard protocol is necessary to be able to compare photographs taken at different times. A standard series consists of a frontal view, a left and right side view and a basal view. An oblique view is more natural but also more difficult to interpret (Figure 123.7). In rhinomanometry, two graphs are produced, one representing the relationship between the pressure and flow in the right half of the nose and the other in the left half of the nose. Nonlinearity makes it difficult to express the relation between pressure and flow in one quantity such as resistance. The respiratory function is expressed by the sum of the curves, whereas the difference between the curves in (normal noses' is determined by the nasal cycle. The nasal cycle describes the rhythm in which the airflow is divided between the left and right nasal passages. Differences between the curves that correlate with symptoms and physical signs indicate a relation with anatomical deformities (Figure 123.8). Acoustic rhinometry is a means of measuring the crosssectional area of the nose as a function of the distance into the nose. Reflections of a sound wave sent into the nose represent these cross-sectional areas. Reflections from the anterior part of the nose are stronger than those from the posterior part. Consequently, cross-sectional areas from
Figure 123.7
The external nose: (a) frontal view; (b) base
view; (c) left side view: (d) right side view.
the vestibule and valve area are more accurately measured than those from the posterior part of the nose, which is less of a disadvantage than it may seem since most pathology interfering with nasal airflow is found in the anterior part of the nose. If the sound cannot easily pass an obstruction, reflections from beyond that obstruction give unreliable information with the measured cross-sectional area being smaller than it really is (Figure 123.9). Olfactometry is indicated when there are symptoms related to smell or for medicolegal reasons. [**/*]
INDICATIONS FOR SEPTOPLASTY Nasal obstruction, crusting, rhinorrhoea, post-nasal discharge, recurrent sinus pressure or pain, epistaxis, headache, snoring and sleep apnoea are mentioned as indications for septoplasty. However, there is little evidence for a causal link between these symptoms and a septal deviation. These symptoms are also seen in patients with a straight septum and, conversely, deviated septa without symptoms are also a common finding. In a retrospectiv~ study, Bitzer et al. found complete relief of symptoms in 10.6 percent of 334 septoplasties, 45.2
123 The septum I 1577
300 Right
200
100
0
3; 0
u:: -100
-200
-300~--r--,---r~~--r--,---.----
-300 -200 -1 00
0
Expiration
: I
100 200 300
understanding of the of deviations and the condition of the mucosa on the physiology of the of nasal nose. A common mistake is to attribute a blockage to a where mucosal 1-'~L>"JlVh or poor aerodynamics are the cause of the "V.Hl~-'H:tU1L.~. Nasal blockage in a seemingly normal nasal cavity is more often associated with lack of understanding of the pathology than with psychological factors. the possibility of making a correct recommendation for a SelJtclpLasty for functional reasons is limited. It ... "',..11" .... "'" eX1JerlerlCe to link the findings of a physical examination to the complaints. Of course there are clear-cut or indications such as a obstruction of the airflow, impaired of the sinus or inaccessibility of the nasal surgery, for in nasal polyposis. The indications for corrections for aesthetic reasons are in general more straightforward than those for functional reasons. 12, 13, 14
Inspiration
Pressure [PaJ
123.8
Rhinomanometry diagram.
SEPTOPLASTY
12
10
8
E Q Q)
6
0
C
ITl
t5
(5
4
2
0
-4
-2
o
2
4
6
Cross-sectional area Figure 123.9
Acoustic rhinometry diagram.
percent were satisfied with the outcome, 35.6 percent were partly satisfied and 19.2 percent expressed their dissatisfaction. In a follow up at 24-64 months, patient satisfaction from 63 to 70.5 percent. In a longer follow up, Jessen et al. ll reported 26 percent of the nine years after surgery. There patlelnts free of is no doubt that there are who benefit from a septoplasty for functional reasons. Nevertheless, the number of with no or limited gain from the procedure in the long term is large. It is the author's opinion that the main reason for this is lack of
Until the 1960s, submucous septal resection as promoted and Killian 16 was standard in Western .l.JuJ.vlu".16 With this a more or less straight septum was obtained in the areas where the skeleton was resected. Two strips of were left one to maintain the dorsum and the other to keep the tip and columella in place. Despite these strips, scar formation and subsequent contraction of the fibrous tissues in the resected part of the were a frequent cause of saddling and retraction of the columella. pe:rtoratlOllS were a common complication, in due to drying of the opposing mucoperichondrium adjacent to the incision. Another drawback of this technWUle was that correction of pathology in the caudal, inferior and parts of the septum was not possible. In 1963, Cottle and van Dishoeck gave a course on nasal surgery in Leiden that laid the foundations for contemporary nasal surgery in Western Europe. The basic COl1CeDtS were to reconstruct instead of resect and to deal with function and cosmetics in one procedure. 1 In the surgeon's pursuit to reduce trauma; many of the promoted Cottle have evolved into more delicate procedures. Furthermore, the open approach, as promoted by Sercer 17 and Padovan 18 and reintroduced by and others, found its place in nasal surgery. It gives access to the tip dorsum and bony pyramid, but is not the first choice for access to the 123.10). procedure, there are six (1) gaining access to the septum; (2) correction of pathology; "'Dn-~A,,'n.-r pathology; (4) shaping removed and bone; reconstruction of the septum; and (6) stabilizing the septum. 20
1578 I
PART 13 THE NOSE AND PARANASAL SINUSES
Gaining access to the septum Hemitransfixion is the basic incision used to gain access to the septum (Figure 123.11). In contrast to transfixion, the incision is not made in the membranous septum but over the cartilaginous septum parallel to the caudal edge, approximately 2 mm posterior to the edge. Then, between the cartilage and the perichondrium an anterior tunnel is made on both sides. If necessary, inferior tunnels complete the access to the septum. In making the inferior tunnels, there is a posterior and an anterior approach.
The latter is called the maxilla-premaxilla approach. It is more complicated and risks damage to the incisive nerve. However, it has the advantage that it can be used in cases where it is difficult to make an anterior tunnel (Figure 123.12). To prevent atrophy of the mucous membranes, the blood vessels must be preserved by advancing in a subperichondrial or subperiostial direction (Figure 123.6). After tunnelling, the inferior part of the septum can be detached from the anterior nasal spine, premaxilla and the maxillary crest. Next an incision between the posterior part of the septal cartilage and the bony septum can be made. This is called a 'posterior chondrotomy'. After these two procedures, the septum can be moved aside, rather like a swinging door. This swinging-door technique gives access to the posterior or bony septum (Figure 123.13).
Correction of septal pathology A deviation due to tension in the septwn, or an inferior edge that has slid along the spine or a maxillary creSt, can be corrected by removing an inferior cartilaginous strip. Dislocations due to fractures can be dealt with intraseptally by mobilization or resection of parts of the septum.
Removing septal pathology
Figure 123.10 Access to tip and dorsum through an open approach tech nique.
More severe deformities require resection of parts of the septum and sometimes of the septal cartilage as a whole. After that, the resected area should be reconstructed preferably with the autologous materials already removed. When these are not available, the patient's ear or rib cartilage might be an alternative. The extent to which septal cartilage and bone can be removed is only limited by the surgeon's abilities to reconstruct the septum afterwards. Nevertheless, resection should be restricted as much as possible to avoid trauma and complications.
Figure 123.11
The hemitransfixion.
Chapter 123 The septum
Figure 123.12
I 1579
Septa I tu nnels.
Reshaping cartilage and bone Cartilage does not heal. Fractures and defects will be filled up by connective tissue. Retraction of connective tissue can alter a good result immediately after surgery into a poor result after some months to a year. The dynamics of the healing process must be understood to enable appropriate correction of the septum. Reshaping should be done with as little trauma as possible, with maximum preservation of straight portions of the septum.
Reconstruction of the septum
- - Perpendicular plate Vomer
,
, Cartilaginous septum
Figure 123.13 Access to the posterior part of the septum, swi ng ing-door proced ureo
Duplications, spines, crests and convexities are the main indications for a resection. Any removed material is saved for the reconstruction later. Straight parts are carefully preserved as a whole, to provide large struts necessary to give support to the dorsum, tip and columella.
Only the patient's own septal cartilage meets the requirements for optimum reconstruction. Other materials such as ear or rib cartilage can be used as a substitute, but are second choice. The use of cartilage from a tissue bank carries the risk of transmitting infectious agents, such as prions and viruses, and requires a good understanding of the mechanical properties of the donor materia1. 21 For these reasons, it is wise not to use these materials if it can be avoided. A strong strip of cartilage under the cartilaginous dorsum should prevent a saddle nose. Tip projection is preserved and retraction of the columella is prevented by a strip of cartilage in the caudal part of the septum. Of course it is best to leave the patient's own cartilage in place in these areas when that is feasible. If not, careful reconstruction is imperative. A mosaic of cartilage pieces can fill up a defect in the centre of the cartilaginous septum to prevent retraction by fibrous tissues of the cartilage supporting the dorsum and columella, which is a long-term complication after resection of the centre of the septal cartilage.
_l_-~ '
_ _
1580 I PART 13 THE NOSE AND PARANASAL SINUSES
Stabilizing the septum
.I Almost all nasal surgery affects both function and cosmesis. Correction of function and cosmesis should be combined in the same procedure. ./ Neither septal deviations nor septal deformities are by themselves an indication for a septoplasty. The objective of functional nasal surgery is to improve the interaction between the air and the mucosa. Lowering the resistance of the nose is of secondary importance. .I In children, if the cartilages of the nose are involved in nasal trauma, the primary objective is to limit growth disturbances of the nose and the face. ./ If possible, nasal surgery in children should be postponed until the nose is fully grown. If surgery in childhood is necessary, the growth centres in the cartilages should not be disturbed. -/ Atrophy of the mucosa after septal surgery should be prevented by preserving the blood vessels in the mucoperi chond rium/muco periosteu m. ./ In septal surgery, reconstruction of the septum is necessary to prevent flutter, atrophy of the mucosa, perforations and to maintain support of the external nose.
There are different ways to keep the septal skeleton in place during healing. First of all, a dressing is put into the nose to bring the mucosa together. In this way, the septum is squeezed between the blades holding the skeleton in place. Mattress sutures have the same effect. Splinting by so-called nasal splints is effective in stabilizing reconstructions that are more extensive. They have the advantage that they can stay in the nose and allow the patient to breathe through the nose, thus prolonging the time the septum is supported. It should be noted that nasal packs are very uncomfortable for the patient. Furthermore, there are a number of suture techniques to fixate the reconstructed septal parts. Techniques vary, according to the stability of the septum and the surgeon's preferences. [**1*]
KEY POINTS • The mucous membranes can he seen as the ' effector organ of the nose. They facilitate the functions of th~ nose~ olfaction, heating, humid ification and defence. • R~ther complex aerodyna mics are necessary to bring the air into contact with ,the m ucous membranes. This cannot be obtained wi thout a certa.in amount of resistance. • The sqll tum is an essential structure to maintain the function and shape of the nose. • Nasa) blockage should primarily be seen as an indication of disturbed nasa! frmclion. A feeling of nasal blockage i~ not an indication for functional nasal surgery unless a correctable disturbance of th e airflo\\' can be demonstrated. • There is insufficient evidence that repositionin g the nasal :oieptum after birth trauma in newborns has a positive effect in the long run. • A number of ~"ystemic diseases can be .,·,- di~wosed at an early stage in the septum.
Deficiencies in current knowledge and areas for future research The following areas have been identified as requiring research; )0- the mechanisms caUSing a feeling of nasal blockage; > the influence of both anatomy and surgery on the aerodynamics of the nose in relation to the interaction between air and mucosa; >- materials for reconstruction of the septum, in the event of autologous materials no longer being available.
REFERENCES Barelli PA, Loch EE, Kern EB, Steiner A (eds). Rhinology: the collected writings of Maurice H. Cottle MD. Warwick, NY; American Rhinologic Society, 1987. 2. VelWoerd CD, Urbanus NA, Mastenbroek GJ. The influence of partial resections of the nasal septal cartilage on the growth of the upper jaw and the nose; an experimental study in rabbits. Clinical Otolaryngology. 1980: 5: 291-302. 3. VelWoerd CD, Urbanus NA, Nijdam DC. The effects of septal surgery on the growth of nose and maxilla . Rhinology. 1979; 17: 53-63. 4. Pirsig W. Surgery of the nose in childhood: growth and late re!'Sults. Laryngologie, Rhinologie, Otologie. 1984; 63: 170-80. 1.
Best clinical practice ,/ After nasal trauma, examination of the internal nose for haematoma is obligatory. A septal haematoma should be treated urgently to avoid a septal abscess. .I In patients with a fever and nasal blockage three to five days after an insignificant nasal injury, a septal abscess should be suspected as a sequela of a missed septal haematoma.
*
Chapter 123 The septum
5.
6.
7.
8.
9.
* 10. 11.
* 12.
Grymer LF, Bosch C. The nasal septum and the development of the midface. A longitudinal study of a pair of monozygotic twins. Rhinology. 1997; 35: 6-10. Grymer LF, Pallisgaard C, Melsen B. The nasal septum in relation to the development of the nasomaxillary complex: a study in identical twins. Laryngoscope. 1991; 101: 863-8. Pirsig W. Growth of the deviated septum and its influence on rn idfacia I development. Facial Plastic Surgery. 1992; 8: 224-32. Huizing EH. Septum surgery in children; indications, surgical technique and long-term results. Rhinology. 1979; 17: 91-100. Maran AGD, LUlTd VJ (eds). Clinical rhinology. Stuttgart: Thieme, 1990. Moore EJ, Kern EB. Atrophic rhinitis: a review of 242 cases. American Journal of Rhinology. 2001; 15: 355-61. Jessen M, Ivarson A, Maim L. Nasal airway resistance and symptoms after functional septoplasty: comparison of findings at 9 months and 9 years. Clinical Otolaryngology. 1989; 14: 231-4. Roblin DG, Eccles R. What, if any, is the value of septal surgery? Clinical.Otolaryngology. 2002; 27: 77-80
13.
* 14. 15.
16. 17.
18.
19.
* 20. 21.
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Bitzer EM, Dorning H, Schwartz FW. Der klinische Erfolg der operativen Korrektur der Nasenscheidewand. Laryngorhinootologie. 1996; 75: 649-59. Dorning H, Bitzer EM, Schwartz FW. Patientenzufriedenheit als Health Care Outcome- das Beispeil der operativen Korrektur der Nasenscheidewand. Gesundheidswesen. 1996; 58: 510-8. Freer OT. The correction of delections of the nasal septum with minimum traumatism. Journal of the American Medical Association. 1902; 38: 636. Killian G. The submucous window resection of the nasal septum. Annals of Otology. 1905; 14: 363-7. Sercer A. Die Dekortikation der Nase. In: Sercer A, Mundlich K (eds). Plastische operation en an der Nase und an der Ohrmuschel. Stuttgart: Thieme, 1962. Padovan IF. External approach in rhinoplasty (decortication). In: Conley J, Dickinson JT (eds). Plastic reconstructive surgery of the face and neck, Vol. 1. Stuttgart: Thieme, 1972: 143-6. Goodman WS. External approach to rhinoplasty. Canadian Journal of Otolaryngology. 1973; 2: 207-10. Huizing E, de Groot JAM (eds). Functional reconstructive nasal surgery. Stuttgart: Thieme Stuttgart, 2003. Gibson T, Davis WB. The distortion of autogenous cartilage grafts: its cause and prevention. British Journal of Plastic Surgery. 1958; 10: 257-64.
124 Nasa I septa I perforations CHARLES EAST AN D SANTDEEP PAU N
Surgical
Definition: Through and through defect or defects of the nasal septum Sym ptomatology Clinical assessment Special investigations Prevalence of septal perforations Management
1582 1582 1583 1584 1584 1585
Surgical repair of septal perforations Key points Best clinical practice
1585 1586 1587 1587
Deficiencies in current knowledge and areas for future research References
1587 1588
The data in this chapter are supported by a Medline search restricted to English papers using the key words nasal, septal, perforation, focussing on diagnosis and surgery. Periodic review publications and textbooks of otolaryngology - head and neck surgery published in English also supported the chapter.
DEFINITION: THROUGH AND THROUGH DEFECT OR DEFECTS OF THE NASAL SEPTUM The exact prevalence of septal perforations is unknown as many perforations are asymptomatic, but in a general otolaryngology practice the clinician will encounter several patients with septal holes each year. Younger and Blokmanis 1 cite an incidence of just over 1 percent, which makes the condition relatively common. It must be remembered that racial traditions and fashion dictate that perforations in various parts of the body are a part of nonnallife and the anterior nasal septum is no exception. The majority of perforations involve the anterior quadrilateral cartilage of the septum. Kuriloff has provided an extensive list of the local and systemic causes (Table 124.1). Currently, the most common cause of perforation in the UK is probably local trauma, although in a' significant percentage, no clear history exists attracting the label of (idiopathic'. The trauma is frequently selfinduced or iatrogenic following surgery to the nasal septum or nasal instrumentation. Injuries to the
cartilagenous skeleton of the nose may result in perforation through a compound fracture of the quadrilateral cartilage in the absence of any external deformity. Recreational drugs, for example crack or cocaine snorted nasally, are becoming increasingly common as a cause of septal necrosis. 3 The prevalence of chronic specific infections producing perforations is smalL but there are a significant number of inflammatory conditions which should be excluded, particularly if the history does not give an easy clue to the aetiology.
SYMPTOMATOLOGY The principle symptoms associated with perforations are crusting, epistaxis and whistling. Other symptoms include a feeling of dryness, emptiness in the nose or a general feeling of discomfort. In a series of 69 septal perforations, Brain 4 showed that 62.4 percent were completely free from any symptoms. Size and position of the hole had a
Chapter 124 Nasal septal perforations I 1583
Table 124.1
Aetiologies of nasal septal perforations. Surface irritants
Infections
Neoplastic
Inflammatory
Nasal surgery Nose picking Septal cauterization (bi latera I) Nasal packing for epistaxis Septal hematoma/abscess
Coca i ne insufflation Cocaine adulterants Heroin inhalation
Syphilis Typhoid Diptheria
Sarcoidosis Crohn's disease Dermatomyositis
Decongestant nasal sprays Lime, cement, glass, salt, dust
Tu bercu losis Rhinoscleroma
Melanoma Adenocarcinoma Squamous cell carcinoma Metastatic carcinoma Lymphoma
Cryosu rgery
Tar and pitch
Lepromatous leprosy
Intubation (nasogastric/ tracheal) Desiccation (ozena, deviated septum)
Fumes (chromic/sulfuric acid)
Leish rna niasis
Arsen ica Is, mercu ria Is
Mucor
Calcium nitrate, cyanide Phosporous, sodium carbonate Copper-smelting fumes
Rhinosporidiosis Alternaria Actinomycosis Asperg i Ilosis Histoplasmosis Cryptocococcosis Coccidioidomycosis Paracoccidioidomycosis Candidiasis
Traumatic causes
Radiation Stab and gunshot wounds Foreign bodies (button batteries)
direct bearing on the presence of symptoms. Anterior perforations and large perforations where the anterior margin is in front of the nasal valve appear to be the most troublesome. This probably relates to the relatively slow mucociliary clearance from the anterior septum, low humidity in the anterior nares compared to controls s and the loss of mucosa, all contributing to dryness and crusting. [***] The accumulation of large crusts around the margin of the perforation produces a sensation of blockage. With large stable perforations, patients may feel the nose is empty or complain of 'blockage', even when nasal airflow is greater than average. These features may be due to turbulence of airflow in the nasal vestibule, although there is little evidence to support this. Huge perforations produce a common nasal cavity resulting in rhinolalia and an inability to clear secretions. 2 [*] Inflammation in the perforation margin leads to recurrent epistaxes, often triggered when the crust separates or is removed. Epistaxis can be quite significant from the sphenopalatine vessels. Large areas of mucosal deficit, particularly where there is cartilage exposure, prevent normal mucus clearance, contributing to localized infection and more inflammation. The local inflammation in the nose is often perceived as a generalized sense of discomfort, felt internally and over the nasal bridge. Over time, necrosis of septal cartilage will lead to enlargement of the hole in 'active perforations', sometimes to such a size that surgical closure is virtually impossible. i
L_-
Rheumatoid arthritis Relapsing polychondritis Wegener's granulomatosis Systemic lupus erythematosus
CLINICAL ASSESSMENT A full history is necessary when investigating septal perforations to cover the wide range of aetiologies. Principally, it is important to identify episodes of nasal trauma, cautery or surgery and, in particular, a history of substance abuse. Though patients may often deny it, aggressive nasal self-toilet with digital trauma or tissues will convert an inflamed mucous membrane to an ischaemic crusty area which ulcerates - the so-called 'pick ulcer'. Continued attempts to remove the crust invariably lead to cartilage exposure, cartilagenous necrosis and subsequent perforation. An overall assessment of the external and internal nasal skeleton should be made together with nasal endoscopy. Endoscopy is the best method to assess the margins and state of the residual septum. Measurement of the dimensions of the hole are performed by introducing a small paper ruler into the contralateral airway and reading the scale through the hole. Saddle deformities, deviations of the nose or septum, columella retraction and intranasal adhesions are commonly seen and may require reconstructive rhinoplasty techniques to correct if surgery is contemplated. Nasal questionnaires using a linear visual analogue scoring system may be used as a measure of symptom severity. Although not essential in routine clinical practice, they do provide subjective assessment for comparing pre- and post-treatment symptoms and are a basic measure of outcome (Figure 124.1).
1584 I
PART 13 THE NOSE AND PARANASAL SII\JUSES
Nasal septal perforation questionnaire
I
NAME:
Please mark you own score by marking a line at the appropriate point.
o = No symptoms, 10 = Worst symptoms. 10 Crusts/scabs 2
Nose bleeds
3
Whistling
4
l\Jasal discomfort
Please mark the appropriate point for your symptoms in Questions 5 and 6
5
My nose feels empty
My nose feels blocked
6
Can clear secretions easily
Can't clear secretions at all
Figure 124.1
Nasal septal perforation questionnaire.
SPECIAL INVESTIGATIONS Because of the wide range of aetiologies for septal perforation, history-taking is crucial. Any signs of inflammation around a perforation, however, should prompt investigation of other anatomical areas in the head and neck, as well as investigations for systemic inflammatory conditions. Nasal perforations may be the first sign of various granulomatous disorders, including Wegener's granulomatosis, and occur with a variety of collagen disorders including relapsing polychondritis, systemic lupus erythematosus (SLE) and dermatomyositis. Of the infective causes, the clinician is guided by the health of the patient, but tuberculosis and syphilis should be excluded. A full blood count, erythrocyte sedimentation rate (ESR), urea and electrolytes, urine analysis, C-ANCA, treponemal investigations, ACE titres and a chest x-ray, together with a nasal swab, provide an adequate baseline. Other symptoms of inflammation in the respiratory tract, for example cough, middle ear effusions, an arthritis or skin rash, should prompt referral to a clinical immunologist. There is little evidence that extensive investigations for patients with healed, stable and asymptomatic perforations contribute to a change in the management, particularly where the aetiology is clear. Routine biopsy of septal perforations to exclude vasculitis has been suggested,6,7 but biopsy rarely reveals anything other than chronic inflammation and is not usually sufficient for a specific diagnosis. Indeed, biopsy may convert an inactive perforation to an 'active state', resulting in significant enlargement of the hole. The role of routine biopsy in idiopathic perforations has recently been questioned. In
two retrospective series, septal biopsy was shown to be nonspecific for Wegener's and was only of value in those perforations with an irregular margin which were clinically malignant. 8 , 9 It is clear that the diagnosis of Wegener's or its reactivation cannot be reliably inferred from biopsy of the nasal septum alone. Practically, therefore, perforations should be biopsied if there is an unexplained aetiology, with persistent inflammation, or if the perforation is irregular. [Grade B] Specimens should be examined for mycobacteria and fungi, and with immunocytochemistry to exclude a neoplasm. 2
PREVALENCE OF SEPTAL PERFORATIONS The prevalence of septal perforations following nasal septal surgery shows wide variation and has been reported as between 1.4 and 25 percent. The prevalence appears higher after submucous resection operations 07-25 percent) than the more conservative septoplasty procedures 0.4-5 percent).l0 [**] The use of nasal splints during septal surgery is known to produce a higher incidence of perforation. l l [***] Splinting is unnecessary in the majority of routine septal surgery unless established adhesions are being treated. Recent retrospective reports 12 have suggested an association between nasal steroid sprays and the development of nasal perforation. It is known that all steroid sprays can cause inflammation over the caudal septum, by direct irritation or their initial vasoconstrictor activity, particularly if there is a septal deviation which takes the brunt of the spray jet. Patients should be directed to use the spray with the opposite hand to the nostril being treated, minimizing the impact
Chapter 124 l'Jasal septal perforations
on the septum. Any ulceration after starting steroid spray use should be allowed to heal by withdrawing the medication.
MANAGEMENT The majority of septal perforations are asymptomatic and require no specific treatment. 4 [Grade C] The more anterior the lesion, the more likely it is to cause symptoms. This probably relates to accessibility by the patient to pick at the nose, but may also be related to fast airflow producing drying in the region of the internal nasal valve. The management can be divided into three groups.
Prevention In a series of 50 perforation repairs at the Royal National Throat, Nose and Ear Hospital, 60 percent had a previous history of septal surgery. 13 Meticulous attention to technique is required in elevating the mucoperichondrial flaps in the correct plane, particularly avoiding overlapping bilateral mucosal tears. Starting the dissection on the easier (usually the concave) side to raise one intact flap first, and using an autograft of cartilage or ethmoid plate to support any tears, is good practice. The mucoperichondrium over large spurs is often very thin, and tears may be inevitable. However, when the spur is removed, there will be a relative excess of mucosa which can be repaired with absorbable sutures. Quilting sutures in the septum after surgery should be tied loosely to allow for post-operative oedema. The authors have seen perforations caused by individual sutures tied tightly in the septum which resulted in ischaemic necrosis. Septal inflammation or ulceration should be treated by withdrawing the source of the irritation and promotion of healing, for example by eradication of pathogenic bacteria, avoidance of aggressive cleaning and use of mucosal protectants (petroleum jelly). Antiseptic silicon barrier creams over six to eight weeks will stabilize the mucosa in the majority of cases. In recalcitrant inflammation, thin reinforced silastic sheeting can be sutured to cover the caudal septum. If there is a large area of cartilage exposure, however, this still may not be sufficient to prevent progression to perforation. When a septal ulcer heals, the scar produced may leave a persistent area of squamous metaplasia which never reverts to a mucosal surface. Periodic and regular use of barrier creams may be necessary.
Nonsurgical =-=-.==
-- -- - - - - - - - - - - - - - - - - - - - - - - - - - - - - -
This, essentially, is aimed at reducing the drying effect in the nasal mucosa to alleviate crusts and epistaxis. Alkaline
.,l,
I 1585
nasal douches, proprietory saline sprays and petroleumbased ointments are commonly used. There are no studies of the effectiveness of this type of regimen, but many patients adopt a twice daily ritual of douching and ointment application. It is usually obvious within six to eight weeks whether this will be effective in maturing the margins of a perforation.
Obturation The principle of obturation is to cover the inflamed mucosal margin. In 1951, Deneke and Meyer14 cited the use of septal obturators in the management of perforations. Inert sheeting (usually silastic) was placed to prevent drying and encourage epithelialization over the cartilage/bony septum to create a mature mucosal edge. Evidence suggests that patients do derive benefit from the use of nasal obturators, but opinion on their usage and effectiveness is divided. Facer and Kern,15 in a retrospective study of 73 patients, reported 72.8 percent of obturators remained in place, but 27.4 percent of buttons were removed or were extruded. [>(-] Brain4 described the long-term outcome of 102 patients with medium or large holes (1 cm perforations or larger). He described a good result in 44.4 and 32.4 percent, respectively. The main benefit from obturation appears to be the control of whistling and epistaxis. Often, crusting and nasal discomfort remain a problem. 6, 16 The feeling of obstruction is improved when crusting is reduced, but the bulk effect of an obturator may increase blockage, particularly in anterior perforations with a narrow nasal valve. Poorly tailored Silastic may irritate the mucosa, particularly with anterior holes close to the membranous septum. Patient interference and movement of the mobile membranous septum against the edge of the obturator can lead to granuloma formation. It is often for these reasons that patients request removal of the obturator.
SURGICAL Enlargement of a nasal septal perforation to prevent whistling was described by Jackson and Coates in 1922,17 but there is little evidence to support its routine use in clinical practice. One retrospective article of widening of the perforation and posterior edge repair in larger holes (IS-50 mm) evaluated the pre- and post-operative symptom scores obtained by a linear visual analogue questionnaire. Benefit was reported for the symptoms of crusting and epistaxis and overall nasal discomfort with a significant reduction in mean scores. This technique appears to offer some value for patients with persistent inflammation who could not retain a nasal obturator and who were deemed unsuitable for surgical repair. [**]
1586 I PART 13 THE NOSE AND PARANASAl SINUSES
SURGICAL REPAIR OF SEPTAL PERFORATIONS The plethora of techniques for septal perforation repair described over the years attest to the fact that there is still a challenging technical problem for the nasal surgeon, although reliable surgical techniques with good outcomes have been published in the last 15 years. The variety of repairs may be classified as: • free grafts: - simple or composite autografts; - allografts; • pedicled flaps: - local nasal mucosal; - buccal mucosal; - composite septal cartilage and mucosa; - composite skin/cartilage; • rotation/advancement of mucoperichondrial or mucoperiosteal flaps. Combinations of techniques have been employed in many small reports. In the larger series of observational outcomes of perforation repairs, two factors emerge that appear to have an important bearing on a successful outcome, to achieve closure in 80-90 percent of cases. The first is that there is sufficient residual mucosa in the nasal fossa which can be mobilized and transposed allowing direct suturing of the mucosal defect (Figure 124.2). The second is the routine use of a connective tissue interposition graft to support the repair. Bilateral mucosal flaps with the main blood supply derived from the sphenopalatine vessels form the basis of most techniques. [*'*] Grafts have been reported using temporalis fascia,18 mastoid periosteum, cranial periosteum,
cartilage (septal, auricular, rib) and bone (either locally or from rib or the iliac crest) .19,20 Small defects can be closed with bipedicled flaps, by making relieving indsions either superiorly or inferiorly. Larger holes up to about 2 cm require larger flaps which are pedicled only posteriorly based on the sphenopalatine vessels, and are effectively transpositionlrotation flaps. 1, 20, 21 Even if complete bilateral mucoperichondrial suturing of the hole is not possible, the use of a connective tissue graft between the leaves allows for epithelialization on the side of incomplete closure, as long as the flaps are proteced from drying out and the reconstruction does not get infected. In the presence of any dehiscence of the sutured mucosal defect, it appears that epithelialization occurs more reliably over fascia than cartilage or bone. Reports using acellular dermal allografts,22,23 instead of fascia appear to give similar success rates. (*] The allografts are expensive, but it must be remembered that donor site morbidity from fascia is not a major issue and the repair is entirely the patients own tissue. The use of other collagen xenografts is still undergoing evaluation. The authors have used at least two layers of either temporalis or temporoparietal fascia, if necessary with a sandwich of cartilage as a composite graft where there is little supporting remaining quadrilateral cartilage (Figure 124.3), for the last six years with a current success rate of 87 percent. Auricular cartilage, which is a useful graft, is often curved and care should be taken anterosuperiorly at the internal valve because any excess thickness at this level risks postoperative nasal block, requiring revision surgery. The nasal fossa is a contaminated area and therefore antibiotic prophylaxis is important. There are no studies as to the ideal length of the course, but the development of sepsis can have a potentially devastating effect on the
I
I
I !
( \ Figure 124.2 Extensive mobilization of the mucosal lining allows a round hole to be closed with sutures in a straight line.
Figure 124.3 Bilateral mucosal flap repair with staggered mucosal rotation/transposition flap closure and connective tissue interposition graft. The fascia should extend to the nasal floor to cover any secondary defect inferiorly.
Chapter 124 Nasal septal perforations I 1587
residual cartilage producing a saddle deformity. Currently, the authors give a ten-day course. 13 There is an anatomical limit to the amount of septal mucosa which can be transposed and this is directly inverse to the size of the septal hole. Large perforations (larger than 2.5 cm), particularly with a large vertical dimension as opposed to horizontal linear holes, still pose a problem. However, by extensive undermining along the nasal floor and inferior meatus inferiorly and under the upper lateral cartilage superiorly, substantial flaps may be created. The careful atraum(ltic elevation of flaps is technically demanding, particularly if the mucoperichondrium is inflamed, atrophic or there is a significant spur of the septum. The surgeon has three options for the approach. 1. Endonasal: 18 This approach is limited principally by nostril size and position of the hole. Design of the endonasal flaps is critical in this approach due to the limited access. Broad-based elevations via hemitransfixion incisions and bipedicled flaps preserving anterior and posterior blood supplies with horizontal relieving incisions together with interposition grafts should give very good results for small holes (up to 0.5 cm). 2. External rhinoplasty approach via a trans columella approach 19 or a columella-philtrum incision: The external approach or its modification by sectioning the columella below the medial crural footplates and connecting to a transfixion and intercartilagenous incisions provides excellent exposure of the septum and lower dorsum, particularly if concomitant rhinoplasty is required and especially when additional grafting is needed to the nasal valve or dorsum. Alar crease incisions only provide limited additional unilateral access and should not be combined with the transcolumella approach because of the risk of ischaemia to the columella flap. It is possible to design larger flaps through this approach and suturing of the mucosal hole is definitely easier than by the endonasal approach. The use of medially based pedicled buccal mucosal flaps have limited use for larger perforations, bu t are useful to repair secondary deficiencies of the membranous septum when the mucosa has been mobilized to close very anterior holes. 3. Midface degloving approach: 24 This is an extensive dissection of the face which has been employed for very large holes (> 2 cm). Used purely as an approach with standard rotation transposition mucosal flaps, it appears to offer little benefit over an external approach for successful closure but with a higher complication rate (vestibular stenosis, 20 percent). Variation of the technique by employing tissue expansion of
the mucosa and skin grafting to the nasal sill appear to improve the success rate and reduce the incidence of nasal vestibular stenosis. Tissue expansion is achieved along the nasal floor using a small (1 x 3 cm) expander over six to eight weeks with a total volume of 4-7 mL. This technique has the advantage of generating more lining for easier mucosal closure, but the extensive relatively traumatic dissection must be weighed against the degree of benefit to be gained by the patient. Reported success in this series was 18 out of 22 patients with holes from 2 to 4 cm diameter. Although there is evidence of good technical success in surgical repair of the perforated septum for small- to medium-sized holes, objective evidence of patient benefit following surgical closure is lim.jted. Lindemann et al. s have shown improvements in nasal physiology particularly in end-inspiratory humidity and a reduction in symptom scores for epistaxis and nasal dryness.
KEY POINTS' More than ,half ofp'ertor"tions" are .. ", asyn\Pto,m~tic
10"
•
I
Best clinical practice '-
.I Meticulous attention to technique in the execution of septal surgery with adequately supported repair in the event of mucosal tears. .j Referral to specialist rhinologist/facial plastic surgeon for repair of small- to medium-sized holes.
Deficiencies in current knowledge and areas for future research
»
»
More supporting evidence of outcome measures including general health status are needed to confirm the benefits of surgical repair. Tissue engineering with the possibility to produce cartilage sheets and stable collagen as implants, which are guaranteed free from infection, will remove the need for a donor site.
1588 I PART
13 THE NOSE AND PARAI\JASAl SII\JUSES
REFERENCES 1. Younger R, Blokmanis A. Nasal septal perforations. Journal of Otolaryngology. 1985; 14: 125-31. 2. Kuriloff DB. Nasal septal perforations and nasal obstruction. Otolaryngologic Clinics of North America. 1989; 22: 333-50. 3. Slavin SA, Goldwyn RM. The cocaine user: The potential problem patient for rhinoplasty. Plastic and Reconstructive Surgery. 1990; 86: 436-42. 4. Brain D. Septo-rhinoplasty: The closure of septal perforations. The Journal of Otolaryngology. 1980; 94: 495-505. 5. Lindemann J, leiacker R, Stehmer V, Rettinger G, Keck T. Intranasal temperature and humidity profile in patients with nasal septal perforation before and after surgical closure. Clinical Otolaryngology. 2001; 26: 433-7. 6. Brain D. The nasal septum. In: Scott B (ed.). Scott Brown's Otolaryngology. Oxford: Butterworth Heinemann, 1997: 4-11. 7. Bridger G. Surgical closure of septal perforations. Archives of Otolaryngology Head and Neck Surgery. 1986; 112: 1283-6. 8. lVIurray A, McGarry GW. The clinical value of septal perforation biopsy. Clinical Otolaryngology. 2000; 25: 107-9. 9. Diamantopoulos II, Jones I'JS. The investigation of nasal septal perforations and ulcers. Journal of Laryngology and Otology. 2001; 115: 541-4. 10. Dommerby H, Rasmussen 0, Rosborg J. long term results of septoplastic operations. ORL Journal for Otorhinolaryngology and its Related Specialties. 1985; 47: 151-7. 11. von Schoenbergm, Robinson P, Ryan R. The morbidity from nasal splints in 105 patients. Clinical Otolaryngology. 1992; 17: 528-30.
12.
* 13. 14.
* 15. 16.
17. 18. 19.
* 20. * 21. 22.
23.
24.
Cervin A, Andersson M. Intranasal steroids and septum perforation - an overlooked complication? Rhinology. 1998; 36: 128. Jayaraj SM, East CEo PDSO foil in composite reconstruction of the nasal septum. Accepted for publication in Journal of Laryngology and Otology, 2007. Meyer R. Secondary rhinoplasty including reconstruction of the nose, 2nd edn. Berlin, Heidelberg, New York: Springer, 2002. Facer GW, Kern EB. Nonsurgical closure of nasal septal perforations. Archives of Otolaryngology. 1979; 105: 6-8. Osma U, Cureoglu S, Akbulut N, Meric F, Topcu I. The results of septal button insertion in the management of nasal septal perforation. Journal of Laryngology and Otology. 1999; 113: 823-4. Jackson Cl, Coates GIVI. Diseases of the throat, nose and ear:. Philadelphia: W. B. Saunders, 1922. Fairbanks DNF. Closure of nasal septal perforations. Archives of Otolaryngology. 1980; 7: 403-6. Goodman WS, Strelzow W. The surgical closure of nasoseptal perforations. Laryngoscope. 1982; 92: 121-4. Kridel RWH, Appling D, Wright WK. Septal perforation closure utilizing the external septorhinoplasty approach. Archives of Otolaryngology. 1986; 112: 168-72. Schultz-Coulon HJ. Experiences with the bridge-flap technique for the repair of large nasal septal perforations. Rhinology. 1994; 32: 25-33. Kridel RWH, Foda H, Lunde KC. Septal perforation repair with acellular Human Dermal Allograft. Archives of Otolaryngology. 1998; 124: 73-8. Foda H. The one-stage rhinoplasty septal perforation repair. Journal of Laryngology and Otology. 1999; 113: 728-33. Romo T. Sclafani AP, Falk AN, Toffel PH. A graduated approach to the repair of nasal septal perforations. Plastic and Reconstructive Surgery. 1999; 103: 66-75.
125 The management of enlarged turbinates LUISA F GRYMER
Anatomy and function of the turbinates Key pOints The enlarged turbinates Key points Turbinate and rhinoplasty Best clinical practice Turbinate and septoplasty Best clinical practice Snoring and sleep apnoea
1589 1589 1590 1590 1590 1590 1590 1591 1591
Chronic rhinitis and rhinosinusitis Best clinical practice Medical management Surgical management Key points Best clinical practice Deficiencies in current knowledge and areas for future research References
1591 1592 1592 1592 1594 1594 1594 1594
The data in this chapter are supported by a Medline search using the key words turbinates, rhinitis and turbinates, turbinates and surgical management
ANATOMY AND FUNCTION OF THE TURBINATES Three (sometimes four) turbinates (or conchae) are attached to the lateral wall of the nose. Normal turbinates are thin, curved, shell-like bones covered by ciliated respiratory mucosa. They divide the nasal airway into three major air passages or meatuses. The respiratory function of the turbinates, mainly the inferior turbinate, is to help create the hlgh inspiratory resistance necessary for normal breathing, ensuring the negative intrathoracic pressure needed for inspiration. The nasal cavity is divided into several parts, each having a specific influence on the inspiratory airt1ow: the vestibulum nasi, the istlunus nasi, the area of the turbinates and the choana. The isthmus is the narrowest part of the airway and the site of highest resistance to airt1ow/ ensuring laminar flow throughout this segment which is often referred to as the 'nasal valve'. It extends from the internal ostium to the first few millimetres of the pyriform aperture. The congestion state of the anterior part of the inferior turbinate influences this segment (Figure 125.1).2 As the nasal cavity increases in cross-sectional area, a diffuser effect takes place
..
resulting in turbulence of air flow and a decrease in flow velocity. 3 The area and configuration of the inferior and middle turbinates facilitates the maximum contact of the air with the mucosa. Humidification, warming and cleansing the air is maximized by the turbulent flow and large mucosal surface area, as well as the rich blood supply, especially on the inferior turbinate. The nasal defence system, including mucociliary transport and cellular and humoral defence, are mainly carried out by the mucosa of the turbinates.
KEY POINTS • The inferior turbinate is the main regulator of nasa1 atrflow and thus normal respiration. • The mucosa of the turbinates is essential to maintain norma'] nasal defence. humidification. w~1rming and cleaning the air. [""*"/'1H]
1590 I PART 13 THE NOSE AND PARANASAL SINUSES
KEY POINTS • Mucosal swel1ing of the turbinates is part of the physio logic vascular changes which take place during respiration. Hyperreactivity, infection and allergy may enhance these changes. Isthmus nasi (MCA - non decong)
Valve area
• Definition of normality and hence of the enlarged turbinates is lacking. [*"*]
Ostium internum (MCA - decong)
TURBINATE AND RHINOPLASlY
Figure 125.1 The dimensions of the dynamic 'valve area' are mainly determined by the state of congestion of the inferior turbinate.
THE ENLARGED TURBINATES Since the latter part of the nineteenth century, different medical and surgical treatments have been developed to treat the enlarged turbinates. However, no definition of an enlarged turbinate exists in terms of objective measurement, and diagnosis is by exclusion criteria when dealing with the sensation of nasal obstruction. In addition, diagnosis is often retrospective based on the effect of a given treatment (for example, reduction of the turbinate) on the impaired nasal patency. The bone and/or the mucosa may be enlarged, but what constitutes pathologic or normal is not well defined and therefore there is controversy over the management of the turbinates in symptomatic subjects,4 Swelling of the nasal mucosa is part of the normal process known as the 'nasal cycle'. There are data indicating that the periodical changes may be alternating from side to side, may change at the same time in both sides of the nasal cavity or may be completely irregular,S, 6, 7, 8 The cyclical changes take place in the nasal cavity, especially in the mucosa of the inferior turbinate, but also the mucosa of the middle turbinate, the septum and the ethmoidal sinus, and present cyclic changes as shown by magnetic resonance (MR) imaging.9 Allergy and infection enhance the degree of swelling and topical drugs, such as steroids and vasoconstrictors, change the rhythm of the cycle.lO The reason for periodical changes in the mucosal congestion is not known and data are lacking about what should be considered as normal swelling.
There is some evidence that aesthetic reduction rhinoplasty changes the internal dimensions of the nasal cavity, mainly due to a change in position of the inferior turbinate. l l , 12 In these cases, the inferior turbinate may be considered relatively enlarged in relation to the nasal dimension after operation. However, one study showed that regardless of the fact that almost 100 percent of cases had reduction of the internal nasal dimensions, only 8 percent experienced nasal obstruction six months after surgery.12 However, the obstruction may recur in the long term. The controversy continues and some surgeons routinely perform inferior turbinate surgery in reduction rhinoplasty to prevent nasal obstruction. The important lack of knowledge of what is normal concerning the skeletal and mucosal characteristics of the nasal cavity contribute to the controversy. [**]
The following options are recommended as reasonable indications for consideration of inferior turbinate reduction in cases undergoing aesthetic rhinoplasty: ./ narrow skeletal dimensions of the anterior part of the nasal cavity; ./ mucosal congestion of the anterior 3-4 cm of the nasal cavity; ./ the sensation of nasal obstruction preoperatively. [Grade D]
TURBINATE AND SEPTOPLASlY Currently, the treatment of anterior septal deviations and nasal obstruction is septoplasty, but there is controversy about turbinate surgery in these cases. The osseous part of both the ,middle and inferior turbinates may have enlarged, as a developmental process on the wider side
Chapter 125 The management of enlarged turbinates
of the nOse, contralateral to marked septal deviations. These septal deformities may be either congenital, as in the cleft palate nose, or following trauma early in childhood. This phenomenon is known as compensatory turbinate hypertrophy, which may be skeletal or mucosal (Figure 125.2). Its existence has been shown objectively, 13 but there is no evidence that it should be treated as a supplementary procedure to septoplasty. A controlled, randomized study 14, 15 showed no subjective benefit from inferior turbinoplasty on the side opposite to a septal deviation, regardless of the degree of deviation either in the short or the long term. However, in the short term and in cases of marked septal deviation, the crosssectional areas increased or were unchanged after turbinate surgery and decreased slightly but significantly in cases without turbinate reduction. However, the longterm stud y15 included only a few patients who originally had marked septal deviations. Mucosal turbinate hypertrophy was objectively demonstrated 14 in 62 percent of patients, regardless of the degree of septal deviation, which was most pronounced on the side of septal deviation (i.e. the narrowest side of the nose). Whether the mucosal congestion is secondary to the septal deviation 16 or a feature common to patients with nasal obstruction due to the septal deviation has not been studied. Since the subjective satisfaction rate after septoplasty is only around 70 percent 14 , 15,16,17 after a few months and 43 percent after five years,15 the controversy continues as to when to perform septoplasty alone and when to reduce the inferior turbinates. Several studies report subjectively good results for nasal obstruction in over 90 percent of cases, following inferior turbinate reduction in cases of minor or no anterior septal deviation, both in the short 18 and long term. 19 [>PI-/*]
I 1591
In cases of anterior septal deviation and nasal obstruction. the following recommendations may be made: ./ Establish the degree of obstruction and the congestion component in both nasal cavities. ./ Marked septal deviation should be corrected by septoplasty. ./ Minor septal deviations and signs of nasal congestion may have other etiologies. Infection, allergy or hypersensitivity should be kept in mind. If conservative medical treatment is not satisfactory and the objective measurements are indicative of small spatial dimensions anteriorly, surgical turbinate reduction should be considered. [Grade DJ
SNORING AND SLEEP APNOEA Nasal airway patency changes with body position and it is reduced when lying down. There is evidence that compared with normals the postural variation of nasal resistance is more pronounced in patients with allergic rhinitis 20 and in nonapnoeic snorers the recumbent position reduces airway patency,21 whilst awake and asleep. In one study,22 over 90 percent of a group of snorers had abnormally high nasal resistance and acoustic rhinometry curves, suggesting engorgement of the inferior turbinate. Snoring is more frequently present in populations with nasal obstruction and inferior turbinate reduction 18 may reduce the frequency of snoring. Many patients suffering from obstructive sleep apnoea (OSA) treated with continuous positive airway pressure (CPAP) devices develop troublesome nasal obstruction. This is probably an increased vasomotor responsiveness, secondary to the use of CPAP. Local steroids may help,20 but are not always effective in controlling turbinate congestion. There is no evidence that surgical turbinate reduction helps in the long term?3 [**/*J
CHRONIC RHINITIS AND RHINOSINUSITIS
Figure 125.2
Compensatory hypertrophy of the middle and
inferior turbinates on the left, wide side of the nose, opposite to a septal deviation.
Nasal obstruction is often the dominating symptom in chronic inflammation/infection of the nose and -sinuses. Vascular engorgement of the nasal cavity is characteristic, mainly of the inferior tui-binate with its well-developed vascular supply. Allergic rhinitis, pregnancy, antidepressant drugs, rhinitis medicamentosa due to long-term use of nasal vasoconstrictors, are diagnoses that should be kept in mind in patients with chronic nasal obstruction (CNO). The group of CNO includes a variety of pathologic and physiologic conditions and principally CNO is not a
1592 I PART 13 THE NOSE AND PARA NASAL SINUSES
(surgical disease'. There are no definitions of indications for inferior turbinate surgery, except that surgery is performed for the subjective feeling of impaired nasal patency. In an attempt to define CN0 18 with acoustic rhinometry, mucosal congestion was found in 76 percent of subjects with CNO, bilaterally in one-third and unilaterally in two-thirds of them. Whether the turbinates are truly irrevernbly enlarged, temporarily engorged due to disturbance of the nasal mucosa or they are enlarged relative to the skeletal dimension of the anterior part of the nasal cavity are questions that make the precise clinical diagnosis of enlarged turbinates difficult in practice. Nevertheless, different studies show inferior turbinate reduction to be effective in more than 90 percent of cases in relieving the chronic feeling of nasal obstruction refractory to medical treatment. The techniques used are numerous and the long-tenn effect is also variable from weeks to years. One controlled, randomized studyl9 suggests submucous resection of the turbinate (SMOFIT), with outfracture of the inferior turbinate bone is effective in the long term, with few adverse effects on the nasal mucosa [***1**] In infectious chronic rhinosinusitis (CRS), the inferior turbinate may be enlarged secondarily to the infection in the middle meatus. However, the current opinion is that the enlargement recedes after sinus infection has been treated. Stammberger24 states that he hardly ever performs reduction of the inferior turbinate in CRS. Occasionally, persistent engorgement of the posterior end of the turbinate occludes the choana. In this situation, removal with a surgical snare is indicated. The role of the middle turbinate (MT) in the development and persistence of CRS is unknown and the role of middle turbinate surgery for CRS remains controversial. The inferior turbinate is very rarely pneumatized, while aeration of the middle turbinate (or concha bullosa, CB) is a common anatomical variant. On coronal computed tomography (CT) scans25 of patients evaluated for sinus disease, 34 percent had CB on at least one side. There was no difference in the overall incidence of inflammatory disease in the ostiomeatal complex in symptomatic patients between those with and without CB. The role of the concha bullosa is still debatable. However, an abnormally enlarged middle turbinate may obstruct the ostiomeatal complex and create problems with the drainage of the paranasal sinuses. In the era of functional endoscopic sinus surgery, some surgeons consider the MT to play a key role in the outcome of endoscopic surgery for CRS. In a prospective, randomized study26 of 1106 patients with CRS, anterior resection of the middle turbinate had significant beneficial effect minimizing the iatrogenic obstruction due to synechiae. This was found in patients with more severe sinonasal disease, but no difference was found in mild cases of CRS. [**1*]
The following are recommended as reasonable indications for consideration of inferior turbinate surgery in adults with chronic nasal obstruction. Patients should meet all the following requirements: .I nasal endoscopy without signs of infection or neoplasm; ./ failure of conservative medical treatment of adequate duration; ./ The complaint should be disabling. [Grade C]
MEDICAL MANAGEMENT There is evidence that intranasal corticosteroids should be used as the first-choice drug in the treatment of nasal obstruction, provided neoplasms and gross skeletal abnormalities have been excluded. More than 100 double-blind, placebo-controlled studies27 have shown efficacy of intranasal corticosteroids on nasal blockage, sneezing and rhinorrhoea, in allergic and in noninfectious, nonallergic rhinitis. Antihistamines for nasal obstruction are ineffective as compared with topical steroids. Vasoconstrictors may be used for a few weeks and awareness must focus on the risk of developing rhirtitis medicamentosa. Use of topical, isotonic saline spray is a recommendable adjunctive treatment in all cases of chronic nasal diseases. (****]
SURGICAL MANAGEMENT The surgical management of the enlarged inferior turbinates has been debated for more than 100 years. Reviews 28 • 29 in this field show that the focus has been placed more on technological advances than to establish a benefit to the patient. The evidence supporting the efficacy of the different procedures remains debatable. The controversy also surrounds the middle turbinate and this has been addressed under Chronic rhinitis and rhinosinusitis. This section will focus on surgery of the inferior turbinates (IT) for chronic nasal obstruction. The chronology of the appearance of the different surgical methods is shown in Table 125.1. The goal of any surgical treatment of the IT should be to improve nasal obstruction and to avoid complications in the short and long term. The different surgical procedures may be classified into mechanical procedures, destructive procedures and turbinate resection procedures (Table 125.2). The complications are primary or secondary haemorrhage, synechiae and crusting ranging from mild to atrophic rhinitis. The reviews 28,29 assessing the benefits and complications of the different procedures come to widely differing recommendations. One states 'laser turbinate reduction is strongly supported because of its
Chapter 125 The management of enlarged turbinates. 1593
relatively effective results with minimal associated morbidity.,28 By contrast, another review concluded 'that it seems that electrocautery, chemocautery, (subtotal) turbinectomy, cryosurgery and laser surface surgery should not be used) as these techniques are too destructive. Intraturbinal turbinate reduction (intraturbinal turbinoplasty) would seem to be the method of choice.'29 In the time between these reviews the first prospective) randomized study comparing electrocautery) cryotherapy, laser cautery) submucosal resection without and with lateral displacement and turbinectomy was published. The study gives extensive objective results with an observation period of between one and four years. The conclusion is that submucosal resection of the cavernous tissue of the IT with lateral displacement of the turbinate bone achieves a long-lasting improvement of the nasal passage with normalization of the mucociliary transport time and without post-operative bleeding. 19
The surgical procedure is described as follows: through a 3-4-mm incision on the head of the inferior turbinate, the submucosal tissue is dissected from the medial surface and inferior edge of the bone by an elevator. Excess cavernous tissue is removed with Hartmann forceps with resection of the posterior end of the turbinate (Figure 125.3). Merocel packing is used.
Table 125.1 Different surgical methods for treatment of enlarged inferior turbinate. Method
Year(s) introduced
Currently in use
1845-1880
+
1869-1890 1882 1904 1906-1911
+ + + +
1930-1953 1952 1953 1961 1970 1982 1977 1994 1998 2002
+
(a)
Thermal coagulation, electrocautery Chemocoagu lation Turbi nectomy Late ra Iization Su bmucous resection tu rbina te bone Pa rtia I resection Injection of corticosteroids Injection of sclerosing agents Vidian neurectomy Cryosurgery Turbi noplasty Laser su rgery Powered instruments Rad iofrequency Argon plasma surgery
Table 125.2
OF SMR
+ + + + + +
Figure 125.3 (a) Incision on the anterior edge of the inferior turbi nate; (b) subm ucous resection of the cavernous tissue of the inferior turbinate (SMR) and outfracture of the turbinate bone (OF); (c) result.
Surgical procedures for treatment of enlarged inferior turbinate, complications and effect.
Mechanical procedures Lateral ization/ou tfractu re Destructive procedures Electrocautery Cryosu rgery Laser su rgery Resection procedures Subm ucous resection Parti aI resection Total resection
Bleeding
-cr~sti ~g.Jsyn~~h!~~e.·ShQ:r~~~~~~~,~eff\~~t,. : lD-~g:te.r~I- ~~fect +/-
-/+ +
+/+ + ++ +
+ +/+ +/+ +/+
+ + +
+/-
+/+ +/+
+ + ++ ++
++ + +
1594 I PART 13 THE NOSE AND PARANASAL SINUSES ).- Controlled. randomized studies of different surgical treatments. with long-term follow up of groups with well-defined diagnoses should be carried out. ). The perception of nasal obstruction at the brain level needs to be elucidated.
New technological devices, such as powered instruments, radiofrequency and argon plasma, are being applied to turbinate reduction. However, only preliminary results are available. The debate on the surgical treatment of the enlarged inferior turbinate will continue, but the way forward has been shown. 19 [****1***1**]
KEY POINTS • The feeling of nasal obstruction Inay be part of the nOTmal nasal physiology. • Endoscopy of the nose and rhinopharynx is necessary to disclose serious causes of nasal obstruction. • Chronic rhinitis usuai!l.y responds to appropriate medical therapy. • In cases without anatom,ical deformities, if medical therapy is ineffective, appropriate surgical reducti,o n of the turbLnates may be effective in 90 percent of cases.
REFERENCES 1.
2.
3.
*
4.
5.
6. .I A thorough history of symptoms and previous medical therapy is necessary to establish the possible etiology of nasal obstruction. .I Chronic nasal obstruction may be due to neoplasms. sinonasal infections. drug abuse, allergy or nasal hypersensitivity. It is mandatory to examine the nasal cavity and the rhinopharynx before offering a treatment. .I If gross anatomical deformities are found. surgical treatment must be considered. .I In nasal congestion with symptoms of allergic rhinitis or nasal hypersensitivity. treatment with intranasal corticosteroids for between one and two months should be the first choice of treatment. ../ If conservative treatment has been used adequately and the nasal obstruction is disabling, inferior turbi nate red uction shou Id be considered. Prospective. randomized. objectively supported studies will hopefully become available in the future.
7.
8.
9.
10.
11.
12.
13.
Deficiencies in current knowledge and areas for future research )- A normal nasal cavity in terms of congestion needs to be defined. > Reliable measurement of nasal airflow changes after medical and surgical treatment of the turbinates - needs to be established.
* 14.
Haight JS. Cole P. The site and function of the nasal valve. Laryngoscope. 1983; 93: 49-55. Grymer LF. Hilberg O. Pedersen OF. Rasmussen TR. Acoustic rhinometry: Values from adu Its with subjective normal nasal patency. Rhinology. 1991; 29: 35-47. Mlynski G, GrOtzenmacher S, Plontke 5, Mlynski B, Lang C. Correlation of nasal morphology and respiratory function. Rhinology. 2001: 39: 197-201. Eccles R. Nasal airflow in health and disease. Acta Otolaryngologica. 2000: 120: 580-95. A recent review of the different mechanisms influencing airflow and background for nasal obstruction. Stoksted P. The physiologic cycle of the nose under normal and pathologic conditions. Acta otolaryngologica. 1952; 42: 175-9. Eccles R. The central rhythm of the nasal cycle. Acta Otolaryngologica. 1978; 86: 464-8. Hilberg O. Grymer LF. Pedersen OF. Spontaneous variations in congestion of the nasal mucosa. Annals of Allergy, Asthma and Immunology. 1995: 74: 516-21. Flanagan P, Eccles R. Spontaneous changes of unilateral nasal airflow in man. A re-examination of the 'nasal cycle'. Acta Otolaryngologica. 1997; 117: 590-5 . Kennedy OW. Zinreich SJ. Rosenbaum AE. Kumar AJ. Johns ME. Physiologic mucosal changes within the nose and ethmoid sinus: imaging of the nasal cycle by MRI. Laryngoscope. 1988; 98: 928-33. Hilberg O. Grymer LF. Pedersen OF. Nasal histamine challenge in nonallergic and allergic subject evaluated by acoustic rhinometry. Allergy. 1995; 50: 166-73. Guyuron B. Nasal osteotomy and airway changes. Plastic Reconstructive Surgery. 1997; 102: 861-3. Grymer LF. Reduction rhinoplasty and nasal patency: Change in the cross-sectional area of the nose evaluated by acoustic rhinometry. Laryngoscope. 1995; lOS: 429-31. Hilberg O. Grymer LF. Pedersen OF, Elbrond O. Turbinate hypertrophy: evaluation of the nasal cavity by acoustic rhinometry. Archives of Otolaryngology - Head and Neck Surgery. 1990; 116: 283-9. Grymer LF. ilium P, Hilberg O. Septoplasty and compensatory inferior turbinate hypertrophy: A randomized study evaluated by acoustic rhinometry. Journal of Laryngology and Otology. 1993; 107: 413-7. The first attempt to define objectively turbinate mucosal hypertrophy and the first prospective, randomized study on compensatory inferior turbinate hypertrophy.
Chapter 125 The management of enlarged turbinates I 1595 15.
Ilium P. Septoplasty and compensatory inferior turbinate
randomised, double-blind, placebo-controlled clinical pilot
turbinaoplasty. European Archives of Otorhinolaryngology.
trial. Laryngoscope. 2001; 111: 1783-91.
1997; 254: 89-92. 16. 17.
solutions. Hyperplastic lower turbinate, Chapter 9. Functional endoscopic sinus surgery. New York: Decker BC,
1991: 360-1.
Holmstrom M, Kumlien J. A clinical follow-up of septal
25.
rhinomanometric examination in the decision concerning
OM, Rosenbaum AE. Concha bullosa: CT evaluation. Journal of Computer-Assisted Tomography. 1988; 12:
778-84.
Grymer LF, Ilium P, Hilberg O. Bilateral inferior
26.
endonasal sinus surgery with and without partial middle
Passali 0, Lauriello M, Anselmi M, Bellusi L. Treatment of
turbinate resection. Annals of Otology, Rhinology and
The first prospective, randomized study of different surgical procedure for turbinate reduction. The results are
Laryngology. 2000; 109: 634-40.
23.
•
27.
Mygind N, Dahl R, Nielsen LP, Hilberg 0, Bjerke T. Effect of corticosteroids on nasal blockage in rhinitis measured by
* 28.
objective methods. Allergy. 1997; 52: 39-44. Jackson LE, Koch RJ. Controversies in the management
based on objective measurements and is long term.
of inferior turbinate hypertrophy: A com prehensive
Hasegawa M, Saito Y. Postural variations in nasal resitance and symptomatology in allergy rhinitis. Acta
review. Plastic and Reconstructive Surgery. 1999; 103: 300-12. This is a comprehensive review of the different
Otolaryngologica. 1979; 88: 268-72.
surgical methods applied to inferior turbinate hypertrophy,
Berg S, Cole P, Hoffstein V, Haight JS. Upper airway
with a different conclusion from other comprehensive
pressures in snorers and nonsnorers during wakefulness
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and sleep. Journal of Otolaryngology. 2001; 30: 69-74.
22.
Havas Th E, Lowinger DSG. Comparison of functional
1996; 34: 50-3.
382 patients randomly assigned to therapy. Annals of Otology, Rhinology and Laryngology. 1999; 108: 569-75.
21.
Zinreich SJ, Mattox DE, Kennedy OW, Chisholm HL, Diffiey
operation. Clinical Otolaryngology. 1988; 13: 115-20.
hypertrophy of the inferior turbinate: Long-term results in
20.
Stammberger H (ed.). Sinus problems and endoscopic
congestion? Rhinology. 1983; 21: 21-7.
turbinoplasty in chronic nasal obstruction. Rhinology.
* 19.
24.
Graamans K. Does septal surgery influence submucous
surgery with special attention to the value of preoperative
18.
in subjects using continuous positive air pressure: A
hypertrophy: Long-term results after randomised
* 29.
Hoi MKS, Huizing EH. Treatment of inferior turbinate
Lenders H, Schaefer J, Pirsig W. Turbinate hypertrophy in
pathology: a review and critical evaluation of the
habitual snorers and patients with obstructive sleep
different techniques. Rhinology. 2000; 38: 157-66.
apnoea: Findings of acoustic rhinometry. Laryngoscope.
This is a comprehensive review of the different surgical
1991; 101: 614-8.
methods applied to inferior turbinate hypertrophy,
Powell NB, Zonato AI, Weaver EM, Li K, Troell R, Riley RW
with a different conclusion from the other comprehensive
et al. Radiofrequency treatment of turbinate hypertrophy
review.
126 Epistaxis GERALD W MCGARRY
Background Vascular anatomy Classification of epistaxis Adult primary epistaxis Secondary epistaxis
1596 1596 1599 1600 1605
Key points Best clin iea I practice Deficiencies in current knowledge and areas for future research References
1606 1606 1606 1606
The data in this chapter are supported by searches in the Medline, EmBase and the Cochrane Library databases using the key words epistaxis, aetiology, management, treatment and therapies in main articles, RCTs and systematic reviews. Search results were augmented by a manual search through major references and texts. Cross-checking was carried out with references from review articles.
BACKGROUND Epistaxis is defined as bleeding from the nose. This prosaic definition belies the difficulties associated with one of otolaryngology's most common and most difficult to treat emergencies. The historical literature contains numerous references to epistaxis and its antiquity is reflected in the fact that the simplest treatment for a nose bleed (pinching the ala nasi) is called the Hippocratic technique. While an extensive review of the history of epistaxis is beyond the scope of this book, much of the historical literature remains relevant and students of this subject are advised to review the writings of Morgagni, who even predicted nasal endoscopy in 1761! 1
VASCULAR ANATOMY Arterial supply The internal and external carotid arteries supply the nose via branches which anastomose extensively within the
lateral wall, septum and across the midline. In 1879, James Little identi fied an arterial plexus on the anterior septum as a frequent site of bleeding and the same plexus was described one year later by Kiesselbach? As a result of these descriptions, the area most frequently implicated in epistaxis is known as Little's area or Kiesselbach plexus. In the posterior nasal cavity, the vessels are larger than those in Little's area and can more easily be traced to their external or internal carotid origin. EXTERNAL CAROTID ARTERY
The external carotid artery supplies the nasal cavity via facial and maxillary branches. The facial artery supplies the most anterior part of the septum (nasal septal rami of the superior labial artery), the vestibule (lateral nasal artery) and a small area of the nasal cavity (ascending palatine artery). The maxillary artery supply is via the sphenopalatine and greater palatine branches. The greater palatine arl."ery supplies the anteroinferior part of the nasal floor and septum.
Chapter 126 Epistaxis I 1597
The sphenopalatine artery is the most important supply to the nasal cavity. It enters through the sphenopalatine foramen and immediately divides into posterior septal and posterior lateral rami. 3 The posterior lateral division gives the inferior and middle turbinate arteries. These vessels were studied in detail by Burnham in 1935 and his work remains the definitive reference on this subject. 4 Burnham described how the inferior and middle turbinate arteries run in bony tunnels within the turbinates. Shaheen postulated that these bony conduits could reduce the likelihood of the arteries being involved in epistaxis. 5 The posterior septal branch of the sphenopalatine artery runs mediaUy across the face of the sphenoid to the posterior part of the septum, then takes an undulating course anteroinferiorly in the mucoperichondrium. Its terminal branches anastomose in Little's area.
INTERNAL CAROTID ARTERY
The internal carotid contributes the anterior and posterior ethmoidal branches of the ophthalmic artery. The anterior ethmoidal artery, after arising in the orbit, runs under the superior oblique muscle to the anterior ethmoidal canal in which it traverses the ethmoid and nasal cavities. It terminates in the region of the ethmoid fovea in a meningeal branch and a larger branch to the nasal roof, olfactory cleft and superior turbinate. The posterior ethmoidal artery is smaller than the anterior ethmoidal artery and is present in only 80 percent of individuals. 6 Like the anterior vessel, this artery runs medially, but this time passes above the superior oblique muscle to enter the posterior ethmoidal foramen situated 5 mm anterior to the optic canal and 10/15 nun behind the anterior ethmoidal foramen. Within its canal, the posterior ethmoidal artery is accompanied by the sphenoethmoidal nerve and a branch of the nasociliary nerve. This vessel also divides into a terminal meningeal branch and a branch to the posterosuperior nasal cavity, olfactory sulcus and sphenoethmoidal recess. [**]
circulations is erroneous as the arterioarteriolar anastomotic network allows varying directions of flow to OCcur. Compensatory anastomotic flow via the fadal arteries is thought to explain rebleeding which may Occur following ligation or embolization.7 [**1
Venous drainage The veins follow the arteries within the mucosa. The exception is the periarterial venous cuff surrounding the intraosseous portions of the inferior and middle turbinate arteries. The veins of the lateral wall drain through the sphenopalatine foramen into the pterygoid venous plexus to the internal jugular vein. Anteriorly, drainage is via superior labial and greater palatine veins to the facial vein and ultimately the external jugular system. Of particular note clinically is the retrocolumellar vein running 2 mm behind and parallel to the columeJla. This vein is in a particularly superficial area and is a common cause of venous epistaxis in children.
Key clinical areas WOODRUFF'S PLEXUS
The role of Woodruff's plexus in epistaxis is frequently discussed. B• 9 In 1949, Woodruff1o described a plexus of prominent blood vessels lying just inferior to the posterior end of the inferior turbinate (Figure 126.1). He commented on how this plexus was a frequent site of adult epistaxis and described 14 cases of bleeding from
INTERNAL AND EXTERNAL CAROTID TERRITORIES
The nasal cavity is the location of the principal internal-external carotid artery anastomoses in the head and neck. There has been debate over the relative importance of each supply to the nasal cavity. Shaheen showed that the area supplied by the ethmoidal arteries was much smaller than had previously been thought. His findings were supported by observing the sphenopalatine branches to the superior meatus and superior turbinate, the comparatively narrow calibre of the ethmoidal arteries and the fact that the larger of the two ethmoidal arteries, the anterior, is absent in as many as 14 percent of cadaver dissections. 5 The view that the middle turbinate marks the watershed between internal and external carotid
Figure 126.1
Endoscopic photograph of woodruff's plexus
(right) : IT, inferior turbinate; NP, nasopharynx; WP, Woodruff's plexus.
-1~---'-.-
1598 I PART
13 THE NOSE AND PARANASAL SINUSES
this area. Many authors describe Woodruff's plexus as a frequent source of so-called 'posterior' epistaxis despite the absence of any numerical evidence to support this. In s 1967, Shaheen attempted to study and define Woodruff's plexus but was W1able to identify the plexus in nasal ethmoidal blocks. Recent study with endoscopic photography and anatomical microdissection confirms the existence of the plexus and confirms that it is a venous plexus. I I [**]
LATERAL WALL OR SEPTAL BLEEDING?
There is general acceptance that most epistaxis occurs from Little>s area, but there is debate on the relative importance of various other sites. Some suggest that Woodruff's plexus is important and others nominate the septum or other regions of the lateral wall as prime sites (Figure 126.2). Numerous studies using various methods and examination techniques have produced diverse findings. 9 , 12, 13, 14, 15 For example, Shaheen 1s failed to find any lateral wall bleeding, while Wurman 9 did not report any septal bleeding. Sixty percent of bleeding points identified by EI-Simil/ 6 were septal, whereas 62 percent of those found by Rosnagle et al.17 were on the lateral wall. In a study of 50 patients with adult primary posterior epistaxis, McGarry 18 identified the bleeding point in 94 percent (6 percent not located despite endoscopy), 70 percent bled from the septum and 24 percent from the lateral wall. There was no side predilection (50 percent left nostril and 48 percent right> 2 percent bilateral). These findings support the observation that posterior, like anterior, epistaxis is predominantly septal in origin. [**]
ANTERIOR ETHMOIDAL ARTERY IN ENDOSCOPIC SINUS SURGERY
Detailed knowledge of this vessel is essential for surgeons carrying out endoscopic sinus surgery and for those planning its ligation for epistaxis. The artery is frequently encountered in a mesentery just below the skull base between the ethmoid fovea and the lamina papyracea. Inadvertent damage to the mesentery can lead to troublesome bleeding from the artery. Transection of the vessel during sinus surgery can result in retraction of the bleeding end into the orbit with subsequent pressure haematoma and risk of visual loss. The vessel can be ligated as a treatment for epistaxis via an external (medial canthal) approach or, in the rare occasion where the bony anatomy permits, endoscopically (transethmoidal).19
SURGICAL ANATOMY OF THE SPHENOPALATINE FORAMEN
The sphenopalatine foramen is the portal for the major arterial supply of the nasal cavi.ty. Lateral to the foramen lies the pterygopalatine space. The foramen is formed by a
Figure 126.2 Diagram of sites of bleeding in posterior epistaxis. (a) Lateral nasal wall; (b) septum. Numbers are percentages (6 percent not located).
U-shaped notch in the vertical portion of the palatine bone which is closed posterosuperiorly by the sphenoid bone. The foramen transmits the sphenopalatine artery, vein and the nasal palatine nerve (maxillary division of tq.e trigeminal nerve). Clinically, this foramen is the key to the procedure of endonasalligation of the sphenopalatine artery (ESPAL). SurgicaJ localization of the foramen can be difficult. Bolger et al. 20 studied a small bony projection which lies anterior to the foramen in 96 percent of cases. This landmark is called the 'crista ethmoidalis' and its recognition. during surgery may help in finding the foramen. (**J
--'
.~
Chapter 126 Epistaxis
SURGICAL ANATOIVIY OF THE BLOOD SUPPLY OF THE INFERIOR TURBINATE
Severe secondary epistaxis is a serious complication of inferior turbinectomy. Understanding the vascular supply of the inferior turbinate may help in both the avoidance and management of this complication (Figure 126.3). At its origin, the artery runs anteroinferiorly in the submucosa where it is vulnerable to damage during radical turbinectomy. On reaching the inferior turbinate, it divides into three parallel branches which run in bony tunnels within the substance of the turbinate. These tunnels with their periarterial cuff of fibrous tissue and venous elements may prevent the artery constricting following turbinectomy and may predispose to postoperative haemorrhage. 4 , 14 Attempts to control haemorrhage following turbinectomy should be directed towards the posterosuperior aspect of the inferior turbinate where pressure bipolar to the submucosal segment of the artery should prove effective. [**] [Grade D]
I 1599
variation with age is sufficiently pronounced to classify epistaxis as childhood (less than 16 years) or adult (greater than 16 years).
Primary or secondary Between 70 and 80 percent of all cases of epistaxis are idiopathic, spontaneous bleeds without any proven . . preClpltant or causaI Clactor. 22 This type of bleeding can be classified as primary epistaxis. As our understanding of the aetiology advances, the number of cases of true primary epistaxis will decrease but, at present, this definition encompasses most cases. A small proportion are due to a clear and definite cause such as trauma, surgery or anticoagulant overdose and can be classified as secondary epistaxis. The distinction between primary and secondary epistaxis is more than academic as the management of each type is quite different, for example, techniques used to control primary epistaxis are unlikely to be successful for s.econdaryepistaxis due to coagulopathy.
CLASSIFICATION OF EPISTAXIS Traditionally, epistaxis has been classified on the basis of presumed aetiology and publications include long lists of factors thought to cause the condition. 21 As most cases are idiopathic and since case control evidence does not exist for most of the putative aetiological factors, a causation-based classification is inappropriate. A clinical classification based on the patterns of presentation of epistaxis is more useful (Table 126.1).
Anterior and posterior epistaxis The terms anterior and posterior epistaxis are frequently used, but their definitions are imprecise and inconsistent. Pearson attempted to standardize the term posterior epistaxis as a bleeding point which could not be located Table 126.1
Structured clinical classification.
Classifi<;ati'on.
Adult or childhood epistaxis There is a pronounced bimodal distribution in the age of onset of epistaxis. The condition is common in childhood, becomes less common in early adult life and then peaks in the sixth decade. Thus, while it can occur at any time in life, this
Primary
No proven causal factor
Secondary
Proven causal factor
Childhood
<16 years
Adult
>
Anterior
Bleeding point anterior to piriform aperture
Posterior
Bleeding point posterior to piriform aperture
External carotid artery
16 years
Internal carotid artery
~
L
~ Superior labial artery
Posterior ethmoidal artery
Facial artery ~ Lateral nasal artery
Ascending palatine artery Maxillary artery ~ Greater palatine artery
~ Sphenopalatine artery - - Lateral nasal branch ------ Posterior septal branch
Figure 126.3
Summary of vascular supply of nasal cavity.
Anterior ethmoidal artery
1600 I PART
13 THE NOSE AI\lD PARAI\lASAL SINUSES
despite examination with a headlight, vasoconstrictors and suction. 8 While this is a clinically useful definition, modern techniques of examination and endoscopy, are likely to see true posterior bleeds moving further and further back! Attempts to define anterior epistaxis as bleeding from Little's area are problematic, due to the lack of a precise definition of Little's area. To standardize the use of the term 'posterior epistaxis' and 'anterior epistaxis', the author proposes that their use be restricted to the following. • Anterior epistaxis: Bleeding from a source anterior to the plane of the piriform aperture. This includes bleeding from the anterior septum and rare bleeds from the vestibular skin and mucocutaneous junction. • Posterior epistaxis: Bleeding from a vessel situated posterior to the piriform aperture. This allows further subdivision into lateral wall, septal and nasal floor bleeding. Further descriptive classification based on the severity and frequency of the bleeding can also be used, e.g. whether recurrent (usually minor and nonlife-threatening) or acute, severe. It is of interest that for adults at least, the severity of an epistaxis is inversely proportionate to its frequency. That is, recurrent primary epistaxis tends to be minor, nonlife-threatening and often easily managed, whereas acute, severe epistaxis is usually a one-time event resulting in hospitalization and carrying a high morbidity. For the remainder of this chapter, the clinical syndromes of adult epistaxis are discussed. Childhood epistaxis is discussed in Chapter 81, Epistaxis in children.
ADULT PRIMARY EPISTAXIS Demography Adult primary epistaxis is the variant which challenges otolaryngologists the most. The condition can occur at any age, but is mainly a disease of the elderly. Between 7 and 14 percent of adults have epistaxis at some time or other, but only 6 percent of cases are seen by otorhinolaryngologists. 23 ,24 The peak presentation is the sixth decade and most large case series reveal a slight male predominance (55 male, 45 female). 14,25 Most cases are minor, selflimiting or easily managed anterior bleeds, but nevertheless a significant number require admission to hospital. The annual rate of admission to otolaryngology units in the north of the UK with adult epistaxis is 30 per 100,000 26 per annum. Fewer than 10 percent of hospitalized patients require a general anaesthetic procedure to secure 27 haemostasis. It is not surprising that such a common haemorrhagic condition of elderly patients is associated with significant morbidity and mortality. After head and neck cancer, epistaxis stands out as a prominent cause of mortality in ear, nose and throat (EJ\TT) patients. [**]
Aetiology By definition, the aetiology of primary epistaxis is unknown, but there are clear suggestions that systemic factors may be important (Table 126.2).
CHRONOBIOLOGY
The frequency of admission is greatest in the autumn and winter months. 28 This seasonal variation correlates with fluctuations in enviromental temperature and humidity.29 A chronobiological rhythm is also observed at the circadian level where onset of bleeding and hospital admission show a biphasic pattern with peaks in the morning and late evening. 30 , 31 There are strong parallels between the circadian rythms of primary epistaxis and those observed in subarachnoid haemorrhage. [***] NONSTEROIDAL ANTIINFLAMMATORY DRUGS
Adult pattern epistaxis is associated with the use of nonsteroidal antiinflammatory drugs (NSAID). Patients are more likely than controls to consume NSAIDs. The NSAID used include prescribed and self-administered compounds, especially aspirin. The action of NSAIDs is mediated via an antiplatelet aggregation effect due to altered platelet membrane physiology.32, 33, 34 [***]
ALCOHOL
Similar aetiological associations to those of NSAIDs have been found with alcohol. Epistaxis patients are more likely to consume alcohol than matched control patients and are more likely to have consumed alcohol within 24 hours of hospital admission than other emergency admissions. The use of alcohol by epistaxis patients is associated with a prolongation of the bleeding time despite normal platelet counts and coagulation factor activity. Once again, the effects of NSAIDs and alcohol mirror those reported in subarachnoid haemorrhage. 35, 36 [***]
HYPERTENSION
This has long been considered a cause of epistaxis. However, a number of large studies have failed to show a Table 126.2
Summary of aetiology evidence: adult primary
eeistaxis. .
.Factor
0"
•~ :
:
- -_~
•
• 0'"
Weather NSAID Alcohol Hypertension, Septa I deviation
Proven association [***] Proven association [***] Proven association [***] No association [***] No association [**]
Chapter 126 Epistaxis' 1601
causal relationship between hypertension and epistaxis. 37 Attempts to correlate epistaxis with secondary effects of hypertension or with the severity of hypertension have proved inconclusive. 38 Even if not causal, elevated blood pressure is observed in almost all epistaxis admissions. This apparent hypertension in acute admissions may be a result of anxiety associated with hospital admission and the invasive techniques used to control the bleeding. [H*]
!
SEPTAL ABNORMALITIES
Septal abnormalities are common and, depending on the definition used, between 1 and 80 percent of the population have a significant deviation. 39 Given such a high prevalence, the perceived association between epistaxis and septal abnormalities could be coincidental. One study found an association between septal deviation and recurrent epistaxis in young subjects. 4o There is no clear case-control evidence of an association between septal abnormalities and adult epistaxis. [H]
Management Effective management of adult epistaxis follows an incremental sequence of interventions (Figure 126.4). The theoretical ideal requires identification of the bleeding point and direct control of the bleeding. First, the patient must be resuscitated, bleeding slowed, the nasal cavity examined and a treatment plan established. Figure 126.4
Management strategy for adult primary
epistaxis.
RESUSClTATION
Given the high prevalence of coexistent cardiovascular disease, prompt and effective resuscitation is required. Sixty-four percent of cases are referred from an accident and emergency department and thus many will already have had some form of therapy.27 First aid by pinching the ala nasi is supported by the frequency with which the anterior part of 'the septum is the source of bleeding. Otorhinolaryngologists should ensure medical students, nurses and other team members are fully aware of the precise technique for compression of the nostrils. In one study of accident and emergency staff, only 43 percent of trained medical and nursing staff could correctly demonstrate the Hippocratic technique. 41 History and examination will help in assessing the amount of blood lost. In all but the most minor of bleeds, intravenous access is established and baseline blood estimations are taken. A detailed history should be taken, looking for predisposing factors. Routine coagulation studies in the absence of a positive history are not indicated. 14, 42 [H]
involved should wear protective visors and clothing as blood aerosol contamination is common, especially when inserting nasal packing.43 Basic equipment includes a couch or reclining chair, headlight, suction, vasoconstrictor solutions (lignocaine and pseudoephedrine solution has now widely superseded cocaine solutions) and a selection of packs, tampons and cautery apparatus. More specialized centres should also have access to rod lens nasal endoscopy equipment and bipolar electro diathermy. [H]
DIRECT OR INDIRECT THERAPIES
Treatment may be divided into direct (bleeding pointspecific therapies) or indirect treatments which do not require identification of the bleeding point. Direct lrealments are logically and theoretically ~uperior and, therefore) a committed search for the bleeding vessel should be undertaken. 8 Direct management
ASSESSMENT
The patient should be assessed in a semi-recumbent position and nursing assistance is mandatory. Everyone
At present only one in five cases admitted to otolaryngology units in the UK are managed by direct control of the bleeding point?7 The reluctance to use direct approaches may be due to a perceived difficulty in
1602 I PART 13 THE NOSE AND PARANASAL SINUSES locating bleeding points, but probably also reflects the fact that over 70 percent of cases are managed by the most junior members of the specialty.27 Anterior epistaxis is usually very straightforward to identify and treat and at present over 90 percent of cases are controlled with silver nitrate cautery. The use of packing for primary anterior epistaxis is unwarranted and should be discouraged. Posterior epistaxis can occur from the lateral wall, floor or septum. As previously discussed, there is evidence to support the septum as the principal locus. Systematic examination with a headlight will identify most bleeding points. Once identified, bleeding points can be directly controlled with bipolar diathermy, chemical cautery (difficult in posterior bleeds), electrocautery or direct pressure from miniature targeted packs.44 [**] [Grade C] Endoscopic control
Failure to locate the bleeding point on initial examination is an indication for examination with a rod lens endoscope (Figure 126.5). Endoscopy indentifies the source of posterior epistaxis in over 80 percent of cases. 9 , 13,26, 44 Endoscopy enables targetted haemostasis of the bleeding vessel using insulated hot wire cautery or modern single fibre bipolar electrodes. 26 Success rates for immediate control by endoscopic guidance are consistently reported in the 90 percent range. 26 Monopolar diathermy should not be used in the nasal cavity as there have been reports of blindness due to current propogation. 45 Adoption of direct (including endoscopic) management strategies has been shown to facilitate outpatient management and to significantly reduce inpatient stay?6 [***/**] [Grade B] Indirect therapies
Failure to find (often the result of failure to look for) the bleeding point is an indication for use of one of numerous traditionally favoured indirect strategies.
Nasal packing
Packing can be anteriorly or posteriorly placed. Anterior packing has been the mainstay of treatment for centuries. Skills required for accurate packing are difficult to acquire and with modern techniques of nasal surgery, less frequently encountered in a surgeon's training. Ribbon gauze impregnated with petroleum jelly or bismuth iodoform paraffin paste (BIPP) is inserted the entire length of the nasal cavity in an attempt to tamponade the bleeding. Once inserted, the packs are left in situ for between 24 and 72 hours. 46 Continued or rebleeding with packs in situ is observed in up to 40 percent of cases. 47 Complications of packing include sinusitis, septal perforation, alar necrosis, hypoxia and myocardial infarction. Packing is usually considered an indication for antibiotic cover, but the evidence base for this is lacking. Modern variations on anterior packing include special tampons (merocel and Kaltostat) and balloon catheters (Brighton or Epistat). Balloons and tampons are favoured by nonspecialists as first-line therapy but are associated with similar complications and rebleed rates to packing. If overinflated, balloons will prolapse anteriorly and posteriorly with the risk of hypoxia and alar necrosis. 48 There is no evidence of greater efficacy for packs, balloons or tampons. Persistent bleeding or rebleeding is an indication for further examination of the nasal cavity and a renewed search for the bleeding point. There is no clear, universally agreed definition of failed packing, but patients who continue to bleed should proceed to surgical management sooner rather than later. [**/*] [Grade D] Hot water irrigation
Irrigation of the nasal cavity with water at 50°C has been proposed as an alternative to packing. Stangerup et aI. report similar levels of success comparing the hot water technique to anterior packing and balloon tamponade. 49 Up to a third of patients find the technique difficult to tolerate and so use of specialized irrigation catheters is recommended. The exact mechanism of action of this treatment is unclear but may, paradoxically, involve reflex vasodilatation and reduction in nasal lumen dimensions. so [***] [Grade D]
Systemic medical therapy
Figure 126.5 Modern single fibre bipolar diathermy probe for endoscopic use.
Tranexamic acid and epsilon aminocaproic acid are systemic Inhibitors of fibrinolysis. Tranexamic acid has been shown to reduce the severity and risk of rebleeding in epistaxis at a dose of 1.5 g three times a day. These drugs do not increase fibrin deposition and so do not increase the risk of thrombosis. Preexisting thromboembolic disease is a contraindication. At present antifibrinolytics are best reserved as adjuvant therapy m recurrent or refractory cases,SI [***] [Grade B]
Chapter 126 Epistaxis I 1603
SURGICAL MANAGEMENT
If the techniques described above fail, surgical intervention is required. Endoscopic diathermy of the bleeding point under anaesthetic may control the bleeding but if the vessel still cannot be controlled (or even located) indirect surgical therapy is indicated. Surgical management for continued epistaxis consists of: • • • •
posterior packing; ligation techniques; septal surgery techniques; embolization techniques.
Posterior nasal packs Posterior packing can be carried out under local anaesthetic. but general anaesthesia is preferrable. Nasopharyngeal tamponade is achieved using special gauze packs inserted transorally and positioned by means of tapes passed from the posterior choana to the anterior nares bilaterally. These posterior 'Bellocq' packs are secured against anterior gauze packing. The securing tapes are tied over padding positioned to protect the columella from pressure necrosis. An easier and perhaps kinder alternative is to insert a Foley urethral catheter (size 12 or 14) along the floor of the nasal cavity until the nasopharynx is reached. The Foley catheter is inflated with up to 15 mL of water, pulled forward to engage in the posterior choana and anterior packing is then inserted. The Foley catheter needs to be secured anteriorly, taking care not to cause pressure over the columella. Posterior packing causes considerable pain and may cause hypoxia secondary to soft palate oedema. Sinusitis and middle ear effusions are common. More serious complications include necrosis of the septum and columella. Antibiotics and opiate analgesia are necessary. Posterior packs should be left in position for a minimum of 48 hours. [*] [Grade D]
increase in popularity of this procedure and it has now largely replaced transantral ligation as the procedure of choice. The operation can be performed with an operating microscope or more commonly using a rod lens endoscopic technique. 52 Under general or local anaesthetic. an incision is made approximately 8 mm anterior to and under cover of the posterior end of the middle turbinate. The incision is carried down to the bone and a mucosal flap is elevated posteriorly until the fibroneurovascular sleeve arising from the sphenopalatine foramen is identified. The foramen can be difficult to identify. but its location is signalled by the crista ethmoidalis. 20 Once the main vessel is identified. it can be ligated using haemostatic clips and divided or coagulated using bipolar diathermy (Figure 126.6).53 In some series, success rates for this procedure have reached almost 100 percent. 54 Complications including rebleeding (anastomoses), infection and nasal adhesions are generally less common than with other procedures. [**] Internal maxiJJary artery ligation
Internal maxillary artery ligation (I MAL) was more frequently used prior to the development of ESPAL procedures. The artery is exposed transantrally via anterior (sublabial) or combined anterior and medial (endoscopic) techniques. In the traditional sublabial approach, an antrostomy is formed taking care to preserve the infraorbital nerve. The mucosa of the posterior wall of the antrum is then elevated and a window is made through into the pterygopalatine fossa. The branches of the internal maxillary artery are identified pulsating within the fat of the fossa and are carefully dissected out prior to clipping with haemostatic
Ligation techniques Ligation is reserved for intractable bleeding where the source cannot be located or controlled by the techniques described above. Knowledge of the blood supply of the nasal cavity and the likely sources of epistaxis will inform the choice of ligation technique. Ligation should be performed as close as possible to the likely bleeding point; thus, the hierarchy of ligation is: • • • •
sphenopalatine artery; internal maxillary artery; external carotid artery; anterior/posterior ethmoidal artery.
Endonasal sphenopalatine artery ligation
Endonasal sphenopalatine artery ligation conforms to the ideal of controlling the bleed as close as possible to its nasal source. Modern endoscopic techniques have seen an
7
Figure 126.6 Haemostatic clips applied to sphenopalatine artery during procedure of ESPAl.
1604 I PART 13 THE NOSE AND PARAI\JASAL SINUSES clips. The proximal internal maxillary artery, descending palatine and sphenopalatine branches are all clipped and ideally divided. An endoscopic variation on this technique uses a middle meatus antrostomy, as an instrument port with a 4-mm endoscope is inserted through a small canine fossa antrostomy. 55 Transantral ligation controls haemorrhage in 89 percent of cases and is comparable to embolization in both cost and efficacy. 56 Complications include sinusitis, damage to the infraorbital nerve, oro antral fistula, dental damage and anaesthesia and rarely ophthalmoplegia and blindness. [**] External carotid artery ligation
External carotid artery ligation (ECAL) represents a step further away from the nasal source of bleeding. Nevertheless, the relative technical ease of this procedure justifies its use in extreme cases. This procedure can be carried out under local or general anaesthetic using either a skin crease incision or a longitudinal incision parallel with the anterior border of the sternomastoid. The carotid bifurcation is identified and the external carotid confirmed, double-checked for arterial branches and then ligated in continuity. Some authors advocate anterior and posterior ethmoidal artery ligation as an adjuvant to this procedure. In one study, external carotid artery ligation secured haemostasis in 14 out of 15 patients. 57 Complications include wound infection, haematoma and neurovascular damage. [**] Anterior/posterior ethmoidal artery ligation
Given the minimal contribution of these arteries to the nasal blood supply, anterior/posterior ethmoidal artery ligation (EAL) is best reserved as an adjuvant to one of the procedures described above or in cases of confirmed ethmoidal bleeding (e.g. ethmoidal fracture, iatrogenic tear). The arteries are approached by a medial canthal incision which is carried down to the bone of the anterior lacrimal crest. Periosteal elevators are then used to elevate and laterally retract the bulbar fascia. The anterior ethmoidal artery is seen as a fibroneurovascular mesentry running from the bulbar fascia into the anterior ethmoidal foramen. The vessel is clipped and divided and dissection is continued to identify the posterior artery which is located approximately 12 mm behind. Endoscopic transethmoidal ligation of the anterior ethmoidal artery has been described, but is unlikely to be technically possible in most cases. 19 The popularity of ligation of these vessels possibly reflects the technical ease of the open procedure rather than any logical reason for ligating vessels with such a small contribution to the nasal blood supply. Septal surgery
When epistaxis originates behind a prominent septal deviation or vomeropalatine spur, septoplasty or submucosal resection (SMR) may be required to access the bleeding point. Some authors have advocated septal surgery as a primary treatment for failed packing. The
rationale is that by elevating the mucoperichondrial flap for septoplasty or SMR, the blood supply to the septum is interrupted and haemostasis secured. Cumberworth et al. 58 showed a strategy involving SMR and repacking to be more effective and economic than ligation in patients who had failed with packing. [***] Embolization
Embolization under angiographic guidance has been shown to control severe epistaxis in between 82 and 97 percent of cases. 56, 59, 60 Under local anaesthetic, transfemoral Seldinger angiography is used to identify the bleeding points and display the nasal circulation. It is essential to exclude arteriovenous malformations, aneursyms and fistulae prior to embolization. Once the bleeding vessel is identified, a fine catheter is passed into the internal maxillary circulation and particles (polyvinyl alcohol, tungsten or steel microcoils) are used to embolize the vessels. The ipsilateral facial artery is also embolized in order to prevent recirculation. Complications include skin necrosis, paraesthesia, cerebrovascular accident and groin haematomas. Embolization is of similar efficacy to ligation techniques, but complications may occur more frequently than following ESPAL. The choice between embolization and ligation is likely to depend on local expertise, availability and experience. [**] [Grade D]
Adult recurrent epistaxis Recurrent bleeding is more commonly seen in children. When recurrent bleeds ocurr in adults, secondary epistaxis is most likely. Bleeding is usually minor and troublesome, rather than life threatening, and it is uncommon to see bleeding by the time the patient presents. A full and detailed history and examination should identify factors such as aspirin use, liver disease or bleeding from the margins of a septal perforation. Rarely, nasal tumours present with recurrent blood-stained discharge which should be distinguished from epistaxis per se. Patients using topical nasal medications (particularly steroid sprays) frequently report minor recurrent bleeds. If a bleeding point can be identified, cautery is used but often no single vessel can be identified and an area of vestibulitis is found. Evidence for the efficacy of topical antiseptic creams is available from paediatric studies and it is likely (but unproven in adults) that chlorhexidine and neomycin creams may reduce the frequency of bleeding. 6l An area of debate is what to do when aspirin, being used for cardiovascular prophylaxis, is responsible for recurrent bleeds. If there is a history of cardiovascular disease or vascular graft surgery then aspirin should not be discontinued, otherwise temporary cessation of aspirin may be required to allow the recurrent bleeding to settle. [*]
Chapter 126 Epistaxis
SECONDARY EPISTAXIS Epistaxis is commonly observed in patients with coagulopathy secondary to liver disease, leukemia or myelosuppression. In such cases, treatment of the epistaxis demands close liaison with haematologists and physicians. The following causes of secondary epistaxis deserve special mention.
Trauma Post -traumatic nasal haemorrhage does not conform to the normal pattern of epistaxis and its origin and severity is almost infinitely variable. Persistent bleeding can occur from the ethmoidal arteries following frontoethmoidal fracture. In this case, the vessels may be lacerated, incompletely divided or even held open by fractures through their bony mesentries. Severe haemorrhage refractory to packing should be managed by open approach ligation. Catastrophic bleeding has been reported after head injuries due to delayed rupture of an internal carotid artery pseudo aneurysm. Thus persistent or unexpectedly severe bleeding even some time after a head injury should be seen as an indication for angiography.62 [*J
Post-su rgery Bleeding can ocurr after almost any nasal surgery and is seldom difficult to manage. An exception is the severe haemorrhage which ocurrs following between 3 and 9 percent of inferior turbinectomies. 63 As previously discussed, bipolar diathermy to the main branch of the inferior turbinate artery will usualy secure haemostasis. Anterior subtotal turbinectomy may carry a reduced risk of post -operative bleeding. 63 Iatrogenic damage to the anterior ethmoidal artery during endoscopic sinus surgery should be managed by bipolar diathermy of the vessel. Retraction of the vessel into the orbit can give rise to a tension haematoma of the orbit and is a surgical emergency (see Chapter 117, Surgical management of rhinosinusitis). Massive and usually fatal epistaxis can result from damage to the internal carotid artery during posterior ethmoid or sphenoid sinus surgery. The bleeding is usually uncontrollable but packing, angiography and embolization may be tried. [HJ
I 1605
work and packing may be required. Bleeding is often from multiple sites and attempts at instrumentation lead to further mucosal damage and bleeding. After resuscitation, anterior packs should be inserted and the haematology team consulted. With large areas of bleeding or oozing, fibrin glue can be used as a haemostatic dressing. 6s When deciding to reduce, stop or even reverse warfarin, the medical history and the severity of the epistaxis must be considered. If the INR is within the therapeutic range and treatment seems to be controlling the bleeding, it may be safe to continue the warfarin. 64 [HJ [Grade DJ
Hereditary haemorrhagic telangiectasia Hereditary haemorrhagic telangiectasia (HHT), or Rendu-Osler-Weber disease, is an autosomal dominant condition affecting blood vessels in the skin, mucous membranes and viscera. Penetrance is variable, but reaches 97 percent by age 50 years and occasional atavistic cases are observed. The genetic abnormality has been located to chromosome 9q (HHTl) and chromosome 12q (HHT2). The classical features are telangiectasia, arteriovenous (AV) malformations and aneurysms. Recurrent epistaxis occurs in 93 percent of cases. 66 Management involves packing, cautery, antifibrinolytics, systemic or topical oestrogens, coagulative lasers, septal dermoplasty, ligation and embolization and, as a last resort, permanent surgical closure of the nostrils (Young's operation) (Figure 126.7). Laser photocoagulation has become a popular therapy and the NdYAG, argon and KTP532
L--_,--------'
~
Moderate
Septodermoplasty Hormones Antifibrinolytic agents Arterial ligation Selective embolization
- - - -~
Warfarin Patients on warfarin constitute between 9 and 17 percent of epistaxis admissions. 27 ,64 Bleeding may be due to overdose or loss of control, but can also occur in patients whose international normalized ratio (INR) is within the therapeutic zone. With warfarin, direct therapies seldom
Coagulating laser e.g. argon
Nasal closure
Figure 126.7 Treatment algorithm for hereditary haemorrhagic telangiectasia. Redrawn 'from Ref. 67, with permission.
1606 I
PART 13 THE NOSE AND PARANASAL SINUSES
lasers have all been used with some success. Large multi centre comparisons of these treatments have not been conducted and, due to the relative rarity of the condition, this situation is likely to persist. Best clinical practice provides an algorithm for management of this condition. 67 A recent study showed that the disability produced by Young's operation was more than offset by an improved quality of life due to reduced bleeding. [H]
Deficiencies in current knowledge and areas for future research )- Publications consistently fail to claSSify epistaXIS or define the study population. Thus studies involve heterogeneous groups of patients and different types of epistaxis making comparisons difficult. as result levelland 2 evidence is scarce.
>-
Multicentre comparisons of treatment and
management strategies do not exist. )- BasiC research is required to identify initiating and
Tumours
aetiological factors.
Nasal tumours seldom present as epistaxis in isolation, but blood-stained discharge with other nasal symptoms (unilateral obstruction, pain, swelling) should alert the clinician to the possibility of carcinoma. The risk, albeit small, of missing a tumour is another good reason for nasal endoscopy in epistaxis cases. Juvenile nasopharyngeal angiofibroma ONA) and haemangiopericytoma (HPC) are rare vascular tumours that can present with recurrent or severe epistaxis in association with nasal obstruction. Treatment of JNA and HPC is mainly surgical, but may include preoperative embolization.
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• Prirnarr and secondary ep ~staxis are different 'r ! conditions requiring different managtnnent strategies. • Direct (bleeding point-specific) therapy reduces hospital stay and morbidity. • Continued bleeding after indirect therapy . ,' ~<" should be seen as all ,in?i,~,ation to move tOl., ;to') ,,: '~,:i?' the next level of ni:~"'~~g'~fu~ntl e.g. Jigatioh' :9~'~ - \ ,
:t:i'i:kr~t:~:. cur;k~;;'I~~onof cfu,l~e in tpei ent
i
l
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\,
"\ _
,_
c
"'!
_ '. --
:.-..1: •• : ......
r
~
<
--.
/
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Caliot PH, Plessis JL, Midy D, Poirier M, Ha
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Journal Neuro-Radiology. 1979; 6'.45-53. 8.
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t.'
~~,,~;:p1i~;,e~tt~lbgi2al i~v!'S;lg~~J~?s jnd' .. . . T' -i'
S.
'i::;~"';
controlling bleeding: 6V¢i 9, O of,>t{';!: f; ' ~ ~ ~ 1:;-'" -._.-. .,' ".\.-, cases wi'lh a low co~:Plj~{lti0n \h'i,te; :,'H: ,~,;i~ ". ~,;, '., • Unusually severe or ~er.gi-~tent hleeding '-,~:"'~ . should initiate. a scar:1:~{f()r ~e~or~f}~, fa,.ctoi:$;:', -"
~.:
Burnham HH. An anatomical investigation of blood vessels of the lateral nasal wall and their relation to turbinates
KEY POINTS
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Morgagni JP. The seats and causes of diseases. Vol. 1. Alaba ma; Gryphon Editions Ltd., 1983: 312-54 (first
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Wurman LH, Sack JG, Flannery JV, Paulson JO. Selective endoscopic electrocautery for posterior epistaxis.
";' • •
Laryngoscope. 1988; 98: 1348-9. 10.
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Best clinical practice
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Chiu TW, Shaw-Dunn J, McGarry GW. Woodruff's nasonasopharyngeal plexus: how important is it in posterior
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KR. Jackson RT. Factors associated with active,
refractory epistaxis. Archives of Otolaryngology Head and
./ Second line: ind i rect therapy (anterior packing);
.I Third line: surgical therapy (ESPAL); ./ Fourth line: angiography and embolization.
Jackson
Neck Surgery. 1988; 114: 862-5 . 13.
O'Leary-Stickney K, Makielski K, Weymuller EA. Rigid endoscopy for the control of epistaxis. Archives of
Chapter 126 Epistaxis I 1607
14. 15. 16. 17.
18. 19.
20.
21.
22. 23.
24.
25. 26.
* 27. 28.
29.
30.
31.
32.
Otolaryngology Head and Neck Surgery. 1992; 118: 966-7. Padgham N. Epistaxis: anatomical and clinical correlates. Journal of Laryngology and Otology. 1990; 104: 308-11. Shaheen OH. Arterial epistaxis. Journal of Laryngology and Otology. 1975; 89: 17-34. EI-Silimy O. Endonasal endoscopy and posterior epostaxis. Rhinology. 1993; 31: 119-20. Rosnagle RS, lanagisawa E, Smith HW. Specific vessel ligation for epistaxis and survey of 60 cases. Laryngoscope. 1973; 83: 517-25. McGarry GW. Epistaxis. MD thesis, University of Glasgow, 1996. Woolford TJ, Jones NS. Endoscopic ligation of anterior ethmoidal artery in treatment of epistaxis. Journal of Laryngology and Otology. 2000; 114: 858-60. Bolger WE, Borgie RC, Melder P. The role of the crista ethmoidalis in endoscopic sphenopalatine artery ligation. American Journal of Rhinology. 1999; 13: 81-6. Maran AGD, Lund VJ. (eds). Chapter 28. In: Clinical rhinology, New York: Thieme Medical Publishers, 1990: 101-4. Stell PM. Epistaxis. Clinical Otolaryngology. 1977; 2: 263-73. Weiss NS. Relation of high blood pressure to headache, epistaxis and selected other symptoms. The New England Journal of Medicine. 1972; 287: 631-3. Lepore ML. Epistaxis. In: Baily BJ, Johnson JR, Kohut RI, Pillsbury HC, Tardy ME (eds). Head and Neck Surgery Otolaryngology, Vol. 1. Ch. 34, Philadelphia, J.B: Lippincott Company, 1993: 428-46. Juselius H. Epistaxis: a clinical study of 1,724 patients. Journal of Laryngology and Otology. 1974; 88: 317-27. O'Donnell M, Robertson G, McGarry GW. A new bipolar diathermy probe for the outpatient management of adult acute epistaxis. Clinical Otolaryngology. 1999; 24: 537-41. Kotecha B, Fowler S, Harkness P, Walmsley J, Brown P, Topham J. Management of epistaxis: A national survey. Annals of the Royal College of Surgeons of England. 1996; 78: 444-6. Provides a snapshot of current practice. Nunez DA, McClymont LG, Evans RA. Epistaxis: a study of the relationship with weather. Clinical Otolaryngology. 1990; 15: 49-51. Danielides V, Kontogiannis N, Bartzokas A, Lolis CJ, Skevas A. The influence of meteorological factors on the frequency of epistaxis. Clinical Otolaryngology. 2002; 27: 84-8. Mehanna H, Robinson K, Gatehouse S, McGarry GW. Otorhinolaryngological Research Society (ORS) - A circadian rhythm in adult idiopathic epistaxis? Clinical Otolaryngology. 1998; 23: 280. Manfredini R, Portaluppi F, Salmi R, Martini A, Gallerani M. Circadian variation in onset of epistaxis: analysis of hospital admissions. British Medical Journal. 2000; 321: 1112. Watson MG, Shenoi PM. Drug-induced epistaxis? Journal of the Royal Society of Medicine. 1990; 83: 162-4.
33.
McGarry Gw. Drug-induced epistaxis? Journal of the Royal Society of Medicine. 1990; 83: 812.
Livesey JR, Watson MG, Kelly PJ, Kesteven PJ. Do patients with epistaxis have drug-induced platelet dysfunction? Clinical Otolaryngology. 1995; 20: 407-10. 35. McGarry GW, Gatehouse S, Hinnie J. Relation between alcohol and nose bleeds. British Medical Journal. 1994; 309: 640. 36. McGarry GW, Gatehouse S, Vern ham G. Idiopathic epistaxis, haemostasis and alcohol. Clinical Otolaryngology. 1995; 20: 174-7. 37. Lubianca-Neto JF, Bredemeier M, Carvahal EF, Arruda CA, Estrella E, Pietsch A et al. A study of the association between epistaxis and the severity of hypertension. American Journal of Rhinology. 1998; 12: 269-72. 38. Lubianca-I\jeto JF, Fuchs FD, Facco SR, Gus M, Fasolo L, Mafessoni R et al. Is epistaxis evidence of end-organ damage in patients with hypertension? Laryngoscope. 1999; 109: 1111 -5. 39. Roblin DG, Eccles R. Review: What, if any, is the value of septal surgery? Clinical Otolaryngology. 2002; 27: 77. 40. O'Reilly BJ, Simpson DC, Dharmeratnam R. Recurrent epistaxis and nasal septal deviation in young adults. Clinical Otolaryngology. 1996; 21: 12-4. 41. McGarry GW, Moulton C. The first aid management of epistaxis by accident and emergency department staff. Archives of Emergency Medicine. 1993; 10: 298-300. 42. Smith 1M, Ludlam CA, Murray JAM. Haematological indices in elderly patients with epistaxis. Health Bulletin. 1988; 46/5: 277-81. 43. Carney AS, Weir J, Baldwin DL. Contamination with blood during management of epistaxis. British Medical Journal. 1995; 311: 1064. 44. McGarry Gw. Nasal endoscope in posterior epistaxis: A preliminary evaluation. Journal of Laryngology and Otology. 1991; 105: 428-31. 45. Vandan Abeele D, Clemens A, Tassignon MJ, van der Heyning PH. Blindness due to electrocoagulation following functional endoscopic sinus surgery. Journal of Laryngology and Otology. 1996; 110: 261-4. 46. Tan LKS, Calhoun KH. Epistaxis. Medical Clinics of North America. 1999; 83: 43-56. 47.: Stangerup SE, Dommerby H, Lau T. Hot-water irrigation as a treatment of posterior epistaxis? Rhinology. 1996; 34: 18-20.
34.
48.
49.
50.
51.
McGarry GW, Aitken D. Intranasal balloon catheters: How do they work? Clinical Otolaryngology. 1991; 16: 388-92. Stangerup SE, Dommerby H, Siim C, Kemp L, Stage J. New modification of hot-water irrigation in the treatment of posterior epistaxis. Archives of Otolaryngology-Head and Neck Surgery. 1999; 125: 686-90. Stangerup SE, Thomsen HK. Histological changes in the nasal mucosa after hot-water irrigation. An animal experimental study. Rhinology. 1996; 34: 14-7. Petruson B. A double-blind study to evaluate the effect of epistaxis with oral administration of the antifibrinolytic
1608 I PART
13 THE NOSE A[\ID PARANASAL SINUSES
drug tranexamic acid (cyclokapron). Acta OtoLaryngologica Suppl. 1974; 317: 57-61. 52. Sharp HR, Rowe-Jones JM, Biring GS, MacKay IS. Endoscopic ligation or diathermy of the sphenopalatine artery in persistent epistaxis. Journal of Laryngology and Otology. 1997; 111: 1047-50. 53. Loughran S, Hilmi 0, McGarry GW. Endoscopic sphenopalatine artery ligation-when, why and how to do it. An on-line video tutorial. Clinical Otolaryngology. 2005; 30: 539-43. 54. O'Flynn PE, Shadaba A. Management of posterior epistaxis by endoscopic clipping of the sphenopalatine artery. Clinical Otolaryngology. 2000; 25: 374-7. 55. White PS. Endoscopic ligation of the sphenopalatine artery (ELSA): A preliminary description. Journal of Laryngology and Otology. 1996; 110: 27-30. 56. Strong EB, Bell DA, Johnson LP, Jacobs JM. Intractable epistaxis: Transantral ligation vs. embolization: Efficacy review and cost analysis. Archives Otolaryngology Head Et Neck Surgery. 1995; 113: 674-8. 57. Waldron J, Stafford N. Ligation of the external carotid artery for severe epistaxis. Journal of Otolaryngology. 1992; 21: 249-51. 58. Cumberworth VL, Narula AA, Bradley PJ. Prospective study of two management strategies for epistaxis. Journal of the Royal College of Surgeons of Edinburgh. 1991; 36: 259-60. 59. Scaramuzzi N, Walsh RM, Brennan P, Walsh M. Treatment of intractable epistaxis using arterial embolization. Clinical Otolaryngology. 2001; 26: 307-9.
60.
61. 62.
63.
64.
65.
* 66. 67.
Moreau S, De Rugy MG, Babin E, Courtheoux P, Valdazo A. Supraselective embolization in intractable epistaxis: Review of 45 Cases. Laryngoscope. 1998; 108: 887-8. McGarry G. Nosebleeds in children. Clinical Evidence. 2004; 518-21. Crow WN, Scott BA, Guinto Jr. FC, Chaljub G, Wright G, Rabassa AE et 01. Massive epistaxis due to pseudoaneurysm. Treated with detachable balloons. Archives Otolaryngology Head and Neck Surgery. 1992; 118: 321-4. Garth RJN, Cox HJ, Thomas MR. Haemorrhage as a complication of inferior turbinectomy: A comparison of anterior and radical trimming. Clinical Otolaryngology. 1995; 20: 236-8. Srinivasan V, Patel H, John DG, Worsley A. Warfarin and epistaxis: Should warfarin always be discontinued? Clinical Otolaryngology. 1997; 22: 542-4. Walshe P, Harkin C, Murphy S, Shah C, Curran A, McShane D. Rapid Communication. The use of fibrin glue in refractory coagulopathic epistaxis. Clinical Otolaryngology. 2001; 26: 284-5. Pau H, Carney AS, Murty GE. Review. Hereditary haemorrhagic telangiectasia (Osler-Weber-Rendu syndrome): Otorhinolaryngological manifestations. Clinical Otolaryngology. 2001; 26: 93-8. Good review of HHT. Lund VJ, Howard DJ. A treatment algorithm for the management of epistaxis in hereditary hemorrhagic telangiectasia. American Journal of Rhinology. 1999; 13: 319-22.
127 Nasa I fractu res
BRENT A McMONAGLE AND MICHAEL GLEESON
Introduction
1609
Com piications
1614
Epidemiology and aetiology
1609
Key points
1615
Classification and pathophysiology
1609
Best clinical practice
1616
Clinical presentation
1611
Deficiencies in current knowledge and areas for future
Investigations
1612
Treatment
1612
1616
research
1616
References
T he data in this chapter are supported by a PubMed search using the key words nasal fracture, focussing on diagnosis and management.
surprising that young men are twice as likely to sustain
INTRODUCTION
a fractured nose as women. Subsequent refracture rates of Treatment of nasal fractures was first recorded 5000 years
5 percent have been reported.4 The peak incidence is in
ago during the early Pharoruc period in Ancient Egypt. The
the IS-3D-year age group when assaults, contact sports
Edwin Smith papyrus describes repositioning of deviated
and adventurous leisure activities are more common.s In
nasal bones with the fingers or elevators, the insertion of
childhood,
splints and the application of external dressings.l Just as
fracture their noses as well and these are often of a
accident-prone
toddlers
not
infrequently
then, nasal fractures are still very conunon.2 Isolated
greenstick nature. Compound and comminuted fractures
fractures of the nasal pyramid account for about 40 percent
are more common in the elderly who are prone to falls.
of all facial fractures. Futhermore, fractures of the nasal bones are often sustained along with other fractures of the facial skeleton.
Delays
in management
can result
in
CLASSIFICATION AND PATHOPHYSIOLOGY
significant cosmetic and functional deformity that is often a cause for subsequent medicolegal action. The manage
Nasal fractures have been classified in a number of ways,
ment of fractures of the nose is an important part of
for example, by the direction of impact and degree of
everyday ear, nose and throat
force applied, the extent and direction of deformity and
(ENT) practice.
the pattern of the fracture.
Nature of inj ury
EPIDEMIOLOGY AND AETIOLOGY Relatively little force is required to fracture the nasal
Most fractures result from laterally applied forces, over 66
bones,
percent in a series reported by lllum et
as little as
2S-75
Ib/in2•3
It is
perhaps
not
al.6 By contrast,
1610 I
PART 13 THE NOSE AND PARANASAL SINUSES
fractures following frontal injuries accounted for 13 6 percent in this series. Greater force is required to fracture the nose with a blow directed from the front as the nasal cartilages behave like shock absorbers.
Frontal bone
}
ThiCk part -+-- Force
from
this direction
Maxilla
Thin part
Extent of deformity
Line of fracture
A five-point grading system has been developed for the extent of lateral deviation of the nasal pyramid: • •
•
•
•
grade 0: bones perfectly straight; grade 1: bones deviated less than half of the width of the bridge of the nose; grade 2: bones deviated half to one full width of the bridge of the nose; grade 3: bones deviated greater than one full width of the bridge of the nose; grade 4: bones almost touching the cheek.
Pattern of fracture
0es 'Oo
�0-s?J.�
Perpendicular plate of ethmoid Sphenoid sinus
Cartilaginous septum
Vomer
Maxillary crest
Figure 127.1
The distal part of a nasal bone is half the
thickness of the proximal part. When it fractures, the nose is apparently deviated but the impression of deviation is optical. It
Nasal fractures can also be subdivided into three broad categories that characterize the patterns of damage sustained with increasing force. This classification has some practical utility as each category of fracture requires a different method of treatment.
is important to recognize this injury. The edges of the stable segment can often be palpated. Figure courtesy of AGD Maran.
'greenstick' variety and significant nasal deformity may only develop at puberty when nasal growth becomes accentuated.7
CLASS 1 FRACTURES
Class 1 fractures are the result of low-moderate degrees of force and hence the extent of deformity is usually not marked. The simplest form of a class 1 fracture is the depressed nasal bone. The fractured segment usually remains in position due to its inferior attachment to the upper lateral cartilage which provides an element of recoil. The nasal septum is generally not involved. In the more severe variant, both nasal bones and the septum are fractured. The fracture line runs parallel to the nasomaxillary suture ipsilateral to the side of the applied force to a point approximately two-thirds along the length of the nasal bone, where the bone becomes much thicker. The fracture line then connects across to the contralateral side and runs parallel and just below the dorsum. The cartilaginous septum is fractured approxi mately 0.5 cm below the dorsum and this aspect of the injury may extend posteriorly into the bony septum, through the perpendicular plate of the ethmoid and skull base. This fracture was first described by Chevallet and bears his name (see Figure 127.1). Class 1 fractures tend not to cause gross lateral displacement of the nasal bones and may not even be perceptible. Deformity generally results from a persis tently depressed fragment, which is often due to impaction of the flail segment beneath the residual nasal bone. In children, these fractures may be of the
CLASS 2 FRACTURES
Class 2 fractures are the result of greater force and are often associated with significant cosmetic deformity. In addition to fracturing the nasal bones, the frontal process of the maxilla and septal structures are also involved. The ethmoid labyrinth and adjacent orbital structures remain intact. As a rule of thumb, if the nasal dorsum is deviated laterally greater than half the width of the nose (grade 2 or greater fracture), then a septal fracture must also be present. The pattern of deformity is determined by the direction of the force applied. A frontal impact tends to comminute the nasal bones and cause gross flattening and widening of the dorsum; while a lateral impact produces a high deviation of the nasal skeleton. What may appear to be a simple dislocation of the quadrangular cartilage from the bony septum is in reality a complex 'C-shaped' fracture that extends from the quadrangular cartilage beneath the nasal tip, posteriorly through to the perpendicular plate of the ethmoid, to the anterior border of the vomer and then forward through the lower part of the perpendicular plate of the ethmoid into the inferior part of the quadrilateral cartilage. This pattern of fracture was first described by Jarjavay and bears his name (see Figure 127.2). Septal fracture-dislocations tend to happen at points of weaknes�. They are where the quadrangular cartilage inserts into the cartilaginous dorsum, the bony septum
r
Chapter 127 Nasal fractures I 1611
pneumocranium and cerebral herniation may complicate this type of injury. The management of this type of nasal fracture is covered in Chapter 128, Fractures of the facial skeleton.
Frontal bone
r------
I
Maxilla Line of fracture
History
Nasal bone
�
Perp ndicular plate of ethmoid
Sphenoid sinus
Cartilaginous septum
Maxillary crest Line of Fracture
Figure 127.2
A class 2 nasal fracture involves the thicker
proximal portion of the nasal bone.
CLINICAL PRESENTATION
It
results in true deviation
and also fracture of the perpendicular plate of the ethmoid and quadrilateral cartilage. Figure courtesy of AGD Maran.
and the maxillary crest. Both the nasal bone and septal fractures need to be reduced together in order to achieve a satisfactory cosmetic result.
CLASS 3 FRACTURES
Class 3 fractures are the most severe nasal injuries encountered and usually result from high velocity trauma. They are also termed naso-orbito-ethmoid fractures and often have associated fractures of the maxillae. The external butresses of the nose give way and the ethmoid labyrinth collapses on itself. This causes the perpendicular plate of the ethmoid to rotate and the quadrilateral cartilage to fall backwards. These movements cause a classic, 'pig-like' appearance to the patient, with a foreshortened saddled nose and the nostrils facing more anteriorly, like the snout of a pig. There is also telecanthus, which may be exaggerated further by disruption of the medial canthal ligament from the crest of the lacrimal bone. Two categories of naso-orbito-ethmoid fractures have been recognized by Raveh. 8 In the first type, the anterior skull base, posterior wall of the frontal sinus and optic canal remain intact. In the second type, there is disruption of the posterior frontal sinus wall, multiple fractures of the roof of the ethmoid and orbit that may extend posteriorly to the sphenoid and parasellar regions. Multiple dural tears, cerebrospinal fluid leaks,
It is prudent to establish how and when the injury was sustained, not only for medicolegal purposes but also because there is a limited period of time during which simple reduction is possible. There will almost certainly be some degree of nasal obstruction associated with the injury, but complete obstruction and persisting pain might indicate the presence of a septal haematoma. Enquiry should be made about any obvious change in the shape of the nose and of previous injuries or past nasal surgery. The patient may have a recent photograph that could be helpful to establish their claim. Other injuries may also be present and may have been overlooked. Diplopia, visual disturbance and epiphora suggest orbital trauma. Loose teeth, an altered bite or trismus indicate the need for a dental opinion. The onset of watery rhinorrhoea and loss of the sense of smell, though uncommon, signal possible skull base damage and the need for a more detailed evaluation. Finally, it is worth enquiring about their leisure pursuits and any occupational hazards that might influence any decision to correct the deformity. Key issues to consider when determining history include: • • • • • • • • • • • •
details of how the injury was sustained; nasal obstruction; change in appearance; epistaxis; hyposmia; watery rhinorrhoea; visual disturbance; diplopia; epiphora; altered bite;' loose teeth; trismus.
Examination
The importance of clear and complete records of the clinical examination cannot be overemphasized. What is and what is not a new injury can be difficult to determine at a later date when litigation is contemplated. Inspect the nose for any external deformity. This may be extremely difficult in the acute situation when swelling may hide an underlying abnormality. A second inspection a few days later may be necessary. Gently palpate the nasal bones for
1612 I
PART 13 THE NOSE AND PARANASAL SINUSES
a step deformity and make note of any surgical emphysema that could suggest a more serious injury. Make a detailed record of soft tissue lacerations. Inspect the nasal cavities and check for the presence of a septal haematoma or deviation. Do not fail to make a thorough general ENT /head and neck examination. Key issues to consider when examining a patient include: • • • • • •
deviation, depression, step deformities; mobility, crepitus, specific areas of point tenderness; generalized swelling; skin lacerations; septal fracture/haematoma/abscess/perforation; mucosal lacerations.
INVESTIGATIONS
The need for nasal x-rays is controversial and in many places it is actively discouraged. Unlike other fractures, nasal x-rays are not required in order to make the diagnosis or aid subsequent reduction. In a prospective study undertaken by Logan et aI.,9 it was concluded that x-rays were not cost effective. [**] Their only possible utility is proof of injury in subsequent litigation. If there is clinical evidence of a more serious facial injury a computerized tomography (CT) scan should be acquired. Samples of any watery rhinorrhoea must be collected in those with suspected cerebrospinal fluid (CSF) leak and tested for �2 transferrin (see Chapter 129, Cerebrospinal fluid rhinorrhoea). TREATMENT
A very significant number of patients, 80 percent in the series reported by Karagama et aI.,5 do not require any active treatment. Many do not have a nasal fracture and, in those that do, the fracture may not be displaced. Soft tissue swelling can produce the misleading appearance of a deformity which disappears as the swelling subsides. Reassurance is all that these patients require and some may heed suggestions to avoid further trawna. Topical vasoconstrictor drops are helpful to alleviate congestion and obstructive symptoms. A reexamination about five days later is prudent where there is uncertainty about the need for reduction. A large number of patients will have a preexisting nasal deformity caused by a previous incident. Manipulation of the nose will, at best, only return it to its most recent appearance. Patients that fall into this category are probably better advised to consider a formal rhinoplasty when everything has settled down some months later. Others will be at continued risk of further injury because of an occupational hazard, sport or leisure activity. It is better to advise this group of patients to undergo a definitive septorhinoplasty when the risk of further injury no longer exists.
The indications for surgical intervention in the acute phase are significant cosmetic deformity and nasal obstruction caused by a septal haematoma. Apart from issues mentioned previously, the only other contra indications for reduction are medical conditions that would make the patient an unreasonable anaesthetic risk. As a general rule, primary care physicians should refer all patients to ENT departments for evaluation if there is any deformity or significant nasal obstruction. Patients with a suspected septal haematoma should be seen urgently at the first possible opportunity. It is the primary care physicians' responsibility to ensure that their patient is seen quickly, certainly within the first few days and no later than one week. Those patients for whom treatment is considered unnecessary should be given the contact details of the ENT clinic lest deformity become apparent over the ensuing weeks.5 The timing of surgical assessment and subsequent reduction is crucial as there is a narrow window of opportunity to correct the deformity. The optimal time for clinical assessment is around four days, by which time much of the oedema will have subsided and any underlying deformity apparent. As stated previously, failure of referral or timely referral is a common cause of litigation in nasal injuries. Review at four days allows sensible planning for reduction of the fracture on an elective operating list within the next two to three days, if it is to be reduced under a general anaesthetic. By seven days, the bony abnormality will be easily palpable and still movable. Further delay makes effective reduction less likely and sometimes impossible without making osteo tomies. In children, healing can take place even more quickly and earlier intervention is indicated. [**/*]
Anaesthesia
Reduction of a fractured nose can be performed under local or general anaesthesia. Local anaesthesia has the advantages of reduced cost and convenience. However, the injections can be painful and the associated distortion of soft tissues can hinder accurate assessment of the reduction. In an awake patient there may be a reluctance to use the force necessary to correct the deformity leading to an inferior outcome. Nevertheless, this method avoids the problem of scheduling patients at short notice on to heavily booked operating lists. Local anaesthetic can be used as a combination of external infiltration with internal application of topical preparations. Lignocaine is injected along the nasomax illary groove, infraorbital nerve in its foramen and around the infratrochlear nerve. Jones and Nandapalanlo recently reported the use of topical EMLA (prilocaine and lignocaine) cream or AMETOP (amethocaine) gel to the external nose instead of infiltration. They found less discomfdrt when the manipulation was carried out using the topical, local anaesthetic preparation compared with
Chapter 127 Nasal fractures I 1613
local infiltration. They achieved similar cosmetic and functional
{****]
results.
Within
the
nose,
sprays,
injections, pastes or packs coated with local anaesthetic are
all
acceptable,
using
combinations
of
cocaine,
lignocaine, adrenaline and phenylephrine. The vasocon strictive element helps to reduce any bleeding associated with mucosal tears from instrumentation during the reduction, but must be used cautiously in hypertensive patients or those with cardiovascular disease. Local versus general anaesthetic as the preferred means for reduction of nasal fracture is a contentious issue and the literature is divided over the influ ence on outcomes.
Ridder et al.II found that there was no significant difference in overall success rate between nasal fractures reduced with local and general anaesthesia. On the other hand, in a retrospective analysis of 324 patients, Courtney et al.4 found a higher number of patients seeking a septorhinoplasty when the initial reduction was per formed
under
anaesthetic (17.2 percent) than (3.2 percent). [**]
local
general anaesthetic
In terms of the overall experience of closed reduction under local anaesthesia, Newton and White12 found that
90.6 percent of patients felt it was less painful than a dental restoration and 96.9 percent would readily under go the procedure again if required. In other studies, nearly all patients found local anaesthesia perfectly adequate and 13, 4 1 [****/***/**] Local. anaesthesia can also
acceptable.
be combined with sedation in an outpatient setting. There are even some circumstances where closed reduction can be performed without any anaesthesia, for example, on a
Figure 127.3
Instruments used in nasal fracture manipulation.
(a) Howarth's elevator, (b) Ashe's forceps (septum): (c) Walsham's forceps (nasal bones).
sports field. However, from personal experience, it is painful!
finger
There are easily identifiable groups of patients who are not
suitable
for
reduction
under
local
anaesthesia.
of
the
dominant
hand
is
placed
along
the
instrument in the line of the nose. In this way, the depth that the instrument has to be inserted into the nasal cavity
Children, patients with low pain thresholds or significant
is easily gauged and inadvertent damage to the orbit
anxiety states are better admitted for general anaesthesia.
avoided
Likewise, attempts at reduction of fractures in which there
fractures can be reduced with these techniques.
has been delay in presentation are better performed under
(Figure 127.4). All class
For many class
1 and most class
2
2 fractures, closed reduction alone
rarely achieves a satisfactory result as the final postion of
general anaesthetic.
the nasal dorsum reflects the deformity of the underlying septum.
Methods of reduction
1 15 16, , ,
17 At least 50 percent of these fractures
remain displaced because of overlapping segments of the fractured perpendicular plate of the ethmoid or septal
The general principle of fracture reduction is to mobilize
cartilage,
the fragments first by increasing and then decreasing the
reduction.
degree of deformity. An initial slight increase in deformity away
from the
side
of
the
blow to
disimpact
which
can
only
be
repositioned
by
open
Occasionally, the bones are fixed, especially if the
the
fracture is old, and osteotomies are necessary to release
fragments, followed by steady movement back towards
the fragments before manipulation. These should be
and often slightly beyond the midline is usually required.
performed cautiously to avoid the risk of extension into
In most cases, the nose will be restored to its original
the orbit or, even worse, intracranially.
IS
position. More often than not, this can be achieved by
Splints or packs may be necessary, depending on the
firm digital pressure. Sometimes instruments are neces
stability of the reduction and the surgeon's preference. A
sary, particularly in those where there has been delay.
splint or plaster applied to the nasal bridge maintains, to
Various
developed
some extent, the position of the nasal bones and prevents
specifically for this purpose, such as Freer, Hills and
accidental displacement. Splints are usually kept in place
Howarth
elevators elevators
and and
forceps Ashe
have and
been
Walsham
forceps
(Figure 127.3). The instrument is held so that the index
for about seven days. It is advisable to refrain from contact sports for at least six weeks.
' __,..
.. _i
:_�___ �__
.
1614
I PART 13 THE NOSE AND PARANASAL SINUSES
some (rhinoplasty' techniques, such as release of upper lateral
cartilages,
hump
removal
and
camouflaging
cartilage grafts?3 Incorporation of these more advanced techniques into the management of the fractured nose requires
expertise,
more
instrumentation
and
more
operating time and this may not always be feasible.
Management of the nasal septum Septal fracture is often missed and is a major reason for poor functional and cosmetic results. Kim et a/?4 found that 46.9 percent of nasal fractures have a concomitant septal fracture. If a septal fracture is present, it is wise to reduce this at the same time as the nasal bones. In a prospective study of 52 nasal fractures, Rhee et a1.25 found that 78.8 percent required septoplasty at the time of reduction
of
nasal
fracture.
In
fact,
a
satisfactory
reduction of nasal bones is often not possible without improving the position of the septum. An often quoted aphorism, 'where goes the septum, so does the nose' is not far from the truth. Septal reduction can sometimes be performed with Ashe's forceps, but often requires a Killian or hemi transfixion incision, elevation of mucosal flaps to expose the cartilage and bone fragments, and replacement and/or Figure 127.4
Determining depth of insertion of instrument
into nasal cavity,
removal of cartilaginous and bony fragments, as in a standard septoplasty. Satisfactory repositioning is aided by the removal of thin strips of cartilage in a vertical direction at the bony-cartilaginous junction and along
Closed techniques for nasal reduction have tradition ally been used, but open reduction techniques may lead to
the maxillary crest. Quilting sutures prevent a dead space from forming and a haematoma collecting.
improved results, despite the increased time and effort involved. Mayell19 and Eichorn et al.2o found satisfactory results in only a third of cases reduced by closed techniques, whereas Illum21 and Watson et az.22 found 71-90 percent of patients had good results after closed techniques.
[**]
Verwoerd17
identified
the
Poor cosmetic result
following
indications for open reduction:17 •
COMPLICATIONS
Attempts to reduce deformity are not always successful.
bilateral fractures with dislocation of the nasal dorsum and significant (preexistent or recent) septal deformity;
Residual deformity has been recorded in 14-50 percent after closed reduction.I8 Factors which contribute to an unsatisfactory cosmetic result include:
•
infraction of the nasal dorsum;
•
extent of the injury;
•
fractures of the cartilaginous pyramid, with or
•
time delay in surgical reduction;
without dislocation of the upper laterals.
•
poor surgical technique;
•
septal fracture unrecognized and untreated;
For depressed tip or flail lateral fractures that are unstable despite closed reduction techniques, Kirschner
(K) wires
can be used. The wire is inserted under fluoroscopic guidance into the depressed fragment as well as neighbour
•
preexisting nasal deformity;
•
postoperative trauma (in recovery room or subsequently); scarring and fibrosis.
ing uninvolved bone (maxilla or frontal bone), and the
•
wires are screwed together externally to maintain the
Unfortunately, it is not uncommon for the shape of the
position. The external wire can be covered by dressings or
nose to change over time as a result of subsequent
from injury. The wires are removed after two weeks?
hump formation. Some patients inevitably require a
plaster to protect the wires from disruption and the patient Some authors advocate a more aggressive approach to the treatment of acute nasal fractures which includes
scarring and fibrosis, loss of tip or dorsal support, or septorhinoplasty despite apparent adequate reduction. In these,
conventional
medial
and
lateral
osteotomy
Chapter 127 Nasal fractures I
techniques should not be
used
as
t he bones tend to
1615
haematoma. Gentle pressure on the bulging area will collection is present.
refracture along the old fracture lines. Mackaj6 advocates
ascertai n that it is fluctuant if a
intermediate and lateral osteotomies, effectively shatter
becomes very unwell with a fluctuati n g fever, severe facial
a triple osteotomy technique, with complete medial,
ing the nasal bones. It is after the allow
wise
to wait at least six months
injury before embarking on septorhinoplasty to
the
fractures
to
heal,
the
oedema
to
settle
completely so the underlying nasal skeleton is evident
and for any fibrosis to develop. The frequency of poor cosmetic res ults can be measured by both
surgeon
and
patient dissatisfaction and subsequent septorhinoplasty
rates. Staffel23 reviewed the literature and found that
when pa t ient satisfaction is reviewed using a question
naire they tend to be more satisfied with the result (79 percent) than
their surgeon (37 percent).
Untreated, an abscess may
develop
and the patient
and cranial pain. Rarely, cavernous sinus thrombosis or forms
other
of
intracranial
sepsis
can
ensue.
The
haematoma or abscess must be drained as soon
possi ble.
as
This can be performed under local or general
anaesthetic either by using needle aspira tion or, pre
ferably,
an
incis i on. Often the collection will have become
organized and so impossible to aspirate. In this situation,
a small window of mucoperiostium should be excised ensuring
there
is
no
corresponding
defect
on
the
contralateral side which could predispose to a perfora tion.
Once drained,
quilting
sutures
from
one side
through cart ilage to the other are inserted to eliminate
the dead space. Packs or splints can be used to provide
gentle pressure on the septum. The patient must be
Nasal obstruction Postoperative nasal obstruction is are many causes that incl ud e:
also common and there
• valve obstruction: collapse of upper lateral cartilages and depressed nasal bones;
reexamined within 48 hours to establish that the
collection has not recurred. The management of a septal
abscess is similar, but with the addition of appropriate an tib i otic therapy. Septal
perforations
may
also
develop
after
nasal
fractures, usually as a result of septal haema tomas and
• septal deviati on; • widened septum (haematoma); • tip ptosis.
their
surgical treatment.
Loss
of cartil aginous septal
support can also lead to a saddle nose deform i t y, as well
These causes need to be considered an d addressed at a
subsequent septorhin oplasty.
as columellar retraction and a broadened septum. This is
why it is imp or tant that all nasal inju ries are assessed within the
fi rst
24-48 ho ur s to exclude these entities and
so that the appropriate referral to an ENT Dep artment can be made.
The correction of a saddle nose deformity generally
Epistaxis Epistaxis at the time of injury may
usually rel at ively
be impres sive but is brief. Occas io nall y , fractures involving
the nasoethmoidal complex can cause laceration to the
requires the incorporation of autologous cartilage from
elsewhere to reconstruct the defect Su itable grafts can be
acquired
from
the
conchaI
bowl
or
costal
region,
although occasionaUy bony septum from the perpend i
anterior ethmoidal artery. This may result in repeated,
cular plate of ethmoid can be used. Septal perforations
the fracture has been reduced. Sometimes, prolonged
and minor
brisk and significant haemorrhage that only stops once
packing or ligation of the artery is required. Bleeding can
the time of reduction, partic ularly if jnstruments are used . Preparation of the nose with
are often asymptomati c, but can be subject bleeds.
S im ple measures,
irrigations and protective ointments,
crustin g
can give long
also be troublesome at
standing relief.
vasoconstrictive agents helps to minimize this blood loss.
tion with pedicled mucosal flap s (see Chapter
The p rovision
to
such as sali ne
of a septal button is
favoured by some, while others embark upon reconstruc
septal perforations) .
124, N as al
Septal complications A submucoperi c h ondrial bleed not infrequently compli
cates nasal fractures. While most septal haematomas are
relati vely limited, some may str i p the mucoperichon
drium over an extended area and dep rive the und erly ing
cartilage of its
source of nutrition. This can lead to u lti mately nasal defo r mity. Septal haematomas present with intense unilateral or bil ate ral nasal obstruction and, on inspection, there is a reddish purple, fluctuant swelling of the cau d a l septum. A cartilage necrosis and
deviated
septum
can
be
confused
with
a
septal
" �_
Na��-ir�-9:hJ,es
arc cqmmon an�'-:a*aren,ess of
. :;:�, ; w�E � ��f:;t'�:les
a�.�erit ·.�nsures
�fma<�
' :_ 'AU:,�sighifitant: nasaJ injliri,es -should be : ' : assess ed by-_a"p!iin:ary,:-pIa:�tiorrer- within 24---"48 hours :-to�_:exclu(le· --and-_specialist-xeferraLmade- if--there is - __ cO$metic deformity andlor n-asaJ obstru c ti on.
,-.':-:�
1616 I
•
•
•
•
PART 13 THE NOSE AND PARANASAL SINUSES
It is impl1rtant to
•
•
each patient
carcfulJy
� Studi es need to be undertaken to determine whether
vigiJant over poten,tia! complications. Document all d
and be
a more aggressive approach to the initial
subsequent lit igat ion.
reduction, septoplasty, 'rhinoplasty techni q ues ) will
Not aU referred pat ients actutlIly hav'c fractures a,od even some with fractures do nnt need surgery. Most cases c an be reduced adequately with dosed techniques, unless the fractures are
preven t subseq u ent septorh i noplasty.
complex or •
assess
a
management of nasal fractures (such as open '
significant septal iractLlfe
dislocation is present. There are no significant differences the outcomes of local versus general anaesthesia: more important predictors of outcome include preexisting deformity, seve[jty of injury" dcl.ay in assessment and poor surgical technique. Residual cosmelic deformity and nasaI obstruction ar.. relatively common compLications and it is wise. to counsel patients ahout these fTom the outst't. A formal septorhlrloplasty can be performed in cases of poor outcome, best performed at least six months after the injury.
.
R EF ERENC ES *
1.
Murray JAM. Management of septal deviation with nasal fractures. Facial Plastic Surgery. 1989; 62: 88-93.
2.
Kim SW, Hoing J P, Min WK, Wan Seo D, Kyo Chung Y. Accurate, firm stabilization
u sing external pins: A proposal
for closed reduction of unfavorable nasal bone fractures and their s i mple classification. Plastic and Reconstructive Surgery. 2002; 110: 1240-6. 3.
Nahum AM. The biomechanics of maxillofacial trauma.
4.
Courtney MJ, Raj apa kse Y, Duncan G, Morr i ssey G. Nasal
Clinical Plastic Surgery. 1975; 2: 59-64. fracture manipulation: a comparat ive study of general and local anaesthesia techniques. Clinical Otolaryngology. 2003; 28: 472-5.
*
5.
Karaga ma YG, Newton JR, Clayton MGG. Are nasal fractures being referred appropriately from the accident and emergency departmen t to ENT? Injury. 2004; 35: 968-71.
6.
Best clinical practice
ilium P, Kr i stensen S, J orge n se n K, Brahe Pedersen C. Role of fixation in the treatment of nasal fractures. Clinical Otolaryngology. 1983; B: 191-5 .
.I Prom p t medical review within 24-48 hours of all
7.
significant nasal i nj uries, with urgent ENT referral
if a septal haematoma or if a class 3 fracture is
se ptaI carti lage. Rhinology. 1975; 1 3: 39-46.
*
8.
present.
telecanthus in 355 cases. Archives of Otolaryngology -
central nervous system (CNS) at initial assessment
Head and Neck Surgery. 1992; 118: 605-14. *
9.
,/ ENT assessment at four to five days if cosmetic
Logan M, O'Orisco(1 K, Masterton J. The utility of nasal bone radiographs in nasal trauma. Clinical Radiology.
deformity or nasal obstruction are present.
/' Closed reduction at seven days, or open reduction if
Raveh J, Laedrach K, Vuillemin T, Zingg M. Management of combined frontonasoorbitaI{sku II base fractures and
./' Exclusion of related injuries to face, orbit, jaws and and appropriate specialist referral if present.
Persig W, Lehmann I. The influence of trauma on growing
1994; 49: 192. 10.
more complex.
Jones
1.
Nandapalan V. Manipulation of the fractured
nose: a comparison of local infiltration anaesthesia and
./ Rev i ew seven days postoperatively with removal of
topical local anaesthesia. Clinical Otolaryngology. 1999;
external nasal splint .
./ No contact sports for at least six weeks
24: 443-6 . 11.
postoperatively.
Ridder GJ, Boedeker CC, Fradis M, Schipper J. Technique and timing for closed reduction of nasal fractures: A retrospectIve study. Ear, Nose, and Throat Journal. 2002; 81: 49-54.
12.
Deficiencies in current knowledge and areas for future research
intravenous sedation: Is it an acceptable and effective treatment? Rhinology. 1998; 36: 114-6. 13.
nasal bone reduction with nasal bone reduction and septoplasty.
local and general anaesthesia. Clinical Otolaryngology. 1990; 15: 343-6.
.
» More. prospective studies are needed to compare
Cook JA, McRae RD , Irving RM, Dowie LN. A randomized comparison of manipulation of the fractured nose under
)- More. prospective studies are required comparing closed and open reduction techni ques
Newton CR, White PS. Nasal manipulation with
14.
Owen GO, Parker Al, Watson OJ. Fractured-nose reduction untler local anaesthesia. Is it acceptable to the patient? Rhinology. 1992: 30: 89-96.
Chapter 127 Nasal fractures I
* 15.
Harrison DH. Nasal inj uries: Their pathogenesi s and
21.
treatment. British Journal of Plastic Surgery. 1979; 32:
273-7.
Murray JAM, Maran AGD. Open v closed reduction of the
22.
nose. Clinical Otolaryngology 1988: 1 3: 491-4.
797-802.
Ve rw oerd C. Present day treatment of nasal fractures: Closed
23.
Staffel J. Optimizing treatment of nasal fractures.
24.
Kim J et al. Analysis of nasal septal fracture combined in
versus open reduction. Facial Plastic Surgery. 1992; 8: 220.
Laryngoscope. 2002; 11 2: 1709-19.
18.
Fernandes S. Nasal fractures: The taming of the shrewd.
19.
Mayell M. Nasal fractures. Their occurrence, manag ement,
Society of Plastic and Reconstructive Surgery 1998; 25:
and some late results. Journal of the Royal College of
852.
Laryngoscope. 2004; 114: 587-92.
nasal bone fracture using CT. Journal of the Korean
Surgeons of Edinburgh. 1973; 18: 31-6. 20.
25. -
bony nasal pyrami d. Laryngologie, Rhinologie, Otologie. 1983; 62: 112-5.
Rhee SC, Kim YK, Cha JH, Kang SR, Park HS. Septal fracture in simple nasal bone fracture. Plastic and Reconstructive
Eichhorn T, Schroeder HG, Kleinsasser O. Follow up
Surgery 2004; 113: 45-52.
examinations of patients with isolated fractures of the
�.--
Watson OJ, Parker AJ, Slack RW, Griffiths MV. Local versus g eneral anaest hetic in the management of the fractured
fractured nose. Archives of Otolaryngology. 1984; 110: 17.
ilium P. Long term results after treatment of nasal fractures. Journal of Laryngology and Otology 1986; 100:
57-64. 16.
1617
* 26.
Mackay IS. The deviated nose. Facial Plastic Surgery. 1986; 3: 253-66.
I , _.� _._� l __ __ .__"__ •
128 Fractures of the facial skeleton SIMON HOLMES AND MICHAEL GLEESON
Introduction Key pOints Aetiology Key points Primary care Best clinical practice Ma ndibular fractures Key points Fractures of the maxilla Key points Zygomatic complex fractures Key points
1618 1618 1619 1619 1619 1620 1621 1625 1625 1628 1628
Best clinical practice Orbital floor fractures Best clinical practice Naso-orbito-ethmoid complex fractures Upper facial third fractures involving the frontal sinus Soft tissue injuries Paediatric facial injuries Best clinical practice Deficiencies in current knowledge and areas for future research References
1630 1630 1631 1631 1632 1632 1632 1633 1633 1633
1630
The data in this chapter are supported by a Medline search using the key words maxillofacial injuries, mandibular fractures, maxillary fractures, orbital floor fractures, nasoethmoid fractures and frontal sinus fractures, focussing on diagnosis, surgery, management and complications.
INTRODUCTION Injuries to the face are relatively common and are the reason for about 10 percent of all accident and emergency department attendances. The integrity and appearance of the face is important for a number of social reasons. After all, first impressions of a person in terms of their intellect, ability, trustworthiness and even sexual orientation are influenced by facial appearance. From a functional standpoint, the facial skeleton provides support to the muscles of facial expression and these in turn act as the sphincter that protects the eyes and make the mouth competent. The facial skeleton holds and supports the eyes in the optimum position for binocular vision and the orbital margins provide additional protection for the globes. In days gone by, the success or clinical outcome of facial fracture management was judged entirely on the
final dental occlusion. While it is important to ensure that a normal bite is achieved, it is just one of the criteria that define today's standard of care. Equally important is the restoration of both the vertical and transverse facial dimensions. This can be achieved by extended craniofacial bone exposure and the use of rigid and semi-rigid internal fixation. In addition, meticulous attention to the repair of soft tissues injuries ensures the best possible cosmetic result.
Cha pter 128 Fractures of the facia I ske leton I 1619 •
t
-
,
'
• [mmedi~te assessm~lilt;::of1p'e airway is' ~en!iaL • Most facial tract U~t~_: ,~U:e~dri.anaged by se trii'~ ~.~ .'rigid internal Iixat'i:b'h-,·th~6~gh extended;;';:" /~.::.;., subperiosteal exposure of the fracture. ,~;: '\'; • Wiring of the jaws is no longer the standard:t' .\:.> of care. . o ·
• Cerebrospinal fluid (CSF) rhinorrhoea ~~l\L : retrobulb~.r_ .haematorna,should :_ b'e · exCluded
in aJl
:¥~~ei~~~d :~~~·~~~::.: ~j..hj~~:2~"·": ~: ~<~(~J'~ "
AETIOLOGY Fractures of the nose, mandible and middle third of the face are usually caused by road traffic accidents, physical violence or attempted suicide. In recent years, the introduction of compulsory seat belts for car drivers and their passengers and crash helmets for motorcyclists has changed the pattern of these injuries in the United Kingdom. Facial damage caused by physical violence or sports accidents are usually low energy injuries that heal well. Higher energy injuries like those sustained in car accidents, military conflicts and attempted suicides, for example, jumping or falling from a height, cause gross comminution of the bones and do not heal as well. It is important to ascertain the exact mechanism of injury not only for medicolegal reasons, but also to ensure that an adequate screening examination is undertaken to detect other injuries and so that a prognosis on the likely stability of any repair can be given.
KEY POINTS • Succcs.sful outcome involves restoration of premorbid facial proportions, dental occlusion and accurate soft tissue repair. • Road traffic accidents) interpersonal violence) "" attempted suicide and sports injuries are the ~. ".~ most common cause of facial frclCt 1!.1 res. • The mechanism of injury will provide insight on the possible degree and extent of the injury and the methods that will be necessary for repair.
Advanced trauma and life-support protocols dictate that a rapid and accurate primary survey should be undertaken in the following sequence: ABCDE 1. Airway. Evaluate and secure the airway, while maintaining alignment of the neck in case there is an unstable cervical spine injury. 2. Breathlng. Make sure that there is adequate ventilation. 3. Circulation. Control sources of blood loss. 4. Disability. Assess the level of consciousness and neurological dysfunction. 5. Exposure. Ensure that all other injuries are iden tifled.
The establishment of a safe airway and effective ventilation is essential so that hypoxia and carbon dioxide retention is prevented and the resultant post-traumatic cerebral oedema minimized. Oral or nasal bleeding, posterior displacement of the tongue secondary to mandibular fractures or the result of posteroinferior displacement of the maxilla in middle third injuries may further compromise the airway. It may be necessary to reduce these fractures immediately and place temporary bridal wires around dentoalveolar segments to increase bony stability. Although the correct surgical procedure for the rapid relief of acute upper airway obstruction is often a cricothyroidotomy) there is occasionally merit in performing an immediate tracheostomy if it can be conducted swiftly and safely. Complex facial injuries involving mandib ular and middle third or nasal fractures are often difficult to manage from the anaesthetic point of view (Figure 128.1) and if there is any likelihood that prolonged ventilation will be required) tracheostomy at the outset is prudent. Haemorrhage from facial fractures can be torrential and demands immediate attention. The use of anterior and posterior nasal packs has been abandoned in favour of the epistat (Figure 128.2). It is important to remember that any injury to the upper middle third of the face is likely to have shattered the anterior skull base. Inadvertent
PRIMARY CARE The initial survey Maxillofacial injuries endanger the airway and can cause profuse haemorrhage. Associated neck injuries are common and should always be suspected and excluded.
L
Figure 128.1
Complex maxillofacial injury following self-
inflicted shotgun injury before tracheostomy.
... ______..1_'
_____~,_.
1620 I PART 13 THE NOSE AND PARANASAL SINUSES skeleton and mandibular outline. If conscious, the patient is asked whether their bite is comfortable and if it feels normal. A full dental examination is necessary so that any fractured or missing teeth that may have been inhaled are identified and accounted for. Finally, the dental occlusion and maxillary or mandibular instability is formally assessed and documented.
Radiographic evaluation
Epistat in anatomical model. Palpation of the posterior balloon in the nasopharynx ensures no intracranial intubation.
Figure 128.2
intubation of the anterior cranial fossa through the cribriform plate or medial wall of the orbit is a distinct possibility and should be borne in mind when attempting to pass any tube through the nose. Intense shock should not be attributed to a facial injury until abdominal, pelvic, orthopaedic or thoracic causes have been excluded. Use of the Glasgow coma scale will alert the clinician to impending intracranial complications. Immediate neurosurgical advice should be obtained if the patient's conscious level deteriorates. Cerebrospinal fluid rhinorrhoea must be suspected in any high-level nasoethmoid or maxillary fracture, while CSF otorrhoea accompanies some temporal bone fractures. Both situations demand prophylactic antibiotic therapy to prevent meningitis. Tetanus prophylaxis should be administered in any nonimmune patient.
Principles of primary management Once the primary survey of the injury has been completed, a secondary survey is carried out to exclude other injuries and to categorize the extent of the facial injury. The soft tissues of the face are carefully scrutinized and any lacerations or cuts noted together with the proximity to relevant anatomical structures including the eyebrows, conjunctival margins, nasal aperture and the vermillion border of the lips. Facial nerve function should be documented and the integrity of the parotid duct assessed. Visual acuity and ocular movements are recorded. Any orbital injury may be complicated by a retrobulbar haemorrhage and retinal detachment, both of which are preventable and treatable causes of permanent blindness. Zygomatic fractures usually extend into the orbital floor and if not detected and treated early are difficult to manage later. A full hard-tissue examination is conducted by palpating the orbital margins, zygomatic projection, nasal
All major trauma patients should have chest, cervical spine and pelvic radiographs as soon as possible. The selection of radiographs of the facial skeleton is discussed later, but it is certainly worth including the facial skeleton on any computerized tomography (CT) scan that might be required for a patient with multiple injuries. Early detection of these injuries greatly simplifies their management. Scanning a patient who is already established in intensive care can be naught with logistical difficulties. The timing of any maxillofacial intervention is controversial. Historically, it was usual to await resolution of any facial swelling before the assessment process began. Patients might wait for five to seven days before surgery was considered. With modern-day techniques there is a trend to fix facial fractures earlier. This policy avoids the so-caUed double insult of accidental and surgical trauma. Swelling can be reduced by nursing the patient in the head up position with ice packs, together with a single dose of dexamethasone. Facial wounds should be cleaned and lacerations closed as soon as possible, if necessary under local anaesthesia. Any facial fracture that communicates with the oral cavity through the periodontal ligament of teeth should be regarded as compound and parenteral prophylactic antibiotics given. Before surgical reduction, it is sometimes useful to obtain dental impressions of the fractured jaws to facilitate treatment planning and the prefabrication of custom-made archbars or splints.
Best clinical practice ./ Maxillofacial fractures can endanger the airway. ./ Be aware of associated cervical spine injuries. .I Consider tracheostomy at the outset in patients with extensive trau mao .I Close soft tissues injuries as soon as possible. .I CT scans of the head and facial bones help to define the extent of both facial and cerebral injuries. .I Do not forget to give tetanus prophylaxis. .I Exclude cervical spine injuries. .I Check visual acuity in all patients with middle third facial injuries lest they have a retrobulbar haemorrhage.
Chapter 128 Fractures of the facial skeleton I 1621
MANDIBULAR FRACTURES
not using IMF is that in severely injured patients a tracheostomy might be avoided. [H]
Introduction The mandible is a parabolic~shaped bone with a complex articulation that consists of paired synovial joints - the temporomandibular joints - and movements that are in part guided by the dental occlusion. In common with fractures of long bones, sa tisfactory rehabilitation of the fractured mandible requires accurate reduction, adequate fixation and mobilization. The traditional method of treatment was immobilization of the fracture with intermaxillary fixation (IMF). This was achieved by wiring the teeth together, in essence, using the teeth as biological bone pins (Figure 128.3). More recently it has been realized that the advantages of such treatment in terms of cost and simplicity were far outweighed by a number of disadvantages. At the ou tset, there were always concerns about the airway lest it became compromised by soft tissue swelling or vomiting. The period of immobilization was uncomfortable and inconvenient for the patient as it imposed dietary restrictions. I. 2 [**] Furthermore, the use of wires placed the surgeon and nursing staff at risk of needlestick injuries. 3 ,4 [*'*"'*"*] To make matters worse, the fixation achieved by this method was often inadequate, particularly if the dentition was incomplete or in bad repair (Figure 128.4). In the last twenty years, there has been a surgical revolution in the management of maxillofacial trauma. The widespread use nowadays of miniplates and extended subperiosteal exposure of the craniofacial skeleton to achieve rigid fixation means that there are now few indications for closed reduction of any facial fracture. In complex panfacial injuries, the mandibular arch is used as a former on to which the fractured maxilla is placed. In this way the correct occlusion is restored. 5 , 6 Without a solid mandible, this can be extremely difficult if not impossible. Fixation of the mandible with plates achieves this. One further and very significant advantage of
Surgical anatomy
Figure 128.3 Eyelet wires fastened to the dentition and interconnected is the simplest form of intermaxillary fixation.
Figure 128.5 Lines of weakness in the mandible that determine the pattern of fractures in the mandible.
The mandible will fracture when subjected to direct and indirect force. Stereotypical fracture configurations are recognized that are determined by the direction and magnitude of the applied force and whether the teeth are in or out of occlusion at the time. Fractures happen at points of potential weakness where the bone is relatively thin (Figure 128.5). The angles of the mandible may be weakened by unerupted wisdom teeth, the parasymphysis by the long root of the lower canine and the condylar neck by its slender anatomy. It is also common for the mandible to fracture in more than one place) for example, the parasymphysis (site of direct violence) and condylar neck (site of indirect violence). It is obviously sensible to look carefully for more than one fracture. Displacement of the fracture depends on a number of factors, the most important of which are the pull of attached muscles, particularly those that close the jaw, the medial pterygoid, temporalis and masseter muscles. and
Figure 128.4 This fracture of the angle of the mandible has been managed inappropriately by intermaxillary fixation - the posterior segment of the left mandible is not controlled. The molar tooth in the line of the fracture should be extracted and an alternative form of fixation applied.
1622 I PART 13 THE NOSE AND PARANASAL SINUSES the direction of the fracture line itself. If the fracture runs forward from lingual to buccal then it is termed vertically favourable as it is less prone to displacement. Similarly, a fracture that runs forward superiorly to inferiorly is termed horizontally favourable. The opposite fracture configurations are termed vertically and horizontally unfavourable, respectively. In the anterior part of the mandible, bilateral parasymphyseal fractures allow the middle fragment to be pulled lingually and this may contribute to airway obstruction. It should not be forgotten that some fractures owe their stability to the integrity of the periosteum. As soon as it is raised, the fracture will become unstable. The muscle attachments to the mandible cause alternate lines of tension and compression. This phenomenon was identified by Michelet and Champy and is exploited in the placement of bone plates. 7 The outer cortical plate of the mandible is strong and provides a solid surface for the placement of osteosynthetic material. Its thickness varies from 2 to 4 mm. The inferior dental nerve runs in a bony canal that is approximately 4 mm from the outer cortical plate in the premolar region and 6 mm in the molar region. The relationship of the dental roots to the outer cortical plate varies from 3 to 6 mm, but abnormal root inclinations due to poor tooth position or orthodontic camouflage may change this and render these teeth more vulnerable to damage by bone screws. [*]
Signs and symptoms The signs and symptoms produced by mandibular fractures are determined by the site of the fracture. Fractures of the body, angle and symphysis are associated with: • a step deformity palpable either externally or intraorally; • asymmetry of the lower dental arch and derangement of the occlusion; • pain and paradoxical movement and crepitus on distraction of the fractured segments; • haematomas in the buccal sulcus or floor of the mouth; • blood-stained saliva; • anaethesia of the lower lip.
Closed reduction techniques As stated previously, the use ofIMF plays a much smaller role in modern maxillofacial surgery. Temporary IMF is only used for more complex fractures when there is limited surgical expertise available. Simple mandibular fractures can be held in normal occlusion and plated without much difficulty.8 Nevertheless, IMP still has a part to play in two groups of patients. First, those with un displaced fractures and no neural deficits who want to avoid more complex surgery and, second, those with unilateral condylar fractures. (** /* 1 In the emergency room, a simple tie wire placed around the teeth either side of a displaced fracture can reduce pain, bleeding from bone ends and make nursing easier in the hours and days before a planned open reduction and internal fixation.
THE INTACT DENTAL ARCH
There are several methods of applying wire to an intact dental arch to provide IMP. Perhaps most well known are eyelet wires. This is very simple but is only possible in those situations where there are two adjacent teeth in contact. The main disadvantage is that it is difficult to combine eyelet wires with elastic traction and it can be awkward to thread wire through tight interdental contact points, particularly in an awake patient. A simple and ingenious modification is the Leonard button (Figure 128.6), an eyelet wire with a small metal disc instead of a loop.
THE INCOMPLETE DENTAL ARCH Arch bars
An arch bar is a strip of metal that is wired to each jaw using several individual teeth. The bar may be prefabricated using a model made from a preoperative dental impression (Figure 128.7), or may be made at the time of
Fractures of the condylar neck are associated with: • tenderness over the temporomandibular joint; • trismus; • deviation of the jaw towards the injured side on opening the mouth; • inability to move the mandible to the side opposite the fracture; • deviation of the jaw to the fractured side at rest with an anterior open bite secondary to gagging of the molar teeth in fracture dislocation; • symmetrical anterior open bite in bilateral fractures of the necks of the condyles.
Figure 128.'6
The Leonard button - a simple device that
facilitates intermaxillary fixation by either wire or elastic bands.
Chapter 128 Fractures of the facial skeleton I 1623
Figu re 128.7 Intermaxi lIa ry fixation has been ach ieved by the use of preformed arch bars connected by elastic bands.
surgery by adapting a preformed pattern. Arch bars can span short gaps within each jaw, but will not cope with large gaps or when there is no posterior tooth. Their main advantage is that they provide a relatively simple means of stabilizing more complex fractures and at the same time provide indirect fixation. Intermaxillary bone pins
A rapid method of intermaxillary fixation has recently been described. 9 A monocortical screw is placed through the mucosa between the canine and first premolar on each side and jaw. The screws are then wired together or connected with elastic bands. It is important to ensure that the path of the screw enters bone and avoids the roots of teeth. These specially designed screws are brittle and care must be exercised when inserting them lest they break. Cast silver splints
Silver splints are rarely used nowadays (Figure 128.8). The splints are prepared from models made from preoperative dental impressions. An indication for their use is in patients who are not stable for transfer to the operating theatre, yet have unstable mandibular fractures or in patients with composite tissue loss. The splint may be made in two parts, one for either side of the fracture. The dental models may be aligned in the dental laboratory and a locking bar made which is fixed by a screw when the fractured mandible has been reduced at the bedside.
Figure 128.8 (a) Sectioned cap silver splints with projection bar. (b) Fracture reduced manually. Acrylic is then applied to the bars and the lab technician fabricates a locking plate. This plate is then screwed in position providing fixation to the fracture.
Gunning splints
Mandibular fractures in edentulous patients provide some of the most difficult problems. IMF can be achieved by modification of their dentures or by fabricating Gunning splints (Figure 128.9) that are wired to the jaws by means of per alveolar, piriform fossa or circumzygomatic wires.
External fixation The use of rigid and semi-rigid fixation has diminished the need for external fixation. External fixation is now
.';"
only indicated for those patients with gross tissue loss as might be seen in the theatre of war and for those with pathological fractures, particularly when the patient is too unwell to undergo extensive surgery. A number of methods have been described and are in current clinical use. By far the simplest is the placement of cortical screws and then connecting them with an external bar made of acrylic. We have found that a mini-Pennig orthopaedic fixator provides an elegant means of stabilizing fractures (Figure 128.10), as well as avoiding pin tract problems and the need for constant tightening and adjustment.
_._ .. .1 ___ . .:..-.
1624 I
PART 13 THE NOSE AND PARANASAL SINUSES
Figure 128.9 Gunning splints used in edentulous patients. The patient's own dentures can be converted for this purpose.
Figure 128.11 Fixation of a fracture in the parasymphyseal region of the mandible using plates. The lower plate has been manipulated beneath the mental nerve.
through the platysma muscle and then blW1t dissection exposes the lower border of the mandible. Condylar neck fractures are approached through a retromandibular incision while higher condylar neck fractures are better exposed through a preauricular incision. I I PRINCIPLES OF MANDIBULAR FIXATION
Figure 128.10 A mini-Permig wrist fixator used to provide external fixation.
Internal fixation ACCESS
Intraoral incisions Wherever possible, bone plates should be placed through an intraoral approach. Mucogingival incisions are made so that the resultant flap includes the periosteum. It is essential that a sufficient cuff of mucosa is raised so that the plate is completely covered after closure. Care must be taken to avoid inadvertent damage to the mental nerve in the anterior region.
Extraoral incisions External incisions are used for the lower border of the mandible and condylar neck. Lower border plates are ideal when there is gross comminution or tissue loss. They are also preferable in fractures of grossly resorbed edentulous mandibles 10 and in alcoholics. In these situations it is better to use bicortical screws and thicker plates that can provide superior fixation. The incision is made two finger breadths below the lower border of the mandible in order to avoid damage to the mandibular branch of the facial nerve. The incision is deepened
The zones of tension and compression mentioned earlier dictate the ideal position and plate configuration around a fracture site. 7 In simple mandibular fractures, monocortical 2-mm plates provide adequate fixation because of the phenomenon ofload sharing between the fracture and the osteosynthesis. In the anterior mandible, two plates are used while posteriorly one plate is usually sufficient 12 and in both situations 6-mm long screws are used. The placement of plates in the region of the mental nerve can be technically demanding (Figure 128.11). In complicated fractures where there is gross comminution, tissue loss or infection, a load-bearing osteosynthesis with rigid internal fixation and bicortical screws are required. CONDYLAR NECK FRACTURES
There is no topic more controversial in maxillofacial trauma than the management of condylar fractures. 13 The 'gold standard) management of most displaced mandibular fractures is reduction and internal fixation. There is just one exception - fractures of the condyle. In the case of condylar fractures, functional adaptation, neuromuscular rehabilitation and altered condylar mechanics tend to compensate for the deficiencies ofIMF in terms of accuracy of reduction. Bilateral displaced condylar neck and high intracapsular fractures generally have poor outcomes and are better managed by an open reduction. 14 • 15 Several factors determine the best approach to the condyle. These include the position of the fracture, availabfe skin creases, tissue laxity and, last but not least, the experience of the operator. A retromandibular
Ch a pter 128 Fractures of the facia I ske leton I 1625 incision provides the most direct and simple approach to the ramus and subcondylar region, albeit that the surgeon has to be careful not to damage the facial nerve. An additional preauricular incision can be usefully employed with higher condylar neck fractures. In recent years, there has been enthusiasm for endoscope-assisted repair techniques that are technically difficult to perform but avoid large facial scars. 16 • 17, 18. 19 Once exposed, the fracture is reduced and fixed with either miniplates,20 lag screws 2 1. 22 or Kirchner wires. 23 [>PI /*]
KEY POINTS
Figure 128.12 Severe multilevel Le Fort fracture with typical 'panda eyes'. An epistat has been inserted to arrest haemorrhage.
Mandibular injuries • Mand ibular injuries are often multiple.
• IMF is no longer acceptable practice for the major~ty of mandibular injuries. • Most fractures are treated with noncompression miniplates. • The managt:itwlH of "'ondylar neck fractures is COIltmVCrilial. • Rndos,c opie techniques nlay have a role in the management of certam ma.ndibular fractur~s.
Signs and sympwms of manclibular fractures include: • bon)' step de.formity; • derangt..-d occlusion; • pam; • sublingual hacmatoma; • blood-stai ned saHva; • mobile teeth in the fracture Line; • anaesthesia of the lip; • trismus. Signs and symptoms of condylar neck fractures include: • tenderness over the temporomandibular joint
rnvtJ); • trismus; • lat.eral open bite; • anterior open bite.
FRACTURES OF THE MAXILLA Introduction Fractures of the midfacial skeleton can be subdivided into lateral (zygomatic) or central (maxillary, nasal, nasoorbito-ethmoid) fractures. The symptoms and signs of maxillary injuries depend on the level of the fracture (Figures 128.12 and 128.13). At the outset, facial swelling
l
may mask the underlying deformity and so it is important to take time and care to evaluate the injury. The classical features of a midfacial fracture are circum orbital ecchymosis (panda facies), facial oedema and emphysema, lengthening of the face and an anterior open bite. Not all of these signs need be present. An infraorbital nerve sensory deficit is not uncommon in higher fractures and bruising at the junction of the hard and soft palate is frequently present.
Surgical anatomy The bone of the midfacial region is generally very thin and offers little resistance to anterior and lateral forces. Le Fort24 described three levels of mid facial fracture (Figure 128.14): [**1*] 1. Le Fort 1. This fracture runs above the floor of the nasal cavity, through the nasal septum, maxillary sinuses and inferior parts of the medial and lateral pterygoid plates. 2. Le Fort 2. This is a fracture which runs from the floor of the maxillary sinuses superiorly to the infraorbital margin and through the zygomaticomaxillary suture. Within the orbit it passes across the lacrimal bone to the nasion. The infraorbital nerve is often damaged by involvement in this fracture. 3. Le Fort 3. This represents a disconnection of the facial skeleton from the cranial base. The fracture traverses the medial wall of the orbit to the superior orbital fissure and exits across the greater wing of the sphenoid and zygomatic bone to the zygomaticofrontal suture. Posteriorly, the fracture line runs inferior to the optic foramen, across the lesser wing of the sphenoid to the pterygomaxillary fissure and sphenopalatine foramen. The arch of the zygoma is also broken.
1626 I
PART 13 THE NOSE AND PARANASAL SINUSES
Figure 128.13 (a) 3D CT reconstruction demonstrating vertical, hOrlzonal and transverse disruption to the entire craniofacial skeleton. (b) Postoperative view, note bilateral titanium orbital floor rec.onstruction.
Figure 128.14
blue, Le Fort
While the Le Fort classification is attractive and accurate
for low energy injuries) in high energy injuries there are very few instances of pure Le Fort fractures and most 5 configurations involve multiple Le Fort levels)2 together with zygomatic and nasal/nasoethmoid components. 6 Sicher and Tandler2 described thickened areas of bone between the maxilla and skull base which act as buttresses. In essence) these thickened areas of bone provide a 7 8 & reconstructlOn2 ' 2 and are key areas £or strategy lor •
osteosynthesis.
2;
(a) and (b) The Le Fort injuries: red, Le Fort green, Le Fort 3.
1;
Signs and symptoms Middle
third
facial
fractures
symptoms and signs: •
epistaxis;
•
circumorbital ecchymosis;
•
facial oedema;
•
surgical emphysema;
•
lengthening of the face;
•
infraorbital anaesthesia;
produce
the
following
Chapter 128 Fractures of the facial skeleton
I 1627
• anterior open bite in Le Fort 2 and 3 fractures; • haematoma at the junction of the hard and soft palate; • floating palate and teeth in Le Fort 1 fractures.
Principles of management EMERGENCY TREATMENT
Midfacial fractures can easily compromise the airway with torrential epistaxes and posterior impaction of the maxilla. The bleeding can be arrested by using epistats or anterior and posterior nasal packs. If retroposition of the maxilla is a problem, it can be pulled forwards using the index and middle finger placed behind the patient's soft palate.
REDUCTION
The maxilla is mobilized by a combination of digital pressure and traction on arch bars or interdental wires. The position of the maxilla is 'eye-balled' with reference to the bony buttresses and dental occlusion. This can be difficult when the bone fragments are comminuted or the dentition is mutilated. Rowe maxillary disimpaction forceps can prove invaluable if the maxilla is impacted.
FIXATION
The maxilla can be stabilized by a number of methods. [**/*]
Intermaxillary fixation This can be used in isolation provided the fracture is at a low level (Le Fort 1) and not grossly displaced. If the fracture is at a higher level, there is the risk of persistent CSF leak by aggravating the maxillary instability and also of permanent lengthening of the midface.
External fixation A1though external fixation techniques have been superseded by internal fixation, there is still a limited role for their use. The maxilla is fixed by attaching a fork to the teeth with a silver cap splint. This in turn is anchored to 'stable bone' above the fracture. This form of external fixation can be applied in the intensive care unit without recourse to an operating theatre and has recently been described in relation to the arrest of midfacial haemorrhage. The halo frame is simple to apply, although the patient will find it difficult to lie down in bed with it on. The Levant frame is elegant29 and more comfortable for the patient when lying down (Figure 128.15). External fixation is extremely rapid and allows the surgeon to make fine adjustment during the initial phase of bony healing in the first two weeks. The main problem with
Figure 128.15
A Levant frame in clinical use to stabilize a Le
Fort 2 fractu reo
external fixation is non accurate reduction and, to a lesser extent, poor facial appearance while the apparatus is worn. Despite this, external fixation has a small but very real role for those patients with multisystem injuries that preclude prolonged anaesthesia and when a mobile maxilla causes an acute airway problem.
Internal suspension This method, initially described in the middle part of the last century,30,31 provides rapid stabilization of a mobile maxilla without the need for external fixation. The fractured maxillary elements are suspended from various points on the craniofacial skeleton above the fracture line, for example the zygomatic arch or orbital rim. A1though rapid and simple to apply, positioning of the maxilla is difficult to achieve and fixation is often relatively poor as the suspension wires are directed posteriorly and this encourages relapse.
Internal fixation Modern management of the fractured maxilla parallels that of the mandible. 32 Internal fixation with 1.5-mm, low-profile miniplates placed along the buttresses provides very satisfactory stabilization of the fractured segments. Access to fractures of the anterior and lateral maxilla can be achieved through a gingivobuccal incision ensuring that there is an adequate cuff of unattached mucosa to isolate the plates from the mouth at closure. The posterior limit of the incision should be no further than the first permanent molar to preserve a good blood supply. The buccal fat pad may be avoided by angling Lhe scalpel blade at 45 to the gingival cuff. Subperiosteal elevation with preservation of the infraorbital nerve allows reconstruction of the paranasal and zygomatic buttresses. The infraorbital rim needs to be reduced and fixed in Le Fort 2 maxillary fractures, nasomaxillary fractures, zygomatic injuries and orbital floor repairs. A number of skin incisions can be used (see Table 128.1) all of which have advantages and disadvantages. 0
1628 I
PART 13 THE NOSE AND PARANASAl SINUSES
Table 128.1
Orbital access.
Advantage
Disadvantage
T ransconju nctival
Good exposure, aesthetic
Slight risk of entropion
Transconjunctival with cantholysis
Excellent exposure
Risk of lid malposition
Transconjunctival with transcaruncular
Excellent exposure of medial orbital wall
Technically difficult
lower eyelid
Straightforward to execute
Risk of increased scleral show, ectropion.
Infraorbital
Rapid, minimal increased scleral show
Poor cosmesis
'Incision
extension Visible scar
Classification KEY POINTS This area is confusing and there is no universally accepted
Maxi41ary fractures • • •
•
•
Maxillary fractures
scheme.
These
fractures
are probably
best classified
according to their rotation about vertical and horizontal
involve the ()rbits. They may disrupt the occlusion. Internal fixation has rep.laced external fi.x(ttion for the maJority of maxillary fractures. Most high-energy ma."{,iHary fTactures are not pure I.e Fort injuries and are also comminuted. Haemorrhage may be arrested ""'ith anterior and posterior nasal packs or cpistats. may
axes. The vertical axis runs between the frontozygomatic
suture and the first molar tooth, while the horizontal axis is the plane of the zygomatic arch. In severe injuries, the bone is dislocated or comminuted and there may be disrupti.on of the orbital floor. Several factors govern the degree
and type of displacement,
for example,
the
direction, magnitude, site of impact, the pu l l of the masseter and the integrity of facial attachments. The zygomatic arch tends to break at its weakest point, just posterior
to
the zygomaticotemporal
suture.
Medial
displacement impinges on the coronoid process of the mandible and limits mouth opening. It is important to appreciate that high-energy injuries tend to be unstable
ZYGOMATIC COMPLEX FRACTURES
and require more fixation in comparison to lower-energy injuries.
Surgical anatomy The body and processes of the zygomatic bone make up the lateral middle third of the facial skeleton. Blows to tills part
Signs and symptoms
of th e face are common and may cause either a depres sed fracture of the entire zygomatic bone or a fracture of
The lateral aspect of the face is best examined from the
the zygomatic arch (Figure 128.16). These injuries were
front, above and behind the patient. It will be swollen
originally termed 'tripod fracture' because of the disruption
and bruised. A subconjunctival haemorrhage is almost
of the three commonly recognized articulations:
invariably present in fractures of the z yg oma tic body
(Figure 128.16). Even if the eyelid is closed by oedema it
1. fro nto -zygomatic;
is essential that the eye is examined and its acuity
2. in fr a orbita l rim;
recorded. Eye movements may be restricted, pa r ticu larl y
3. zygomaticomaxilla ry buttress.
in upward gaze if there is an orbital floor dehiscence
(Figure 128.17).
In fact, there are two further articulations worthy of
and blow-out of the orbital contents
co nsideration:
The zygomatic prominence may be difficult to assess
initially because of soft tissue
1. zygomatic arch;
has decreased,
2. zygomaticosphenoid.
sw elling
but, once this
reduced projection will become more
obvious. A step deformity of the infraorbital margin
The lateral middle third of the face provides support and
may be palpable and the frontozygomatic suture may be
protection for the globe of the eye. Accurate anatomical
tender to touch. In arch fractures, there is often a palpable
reduction
depression and limited
of such
fractures
is
important
for
facial
appearance, optimum function of the eye, and because
mouth opening.
Finally,
the
sensation of the cheek may be altered if there has been
of its close proximity to the coronoid process, for opening
damage to' either the zyg omaticotemporal or zygomati
and closing the ma ndibl e.
cobuccal nerves.
Chapter 128 Fractures of the facial skeleton
Imaging Most fractures are visible on 15 and 30° occipitomental x-rays and indicate where plates should be fitted. ~ 7....' " . ... -:-.~
I 1629
Ultrasound examination has recently been shown to be 33 helpful and can be used intraoperatively to assess the accuracy of reduction. 34 If there are signs of diminished ocular motility, a Hess charting should be obtained together with coronal and axial CT images, especially if there is any doubt about where fixation points should be placed. 35 [**1*]
Management
Figure 128.16
Minimally displaced fractures may be managed conservatively with a full explanation to the patient and instructions not to blow their nose for a period of two to three weeks. It is prudent to review the patient after ten days when much of the swelling will have resolved to make sure that no active intervention is required. Displaced fractures require reduction with or without fixation. Reduction may be achieved in a number of ways. The precise method will depend on the surgeon's preference and the configuration of the fracture. Each method has its advocates and offers certain advantages over others (Table 128.2).
Typical appearance of a patient with a
fractured zygoma, A slight depressi'on of the cheek is clearly vis'lble and he has a subconjunctival haemorrhage.
GILLIES TEMPORAL APPROACH
Figu re 128.1 7
Red uced ocular movement and enophthal mos
associated with an orbital floor injury.
Table 128.2
Approach Gillies
Zygomatic complex fractures - advantage and disadvantages of surgical approaches.
Indication
Advantage
Disa~~~!~d~J-:;,~X~~':::',;~::;~:_;~~:,::;;/:::;;~5.· .
Medially displaced body fractures,
Elevating site distant from
Requires skin incision, may be
zygomatic arch fractures Dingman
The hair is shaved just anterior to the ear and both infraorbital margins are exposed for comparison. Following infiltration with local anaesthetic and adrenaline solution, a small incision is made down to the superficial temporal fascia. The fascia is then incised and an elevator is passed down on the temporalis muscle so that its tip lies just under the fracture. The bone is then elevated.
Medially displaced body fractures
fixation site Uses common skin incision to that of frontozygomatic access
conspicuous in the bald patient May be difficult to plate frontozygomatic suture and elevate simultaneously. Incision may become stretched
Poswillo hook
Posteriorly displaced fractures Not arch fractures
Good mechanical advantage, quick, only one suture required
Access point of hook is prominent on the lateral cheek prominence and may be noticeable
Keen
Medially displaced fractures, arch
Avoids cutaneous scars
fractures
Does not address displacement at the frontozygomatic sutu reo Elevation and plating at this site are difficult simu Itaneously. Theoretical contamination of the fracture site with oral microorganisms
Coronal
laterally displaced arch .fractures
The only approach for this rare fracture
Extensive surgical exposure
1630 I
PART 13 THE NOSE AND PARANASAl SINUSES
DINGMAN SUPRAORBITAL APPROACH An incision is made to expose the frontozygomatic suture. An elevator is then passed posterior to the zygomatic
Retrobulbar haemorrhage
body and the fractured segments elevated.
Retrobulbar hae morr!1�e, �c;��,tf��n-yq�Y� l . � ' •
•
POSWILLO HOOK
•
The point of application of the hook is the intersection
•
of a line drawn vertically from the lateral orbital margin
•
and a horizontal line drawn from the inferior margin
•
of the nose. The hook is inserted through a stab incision
•
and the zygoma lifted back into position.
decreased visual a citiiYi
' >�,,, . , '�7
-
,r:',': ,,.
diplopia;
ophthalmoplegia;
proptosis; tense
globc�
dilated pupil;
loss of direct tight reflex.
INTRAORAL OR KEEN APPROACH
A mucogingival incision is made in the buccal sulcus in
Best eUnical practice
the molar/premolar region. An elevator may be passed behind the zygomatic body to elevate the fracture.
Management involves:
Fixation may not be necessary for medially displaced
./ dexamethasone 4 mg/ kg bolus, 2 mg/ kg, six hourly;
fractures, those of the arch or fractures can be rotated
./ acetazolamide 500 mg i.v.;
around the vertical axis. 36, 37 Unstable fracture configura
./ mannitol 20 percent. 200 mL;
tions tend to be those with inferior displacement of the
./ finally. remove the sutures and consider surgical
arch and those with rotation around the horizontal axis.
decompression by a lateral cathotomy.
Diastasis at the frontozygomatic suture and high-energy injuries are typically unstable. Closed reduction does not allow examination of the articulations of the zygoma. Minor discrepancies may be missed and only come to light some days later. The difficulty of accurate intraoperative assessment of reduc tion has been highlighted recendy by Stanlet8 who suggested the use of intraoperative CT scanning. In reality, surgical exposure of the relevant articulations together with experience ensures good outcomes for the over whelming majority of patients. The zygoma may be plated at
the
frontozygomatic
suture,
infraorbital
margin,
zygomatic buttress and zygomatic arch.39 Wound closure
ORBITAL FLOOR FRACTURES Introduction The form and function of the globe depends on the integrity of the bone and soft tissue of the orbit. Blunt trauma to the globe43 or adjacent bone can lead to a fracture of the thin bone of the orbital floor.44
[**]
is extremely important. Optimal draping of the soft tissues requires meticulous closure of the periosteum over the plates. Some surgeons 'hitch' the deep tissues to superior tissues in order to provide further support.40
Postoperative care
Signs and symptoms The cardinal signs
of an
enophthalmos
hypoglobus
and
orbital
floor
fracture
(depressed
are
pupillary
level). Enophthalmos is most apparent when the con tralateral eye is normal. Other signs include supratarsal
The patient is instructed not to blow their nose and
hollowing, hooding of the eye, narrowing of the palpebral
for the first twelve hours
they should be closely observed
fissure width and an infraorbital nerve deficit. A small
for signs or symptoms of a retrobulbar haemorrhage.
fracture of the orbital floor can lead to a trap door
visual acuity and a palpable increase in ocular pres
becomes trapped in the fracture configuration, then
Increasing
pain, proptosis, ophthalmoplegia, diminishing
sure should alert the attendant to this and indicate the need for urgent exploraton and evacuation of any
phenomenon,
If
the orbital fat or inferior oblique muscle
interference with muscular function results in diplopia on upward gaze
(Figure 128.17).
haematoma.
Most long-term complications relate to malunited fractures. It is important to realize that early accurate
Imaging
anatomical reduction provides the best results. Secondary
reconstruction is difficult because of bony remodelling
and fibrosis in the overlying soft tissuesY' 42
In
the
past,
surgeons
relied
on
plain
radiographs,
occipitomental views, to gain information on the orbital
Chapter 1 28 Fractures of the facial skeleton I
1631
Management Significant
orbital
floor
injury
requires
exploration
and repair. The approach will be determined by the size and position of the blow-out fracture.
All soft tissue
components should be mobilized and supported by a
graft. Various grafts and materials have been used for
this purpose. Silastic and polydimethylsiloxane (PDS)
are readily available and most suited for smaller defects. Silastic has a tendency to become infected and extrude.47 For
larger
blow-out
fractures)
bone
obtained
from
either the iliac crest, rib or calvarium are preferable. Titanium alloplasts,48 either prefabricated or custom made using CAD-CAM technology are
extremely use
ful especially when there are concomitant complex fractures.
Endoscopic
been described49 and purposes.
50, 51
zygomatic
transantral repair
has
is certainly useful for diagnostic
NASO-ORBITO-ETHMOID COMPLEX FRACTURES Definition and classification Naso-orbito-ethmoid (NOB) fractures involve the anato
mical confluence of the nose, orbits and ethmoids. This is a complex area and these injuries are often over Figure 128.18
CT scan showing a fracture of the left orbital
floor with herniation of the orbital contents_
looked.
Reconstruction at a
later
date is extremely
difficult. The most useful classification of these injuries was devised by Markowitz et
ai.52 who defined them in
terms of their attachment to the medial canthal ligaments
(Table 128.3). [**/*] rim and floor. CT images are far superior and much more reliable, particularly
in respect of the orbital floor45
(Figure 128.18). More recently, surgeons have begun to use ultrasound to diagnose orbital floor
injuries.33•46
Signs and symptoms Loss of nasal projection and tipping up of the end of the
nose are
(Figure 128.19).
��- Best clinical practice Ophthalmology review ,/ Assessment of visual acuity is mandatory. Retrobulbar haemorrhage causing loss of sight is a rare occurrence but is treatable and should be sought in every orbital injury.
,/
Hess charting allows comparison of the visual fields of each eye. Postoperative charting can be used to assess the quality of repair.
./ Hertel exophthalmometry gives an objective analysis of the position of the globe. It has limited value in acute trauma_
common features of these
injuries
Splaying of the nasal root and tele
canthus indicates gross comminution. There is usually
Table 128.3
Classification of naso-orbito-ethmoid complex
fractures.
CI assification Type I
Single large central fragment bearing the canthal
Type II
Fragmentation of the central fragment. medial
Type III
Comminution of the central fragment with no bone
ligaments canthal ligaments attached to bone attached to canthal ligaments
Reprinted from Ref. 52. with permission.
' --L_-
1632
I PART 13 THE NOSE AND PARANASAL SINUSES
SOFT TISSUE INJURIES The management of the soft tissue component of a significant facial injury is o ft en given a dis proportionate [**] It should be remembered that patients
low regard.
rarely appreciate the perfection of any fracture reduc tion, but are all too aware of the most minor scar. Careful examination of sutured wounds shows that the
quality of repair is often poorer than expected and consequently
a
less
than
satisfactory
result
can
be
expected.59 Facial wounds should be closed as soon as possible
provided
that
they
are
clean.
Meticulous
debridement with antiseptic solution is essential. Grit
from the roads can tattoo wounds badly and be a real
problem and are best removed using a sterile nylon
w i t h a naso-orbito-ethmoid fracture with typical loss of nasal projection and tilting of the nasal tip. Figure 128.19
Patient
scrubbing brush. The
literature
is
replete
with
references
to
the
avoidance of radical wound excision in these injuries. Experience with cutaneous malignancy demonstrates that
blunting of the canthal angle and movement of the medial canthus can be elicited by displacement of the lateral palpebral ligament.
sizeable areas of tissue loss
can
be dealt with primarily, so
some selective removal of poorly viable wound margins would appear to be sensible. It is crucial to ensure that
any underlying bony injury is repaired to enable correct support and soft tissue draping. The
facial
nerve
Management
quently damaged
Type
hours,
and
parotid
duct
are
fre
in significant soft tissue injuries. T he
facial nerve is easiest to :find and repair in the first 48 1
fractures can be stabilized using miniplates.
Surgical access is through a coronal flap intraorally and
while
stimulated.
the
Sadly,
peripheral
branches
can
still
be
recognition of this injury is often an
subciliary incisions may be required. Type II and III
delayed. Epineural repair using
fractures are also repaired with miniplates, but require a transnasal canthopexy to reduce the telecanthus and hold
provides the patient with the best chance of a good
the position of the medial canthal ligaments. This is
operative microscope
recovery. Identification and alignment of key landmarks such
accomplished by means of plates and/or a wire. Injuries to
as
the lacrimal duct are best managed expectantly, unless an
margin of nose, ear and eyelids is essential for a good
open laceration has divided the system.
cosmetic
the
(410
vermillion result.
border of the
Similarly,
the
lip,
use
eyebrow,
of deep
alar
sutures
vicryl or equivalent) to take tension out of the
wound and to avoid dead space together with appropriate skin sutures
UPPER FACIAL THIRD FRACTURES INVOLVING THE FRONTAL SINUS Fractures
involving
the
frontal
sinus
may
lead
to
deformity and be complicated by infection. These injuries are classified according to the involvement of the anterior and/or posterior table and whether or not there is damage
(5/0
or
6/0
monofilament) produces the best
results. Shelved lacerations should be managed by placing sutures with a bigger 'bite' on the more depressed side, and triangular edges by the 'corner �titch' technique. Sutures are best supported by steristrips and removed after four to seven days. Chloramphenicol eye ointment can be applied to the wound four times daily for one week.
to the nasofrontal duct.s3 The principal aims of treatment
The patient sho uld be instructed in wound care and
are to leave the patient with a safe and functional sinus
told to avoid direct sunlight on the wound for one year.
and with no cosmetic deformity. Fractures of the anterior table may be treated conservatively if there is no cosmetic
deformity, while displaced fractures require reduction and fixation.
Fractures of the posterior
table
demand a
At the review appointments, consideration of surgical
intervention of whatever form should be deferred for at least 9-12 months.
neurosurgical opinion and may need an obliterative procedure
or
cranialization with obliteration
of the
frontonasal recess and its lining. 54, 55, 56, 57 Persistence of
PAEDIATRIC FACIAL INJURIES
the epithelial lining with inadequate drainage predisposes
FortunateLy) serious maxillofacial
to mucocoele formation.58
group are uncommon. Minor injuries, particularly
[***/**/*]
injuries
in
this age
s oft
Chapter 128 Fractures of the faclal skeleton I 1633
tissue and dentoalveolar are, however,
fre que nt
.
The
Best clinical practice
treatment concepts and protocols are similar to adult
.
60 p atIents .
Paediatric dental injuries ./ Consider whether the injury might be a nonaccidental
Soft tissue injuries
injury.
.I Reimplant avulsed teeth as soon as possible.
Minor soft tissue injuries are managed in the same way as
.I Use short screws and take care not to damage
ad ult pat ie nt s but most will require general anaesthesia ,
unerupted teeth.
or sedation. It is important to ensure that ade q uate
.I Remove plates three to six months after surgery.
wound toilet and debride ment is achieved. Consideration
.I Manage condylar fractures conservatively.
should be given to excision of wound mar gins and the use of resorbable
sutures
anaesthesia for suture
to
avoid
removal
.
general
unnecessary
Cyanoacrylate glue can
be used with care but not in the presence of substantial connective t issue damage.
Deficiencies in current knowledge and areas for future research
Injured anterior teeth
)0. The controversy on the virtues of open and closed D ental injuries to the upper anterior teeth are extremely
management of condylar neck injuries will persist.
common,
The management and outcomes of intracapsular
th eir management and prognos i s is extremely complex . The optimal treatment protocol is but
determined by a
number
fractures may well become revolutionized by
of factors that relate to the type
aIloplastic materia Is.
of tooth fractured, the presence and level of any root fracture,
the
opinion
is
vitality
of
the pulp
and
the
»- Endoscope-assisted procedures may become the
st at e of
standard of management for condylar and orbital
development of t h e root. It is e ss ent ial that an expert paedodontis t
sought from .
a maxi llofac ial
surgeon
fractures if outcomes can be seen to be improved.
or
Fractured teeth can be temporar i ly re
paired, exposed p ulp s capped with calcium hydroxlde based pastes and mobile teeth splinted to adjacent teeth. Anterior permanent teeth that have been avulsed should
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1634 I PART 13
THE NOSE AND PARANASAL SINUSES
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129 Cerebrospinal fluid rhinorrhoea ANDREW H MARSHALL AND NICHOLAS S JONES
Definition Risk of meningitis Physiology Aetiology Management Reasons for failure
, , . .
." '~'.
1636 1636 1636 1636 1637
Key points Best clinical practice Deficiencies in current knowledge and areas for future research References
1641 1641 1641 1642
1641
. \
-
'.
~
•
I
..
_ '
_.
The data in this chapter are supported by a Medline search using the key words cerebrospinal fluid, endoscopy, paranasal sinuses, rhinorrhoea, surgery and beta-2 transferrin.
DEFINITION Cerebrospinal fluid (CSF) rhinorrhoea is the leakage of CSF from the subarachnoid space into the nasal cavity due to a defect in the dura, bone and mucosa. The origin of the fluid may be from the anterior, middle or posterior cranial fossae. The fluid may escape directly into the nose from a defect in the anterior cranial fossa, either via the frontal, ethmoid or sphenoid sinuses or from the cribriform plate. A CSF leak from the middle or posterior cranial fossa usually communicates with the nasal cavity via the mastoid cavity and middle ear through the Eustachian tube.
RISK OF MENINGITIS The risk of developing one or more episodes of meningitis with CSF rhinorrhoea has been quoted as varying from 2 5.6 1 to 60 percent. The most comprehensive study to date indicates there is a 9.8 percent annual risk of 3 developing meningitis. Most authors report that up to a third of patients undergoing repair have had bacterial 4 meningitis prior to repair. ,5 Some authors argue that
there is some residual risk despite there being no evidence of an active leak6 and would advocate surgical repair in all cases with a proven history of CSF rhinorrhoea, but there is inadequate evidence to support this at present. The time from the onset of rhinorrhoea to developing meningitis varies widely and in one study ranged from 2 to 2285 days with a mean time of 499 days.4 [H]
PHYSIOLOGY Cerebrospinal fluid is produced by the choroid plexus in the lateral, third and fourth ventricles of the brain. The intracranial CSF volume has been estimated at 123 mL? It is secreted at 'a rate of 0.35-0.4 mL per minute, meaning that 50 percent of the CSF is replaced in five to six hours.
AETIOLOGY Various authors have suggested methods of classifying the causes of CSF rhinorrhoea. The most widely quoted is that of Ommaya. 8 ,9 The causes of CSF rhinorrhoea are varied (see Table 129.1). Historically, the most common
Chapter 129 Cerebrospinal fluid rhinorrhoea I 1637
Table 129.1
Causes of CSF rhinorrhoea. t"
Acquired
Idiopathic
Congenital
Meningocoele or men i ngoencepha locoele Congenital skull base defects Congenital hydrocephalus
Cause is unknown, possibly intermittent increases in in tracran ial pressure
Surgical
Nonsurgical
Intranasal surgery Endoscopic sinus surgery Transcranial approaches, including surgery to the middle and posterior cranial fossa
Skull base fractures Open or penetrating injuries Post-traumatic hydrocephalus
~··~;·:\·\, f;: ... .
: '. '~::.<~;':_\i'-~~'/'~:~::":: :"':" -';
Inflammatory
Neoplasrrt ~ · .
Erosive lesions: mucocoeles, polypoid disease, cystic fibrosis, fungal sinusitis. osteomyelitis Post-infective hyd rocephalus
Neoplasm invading the skull base Intracran ia I abnorma Iities causing hydrocephal us
,.; (_:.;,
Adapted from Ref. 10, with permission.
Figure 129.1 sinuses.
A skull base fracture of the posterior ethmoid
cause was head injurT (Figure 129.1) and one study estimates 2.6 percent of head injuries result in CSF rhinorrhoea. 4 However, with the development of new surgical procedures the aetiology has changed dramatically and the majority of large series now site iatrogenic trauma as the most common causeY' 12, 13, 14,15 The most common surgical causes are headlight intranasal surgery (Figure 129.2), endoscopic sinus surgery, craniotomy or a transsphenoidal hypophysectomy. The incidence of CSF leaks complicating endoscopic sinus surgery varies from 016 to 2.5 percent. 17, 18 It should be noted that most rhinological operations can cause CSF rhinorrhoea, including simple headlight polypectomy,l1 and on occasion, septoplasty.15 [**J The onset of CSF rhinorrhoea may be delayed from the time of the initial insult. The possible reasons for this are the delay in the dissolution of a haematoma at a fracture
b
Figure 129.2 A coronal CT scan showing a pneumocephalus following an intranasal polypectomy.
site, or intracranial pulsation causing herniation and eventual separation of the dura through a nonhealed fracture site. 19
MANAGEMENT It is imperative to establish the diagnosis of CSF
rhinorrhoea beyond doubt before considering surgical repair. If this is not done, patients may be subjected to unnecessary surgical intervention and its attending
-,./------
1638 I PART 13 THE NOSE AND PARANASAL SINUSES morbidity.20 Unilateral autonomic rhinitis or rhinorrhoea following the spontaneous rupture of a mucus retention cyst in the maxillary sinus can feign a CSF leak. 20 The diagnosis should be approached methodically by eliciting an accurate history, examining the patient and using appropriate investigations that must include immunofixation of beta-2 transferrin. The majority of patients will present with intermittent or continuous rhinorrhoea. This is usually unilateral, but may be bilateral. There is often a history of previous surgery or a head injury. Rarely, recurrent meningitis may be the only indication that an abnormal communication with the nasal cavity exists. Up to 40 percent of patients complain of headache. 21 Nasendoscopic examination should be performed in the outpatient clinic by an experienced rhinologist. This ll alone may identify the site of the leak in 36 percent or may identify the cause, such as an encephalocoele (Figure 129.3)?2 Otoscopy should be performed to exclude a middle ear effusion, as a defect in the middle or posterior cranial fossa can be the origin of the CSF rhinorrhoea. The investigations include: • laboratory investigation of rhinorrhoea fluid; • imaging; • intrathecal dyes and markers.
Laboratory investigation The only test that should be used to determine if a sample is CSF or not is immunofixation of beta-2 transferrin. Glucose oxidase testing is not acceptable and should be confined to the past. 23 , 24 Beta-2 transferrin is a protein involved in ferrous ion transport and it is also found in perilymph and aqueous humour. The sensitivity
of this test is 100 percent with a specificity of 95 percent. 25 ,26 Only a few drops of CSF is required and if necessary the sample can be posted to the laboratory for analysis,27 The physician should be aware that certain conditions cause abnormal transferrin metabolism and thus the beta-2 form can appear in the blood, which could potentially lead to a false-positive result. These are as follows: chronic liver disease, inborn errors of glycogen metabolism, genetic variant forms of transferrin, neuropsychiatric disease and rectal carcinoma?8,29 For this reason, some au thors recommend taking a simultaneous blood sample to exclude this possible source of error,30 whilst others do not feel this is necessary.ll,31 If the patient is unable to collect enough fluid for analysis, the diagnosis should be questioned as this is unusual when there is a genuine CSF leak. [** I*J IMAGING
Some authors favour computerized tomography (CT) cisternography (initially with metrizamide, or the newer agent iohexol). This has fallen from favour as it is an invasive procedure with the potential side effects of headache, nausea, vomiting or seizures 32 and is of no use in detecting inactive leaks. 33 With the advent of high resolution computerized tomography and magnetic resonance imaging (MRI) and fluorescein lumbar puncture, these modalities now form the mainstay of investigation. High resolution coronal scans (l-2-mm slices) can offer detection in up to 84 percent of cases in a large series,34 but these should be interpreted with caution if there has been a previous skull base surgery as they will almost inevitably show a large defect in the absence of a true leak.20 Axial views are helpful in detecting leaks from the posterior wall of the frontal sinus and sphenoid sinus. There is the possibility of both false-negative and false-positive findings, particularly after skull base trauma or a craniotomy, and the scans should always be interpreted in light of other clinical signs and investigations (Figure 129.4).35 [**] A T 2-weighted MRI is the preferred imaging modality of some authors and rates of detection of 100 percent are claimed. 36 ,37 A sensitivity of 80 percent was noted in a series of 36 patients who underwent surgical exploration 3S allowing verification of the scan findings. MRl is advisable 22 in the case of encephalocoeles to delineate the contents and vascularity of the sac before surgical exploration. [**] Most clinicians would use both modalities if doubt exists as to the site of the leak (Figure 129.5).
cr
Intrathecal dyes and markers
Figure 129.3
An MRI scan of an encephalocoele.
Historically, many dyes (methylene blue, indigo carmine) or radioactively labelled markers have been introduced intrathecally to aid leak detection. Only fluorescein has stood the test of time and is in common use today. It can be exceedingly helpful either preoperatively in an
Chapter 129 Cerebrospinal fluid rhinorrhoea I 1639
Figure 129.6
A 24-guage polymedic 'pencil-point' needle.
Figure 129.4 Bilateral fluid levels in the sphenoid sinus in a patient listed for a craniotomy. This proved not to be due to a CSF leak.
History suggestive of leak
!
8eta-2 transferrin, scope and high resolution CT scan
/ Positive beta-2 transferrin
/
Negative scope/HRCT
Positive scope/HRCT
t
t
T2-weighted MRI
Fluorescein LP at surgery
Surgery and fluorescein LP if possible multiple leaks
Negative beta-2 transferrin
Retest
t t
Negative
Reconsider medical diagnosis
~
Figure 129.7 Fluorescein tracking down the postnasal space from a defect in the roof of the posterior ethmoid sinus, not detectable on CT or MRI scanning.
T2-weighted MRI
~ Diagnostic fluorescein LP
Figure 129.5
Algorithm for management of CSF rhinorrhoea.
outpatient setting, intraoperatively or both. 39 Typically, O.25mL of 5 percent fluorescein is mixed with lOmL of CSF from a routine lumbar puncture,40 the mixture is introduced via a polymedic pencil~point spinal needle (Figure 129.6)41 and the patient is placed in the Trendelenberg position for approximately one hour. Then, endoscopic examination is performed, and if positive the fluorescein can be seen coming from the defect (Figure 129.7). The use of a blue filter on the endoscope light source can increase the ease of detection. If, at operation, fI uorescein is not seen then the
anaesthetist can temporarily raise the intracranial pressure, by making the patient cough on their endotracheal tube) as this will often cause the fluorescein to appear through the leak. Complications using a fluorescein lumbar puncture have been described but with higher concentrations than recommended here. They include knee and ankle clonus) seizures, opisthontos and cranial nerve defects. 42 None of the above complications have been permanent and their occurrence is extremely rare. Previous spinal surgery may prevent the use of fluorescein lumbar puncture.
Antibiotics There is debate as to whether antibiotic prophylaxis should be prescribed in patients with known CSF
.J ~,
_'_' __'''-
1640 I PART 13 THE NOSE AND PARANASAL SINUSES 43 rhinorrhoea. One meta-analysis by Brodie concluded that there is a significant reduction in the incidence of meningitis with prophylactic antibiotic therapy, although this report excluded one of the largest series that found the opposite. 44 Other authors do not agree and state there is no advantage or disadvantage of using prophylactic antibiotics. 45, 46 Others go further and would not recommend propylaxis in the absence of any intranasal infection as this can lead to a change in nasopharyngeal flora potentially causing a partially treated or gramnegative meningitis. 44 ,47 [**1*]
Surgery Once the site of the leak or leaks has been determined, the correct surgical approach that will give the maximal chance of a successful closure with the minimum amount of morbidity should be chosen. Traditionally, the two options available were a craniotomy or an extradural external approach. With the development of endoscopic sinus surgery, this is now the approach of choice with excellent success rates and minimal surgical morbidity.48 The exception to this is a defect associated with malignancy. INTRACRANIAL APPROACH This approach is via a craniotomy. The morbidity associated with this is significant and mortality can be as high as 2.6 percent. 6 It may still be the method of choice if there is coexisting intracranial pathology causing the leak that requires excision. It allows excellent visualization of the fistula from above. The associated morbidity includes almost certain anosmia due to retraction of the dura off the cribriform plate, postoperative intracerebral haemorrhage,49 cerebral oedema,50 epilepsy,51 frontal lobe dysfunction causing memory and concentration deficits, and potential osteomyelitis of the frontal bone flap. In addition, repair by this technique requires at least five days in hospital, hair loss along the incision line and a period without driving until the patient is judged to have recovered from the operation. The success rate achieved by one procedure from this approach varies from 50 to 73 percent. 52,53 The techniques described use a combination of pedicled periosteal flaps, dural flaps or fascial grafts. 53 Cranialization of the frontal sinus with a pericranial flap gives the best results when the craniotomy technique is used to repair anterior skull base 54 defects. [**]
EXTRACRANIAL APPROACH This remains the method of choice for accessing most leaks of the posterior wall of the frontal sinus that defy an endoscopic approach (Figure 129.8). A small minority that are medial can be repaired endoscopically. The
Figure 129.8 A CSF leak. originating from the posterior wall of the frontal sinus secondary to craniotomy.
approaches described are as follows: via an external ethmoidectomy for access to the cribriform plate and fovea ethmoidalis, transmastoid for defects in the tegmen and petrous temporal bone, transseptosphenoidal for access to the sphenoid sinus and via a coronal or eyebrow incision to the frontal sinus using an osteoplastic flap. In all these techniques, a variety of methods can be employed to close the defect. In the frontal and sphenoid sinuses the mucosa can be removed, the defect patched with a fascial graft and the sinus can be obliterated by packing with fat. 19, 50 This technique can be used in the other approaches and pedicled or free mucosal grafts from the nasal septum or turbinates can be used to support the graft. The morbidity associated with this procedure includes facial numbness, septal perforation and orbital complications, including diplopia and epiphora. 55 The success rates vary from 76 to 100 percent. 19, 50, 56, 57 An extradural approach does have the advantage that it minimizes the incidence of intracranial complications. [**]
ENDOSCOPIC SURGERY This is the method of choice for repairing the majority of CSF leaks. It has minimal patient morbidity and the success rates are excellent at 76-97 percent. 10, 11,13,14,58,59,60.61 A recent meta-analysis estimates the success rate at the first attempt to be 90 percent. 10 The patient will retain their sense of smell providing it was intact preoperatively.14 Many operative techniques and different types of graft material have been described. B • 40, 60, 61, 62, 63, 64, 65, 66, 67, 68 The grafts described include a nasal mucosal flap, free graft of nasal mucosa which may be a composite graft incorporating turbinate bone, conchal or septal cartilage, temporalis fascia and fascia lata which may be supported by fat. All of these techniques give a good success rate. All techniques require accurate localization of the leak intraoperatively. The edges of the defect are then freshened. The graft material is then placed into the defect as an
Ch apter 129 Cerebrospinal fI uid rh i norrhoea
underlay graft where possible. Some authors use fibrin glue to seal their graft, but we along with many authors do not feel this is necessary. The majority of authors support their graft using nasal packing, such as oxidized cellulose followed by a bismuth and iodoform paste pack (BIPP), and nearly all use antibiotic cover for the procedure. Some authors advocate using a lumbar drain to decrease intracranial pressure in the immediate postoperative period, but we have not found this necessary. The patient should be advised not to blow their nose, to sneeze with their mouth open and not to stifle sneezes to avoid any abrupt increase in intracranial pressure, whilst they have an active Jeak and for a month postoperatively. The supporting pack should be removed seven to ten days after surgery. The incidence of iatrogenic leaks from endoscopic sinus surgery is significant and if a leak is recognized during sinus surgery, it can and should be safely repaired during the same procedure. If the leak is caused by an encephalocoele, this can also be treated endoscopically in selected cases. 22 It is now possible to access the frontal sinus endoscopically by removing the 'beak' or posterior aspect of the anterior wall of the frontal sinus to enable wide access. Some patients may have a small leak following an endoscopic repair that seeps around the pack when the patient has been extubated. This can be disconcerting, but these often stop over the first few days and remain successful. [***1
REASONS FOR FAILURE Raised intracranial pressure is the most common reason for failure to repair a CSF leak. This diagnosis may be difficult to diagnose preoperatively as the leak lowers the intracranial pressure. Thus the diagnosis may only come to light following repair of the leak. The raised intracranial pressure may be due to an obvious cause, such as stenosis of the aqueduct of Sylvius, or it may be benign intracranial hypertension, which mainly occurs in obese young women with vague menstrual irregularities. A raised intracranial pressure is far more prevalent in patients with a spontaneous CSF leak. 61 , 62, 63 If imaging shows dilated cerebral ven tricles then a neurosurgical procedure to lower the pressure, such as a shunt, should be performed at the time of repair of the leak. 12
• The endoscopic closure of a, cerebrospinal fluid leak-is now the treatment- of-choice in the ~ajor'ity o( patients. • A meta-analy.sis .of the !llan,agement of C$F, leaks supports their endoscopic closure. [H]
I 1641
• Multiple skull base defects (> 5 cm) usually require a craniotomy with cranialization of .the frontal sinus,~da p~~lcrp.ni,i:U,fla'p. ':: .. • The priinary reaSon for failure.; is .if there .'is, .a high pressure, system and these' more . " . common in thegrotip',With sp(Hl~aneDus_ l.eaks and may requite a' shunt. • It is essential fo "confirm-- the diagnosis -of a CSF leak by -testing fluid using the . immunofixation ofbeta-2' transferrin.
are.
Best cUnical practice .I Endoscopic repair has revolutionized the repair of CSF leaks and minimized the morbidity and mortality associated with surgical repair. .I It is vital to confirm that any clear rhinorrhoea is CSF by testing it, using the immunofixation of beta transferri n. ./ Imaging techniques including high definition CT scans and T2-we[ghted MRI will detect the site of the leak in most patients. Where the site of a leak is uncertain or there is the possibility of more than one defect, then a pre- or peroperative Auorescein lumbar puncture will help in the remaining patients. ./ Rarely, defects of the posterior wall of the frontal sinus are inaccessible using the endoscope and then an extradura I approach is preferable. ./ Large or multiple defects may require a craniotomy when cranialization and a pericranial flap give the best results.
Deficiencies in current knowledge and areas for future research It is often not possible to predict which patients have a high-pressure system that will require a shunt. 61 Whilst the patient has an active CSF leak, the pressure is not raised and measuring it with a lumbar puncture is unhelpful. In the authors' experience, in the first few days after repairing the leak the pressure is often not raised, even in patients who go on to leak again and require a shunt. One study showed a proportion had a raised pressure after the leak was stopped, but interestingly there was no mention of these patients going on to have another leak.62 Whilst approximately 50 percent of repaired spontaneous leaks recur compared with less than 2 percent due to other causes if spontaneous leaks are excluded,61 it is not clear which spontaneous leaks require a shunt when these patients
.J._'_~
....
1642 I PART 13 THE !\JOSE AND PARANASAL SINUSES first present, unless there are signs of hydrocephalus or a raised intracranial pressure. Signs of an empty sella, skull base erosions or benign intracranial hypertension make it more likely that these patients will have a raised pressure system, but they are not specific or sensitive enough for the patient to justify a shunt at the first repair. At present, patients with a spontaneous leak undergo an attempt at repair and if this fails a shunt is inserted at the next attempt. It would be helpful to have a more accurate predictor of which patients would 61 require a shunt.
13.
14.
15.
16.
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computerized tomography and cerebrospinal fluid rhinorrhea. Archives of Physical Medicine and Rehabilitation. 1992; 73: 599-602. 33.
leaks. New techniques will improve the management of unilateral clear nasal discharge. British Medical Journal.
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50.
the craniotomy site. Neurosurgery. 1996; 39: 1114-22. McCormack B, Cooper PR, Persky M, Rothstein S.
Post KD. Intracerebral hemorrhage occurring remote from
Chow JM, Goodman 0, Mafee MF. Evaluation of CSF rhinorrhea by computerized tomography with
Extracranial repair of cerebrospinal fluid fistulas:
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Simmen 0, BischoffTh, Schuknecht B. Erfahrungen mit der abklarung von frontobasisdefekten, ein diagnostisches
Tech nique and resu Its in 37 patients. Neurosurgery. 1990; 27: 412-7. 51.
Tolley I'JS, Brookes GB. Surgical management of cerebrospinal fluid rhinorrhoea. Journal of the Royal
Eljamel MS, Pidgeon CN. Localization of inactive
52.
cerebrospinal fluid fistulas. Journal of Neurosurgery. 1995; 83: 795-8.
Tolley NS. A clinical study of spontaneous CSF rhinorrhoea. Rhinology. 1991; 29: 223-30.
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37.
College of Surgeons of Edinburgh. 1992; 37: 12-5.
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Neuroradiology. 1995; 1: 177-81. Stafford Johnson DB, Brennan P, Toland J, O'Dwyer AJ. Magnetic resonance imaging in the evaluation of 837-41. Gupta V, Goyal M, Mishra N, Gaikwad S, Sharma A. MR
closure. Journal of Neurosurgery. 1969; 30: 399-405. Donald PJ. Frontal sinus ablationby cranialisation: a report of 21 cases. Archives of Otolaryngology. 1982; 108: 590-5.
55.
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Ray BS, Bergland RM. Cerebrospinal fluid fistula: Clinical aspects, techniques of localization, and methods of
Kelley TF, Stankiewicz JA, Chow JM, Origitano TC, Shea J. Endoscopic closure of postsurgical anterior cranial fossa
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cerebrospinal fluid leaks. Neurosurgery. 1996; 39: 743-6. Hubbard JL, McDonald TJ, Pearson BW, Laws ER.
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Spontaneous cerebrospinal fluid rhinorrhea: Evolving
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concepts in diagnosis and surgical management based on the Mayo Clinic experience from 1970 through 1981.
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Hughes RGM, Jones NS, Robertson IJA. The endoscopic
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Brodie HA. Prophylactic antibiotics for post traumatic cerebrospinal fluid fistulae. Archives of Otolaryngology, Head and Neck Surgery. 1997; 123: 749-52. Moralee SJ. Should prophylactic antibiotics be used in the management of cerebrospinal fluid rhinorrhoea following endoscopic sinus surgery? A review of literature. Clinical Otolaryngology. 1995; 20: 100-2.
Gjuric M, Goede U, Keimer H, Wigand ME. Endonasal endoscopic closure of cerebrospinal fluid fistulas at the anterior cranial base. Annals of Otology, Rhinology, and
Moseley JI, Carton CA, Stern WE. Spectrum of complications in the use of intrathecal fluorescein. Journal of Neurosurgery. 1978; 48: 765-7.
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Neurosurgery. 1985; 16: 314-21. Yessenow RS, McCabe BF. The osteo-mucoperiosteal flap
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Wormald PJ, McDonogh M. 'Bath-plug' technique for the endoscopic management of cerebrospinal fluid leaks.
Journal of Laryngology and Otology. 1997; 111: 1042-6. Mirza S, Thaper A, McClelland L, Jones I'JS. Sinonasal .cerebrospinal fluid leaks: Management of 97 patients over 10 years. Laryngoscope. 2005; 115: 1774-7. This paper gives an account of the problems that relate to spontaneous CSF leaks and raised intracranial pressure.
1644 I 62.
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PART 13 THE NOSE AND PARANASAL SINUSES
Schlosser RJ, Wilensky EM, Grady S, Bolger W. Elevated intracranial pressures in spontaneous cerebrospinal fluid leaks. American Journal of Rhinology. 2003; 17: 191-5. Dunn CJ, Alaani A, Johnson AP. Study on spontaneous cerebrospinal fluid rhinorrhoe: Its aetiology and management. Journal of Laryn9ology and Otology. 2002; 119: 12-5. Stankiewicz JA. Cerebrospinal fluid fistula and endoscopic sinus surgery. Laryngoscope. 1991; 101: 250-6. Papay FA, IViaggiano H, Dominquez S, Hassenbusch SJ, Levine HL, Lavertu P. Rigid endoscopic repair of paranasal
66.
67.
68.
sinus cerebrospinal fluid fistulas. Laryngoscope. 1989; 99: 1195-202. Hao SP. Transnasal endoscopic repair of cerebrospinal fluid rhinorrhea: An interposition technique. Laryngoscope. 1996; 106: 501-3. Mattox DE, Kennedy DW. Endoscopic management of cerebrospinal fluid leaks and cephaloceles. Laryngoscope. 1990; 100: 857-62. Simmen D, Jones N. Skull base surgery. In: Simmen D, Jones N (eds). Manual of endoscopic sinus surgery and its extended applications. Chapter 15, Stuttgart: Georg Thieme Verlag, 2005: 240-55.
130 Granulomatous conditions of the nose DAVID J HOWARD AND VALERIE J LUND 1645 1645 1649 1653 1653 1654 1655
Definition Sa rco idosis Wegener's granulomatosis Churg-Strauss syndrome Eosinophilic granuloma Giant cell granuloma Cho lesterol gran uloma
• ,
.
1655 1657 1657
Granulomatous neoplasia Key points Best cl i ni cal practice Deficiencies in current knowledge and areas for future research References
. •
.
.
~
'..
1657 1657
. . . ,- r ••
.r
#.,.
,.
~..
....
I
The data in this chapter are supported by a Medline search using the key words granulomatous disease, Wegener's granulomatosis, sarcoidosis, nose and paranasaJ sinuses. Levels of evidence 1-4 and clinical recommendations grades A-D have been used throughout.
DEFINITION The principal element of a granulomatous condition is self-evidently a granuloma, consisting of macro phages, epithelioid cells and mu1tinucleated giant cells. This histologic configuration is encountered in a number of infective inflammatory and neoplastic conditions of the nose and sinuses (Table 130.1) and also forms part of a spectrum of conditions in which vasculitides plays a role. Inflammation of the blood vessels may be primary or secondary and is further classified according to the size of vessel affected (Table 130.2). Whilst many of these conditions are systemic, they may preferentially target or present in the upper respiratory tract and the ear, nose and throat (ENT) surgeon must maintain a continuous low threshold of suspicion to establish the diagnosis at the earliest opportunity.
frequently involves lymph nodes, skin, lungs, eyes, liver, spleen and the small bones of the hands and feet It is found throughout the world, although there is a higher incidence in the southeast United States and Scandinavia where 64 out of 100,000 people were found to have pulmonary sarcoidosis in Stockholm. The ratio of occurence in black to Caucasian people is 12:1 in the United States. 3 , 4 Cutaneous lesions were first described by Besnier s in 1889 as 'lupus pernio', a term that is still used but the generalized nature of the condition was recognized ten years later by Boeck6 who noted four of his nine patients had nasal disease which preceded the skin lesions. The distribution of clinical manifestations to some extent reflects the bias of the treating physician, but it is generally agreed that nasal manifestations are almost always part of multisystem sarcoid which may have been present for some years 0-20 years, mean 4.4 years).7
SARCOIDOSIS
Age and sex
Introduction
Sarcoidosis is a conclition of young adults between the third and fifth decades with a female preponderance of 2: 1) which is higher in those with upper respiratory tract manifestations.
Sarcoidosis is a systemic condition of unknown aetiology which may affect any part of the body, but most
1646 I
PART 13 THE NOSE AND PARANASAL SINUSES
Table 130.1
Granul omatous co n d itio ns affect i n g the nose a n d s i n u ses. "
Inf�ctivea
",
'
J.'
N�Pla� k • �
•
1
� ',
'
•
Bacteria Tubercu los i s
Myobacterium tuberculosis
Wegener's gra n u lomatosis
T-ce l l lymp homa
Leprosy
Myobacterium leprae
Sarcoidosis
( M i d line let hal
Rh i noscleroma
Klebsiella rhinoscleromatis
Churg-Strauss syndrome
Syp hilis
Treponema pallidum
Cholesterol granu loma
Actinomycosis
Actinomyces israeli
Eos i n ophi l i c g ranuloma
granuloma)
Fungal Asperg i l lus
Asp. fumigatus, flavus, niger
Zygomyc.osis
Conidibolus coronatus Rhizopus oryae
Derrnatacietes
CUlVularia Alternaria Bipolaris
Rh inos porid iosi s
Rhiosporidiosis seeber;
B lastomycosis
Blastomyces dermatitidis
Histop lasmosis
Histoplasma capsulatum
Spo rotrichosis
Sporotrichum schenki;
Cocci d i 0 i d i mycosis
Coccidiodes immitis
Cryptococcus neoformans
Protozoa
Le ish rna niasis
Leishmania spp.
aCovered in Chapter 115, Specific chronic infections and Chapter 114, Fu ngal rhinosinusitis. Modified from Ref. 1, with permission.
Table 130.2
Pri,mary vascul itis according to different vess e l size.
' ;'�4��,�;�e�:i��';�'�;6';'�ro a:l� !p��d.}��f.eJ��
.
Ta kayasu arteritis Giant cell (tem poral) arteritis
'
;
�
M,ed'ium�si'z�d i,I,nd .
'·$lY,la·iL'DI·�.od".y�S�� ,I� Polyarte r itis nod osa C hurg-Strauss
Granulomatous angi itis of the central nervous system
syndrome Wegener's granulomatosis
Small blood '
vessels
i '"
.
. Mi.�c�na·')eo·us.· ·.StcoJl(i�a.'1':v:is cunti5 co n d itio n s . ; . .� .;c .
Bue rge r's
Microscopic
disease
polya n g i it i s
Schonlein-Henoch
Be hr;et's d i sease
synd rome Cutaneous
Kawasaki
leu kocytociastic
disease
an giitis
,"
'•
. " ".
>:.�, .
I nfection-re lated vascu litis Ser um sick ness or d rug hypersensitivity related vasculitis Hypocomp leme ntemic u rticarial vasculitis Vasc u l itis associated with r h eumatic connective tissue diseases VaSCU l i t i s associated with other systemic diseases Ma ligna nc.y-rela ted vascul itls Post-t ran s p lant vasculitis Pseud ovasculit ic syndromes ( myxoma, e n d ocard itis, Sneddon synd rome)
Reprinted from Ref. 2, with permission.
Aetiology The aetio lo gy
of sarco ido si s is unknown, but susp1ClOn on various infective agents, chemicals (includ ing beryllium and zirconium), pine po ll en and even 8 peanut dust. Whilst the type IV del ayed hypersensitivity reaction is often depressed in sarcoid patients, there is no g e neral de p re ssi o n of celt-mediated i mmunity and type I has fallen
and humeral ant ibo d y responses
are normal. However, protein levels are raised in particular gamma globulin in those of African descent.9 There also a ppe ars to be an increase in c irculat ing i mm u n e complex es in the acute phase with a decrease in circulating lymphocytes, particularly T cells of which 10-20 percent are atypica1.10 One suggegtion for the path og enesis of sarcoid is that it is a process initiated by an ant ig e n presenting ceil, probably total plasma
Chapter 130 Granulomatous conditions of the nose I
an alveolar macrophage. Subsequently, there is an IL-1 and 1L-2 driven T-Iymphocyte proliferation. Monocytes are attracted from the blood by monocyte chemotactic factor (1L-8) and held at the site of reaction by macrophage migration inhibition factor. Monocyte acti vation by lPN-gamma occurs and this stimulates calcitriol production, which in turn causes macrophage fusion to epithelioid cells and granuloma formation. The persis tence of the granuloma may be ascribed to continued antigenic stimulation, failure of suppressor-regulating mechanisms and/or abnormalities in the regulation of the cytokine network.
In the nose, the mucosa often has a rather character istic granular appearance, sometimes referred to as a (strawberry skin' (Figure 130.1). The mucosa refers to the tiny pale granulomas against an otherwise erythematous mucosa. This is generally very friable and leads to complaints of nasal congestion, crusting and mucopuru lent discharge which is often blood stained (Table 130.3).
Table 130.4
In 1985, Scadding and Mitchellll recommended the following definition (sarcoidosis is a disease characterized by the formation in all of several affected organs or tissues of epithelioid cell tubercules, without caseation though fibronoid necrosis may be present at the centres of a few, proceeding either to resolution or to conversion into hyaline fibrous tissue: Thus the sarcoid granuloma is characterized by epithelioid cells surrounded by lympho cytes and fibroblasts but devoid of caseation. Crystalline or calcified inclusion bodies are sometimes seen, e.g. Schau mann bodies. However, the histological picture is not diagnostic and similar granulomas can occur in a number of other conditions including berylliosis and fungal disease.
Frequency of clinical involvement of
extrapulmonary organs in sarcoidosis.
Extrathoracic sites
i I�
Histology
1647
"'''_''''_.' .
Peripheral nodes
73
Skin
32
Liver
21
Eye
21
Spleen
18
Bone
14
Salivary glands
6
Joints
6
Heart
5
Nervous system
5
Kidneys
4
Nose and mouth
3
Lacrimal glands
3
Skeletal muscle Larynx Stomach and intestine Uterus
Clinical features Sarcoidosis is a multisystem disease primarily affecting the lower respiratory tract but which may involve the upper respiratory tract, often more frequently than previously realized.12 The extent to which this occurs varies from report to report (Tables 130.3 and 130.4). Ninety percent of patients with sarcoidosis will have evidence of thoracic involvement either within the lung itself or affecting intrathoracic lymph nodes and classi cally the disease has been staged dependent on the extent of this involvement. Table 130.3
Incidence
(0/0)
of symptoms in patients with nasal
sarcoidosis,
Nasal stuffiness and obstruction
88
Crusting
63
Blood-sta'lned discharge
37
Purulent discharge
30
Facial pain
22
Mucoid discharge
15
Anosmia Revised from Ref. 7. with permission.
4
Figure 130. 1
Sarcoidosis. Typical appearances of nasal lupus
pernio,
-
.___.__
.1
____
______ _
1648 I
PART 13 THE NOSE AND PARANASAL SINUSES
The anterior nasal septum may perforate, particularly if traumatized, for example, by surgery which may lead to collapse of the nasal bridge. The nasal bones may be involved by a process similar to the dactylitis seen in the fingers and patients may present with a soft tissue mass or expansion of the nasal bridge associated with thickening and discolouration of t he overlying skin as in classic lupus pernio (Figures 130.1, 130.2 and 130.3). This may respond dramatically to medical treatment. 13 The para nasal sinuses may also be affected by the process andlor become secondarily infected. As a consequence, facial pain is experienced by one in five patients with nasal sarcoid and the sense of smell may be affected due to
Figure 130.2
Sarcoidosis. Typical appearances of lupus pernio
on the cervical skin.
mechanical obstruction of the olfactory cleft by crusting or fibrosis or as a result of direct neuropathy. In addition to nasal manifestations, lymphoid hyper plasia and adenoidal enlargement can lead to otitis media with effusion and sleep disturbance may result from involvement of the tonsils, soft palate, naso- and oropharynx. The soft tissue of the supraglottic larynx may become thickened and increasingly swollen produ cing dyspnoea and change in voice quality.
Diagnosis Unfortunately, no one test is pathopneumonic for sarcoidosis. Diagnosis usually relies on a combination of histology, imaging, haematology and clinical acumen. The most reliable test, the Kveim, has regrettably been withdrawn in the UK over fears of virus and prion transfer though without any substantive evidence for this.14 The angiotensin converting enzyme (ACE) is often elevated sometime during the course of the disease ( rai sed in 83 percent of patients with active sarcoid), IS but it is also elevated in a number of other conditions such as tuberculosis, leprosy and primary biliary cirrhosis. The erythrocyte sedimentation rate, serum globulin and serum and urinary calcium levels are sometimes elevated and a full blood count may show mild anaemia, leucopenia, thrombocytopenia and eosinophilia, but clearly none of these tests are specific. Investigation of the lower respiratory tract including imaging (chest x-ray, computerized tomography (CT)) (Figure 130.4), perfusion studies, bronchoalveolar lavage and gallium-67 scanning, are generally performed com bined with biopsy of potentially affected tissue such as the lung, skin and lymph nodes.16 Biopsy of nasal mucosa is only of use if it appears abnormal as random biopsy of macroscopically normal mucosa is usually negative (in 92 percent of cases).7 Plain x-rays of the nasal bones may show rarefraction or punctate osteolysis in up to a quarter of cases17 and this, together with soft tissue changes, may be shown by CT scanning (Figure 130.5). This will also demonstrate secondary involvement of the sinuses though will not distinguish between active disease and secondary infection . Magnetic resonance imaging (MRI) of the brain is increasingly undertaken to establish central nervous system (CNS) involvement.
Treatment
Figure 130.3
Sarcoidosis. Coronal section through nasal septal
cartilage showi ng an erosion by 9 ranu lomatous lesions.
Some patients with limited disease undergo spontaneous remission without specific treatment, though the maj ority are offered some form of systemic therapy. This consists of a combination of oral steroids, methtotrexate and hydroxychloroquine, depending on the severity of the disease. Topical treatment may be offered for nasal
----
I 1649
Chapter 130 Granulomatous conditions of the nose
though endoscopic sinus surgery can be undertaken for secondary bacterial infection with success in selected
cases.18
[**]
WEGENER'S GRANULOMATOSIS
Definition A condition, characterized by granulomatous inflamma tion
involving
the
tract
respiratory
and
necrotizing
vasculitis affecting small- to medium-sized vessels (e.g. capillaries, venules, arterioles and arteries) with necrotiz ing
glomerulonephritis,
common. 19 Although the 20 after his article on
is
condition bears Wegener's name
rhinogenic granulomatosis in 1939, it should really be attributed to Klinger. 21 The pathological hallmark is the coexistence of vasculitis and granulomas and classically involves
a triad of
airway,
lung
re nal
and
disease.
However, it is i ncreas in gly recognized that limited forms
of the condition can occur.22. 23 Thus,
the true
in stan ce of
the condition is difficult to determine. Whilst up to 1967 only 138 une q uivocal cases had been recorded
in the
literature,24 clearly this was a gross underestimate of the true incidence which is now becoming apparent largely Figure 130.4
Posterior-anterior chest x-ray showi ng typical
pulmonary infiltrates in systemic sarcoidosis.
due to the introduction of the antineutrophil cytoplasmic 25 antibody test (ANCA).
Age and sex The age of presentation in our own cohort of over 90 p atients has ran ged from 15 to 73 years, although it has been reported in children. Halstead's series26 reports significant numbers of patients under 25 years of age and these young patients were usually noted to present with a generalized form.
Aetiology The
aetiology
of
Wegener's
granulomatosis
remains
unknown. Its inflammatory nature and its resemblance to polyarteritis nodosa suggests that it represents some form Figure 130.5
Coronal CT showing sclerosis and osteolysis of
the nasal bones associated with a soft tissue mass in nasal sarcoid.
hypersensitivity
reaction
with
that this
an
immune
been postulated
may be related to inhaled bacteria, which would
explain the frequency with which the respiratory tract is involve d. The deposition of the immune complexes is
symptoms including intranasal steroids, either sprays or drops, glucose and glycerine drops and various forms of nasal douching and irrigation. Nasal symptoms may also be -helped by the systemic medication. Surgery generally is contraindicated for both cosmetic or functional indica tions,
of
response to an unknown stimulus. It has
particularly
in the presence of active
disease,
thought to
be resp ons ibl e for vasculitis
in other condi
tions, but these have only been demonstrated in a
small
proportion of patients with Wegener's granulomatosis. McDonald and De Remee27 studied biopsies subjected to
immunofluorescence microscopy, but rarely found de posits
of immunoglublin
or
complement.
aetiological and diagnostic point of view,
From the
an
most
_ __. _ _ 1 ____ ._---=----
1650 I PART
13 THE NOSE AND PARANASAL SINUSES
important finding of recent years was that reported by van der Woude in 198528 who found antibodies reacting with the cytoplasm of ethanol-fixed granulocytes and monocytes in 25 patients with Wegener's granulomatosis. It then became clear that two main forms of ANCA could be found: perinuclear or pANCA and cytoplasmic or cANCA. In general, patients with Wegener's granuloma tosis have cANCA, whereas pANCA (and occasionally also cANCA) may be found in some other conditions,
PULMONARY SYMPTOMS The majority of patients with active disease experience pulmonary symptoms at some point, cough, haemoptysis or pleuritic pain. The pulmonary lesions often cavitate and can be seen radiologically in most patients. These may be the presenting symptoms and the diagnosis may be aided by flexible bronchoscopy and lung biopsy. Encapsulated lung abscess formation can occur.
such as microscopic polyartertitis. The tests may be done by indirect immunofluorescence or radioimmunoassay 9 30 and titres correlate well with disease activity.2 ,
RENAL SYMPTOMS Between 30 and 90 percent of patients will develop renal symptoms, although the organs may be spared in more limited forms of the disease. Both casts and red cells appear
Clinical features
in the urine and early treatment is vital since damage is
Although the condition is characterized by necrotizing granulomas with vasculitis
of the
upper and lower
respiratory tracts and in the focal necrotizing glomer ulonephritis, any part of the body may be affected and in the active cases this involvement may be widespread at the onset. The frequency with which different sites
are
irreversible. Microscopic evaluation of a midstream speci men of urine remains a simple but important test in the diagnosis and management of Wegener's granulomatosis. Renal biopsy is not essential but it must be remembered that Wegener's is one of a number of diseases which produces segmental or diffuse glomerulonephritis.
involved, both at presentation and subsequently, varies with the interest and specialty of the reporting physi31 Clans. As 1ate as the early 1970s, Wegener's granuloma. tosis remained a serious and lethal disease with patients frequently dying within a six- to eight-month period. Rapid diagnosis remains of great importance since a fulminating course with a fatal outcome can occur in as little as 48 hours. Duration of symptoms before a diagnosis is made remains highly variable and can be more than a year in some cases or even longer. The possibility of latent, incomplete and limited forms of the disease, as well as the classic 'full blown' condition is now recognized, though it is unknown whether all limited forms eventually progress and what triggers this trans formation. However, it is apparent that most patients
OCULAR SYMPTOMS The most common ocular manifestations of Wegener's granulomatosis are conjunctivitis, dacrocystocystitis, epi scleritis and corneal ulceration, but optic neuritis and retinal artery occlusion can also occur. Approximately 20 percent of patients may experience proptosis from a granulomatous mass' within the orbit or extending from the adjacent sinuses
(Figure 130.6). Delayed or inadequate
treatment is responsible for failure to control many orbital systems and loss of vision has been frequently documen ted. Blindness, unilateral or bilateral, is an important cause of morbidity in Wegener's patients, inadequate ,and intermittent systemic therapy predispose this problem.
start with relatively minor ENT symptoms, which may be overlooked by both the patient and the doctor. These often
include
a
variable
degree
of
epistaxis,
nasal
obstruction and bloody crusts in the nose. Destruction of the intranasal structures including the septum may follow, leading eventually to nasal collapse. Minor nasal surgery and/or repeated biopsies during this period may add to the problem. In addition, many patients may 3 complain of significant facial pain. 2 Patients frequently complain of progressive malaise, pyrexia,
weight
loss
disproportionate to
and the
notably
clinical
feel
very
findings.
unwell,
This
often
results in a delay in diagnosis. The nose and sinuses are involved in more than 80 percent of patients, though it is important to point out that while there is intranasal destruction of bone and cartilage in some patients with Wegener's leading to septal perforation and a character istic nasal collapse, there are none of the gross destructive changes of the midfacial skin seen in T-cell lymphomas and basal cell carcinomas.
ORAL SYMPTOMS A wide variety of oral lesions have been described, the most commonest being a hyperplastic granular lesion of the gingiva beginning in the area of the interdental papillae. If a tooth is lost, the socket may fail to heal. Extensive ulcerative stomatitis has also been reported.
OTOLOGIC SYMPTOMS Approximately one-third of patients may develop acute otitis media or otitis media with effusion. There may be deafness, pain and suppuration. Facial nerve paralysis has also been recorded. Both conductive and a sensorineural hearing loss occur and while otitis media with effusion may be secondary to inflammatory changes within the nasal cavity, Wegener's granulomatosis of the temporal bone
with necrotizing
granulation
tissue
tympanic cavity has been documented.
filling the
Chapter changes
130 G ranulomatous conditions of the nose •
and
are
contraindicated
inflammation and scarring.
leading
to
Localized disease
1651
further with a
positive c-ANCA test has been well documented33 and requires ruling out, particularly in an adult presenting with an apparently idiopathic subglottic stenosis. Ex tensive laser resection of subglottic stenosis caused by Wegener's is frequently not only unsuccessful, but aJso causes further stenosis. Gentle dilation, occasional soft internal
stenting and
localized
steroid
injection
are
advised?4
OTHER SYMPTOMS The generaJized vasculitis may produce ulceration of the skin, particularly of the distal arms and legs. Polymyalgia and polyarthritis have been described. Direct nervous
of patients in latter is caused by granulomatous invasion of neuraJ tissues, intracerebral or meningeal granulomas, as well as neuritis vasculitis. Any cranial
system involvement occurs in 10-15 percent some series.
nerve
may
This
be
involved.
The
ability
of
Wegener's
granulomatosis to affect any organ in the body makes it a possible diagnosis in a wide range of obscure and bizarre clinical presentations.
Diagnosis The cANCA test is positive in 95 percent of patients with generalized active disease. This sensitivity falls to 60 percent with localized disease affecting the respiratory tract. Thus, in addition to the cANCA, a full blood count, erythrocyte sedimentation rate (ESR), c-reactive protein
(CRP) level, serum urea and creatinine, as well as any other test relevant to the differential diagnosis, e.g. serum angiotensin converting enzyme (SACE) should be re quested. Urine analysis for casts and red blood cells together with renal clearance studies, chest x-ray and other respiratory function tests should be performed. Tissue biopsy may be helpful, bu t in isolation is rarely diagnostic
and
has
been
superseded
by
the
above
investigations. When biopsing the nose, it is important to obtain representative tissue ideally from the septum and turbinates. The main histological features, though not pathopneumonic, are as follows:
Figure 130.6
(a,b) Axial CT scans showing sclerosis and
opacification of the nasal cavity associated with widespread
•
vasculitis is mandatory for the diagnosis and
•
granulomas are of the epithelial cell type being may show fibrinoid necrosis, but can also be non-necrotic; large, irregular and lined with histocytes. They
infiltration of the orbit in Wegener's g ranulomatosis. •
LARYNGEAL AND TRACHEAL SYMPTOMS LaryngeaJ involvement is unusual, but when present the subgl ottis and upper trachea are most commonly affected.
This may present a serious problem with laryngotracheal obstruction. Biopsies frequently show only nonspecific
fibrinoid vascular necrosis is a common finding; the
multinucleated giant cells are often present and eosinophils are numerous.
In those patients with a negative c-ANCA and biopsy, in whom the r e is clinical suspicion of Wegener's, the c ANCA should be repeated and patients kept under regular review.35
.f�_,- ,
1652 I PART Table tology
13 THE NOSE AND PARANASAL SINUSES
130.5 shows the American College of
criteria
for
the
class ification
of
Rheuma
Wegener's
gr anulomatosi s.
with exacerbation of disease in some individuals. None
theless, regular review and monitoring of haematologlcal,
pulmonary and renal indices is vital [**] Unfortunately, despite many reports of good
initial
control of Wegener's gran ulomatos is using a combination
Imaging
of
prednisolone
azathiprine, the
Computerized tomography a nd MRl demonst rate muco
and
either
cyclophosphamide
or
majori ty of long-term studies emphasize
the cont inuin g problems faced by these patients. Harri
(Figure 130.7).37 E ighty- six percent showed
son's experience during 27 years at the Royal Natjonal Throat Nose and Ear Hospital 40 showed the varied course
nonspecific mucosal thickening in the nasal cavity or
which this disease can take. Prednisolone (60-80 mg/day)
destruction and 50 percent new bone for mation in the
rog/day) should produce a dramatic improvement in
the sinus cavities. In addition, the or bit was
acute disease. The ESR may fall slowly and gradual
sal thickening and superadded infection in a series of 28 patients
paranas al sinuses, 75 percent showed evidence of bone
walls of
affected in 30 percent of these pa tients. Whilst
the
with cyclophosphamide (2 mg/kg) or azathioprine (200
reduction of both dru gs has to be based on clinic a l and
d i agnosis of sys temic Wegener's granu lomatosis is made
Labor a tory assessment. It is not possible to generalize, but
cl ini ca lly,
with the exception of
in
a patient without a history of previous
sino nasal surgery the combination of bone destruct ion
the fulminating, progressive cases,
initial control is now the norm . In Harrison and Lund's
and new bone forma tion on CT is virtually diagnostic of Wegener's, especi a lly when accompanied on MRI by a fat signal from the sclerotic sinus wall. These changes may be importan t di a gnostically in localized sinonasal Wegener's, where the clinical diagnosis may be uncertain and the cANCA test can be negative. Imaging of the chest may show progres sive cavitation followed by fibrosis.
Treatment The report by Fahey et
al.38 in
1954, suggesting that steroids
and a variety of cytotoxic drugs could improve short-term prognosis, has subsequent ly resulted in
over 90 percent of
patients with Wegener's granulomatosis obtaining pro longed remission. Renal damage prior to commencing treatment is the major prognostic factor and therapy should be begun as soon as the diagnosis is suspected rather than waiting for histologica l verification. The ESR, CRP
all been used to monitor clinical it was hoped that the demonstration of a rising titre of cANCA might be used to predict and pre em pt imminent relap se. Unfortunately, this has not proved as useful as hoped. 39 The cANCA frequently becomes negative when the disease is under cont rol, but this is not
Wegener's in the nose with septal destruction hyperostosis and
always the case and conversely may remain negative even
opacification of the sinuses together with orbital infiltration.
a nd c-ANCA test have
progress and
Table
130.5
Figure
130.7
Coronal CT showing typical appearances of
1990 ACR criteria for the classification of Wegener's granulomatosis (number of criteria present rule).a
Cr-iteria·
Definition
'�
"
"
>�
,� ,�'
'��.:.:- " ' : ., ..�: ';'!L';; ;:;� "t��. ,....r
)
" ,
Nasal or oral inflammation
Development of painful or painless oral ulcers or purulent or bloody nasal discharge
Abnormal chest x-ray
Roentgenogram of the chest showing the presence of nodules, fixed infiltrates or cavities
.�:
Urinary sediment
Microhematuria (over five red blood cells/HPF) or red cell casts in the urine sediment
Granulomatous inflammation on
Histologic changes showing granulomatous inflammation within the wall of an artery or in the peri
biopsy
or extravascular area (artery or arteriole)
aFor classification purposes, a patient shall be said to have Wegener's granulomatosis if he/she. has satisfied any two or more of thes e four criteria. This rule is associ ated with a sensitivity of 88.2 percent and a specifity of 92.0 percent. After Leavi tt et 01.16
Chapter 130 Granulomatous conditions of the nose
I 1653
100
Finally, the nasal symptoms can be managed by topical
percent immediate control in 48 cases and, over a 20-
preparations including an intranasal steroid, glucose and
series,
azathioprine with prednisolone produced
year follow up in some patients, no patients have had
glycerine drops and alkaline/saline douching and irrigation.
significant complications such as alopecia, leucopenia or
It has been recommended that surgeons should not
iatrogenic haemorrhagic cystitis. In contrast, a major
undertake augmentation rhinoplasty and/or closure of the
complication of cyclophosphamide is leucopenia, and
septal perforation unless the disease process has been
alopecia may occur even with low dosage. Approximately
quiescent for some years. A series of 12 out of 13 patients in
40 percent of patients taking this drug may have some
remission from Wegener's ultimately had a successful result
bladder bleeding which is a considerable disadvantage in
from dorsal augmentation without reactivation of disease.44
patient management when the urine is being assessed for the possibility of red cells. In view of the unavoidable side effects of continued steroid and cytotoxic treatment, there is an obvious desire by both the patient and the doctor to reduce or stop treatment as soon as possible. However, there is no doubt that this is a cyclical disease and clinical flare up may result in
considerable tissue reaction,
damage and subsequent fibrosis. These are best avoided. Outstanding examples of this are the fibrosis which in the orbit can result in painful proptosis, visual defects or blindness, and in the lungs with increasing pulmonary fibrosis with consequent severe dyspnoea. Although both ESR and ANCA tests are of value in monitoring the disease, change can occur suddenly and the patient is often aware of variations in their well-being in the absence of altered haematological tests and,
in our
experience, some are particularly sensitive to changes in dose. They should, therefore, be listened to with care and their medications altered appropriately. In Harrison and Lund's series, there are patients who
CHURG-STRAUSS SYNDROME In 1951, Churg and Strauss45 described a syndrome of systemic vasculitis and asthma. Churg-Strauss syndrome is defined as eosinophil-rich and granulomatous inflam mation involving the respiratory tract and necrotizing vaculitis affecting small- to medium-sized vessels and associated with asthma and eosinophilia.46 Histologically, the
lesions
interstitial
show a
necrotizing
granulomas
and
giant
cell
eosinophilic
vasculitis, pulmonary
infiltrates. Patients present with bronchial asthma, nasal polyps and eosinophila, combined with systemic vascu litis.
There
may
also
be
nasal
crusting
and
septal
perforation, but the condition may be differentiated from Wegener's by
the
other
elements
of
the
syndrome.
Treatment again is primarily with oral steroids and the usual combination of medical and surgical therapy for the nasal polyps as required.
[**]
have, after many years, managed to stop their medica tions, but it has been impossible to predict the likelihood of
any
individual
particularly
after
patient
suffering
immunological
late
recurrence,
challenges
such
EOSINOPHILIC GRANULOMA
as
influenza or pregnancy. It requires a delicate balance
Definition
between the intrinisic risks of a hazardous relapse against the
surety
of
drug
toxicity,
and
for
the
moment
permanent follow up remains essential. Whilst cyclophosamide has greater side effects, it is generally used for the more severe disease with renal involvement. It may be used in high-dose intravenous pulsed form in severe disease. Plasma exchange immu noglobulin infusion and other drugs, such as methotrex ate and cyclosporin, have been or are being used in some centres.
Mycophenolate mofetil is being used as an
alternative to azathioprine by some physicians. Finally, it should be remembered that all patients on long-term
This
is
a
clonal
proliferation
of
Langerhans'
cells
associated with a heterogeneous inflammatory infiltrate of eosinophils, histiocytes, lymphocytes, plasma cells and neutrophils. It is now regarded as a neoplastic condition with a variable clinical course.47,48 It is also considered a manifestation of histiocytosis-X and is sometimes referred to as Langerhans' cell histiocystosis and Langerhans' granulomatosis.
Clinical features
oral steroids should undergo bone densitometry and be offered one of the bisphosphonates, such as alendronate sodium, if there is any evidence of bone 10SS.41 Once remission has commenced, medications may be
Whilst all organs may be affected, eosinophilic granuloma predominantly occurs in bones. The skull is a common site of involvement, in particular the temporal, frontal
reduced but it is important not to do this too precipitately
and parietal bones. A wide age range from infancy to over
or an acute exacerbation may occur. After many years of
80 years has been recorded, but about 85 percent of cases
oral steroids, patients may require a small maintenance
are detected in the first three decades of life and 60
dose of 5-10 mg of predinsolone per day to compensate
percent are young children. Males are affected twice as
for. irreversible adrenal suppression. The possible role of
frequently as females. The usual presentation is a painful
infection in the activation of disease has led to the use of
swelling of the involved bone, often for many months
cotrimoxazole in some milder cases.42, 43
associated with cervical lymphadenopathy. Mandibular
1654 I PART 13
THE NOSE AND PARANASAL SINUSES
lesions produce toothache, gum ulceration and loose
otherwise referred to as 'giant cell reparative granuloma' or
teeth, whereas involvement of the temporal bone may
'giant cell reaction of bone'. It was first described by Jaffe
simulate acute mastoiditis.
in
195351 in the jaws, though other craniofacial sites have
been reported. These lesions commonly occur in children and young adults and are benign despite the presence of
I maging
mitoses which may cause the inexperienced pathologist
Radiological evaluation shows punched out bony lesions and in the jaws radiolucent areas around the teeth. Lesions in the skull often show bevelled margins due to angulated destruction of the cortical bone.
difficulties. The giant cells do not contain multiple nuclei as
in true
giant
cell tumours.
Bilateral symmetrical
involvement of the jaws by giant cell granulomas is seen
in cherubism, a rare inherited childhood condition (Figure 130.8).52.53 True giant cell tumours involving the craniofacial bones are quite rare especially in children
Histology Macroscopically the lesions are soft and yellow or red brown in colour and biopsy material is best obtained by curettage.
Microscopically,
the
Langerhans'
cells
are
mixed with other inflammatory cells including histocytes, eosinophils, plasma cells and neutrophils. The cytoplasm of
the
Langerhans'
Charcot-Leyden
cells
crystals
may
be
may be
eosinophilic
found
in
and
ordinary
histiocytes. There is intense osteoclastic activity at the periphery of the granuloma due to prostanglandin and cytokine production by the Langerhans' cells.49 During the healing phase of the granuloma, the stroma becomes increasingly fibrotic. Prognosis has been associated with increasing numbers of eosinophils.
Treatment Treatment depends on whether or not the eosinophilic granuloma is localized and/or solitary. The ratio of solitary to polyostotic disease is probably > 5: 1 and is sometimes termed 'type II disease'. In addition, some have been noted to spontaneously regress and disappear over time. With unifocal disease the combination of curettage/excision and radiotherapy is usually curative provided that no new lesions develop within approximately one year. However a proportion of the patients will develop a generalized disease with hepatosplengomegaly, lymphadenopathy, skin lesions and further osseous lesions, so called 'type I disease'. The course of this can be rapid with a poor prognosis and additional chemotherapy has been advocated in these circumstances. At present the most effective chemotherapy regime appears to be etoposide and steroids given for periods
of
12 months or more dependent on the
response.50 Recently, alpha interferon and bone marrow transplantation have also been used successfully.
GIANT CELL GRANULOMA Definition Benign granuloma-like aggregates of giant cells in a fibrovascular stroma characterize this benign condition
Figure 13q.8 (a,b) Coronal CT scans of upper and lower jaw showing typical appearances of cherubism.
Cha pter 130 Granulomatous conditions of the nose
and
young
microscopic
adults.
To
appearance
add of
to
giant
the
confusion,
cell
the
granulomas
is
I 1655
duration of symptoms of three years. The lesion may affect the maxilla or frontal sinuses producing expansion
indistinguishable from that of solid variant of aneurysmal
of the bone, cosmetic deformity and displacement of
bone cyst and must also be distinguished from the giant
adjacent structures, such as the globe.
cell lesions associated with hyperparathyroidism.
Imaging
Clinical features Pain and swelling over the affected bone most commonly occurs though diplopia, while frontal headache, hearing loss, vertigo and tinnitus have also been reported. Most patients are under 20 years of age and there is a female to
The lesion produces a cyst-like expansion of the bone andlor sinus which is opaque on CT and does not . enhance with contrast. A very high signal is produced on all MRI sequences.
male preponderance of 2: 1. The maxilla and mandible are most commonly affected followed by the sphenoid and tempora1 bones. 51 ' 5 4
Histology
Imaging
ing
It has a typical appearance of granulation tissue contain foreign
body-type giant
cells surrounding
clefts
created by the cholesterol crystals.
The lesions are expansile and lytic with a 'soap bubble' centre and well-demarcated edges.
Treatment Histology
Surgical excision by whatever route facilitates complete
Tissue is unremarkable macroscopically. Microscopically, the granuloma has a cellular fibroblastic stroma contain
removal of the granulation tissue to prevent 'recur rence,.5 5 ,5 6
[**]
ing aggregates of giant cells. These are smaller and have correspondingly fewer nuclei than in a true giant cell tumour.
Biochemical
investigations
(serum
calcium
GRANULOMATOUS NEOPLASIA
phosphate and alkaline phosphase) should be undertaken to
distinguish
it
from
the
brown
tumour
of
hyperparathyroidism.
Introduction Many terms, most notably 'midline destructive granulo ma' have been used to describe the condition now shown
Treatment
to
Curettage alone is associated with recurrence in
15
percent of cases and excision should be undertaken where possible. 54
[**]
be a TINK
cell
lymphoma. 5 7, 58
This tumour
is
responsible for the classical destruction of the midface and has caused great controversy and pathological debate. It was first described by McBride59 with a subsequent comprehensive account of the clinical and histological features by Stewart.60 In the past, death resulted from intercurrent infection of disseminated lymphoma due to a failure of diagnosis or insufficiently aggressive oncologic
CHOLESTEROL GRANULOMA
treatment. Recently, similar appearances of aggressive midfacial destruction caused by cocaine abuse have been
Definition
reported in which tests for granulomatous diseases and
Granulomatous reaction to cholesterol crystals preCIpI tated
in
the
tissues
are
presumed
to
result
lymphoma have been negative.61
from
haemorrhage andlor trauma.
Age and sex Age and sex
TINK cell lymphoma may occur at almost any age from the first to the ninth decade, though the median is fifth or
In 12 personal cases, the age ranged from 26 to 56 years (mean 38 years) with a male preponderance and a mean
sixth decades. A male preponderance has been reported in some series though not others. 40
1656 I
PART 13 THE NOSE AND PARANASAL SINUSES
Clinical features
antigen should be applied as approximately 80 percent
Whilst patients usually present
phenotypes. Histologically, the infiltrates are polymorphic
of the peripheral T-cell lymphomas will show aberrant
with aggressive destruc
tion of the middle of the face, classically the disease has been divided into three stages. 1. Prodromal. This may last for many years with the
patient complaining of persistent nasal obstruction and rhinorrhoea for which
the patient
may be offered surgery.
2. A period of activity when areas of necrosis develop on and around the nasal cavity associated with purulent discharge, crusting and tissue loss. Progressive destruction of the nasal framework, palate, upper lip extending into the pharynx and
and atypical cells tend to be arranged in a necrotizing angioinfiltrative growth pattern.
Infiltrates consist of
neoplastic atypical T-lymphocytes mixed with plasma celis, small lymphocytes, histiocytes, eosinophils and also some immunoblasts.62 Granulomas and
giant cells are not
present in T-cell lymphomas; thrombosis and necrosis are, however, common findings.
An association with
Epstein-Barr virus has been reported and may be of help in the early differential diagnosis of the condition.63,64
The exact classification of these peripheral T-cell lym phomas remains under evaluation.
orbit and skull base occur often associated with pyrexia secondary to infection
(Figures 130.9 and
130.10). 3. The terminal stage. Haemorrhage associated with the gross mutilation of the face and exhaustion lead eventually to death. The process may take a number of years and be associated with systemic
Imaging Dramatic and progressive destruction of the midline soft tissue and bone without a gross tumour mass are typical, though similar to that seen in some cases of Wegener's.
metastases.
T re atment Diagnosis These lesions, previously described as midline granulo The nasal T-cell lymphoma still presents a diagnostic
mas, were initially treated with low-dose radiotherapy.65
problem because the atypical cell infiltrates are often
This occasionally produced a dramatic response, but no
dispersed in necrotic areas. Good quality representative
long-term cures.
biopsy material from tissue beneath the slough and crust
Nowadays,
we recommend that all
patients must be treated with radical full course radio
is essentiaL
Immunohistochemistry using a panel of
therapy of 55 Gy or more with wide
monoclonal
antibodies
including the nose, sinuses and palate. Recurrence or the
Figure 130.9
lINK cell lymphoma affecting the midface with
ea rly ulceration.
against
T-cell
differentiation
Figure 130.J 0
field coverage
lINK cell lymphoma of the midface with
significant central destruction.
.
,
..
�
Ch a pter 130 Gra n u lomato u s co n d i ti o ns of the nose I
development of disseminated
lymphoma worsens the
1657
REFE R E N CES
prognosis and chemotherapy may be advocated in those lesions classified as high grade.66 There are few large clinical series with five - year survival rates ranging from 46
*
1.
Lund VJ . G ra n u l o m a tous d ise a se a nd tu mo u rs o f th e nose and para nasal s i n uses. I n : Ken nedy DW, Bolger WE,
to 63 percent, but relapse may occur within a few months of treatment up to 20 years or later. [**]
Zinreich SJ (eds) . Diseases of the sin uses diagnosis and management. H ami l ton, Lo ndon : BC Dec ker, 200 1 : 86. 2.
Lie JT. C l ass i fication and histo p a thologic s pec ificity of syste m ic vacu l i tis. In: Anse l l BM, B acon PA, Lie TJ, Yazici H (eds). The Vasculitidies Science and practice. Londo n :
KEY PO I NTS •
".-t r t
Many pat ients wi t h syste m i c gra n u lo m atous
' .'l= , "
6rst to ENT surgeons. It is important to maintain a low t h resh o ld of susp icion i n o rder t o make an early d iagnosis and ilvert more s,evere systemic disea.se. The presence of bloo d-stai1ned d ischarge and crust should always suggest a gra n ulomatous d isease. No one t est is completely reliable and it is a combination o f cli n i ca l fInd i ngs combi ned wi th s u p port ive invest i gations that clinche..; t he diagnosis. The ma n ageme n t i s uSllallly m ult i d i s ci p l i n ary.
C h a p m a n & H a l l Med i ca l , 1 99 6 : 2 5. 3.
Concepts of e p i d emiology of sa rco idosis : Pre l imi n a ry
cond i t ions present
•
•
•
Cumm i ng s M M , D u n n e r E, Schmidt R H , Barnwe l l H B. report of 1 , 1 94 cases r e vi e w e d with pa rticu l a r refe rence to geogra ph ic eco l ogy. Pos tgrauate Medicine. 1 9 56; 1 9 : 43 7 -46.
4.
Creston J E, Dibble PA. Nasa l sarcoidosis. Archives of
5.
Besn ier E. Lu pus pernio d e l a face. Annales de
Otolaryngology. 1 9 61 ; 74: 2 1 0-8. Dermatologie et de Syphiligraphie. 1 889 ; 1 0 : 333-6. 6.
Boeck C. M u l ti ple benign s a rco'ld of the ski n . Journal of
7.
W i lson R, Lu n d V, Sweatma n M. Upper respira tory tract
Cutaneous Diseases. 1 899 : 1 7 : 543-53. involve m e n t i n s a rcoi dos i s a nd its m a n ageme n t. European Respiratory Journal. 1 998 ; 1 : 2 69-72 . 8.
W ri g ht R E, Clairmont AA, Perl J H , Butz WC. I ntra nasal sarcoidosis. Laryngoscope. 1 9 7 4 ; 84: 2058-64.
9.
Best cl in ical practice
Friou GJ . De l ayed cuta neous hypersensitivity i n s a rco i d osis. Journal of Clinical In vestigation. 1 9 52 ; 3 1 : 630-5 .
./ Any patient w i th b l ood-sta i ned d i scharge a nd
10.
cru s t i n g in the nose has a g ra nulomatous condition
i n sarcoid os is. American Review of Respiratory Diseases.
until prove n otherwise.
./ Seco n d a ry or terti a ry referra l may be requi red to
1 9 68 ; 98 : 1 07- 1 0 . 11-
Scadd i n g J G , M itche l l O N . Sarcoidosis, 2 nd edn. Lond on :
1 2.
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h ist@l l o g i c param eters i n g i a nt ce l l l esions o f t h e jaws a n d
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I 1659
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131 Abnorma Iities of smell RICHARD L DOlY AND STEVEN M BROMLEY
Introduction Anatomy and physiology Olfactory disorder classification Clinical evaluation of smell function Causes of smell disturbance Treatment of smell disorders Key points
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1660 1661 1664 1664 1666 1670 1672
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Best clinical practice Deficiencies in current knowledge and areas for future research Appendix Acknowledgements References
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1672 1673 1674 1674
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Many of the papers referred to in this chapter come from the author's own laboratory. Most other references were derived from multiple searches on PubMed and Psychlnfo.
INTRODUCTION The ability to detect environmental chemicals is a primary function of the nose. A proper functioning sense of smell allows a person to discriminate between thousands of largely organic, low molecular mass, volatile compounds and provides information regarding: (1) the safety of a substance or environment (for example, spoiled food, leaking natural gas); (2) the aesthetic properties of everyday objects (for example, rose, dirty laundry); and (3) elements of basic communication (for example, mother/infant interactions). When combined with gustatory and somatosensory stimuli, the sense of smell determines the flavours of foods and beverages, and aids the process of digestion by triggering normal gastrointestinal secretions. Moreover, the olfactory system contributes significantly to a person's quality of life. Among 750 patients presenting to our centre with largely olfactory problems, more than 68 percent experienced altered quality of life, 46 percent described changes in appetite or body weight,
and 56 percent reported influences in daily living or psychological well-being. l Loss of smell can result in significant psychological disruption and even generate feelings of physical and social vulnerability and victimization. 2 The importance of smell is also emphasized by the consequences of its loss in those who depend on it for their livelihood (for example, cooks, homemakers, firefighters, plumbers, wine merchants, chemical plant workers, etc.). Loss of smell can also adversely affect nutrition, especially in the elderly.3 Although otorhinolaryngologists can be the first physicians who patients with smell complaints visit, some patients find themselves making repeated appointments to multiple physicians until their olfactory problem is adequately addressed. Unfortunately, olfactory health is generally disregarded by physicians. This is beside the fact the abnormalities of smell are ubiquitous. Recent estimates suggest that there are at least 2.7 million (1.4 percent) adults in the United States with olfactory dysfunction; presumably similar numbers exist worldwide. 4 Also, most patients who complain of decreased
Chapter 131 Abnormalities of smell.
'taste' function actually have an unrecognized impairment of smell. l Diminished 'taste' is typically due to loss of flavour sensations derived from retronasal stimulation of the olfactory receptors, rather than impairment of tastebud-mediated sensations, per se. 3 Importantly, a patient's lack of olfactory function can be an early sign of a number of serious disease states, including nasopharyngeal carcinoma, Alzheimer's disease, Parkinson's disease, frontal meningiomas, multiple sclerosis (MS) and sinus infections. 5,6 While some patients initially present to their physicians with a frank complaint of smell impairment, others can be completely unaware of their dysfunction, making routine clinical assessments of olfaction imperative. The necessity of the physician to properly evaluate for abnormalities of smell function is also supported in the medicolegal arena, with claims of accidental and iatrogenic smell disturbance often resulting in substantial financial awards. Routine clinical quantitative measurement of smell function can now be easily performed in the office setting, allowing a physician to: (l) validate and characterize a patient's olfactory complaint; (2) identify patients who might be malingering; (3) quantify and document known presurgical smell impairment; and (4) longitudinally follow the course of smell function in the midst of a therapeutic intervention or during recovery from previous loss. This chapter summarizes important aspects of olfactory anatomy and physiology, describes the common olfactory disorders encountered in clinical practice, and provides current practical techniques for the evaluation and management of smell disturbance.
ANATOMY AND PHYSIOLOGY The nose: Structure in relation to smell The human nose contains two complex, independent nasal passages which are dynamic conduits that sub serve both respiration and olfaction. The nasal cavities not only warm and humidify inspired air, bu t they help to eliminate most airborne pathogens and environmental pollutants - a number of which can be toxic to the olfactory system? The olfactory neuroepithelium exists within a small region of nasal mucosa (said to be approximately 2 cm 2) in the upper recesses of the nasal chambers lining the cribriform plate and sectors of the superior turbinate, middle turbinate and septum (Figure 131.1).8 This specialized epithelium is situated behind the approximately I-mm wide olfactory cleft, making it difficult to observe even with modern endoscopic devices. 9 While most of the airstream coming into the nose is shunted through the passages around the inferior and medial turbinates and along the septal wall, only 10-15 percent of the air reaches the olfactory
Figure 131.1
1661
CT scan of paranasal sinuses and associated
nasal structures. The asterisk is within the right maxillary sinus, below the right eye. The inferior portion of the middle turbinate is indicated by the white arrowhead and the inferior turbinate by the circle. Note the attachment of the middle turbinate to the cribriform above. A short white arrow is in the left anterior ethmoid sinus and points to the anterior ethmoidal neurovascular bundle as it emerges from the left orbit and courses along the roof of the ethmoid. The central small open arrow is located in the anterior cranial fossa directly above the bony crista gaili. The long thin arrow situated with the olfactory cleft points to the cribriform plate. The five-pointed star in the right olfactory fossa is adjacent to the vertical lamella of the cribriform plate. Repri nted from Ref. 8, Copyrig ht
©
1995 by
Marcel Dekker. Inc.
neuroepithelium. lO Thus, minor changes in nasal architecture and airflow can result in substantial airflow blockage to olfactory regions without much impairment in nasal respiratory ability.7,11 For example, relatively small polyps located in the superior meatus can deflect incoming air currents away from the olfactory cleft, resulting in smell impairment.l1 On the other hand, too patent of an airway, as seen with excessive turbinate removal, can improperly shunt air away from the olfactory cleft, resulting in a decrement in olfactory acuity.12 It is important to remember that while chronic rhinosinusitis can lead to swelling of the mucosa and a mechanical conductive block, there is evidence for local inflammatory toxicity to the olfactory neuroepithelium that may not be alleviated with surgical intervention. 13 A significant amount of retronasal airflow from the nasopharynx occurs during swallowing and deglutition. This retronasal route is vital to the production of flavour from swallowed foods - adding smell to both taste and touch. The human nasal passage is intermittently affected, at least in some individuals, by the 'nasal cycle'. This cycle, an autonomic ultradian rhythm of periodic
--,j ------,-------
1662 I PART 13 THE NOSE AND PARANASAL SINUSES alternating side-to-side nasal turbinate engorgement and disengorgement, is said to occur in 80 percent of the normal population with a cycle frequency ranging from 40 minutes to four hours. 7 The nasal cycle itself, which is less frequent in the very young and the very old, does not appear to affect overall olfactory sensitivity in the normal nose; however, intermittent engorgement in the context of a pre-existing structural distortion can result in a noticeable, albeit transient, blockage of a nasal passage (for example, when turbinate adhesions are present).
Four neural systems within the nose Most land mammals have four specialized neural systems within the left and right sides of the nose: (1) the main olfactory system (cranial nerve I or eN 1); (2) the accessory olfactory system (i.e. the vomeronasal system); (3) the trigeminal somatosensory system (eN V); and (4) the nervus terminalis or terminal nerve (eN 0).14, IS While eN I mediates common odour sensations (for example, vanilla, rose and chocolate), eN V mediates both chemical and nonchemical stimuli in the form of somatosensory sensations (for example, irritation, burning, cooling, tickling, touch). eN V is also responsible for inducing reflexive responses, such as secretions of mucus and halting of inhalation, that help to prevent or minimize chemically or thermally induced damage to the linings of the nose and lungs. The vomeronasal system is nonfunctional in humans, while a rudimentary vomeronasal tube is present on each side of the septum with an opening into the human nose, it has no centrally projecting nerve and humans do not possess an accessory olfactory bulb, the target of such a nerve. eN 0 was discovered after the other cranial nerves had been named and consists of a loose plexus of ganglionated nerves that, in most mammals, is in close proximity to the vomeronasal organ and nerve. It has been suggested by some that eN 0 may be a vestige of an ancient nerve whose function was lost or superseded by other parts of the nervous system, although this argument is weak, given that it is so well conserved among a wide range of vertebrates, including humans.
Olfactory neuroepithelium and neural transduction Before neural transduction can begin, odourants must: 1. enter the nose during either active (sniffing) or
passive (diffusion) processes; 2. pass through the olfactory cleft; 3. move from the air phase into the largely aqueous phase of the olfactory mucus.
Mucus is important in that it ensures a moist and protective environment for the olfactory neuroepithelium, and aids in dispersing odourants to the olfactory receptors. From the mucus, odourous chemicals either diffuse or are transported by specialized proteins (termed 'odourant-binding proteins') to the receptors. The olfactory neuroepithelium has an ultrastructure of variable uniformity and, contrary to many textbooks, cannot be discerned reliably from the surrounding respiratory epithelium by the naked eye. It is a pseudo stratified columnar epithelium, supported by a highly vascularized lamina propria. Throughout life, islands of respiratory-like epithelial metaplasia appear within the epithelium, presumably as a result of cumulative viral, bacterial and other insults. 14 In the adult, at least six distinct classes of cells - defined morphologically, biochemically and functionally - can be identified within the neuroepithelium (Figure 131.2): (1) the bipolar sensory receptor neuron is derived embryologically from the olfactory placode, is of central nervous system (eNS) origin and extends odourant receptor-containing cilia into the mucus; (2) the supporting or sustentacular cell insulates the bipolar receptor cells from one another, regulates some elements of mucus production and may aid in the degradation of odourants; (3) the duct cell of Bowman's glands secretes most of the mucus within the olfactory receptor region; (4) the poorly understood microvillar cell, located at the surface of the epithelium, sends tufts of microvilli into the nasal mucus; (5) the horizontal (dark) basal cells, one of two main classes of stem cells within the basement membrane of the epithelium, and (6) the globose (light) basal cells, a multipotent basal cell that can give rise to neurons and nonneuronal cells, including the horizontal basal cells. 14 The number of olfactory receptor cells exceeds that of any other sensory system except vision; collectively, the surface area of the cilia is quite large - exceeding 20 cm 2 in the human. IS Seven domain transmembrane olfactory receptors, which reflect the expression of the largest known vertebrate gene family (on the order of 1000 genes or pseudogenes, accounting for approximately 1 percent of all expressed genes), are found on the 10-30 cilia that project into the nasal mucus from each of these cells. 16 Approximately 6 million receptor cell axons ultimately coalesce into 30-50 fascicles, termed the olfactory fila, which traverse the cribriform plate and pia matter to synapse with second-order neurons within the glomeruli of the olfactory bulb. The olfactory receptor neurons primarily use the neurotransmitter glutamate to excite olfactory bulb (OB) neurons, while dopamine appears to be a necessary modulator of olfactory nerve input. 17 The process of actually transforming the chemical energy of receptor binding into a neural signal- signal transduction - requires a. complex cascade of events, some of which involves activation of G proteins (for example, that of an
Chapter 131 Abnormalities of smell
I 1663
The olfactory bulb and central projections
Low-power electron micrograph (x 670) of a longitudinal section through a biopsy specimen of human olfactory mucosa taken from the nasal septum. Four cell types are indicated: ciliated olfactory receptors (e), microvillar cells (m), supporting cells (s) and basal cells [b). The arrows point to ciliated olfactory knobs of the bipolar receptor cells. d, degenerating cells; bs, base of the supporting cells; Ip, lamina propria; n, nerve bundle; bg, Bowman's gland. Photo courtesy of David T Moran.
Figure 131.2
olfactory-specific subtype, Golf) and various secondmessenger enzymes. lS , 19 It is important to recognize that the olfactory nerve cells, as well as the proximal extraneural spaces, can serve as conduits for the movement of viruses and exogenous agents from the nasal cavity into the brain. This was reCOgnized many years ago as a major route of polioviruses into the brain, leading to programmes to cauterize the olfactory epithelium of school children with zinc sulphate in Toronto and other major cities to avert contracting polio during epidemics. This 'olfactory vector' route has been proposed as a potential explanation for both the olfactory loss and the aetiology of some forms of common neurodegenerative diseases, such as A1zheimer's disease and idiopathic Parkinson's disease,2o although evidence for this hypothesis in these cases remains largely circumstantial.
The olfactory bulbs are complex structures located on the ventral surface of the frontal lobes directly over the cribriform plate. The first synapse of the incoming bipolar olfactory receptor cell neurons occurs within spherical structures making up a distinct layer of the bulb - the glomeruli. A given receptor cell projects to only one glomerulus and any given glomerulus appears to receive most of its input from a restricted region of the epithelium. The main afferent second-order neurons are termed 'mitral' and 'tufted' celis. A considerable amount of convergence of information occurs at the level of the glomeruli. The mitral and tufted celis, in turn, send collaterals that synapse within the periglomerular and external plexiform layers) resulting in 'reverberating' circuits in which negative and positive feedback occur. The apical dendrites of the mitral and tufted cells are influenced by interneurons and centrifugal fibres, most of which are GABAergic or dopaminergic?l It is generally believed that the olfactory system is unique among sensory systems in that information from the sensory receptors is sent directly, and primarily ipsilaterally, into cortical regions without synapsing in the thalamus. However, some cortical projections from primary to secondary (i.e. orbitofrontal) cortex do ultimately relay through the thalamus) and there are some contralateral projections via the anterior commissure. The latter arise largely from pyramidal cells of the anterior olfactory nucleus (AON), a structure whose cells are primarily in the rostral olfactory peduncle. Higherorder brain regions in addition to the AON that are targetted by the mitral and tufted cells of the bulb include (from rostral to caudal): (1) the piriform cortex; (2) the olfactory tubercle; (3) the entorhinal area; (4) the amygdaloid cortex (a region contiguous with the underlying amygdala); and (5) the corticomedial nuclear group of the amygdala. There is a rich supply of centrifugal fibre projections from sectors of the olfactory cortex and other central structures to the olfactory bulb which modify and control olfactory input. 21,22 Structures involved in centrifugal activity include the AON, piriform cortex, lateral entorhinal cortex, regions of the amygdala, raphe nuclei, locus ceruleus and regions of the hypothalamus?2 Third-order projections occur, in a reciprocal fashion, to numerous regions, including the mediodorsal nucleus of the thalamus, the posterior and medial hypothalamus, the hippocampus, and the orbitofrontal cortex, the latter of which also receives second-order projections. Areas of the cortex that result in smell perception when stimulated include the prepiriform and intermediate piriform cortices. Lesions of the olfactory system anterior to the olfactory trigone (including the neuroepithelium, fila) bulb and tract) can result in total lack of smell on the affected side. However, lesions within olfactory structures more posterior to the olfactory trigone do not typically cause comp 1ete 1oss. 22' 23
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1664 I PART 13 THE NOSE AND PARANASAL SINUSES
OLFACTORY DISORDER CLASSI FICATION Olfactory disorders are classified according to standard schemata. It is important to differentiate between a patient's chemosensory complaint and the findings of objective testing, which are not always in congruence. Anosmia refers to an inability to detect qualitative olfactory sensations (i.e. absence of smell function). Partial anosmia defines an ability to perceive some, but not all, odours; hyposmia or microsmia refers to decreased sensitivity to odours. Hyperosmia reflects increased sensitivity to common odours. Dysosmia (sometimes termed cacosmia or parosmia) is distorted or perverted smell perception to odour stimulation. Phantosmia is a dysosmic sensation perceived in the absence of an odour stimulus (also known as olfactory hallucination) and olfactory agnosia refers to an inability to recognize an odour sensation, even though olfactory processing, language and general intellectual functions are essentially intact, as in some stroke patients. Other less commonly used terms include heterosmia - a condition where all odours smell the same; presbyosmia - a decline in smell sense with age and osmophobia - a dislike or fear of certain smells. Presbyosmia is less specific than the other terms noted above (for example, it does not distinguish between anosmia and hyposmia) and is laden, by definition, with the notion that it is age per se that is causing the age-related deficit. Olfactory dysfunction can be either bilateral or unilateral (sometimes termed binasal or uninasal). Bilateral testing usually reflects the better functioning of the two sides of the nose.
CLINICAL EVALUATION OF SMELL FUNCTION History Proper assessment of a patient's smell function requires (1) a detailed clinical history, (2) quantitative olfactory testing and (3) a thorough physical examination emphasizing the head and neck with appropriate brain and rhinosinus imaging. It is important to recognize that patients frequently confuse 'taste problems' with true smell loss, and that many deny any olfactory disturbance until formal testing proves otherwise. Several focussed questions can help establish the nature of the olfactory disturbance. Was olfactory functioning previously normal? Does the patient have a problem with smell, taste or both? What is the timing of onset, duration of impairment and pattern of occurrence? Sudden olfactory loss can be consistent with possible head trauma, ischaemia, infection or a psychiatric condition. Gradual loss may indicate a progressive and obstructive lesion in or around the nasosin us region, particularly if the loss is unilateral. Intermittent loss may suggest an inflammatory process in association with ?-asal and sinus disease. Is the problem
seasonal, suggesting an allergic seasonal rhinitis? Is there a history of precipitating antecedent events, such as head trauma, viral upper respiratory infections, chemical or toxin exposures and nasosinus surgeries? Does the patient have any nasal discharge that is mucous-appearing (for example, allergy), purulent (for example, infection), or clear (cerebrospinal fluid (CSF) rhinorrhoea after traurna)? Does the patient use drugs of abuse, such as intranasal cocaine, ethanol or tobacco? Each of these substances has been associated with some form of olfactory impairment; for example, chronic alcoholism can result in significant impairment in smell discrimination 24 and cigarette smoking results in a loss of olfactory ability that is proportional to the cumulative smoking dose. 25 Cessation of smoking can result in improvement in olfactory function over time. It is essential to determine all medications used by the patient since many reportedly cause smell and taste disturbance. Indeed, smell or taste loss or disturbances are reported in the Physicians' Desk Reference (PDR) as a potential side effect of hundreds of medications. 26 Does the patient have comorbidities that can contribute to smell impairment, such as renal failure, liver disease, hypothyroidism, diabetes or dementia? Delayed puberty in association with anosmia (with or without midline craniofacial abnormalities, deafness and renal anomalies) suggests the possibility of Kallmann's syndrome or some variant thereof. Is there a recent history of epistaxis, discharge (clear, purulent or bloody), facial numbness or weakness, nasal obstruction, allergies, headache or irritation (i.e. signs that may have localizing value)? A positive family history suggests a genetic aetiology. A history of headache suggests sinusitis, migraine or intracranial tumour. Are smells present without an obvious stimulus? A simple partial seizure or aura may not be obvious and other signs of ictal activity should be explored (for example, limb shaking, difficulties with speech, unresponsiveness, automatisms, loss of consciousness and deja vu). Given the strong relationship of Alzheimer's disease and idiopathic Parkinson's disease to smell impairment, one should also look for memory- and parkinsonismrelated complaints in older patients. A physician should also be aware of pending litigation and the possibility of malingering since olfactory loss is a compensable injury.
Physical examination and evaluation Patients complaining of smell disturbance typically require a general assessment of the head and neck and more detailed otolaryngological and neurological examinations. Are there any signs of trauma such as healing wounds, scarring or distorted nasal or skull architecture? Inspection of the nasal passages can begin with a simple nasal forceps examination to view the peripheral nasal cavity for signs of polyps, congestion, deviation of septum or inflammation. However, this method is limited, and
Cha pter 131 Abnormalities of smell •
often nasal endoscopy, employing both flexible and rigid scopes, is needed to ensure thorough assessment of the olfactory meatal area. A deviated septum, per se, does not imply a smell disturbance since the olfactory cleft can remain patent; however, the additional presence of polyps, masses and adhesions of the turbinates to the septum may adequately obstruct airflow. Rarely, foreign bodies can be present, particularly in the context of a psychiatric disturbance. Nasal mucous membranes must be examined for colour, surface texture, swelling, inflammation, exudate, erosion, ulceration, epithelial metaplasia and atrophy. The presence of mucopus above the Eustachian tube orifice suggests posterior ethmoid and/or sphenoid sinus disease. However, mucopus below the Eustachian tube implies involvement of the ostiomeatal complex. A pale mucous membrane suggests allergy, usually as a result of oedema within the lamina propria. Atrophy of the lamina propria is suggested by unusual spaciousness, dryness and crusting, as is seen in atrophic rhinitis. Exposures to environmental or industrial pollutants can result in metaplasia within the epithelium, in addition to swelling, inflammation, exudates, erosion and ulceration. The neurological evaluation should focus on cranial nerve function, with particular attention to the optic nerve (CN II), trigeminal nerve (CN V) and the facial nerve (CN VII) (see next paragraph for CN I). Visual acuity, visual field and optic disc examinations aid in the detection of possible intracranial mass lesions resulting in increased intracranial pressure (papilloedema) and optic atrophy, especially when considering Foster Kennedy syndrome (described below). General sensation over the face should be assessed (for example, cotton, pinprick, temperature). The nasal tickle, performed by using cotton to tickle the inside of one nostril, is also useful since an asymmetric withdrawal response suggests impairment of trigeminal fibres within the nose. The face should be symmetrical and full strength, with intact taste on the
1665
anterior two-thirds of the tongue bilaterally. Signs of frontal lobe injury and memory impairment may also aid in the diagnosis. Biopsy of the olfactory epithelium is occasionally helpful. However, the interpretation of such biopsies is complicated by sampling issues and the fact that metaplasia of respiratory-like epithelium occurs throughout the olfactory epithelia in persons with no olfactory problems. Some laboratory tests, such as blood serum tests, may also be helpful in evaluating for underlying medical conditions suggested by history and physical examinations, such as infection, nutritional deficiencies (for example vitamin B6, B12), allergy, diabetes mellitus and thyroid, liver and kidney disease. 3 Contrary to many textbooks, there is no proven efficacy of zinc or vitamin A treatments, except in cases where frank deficiencies are lacking.
Quantitative olfactory testing Several standardized and practical psychophysical tests have been developed over the last several years, including a number of brief self-administered tests ranging from the three-item Pocket Smell Test™ to the 40-item University of Pennsylvania Smell Identification Test (UPSIT)?7 The UPSIT is commercially known as the Smell Identification Test™ and is the most widely used olfactory test, having been administered to an estimated 400,000 patients since its development (Figure 131.3).28 The UPSIT can be selfadministered in 10-15 minutes by most patients in the waiting room, and scored in less than a minute by nonmedical personnel. Available in American, British, Chinese, French, Italian, German, Spanish and Japanese versions, this test consists of four booklets containing ten microencapsulated (scratch and sniff') odourants apiece. Test results are in terms of a percentile score of a patient's performance relative to age- and sex-matched controls,
Fig u re 131.3
The four booklets of the
40-odourant University of Pennsylvania Smell Identification Test (UPSIT; commercially known as the Smell Identification Test
rM ).
Each page
contains a microencapsulated odourant that is released by means of a pencil tip. This test. which has been administered to approximately 400,000 patients since its development, is the most widely used olfactory test in the world, with English, french, German, Japanese and Spanish versions available. The UPSIT is considered to be the 'eye chart for the nose'. Photo courtesy of Sensonics. Inc., Haddon Hts., NJ 08035 USA. Copyright
©
2000 by Sensonics, Inc.
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1666 I PART 13 THE NOSE AND PARAI\lASAL SINUSES and olfactory function can be classified on an absolute basis into one of six categories: normosmia, mild microsmia, moderate microsmia, severe microsmia, anosmia and probable malingering. Since chance performance is 10 out of 40, very low UPSIT scores reflect avoidance, and hence recognition, of the correct answer, allowing for determination of malingering. The reliability of this test is very high (test-retest, r=0.94). Although most olfactory problems are bilateral, and bilater81 testing reflects the better functioning side of the nose, in some instances unilateral testing is warranted. 23 To accurately assess olfaction unilaterally, the naris contralateral to the tested side should be occluded without distorting the patent nasal valve region. Such occlusion not only prevents air from entering the olfactory region from the naris (orthonasal stimulation), but prevents active movement of odour-laden air into the occluded side from the rear of the nasopharynx (retronasal stimulation). An easy way of doing this is to seal the contralateral naris using a piece of Microfoam™ tape (3M Corporation, Minneapolis, MN, USA) cut to fit the naris borders. The patient is instructed to sniff the stimulus normally and to exhale through the mouth. While, in most cases, olfactory dysfunction can be adequately characterized by the UPSIT, some physicians employ, alone or in combination with the UPSIT, a smell threshold test. A commonly employed test uses phenyl ethyl alcohol as the odourant and establishes the threshold employing a staircase procedure. 29 Thresholds determined using this procedure are similar in principle to audiometric thresholds using the von Bekesy procedure. Like the UPSIT, threshold testing can be done either bilaterally or unilaterally. The recording of olfactory event-related potentials (OREP) is available in some specialized medical centres as an additional means of assessing the integrity of the olfactory system. Using brain electroencephalography (EEG), the test consists of discerning synchronized brain activity recorded from overall EEG activity following brief presentations of odourants. Unfortunately, OREP testing requires complex, specialized and expensive equipment capable of delivering a well-delineated 'square wave' odourant pulse into the nose within the background of continuously flowing warmed and humidified air. Although OERPs can be useful in some cases in detecting malingering and are generally sensitive to alterations in olfactory function, unlike their visual and auditory counterparts they are unable to discern where in the pathway the anoII).aly exists that is causing the problem.
Imaging studies There are multiple ways of medically imaging patients with smell disturbance. Plain radiographs are rarely useful due to an inability to capture details of the osteomeatal
complex. Computed tomography (CT), on the other hand, has proven to be the most useful and cost-effective technique to assess sinonasal tract inflammatory disorders, and is superior to magnetic resonance imaging (MRI) in the evaluation of the bony structures (for example, ethmoid, cribriform plate, olfactory cleft). In particular, coronal CT scans are useful in evaluating paranasal anatomy. MRI is better to evaluate soft tissue and is the technique of choice to image the olfactory bulbs, tracts and cortical parenchyma. Positron emission tomography (PET), single-proton emission computed tomography (SPECT) and functional MRI (fMRI) presently have limited usefulness outside research institutions.
CAUSES OF SMELL DISTURBANCE There are a number of known aetiologies, many nonmutually exclusive, for olfactory disturbance. These are listed in the appendix to this chapter. The majority of cases of presumably permanent chronic anosmia or hyposmia are due to prior upper respiratory infections, head trauma and nasal and paranasal sinus disease - most causes reflecting permanent damage to the olfactory neuroepithelium. l [****] Despite extensive evaluations, a substantial proportion remains idiopathic. In general, loss of olfactory function can be subdivided into two classes: (1) conductive or transport impairments from obstruction of the nasal passages (for example, chronic nasal inflammation, polyposis, etc.); and (2) sensorineural impairment from damage to the olfactory neuroepithelium, central tracts and connections (for example, viruses, airborne toxins, tumours, seizures, etc.). In some circumstances, it is difficult to classify an olfactory disorder into one of these classes, because of both blockage of airflow to the receptors and damage to the receptors or other elements of the olfactory neuroepithelium, can be present. Chronic rhinosinusitis, for example, can produce damage to the olfactory membrane in addition to blocking airflow, and altered membrane function can, over time, lead to degeneration within the olfactory bulb, a central structure. Although we are currently able to treat many causes of olfactory disturbance due to conductive factors or inflammation of the olfactory epithelium, most olfactory disorders due to sensorineural factors remain untreatable. In most cases, hyperosmia reflects a patient's heightened response to an odour, rather than an increased ability to smell, per se. This problem has been reported in some conditions associated with a change in hormone balance, such as in pregnancy and Addison's disease (adrenal-cortical insufficiency), as well as migraine, drug withdrawal, epilepsy (intericatal period), multiple chemical sensitivity and psychosis. While hyperosmia is relatively rare, dysosmia is more common. Usually
Chapter 131 Abnormalities of smell
dysosmia reflects dynamic alterations of degeneration or regeneration within the olfactory neuroepithelium over time and it is not uncommon for patients who eventually develop anosmia to report having experienced weeks of dysosmia preceding the experience of anosmia. Dysosmia implies an olfactory system that is intact at least to some degree, as total smell loss does not typically accompany most cases of dysosmia. l [***] Severely debilitating, long-lasting and intractable chronic dysosmias have been treated by surgical ablation of regions of the olfactory neuroepithelium, or by surgical removal of a diseased olfactory bulb or bulbs. 30 Olfactory hallucinations or phantosmias can occur from a problem anywhere along the olfactory neural pathways, from the nose to the cortex. Sometimes they are associated with ictal epileptiform activity (for example, simple partial seizures), nasal sinus disease (for example, infection) and head trauma. If someone believes a smell is present (hallucination) and persistently gives this smell personal reference to outside events, despite contradicting evidence, this patient may suffer from olfactory reference syndrome - a depression-related disorder. In some cases, there may be a pathological correlate in the form of right hemispheric lesions. 3l Olfactory agnosia is an extremely rare phenomenon, although is appears to be less commonly investigated than visual and auditory agnosia. It is associated with lesions of the right inferior temporal lobe and is often linked to prosopagnosia (agnosia for familiar faces). The more common disorders or entities associated with olfactory impairment are discussed in detail below, beginning with the more frequent ones.
Upper respiratory infection Upper respiratory viruses, such as those associated with the common cold and influenza, are considered the most common aetiology of permanent olfactory loss in man. Other infectious causes that have been reported include hepatitis, herpes simplex encephalitis, pneumonia and variant Creutzfeldt-Jacob disease. It is not clear what predisposes someone to virus- and bacteria-induced smell dysfunction or the precise mechanisms behind it. Often the smell-affecting respiratory illness is described as being more severe than usual. In a study of olfactory biopsies of four patients with anosmia and 11 patients with hyposmia due to a viral illness, Jafek and colleges 32 noted that patients with anosmia had markedly reduced numbers of receptors and those receptors were abnormal compared with those patients with hyposmia. Given the ability of the olfactory receptor neurons to regenerate, spontaneous recovery of some smell function is theoretically possible over a prolonged period. However, complete recovery is less likely the longer the patient has the loss and is inversely related to the degree of dysfunction. In general, it is necessary to exclude other
I 1667
aetiologies prior to making a diagnosis of post-viral anosmia. Human immunodeficiency virus (HIV)-infected patients are said to show an early impairment in odour thresholds and a later decline in odour identification and discrimination function which appears to parallel a general reduction in cognitive abilities. 33
Head trauma Head trauma often results in smell loss, particularly where rapid acceleration/deceleration of the brain occurs (i.e. coup/contrecoup injury) (Figure 131.4). Blunt trauma to the occiput has been found to produce greater olfactory loss than trauma to the front of the head. 3s Following head trauma, the loss of smell is usually, but not always, immediate. However, it may take a while for the patient to recognize the presence of the dysfunction. Common mechanisms include disruption from shearing forces of the olfactory fila through the sinonasal tract, and direct contusion and ischaemia to the olfactory bulb and frontal and temporal poles. Fracturing of the cribriform plate is not a prerequisite for smell loss. The prevalence of olfactory loss following head trauma is around 15 percent and is proportional to the severity of the injury.3s, 36 [***] As would be expected, such prevalence is much higher in patients referred to specialized smell and taste centres for evaluation and treatment. For example, among 268 patients evaluated at our centre who had experienced head trauma, 66.8 percent had anosmia, 20.5 percent hyposmia and 13 percent had normal smell function. MRI images may reveal damage to the olfactory bulbs, tracts and areas of the temporal and frontal 10bes. 36 Animal research shows that intracranial haemorrhage and ischaemia can lead to degeneration of the olfactory epithelium without transection of the olfactory nerves. 37 [****] Iatrogenic trauma, such as surgery, can cause smell impairment and has been seen with such procedures as . ' 38 SlllUS surgery and cramotomy.
Nasal and sinus disease While the olfactory impairment that follows a viral syndrome or head trauma can be classified as sensorineural, the dysfunction that results from nasal and sinus disease is usually considered conductive - in other words, there is impaired airflow to the olfactory receptors. Theoretically, any inflammatory or obstructive process in the nose can result in a disturbance of smell function, with common examples being allergic rhinitis, rhinosinusitis, nasal polyposis, intranasal tumours and previous nasal surgery. In the evaluation of 240 patients with allergic rhinitis, Rydzewski and colleagues 39 found that 21.4 percent of patients had smell impairment and there was a significant correlation between olfactory thresholds and levels of eosinophils in the blood and nasal discharge.
1668 I
PART 13 THE NOSE AND PARANASAl SINUSES
(bl
Mechanisms of post-traumatic olfactory dysfunction. (a) Injury to the sinonasal tract; (b) tearing of the olfactory fila; (c) cortical contusions and brain hemorrhage. Redrawn from Ref. 34.
Figure 131.4
Treatments in the form of surgery (for example, excision of polyps) or medication (for example, administration of topical or systemic steroids) may improve olfactory function in some cases; however, complete return is not typical. Thus, while chronic rhinosinusitis can result in nasal airflow blockage, there is also a component of direct toxicity to olfactory neurons and impaired ciliary motility resulting in abnormal clearance of mucus. These combined factors make anyone treatment modality limited. In one study, it was found that systemic steroids can temporarily reverse conductive olfactory impairment in 83 percent of patients, while topical steroids helped in only 25 percent of patients - making systemic steroids a useful diagnostic too1. 40 The severity of histopathological changes within the olfactory mucosa of patients with chronic rhinosinusitis is positively related to the magnitude of olfactory loss, as measured by the UPSIT. 4l Biopsies from the neuroepithelial region of patients 'with nasal disease are less likely to yield olfactory-related tissue than biopsies from controls. 42 Anosmic rhinosinusitis
patients generally exhibit a more pathological epithelium (for example, disordered arrangement of cells and increased islands of respiratory epithelium) when compared to nonanosmic patients with rhinosinusitis. 43 Excessive dryness of the nasal mucosa - as seen in atrophic rhinitis, Sjogren's syndrome and repeated nasal surgery - can cause olfactory dysfunction, since a moist receptor environment aids chemoreception and transd uction.
Tumours and mass lesions A number of tumours in and around the olfactory bulbs or tracts can cause olfactory disturbance. Examples include olfactory groove meningiomas, frontal lobe gliomas and suprasellar ridge meningiomas arising from the dura of the cribriform plate. Due to the olfactory nerve's close location to the roof and medial wall of the orbit, as well as the optic nerves and tracts, structural
Chapter 131 Abnormalities of smell
lesions affecting smell may also affect vision. Also, olfactory tumours may extend into the frontal lobes resulting in symptoms of dementia and possibly the release of primitive reflexes (for example, grasping, snout and glabellar). Mass lesions need not be in the olfactory tracts to cause smell impairment. Ishimaru and colleagues 44 identified two patients with hyposmia from tumours to the right frontal lobe; the hyposmia reversed with craniotomy and tumour resection. Mass lesions around the olfactory region can result in a FosterKennedy syndrome, which consists of: (1) ipsilateral anosmia; (2) ipsilateral optic atrophy and (3) contralateral papilloedema secondary to raised intracranial pressure. 45 Pseudo-Foster-Kennedy syndrome has been reported in patients with increased intracranial pressure who had previous unilateral optic atrophy.46 Similarly, tumours in central regions of olfactory processing (for example, mesial temporal lobe) can also potentially affect smell. Headache often accompanies a complaint of smell loss when the aetiology is a mass lesion. Lymphoma has been known to infiltrate into olfactory areas and cause dysfunction. Similarly, granulomatous diseases - such as syphilis, sarcoidosis, systemic lupus erythematosus (SLE) and Wegener's granulomatosis - often result in anosmia. In patients suspected of having a neoplasm, neuroimaging is essential.
Neurodegenerative diseases Olfactory deficits have been described in a number of neurological disorders (see Appendix). Importantly, olfactory dysfunction may be the first clinical sign of Alzheimer's disease (AD) or idiopathic Parkinson's disease (PD). Smell testing is useful in identifying persons who have PD, as well as those who either have, or are at risk for having, AD. In PD, bilateral olfactory deficits occur before the onset of most of the classical neurological signs and symptoms and are unrelated to disease stage, use of anti-parkinson medications, duration of the illness and severity of the motor symptoms, such as tremor, rigidity, bradykinesia or gait disturbance. 5, 6 [***] Measurement of smell function can be useful to distinguish PD among the other disorders that share many nonolfactory symptoms and signs, such as progressive supranuclear palsy, multiple system atrophy, parkinsonism induced by the proneurotoxin 1-methyl4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), and essential tremor. 6,20 [***] Given a male patient suspected of PD based on history and physical examination who is less than 60 years of age, an UPSIT score of 31 carries a 91 percent sensitivity and 88 percent specificity of correctly diagnosing a patient suspected of having PD. 6 In a woman suspected of PD who is less than 60 years old, an UPSIT score of 33 carries a 79 percent sensitivity and 85 percent specificity.6 [***]
I 1669
With regard to AD, Graves and colleagues 47 found that olfactory dysfunction in the presence of one or more APOE-e4 alleles was associated with a very high risk of subsequent cognitive decline, and smell testing identified people who came to exhibit later cognitive decline better than did a global cognitive test. [***] Devanand and collegues48 found that patients with mild cognitive impairment scored lower on the UPSIT than did the controls, and that patients with low UPSIT scores ( < 34) were more likely to develop AD than the other patients. When low UPSIT scores were accompanied by a lack of awareness of olfactory deficits on the part of the patients, they found that this predicted the time to development of AD. UPSIT scores from 30 to 35 showed moderate to strong sensitivity and specificity for diagnosis of AD at follow up. [***] In later life, Down syndrome patients show similar clinical and pathological changes to AD patients and have lower performance on a modified UPSIT compared to mentally-retarded matched controls. 49 [****] The olfactory loss associated with multiple sclerosis is directly proportional to the number of MS-related demyelinating lesions in central brain regions associated with olfactory processing (for example, inferior middle temporal lobe and periorbital frontal cortex).50 [****] Olfactory function actually increases and decreases as the plaque numbers increase and decrease. 51 Therefore, knowledge of a patient's UPSIT score can be predictive of the plaque load in the olfaction-related regions. [****] Schizophrenia is associated with significant deficits in odour identification and threshold sensitivity. 52 [****] The fact that there is an inverse correlation with UPSIT scores and disease progression suggests that there may be progressive neurodegenerative changes within olfactoryrelated pathways and smell testing can potentially be used as a marker of disease progression. 52
Epilepsy and migraine Olfactory auras, also described as hallucinations, are rare. When they are present, they are often associated with seizures and headaches. Olfactory auras consist of sudden unexplained sensations of smell that are usually, but not always, unpleasant and are rarely isolated events. 53 In epilepsy, mesial temporal lobe structures involved in the usual processing of odour information such as the amygdala and hippocampus - have been implicated as the generators of ictal olfactory sensations (simple or complex partial seizures) that often evolve into secondarily generalized seizures. 54 Common aetiologies include mesial temporal sclerosis and tumours. 54 Some cases of epilepsy have been associated with hyperosmia during the interictal period, although most patients with long-standing epilepsy and intractable
1670 I PART 13 THE NOSE AND PARANASAL SINUSES elderly patients, including ones who are healthy and taking no medications (Figure 131.5).57 Under the age of 65 years, approximately 1 percent of the population has major difficulty in smelling. Between 65 and 80 years, this increases remarkably, with about half of the population experiencing a demonstrable decrement in the ability to smelL Over the age of 80, this figure rises to nearly 75 percent. 54 [***] Despite the association with age, the complaint of smell loss should never be attributed simply to age, as often an accumulation of damage over the years is the culprit and a single event, such as a bad cold, can be the precipitating factor. In general, the age-related changes in smell function are reflected not only in damage to the olfactory receptors but related decreases in number of glomeruli within the olfactory bulb. 58 Interestingly, age-related occlusion of the foramina of the cribiform plate has been observed, pinching off the axons of the olfactory receptor cells as they enter the brain cavity. Whether age-related factors increase the susceptibility of the epithelium to damage from exogenous agents is not clear, but likely. What is clear, however, is that smell loss in older people adversely affects the quality of life. Chemosensory loss has been implicated as a cause - particularly in the elderly - of malnutrition, weight loss, impaired immunity and worsening of a medical illness. 3
seizure activity, such as candidates for temporal lobe resection, are hyposmic. 53 The effect of migraine on smell function is less well understood. The concept of certain smells provoking or exacerbating a migranous headache - osmophobia - may exist similar to that of photophobia or phonophobia.
Other causes and considerations Fewer than 5 percent of patients who present to a specialized centre for smell and taste disorders have a chemosensory disturbance that can be directly attributed to an exposure of a toxic compound. l There are numerous chemical agents that have been reported to affect smell function, including acrylates, cadmium, benzene, formaldehyde, solvents and nickel dust, among others (see Appendix).55 Tobacco smoking results in diminished olfactory ability as a function of cumulative smoking dose and, importantly, smoking cessation can result in improvement in olfactory function over time. 25 [***] Medications are also a common cause of smell disturbance and should be considered early, especially in the context of a new drug therapy (see Appendix).56 Several endocrine disorders exhibit disorders of smelL For example, Kallmann's syndrome, or hypogonadotropic hypogonadism with anosmia, is an X-linked or autosomal recessive neuronal migrational disorder associated with aplasia of the olfactory bulb and hypogonadism (pituitary involvement). [****] Similarly, patients with septo-optic dysplasia (de Morsier's syndrome) can have hyposmia, visual symptoms and precocious puberty. Age-related deficits in smell function are well documented and decreased smell function is present in most
TREATMENT OF SMELL DISORDERS The most effective treatments available are those for conductive anosmia, where there is an obstruction of airflow through the nose to the olfactory neuroepithelium. As noted above, the typical causes of mechanical obstruction include nasal sinus disease,
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Figure 131.5 Scores on the University of Pennsylvania Smell Identification Test (UPSIT) as a function of age and gender in a large heterogeneous group of subjects. Numbers by data points indicate sample sizes. Redrawn from Ref. 57 Copyright © 1984 by the American Association for the Advancement of Science.
Chapter 131
including inflammation, and intranasal neoplasms. After diagnosis is confirmed using tools such as nasal endoscopy and CT scanning of the sinuses, the next appropriate course of action may include topical or systemic steroids. Conductive and sensorineural olfactory losses are often distinguishable using a brief course of systemic steroid therapy, since patients with conductive impairment frequency respond positively to the treatment, although long-term systemic steroid therapy is not advised. Topical nasal steroids are often ineffectual in returning smell function because the steroid fails to reach the affected regions in the upper nasal passages. Increased efficacy occurs when the nasal drops or spray are administered in the head -down and forwards position. 40 Proper allergy management is essential and may require the use of an antihistamine. When a bacterial infection is suspected (for example, infectious rhinosinusitis), a course of antibiotics should be used. Surgery should be considered for: (1) very large and medically refractory polyps or (2) situations where a malignant neoplasm is suspected. Importantly, pre- and post-intervention olfactory testing should be performed to establish intervention efficacy, as well as to screen for subsequent slow relapse that is characteristic of most conductive disorders. In cases where rheumatologic granulomatous disease is suspected, such as Wegener's granulomatosis or sarcoidosis, further immunomodulation using agents such as cyclophosphamide or methotrexate may be necessary. Sensorineural impairment of olfaction is typically more difficult to manage and the prognosis for patients suffering from long-standing total loss due to upper respiratory illness or head trauma is poor. The majority of patients who recover smell function subsequent to trauma do so within 12 weeks of injury.35 Patients who give up smoking typically have dose-related improvement in olfactory function and flavour sensation over time. 25 Central lesions, such as CNS tumours that impinge on olfactory bulbs and tracts can often be resected with significant improvement in olfactory function. When epilepsy or migraine is suspected, a course of antiepileptic or antimigraine medications may prove beneficial. .Medically refractory epilepsy resulting in olfactory disturbance can be successfully treated with surgery. For example, Chitanondh 59 reported successful treatment of seven patients with seizure disorder, olfactory hallucinations and psychiatric problems by stereotactic amygdalotomy, concluding 'stereotactic amygdalotomy has a dramatic effect on olfactory seizures, auras and hallucinations. It is a safe surgical procedure and can be done without neurological deficit.' In patients with multiple sclerosis, immunomodulatory therapies, including interferon-beta and occasional steroids, is the mainstay of treatment. When depression or psychosis is suspected, a course of an antidepressant and appropriate psychiatric referral may be necessary.
Abnormalities of smell I 1671
Medications that induce distortions of olfaction can often be discontinued and replaced with other types of medications or modes of therapy. In addition to direct effects on the olfactory system, the side effects of many medications is to detrimentally dry the nasal mucosa (for example, anticholinergics). Dopaminergic and cholinergic therapies do not improve the olfactory dysfunction seen in Parkinson's disease, and there is no evidence that neuroleptics alter the olfactory loss of patients with schizophrenia. Despite the fact that there are advocates for zinc and vitamin therapies, there continues to be no strongly compelling evidence that these therapies work, except in cases where frank zinc or vitamin deficiencies exist. In patients with complete anosmia, supportive measures are necessary to protect them from further harm. Thus, 1. Smoke and carbon monoxide detectors need to be
installed and properly working. 2. When possible, electrical appliances should be
used instead of gas appliances. 3. Expiration dates for food products should be
scrutinized and old food items checked by someone with normal smell function or discarded. 4. A balanced diet, particularly in the elderly, must be kept to prevent weight loss and malnutrition. Adding flavour enhancers (for example, monosodium glutamate, food colouring, chicken or beef stock) to foods can also help with their appeal. A physician needs to be cognizant of medicolegal ramifications in his or her evaluation and management. In cases of personal injury, malingering is not uncommon and may be distinguished from true anosmia by the pseudo-disappearance of trigeminal function or unusually low UPSIT test scores (i.e. those below chance responding), suggesting active avoidance of the correct answer.
Prognosis Prognosis for recovery appears to vary depending on the severity of the disturbance. For example, for patients whose odour identification ability is less severe (for example, UPSIT scores above 25), the prognosis for complete recovery is much better than for those with complete anosmia. An important part of management for many patients is to use quantitative olfactory testing and establish the true degree of olfactory loss that exists since prognosis relates to some degree to the magnitude of the loss. Such testing also places the patient's problem into overall perspective and many older patients often find it rather therapeutic to know that, while their smell function is not what it used to be, it still falls above the average of their peer group.
1672 I PART 13 THE NOSE AND PARANASAL SINUSES
• T he numb¢r :~tr~~~~~r::-ce:lls in :tl)e olfact.ory system : ex~~~-d$, . tha't of-~y' otb,e,r _: sen~ory, system ~p'art from vision. , , • .Sm'eil -dysfu~ct~on ~~ be 'an ~riy' slgn of - serious diseases, including n~opharynge~ carcinoma, ,Alzheimer's, diseCl-,Sel 'Parkinson's . disease, frontal meningio:pi.as,. rnultiple sclerosis, schii~phre~ia .and clIT'o nic ' . rhiQ~s}!.Ousi~s;~, ' "-" . , . ',,' '. : • ,Smell loss may be predictive,of ,(uture . cogniti~e d~cline in older people. • Decreased: smell function l,s relatively '" co~on afte~ ' the,' age,9f 6? year~: .'. 'M ost' complaints. of taste ,loss ~eflect olfactory lo~s, which 'adversely influences the flavour of foods, via .retronasal"s.timulation ,of :the " , ~lfact~rY re~ep.tors· -'during deglu:6i,tion'. ", • The 'olfactor.y , epitheli~, und~goes ' cumulative, damage fr'9m ·viral, ,ba,cteri-~ ,and. other .insw}s over time. .. Numerous ,exogenous agents;: inCluding , viruses, bacteri,a and ,heavy met'als,- 'can 'enter , the brain via the olfactory rnucos~. • 'Standatdiied ,rriea~s· o( qual}titativ'e ly" ':. ' , assessing,·stneU- :fuhction "in, the, Glini~ 'are 'noWwidely"available. ' .. The most 'common causes of permanent' , .. .- ' smell 'loss are uppe'r respiratory iiife-ctio-ns, head trauma and ·chronic 'nasa! a'nd paranasal , sinus disease. • Dyso'smia typically signifies same degree .of ' neurcil function Within 'the olfactory epithelium. • 'The pre~aience" of o]f~ctory loss following head trauma is around 15 percent and is proportional ' to the severity of the injury.
Best clinical
pra~tice
.; A clear distinction between a complaint of taste loss secondary to lack of flavour due to olfactory loss and true taste loss (i.e. sweet. sour, bitter and salty sensation) must be ascertained . ./ Quantitative assessment of dysfunction is critical to determine validity of the patient's complaint, the degree of dysfunction, establishing treatment efficacy and determining prognosis . ./ Antibiotics should not be given unless indication of bacteria! involvement is present, as some adversely influence smell function. ./ Dysosmias that decrease in frequency usually represent alterations in the olfactory membrane.
./
./
.I ./
.;
However, progressive dysosmias may reflect partial seizures or other eNS phenomena often treatable with antiepileptic medications. Most reported pharmacological treatments for smell disturbances, including zinc, vitamin A. and (i-lipoic acid, are not effective unless frank deficiencies are present. A short course of systemic steroids can be used to determine whether smell loss is due to transport problems or neural damage to the receptors. An inflammatory basis for smell loss can be present even though the nasal airway is generally patent. Routine brain MRls rarely provide adequate visualization of the olfactory bulbs and tracts, and specialized MRls that provide mUltiple cuts through these structures are often needed to ascertain their presence or health (e.g. in cases of congenital anosmia). Decreased smell function can be an early sign of neurodegenerative diseases, and in some patients referral for detailed cognitive testing may be warranted.
Deficiencies in current knowledge and areas for future research P The medical community needs to become better educated regarding the importance of the chemical senses for the well-being and everyday function of human-beings and to realize that accurate assessment of these senses is critical for : (1) establishing the validity of a patient's complaint; (2) distinguishing between complaints of taste and olfactory dysfunction: and (3) monitoring the efficacy of treatment regimens. »- The basis of the olfactory loss in the earliest stages of a number of neurodegenerative disorders, including Alzheimer's disease and idiopathic Parkinson's disease, needs eluc.idation, as gene therapy and other therapeutic modes may be of future value in reversing not only the olfactory dysfunction, but other elements of these diseases . »- There is dire need to establish the mechanisms involved in olfactory cell degeneration and regeneration, as well as in the production of appositional bone growth in the region of the foramina of the cribriform plate, which may be an age-related process. A greater understanding of these and related phenomena, such as the nature of inflammation associated with rhinosinusitis, may ultimately lead to topical or systemic treatments that can mitigate smell dysfunction secondary to damage to the olfactory receptor cells or closure of the foramina of the cribriform plate.
Chapter 131 Abnormalities of smell
APPENDIX
Category
Reported agents, diseases, drugs, interventions and other aetiologic categories associated in the medical or toxicologic literature with olfactory dysfunction. Note that categories are not mutually exclusive.
Hyperl i poprote i ne mia medications
Intranasal saline solutions with
Category Air pollutants and industrial dusts
Drugs
I 1673
Acetone Acids (for example, sulphuric) Ashes Benzene Benzol Butyl acetate Cadmium Carbon disulphide Cement Chalk Chlorine Chromium Coke/coal Cotton Cresol Ethyl acetate Ethyl and methyl acrylate Flour Formaldehyde Grain Hydrazine Hydrogen selenide Hydrogen sulphide Iron carboxyl Lead Nickel Nitrous gases Paint solvents Paper Pepper Peppermint oil Phosphorus oxychloride Potash Silicone dioxide Spices Trichloroethylene Adrenal steroids (chronic use) Amino acids (excess) Analgesics Anaesthetics, local
Anticancer agents (for example, methotrexate) Antihistamines (for example, Chlorpheniramine malate) Antimicrobials
Antirheumatics Antithyroids
Antivirals Cardiovascular/hypertensives Gastric medications
Local vasoconstrictors Opiates
Psychopharmaceuticals (for example, LSD, psilocybin) Sympathomimetics
Endocrine/metabolic
Infections - viral/ bacterial
Lesions of the nose/ airway blockage
Atrophic rhinitis Chronic inflammatory rhinitis Hypertrophic rhinitis Nasal polyposis Rhinitis medicamentosa Atrophic rhinitis Structural abnormality
Cysteine Histidine Antipyrine Cocaine HCI Procaine HCI Tetracaine HCI
Medical interventions Griseofu Ivi n Lincomycin Macrolides Neomycin Pencillins Streptomycin Tetracycl i nes Tyrothricin Mercury/gold salts o-Penicillamine Methimazole Propylthiouracil Thiouracil
Addison's disease Congenital adrenal hyperplasia Cushing's syndrome Diabetes mellitus Froelich's syndrome Gigantism Hypergonadotropic hypogonadism Hypothyroidism Kallmann's syndrome Pregnancy Panhypopituitarism Pseudohypoparathyroidism Sjogren's syndrome Turner's syndrome Acquired immunodeficiency syndrome (AIDS) Acute viral rhinitis Bacterial rhinosinusitis Bronchiectasis Fungal Influenza Rickettsial Microfilarial Adenoid hypertrophy Allergic rhinitis
Artovastatin calcium (Lipitor) Cholestyramine Clofibrate Acetylcholine Acetyl, ~-methylcholine Menthol Strychnine Zinc sulphate Codeine Hydromorphone HCI Morphine
Amphetamine sulphate Fenbutrazate HCI Phenmetrazine theoclate
Perennial Seasonal
Deviated septum Weakness of alae nasi
Vasomotor rhinitis Adrenalectomy Anaesthesia Anterior craniotomy Arteriography Chemotherapy Frontal lobe resection Gastrectomy Hemodialysis Hypophysectomy Influenza vaccination Laryngectomy Oophorectomy Paranasal sinus exenteration Radiation· therapy Rhinoplasty Temporal lobe resection Thyroidectomy
Cimetidine
(Continued over)
1674 I PART 13 THE NOSE AND PARANASAL SINUSES ~~f;ategory
Category
~'. ~~
Neoplasms in tracrania I
Frontal lobe gliomas and other tumours Midline cranial tumours
Olfactory groove/cribriform plate meningiomas Osteomas Paraoptic chiasma tumours
Neoplasms intranasal
Temporal lobe tumours Neuro-olfactory tumours
Other benign or malignant nasal tumours
Neoplasms - extranasal and extracranial
Neurologic
Nutri tiona 1/ metabol ic
Breast Gastrointestinal tract Laryngeal Lung Ovary Testicular Amyotrophic lateral sclerosis Alzheimer's disease Cerebral abscess (especially frontal or ethmoidal regions) Down syndrome Familial dysautonomia Guam amyotrophic lateral sclerosis (ALS)/PDI dementia Head trauma Huntington's disease Hyd rocephal us Korsakoff'S psychosis Migraine Meningitis Mu Iti pie sclerosis Myaesthenia gravis Paget's disease Parkinson's disease Refsum's syndrome Restless leg syndrome Syphilis Syringomye lia Temporal lobe epilepsy Hamartomas Mesial temporal sclerosis Scars/previous infarcts Vascu lar insufficiency/anoxia
Abetal i poprotei naem ia Chronic alcoholism Chronic renal failure Cirrhosis of liver
Gout Protein calorie malnutrition Abetalipoproteinaemia Total parenteral nutrition without adequate replacement Trace metal deficiencies
Parasaggital meningiomas Tumours of the corpus callosum
Aneurysms Craniopharyngioma Pituitary tumours (especially adenomasl Suprasellar cholesteatoma Suprasellar meningioma Esthesioe pithe lioma Esthesioneuroblastoma Esthesioneurocytoma Esthesione uroe pi thel ioma Adenocarcinoma leukaemic infiltration Nasopharyngeal tumours wi th extension Neurofibroma Paranasal tumours with extension Schwannoma
Whipple's disease Vitamin deficiency
Pulmonary Psychiatric
Copper Zinc Vitamin A Vitamin B6 Vitamin B12
Chronic obstructive pulmonary disease Anorexia nervosa (severe stage) Attention deficit disorder Depressive disorders Hysteria Malingering Olfactory reference syndrome Schizophrenia Schizotypy Seasonal affective disorder
ACKNOWLEDGEMENTS This contribution was supported, in part, by the following grants from the National Institutes of Health, USA: POl DC 00161, R01 DC 04278, RO 1 DC 02974 and ROt AG 17496. Disclosure: Dr Doty is a major shareholder in Sensonics, Inc., a manufacturer of tests of taste and smell.
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Chapter 131 Abnormalities of smell
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27: 181-96.
132 Orbital and optic nerve decompression VALERIE J LUND AND GEOFFREY EROSE
I ntroduc tion
1677
Applied surgical anatomy
1677
Key points
Orbital decompression
1 679
Deficiencies in current knowleqge and areas of future
Best clinical practice
1684
Decompression of the optic nerve
1684
Best clinical pract ice
1685
1 685
The 'implodin g' antrum
1 686 1686
research
1686
References
A Medline search was performed using the key words orbital decompression, optic nerve decompression, imploding
antrum and silent sinus syndrome. All surgical procedures are Grade B/C.
cavity and ethmoidal labyrinth medially, the maxillary
INTRODUCTION
sinus and occasionally infraorbital ethmoidal cells infer The orbit, surrounded on three sides by the paranasal
iorly and laterally, the infratemporal fossa and middle
sinuses, is an area of considerable interface between
cranial fossa. The apex of the orbit leads directly into the
otorhinolaryngologists and ophthalmologists. Inflamma
middle cranial fossa.}' 2,
tion, infection and neoplasia can spread in both directions and may happen both accidentally and intentionally. This relationship has been heightened by the advent of
The
orbit
is
a
3,4
[****]
quadrilateral
pyramid,
with
its
base facing forwards, laterally and slightly inferiorly
(Figure 132.1),
and it contains the globe, extraocular
endoscopic sinus surgery in both a positive and negative
muscles, nerves, vessels and some associated structures
sense. However, armed with a clear understanding of the
such
anatomy and careful clinical and radiological assessment
the adult Caucasian orbit is 30 mL, 70 percent of which
as
the lacrimal apparatus. The average volume of
it can be an area of considerable mutual benefit for ENT
is occupied by retrobulbar and peribulbar structures.
surgeons, eye surgeons and patients alike. This chapter
As it constitutes a fixed bony cavity, a 4-mL increase
will concentrate on three principal conditions: orbital and
in retrobulbar tissue volume produces about
optic nerve decompression, and the imploding antrum or
proptosis.5
6 mm of
'silent sinus' syndrome.
Medial wall APPLIED SURGICAL ANATOMY
of orbit
The importance of the anatomy of the orbit to the
This wall is of most significance to the otorhinolaryn gologist. It is composed of:
otolaryngological surgeon lies mainly in its relationships
•
the frontal process of the maxilla;
with the anterior cranial fossa lying superiorly, the nasal
•
the lacrimal bone;
1678 I
PART 13 THE NOSE AND PARANASAL SINUSES
a Patterson s approach to an external ethmoidectomy; in '
9
percent the origin of the muscle is intraperiosteal with no
bony attachment, thus faciliating dissection. The floor is generally thin
(0.5-1 mm) and the commonest site for
blow-out fractures is medial to the infraorbital canal. The infraorbital foramen and the optic foramen are separated
by an average distance of 46 mm and the average distance from the posterior wall of the maxilla to the infraorbital foramen is
about 25 mm.
Superior wall The roof is triangular and composed of the orbital plate Figure 132.1
The orbit. A, anterior ethmoidal foramen; p. posterior ethmoidal foramen; 0, optic canal; E, l am ina p apyracea of ethmoid; M. maxil l a; L. lacrimal bone. • •
the
region. The extent o f frontal and ethmoidal sinus invasion is variable but may go as far as the zygomatic process or ethmoidal ( O nodi)
the body of the sp henoid. lies
.
optic foramen which can be surrounded by spheno
the lamina papyracea of the ethmoid;
Anteromedially
of the frontal and lesser wing of the sphenoid The bone is
thin (generally less than 3 mm) except in the sphenoid
cells (Figure 132.2). The superior
margin has a supraorbital notch or foramen, transmit ting
fossa
for the
lacrimal
sac,
demarcated by anterior and posterior lacrimal crests.
the respective vessels and nerves
,
and in 50 percent of
the pop ulat ion a frontal notch, lying more medially.
Foramina for the anterior and posterior ethmoidal vessels
The trochlea
and nerves are located at the frontoethmoid suture, where
the tendinous part of the superior oblique muscle to the
the medial wall joins the roof and their position is variable;
is
a
connective tissue sling
anchOring
orbital wall and the trochlear fovea, a small depression
24-12-6' has been suggested, based respectively
lying close to the s uperomedial orbital margin . In about
crest to the anterior ethmoidal foramen, from the anterior
pulley are ossified and the tendon runs in a synovi al
a
on the average distance (in mm) from the anterior lacrimal to posterior ethmoidal foramen, and from the posterior
ethmoidal foramen to the optic canal.6 The ethmoidal an
foramina are also taken as
indication of the level of the
cribriform plate, but are only a rough guide as
16 percent
of individuals have no anterior ethmoidal foramen , 30 percent have multiple foramina and
4.6 percent have
10 percent of individuals the ligaments attaching the
sheath within the pulley.
Incis ions should be placed
to avoid damage to the supratrochlear and supraorbital nerves,
the levator
trochlea
- all structures rel ated to t he superior orbital
margin.
palpebrae
superioris
muscle
none.7 The medial wall is extremely thin in parts and may
be naturally deficient and thus a poor anatomical barrier to the spread of sinonasal pathology.
Inferior wall The floor is composed of three bones: 1. the large orbital plate of the maxilla;
2. the zygomatic orbital plate anterolaterally; 3. the orbital process of the palatine bone.
The infraorbital foramen, lying halfway along the inferior rim, is vertically in line with the superior orbital notch and
is
anterior
continuo us with
the
infraorbital
canal.
( and occasionally middle superior)
The
alveolar
nerves join the infraorbital nerve within the canal which, if damaged, may lead dentition
.
8,
to denervation
of the upper
9 Lateral to the nasolacrimal duct is a pit
marking the origin of the inferior oblique muscle, which
is the only extrinsic muscle to take origin from the anterior part of the orbit and may be encountered during
Figure 134.2 Coronal CT scan of the sinuses sh owing a sph enoeth moidal (Onodi ) cell .
and
r
Chapter 132
Lateral wall
The lateral wall is composed of: • the greater wing of the sphenoid; � the orbital surface of the zygoma; • the zygomatic process of the frontal bone.
The superior orbital fissure lies between the greater and lesser wings of the sphenoid. Through it pass cranial nerves III, IV, V I, the ophthalmic branch of V and the superior ophthalmic vein. The fissure is at least 28 mm from the frontozygomatic suture at the rim, and due to this depth and the curvature of the lateral wall it is rarely at risk in intraorbital procedures.
Changes with age
Exploration of the orbit in children is, fortunately, rare and growth of the orbit occurs with the development of the facial skeleton. Initially, the orbital fissures are large, the orbital index (orbital height/orbital width x 100) is high and the volume is great so that there is little change in the overall size after seven years of age. The orbital fissures are relatively larger and while an infraorbital foramen is usually present at birth, the canal may not be fully formed, remaining open to the orbital surface for some years. Resorption of bone happens with advancing age, leading to defects and widening of the fissures. The female orbit is, in general, more elongated and relatively larger than that of the male.
Periorbita
The importance of the orbital periosteum lies in its ability to protect the orbital contents and to resist spread of infection and malignancy. It is adherent to the orbital margins, sutures, foramina, fissures and lacrimal fossa and is continuous with dura through the superior orbital fissure, optic canal and ethmoidal canals. It encloses the lacrimal fossa . and surrounds the duct as far as the inferior meatus. It must, there fore, be dissected from its attachments with care, at the least to avoid troublesome prolapse of fat into the operative field. The extremities of the tarsal plates in the lids are attached to the orbital margin by strong fibrous structures - the palpebral (canthal) ligaments. The medial canthal ligament comprises the preseptal and pretarsal heads of orbicularis oculi muscle and each of these has a superficial and deep component. The superficial heads fuse medially to form that part of the medial canthal ligament that attaches to the anterior lacrimal crest and the deep heads attach to the posterior lacrimal crest. The superficial heads may be detached with impunity during surgery,
Orbital and optic nerve decompression I 1679
but a complete loss of tendinous fixation leads to an unopposed action of the orbicularis muscle and canthal dystopia - with a rounding of the medial canthus, disappearance of the caruncle and increased intercanthal distance. The fascia bulbi (Tenon's capsule) is a thin membrane surrounding the globe from the cornea to the optic nerve. Inferiorly it is thickened to form the suspensory ligament of Lockwood, the importance of which becomes evident after radical maxillectomy.lO
Radiological evaluation of the orbit
In addition to clinical evaluation, important information is provided by radiological assessment and thin-slice computed tomography (CT) remains the investigation of choice in orbital disease - being readily available, fast and providing the surgically most useful information. Different protocols may be required, dependent upon whether the sinus or orbital anatomy is to be optimally imaged. Magnetic resonance imaging remains a secondary investigation to CT and, wherever uncertainty exists after CT, may be helpful in elucidating the relation ship between the optic nerve and orbital or optic canal lesions.11, 12, 13 [****]
ORBITAL DECOMPRESSION Introduction
The finite capacity of the bony orbit means that increases in tissue volume usually result in anterior displacement of the orbital contents. The commonest example of this is thyroid eye disease where hypertrophy of the extraocular muscles and fat produce at least cosmetic embarrassment and at worst corneal exposure, ulceration and even prolapse of the globe. Involvement of the muscles may lead to diplopia and compression of the optic nerve at the orbital apex leading to visual loss. The creation of greater orbital volume by removal of one or more walls dates back to 1911 when Dollinger described removal of the lateral wall.14 Neither this alone nor removal of the orbital roof as advocated by NaffzigerlS produced significant reduction in axial prop tosis, but may allow some outward prolapse of orbital tissue when decompression of the nerve is required. A more satisfactory surgical decompression results from removal of the medial and inferior walls, either individually or combined. Walsh and Ogura16 employed a transantral approach, whereas Harrison1? advocated a modified Patterson's external ethmoidectomy, through an external incision based in the nasojugal fold; this incision, albeit relatively innocuous, can be avoided by a transconjunctival approach. These procedures aim
1680 I
PART 13
THE NOSE AND PARANASAL SINUSES
to remove the entire medial wall from the level of the ethmoidal vessel superiorly, down and across the orbital floor to a line medial, and in some cases lateral, to the infraorbital nerve - and posteriorly
as
far as the orbital
apex. A transnasal endoscopic approach may be utilized to remove the entire medial wall and medial part of the orbital floor, but in more severe cases a
three-wall
decompression via a lower eyelid swinging flap is most effective.18
[**/*]
Indications Although
decompression of the orbit is most com
monly performed for thyroid eye disease, other indica tions include vasculitis, sphenoid wing meningiomas with compressive optic neuropathy and large myopic globes.
Therapeutic options In addition to correction of thyroid status and cessa tion of smoking, other medical therapies for
active
thyroid eye disease include high-dose corticosteroids, low-dose orbital
radiotherapy or immunosuppression
with agents such as azathioprine. Where these fail, or are deemed inappropriate, surgical decompression may be undertaken primarily or as a secondary procedure.
Preoperative assessment Patients should undergo CT of the orbit and sinuses to demonstra te anatomy, covert disease and to assist with the diagnosis of proptosis. In thyroid eye disease, axial cuts optimally demonstrate hypertrophy of the extra ocular muscles (and orbital fat) with associated axial proptosis and often a degree of autodecompression into the ethmoidal labyrinth - producing the classical 'Coca Cola' bottle sign
(Figure 132.3). For an endoscopic
approach, coronal scans carried out on wider window
widths are required to show the detailed anatomy of the lateral nasal wal1.19 All patients should be under the care of an ophthal mologist with an interest in thyroid eye disease and should have undergone a full preoperative assessment including degree of proptosis, assessment of eye move ments and diplopia, and measurement of visual acuity
Figure 132.3 (a) Axial and (b) coronal CT scans in thyroid eye d i sease showing the classical 'Coca Cola' bottle sign of autodecompression (axial) and com pression of orbital apex due to enlarged extraocular muscles.
and colour vision. A detailed discussion of the potential benefits and complications of the procedure must take place with the patient, in particular, highlighting the possibility of temporary or permanent double vision.
The patient must be aware of the possible need for
Surgical techniques ENDOSCOPIC DECOMPRESSION
strabismus surgery and subsequent eyelid surgery, parti
The procedure is performed under general anaesthesia
cularly for upper lid retraction.
with additional vasoconstriction provided by Moffat's
Chapter 132
solution (2 mL 10 percent cocaine solution, 2 mL I: 1000 adrenaline and 1 mL of 2 percent sodium bicarbonate) instilled in the anaesthetic room. Additional haemostasis is achieved by positioning the patient in a reverse Trendelenberg position, by use of mild to moderate hypotensive anaesthesia and the application of topical 1:1000 adrenaline on ribbon gauze to the surgical field. A standard endoscopic sinus dissection is performed commencing with uncinectomy and infundibulotomy using a Freer's elevator or sickle knife. An anterior portion of the middle turbinate is often removed to facilitate the dissection. The anterior and posterior ethmoids are exenterated, defining and skeletonizing the lamina papyracea. T he dissection is continued from front to back, defining the skull base and ethmoidal vessels if easily apparent. The posterior ethmoids are opened as far as the sphenoid, which is then incorporated into the cavity by enlarging the natural ostium laterally. The sphenoid ostium can usually be visualized directly or palpated in the sphenoethmoidal recess lying approxi mately 1 cm above the posterior choana and 1-2 mm lateral to the nasal septum. Although decompression is usually not necessary beyond the ethmosphenoid junc tion, it is an advantage to define this area in case a second procedure should be required in the future. Where there is severe visual impairment at presentation, it may be necessary to remove the thick bone of the orbital apex using an endoscopic drill specifically designed for this purpose. The largest possible middle meatal antrostomy is fashioned, mainly into the posterior fontanelle to allow adequate access to the medial floor of the orbit. The bone of the lamina papyracea and medial orbital floor can be removed either with a small tympanic drum elevator or Freer's elevator. The bone at the junction of the medial floor and medial orbital walls is thick and strong down-biting forceps are usually required or the bone drilled in exceptional cases. Care should be taken when removing the bone superiorly to avoid damage to the skull base, which might produce a cerebrospinal fluid leak and/or haemorrhage from the ethmoidal vessels. Anteriorly the bone may be removed with back biting forceps, curettes or ball-tipped seekers as far as the anterior attachment of the uncinate process with the maxillary hiatus. Care should be taken not to damage the nasolacrimal duct that runs just anterior to this point. Lastly, removal of the bone across the floor of the orbit is undertaken, although it is rarely possible to reach the infraorbital nerve nor indeed advisable as this may lead to paraesthesia. Bone can be removed anterosuperioriy in the region of the frontal recess, but should be retained in the immediate vicinity of the recess to avoid occlusion of this area when orbital fat prolapses into the surgical field. Decompression will not occur unless the orbital periosteum is incised and this may be carried out with a sickle· knife or disposable myringotome. The maximwn disruption of periosteum may be achieved by making
O rb i tal and optic nerve decompression . 1681
H isto lo g i cal section ( axial plan e throug h the apex) showing the intimate relationsh i p of the posterior ethmoidal cel l s to the medial rectus muscle and o p t ic nerve (haematoxyl in and eosin ) . Figure 132.4
optic
several longitudinal incisions, starting posteriorly and working from inferolaterally to superior. These incisions can be connected by vertical cuts, although great care must be exercised to ensure that structures deep to the periosteum (e.g. mediaJ rectus muscle) are not damaged (Figure 132.4). Gentle pressure on the globe encourages fat prolapse into the surgical cavity, which can be encouraged by gently teasing out the fat to break up some of the sep tations, but taking care not to create significant bleeding or damage to underlying structures. Ideally, the orbital contents should fill the majority of the ethmoidal cavity but should not block the drainage of the frontal or maxillary sinuses which could lead to secondary infection. A small TeJfa dressing, which is removed the following morning, is inserted at the end of the operation and the patient is told to avoid nose blowing for at least two weeks postoperatively otherwise this may result in surgical emphysema or even prolapse of the globe in the early postoperative phase. Patients are usually discharged on the first postoperative day unless, very rarely, there has been significant bleeding or bruising.
THREE-WALL DECOMPRESSION THROUGH A MINIMAL INCISION
A
horizontaJ canthotomy of about 1.5 cm is made and inferior cantholysis performed, this release of the lower eyelid being extended medially by division of the conjunctiva, inferior retractors and orbital septum at a point 1 mm below the tarsal border. A 4/0 nyJon suture is used to close the free conjunctival edge to the upper eyelid, this both protecting the cornea and tautening the orbital septum which facilitates the dissection of the suborbicularis plane down to the inferior orbital rim. Lateral waH removal is accomplished through a perio steal incision placed about 7-8 nun outside the orbital
I I
l_
' -� L__
1682 I
PART 13
1
THE NOSE AND PARANASAL SINUSES
rim, with a periosteal flap being raised towards and into
the orbit. A coronal-plane osteotomy is made 3 mm behind the lateral orbital r im and a back cut, placed in the axial plane, is made just above the zygomatic arch. The
bone fragment behind the rim is then out fracture d , using -
a ham me r and gouge, and the bone window enlarged
much
as
as
required, the 3 mm spur of bone at the orbital
rim being left undisturbed. The lateral wall periosteum
is opened along a line just behind the arcus marginalis and two sagittal incisions placed, one above and one
below the orbital lobe of the lacrimal gland - freeing the anterior pole of the gland and allowing it to be 'floated'
back i nto the bone defect; this repositioning of the gland,
together wi th the marked reduction in proptosis, restores
the 'normal' upper eyelid sulcus. The periosteum inferior to the lacrimal gland is also excised and the fat freed to allow prolapse into the lateral wall defect. For removal of the medial wall and orbital floor, the orbital periosteum is undermined posteriorly from the infer io r orbital rim, with extension superomedially up to the level of the ethmoidal vessels at the frontoethmoidal suture. An anterior and posterior ethmoidectomy is then performed and the periosteum excised completely from the area corresponding to that of bone removal. If further decompression is needed, the orbital floor is down fractured medial to the infraorbital nerve (using a heavy gauge artery clip) and the bone fragme nts removed piecemeal until reaching the back wall of the maxilla;
dependent upon the required degree of decompression, the lateral extent may be varied from just medial to the infraorbital nerve to far laterally (with complete removal of the bone from around the nerve). It is important to retain the anterior two-thirds of the maxilloethmoidal bone strut, as this prevents fat prolapse from blocking maxillary aeration with subsequent secondary imploding antrum syndrome?O
Using a 4/0 absorbable suture, the remaining bar of lateral periosteum - to which the upper limb of the
canthal tendon remains fixed - is sutured back around the spur of intact lateral
orbital rim and a slip of the lower
tarsus reattached to the upper limb of the canthal tendon.
After placement of a vacuum drain through the lateral wall
defect
into
the
orbital
tissues,
the
superficial
tempor al fascia is clos ed with absorbable sutures
and
the skin incisions closed in layer s The lower lid is placed .
Figure 132.5
(a) Axial and
(b)
coronal CT scans
of
patient
with th y ro i d eye disease before and after endoscopi c _ decompression.
on traction to the forehead using a 4/0 nylon 'Frost' suture and a firm dressing applie d until the following day. The vacuum drain is removed when appropriate, almost always within 12 hours, and the vision checked at any
time should there be severe or increasing periocular pain.
underestimated. In a cohort of nearly 60 cases, the reduction in axial p ropt os is with transnasal decom
pression is comparable to that achieved by external or transantral approaches to the medial wall and floor of the orbit. Most authors report a mean reduction in axial
Results
proptosis of 3-4 mm ment
can
be
achieved
The majority of patie nts unde rgoing orbital decompres
endoscopic approach
sion do so for corneal exposure and cosmetic embarrass
Rizk
ment, the psychological effects of which should not be
from an endoscopic approach
(Figure 132.5).21, 22, 23, 24, 25, 26, 27,28 Additional improve-
et
by
the
combination
of an
with a modified Caldwell-Luc, with
az.29 rep orting
a
mean decompression of 4.83 mm
in nine patients - this being similar to the results achie ved
Chapter 132
Orbital and optic nerve decompression I 1683
Fig u re 132.7 CIin ieaI photographs showi ng a patient (a) before and (b) after right-sided three-wall decompression with prolapse of the globes possible prior to the surgery.
Complications Figure 132.6
Axial CT scans of patient with thyroid eye disease (a) before and (b) after three-wall decompression.
Apart from minor and temporary orbital bruising, the main complication after orbitaJ decompression relates to diplopia, which may be an exa cerbation of a pre-existing problem or may happen de
novo.
D i plop ia is partic ularly
If greate r
associated with inferomedial decompressions, probably
sion may be undertaken through a lower lid swinging
fibrotic medial recti. The exacerb atio n is temporary in most patient s with them often returning to their preoperat ive status (or better) d uring the weeks after surgery. In a ser1es of 23 patients u ndergoing endoscopic
by the conventional transantral approach.3o•31
recession is req uired however, a three-wall decompres ,
flap, with an average reduction of proptosis of
7.2 mm
(Figure 132.6). The vast majority of recession can be appreciated at the end of the operation and there is only minimal change in proptosis after surgery (Figure 132.7). In those cases where vision is compromised with reduced visual acuity and/or colour vision, an endoscopic 25 26. 32 approach will stabilize and improve the situation. , ,
Indeed, an endoscopic approach to the orbital apex can be
resulting from a predominant effect of prolap se of the ,
decompression, 14 had double vision postoperatively, but
of binocular single vision improved in four of the w ith pre-existing d iplopia ; 11 patients required st r ab i sm us surgery, of whom nine had manifest strabis
the field eight
mus before decompression.28 Owing to compressive optic
some p a t ie nts with preoperative squint
undertaken following a conventional three-wall decom
neuropat hy
to be affected.
this problem after the opt i c neuropathy is relieved by
pression in those rare individuals where vision continues Once recession of the globe
has taken place, patients
of a 'staring' appearance, mainly due to upper eyelid retraction and this may be dealt with in the months fo llow i ng decompression when the eyes have
may stiJJ be aware
stabiJized. 33,34
,
may not be aware of diplopia and may only appreciate decompression .
is those with restr icted motility and within 20° of the primary posi tion preoperatively who are most likely to require subsequent muscle As expected, it
dip lopia sUIger/
5
and some have advocated performing medial
1684 I
PART 13
THE NOSE AND PARANASAL SINUSES
rectus muscle recession at the time of decompression.26
Indications
of the medial wall and floor will minimize this complica
Indications for orbital apex and optic nerve decompres
Preservation of an inferomedial bony strut at the junction
tion24,36 and a prism may be used during the initial
postoperative period while the situation stabilizes. Given
the elective nature of the procedure, it is important that
patients clearly understand the potential risks and possible need for future surgery. 37 Epiphora may arise or be exacerbated after surgery, although it rarely persists unless the nasolacrimal duct has been directly damaged - which happens most often with external approaches, such as that of Patterson. Paraesthesia
in the territory supplied by the
infraorbital nerve is primarily associated with approaches in which the whole of the orbital floor is removed. Prolapse of the orbital contents into the ethmoidal infundibulum andlor frontal recess may lead to secondary bacterial sinusitis, an 'imploding' maxillary antrum and even mucocoele formation?O This is least likely to happen with an endoscopic approach, due to the large middle meatal antrostomy and preservation of the bone adjacent to the frontal recess. Cosmetic problems from the external incisions are rare,
although patients may get
some loss of con
tour in the temporal fossa after removal of the lateral orbital walL
sion include: •
trauma;
•
thyroid eye disease;
•
neoplastic compression, e.g. meningioma;
•
fibrosis due to chronic inflammation, e.g. Wegener's granulomatosis.
The commonest indication has been for post-traumatic visual loss owing to direct or indirect injury, such as skull base
fracture, a
foreign body or haematoma. These
patients have often suffered multiple injuries, and due to the condition of the patient, the visual loss may not
be immediately apparent. It is not known how long the optic nerve can survive
in man after interruption of its
blood supply although some animal experiments suggest
irreversible damage happens after 90 minutes. As there have been anecdotal reports of recovery even days after injury, surgery may still be considered where there is no contraindication. Attempts have been made to compare surgery and mega dose parental steroids, and whereas 8 the latter treatment has been recommended,3 �nother
study by Levin et al.39 comparing both surgical and medical modalities concluded that neither should be considered as a standard of care.
[**1*]
Dysthyroid optic neuropathy may not be adequately
Best clini
relieved by orbital decompression if the sphenoid air cells
.I
The com m onest indication for orbital decom pression is thyroid eye disease although it is u ndertaken in the m inority of patients with this condition. .! Severe proptosis or com p ression of the optic nerve at the orbital apex may threaten vision and require urgent decom pression. .I Patients must understand the potential com p lications and additional treatments that may be required. .I Good results m ay be achieved in mild to moderate cases by an endosco pic approach to the medial and inferior w alls, w hereas a lower eyelid swing ing flap approach for graded removal of up to three wal ls of the orbit o ffers the best resul ts fo r more severe cases.
extend far anteriorly; in such cases it may be necessar y to extend the decompression further posteriorly by removal of part of the lateral wall of the sphenoid. Occasionally patients
with b enign or malignant tu
mours of the skull base may develop compression of the orbital apex in situations where complete resection of the tumour is not possible. Meningiomas of the skull base produce a hyperostotic reaction in adjacent bone together
with a mass effect from the soft tissue component that may directly impact on the orbital apex. These changes often
predominantly affect the lateral compartment of the apex enabling space to be created medially, thereby buying time for patients in whom the course of disease is often indolent Other tions,
indications
such
as
have
Wegener's
included vasculitic granulomatosis
and
condi even
radiation neuritis - although here the results have been
DECOMPRESSION OF THE OPTIC NERVE Introduction
Surgical techniques
The orbital apex and optic nerve may be decompressed in a variety of circumstances and by a range of approaches. Fine detailed axial and coronal
disappoin ting.
CT scanning allows precise
determination of the anatomy and underlying pathology
which has necessitated the need for surgery although the criteria for intervention remains to be determined and the
number of cases undertaken relatively few.
The orbital apex may be approached externally from above, laterally, medially or combinations thereof. An extracranial
transnasal
endoscopic
approach
may
be
employed for medial decompression but, when a more extensive unilateral or bilateral decompression of the nerve is required, a craniofacial approach should be considered.
Chapter 132
Orbital and optic nerve decompression I 1685
ENDOSCOPIC OPTIC NERVE DECOMPRESSION an
In many circumstances
already been undertaken;
procedure leading to
orbital decompression has if
not,
the
steps
the junction of the
of this
.I
Fol lowing trauma, optic canal decompression is u ndertaken more in hope than expectation but anecdotal reports suggest that where there is no contraindication to s urgery, this may be worthwhile. There is, however, no definite evidence of benefit for this procedure after trau matic optic neuropathy. .I In cases of thyroid eye disease where there is an anteriorly positioned sphenoid. further extension of orbital decompression towards the orbital apex may produce significant improvement in vision. .I Optic nerve decompression shou ld be considered in cases of uni l ateral or bilateral optic nerve compression due to incurable fibrosis or tumours.
posterior
ethmoid with sphenoid sinuses are undertaken. The bone thickens at this point and often needs to be thinned using an irrigated sheathed endoscopic drill prior to removal, The dissection can be continued along the lateral wall of the sphenoid to a variable degree dependent upon the individual pathology and anatomy. The orbital perios teum is then incised from posterior to anterior using a disposable sickle-bladed knife, The depth and extent of this again varies from case to case but includes release of
the tendinous ring of Zinn in most cases. In theory, complete opening of the optic nerve sheath should result in a demonstration of cerebrospinal fluid but, in practice,
this is rarely seen, It should be remembered that the ophthalmic artery may lie
in the inferior medial quadrant
of the optic nerve sheath in approximately 15 percent of cases40 and therefore incisions should be restricted to the superomedial quadrant. However, in cases of extrinsic compression of the nerve, there should be no need to open the sheath,
THE IIMPLODING' ANTRUM Indications and surgical techniques
A
EXTERNAL APPROACHES
condition has been recognized in which increasing
enophthalmos occurs associated with contracture of the 20 49 50 " 1ater al maxillary antrum IpSl The antrum IS usua 11y >
Similar amounts of bone may be removed via external frontoethmoidectomy approaches, such as that of Lynch Howarth. Where more extensive bone removal is required, a craniofacial approach allows decompression of the optic 41 42 '
nerve up to the optIC ' c h'Iasm on one or both SI'des.
.
.
opacified on imaging and, while the condition has been described
as
happening
spontaneously,
it
may
be
associated with obstruction of the ethmoid infundibulum after orbital decompression.2o Goldberg
et
[** /* ] al,36 suggested that retention of an
inferomedial strut of bone between the maxillary and ethmoid during orbital decompression provides the globe
Results
with support and prevents hypo globus. It would, how
Relatively few large series of this procedure have been published and these have largely related to post-traumatic decompression.43, 44. 45, 46
In
a
personal
series
of
14
patients undergoing endoscopic decompression, the pro
cedure was most successful for those with thyroid eye
disease and sphenoid meningioma in which long-term 4 improvement in vision was attained. 7 Primary or secondary optic nerve decompression was undertaken in seven patients undergoing craniofacial resection for sino nasal neoplasia, two of whom had already lost one eye. Although in four cases disease ultimately rendered the
patients
blind,
the
decompression
preserved
or
improved failing vision in two individuals until close
to their deaths and offered useful palliation.48
ever, appear that maintenance of maxillary aeration rather than direct support of orbital tissues - is more significant in avoiding this problem as evidenced by the deve1opment 0 f 1'd'lOpat h'IC cases.
50 51 .
In both idiopathic and secondary imploding antrum syndrome there is a paucity of sinus symptoms. The idiopathic condition is associated with a high incidence of abnormal nasal anatomy, the majority of patients having a nasal septal deviation to the affected side and many having an abnormal lateralized middle turbinate
0 (Figure 132.8).5 After bone-removing orbital decom
pression, globe
has
an
initially
occasionally
symmetrical been
recession
followed
by
of
the
increasing
unilateral enophthalmos, usually on the left side, Where
CT scanning confirms occlusion of the maxillary sinus
drainage, an endoscopic middle meatal antrostomy may be
Complications These include acute postoperative visual loss, diplopia and, theoretically, a cerebospinal fluid leak (although, in practice, rarely encountered),
performed to drain the mucus and stabilize the situation.
Restoration of the globe position may be difficult after three-wall decompression, as there is less neighbouring bone to facilitate reconstruction; mobilization of orbital contents and antral placement of a Whitehead's varnish pack for three weeks (via an anterior antrostomy) has, in
J____
•__.>__, _ _
1686
I PART 13 THE NOSE AND PARANASAL SINUSES
Deficiencies in current knowledge and areas of future research >- The exact cause of changes in the fat and muscles in thyroid eye disease remains unknown and requires further elucidation. ). In view of the probable benefits of high-dose steroids after major injury, a placebo-controlled randomized trial comparing medical and surgical therapies for optic canal decompression is hard to justify.
REFERENCES 1.
Wolff E. Anatomy of the eye and orbit, 7th edn. Revised by R Warwick, London: HK Lewis, 1976.
2.
Figure 132.8
with lateralized middle turbinate and lowered orbital floor in an
tmao many icasntaeisn) prthoeveimd preffoevectidveposiprtioonduciof nthgesuglffiobecie?nOt fibrosis vibePatsiinioegnnttsfeomusml oporwitnagrywarrebutposneidoctioofcniasaniogpotnalofelyntthiraeelqglinuiocrberiena)gstehciionsrusdoublecutaliolnye with prisms or further surgery.
3.
Kanski JJ. Clinical ophthalmology, 2nd edn. Oxford:
4.
Roper-Hall MJ. Stallard's eye surgery, 7th edn. London:
Butterworth-Heinemann, 1989.
idiopathic case.
Wright. 1989.
in
Complications be
Doxanas MT, Anderson RL (eds). Clinical orbital anatomy. Baltimore: Williams Et Wilkins, 1984.
Coronal CT showing imploding maxillary antrum
5.
Gorman CA. The presentation and management of endocrine ophthalmopathy. Clinics in Endocrinology and Metabolism. 1978; 7: 67-96.
*
6.
Rontal E, Rontal M, Guildford FT. Surgical anatomy of the orbit. Annals of Otology, Rhinology and Laryngology. 1979; 88: 382-6.
7.
Shaheen OH. 'Epistaxis in the middle-aged and elderly'.
8.
Wood Jones F. The anterior superior alveolar nerve and
MS thesis, University of London, 1967. vessels. Journal of Anatomy. 1939; 73: 583-91. 9.
Harrison DFN. Surgical anatomy of the maxillary and ethm'Jidal sinuses - a reappraisal. Laryngoscope. 1971;
wt'-r:�:;tog�'e'r;,'WithiconsideJaQle , , .vaofsq:lliti¢:·�ond-ition�' nt . e : ; :i!'�i;!i��f'1�i:�;;;;r;; , adacchiryevocedy,-swtoitlrhinlenosdohastomyaJ.and- results the be ' fl o or b l o wo ut ' . KE¥ POfNTS: '.
•
:
.....
"""!�;. 0,/ - .'
: . � .�.
-.
...'-·.r ·:
.. ,
' ;. �
-
� I"
" ?" '" �
.
..
"
_':'�
••
�l.
-
-
10.
.-
' ' An>-�N'1{�utg�� and",ciphth,�lIDQlo�srmay',c
'
'- "
81: 1658-64.
'
:; -' .: '
':
beD:etlt .to, : ." tJAe�:patient.,:'·" ,/ �;,�-f'1 ��;N \:f(_ ')i<:���: ., , A�ra�ge,'bf'c.onditiorrs inclu:d�rig:-:drbitaJ. C>',"" , :,::
,.
Mechanisms of global support and post traumatic enophthalmos. I. The anatomy of the ligament sling and its
,"_
-
•
relation to intramuscular cone orbital fat. Plastic, and Reconstructive Surgery. 1985; 77: 193-202.
"
cO,tnp�ta.ti9ns mucocoele$,
'ba-¢terlaL-rhinosiUP-_sltisi,: �"
�nd
de'¢Qmpre�si.on;':'although tair
media wall' or orbital , fr.actures. ,: ' : -
'
,
"
".
Lloyd GAS. Radiology of the orbit. Philadelphia: WB
12.
Bilaniuk LT, Zimmerman RA. Computer-assisted
Saunders, 1975. tomography: sinus lesions with orbital involvement. Head and Neck Surgery. 1980; 2: 293-301. 13.
Dutton JJ. Radiographic evaluation of the orbit In: Doxanas MT, Anderson RL (eds). Clinical orbital anatomy. Baltimore: Williams & Wilkins, 1984:
may,
repair '6f
Manson PW, Carmella M, Clifford MA , Iliff NT, Morgan R.
35-6. 14.
Dollinger J. Die drickentlastlung der augenjokle durch entfurnung der aussern orbitalwant bei hochgradigen expohthalmos und koneskutwer hornhauterkrongkung. Deutsche Medizinische Wochenschrirt. 1911; 37: 1888-90.
Chapter 132
1 5.
1 6. *
1 7.
1 8. 1 9.
20.
21 .
22. 23.
24.
25.
2 6.
27.
28.
29.
30.
*
31.
Naffziger HC. Prog ressive exo phthal mos fo l lowing thyroidectomy: its pathology and treatment. Annals of Surgery. 1 93 1 ; 94: 582-6. Walsh TE, Og u ra JH. Transantral orbital deco m p ression for malignant exophthal mos. Laryngoscope. 1 957 ; 6 7 : 544-9. Harrison D FN. Su rg ical approaches to the med ial orbital wal l . Annals of Otology, Rhinology and Laryngology 1 981 ; 90: 41 5-9. McCord J r CD. Cu rrent trends in orbital d ecom pression. Ophthalmology. 1 985; 92: 2 1 -33. Lund VJ , Savy G, Lloyd GAS. Opti m u m i m ag ing for endoscopic sinus su rg e ry. Journal of Laryngology and Otology 2000 ; 1 1 4: 395-7. Rose GE, Lund VJ. Cl ini cal featu res and treatment of l ate enophthal mos after orbital deco m p ression a cond ition sugg esting an etiology for idiopath ic ' i m ploding antru m' (si l ent sinus) synd rome. Ophthalmology. 2003 ; 1 1 0 : 81 9-26. Kennedy OW, Goodstein ML, M i l le r NR, Zinreich SJ. Endoscopic transnasal orbital decomp ression. Arch ives of Otolaryngology Head and Neck Surgery. 1 990 ; 1 1 6 : 275-82. Metson R, Dal low RL, Shore JW. Endoscopic orbital decom pression. Laryngoscope. 1 994; 1 04 : 950-7. Ulual p SO, Massaro BM, Tooh l l l RJ. Cou rse of proptosis in patients with G raves' d isease after endoscopic orbital decomp ression. Laryngoscope. 1 999; 1 09 : 1 2 1 7-22. Wright ED, Davidson J, Code re F, Desrosiers M . End oscop ic orbital deco m p ression with preservati on of an infe romed ial bony strut: minimization of post-operative d i p lopia. Journal of Otolaryngology 1 999; 2 8 : 252-6. Eloy P, Trussart C, Jouzdani E, Col let S, Rom bau x P, Be rtrand B. Transnasal endoscop ic orbital decompression and G raves' ophthalm opathy. Acta Oto-Rhino Laryngologica 8elgica. 2000 ; 54: 1 65-74. M ichel 0, Oberlaner N, Neugenbaue r A, Fricke J, R ussmann W. Pre l i m inary re port : long-te rm results of transnasal orbital decompression in malignant G raves' ophthal mopathy. Strabismus. 2000 ; 8 : 1 1 3 -8. Wee DT, Carney AS, Thorpe M, Wormal d. Endoscopic orbital deco m p ression for G raves' ophthal mopathy. Journal of Laryngology and Otology 200 2 ; 1 1 6 : 609. Roberts CJ, M u rphy M F, Adams GGW, Lund VJ . Strabismus fol l owing endoscopic orbital decompression for thyroid eye d i sease. Strabismus. 2003 ; 1 0 : 1 -9. Rizk SS, Papag eorge A, Liberatore LA, Stacks EH. B i l ateral s i m u l ataneous orbital decompression for G raves' orbitopathy with a com b ined endoscopic and Cal dwell-Luc app roach. Archives of Otolaryngology - Head a n d Neck Surgery. 2000 ; 1 22 : 2 1 2-6. Warren JD, Spector JC, B u rde R. Long-term fol low-up and recent observations on 305 cases of orbital deco m p ression for dysthyroid orb itopathy. Laryngoscope. 1 989 ; 9 9 : 3 5-40. Garrity JA, Fatou rechti V, Bergstral h EJ, Bartley G B , Beatty CW, De Santo LW et al. Resu lts of transantral orbital deco m p ression in 428 patients with severe G raves'
*
32.
33.
34.
35.
36.
37.
38.
39.
40. *
41 .
42.
43.
44.
45.
46.
Orbital and optic nerve deco m p ression I 1687
ophthal mopathy. American Journal of Ophthalmology 1 993 ; 1 1 6 : 533-47. Lund VJ , Larkin G, Fel l s P, Adams G. Endoscopic orbital deco m p ression. Journal o f Laryngology and Otology 1 997 ; 1 1 1 : 1 051 -5. Stark B, Ol ivari N. Treatment of exophthal mos by orbital fat removal . Clinical Plastic Surgery. 1 993 ; 20: 285-9. Troke l S, Kazi m 1Vl , Moore S. Orbital fat removal : deco m p ression for G raves' orbitopathy. Ophthalmology. 1 993 ; 1 00 : 674-82. I\l u ne ry WR, Nunery CW, Martin RT, Truong TV, Osborn DR. The risk of d i p lopia fol l owing orbital fl oor and med ial wal l decompression in su btypes of ophthal m i c G raves' disease. Ophthalmic Plastic Reconstructive Surgery. 1 99 7 ; 1 3 : 1 53-60. Goldberg RA, Shorr N , Cohen NS. The med ial orb ital strut in the prevention of post decom pression dystopia in dysthyroid op hthal mopathy. Ophthalmic Plastic Reconstructive Surgery. 1 99 2 ; 8 : 32-4. Kraus OJ, B u l lock JD. Treatment of thyroid ocu lar myopathy with adj ustab le and nonadj ustab le sutu re strabismus s u rg e ry. Transactions of the American Ophthalmological Society 1 993 ; 9 1 : 67-84. Bracken M B, She pard MJ, Holford TR, Leo-Su m m ers L, A l d rich EF, Fazl M et al. Ad m inistration of methyl prednisolone for 24 or 48 h o u rs or ti ri l azad mesylate for 48 h o u rs in the treatment of acute sp inal cord inju ry. Journal of the A merican Medical Association. 1 99 7 ; 2 7 7 : 1 597-604. Levin LA, Beck RW, Jose ph M P, Seiff S, Kraker R. The treatment of trau matic optic ne u ropathy: the International Optic Nerve Trau ma Study. Ophthalmology 1 999 ; 1 06 : 1 268-77. Lang J. Clinical anatomy of th e nose, nasal cavity and paranasal sin uses. Stuttg art : Th ieme, 1 98 9 : 1 28. Lund VJ , Howard OJ , Wei WI, Cheesman AD. Craniofacial resection for tu mors of the nasal cavity and paranasal sinuses - a seventeen year expe rience. Head and Neck Surgery. 1 99 8 ; 20: 97-1 05. Li KK, Teknos TN , Lai A, Lau retano A, Terre l l J , Joseph M P. Extracranial optic nerve decom pression: a 1 O-year review of 92 patients. Journal of Cran iofacial Surgery. 1 999; 1 0 : 454-9. Tandon DA, Thakar A, M ahapatra AK, G hosh P. Trans eth m oidal optic nerve deco m p ression. Clinical Otolaryngology. 1 994; 1 9 : 98-1 04. Luxenberger W, Stam m berger H, Jebeles JA, Walch C. Endoscop ic optic nerve deco m p ression: the G raz experience. Laryngoscope. 1 998; 1 08 : 873-82. M au rer J, Hinni M , M ann W, Pfeiffer N. Optic nerve decompression in trau ma and tumor patients. European Arch ives of Oto-Rhino-Laryngology 1 999; 2 5 6 : 341 -5. Kountakis SE, lVlai l i ard AA, EI-Harazi SM, Long h ini L, U rso RG. Endoscopic optic nerve decompression for trau matic b l indness. Otolaryngology and Head and Neck Surgery. 2000 ; 1 23 : 34-7.
1688 I
PART 1 3
THE NOSE AND PARANASAL SINUSES
47.
Rose GE, Lund VJ. Endoscopic transnasal orbital decom pression for visual fai l u re due to sphenoid w ing mening iom a. Eye. 2006; 20 : 1 2 1 3- 1 9. Lund VJ, Howard DJ, Chees m an AD. Proceedings 4th 48. International Conference on Head Et Neck Cancer. Head Et Neck Cancer Proceedings. The orbit. Eval u ation and intraoperative m anagement. 1 996; 4: 1 020-7. 49. Soparkar CNS, Patrinely JR, Cuaycong MJ, Dai ley RA, Kersten RC, Ru b in PA et 01. The silent sinus synd rome. A
50.
51.
cause of spontaneous enophthal mos. Ophthalmology. 1 994; 1 0 1 : 772-8. Rose GE, Sandy CJ , Hal berg L, Moseley I. Cl inical and rad iolog ical ch aracte ristics of the i m ploding antru m , or 'si l ent sinus', synd rome. Ophthalmology. 2003 ; 1 1 0 : 8 1 1 -8. Davidson J K, Soparkar CN, Wi l l i ams J B , Patrinely JR. Neg ative sinus pressure and normal predisease i m ag ing in silent sinus synd rome. Arch ives o f Ophthalmology. 1 999; 1 1 7 : 1 653-4.
133 Dacryocystorhinostomy
NEIL FERGIE AND NICHOLAS S JONES
Introduction
1689
Dacryocystorhinostomy in children
1696
History
1689
Common canalicular obstruction
1696
Surgical anatomy
1690
Key points
1696
Indications
1690
Best clinical practice
1696
Preoperative assessment
1691
Deficiencies in current knowledge and areas for future 1697
Operative techniques
1691
Variations in surgical technique
1694
References
1697
Complications common to all approaches
1695
Further reading
1698
The role of antimitotic agents
1695
The data
research
in this chapter are supported by a Medline search using the MeSH headings combinations of DCR, canaliculodacryocystorhinostomy, Lester J ones, epiphora, n asolacrimal 5 tlu o roura cil
dacryocystorhinostomy,
-
,
-
,
mitomycin C and antimetabolites.
INTRODUCTION
bone removal following the creation of a middle meatal
Epiphora (excessive tearing) is a common complaint. For
matous conditions, such as Wegener's granulomatosis and
some this is a minor inconvenience but for others it can
sarcoidosis.
be
extremely
antrostomy, mid face fractures, malignancy and granu lo
troublesome,
and
a
source
of
social
embarrassment as it can alter refraction and mean that
the patient has to wipe their eye(s) perp e tu ally Epiphora .
The incidence of nasolacrimal obstruction is estimated to involve approximately
10 percent at to 35-40 percent at 90 years of age l
40 years increasing
.
can also be secondary to the excessive production of tears or arise from proximal obstruction in the drainage system at the punctum or common cannaliculus. While obstruction of the nasolacrimal system may present
with epiphora,
it may
also
present
with
a
mucocoele (Figure 133.1a), pyocoele or recurrent acute dacryocystitis (Figure 133.1b).
In the majority of cases the cause of the obstruction is unknown. Such idiopathic obstruction becomes more conunon
with
preponderance.
increasing Other
less
age
and
common
shows
a
causes
female include
surgical trauma, especially following excessive anterior
HISTORY The first report of dacryocystorhinostomy (DCR) was by Caldwell
in 1893?
Caldwell
created
a
An
ENT surgeon
rhinostomy
using
by an
profession
.
intranasal
approach by removing a por tion of the inferior turbinate and following the nasolacrimal duct to the lacrimal sac.
As can be imagined this would have involved considerable skiU given the equipment available at the time and it did not gain popularity.
Toti,3 in
1904, is credited with the
__ 0______
O _00 io ___
1690
I PART 13 THE NOSE AND PARANASAL SINUSES
They continue for 10 mm before uniting to form the common canaliculus, which has a short course of 3-5 mm angled forwards before entering
the posterior-lateral
aspect of the lacrimal sac. Occasionally there is no common
canaliculus with the
superior
and inferior
canaliculi entering the lacrimal sac independently. The nasolacrimal duct exits from the inferior point of the lacrimal sac and continues in an inferior direction with a slight lateral or medial angulation for 12 mm before entering the nose 10-15 mm behind the anterior end of the inferior turbinate and 16 mm above the floor of the nasal cavity high in the inferior meatus. It is guarded at this point by Hasner's valve. The lacrimal bone that articulates
inferiorly
with
the
base
of
the
inferior
turbinate forms the posterior wall of the bony canal while the frontal process of the maxilla forms its anterior boundary. The lacrimal sac itself lies protected in the concavity of the lacrimal fossa in the medial orbital wall. The lacrimal fossa is formed by the lacrimal bone and by the frontal process of the maxillary bone. The latter forms the anterior lacrimal crest and the remainder of the anterior part of the lacrimal fossa and comprises very dense bone. Rarely, the maxillary bone can form the whole of the lacrimal fossa. The posterior aspect of the inferior portion of the lacrimal sac lies on the very thin lacrimal Figure 133.1
(a) Nasolacrimal mucocoele; (b) dacryocystitis.
bone
and
this
area,
which
is
immediately
anterior to the attachment of the uncinate process, is easily entered using an endonasal approach. The lacrimal
first description of an external approach more than a decade after Caldwell had described the operation via the endonasal approach. The external approach was subse quently modified by many surgeons including Dupuy Dutemps and Bourget,4 who emphasized the importance of sutured mucosal flaps. With the development of modern nasal endoscopes almost 100 years later a resurgence of interest in the endonasal approach has taken place. The early results by this approach included those described by Steadmans and McDonagh and Meiring6 although the instruments in the 1980s were not ideal and these have since been refined with improved results. Massaro et
az.7 produced the first report using a laser
technique to aid endonasal DCR using an argon blue green laser, and Gonnering et
fossa is 15 mm in length, 4-8 mm in breadth and 2 mm
in depth with the sac having two-thirds of its height above the insertion of the middle turbinate and one third below. The sac is encapsulated in a dense layer of fascia with contributions
from
the
medial
canthal
tendon,
the
orbicularis oculi muscle and the periosteum of the medial orbital wall. This has the effect that infection within the sac tends to remain confined to the sac causing increasing pressure and pain but without spread into the orbit or face. In
approximately 8 percent of cases, an anterior
ethmoidal air cell, the lacrimal cell, lies medial to the lacrimal bone and has to be opened in order to gain access to the lacrimal fossa.
al.s subsequently reported
using both the CO2 and KTP laser.
INDICATIONS In general, a DCR is indicated where there is symptomatic
SURGICAL ANATOMY
distal obstruction of the nasolacrimal duct that is not relieved by simple probing and syringing.
It is not
The lacrimal drainage system consists of the superior and
indicated
inferior canaliculi , common canaliculus, lacrimal sac and
obstruction lies elsewhere in the canaliculi or puneti as
nasolacrimal duct. Commencing with a punctum in each
the operation will not bypass these areas.
eyelid (approximately 6 mm from the medial canthus) the
as
the
sole
procedure
where
the
site
of
In many patients there is some proximal obstruction
canaliculi initially run at 90° to the lid margin for 1-2 mm
associated. with distal blockage. In such cases, gentle
before turning to run parallel with the lid margin.
probing and dilatation in conj unction with a DCR and
Chapter 133 Dacryocystorhinostomy I
insertion of stents can be performed although the results
lower success rates as thick bone will make an endonasal
of such an approach are not as favourable in cases of pure
approach more difficult.
distal blockage. Where functional obstruction exists as
approach should be considered.
evidenced by free flow on syringing along with failure of the pump system on scintigraphy, a
1691
In these cases an
external
A dacrocystogram can demonstrate diverticula, steno
DCR may be
sis, strictures, dacryoliths or a tumour but it will rarely
performed but the results of such an approach tend to
give any useful information prior to surgery unless there
be variable, indicating that relying on gravity to drain the
is a mass within the sac or an atypical feature such as a
tears is often insufficient although one recent report
bloody discharge. Dacryoscintigraphy using the radionucleotide 99MTc
provides excellent results.9
90 percent of tears drain through the inferior
may be a helpful adjunct in assessing whether there is a
canaliculus, obstruction of this or the common canalicu
functional problem. This is the case when there is free
As
lus can be bypassed but requires a more extensive
flow on syringing along with abnormal fluoroscein dye
procedure (see under Common canalicular obstruction).
disappearance tests. If there is a bloody discharge from the punctum malignancy must be excluded especially in the presence of an irreducible swelling at the medial canthus. Computed
PREOPERATIVE ASSESSMENT
tomography (CT) scanning is not part of the routine
Syringing and probing together are the main methods of identifying
the
site
nasolacrimal system.
of
any
obstruction
within
flushing saline through the
inferior canaliculus.
inability
the
to
flush
the
Syringing is achieved by gently through
inferior
An
canaliculus
indicates obstruction at the site of the punctum or inferior canaliculus while reflux of saline through the other canaliculus indicates the obstruction is more distaL Gentle skilled probing with a
'0' Bowman's probe will (Figure
assist in confirming the level of the obstruction
133.2). It is crucial that the mucosa is not damaged and that a false passage is not created. Massaging of the sac may produce a discharge from the
work-up for DCR but is appropriate if there are specific concerns with regard to the possibility of malignancy or if there has been a facial fracture. Fine rigid dacryocystocopes of
0.7 mm diameter have
allowed examination of the proximal lacrimal drainage system and direct visualization of obstruction at this level although such techniques are still evolving. A number of other methods of evaluating the lacrimal system have been described including ultrasound, mag netic resonance imaging, magnetic resonance dacryocys tography and CT dacryocystography. These techniques do not have any value in the routine preoperative investiga tion of patients.
[**/*]
puneti consistent with chronic dacrocystitis. A mucocoele or pyocoele produces a swelling inferolateral to the medial canthus
(Figure 133.1a).
Nasal endoscopic examination is mainly aimed at excluding anatomical abnormalities that may interfere with successful endonasal surgery but will also detect any rare pathology that may affect success rates. A history of trauma involving the lateral nasal wall is likely to result in
OPERATIVE TECHNIQUES The techniques available are: • • •
external D CR; endonasal DCR with conventional instruments; endonasal laser-assisted DCR.
These are compared in
Table 133.1 and explained in more
detail below.
External DCR An external DCR can be performed making a low Howarth's incision. The lacrimal sac with its attached periosteum is dissected free from the lacrimal fossa and is retracted laterally. A rhinostomy of 1.5 cm is created taking care not to damage the nasal mucosa. A vertical slit is made in the exposed nasal mucosa and, similarly, a corresponding vertical slit is made in the lacrimal sac and the flaps created are sutured together to create an epithelially lined rhinostomy. Visibility and access of the intranasal anatomy is restricted and a lacrimal air cell can Figure 133.2
Probing of the inferior canaliculus.
be overlooked.
i ' __ • •• ____.1. _______
1692
I PART 13 TH E NOSE AN D PARANASAL SI N USES
Table 133.1
Comparison of techniques. 1
.' Endonasai 6'CR
External DCR
'1"
;J
... 1
Local
Anaesthetic
General
General or local with sedation
Expense
Low
low
Initial high capital outlay
External scar
",
X
X
Operating time
l'
�
10, 11
��
14,15,16
17, 59-100%
Success rate
>
H aemorrh age
l'
-+
��
Day case
No
Potential
Yes
Disruption of lacrimal pump function
yt'
X
X
1',
82_95CVo'2,13,
90%
lB, 19,20.21
increased;�, decreased.
Figure 133.3
I ncising the mucosa over the left anterior
Figure 133.4
Iau!mal crest (cadaver).
Endonasal OCR with conventional instruments An incision is made in the mucosa overlying the anterior
lacrimal crest
(Figure 133.3) and a posteriorly based
mucoperichondrial flap is raised. The anterior lacrimal crest can be identified as a white vertical ridge of bone immediately
anterior
Removing the bone of the left anterior lacrimal
crest with a punch (cadaver).
to
the
middle
turbinate.
anterior lacrimal crest is removed using a punch
posterior flaps. These flaps of sac mucosa are then placed in contin ui ty with the mucosa of the nasal wall
133.6),
(Figure
A stent may then be inserted. With this approach
the lacrimal sac is widely exposed and the common canaliculus can often be seen.
The
(Figure
133.4) and more superiorly a coarse diamond drill helps
Endonasal laser-assisted OCR
as the bone is thicker there. Posterior to the anterior lacrimal crest is the uncinate process, and just lateral to
The
canaliculus
is
dilated
to
allow
passage
of
a
the uncinate process is the thin lacrimal bone that forms
vitreoretinal light probe. The light probe should idea lly
the remainder of the medial aspect of the lacrimal fossa.
be passed
This bone is paper thin and is easily resected. To create a
inferiorly to avoid trauma to the inferior canaliculus and
large rhinos t omy also requires excision of the upper part
to encourage placement of the ostia in a dependent
of the ant eri or lacrimal crest using a diamond burr
position avoiding the potential of a 'sump'
al though in children the bone can be removed with a
This is then advanced into the lacrimal sac and
th rough the superior canaliculus and angled
within the sac. the point
Kerrison punch. The sac is exposed and has a dark red
of light can be seen endoscopically act ing as a guide for
(Figure 133.5). The sac is divided vertically with either a sickl e knife or a
the area to fashion the rhinostomy
colour and is firmer than nasal
m ucosa
(Figure 133.7). In 8
percent, a lacrimal or anterior agger nasi cell lies between
45° beaver scalpel. A probe placed within the sac, tenting
the sac and the lateral nasal wall and will result in a
it medially, facilitates incision. Microscissors are then
diffusion of this li gh t
used both inferiorly and superiorly to create anterior and
be opened prior to gaining entry to the lacrimal fossa .
(Figure 133.8). This cell will need to
Chapter 133 Dacryocystorhinostomy I
Figure 133.5
1693
Incising the left lacrimal sac (cadaver),
Figure 133.7
Transmitted light from light probe within the
left lacrimal sac viewed endoscopically.
Figure 133.6
Flaps fashioned and retracted to widely expose
the left lacrimal sac (cadaver).
Confusion
can
arise
in
mistakenly
following
the
reflection of the aiming beam of the laser in the belief that it is the transmitted light from the vitreoretinal light probe in the sac. Reducing the illumination from the
Figure 133.8
Diffusion of light through a large right lacrimal!
agger nasi air cell.
endoscope will help visualize the light probe if it is dim because of a lacrimal cell or a thick-walled mucocoele. A variety of different lasers have been described for this
roughen the surface and cause trauma to the common
surgery. At optimum power the laser ablates tissues, but at
canaliculus when it is removed. It is replaced with a
suboptimum levels, which can happen if the beam is at an
lacrimal probe that can be used to tent the sac medially
angle, not focused or at suboptimum power settings,
and help localize the area of mucosa that is ablated as well
burnt tissue can accumulate. The laser cannot ablate
as making further widening of the ostium easier.
charcoal and so with continued use heat is dissipated
The rhinostomy is enlarged to 5-8 mm diameter. A
through the charred tissue with the risk of thermal injury.
silicone stent may then be passed through both superior
Gentle curettage of the charcoal can be performed and the
and inferior canaliculi to create a loop at the medial
laser can then be used again. Suboptimal ablation can be
canthus and be retrieved from the nose with fine nasal
used to advantage
forceps and secured
if the surgeon wants to
achieve
haemostasis. Suction is required to remove the laser plume.
Once the sac is exposed, the light probe is
withdrawn to avoid damage to its metal sleeve, which can
; I
(Figure 133.9). The loop should not
be excessively tight as it can cause granulations at the rhinostomy canaliculi.
site
and
can
'cheese-wire'
through
the
1694
I PART 13 THE NOSE AND PARANASAL SINUSES
that avoids these problems and provides stereoscopic vision but is more cumbersome to manipulate. Some workers do not insert a stent while others leave a stent in for several months. There is no clear evidence to recommend either approach over the other.22 The size of the ostium has been reported by some authors to affect success rates but again there is no clear information to support this. 22 Transcanalicular DCR involves passing a laser fibre through the canaliculus in a similar manner to the passage of the light probe in endonasal laser-assisted DCR. A 600
micron optical fib re is ideal for this purpose.
The position of the laser is confirmed endonasally. The laser is then used to create a rhinostomy towards the nasal cavity and enlarged. This technique was initially described 23 24 , and while attractive, there remain a number
in 1992,
of concerns regarding this technique. Damage to the canaliculus can occur if there is a leak of laser energy from the laser fibre and there is a tendency for the fibre to be directed posteriorly in the direction of the orbit, which can result in ablation of the posteromedial wall of the lacrimal sac or entering the orbit if not performed with Figure 133.9
A silicone stent in place following a left
endonasal visualization to control its direction.
endonasal laser OCR.
The
stoma created tends to be small and posterior. There does not, therefore, appear to be any clear advantage to this method, with the increased possibility of inadvertent damage resulting from it.
CHOICE OF LASER FOR ENDONASAL LASER-ASSISTED
Balloon dacryocystoplasty involves the passage of an
DACRYOCYSTORH INOSTO MY
The laser should have the ability to vaporize soft tissue and bone, should have good haemostatic properties, be deliverable
through
a
flexible
laser
fibre
and
be
inexpensive. The CO laser has poor haemostatic properties, is poor 2 at bone ablation and cannot be delivered through an optical fibre, making it unsuitable for this purpose. The argon laser produces ablation by contact with tissue and has poor bone ablation. The Nd:YAG laser has good tissue ablation but poor haemostatic properties. The Ho:YAG, the KTP/532 and the diode lasers are all suitable for this procedure. The Ho:YAG laser effectively vaporizes bone and has good haemostatic properties but has the disadvantage of a tendency to spatter requiring repeated cleansing of the endoscope lens. The KTP/532 star pulse laser has similar advantages but avoids this problem. The diode laser has a single-use fibre increasing the expense per procedure of this laser. The erbium:YAG laser is likely to be ideally suited to this surgery but as yet no suitable delivery system exists for its use. [**/*]
angioplasty balloon catheter over a protected guidewire. Inflation
of
the
balloon
dilates
the
stenosis.
This
procedure can be performed under local anaesthetic as a day case. Results of this technique have shown mixed initial success rates with a predisposition to restenosis. Reported success rates range from 23 to 70 percent, but with variable lengths of follow-up and inclusion criteria. Of the larger studies Lee et
al.25 reported a
23 percent
success rate in 81 eyes at two years, Janssen et
al.26 a 70
percent in 100 eyes over a 5-48 month follow-up, Ilgit et
al.27 a 66 percent success in 80 eyes at 6-18 months and al.28 a 44 percent success at 12 months in 52
Fenton et
eyes. The largest study involving 430 eyes in 350 patients had a one-year patency of 48 percent and a five-year patency of 37 percent.29 While a simple and safe procedure, the disappointing results, in particular the high recurrence rates, limit the usefulness of dacryocystoplasty at present. The external approach usually
requires a general
anaesthetic with an overnight stay. The facial scar usually heals well unless the line of incision is not broken in the shape of a silhouetted seagull and placed relatively high
VARIATIONS IN SURGICAL TECHNIQUE An endoscope is most commonly used as it is manoeuvr
able, but the lens requires repeated cleaning as it becomes obscured by the laser plume, blood and debris. An operating microscope with a 300-mm lens may be used
on the side of the nose. If the incision is not broken and is nearer the medial canthus a web can occur. Extensive dissection around the medial canthus is required with the potential for injury to normal lacrimal pump function. In some cases there is haemorrhage, resulting in bruising, swelling ano-, occasionally, nasal packing is necessary. Revision surgery by the same approach can be difficult as
Chapter 133 Dacryocystorhinostomy
opposed to endonasal techniques where it is straightfor ward. The main advantage is that consistently high success rates have been achieved by this approach but whether this is reflected in normal practice is debatable as the results from an audit of a nonselected group suggest.20
I 1695
•
migration of stents and cheese-wiring if it is too
•
sump syndrome when the rhinostomy is high and
•
tight;
mucus collects within the sac; haemorrhage.
While routine biopsy is not required, excellent views of the lacrimal sac are obtained allowing biopsy of the lacrimal sac if it looks abnormal. The advantages of endonasal laser dacryocystorhinost
THE ROLE OF ANTIMITOTIC AGENTS
omy (ELDCR) are that there is no external scar, it can be
The two most common causes of failure in DCR surgery
carried out as an outpatient and in those who are not fit
are closure of the surgically created osteotomy with soft
for general anaesthetic, e.g. with severe cardiovascular
tissue
disease or on warfarin. It produces minimal bleeding and
Antiproliferative agents applied at the osteotomy site
and
obstruction
at
the
common
canaliculus.
low primary and secondary haemorrhage rates, a short
may reduce the fibrosis and hence reduce the failure rate.
operating time and less disruption of medial canthal
This has been demonstrated in other areas of ophthal
anatomy and lacrimal pump function. The disadvantages
mology where the application of antimitotic agents in
of this approach are that laser precautions are required,
trabeculectomy improved success rates in
the expense of the laser and, although there is a wide
Mitomycin C (MMC) and 5-fluorouracil (5-FU) have
glaucoma.
variation in success rates, there appears to be, overall, a
been equally successful in this regard.34 Both agents have
higher failure rate due to stenosis and scarring at the 1 1 1 rhinostomy site. 8, 9,20,2 ,30
been
Endonasal DCR has many of the advantages of ELDCR but avoids the disadvantages of the external approach. It does have a longer operating time and increased risk of
shown
to
have useful
activity
in
vitro.
Seven
randomized controlled trials comparing the effect of antimitotic agents against controls have been identified. The most impressive results for supporting their use in
external surgery were those obtained by Liao et aI.35 in a
haemorrhage when compared with ELDCR but appears
prospective randomized controlled study which showed a
to have success rates rivalling those of external DCR with
significant
most series reporting success rates of 80-90 percent. It is a 1 1 1 1 1 1 good technique! 2, 3, 4, 5, 6,3
application of MMC of 0.2 mg/mL for 30 minutes. In
improvement
in
success
rates
with
the
the group treated with MMC 95.5 percent were symptom
In the literature, comparison of the results of different
free compared with 70.5 percent in the conventional
approaches available is far from straightforward with a
untreated group. The results obtained statistical signifi
dearth of prospective studies comparing the techniques.
cance, in part, due to the low success rate in the
In addition, reported results of individual techniques
conventional group. [***] A further four studies have
use different selection criteria, different reporting of
been reported using antimetabolites in external DCR
successful outcomes and different times as the end
surgery. Of these, all suggested a small benefit in the
point. That being said, the only prospective randomized
MMC group but none were significant. Different doses
trials conducted to compare external and endoscopic
and times of application ranging from 0.2 to 1 mglmL
DCR
were
undertaken
by
Hartikainen
et
aI.32,33
These trials reported success rates for external DCR and ELDCR of 91 and 63 percent, respectively (p=0.016).32 In
and
from
two
to
30
studies.36, 37,38,39 [***]
minutes
were
used
in
these
Two further randomized controlled trials were identi
with
fied that used these agents in endonasal approaches. The
those having endonasal DCR the success rates were 91
first, a randomized double-blind placebo-controlled trial,
versus 75 percent (p=0.18),33 although numbers were
looked at laser procedures with follow-up at 12 months40
comparing
patients
undergoing
external
DCR
Uncontrolled
with 5-FU being applied at a dose of 0.5 mg/mL for five
observational series show widely varying results for any
minutes. Overall success rates of 76 percent in the treated
small
with
32
cases
in
each
group.
given technique with the general impression supporting
group versus 63 percent in the placebo group were
the conclusions of the above citation, however, clear
obtained. While showing benefit in the treated group this
evidence is lacking. [**/*]
failed to reach statistical significance although a type B error
cannot
be
excluded.
In
another
study
using
conventional instruments and an endonasal approach,
COMPLICATIONS COMMON TO ALL APPROACHES Complications include:
0.5 mg/mL of 5-FU was used for two and a half minutes. No difference was found after a minimum follow-up of 1
nine months for either primary or revision surgery.4 [***] Without
further
information
it is difficult to be
•
failure - this may be due to granuloma formation or
•
scarring at the site of the rhinostomy;
good theoretical evidence to support their use and in vitro
adhesions between traumatized nasal surfaces;
experiments but no clear benefit has been demonstrated.
categorical about any benefit of these agents. There is
1696
I PART 13 THE NOSE AND PARANASAL SINUSES
Their use has not yet been adopted
in DCR surgery
routinely.
recently,
tube
insertion
has
been
reported
via
an
endonasal approach47 but this method awaits medium and long-term evaluation.
DACRYOCYSTORHINOSTOMY IN CHILDREN Epiphora is common in newborns with an incidence as
high
as
20
percent
being
reported.
Congenital
nasolacrimal duct obstruction usually happens at the distal end of the nasolacrimal duct and is membranous. Fortunately, more than 95 percent neous resolution in the first
will undergo sponta
12 months, and in the
remaining cases a further 60 percent in the succeeding 12 months.42
[**]
No treatment should be considered until at least 12 months of age in view of the high resolution rates and
the observation that no detrimental effect has been found in those who did not resolve when this policy has been
Ca naliculodacryocystorh i nosto my This involves resection of the stenosed region of the common canaliculus with primary anastomosis over a stent in conjunction with
a DCR.48 This has proved useful
for distal canalicular obstruction with greater than 8 mm of patent proximal canaliculus10 and the more medial the obstruction, the greater the success rate. Trials attempting to laser common canalicular pathol ogy using the O.7-mm rigid fibreoptic endoscope with a delivery channel are underway, but this technique is yet to be of proven benefit.
[*J
adopted. Thereafter) the standard treatment is syringing and probing, usually under general anaesthetic in this age group. It may be beneficial for this to be undertaken as a collaborative procedure between the ophthalmologist and
KEY POINTS
ENT surgeon42 so that probing through Hasner's valve
•
can be visualized and the inferior turbinate outfractured under direct vision. Such an approach has the advantages that the correct passage of the probe can be confirmed
•
Therapeutic procedures, such as an infracture of the inferior turbinate, syringing and stenting, can be under taken at the same time. If stenosis is apparent then, in
•
[*]
COMMON CANALICULAR OBSTRUCTION •
Medial mucosal common canalicular obstruction is the
•
most common cause of proximal obstruction and is due
•
a
rates.
long-term is idea] in those with coagulopathies and those who are unfit for general anaesthetic. DCR is primarily carried out for distat nasolacrimal duct obstruction and therefore' an accurate preoperative diagnosis of the site' of obstruction is essential. Endonasal techniques are the least invasive:' >- ": The role of antimitotics,_ is uncertain; , An expectant policy sh6u1d --be! adopted'cin''.,: children, at least untjl-12· niohlhs�O{ age.-' .'� ' The best approach fOf.:'COITl.O}oh , e�n �icillaf" , obstruction ,is uncertain, and reIies on the IJ��.:, �"',,:,,;: -:,\ '1 result of further�sf!I4l,���(�'?<"" <""�, /. � " Laser OCR, white giving poorer
p atency rates)
general, long-term stenting should be employed with a
to
external DCR and the with conventional
instruments give the best long,-term patency
with a more accurate diagnosis of the site of obstruction.
DCR being the final resort.42
Convts'ntioflal
cndonasai apprt1ach
thin membrane which can be treated with DCR and •
stenting. Where there is a dense fibrous membrane or stenosis two approaches may be considered.
"
_
"
.
, �
Insertion of Lester-Jones tube First described in 1962 by Jones,43 this involves the insertion
of
a
permanent
indwelling
ceramic
tube
between the nasal cavity and the conjunctival sac at the medial canthus to act as a channel to drain tears and completely bypass the lacrimal drainage system. This has traditionally been inserted via an external approach. Large series report success rates of 83-100 percent)43, 44,45,46 but
I
Best c:linical practice
-
./ Make sure that the diagnosis of distal nasolacrimal duct obstruction is correct as a DCR does not help proximal obstruction and is often of little help if there is a functional problem.
there are complication rates in excess of 50 percent of
./ The best results are reported from an external DCR or
obstruction,
./ Endonasal techniques are less invasive.
cases in some series - comprising tube displacement) granulations,
malposition)
hypermobility
and infection.44 Most of these can be managed with the
main problem being that of tube displacement. More
' an endoscopic OCR using conventional j nstruments.
./ ELoCR is the method of choice when a patient is
49 A relative indication for ELDCR is for anticogulated.
Chapter 133 Dacryocystorhinostomy
a revision OCR as there is often only a thin
,I'
*
9.
I 1697
Wormald P J, Tsirbas A. Investigation and endoscopic
membrane blocking the rhinostomy and only this
treatment for functional and anatomic obstruction of the
needs to be ablated.
nasolacrimal duct system. Clinical Otolaryngology. 2004;
Results are poorer in sarcoidosis and extremely poor in Wegener's granulomatosis where any instrumentation
29: 352-6. 10.
induces marked adhesions and stenosis.
.I It is important to exclude any other pathology, e.g.
H urwitz JJ, Rutherford S. Computerized survey of lacrimal surgery patients. Ophthalmology. 1986; 93 : 14-9.
11.
Tarbet IU, Custer PL. External dacryocystorhinostomy . Surgical success, patient satisfaction, and economic cost.
malignancy in the nasolacrimal sac or paranasal sinuses.
Ophthalmology. 1995; 102: 1065-70.
* 12.
Wormald P J. Powered endoscopic dacryocystorhinostomy. Laryngoscope. 2002; 112: 69-72.
13.
Eloy P, Bertrand B, Martinez M, H oebeke M, Watelet JB, Jamart J. Endonasal dacryocystorhinostomy:
Deficiencies in current knowledge and areas for future research
indications, technique and results. Rhinology. 1995; 33: 229-33. 14.
Wiedenbecher M, Hosemann W, Buhr W. Endoscopic
Despite a wealth of articles relating to OCR surgery
endonasal dacryocystorhinostomy: results in 56 patients.
many aspects, such as the following, remain uncertain.
Annals of Otology, Rhinology and Laryngology. 1994; 103:
)- Are stents required, and if so what is the optimum length of time for placement?
>- Is size of the ostium important in terms of successful
363-7. 15.
endoscopic transnasal dacryocystorhinostomy. Eye. 1993;
outcome and what is the optimum size? )- Do antimitotics help patency rates?
Whittet HB, Shun-Shin GA, Awdry P. Functional
7: 545-9. 16.
)- Does laser ablation of common canalicular pathology
Sprekelsen MB, Barberan MT. Endoscopic dacryocystorhinostomy: surgical technique and results.
succeed?
Laryngoscope. 1996; 106: 187-9. 17.
Sadiq SA, H ugkulstone CE, Jones NS, Downes RI\J. Endoscopic holmium:YAG laser dacryocystorhinostomy. Eye. 1996; 10: 43-6.
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Dalgleish R. Idiopathic acquired lacrimal drainage obstruction. British Journal of Ophthalmology. 1967; 5 1:
101: 1793-800. 19.
463-8. 2.
dacryocystorh inostomy. Laryngoscope. 1994; 104:
Caldwell GW. Two new operations for obstruction of the nasal duct with preservation of the canaliculi, and an
269-74. 20.
incidental description of a new lacrimal probe. New York Toti A. l\Juovo metodo conservatore di cura radicale delle
1994; 101: 955-9. 21.
suppurazioni croniche del sacco lacrimale
(dacriocistorinostomia) . 4.
Reconstructive Surgery. 1993; 9: 231-6. 22.
Camara JG. Endonasal dacryocystorhinostomy. A report by
dacryocystorhinostomie et ses resultats. Annales
the American Academy of Ophthalmology. Ophthalmology.
Steadman GM. Transnasal dacryocystorhinostomy.
2001; 108: 2369-77. 23.
107-11.
7.
McDonogh M, Meiring J H . Endoscopic transnasal
110: 170-1. 24.
Levin PS, StormoGipson OJ. Endocanalicular laser-assisted
dacryocystorhinostomy. Journal of LarYngology and
dacryocystorhinostomy: an anatomic study. Archives of
Otology. 1989; 103: 585-7.
Ophthalmology. 1992; 110: 1488-90.
Massaro BM, Gonnering RS, Harris GJ. Endonasal laser
25.
dacryocystorhinostomy; a new approach to nasolacrimal
. 8.
Christenburry JD. Transcanalicular laser dacryocystorhinostomy. Archives of Ophthalmolo.gy. 1992;
Otolaryngology Clinics of North America. 1985; 18: 6.
Woog JJ, Kennedy R H , Custer PL, Kaltreider SA, Meyer DR,
Dupuy-Dutemps SL, Bourget M. Procede plastique de d'Oculistique. 1921; 158: 241-61.
5.
Reifler OM. Results of endoscopic KTP laser-assisted dacryocystorhinostomy. Ophthalmic Plastic and
Clinica Moderna (Firenze). 1904;
10: 385-7.
Bousch GA, Lemke BI\J, Dortzbach RK. Results of endonasal laser-assisted dacryocystorhinostomy. Ophthalmology.
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Metson R, Woog JJ, Puliafito CA. Endoscopic laser
Lee J-M, Sung H -Y, H an Y-M, Chung G-H, Sohn M- H, Kim C-S et al. Balloon dacryocystoplasty: Results in
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the management of complete and partial obstructions
1172-6.
of the nasolacrimal system. Radiology. 1994; 192: 503-8.
Gonnering RS, Lyon DB, Fisher JC. Endoscopic laser assisted lacrimal surgery. American Journal of Ophthalmology. 1991; 111: 152-7.
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Janssen AG, Mansour K, Bos JJ. Obstructed nasolacrimal duct system in epiphora: long-term results of
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PART 13 THE NOSE Af\ID PARANASAL SINUSES
helical computed tomography. Archivos de 10 Sociedad
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Espanola de Oftalmologia. 2000; 75: 611-8.
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Ilgit ET, Yuksel 0, Unal M, Akpek S, Isik S, Hasenreisoglu B.
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Steinsapir KD, Glatt HJ, Putterman AM. A 16-year study of conjunctival dacryocystorhinostomy. American Journal of
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34.
Jones LT. The cure of epiphora due to canalicular
treatment of nasolacrimal canal obstructions. Rhinology.
randomized comparison of external
* 33.
MacEwan CJ, Young JDH, Barras CW, Ram B, White PS. Value of nasal endoscopy and probing in the
outcome in 350 patients. Journal of Vascular and
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Zilelioglu G, Ugurbas S H , Anadolu Y, Akiner M, Akturk T.
of adult eiphora. Eye. 2001; 15: 67-9. Balloon dacryocystoplasty: results and factors influencing
30.
Bakri K, Jones NS, Downes R, Sadiq SA. Intraoperative
48.
Doucet TW, Hurwitz JJ. Canaliculodacryocystorhinostomy
dacryocystorhinostomy. British Journal of Ophthalmology.
in the treatment of canalicular obstruction. Archives of
2000; 84: 903-6.
Ophthalmology. 1982; 100: 306-9.
You YA, Fang CT. Intraoperative mitomycin C in
49.
Smithard A, Wynne 0, Bingham BJ, Jones NS.
dacryocystorhinostomy. Ophthalmic Plastic and
Endonasal laser dacryocystorhinostomy: its role in
Reconstructive Surgery. 2001; 17: 115-9.
anticoagulated patients. Laryngoscope. 2003; 113:
Yalaz M, Firinciogullari E, Zeren H. Use of mitomycin C and
1034-6.
5-fluorouracil in external dacryocystorhinostomy. Orbit. 1999; 18: 239-45. 38.
Kao SCS, Liao CL, Tseng JHS, Chen MS, Huo PK.
FURTHER READING
Dacryocystorhinostomy with intraoperative mitomycin C. Ophthalmology. 1997; 104: 86-91. 39.
Simmen 0, Jones NS. Selected procedures. Chapter 14. In:
Gonzalvo Ibanez FJ, Fuentes Fernandez I, Fernandez Tirado
Simmen 0, Jones NS (ed.). Manual of endoscopic sinus
FJ, Hernandez Delgado G, Rabinal Arbues F, Honrubia
surgery and its extended applications. Stuttgart: Thieme,
Lopez FIVI. External dacryocystorhinostomy with
2005: 194-201.
m itomycin C. Clinical and anatomical evaluation with
134 Conditions of the external nose
MICHAEL O'CONNELL
1711
I ntrod uction
1699
Best cl i n ical practice
Acute nasal infection
1700
Connective tissue d iseases
1711
Key points
1701
Nasal destructive l esions
1713 1713
Best clinica l practice
1702
Key points
Chronic nasal infection
1702
Best clinica l practice
1714
Key poi nts
1704
Dermatolog ical d isease
1714
Best clinica l practice
1704
Key points
1715
Neoplasms of the nose
1704
Best clinica l practice
1715
Key points
1709
Deficienci es in current know l edge and areas for future
Best clinical practice
1709
Sarcoi dosis
1710
References
1716
Key pOInts
1711
Further reading
1717
I
'"
. .
.
.- . :.� :� .."� ,'
"-.
,. .
-
.
"
. :
1716
research
.
The data in this chapter are supported by a Medline search using the key words external nose, facial skin disease, facial skin lesions, nose disease, nose lesions and focusing on aetiology, diagnosis, management and pathology.
INTRODUCTION
The aim of this chapter is to detail the various pathologies
affecting
the
external
nose,
providing
a
The nose occupies the central feature of the face and is a
reference base for the facial specialist and an overview
potent perceived projection of the individual. Pathology of
of the clinical history of diseases that involve this area.
the external nose produces not only concern for the patient
Facial plastic techniques for reconstructing nasal tissue
with regard to causation but also apprehension as to the
loss are an essential treatment modality for the manage
aesthetic consequence of the condition. The clinician must
ment of many of these conditions but are beyond the
take both these aspects into consideration. The exterior of
scope of this section. Further information is provided in
the nose, including the nasal vestibule, is composed of skin
Chapter 205, Grafts and local flaps in head and neck
and this chapter is primarily concerned with cutaneous
surgery and from key references at the end of the chapter.
disease. Furthermore, it is essential that the specialist should
Several dermatological terms are necessarily incorpo
not consider the nose in 'diagnostic' isolation as disorders
rated in the text and are defined thus: a macule is a flat
of this region may form part of a generaJized facial
lesion within the skin; a papule denotes a circumscribed
condition or represent visible evidence of underlying local
raised lesion in the dermis or epidermis, being con
or systemic disease. The modern clinician must, therefore,
ventionally less than
have an insight into such problems that potentially cross the
comparable to a papule but has a size greater than 1 em;
boundaries of several branches of medicine.
finally, a plaque is an irregular, superficial lesion that is
1 em
in diameter; a nodule is
1 700 I
PART 13 THE N OSE A N D PARANASAL S I NUSES
marginally raised and has a large surface area relative to its height. ACUTE NASAL I N FECTI O N Bacterial i nfection
Bacterial infections of the nose and face, as elsewhere, are recognized by the classical signs of acute erythema, oedema and tenderness and may be accompanied by indicators of systemic injury such as pyrexia and malaise. Commensal bacteria residing in the upper respiratory tract are the main pathogens with 30 percent of patients intermittently harbouring Staphylococcus aureus in their nose and 10 percent carrying Streptococcus pyogenes in their nasop harynx. 1 Persisting, extreme or recurrent disease may indicate an underlying pathology, as in diabetes mellitus or immunocompromised states. Bacter ial infection involving the nose rarely results in severe or fatal complications with retrograde spread of infection along the valveless facial veins to the cavernous sinus. Thrombosis of this region produces periorbital swelling, chemosis, ophthalmoplegia and pupillary changes. [**]
levels over a period of weeks. Cellulitis is similar to erysipelas but the surface lesion is less well defined as inflammatory changes involve deeper connective tissue layers. Appropriate oral or intravenous antibiotics are required depending on the severity of disease. IMPETIGO
This superficial contagious infection of the skin happens in outbreaks. Group A streptococcus is the most common pathogen but not the only identified organism and two distinct forms exist. The bullous variety involves the face, among other areas, and presents as an area of erythema with tense bullae 1-2 cm in diameter that subsequently rupture to leave surface crusts. The nonbullous form is characterized by transient vesicles that enlarge, burst and leave yellow crusts. The face is commonly affected by this latter group and is the more usual presentation in children. Venepuncture and blood culture are required as nephrogenic forms of streptococcus remain an important, albeit rare cause of glomerulonephritis. Staphylococcal infection occasionally leads to widespread shedding of epidermis producing the 'scalded skin syndrome' or Lyell's disease. Systemic antibiotics are essential to resolve these infections.
VESTIBULITIS
This is an inflammation of the nasal vestibular skin either from infective agents, trauma, particularly of the finger variety, or excoriation from rhinitis. Crusting is evident and mild to moderate discomfort is reported. Topical agents such as steroids or antibiotics are prescribed according to aetiology. A specific presentation of vestibulitis is the furuncle or common boil, which arises in the hair-bearing region of the nasal vestibule and results from Staph. aureus infection of the follicle. Initially a tender nodule with surrounding inflammation and induration, it subsequently swells and generally discharges into the anterior nares. Several boils may coalesce to form a carbuncle but both presentations respond quickly to local antiseptics and oral antibiotics. ERYSIPELAS
Such an infection is heralded by the onset of a bright red, flat, shiny and well-defined lesion in the middle third of the face. Outward extension from the nose is typical and erysipelas may involve the midface in a 'butterfly' or malar distribution, centring on the nose and spreading symme trically across the cheeks. The provoking organism is a group A streptococcus which enters through broken skin to infect the dermis. Less commonly, other streptococci including Strep. pneumoniae, Staph. aureus or Haemophil Ius inJluenzae produce an identical clinical picture. The involved region has an indurated appearance and bullae or vesicles may be seen. The diagnosis is made clinically, but antistreptolysin titres can be assayed and show increasing
Viral i nfecti o n HERPES SIMPLEX
Type 1 herpes simplex virus is primarily responsible for facial lesions classically involving the lips, perioral region, cheek and mouth. Infection is heralded by redness, itching or stinging followed by an outbreak of small grouped vesicles in the symptomatic area. Initially clear, the vesicle fluid becomes cloudy and purulent. The lesions subsequently desiccate and finally crust with complete resolution taking place over one to two weeks; however, infection can occasionally persist, proceeding to malaise, severe inflammation and necrosis. If required, the virus can be cultured from the mucopurulent fluid in these vesicles. In patients with atopic eczema and certain other skin conditions, the herpes virus can lead to eczema herpeticum, a condition characterized by potentially life threatening systemic infection and requiring treatment with parenteral acyclovir. The herpes virus has the ability to remain dormant in sensory root ganglia for long periods of time. Stress, surgery, sunlight and a variety of unrelated factors may precipitate recurrence of vesicles in the previously affected area. Repeated infections require early treatment with topical acyclovir. HERPES ZOSTER
Herpes varicella virus is responsible for chickenpox and following primary infection the infective agent has the
1701
Chapter 134 Con d itions of the external nose I
ability to lie dormant
in sensory nerve ganglia. Reactiva
tion of the virus is denoted by severe pain, malaise and fever followed by an erythematous macular or papular eruption within the distribution of the nerve. Twenty four hours later vesicles appear, which are clear, then cloudy, later crust and finally disappear after one to two weeks. Secondary infection is common and may prolong recovery. Involvement of the maxillary division of the trigeminal nerve produces vesicles on the cheek, nose and vestibule whereas infection of the nasal tip, an area supplied by the external nasal branch of the ophthalmic division of the trigeminal nerve, is associated with severe conjunctivitis. Vesicle fluid or nasopharyngeal secretions are potentially infective to close contacts, with develop ment of chickenpox in previously uninfected individuals. A disseminated form occasionally arises with widespread haemorrhagic, bullous and infarctive eruptions that heal with scarring. Topical acyclovir is
beneficial for local
lesions, but recurrent disease requires oral acyclovir which is most effective infection.
if prescribed early in the course of
lmmunocompromised patients can present
with florid outbreaks and are treated with parenteral
Figure 134.1
Mo l l uscu m contagiosum.
although
centre,
predominate.
larger
wart-like
lesions
sometimes
Itching can lead to secondary infection;
however, the condition is mostly self-limiting. Profuse eruptions are seen in immunocompromised adults and patients with the acquired immunodeficiency syndrome (AIDS). Cryotherapy is effective
if needed.
acyclovir. In recurrent zoster cases oral steroids, along with analgesia and rest, lessen the pain.
FACIAL INFECTIVE RASHES
The exanthems are a group of infections characterized by fever and subsequent epithelial
WART VIRUSES
Infection with the human papilloma virus (HPV), a
DNA
virus, produces a benign localized neoplastic growth of epidermis. Classification previously based on clinical or histological
appearance
has
now
been
eruption.
They may
involve the face and occasionally present to the hospital
enhanced
specialist.
Measles is associated with a macular rash,
initially detected behind the ears and typified by white Koplik spots on the oropharyngeal mucosa. The rash
by
spreads over the face, becomes papular and in a few cases
forms may involve the face and all are raised, hyperker
characterized by a pink macular rash on the face, trunk
identification of antigenic types. Clinically, three
different
atotic lesions. Verruca vulgaris or common wart (HPV types 2 and
4) describes an uneven domed papule that
may arise on any skin site. The filiform variety (HPV 2 and HPV
4) is a pendunculated lesion frequently seen on the 3) are flat
cheek, nasal tip or columella. Flat warts (HPV
topped 1-2 mm excrescences, often appearing in consider able numbers, which sometimes coalesce to form larger lesions. Most are self-limiting and in children therapy is
haemorrhagic and bullous lesions develop. Rubella is and limbs that fades after one to two days while cases of infectious mononucleosis occasionally demonstrate
disease is denoted by a crusted nodule at the site of injury and subsequent regional lymphadenopathy up to one month later. At this later stage a macropapular rash may be apparent on the face.
rarely required. Warts on the nasal tip are unsightly and treatment may be requested. Cryotherapy, cautery
and
curettage, topical salicylic acid and formaldehyde prepara tions, or surgery, are all effective. Flat warts are more
difficult to treat because of their large numbers and staged
curettage of one area at a time is advisable.
" .+-
KEY
.
POINTS
:. Bacterial infection •
Bacterial i n fect io n may
MOLLUSCUM CONTAGIOSUM
virus from the poxvirus group is responsible for
this epidermal and mucous membrane infection that involves the face
(Figure 134.1). It is not contagious,
despite its description, and arises in temperate climates. Molluscum contagiosum presents as an eruption of small, 2-4
itnt
nun,
dome-shaped waxy papules with an umbilicated
Toe classical
evident. •
� .
nose
_ '.
variety .of W�ys,_ inf�ctiQ.!1. ar.� : , : ': . - -, -;' _ .
" ".:
malar rpsh is.. , als6 seen in
�. .. §Y�1,��C lupus,. eryihe�atosus (SLE).
.:·.�;.;;'.J�.mp�<)comproQ1ised' patients Cpl present seyere- forms of infection. /whh-unusuafor �;-:.:x...; .l.f� ·. ":-1:,, .:::. ' �.� , ... .
_.,-. _ '/' I
: _�.
'
I
,
.
and\ :
tend to ·reside.·iIi., th�
Provoking organisms
(Butterfly' or
a
the
,,�.
signs of microbial
upper..a.ero4-.igesti;v�,� .t a�
•
I
affect
surrounding t�-lcial skin in •
A DNA
a
macropapular rash in a similar distribution. Cat scratch
"
1 702
NOSE AND PARANASAL SINUSES
I PART 13 THE
indolent localized presentation of tuberculosis involving
j,
Viral infection
•
may result in ,infeCtioii':otl<;>taJ' . , neopIastk change," , , . " Herpes si mplex and ZQster 'lri''fection are�"':: '"
.'
Herpes
�
.,
I
malar and cervical regions .
Virusel\
charact,erized
.
Lupus vulgaris is a post-primary form of tuberculosis
0: '
,�-'
by self-H.l1)itfugY�icula:r l�io:hd�
arising
'.
"
.
.
recurrent, .
moderate
a
degree
of
produces extensive tissue destruction and scarring. The
dls�as:e/'?�"-.
with
disorder following a chronic course over many years and
s·impkx 'and �oster virUses have:'the
, ability to produce-
individuals
in
immunity and can affect any age. It is a progressive
,:. ...
disease is more frequent in women but is now uncommon in North America and Europe. The infection may arise from· inoculation, direct suffusion from infected under
.
J
Best clinical practice
Bacterial infection
lying tissue, or lymphatic spread from adjacent mucous membranes. In nasal involvement haematogenous trans mission
has been implicated, however, the origin is often
obscure. Histopathology reveals typical dermal tubercles consisting of epitheloid cells, giant cells and central
.1 Topical or syste m ic an ti biotics p rod uce rapid recovery.
caseation
./ The presence of eye signs a nd changes in p upi l la ry
necrosis,
although
findings
are
frequently
variable and confusing.
reactivity in an acute ly i l l patient may ind icate
Lupus vulgaris typically arises in normal skin and 80
cave rnous sinus thrombosis.
percent of lesions are located in the head
and
neck region
with the nose being the predominant target.4 Presentation
Viral infection
is
.I Topica l acyc lovir is i n d icated ear ly in the treatment of
denoted
by
a
gelatinous plaque
acute he rpes simplex i nfections.
darkens.
./' Ora l acyclovir is req uired fo r the ma nagement of
This
plaque
described as having
recurrent herpes zoster infection.
solitary,
soft,
tiny,
reddish-brown,
(Figure 134.2), which subsequently an
consists
of nodules,
classically
'apple-jelly' colour, which slowly
infiltrate local tissues. Equally, the epidermal reaction may be minimal
with scaling being the only
evidence of
infection. Progress of the disease is marked by ulceration and scarring, and the affected area of skin slowly extends combining regions of involution and expansion. Depend
CHRONIC NASAL INFECTION
ing on the response of local tissues different sequelae ensue. The plaque may advance with marked erythema and
Cutaneou s tuberculosis and lupus vulgaris
minimal ulceration. The disease may become hypertrophic with tumour-like outgrowths and deep tissue infiltration.
Tuberculosis is the most common cause of death from a
Sometimes ulceration and scarring predominate, resulting
single infectious agent with an expected incidence rising to 12 million cases worldwide by 2005.2 Human
in local necrosis, deformity and extensive disruption of
immunodefidency virus
found within the nasal cavity.
(HIV) infection is, in part,
nasal cartilage. Rhinitis is often evident and nodules
[**]
responsible for the resurgence of tuberculosis, but has made only a small contribution to UK figures. 3
In
developed countries, where such infection is infrequent, the
increase
has
been
less
dramatic
and
thus
this
condition is easily overlooked when considering diag nosis. The course of the disease depends upon the properties of the infecting organism and the competence of the host to control such
an
infection.
Cutaneous tuberculosis is
[**J
responsible for a small
with Mycobacter ium tuberculosis and M. bovis species being the main
number of the total cases of infection,
pathogens. The most common type to affect the nose is
lupus vulgaris but other forms of tuberculosis also involve this
region.
Direct
inoculation
of
the
skin
by
the
provoking organism can result in scrofuloderma, which
likewise has a proclivity for the face and is characterized by subcutaneous doughy nodules that ulcerate and create multiple sinuses. Recently, there has been the
incidence
particularly
in
of
atypical
children.
an
increase in
mycobacterium
This
is
associated
infection with an
Figure 134.2
Tubercu losis of the nose - lupus vulgaris.
can
be
1703
Chapter 134 Conditions of the external nose I
Untreated, lupus vulgaris follows a chronic course that waxes and wanes over many years. Its hallmarks are scarring, contractures and tissue destruction producing disfigurement and loss of function. Tuberculous foci, particularly in the lung or lymph glands, are present in a significant number of patients. Chronic lesions can be complicated by the development of squamous malignancy and to a lesser extent basal cell carcinoma (BCC). Differentiation from leprosy and sarcoidosis may be difficult and histological sampling plus microbiological culture is required for diagnosis. Treatment is with standard antituberculosis therapy.
rounded periosteal swellings of the nasal processes of the maxilla. For treponemal infections investigation relies on standard serological testing, although in early disease this may prove negative. In the primary stage smears from the syphilitic lesion viewed by dark-ground illumination generally reveal the organism and biopsy is reserved for doubtful cases. Treatment comprises local toilet, debride ment and topical mercury ointment to the nasal vestibule combined with systemic penicillin therapy. These mea sures rapidly arrest the disease process. Syphilis serology is also positive in cases of yaws and treatment again requires penicillin.
Syph ilis Un u s u a l bacte ria l infections
Syphilis arises from infection by the spirochaete, Trepo and is now an uncommon disease. The lesion of primary syphilis is the chancre and is seen as a firm, painless nodule that may unusually be located on the external nose or nasal vestibule. It presents at the site of treponemal inoculation approximately three weeks after contact. Vague constitutional symptoms can be experienced and cervical 'rubbery' nodes may be evident. The nodule ulcerates and disappears within one to two months, sometimes leaving a small scar. Secondary syphilis, evident at six to ten weeks post contact, is occasionally associated with a mucopurulent rhinitis, nasal crusting and vestibular fissuring. The characteristic white mucous patches found in the oral cavity are not seen around the nose. Papular lesions are typical of this stage, particularly on the abdomen and limbs. The gummatous lesion indicative of tertiary syphilis is the more usual form to involve the nose and appears at any time after the second stage. The gumma is a painless nodule which breaks down to form a 'punched out' ulcer that attacks the mucosa, periosteum and bone of the nose with subsequent atrophy and scarring. The external nose is initially spared although tenderness and swelling over the nasal bridge are reported. Subsequently, syphilitic destruction of nasal bone and skin leads to collapse and disfigurem ent. Congenital infection presents a few weeks after birth with purulent rhinorrhoea or 'snuffles' and fissuring around the vestibule. The lesions of secondary or tertiary syphilis can both be present and saddling of the nasal dorsum becomes evident at three to four years of age. In the latent variety of congenital infection such signs may be deferred until puberty. Yaws is a disease similar to syphilis but is caused by extragenital infection with T. pertenue. It afflicts younger age groups living in central Africa and the West Indies. The organism has a propensity for skin although the nose is rarely involved by the typical papillomata or ulcerating nodules. On rare occasions extensive disease can lead to complete destruction of the midface region. A specific type of yaws, Goundou, sporadically results in bilateral nema pallidum,
Several unusual infections should be considered when classifying infections of the external nose. Rhinoscleroma is a chronic granulomatous disease resulting from infection by Klebsiella rhinoscleromatis and is predominately found in southern Europe, north Africa, Pakistan and Indonesia. Within the nose appearances are suggestive of atrophic rhinitis but later bluish-red, nonulcerating nodules develop around the nasal vestibule. Subsequent involvement of the alar margin and nasal tip produces specific external disfigurement, christened the 'Hebra' or 'tapir' nose. Mycobacterium leprae is responsible for the chronic granulomatous infection, leprosy, an acid- but not alcohol-fast bacillus that is prevalent in central Africa, India and South America. The tuberculoid type produces cutaneous anaesthetic patches that can involve the nasal surface. Lepromatous leprosy commonly attacks the nasal mucosa, and facial skin shows nodular infiltration particularly around the nose, pinna and chin. Later involvement of nasal cartilage produces eventual external deformity.
F u n g al a n d protozo al infection
Fungal and protozoal infections primarily invade the nasal mucosa but extensive disease has the potential to spread to the external surface. Such pathologies are unusual in the UK but may require consideration in immunocompromised patients or travellers. Rhinospor idiosis is a disease of the mucous membranes that occasionally involves the skin, and characteristic polypoid or nodular lesions at times involve the nasal surface. Actinomyces israelii is found in the oral cavity of normal individuals and in a number of cases produces cervico facial infection. As the disease spreads, facial skin involvement is noted by the presence of a hard, indurated mass sometimes associated with multiple sinus dischar ging pus. Cryptococcosis initially results in pulmonary disease and infrequently involves the nose with the
._
,
__
I
_ ____ _ _ ______ ,
1704 I
PART 13 THE NOSE AND PARANASAL SINUS ES
potential for external ulceration. Leishmaniasis is classi fied as visceral, cutaneous or mucocutaneous according to
the provoking organism and is a protozoal infection
occurring in Central and South America. Transmission is
by the sandfly and bites, often around the nose, are foUowed by a small papule that ulcerates and heals leaving
a scar. Poplypoid growths are typical and extensive soft tissue and cartilaginous
may ensue.
destruction
Chapter 114, Fungal rhinosinusitis, for more details.
KEY •
See
POINTS
Tuberculosis i� increasing in inciden'ce and
, this is>. in part, linked"to the rise in AIDS , infec,tjo'il. It is' unusual in developed countries. . • Lupus .V}llgari� �s' th� fr1 9st' usual fOfm to, . "
•
involve the .nos�.-"'
'Lupu$"vulgaris.
:.
j�, a 'ehrmiic disease
,''Characteriz€d ' by; s(:a"iri�g.,and tissue ' :.� . ,4est� �ti\> .;", ",·! ": : , . , . �yphHis />a(ely. ��volvesc,the, ext,e-rnal nose. '
�
._' I
'• • ,
Terti
_
__
.
�Hr� apd �ongenital syp hilitic lesions may
. resul( i.ri. �xiernal' nasal
,'Qestr-ucti�n:�:":.;c_ '.:
�
','
deformit,y,. or. tissue .
' y
•
,
Best clinical practice
Figure 134.3
.I Chronic infective processes involving the nose are
Keratoacanthoma. Globular lesion with central
keratin-fi lied pi ug.
ra re but req ui re consi d eration in im munocomprom ised patients.
.I Antituberculosis therapy is indi cated in the treatment of lupus vulgaris.
associated with increased incidence. A possible role for a viral agent has been suggested, although this has not been
satisfactorily proven. Histopathological
ana1ysis reveals a tumour denoted by
p roliferating keratinizing cells centred on hair follicles.
Lesions are confined to the dermis) and neoplasia is
NEOPLASMS OF THE NOSE
signified by the presence of occasional mitotic figures and
some cellular atypia. Histological findings are similar to
Keratoacanthoma
those of SCC, lending support to the belief that the two
pathologies have a similar origin;
however,
this still
Keratoacanthoma) or molluscum sebaceum, is a benign
remains a hypothesis.
that follows a specific growth pattern terminating in
coloured or red lesion, which grows rapidly for up to six
cutaneous tumour, probably arising from hair follicles, complete resolution
(Figure 134.3). It is one-third as
Keratoacanthoma presents as a firm, round, flesh
weeks. The epidermis is glistening and telangectasia are
(SCC).5 Such
evident beneath the surface. T he lesion becomes globular
mostly in white races) with men affected two to three
however, surrounding tissue remains normal. Resolution
common as squamous cell carcinoma
lesions happen from middle age onwards and are seen times more commonly than women.
[**]
Lesions predominantly target sun-exposed areas with
and develops a central hom-filled or keratotic plug,
takes place, on average, three months later, although
complete healing can take up to a year. Shedding of the
75 percent being found on the nose, lip, cheek and eyelids.
keratotic plug signifies recovery and characteristically a
of
particular1y
Ultraviolet radiation is therefore implicated in the genesis keratoacanthoma,
although
industrial
occupations
involving contact with tar and mineral oils are also
scar is left. Rarer variants include recurrent forms, seen
in occupationally
related
lesions
or
in
Muir-Torre syndrome. T he latter condition describes an
Chapter 134 Conditions of the external
nose. 1705
assoCIatIOn between sebaceous adenomas and internal
malignancy. Occasionally, tumours may reach a size of 50 mm or more. The
differential diagnosis is
with squamous skin
carcinoma, however, the rapid growth phase and resolu
tion characteristics of keratoacanthoma indicate a benign course. Treatment is by simple curettage but this may compromise
samples
for
histopathological
analysis.
Radiotherapy and 5-fluorouracil have been employed
with
success,
particularly
for
persistent or recurrent
forms. Excision biopsy should be used if doubt as to
the diagnosis persists and this also provides an opportu nity to leave a more controlled scar. Figure 134.4
Actin i c (so l a r) keratosis Solar damage to the skin, particularly in fair-skinned individuals, can induce dysplastic epidermal cell change, and 1
percent of cases proceed to
frank squamous
malignancy.6 Initial injury is designated by
an
aggregation
of small telangiectatic vessels that later develop into a brown or yellow macule with a tough adherent scale. Lesions extend to several centimetres in size and rarely happen in isolation. Often, patients possess a weather beaten look and exhibit skin yellowing due to solar elastosis. The scale thickens and may be sufficiently hypertrophic to form a cutaneous horn. Control of actinic
keratosis
with
liquid nitrogen,
curettage,
or
topical 5-fluorouracil for large areas, is effective, but in all cases prevention should be encouraged as keratosis may rescind with appropriate sunscreens and reduced sun exposure.
Ulcerated SCc. Surro unding tiss ue is markedly
indurated.
[**]
apparent. Differentiation from keratoacanthoma is often difficult but sec follows a slower clinical course. Small growths can be removed by curettage although this reduces specimen quality for histological investiga tion. Surgical excision should include a 3-5-nun cuff of normal tissue and deep margins must be considered. On the nose primary closure is often not feasible, but good restoration of aesthetic integrity is possible with employ ment of local or regional tissue. Optimal results require precise replacement of excised tissue structures
with
equivalent material. Radiotherapy and cryotherapy are satisfactory treatment alternatives. T he presence of well-defined, flat erythematous lesions in older patients with a history of sun exposure and
histological evidence
of intraepidennal
carcinoma
is
termed Bowen's disease. The initial macule enlarges in an irregular manner and is associated with a whitish scale. Approximately 5 percent of cases will develop invasive Sec.IO Treatment by rapid freezing with liquid nitrogen,
Squamous cel l carcino m a
cauterization, topical 5-fluorouracil or surgical excision
Squamous carcinoma results from malignant change in the epidermal keratinocyte and has an incidence of 100,000 population in the
are
rapidly
increasing,
UK/
in
36 per
provides reasonable control although recurrences are common.
[""*]
although case numbers
particular,
in
Australia.8
Epidemiological data and aetiological factors are similar
Basa l ce l l carcinoma
to Bee but exposure to hydrocarbons, particularly tar radiation are
T he commonest skin cancer in white races is BCe and
additionally implicated in see pathology. Proliferation
and mineral
oils,
thermal
factors
and
recent figures indicate maximal incidence in Australia
of neoplastic cells generally arises in damaged skin
with 726 cases per 100,000 population.ll It is a neoplastic
including scar tissue, areas of chronic ulceration and
proliferation of cells that resemble basal cells of the
benign dermatoses
epidermis, although the precise origin is still unclear.
(Figure
134.4).
Furthermore, zones of
active chronic keratosis and Bowen's disease are recog
While locally invasive, metastases happen in only 0.1
nized sites for potential development of sec and, overall,
percent of cases. 12 Basal cell carcinoma is commoner with
metastases are found in 10 percent of patients.9 Initial
presentation,
as
an
erythematous
[***1**]
plaque,
verrucous growth or domed nodule, is often innocuous but concern arises with subsequent surface crusting, ulceration and bleeding. The lesion is characteristically firm and surrounding tissue is unexpectedly indurated, while in later stages fixation to underlying structures is
advancing
age
and affects
men
more
than
women,
however, current data reveal changing trends with an increasing incidence in younger age groups, women13 and
in Australia, Europe and the USA.14
[**)
The single most important aetiological factor for developing Bee is solar radiation. It is suggested that intermittent excessive sun in childhood is more important
_I __ -_O ___
1706
I PART 13 THE NOSE AND PARA NASAL SINUSES
than cumulative exposure. IS Predisposing phenotypic influences include light skin colour) poor tanning ability) blonde or red hair, freckling in childhood and Celtic ancestry. As would be presumed, southern Mediterranean and black races are relatively untroubled by BCc.16
Acquired immunodeficiency syndrome, immunosuppres
sive therapy and arsenic exposure are related to BCC formation, particularly on sun-protected sites of the body. Tumours also display a bias for areas of skin damage including vaccination sites, chronic ulcers or burn scars. Studies of inherited conditions that predispose to BCC formation)
i.e.
albinism)
naevoid BCC syndrome or
Gorlin's syndrome and xeroderma pigmentosa, indicate that inactivation of a tumour suppressor gene on the long arm of chromosome 9 may be a significant feature in the genesis of BCc.17
[***]
Thirty-two percent of BCC presents on the nose,
Figure 134.5
Typical nodular BCe.
Figure 134.6
Morpheaform BCe. These are difficult to id enti fy
adjacent cheek and orbit.ls A variety of lesions may be seen and occasionally these are unevenly pigmented.
The
nodular variety is typically a slow-growing dome-shaped papule with a telangiectatic surface and pearly border. The lesion initially appears innocent but fails to heal, then crusts and eventually ulcerates (Figure 134.5). Other nodular forms pursue a relatively innocuous path for much of their clinical course,
presenting as a small
erythematous papule or plaque, a keratotic patch or as a pedunculated lesion resembling a pyogenic granuloma. The superficial type of BCC manifests itself as a scaly plaque with raised edges. In this form, margins tend to be indistinct and several neoplastic foci may reside within the lesion
making
excision
difficult.
Morpheaform
BCC
appears as a white or yellow plaque which develops telangiectasia, sometimes ulcerates and forms a scar-like lesion that is difficult to define and diagnose (Figure
134.6). This group appears exclusively on the face, presents
late and extends deeply. Less commonly, histopathology
and
define.
identifies a basosquamous BCC containing elements of basal and squamous tumour cells, which pursues a more
reconstruction. In general, basosquamous tumours and
aggressive clinical course than BCC alone.
morpheaform BCCs are more aggressive tumours and
[**]
Numerous treatment regimes are employed to establish
require wider excision. [Grade
D]
histological diagnosis and provide complete resolution of the tumour. Intralesional injection of interferon and photodynamic therapy provide good control of BCC, but
Melanocytic lesions
such measures are still not as successful as traditional techniques. Shave biopsy or curettage and cautery can
These may involve the nose and cheek and arise from
adequately remove small lesions but for larger BCC,
alteration in growth patterns of the melanocyte) which
surgery provides the best aesthetic results and radio
produces a range of benign, premalignant and overtly
therapy may be employed in older patients. A 4-mm
malignant lesions. Recognition and distinction is im
margin of clear tissue is recommended and excision
portant) as malignant melanoma is eminently treatable
should
when identified early in its natural history.
involve
the
dermal
layer.19
In
aesthetically
important sites) such as the nasal tip, primary closure may not be possible and local flap repair) free grafts or temporal flaps may be required. Moh's surgical technique
of sequential tumour excision under frozen section control is appropriate for tumours in difficult areas such as the medial canthus. This allows precise excision of the tumour mass and conservation of normal tissue for
Melanocytic naevi are a heterogeneous group that include congenital and acquired lesions. Congenital naevi appear at birth but also include early-onset lesions that are histologically similar and appear in the first five years of life. Initially pale, they enlarge) darken and develop terminal hairs. T he giant form is usually present from birth and may reach a size of 20 cm. It is particularly
Chapter 134 Conditions of the external nose I
1707
disfiguring and malignant transformation happen in 4-6 percent of cases. 20 Smaller forms are prevalent on the face and differ in that malignant change is less common and tends to arise later
during adolescence. [**]
Acquired naev i present an
mos tly during childhood and
adult has an average of 20-30 naevi.
2L
Both this
number and the lesions remain stable through life and rarely become
malignant . Naevi result from proliferation Cells
of melanocytes at the dermo-epidermal junction.
remainin g at this location , junctional naevi, appear as dar k
brown
macules
with
spots
of
black
pigment.
solely in the dermis, form
Intradermal n aev i, situated
macules, papu les or wart-like growths that may or may not be pigmented. Compou nd naevi are composed of junctional and dermal elements and result in raised
brown lesions. In childhood, a rapidly growing red papule or nodule on the face is a spindle or Spitz naevus. This is entirely benign but histologically tends to be con fused with early
malignant
melanoma. [**]
Atypical naevi are a group of lesions that are unevenly pigmented, larger and more irregular than the usual acquired naevi. They are associated with a degree of inflammation
and
analysis
reveals
features
that
are
uncharacteristic of benign growths. In a familial setting these lesions are linked to a high risk for
m al i gnan t
melanoma, but in sporadic cases there is a lesser, although st ill significant, chance of sinister t ransforma tion.
Figure 134.7
Superficial malignant melanoma with varying
colour and irregular outline.
horiz on tal growth phase and close inspection reveals a variety of hues w ithin the lesion, i.e. black, blue, brown and white. Nodular types are rare on the face and appear as a red nodule with a marked vertical growth pattern. These are deep tumours that grow rapidly and have a poor prognosis. Lentigo melanoma is found in older patient s, often on the face, as a flat brown-black patch which extends horizontally for months to years. Nodule formation
heralds
deep
invasion
conve r sion. Histological
diagnosis
is
requir ed
malignant
and and
SUSpICIOUS
lesions 1-2 em in diame t er should be excised with a clear circumferential
MALIGNANT MELANOMA
Malignant melanoma is the leading fatal illness arising in skin and its incidence is rising faster than any other neoplasm. Mean age at presentatio n is in the sixth dec a de although an increasing number of cases are presenting in younger age groups. There is a female prepo n derance and the most important aetiological factor is intense inter mittent sun exposure
in
fair-skinned individuals. A
mal ignant
treatment.
ma rgin of 1-2 mm The depth of the .
melanoma is essential for planning further
Confirmed lesions less than I-mm deep can be
removed with a l-cm margin of normal tissue. For lesions greater
than l-mm deep) opinion is divided and trials are Patients
currently comparing excision margins of 1-3 cm.
must be fully examined for related disease which will involve other treatment mo dalities.
positive family h i story is identified in 2-5 pe r ce nt of individuals. Pathologically,
malignant melanoma is charac terized by
malignant melanocytes invading the dennis, and the depth 22 of the lesion is the main prognost ic indicator. Lesions
Kaposi's sarcoma Kaposi's sarcoma (KS) is a rare tumour, possibly arising
less than 0.76-mm th ickn es s have a 100 percent five-year
from lymphatic endothelial cells) and consis ts of several
survival which decreases to 80 percent for melanomas loS-mm deep.23 Growt h is horizontal
epidemic spread of this tum our among young male
and vertical, however, increase in lesion height indicates
homosexuals was recognized as part of a new disease - the
between 0.76 and
enhanced invasive potential and decreased import ant
survival.
[**]
subtypes each runni ng a distinct clinical course. The
acquired immunodeficiency syndrome (AIDS). Evidence
malignant
suggests that a sexually communicated infectious agent
melanoma from other lesions are asymmetry, irregular
cotran sm itted with the HIV causes this form of KS?4
The
features
dist inguishing
outline, varying colour and a diameter more than 1 cm. Tn addition, pruritus, bleeding and inflammation should not
be ignored in suspicious cases. Malignant melanoma may not present as a pig mented lesion and less comm only can involve mucosal surfaces such as the nose. S everal forms exi st and the superficial spreading type is
Recently, human herpesvirus-8/KS-associated herpes virus has been postulated for this infective role.25 Human
immunodeficiency
[***1*]
virus-related
KS
com
monly presents on the feet and occasionally involves the head and neck region, p art icularly the ears and nose. Early lesions appear as small pink or red macules, or
main variant to involve the face (Figure 134.7).
brown papules. These progyes s to multiple violaceous
Commencing as a brow n macular lesion it exh ibits a long
nodular lesions, which subsequently coalesce and are
the
___
--
_.1 __ �.-
1708 I
PART 13 TH E NOSE A N D PARANASAL S I NUS ES
aesthetically unacceptable. Diagnosis is usually obvious but biopsy may be required. Ionizing radiation, poly chemotherapy and antiretroviral medication are em ployed and produce variable long-term benefits. Vascu l a r l es i o n s
This is a heterogeneous group that includes neoplastic lesions and abnormalities of vascular structure. Capillary haemangiomas are hamartomas and most commonly arise on the head and neck, affecting 2.6 percent of all live births. They are noted soon after birth as pink to red macular lesions that rapidly increase in size. The lesion becomes raised, papular or polypoid and takes on a darker hue appearing dark red or purple. Tumours then enter a quiescent phase and subsequently regress with 70 percent disappearing by the age of seven. Treatment is rarely required unless important structures are compromised. In such cases, or when tumours persist, surgery is the most effective therapy. Cavernous haeman giomas are less common than their capillary counterpart and consist of large dilated venous channels or sinusoidal blood spaces. Lesions lie deeper within the dermis and appear during the first months of life as an ill-defined, smooth bluish-red growth. Rapid expansion ensues but involution is unfortunately much less common. In addition, cavernous haemangiomas may be linked to certain congenital conditions, i.e. Klippel-Trenaunay Weber or Maffuci's syndromes. Treatment, whether it be surgery, radiotherapy or cryotherapy is difficult and the result often disappointing. Pyogenic granuloma can involve the nose, particularly in children, young adults and pregnant women, present ing as a dark red polypoid and lobulated mass of newly formed capillary vessels that may reach several centi metres in size. Its precise aetiology is unclear although trauma and infection have been suggested to play a role. The granuloma grows rapidly, ulcerates and eventually crusts, suggesting a malignant process, however the histology is entirely benign. Although involution happens, particularly post-partum, surgical excision or curettage and cautery are usually required. Naevus flammeus is a vascular abnormality causing dilation and swelling of areas of skin and presents in two forms. The 'stork bite' or 'salmon patch' is a vascular coloured area sometimes located on the glabella but more usually on the nape of the neck. It is extremely common and those involving the nose mostly resolve in the first year. The more unusual and unsightly 'port-wine stain' encompasses the nose and adjacent cheek in a distribution that follows the trigeminal nerve. Commencing as pink patches the lesion persists, darkens to a deep violaceous colour and later becomes nodular, adding further to the aesthetic disfigurement. In addition, some cases are associated with cerebral vascular abnormalities as in the Sturge-Weber syndrome. Treatment is difficult and the
usual modalities are employed with limited success. Surface tattooing may help and while the introduction of the argon laser has improved on previous results it is still not a complete answer. Hereditary haemorrhagic telangiectasia, or Rendu Osler-Weber syndrome, is an autosomal dominant condition characterized by abnormal small vessels located in the skin, mucous membranes and viscera. The vessel abnormality occurs in different forms which generally present at about adolescence with spontaneous haemorrhage. Regarding the nose, the most usual problem is epistaxis but inspection of adjacent skin may reveal the characteristic petechiae. Pulmonary arteriove nous fistulas are common and gastrointestinal involve ment is to be expected. Treatment is aimed at managing bleeding episodes or anaemia, and electrocauterization or laser therapy of individual lesions provides cosmetic benefit.
Fibroa d n exa l tu m o u rs
These tumours arise from supporting subcutaneous connective tissue structures. In themselves they are rarely important but may mimic neoplastic pathology or present as unsightly blemishes. Few are exclusive to the nose and they are generally classified after diagnostic eXCISIOn. Dermatofibromas are partially pigmented, keratotic lesions that reach sizes of up to 1 cm and generally persist through life. Histology reveals spindle cells and such growths belong to the benign fibrous histiocytoma group. A common lesion, usually on the side of the nose in elderly people, is the fibrous papule. They appear in groups as small flesh-coloured 5-mm growths. Once growth is completed, the lesions remain stable but tend to persist. Trichoepitheliomas are a rare entity which present as small, rounded pinkish nodules on the cheeks, eyelids and nose. They are entirely benign but tend to increase in size and number and sometimes form abortive hairs. Differentiation, clinically and histologically from BCC can be difficult although the presence of hair-like structures is reassuring. Angiofibromas are small flesh-coloured or reddish brown dome-shaped papules 2-3 mm in size. These diagnostic lesions are located on the cheek and side of the nose, particularly in the nasolabial crease. They form part of an autosomal dominant condition known as tuberose sclerosis that may exist with seizures, mental retardation, cardiac and renal abnormalities. Family members require examination and genetic counselling. Cysts
Cutaneous' cysts are located either intradermally or within the subcutaneous tissues and present in two main forms.
1 709
Chapter 1 34 Cond i tions of the external nose I
Epidermoid
are
cysts
by
lined
stratified
squamous
KEY
ep ithelium and contain keratin debris. Men are mostly affected and such cysts generally a ppear a fter puberty. In
some
with
prepuber tal
i n testina l
maJ ignant
cases
there
is
th a t
h ave
the
polyps
cha nge,
a
an
potential
known
condition
•
association
as
for
[n
Dermoid cysts are rare and often p rese n t from birth
•
in size
and p ossibly originate fro m incl usion of epidermal tissues embryonic
development.
•
A
presumed dermoid cyst over the nasal roo t sh ould be treated cautiously as th is may represent a nasal glioma or
•
meningoencephalocoele with potential co m m unica tion to the cranial cavity. Imaging and needle asp i rat io n o f the
of the les ion
mass are necessary to confi rm the sou rce before proceeding to excisi on. Milia are small versions
1 -2-mm cys ts th at are mlma ture
o f epidermoi d
cysts and
are
reco gn i zed
trauma,
cond i tio ns
_: ,
pa t ients.
•
Bee is
•
Bee is
•
Nose
the commonest skin cancer, locally i nvasive but rarely
a nd midface a r e common sites [o r Bee. Di fferent clinka J form of Bee -p r,est.'flo t and diagnosis can be di fficult
•
dermabrasion,
burns or bullous disease. Treatment involves shelling o u t
... �!
the cyst with the tip o f a hypodermic needle. A s they present in considerable numbers, this is a t ime-consu m
Melanocytic lesions
ing process.
•
Mel a nocyt ic lesions present i n nu merous
face and trunk. Multiple tumo urs o f the face with a
•
similar histology are found in dark-skinned races but are
-.
Ve rtical groWth is
Sebo rrhoeic keratoses
•
These are benign tumours which p redo minately a ffect
•
elderly people and arise from an increase o f normal keratinocytes in the epidermis. Males a nd fe males a re equally affected and lesions are commoner in wh ite races.
•
They present in any location but are most frequent on the
in younger
a ge
asymp tomatic, Typically, the
groups. however,
These
keratoses
itching
ca n
be
are
m os tly
a
feature.
/.
-.
-. . � :� . -
fo rm s . Recogni t i o n is i mport ant t o identi fy potcnt i ally neoplast ic lesions. Congenital naevi have the po t en t.i al fo r ma l ignan t change. Acquired naevi develop mostly d u r i n g c h i l d h ood and rem ai n s t a b l e d u ri ng ad ult life. Malig.nant cha nge is r -a re. MaJ i gn an t melanoma is t he leading fatal skin dis�ase. Neo p �as ti,c growth is horizontal and vertic�,
known as dermatosis papula n igra, and generally appear
/ ,
metasta� izes.
as
smooth white globules around the fa ce. They appear spontaneo usly but can follow
these
Lesions.
lesion
appearing on the nose as a midline mass anywhe re fro m
during
t he i n c i d e n ce of
'
va riety of
Keratoacanthoma is a ra p idly growi ng benign ' that s ubsequentl.y resolves. It may r m i m i c Sec. Lo ng-term s u n exposure can produce spec.ific ' 'ac t i n ic' cutaneous change and I percen t of , caS(1S proceed toO frank squ a m o us maligna ncy'- " Squamous carcinoma usually a 6ses in sun d a m a ge d skin and metas t as i zes i n 1 0 pe rce n t of cases. I n t raepidermal sec, Bowen's disease, becomes frankly invasive i n 10 perce n t of
•
prevent recurrence.
sites
general,
a
a l ign a n t
is increasing.
syndrome. Su rgical excision of the ep idermoid cyst is
aberrant
m
ben i g n , premal i gna n t and
often required and the entire cyst wall is rem oved to
in
with
Solar exposu lie is associated
Ga rdner's
the glabella to columella. They rarely exceed 4 cm
..' ..
POI NTS
" progn�:)sis� ' -
�
associa,��d Wi�h poorer .
.
.
:,
}
_.
"
<;' i ,
skin lesion has a 'stuck on' appearance
and develops as a superficial roun d verrucous p laque th a t varies in colo u r from yellow t o black. Over time their numbers
increase
with
sizes
ranging
from
a
few
millimetres to several centimetres. They tend to persist
.,/ A variety of treatment modali ties for cutaneous
and can be confused with melanotic lesions, although
n eo plas t i c lesions are available but s u rgery provides
malignant transforma tio n does not happen. A s imp le
good control.
curetting o r freezing technique is sufficient, however recurrence is n o t un us u al. MUltiple seborrhoeic keratoses may be a familial trait inherited in an autosomal dominant mode. S ometimes a pro fuse erup tion of seborrhoeic keratoses follows an inflammatory dermatosis o r occurs as a manifestation o f i nte rnal, particu larly gastrointestinal malignancy - the
Leser-Tn�lat sign.
.I An adeq uate m a rgin of clea r tissue must be excised w i th the lesion.
.I Excision should extend into the d ermis. .,/ Regarding the nose, good knowledge of facial plasti c techniq ues is needed to ensure sat isfactory excis ion and to preserve fun ct i on and cosmesis.
./ Preven tion in t h e form of ad e q u ate sun protection sho uld be advised_
_ _
_
_ _ _ _ __ _ _
_ _ __ _
_ __
,i..:. _....L--.. -
.....
17 10
I PART 1 3 TH E NOSE A N D PARANASAL S I N U S ES
M e l a n ocyt i c l esions .I M e l a nocytic l esions demonstrati ng asym metry, i rreg u l a r o u tl i n e, va rying colou r and s ize m o re th a n 1 cm have a h ig h e r risk of ma l ig na n cy.
.I Suspi cious lesions 1 - 2 cm in size are excised w i t h a 1 - 2-m m m a rg i n .
.I Confi rmed l esions l ess than O.76-m m de pth req u i re exc ision with a 1 -cm m a rg i n. G reater tha n this a 1 -3-cm m a rg i n is ne cessary.
SARCO I D O S I S Sarcoidosis i s a multisystem d isease denoted b y the presence of characteristic granulomas in affected tiss ues. It has worldwide distribution, b ut is more frequent in developed co untries, particularly among no rthern Eur opeans and American Afro-Caribbeans .26 Epidemiologi cal data indicate a slight female preponderance and presentation mainly in the 20-40 age group. The aetiology of sarcoidosis is unknown, however, genetic influences and
a role for
M. tuberculosis are c urrently topical.
Immunolo gical changes
comprise
depression
of cell
mediated immunity and a rise in serum immunoglobu lins, although such findings do no t appear to co rrelate with
the
course
of
disease.
Granulomas
co nsist
of
epitheloid cells, and usu ally, multinucleate giant cells. Lymphoid cells surro und the granulo ma but are generally sparse and give the appearance of a 'naked tubercle'. Fibrinoid necrosis is o ften evident but caseation is absent. The clinical picture of sarco idosis is extremely varied and reflects the far-reaching nature of the disease with few, if any, o rgans escaping potential involvement. Lymp h glands, lungs, liver, spleen, skin, eyes, salivary glands and the small bones of the hands and feet are among the most
Fi g u re 1 34.8
Sarcoidosis of the nose - l u pus pernio.
frequently involved regions. Onset can be indicated by fever,
may be
rim and the affected nasal surface appears shiny and
unheralded. S arcoidosis is p redominately a generalized
malaise
and
weight
loss
b ut equally
stretched. Ulceration is unus ual, but facial skin lesions
disease process that follows a protracted, often unpre
persist and are disfiguring. O ften, the nasal vestibule and
dictable and mostly benign course.
mucosa show evidence of granulomatous involvement,
Cutaneous sarcoid arises fro m deposition o f granulo
appearing
as
small yellow pap ules
or
no dules
with
mas in the dermis and is evident in 25 percent of patients
subsequent nasal swelling, crusting, blockage and ulcera
with systemic disease.27 Skin lesions can appear alo ne, and
tio n .
fo r reasons that are not clear, are particularly aggressive
cartilaginous and b o ny septum may perforate resulting
and
in nasal saddling and distortion.
atypical
in
Afro- Caribbean
races.
The
nose
is
classically asso ciated with lupus pernio but other sarcoidal
The
nasal
bones
can
be
infiltrated
and
the
Other fo rms o f cutaneous sarcoidosis also involve the
skin lesions affect this area. Nasal pathology is linked with
nose and face. Annular lesions have a violaceous co lour
persistent pulmonary infiltration and fibrosis, uveitis and
with
bone cysts. Erythema nodosum is the most frequent
circumference. The rare angiolup oid typ e has a marked
no nspecific cutaneous manifestation of sarcoidosis.
telangiectatic
Lupus pernio is plaque
that
a chronic, bluish-red,
symmetrically
infiltrates
the
indurated nasal
skin
(Figure 1 34.8 ) ; however, the cheeks, ears, fingers, hands
and toes may be similarly d amaged. Nodules are found at
the periphery o f the lesion o r o ccasio nally aro und the alar
a
paler
atrophic component
centre and
and is
darker
elevated
customarily
fo und
adjacent to the nasal bridge below the inner canthus. Papular eruptions are characterized by the appearance of up to several hundred small orange lesions that primarily
involve
the
face,
o rbital
margin
or
nasolabial
fold .
S carring is uncommon except in papular and annular
Cha pter 1 3 4 Cond itions of the external nose I 1 71 1
types. Sarcoid granulo mas show a predilection fo r scar tissue, which becomes p urple, swollen and tender and may be the initial or only indicator of disease. Histological
evidence
of sarcoid granuloma from
b iopsied tissue is the most imp o rtant investigation fo r establishing diagnosis. Cutaneous disease is easy to access but is less reliable and more cosmetically unsuitable than other sites such as lymph no des. In lup us pernio the nasal mucosa provides a suitable sampling location and lower lip biopsies, even in the absence of visible disease, should
CO N N ECTIVE TIS S U E D I S EASES This
uncommon
group
of
diseases
mosdy
targets
co nnective tissue structures producing a diverse range o f local a n d systemic consequences. While this may suggest a unifying aetiological and pathological relatio nship, debate persists as to the true nosology of these disorders. The external nose is involved, u su ally as part o f the injury to facial connective tissu es.
be considered. The Kveim test is positive in many patients
although this rate decreases with chronicity. Chest x-ray reveals abnormalities in 90 percent of cases, however, imaging of hand bones does not show cystic change until the later stages of sarcoidosis. In active disease, a raised erythrocyte
sedimentation
rate
(ESR)
and
abnormal
serum calcium are to be expected. Angiotensin-converting enzyme is elevated in 60 percent of patients but is not necessarily diagnostic as increased values are also fo und in liver disease and diabetes mellitus. Local
or
intralesional
stero ids
are
effective
for
cutaneous lesions but aggressive and persistent sarcoidosis or
disfiguring
skin
disease
requires
systemic
steroid
therapy. Methotrexate has b een used in lup us pernio with some success and a variable resp o nse has been obtained
from
chlorambucil
and
azathioprine.
The
antimalarial chloroquine has also b een prescribed fo r chronic skin lesions. Cosmetic preparations and laser therapy are an important adjunct in lupus pernio to overcome the visible and p ersisting skin deformity.
[H]
Lu p u s eryth em atos u s Lupus erythematosus encompasses a number o f disorders characterized by co nnective tissue damage and d emon strable autoimmune patholo gy. Genetic factors, environ mental
irritants,
such
as
sun
exposure,
ultravio let
radiation and drugs, including iso niazid and chlorpro mazine, are also implicated. The presentation and course varies from a relatively benign illness to a life-threatening disorder that is more common in women and has a maximal incidence aro und the fourth decade . Patients o ften report a background history o f Raynaud's phenom enon or chilblains. Two main fo rms exist: systemic lupus erythematosus ( SLE) which affects b oth skin and internal organs and discoid lup us erythematosus ( D LE) which is predominately a cutaneous disorder. A third, possibly intermediate variant, subacute cutaneous lupus erythe mato sus, rarely involves the face. Nonspecific cutaneous disease is also seen in lupus erythematosus.
' /. .
D I SCO I D L U P U S E RYTHEMATOS U S
Discoid lupus erythemato sus i s characterized b y chronic cutane o us exp o sed
disease
areas,
i.e.
predo minately the
face
and
lo calized neck,
to
light
although
a
disseminated form involves the limbs and trunk. A rash is the initial presenting sign with the cheeks, nasal bridge, ears, neck and scalp being the favoured sites. Histopathol
- (:
ogy reveals degeneration in the dermis and basal layer of the epidermis .
. C�;�i�np;��t�t���l�:�J��tt'.': •. ,
Well-defined erythematous plaques are characteristic and can reach up to 15 cm in width. These possess a
..,
covering adherent scale, which when removed reveals dilated follicles plugged with keratin, and is described as the 'carpet tack' sign. Excessive keratosis may p roduce warty lesions that are particularly common on the nose. In the tumid fo rm of DLE, lesions are swollen, brawny,
" I� Best cl i nical pra'ctlce , I
..I D i ag nosis is difficult des p ite a va rie ty of tests. B iopsy evidence is the most conclu sive proof of sarcoi dosis.
, ./ The d isease fol lows a protracted and benign cou rse .a nd corticosteroids provide the best means of control.
warm and tender and involve the entire face and nose.
-
Nasal mucosal lesions are less common, happening in only 9 percent of cases?8 The typical DLE plaque consists o f an active erythem atous scaly margin encl osing a central area of scarred, hyp opigmented, atrophic skin. Untreated, lesions persist, however, even with successful therapy the peripheral margin of the plaque may remain active fo r many years and DLE leaves a legacy of permanent scarring
_ ___
._L.__'�'-"
1 7 12
I PART 1 3 TH E N OSE AN D PARANASAL S I N U S ES
(57 percent) , scarring alopecia ( 3 5 percent) and pigment abnormalities ( 35 percent)?9 A small proportion of p atients (6.5 percent) will develop SLE?O [**] Haematological
present
in
and
serological
abno rmalities
are
50 p ercen t of patients,3 1 however, DNA
antibodies are not significantly raised and the diagnosis is usually established on skin biopsy. Treatment relies on fluo rinated
topical
steroids
in
and
refractory
cases
antimalarials are prescribed. Advice on sun protection is necessary and cosmetic camouflage techniques may be
[ * *]
ap p ro p riate .
SYSTEM I C LU PUS ERYTH EMATOSU S
Systemic lupus erythematosus is a co mplex systemic disease with wide-ranging manifestations and to date its precise cause is unclear.32 Immunological findings are
Fig ure 1 34. 9
specific
d i stribution i s see n i n erysi pel as.
and
include
evidence
of
nonorgan-specific
M a l a r ra sh of SLE. A similar 'butterfly'
humoral autoantibodies, decreased cell-mediated immu nity and a reduction of activated B cells. The relevance of ultraviolet light, which may p recipitate or exacerbate SLE in 60 percent of patients,33 the role of bacteria and viruses, and the relationship of SLE to certain drugs, has not been determined. Involved tissue shows fibrinoid necrosis,
collage n
thickening
.
necrosis
[ *]
and
vascular
endothelial
Systemic lupus erythematosus presents either as an acute fulminating illness with feve r, weight loss, anorexia and
malaise
or more slowly with
skin lesions
unpredictable and is marked by relapse and remission many
years.
Arthritis,
cutaneous
lesions
and
nephritis are all present in over 80 percent of patie nts during the pleurisy,
course of the
pericarditis,
disease.
Lymphadenopathy,
hepatospleno megaly
and
central
nervo us system symp toms are frequently evident. A skin rash is the presenting feature in 25 percent of patients34 with cutaneous erythema on light-expo sed areas being the most commo n sign. Intense, symmetri cal, facial
erythema
involving
the
cheeks,
sparing
the
nasolabial folds a n d bridging over the nose - the (b utterfly or malar blush' - is classically but not solely asso ciated with SLE
(Figure 134. 9 ) . A macropapular eruption
but distinction from DLE may be difficult. Mild disease responds to topical or systemic steroids and antimala rial therapy. Aggressive SLE requires systemic steroid preparations and immunosuppressive therapy.
[**]
Derm ato myos iti s
and
subseq uent systemic involvement. The clinical history is over
antibo dies to double-stranded DNA is specific for SLE. Histology reveals typical changes induced by the disease,
D ermatomyositis is an autoimmu ne inflammatory dis order involving skin and muscle.
O nset is acute or
insidious and p resenting symptoms include rash, p roximal
muscle weakness and dysphagia arising from pharyngeal muscle
involvement.
Nonspecific
cutaneous
changes
present as a dusky redness involving the face, neck, trunk and
limbs
but
the
appearance
of violaceous
facial
erythema with periorbital oedema is diagnostic. Treatment involves corticosteroids and immun osu p p ressive therapy, although a chronic course with l ong remissions is usual. Facial lesions tend to fade although some scarring and p igmentation may remain. In a p roportion of patients, there is an associated underlying maligna n cy.
with
slight scaling is frequently noticed and can occupy a similar malar distrib utio n . Facial oedema and bullo us
System ic sc l e rosis
lesions are also reported and D LE-type plaques are fo und in 30 percent of cases. A tender, warm and swollen nose
Scleroderma is characterized by skin sclerosis with the
may signify relapsing nasal chondritis bUL cartilaginous
ues L ru c l ion of hair follicles and sweat glands. Il happens
collapse is not a sequel. Nasal septal ulceration is evident
either
in 5 percent of patients and may lead to perforation and
disorder. Lo calized disease, known as morphoea, generally
ep istaxis 35 Changes in facial skin result in a tightened, .
bound-down appearance, often with pigmentary ch an ges
.
Definitive diagno si s for SLE is difficult and a wide
as
a lo cal phenomenon or as part of a multisystem
does not involve the fa ce although a fro ntoparietal fo rm
presents
as
range of tests is necessarily required. Haematological
' sabre cut'.
Autoantib odies, particularly t he antinu clear variety, while
condition
abnormalities are common and the ESR is usually raised.
consistently present are not diagnostic, but the finding of
a disfiguring linear, depressed, sclerotic scar
extending fro m the glabella to the scal p and is likened to a Scleroderma •
also
exists
as
part
of a multisystem
of unknown aetiology, known as systemi c
sclerosis, and is
associated
with vascular damage to small
Chapter 134 Conditions of the exte rna I nose I 1 7 1 3
arteries. The skin, muscu los kele tal, gas troin t esti nal, car
reflecting granulo matous involvement o f the
internal
diopulmonary and ren al systems are most often targeted .
nose. Collapse or even necrosis of the nose indicates
Cutaneous changes primarily involve the face and hands
infiltration o f underlying bone and cartilage. Cutaneous
with the sclerotic p rocess producing tighten ing of facial
lesions appear as small red or purp le, blisters, nodules a n d
becomes shiny, fadal wrin kles are lost, tel a ngiectasia are
discussion is provided in Chapter 1 30, Gran ulomatous
skin and a 'bound down' appearance. Th e epidermis
evident and the nose appears beaked. In add ition , the
ulcers
that
occasionally
embrace
the
nose.
Fur ther
conditions of the nose.
mouth tightens pro ducing a 'purse-string' appearance
and the vermillion border fa des. I nvo lvement o f the fingers prod uces sclerodactyly and su bcutaneous calci fi cation or calcinosis i s detectable.
Di agnosis i s made
clinically and treatment provides sym p tomatic support bu t the history is chronic, varied
and unp redictable.
Scleroderma may present with elem ents o f o ther co n nective tissue disorders, i . e . mixed connect ive disease or as p art
of a restricted
cuta neous
tissue disease
confined to the hands and face and associated with calcinosis, Rayna ud's phenomen o n , oesophageal dysfunc tion, sclerodactyly and telangectasia or CREST syndrome.
NASA L D ESTR U CT IVE LES I O N S Nontraumatic alteration to nasal shape o r evidence of tissue destru ction is an event that should warn the clinician of significant underlying rhinological disease. Congenita l disruption of nasal development is rare but presents i n different forms including agenesis, bifidity and alar hypoplasia. A number o f syndromes produce definite external deformity such as the beaked nose of Apert's or Cro u zon's, the large and u pturned nose as in Fryn's and the flattened o r depressed nose of Binder's.
Intern al
di sease, s u ch as sarcoidodsis, lupus vulgaris, syphilis, rhinoscleroma or leprosy
Relaps i ng po lych o n d r i t i s This i s a rare disease typified b y inflammatory changes i n cartilaginous structures with subsequent degeneration and fibrosis. Evidence supports a n autoimmune process with
au toantibo dies
component
directed
of cartilage,
type
against II
an
importan t
collagen.
Auricular
chondritis along with arthritis are the usual presenting features. In general, o n ly o ne ear is affected at any o ne time and ear lobes are spared. Nasal involvement is seen in 60 percent of patients and is heralded by sudden o nset of redness, warmth, swell ing and tenderness that subsides after two to fo u r weeks bu t recurrence invariably happ ens weeks to months later. Cartilage is replaced by fibrous tissu e with loss of function and cosmetic defonnity. The eyes, larynx, inner ear and cardiovascular system may also be incl uded. T he ESR is consistently abno rmal and histology, i f needed, reveals a perichondrial inflammatory infiltrate. Corticosteroids are the backb one of management, although cyclo spo ri ne and metho trexa te are sometimes required. T he disease is unpredictable
can
ultimately include the
cartilaginous structures, particularly the septum, with
and may follow a relatively benign cou rse,
although involvement of laryngeal cartilage can lead to airway collapse or stenosis.
l oss of tissue and consequent dorsal defo nnity. In other cases, disease processes directly involve nasal cartilage, e.g. relapsing polyc hondritis or infiltrate cutaneous tissues, as in scleroderma. Ulceration or destruction of nasal tissue is
a rare event and is disease,
lupus
p o ssible sequel in late malignant
a
vulgaris,
tertiary
syphilis,
Wegener's
gra n ulomatosis, l eishmaniasis and cryptococcosis. ln addition, there is a poo rly defined gro up character ized by necrotizing nasal disease, which results in extensive mid facial
destructio n.
Labels
include
lethal
midline
granuloma , polymorphic reticulosis, S tewart's granuloma and
lymp h omatoid
granulomatosis.
Current
o pinion
suggests that these different diseases are, in fact, the result of a single path o logy - T-cell lymphoma. This is a localized disorder producing slow progressive destruction of the nose, characteri zed by areas of infarction, ulceration and necrosis of bone . The histological picture reveals atypical lymphocytes, but distinct evidence of neoplasia is o ften diffic ult to iden tify. The exact clinicopathological picture is still not clear bu t may encompass a spectrum of disease, which includes the development of lymp homa in its patho logical course. Fo r aU these situations the clinical picture
combined
with
thorough
investiga tion
and
h isto logica l analysis is essential.
Weg ener's g ra n u l o m atos i s This rare disorder is characterized b y granulomato u s infiltration a n d destruction of the
upper
and lower
respira tory tracts, in combination with a general necro ti zin g vasculitis
and
glomerulonephritis.
The
disease
presents either acu tely or insidiously taking many years to 'evolve and nasal mucosal disease is alm ost always
p resent at some stage. The external nose is not a p rim ary target but p atients often remark on nasal discomfort
" , b t
'
"
Kty' 'P01NTS '
... -�
-
., : Th� .,nose way be involved m · el theh�])LE, or 1 ,
SLE..
!
"
"
,
'
.
," .,.
"
'
---:-
'
. ' DLE is a ch ro nic cuta neous , dise.ase ,arising on 'sun -ex.posed area s and charact ��ized by
�q
p)aque formation with subs , �ent scariing ,
-
...;
1714 I
PART 1 3 TH E N OS E AN D PARANASAL S I N US ES
SLE presents a-S', acute- fuliriinstbpg' or chronk disease and 2 5 percenco f - qases develop , a
•
t ip ,
midfacial ' bu t terfly' rash. Periorbital oedema and violaceous fac�l ' erythema arc diagn.<;>stic. o f der m atomyositt�;. � r',� ' • Systemic sclerdsi�� ;�ay. involve the face and is' , :,' �' \ :· ;:th?-r��-ter!�.eQ: 'by� tiglltenirlg 6f the facial skin : ; :' <; : aIid ;'�pp,eM 'aP.ce" (jf a bea,k'ecfn,ose.;. ' " :' ' � " � ' R¢l�psin:g::poiychorrdiitis i�v�lves the nasal ' , ' ·,'� btrtilag�( in 60 percent df pat ients and may , c' -:'::>�;';;, }iSWt i n nas.il� defor:m ity.' : ' ' ' \ ")' vV'�,g('ner's gra o�� m at osi� invaFiahly i n vo lve s � � �\., ".?J:he' nosc du ririg the coti,�S�" of dise:ase and . �an,� .: : :; , , : :' : " ', i 'event ually result i11 naS:ar-' de� t:r:u�.tipn/' '. : ', ' . : . ..�< NaS�l :de$�ru,�ti&il:?br· 'ti.lce�ti0ir ' is a r�re , : ,- ".ceverit.--Th{ de¥e1c)pm�Iit· of: a localized T-gefl . ' " , �\ ' lyipp�(jiha ' shorrI
•
· - ' :.
"
·· , "
c
,�
' ·
�
.
j ;.� .f
-,_
.
,
•
'+1,1';' I
"
/l '- -',
, •
'.
,
al ar
rim
and
co l u mella
tissues
results
from
a
p rogres s ive increase in co n n ective t issue , s ebaceo u s gl a nd
� I
•
hyper p la s ia and ch ronic d ee p inflammation, although s igns of rosacea may not be evident
(Figure 134.10).
Phymas may al s o involve the chin, glabella a n d eyelid. Several for ms exist. Glandular types show a massive
in creas e in
sebaceous gla n d s resulting
in a p itte d, dented,
distorted a n d asymmetrical surface. Fibrous rhinophyma are diffusely en larged a n d more symmetrical. Ectatic sur face veins characterize the fibroangiomatous group and
the
actinic
fo rm
is
distinguished by distorting
no d ular masses of elast ic tissue.37 Tre atment
[HI"']
of rosacea is difficult and
cure may not be
p ossible. Re as o nable results are obtained with long-term
antibi o tics , p articularly topical metronidazole and oral tetracyclines, an d some successes have been reported with synthetic reti noids . Topical steroids should be avoided as they may cause rebound erythema but skin care and sun
protection should be discussed. Rhinophymas may be removed and the nose contour re-established with paring techniques, using a scalpel or Silver's knife, or electro
Best cl i n ica l practice
coagu lation. Carbon dioxide, argon and p ulsed dye lasers have also been emp loyed to good effect.
,/ I n l u pu s eryth e m a tos us, a va riety of sero l og ica l tests ca n be performed but a n ti bod ies to d o u b l e-stra nded
Eczema a n d d ermatitis
DNA a re spec i fi c fo r SLE. ,/ For co n n ective t issue d isease cort icoste roids a n d i m m u n os u p p ressive therapy a re the m a i n t h e ra p e u t ic
These are interc h a n g eable terms covering a wide variety of
a g e n ts.
conditio ns and may involve facial skin. Eczema is a
cuta neous i n flam ma tory condition, possibly arising from
DERMATO LOG I CAL D ISEASE Rosacea This
is a disease p ro cess i nvolving the central
face,
ch aracterized by the fo rmation of papules and pap ulo pus t u l es o n a
b ackg ro u n d o f eryth ema , oedema
and
te la ngectasia. It is most noticeable in the 40-S0-year age gro up and predominantly affects women with fair skin and of Celtic ancestry. Its pr ecise origin is unknown but genetic facto rs appear to be
relevant and affected p atients
always have evidence of s un -da maged skin.
36
Despite this,
p e op le with outdoor occupations do not seem to be at increased
risk.
The nose, cheeks,
chin,
fo rehead and
glabella are
mostly involved, Patients report a h i sto ry of excessive
flush ing or blush ing in a pp ro p riate situatio ns. This increases in frequency, cul m inating in a persistent dark red erythema involving the central face. Papules, p ustules and telangectasia are evident i n the affected area, however,
comedones are absent, and therefore differentiate the disease from acne vulgaris.
and r are devel o p men t of rosacea, arising almost in men, is rhinophyma. Overgrowth of the nasal
A late
solely
Figure 1 34. 1 0
R h i n o p hyma.
Chapter 134 Co nditio ns of the extern al nose I 1 7 1 5
atopic or endogenous causes, which exhibits scaling ,
partially
depigmented
white
macules
appearing
on
vesicular lesions and exudation . Pruritus and scratch ing
exp osed areas and brown p atches evident o n covered
course with eventual cutaneous t h ickening o r l ichenifica
can be cleared with selenium sulphide s h ampoo. Drug
are the main symptoms and the d isease runs a chronic tion. Contact dermatitis results from contact between ski n and
a
substance in touch with the skin that produces
epidermal d amage. The substance, which ca n be fo u n d at
regi ons. A causative yeast, P.
orbiculare, is res ponsib le a nd
reactions are manifold and may involve the nose in several
situations. To pical app lication of medication to the eye or
nose,
especially with externa l
use
of aminoglycosi d e
home or in the workplace, i.e. occupational derm a t i t is,
p reparations
epidermis. Erythema, o edema and vesicles typ ify the
thiazide diuretics may generate rashes in su n-exposed
may produce an a llergic or irri tant reaction wit h in the
eczem atous
can
produce
change.
a
contact
Tetracycline,
dermati tis
sulphonami des
wi th and
acute form, but over time l iche nific a tion, scaling and
area s includ ing th e face. A thorough drug hist ory sh o u ld
extensive epidermal dam age e nsues.
always be elicited.
Seborrhoeic dermatitis
Pe m p h i g o i d
This disorder i s typified by the presence o f d iscrete erythematous
yellow scale.
p atches,
often with
a superficial
greasy
Pityrosporum o vale, a no rmal co mmensal
yeast, can be identified from the lesion site, altho ugh i ts precise relatio nship to the condition is u nclear. Adult males
are m ostly affected, p articularly those pro ne to scaling and dandruff. The central face, particularly
in the nasal furrows
and groin are the usual s ites and
there m ay be an
and nasola bial folds, sca lp, ears, eyeb rows, stern um, axiUa associated blepharitis or otitis externa. Topica l steroids
produce
improvement
but
a re only useful
for
short
periods. Topical o r systemic triazole a n tifungal prepara
tions a re beneficial and sal icylic acid o r ich th am mol can be
employed
for long-term
care.
More
aggressive
forms
happen in AIDS p atients and i n infants u nder s ix mo n ths.
In
an
elderly p atient, the app earance o f tense bullae o n a
p receding rash or normal skin suggests
a
d iagnosis o f
pemphigoid. Th e lim bs a nd trunk are predominately
involved, although the face and nose may be i ncluded . The
condition
persists
for
m any
m o nths
and
oral
corticostero i ds aid recovery. Scarring is not a feature.
Pern i o sis Chilblains are tender, erythematous, itchy lesio n s tha t
blis ter and ulcerate. This inflamma tory reaction is a n
abnormal response t o cold temperatures and appears o n fingers, toes, legs, ears and n o s e . A genetic influence is
s ugges ted
by
positive
family
histories
and
systemic
conditions, especially arterial disease, are releva n t. P re
ventative measures to p rovide warmth are valuable hut traditional techniques employing
Acne vu l g a ris
ultraviolet
radiati o n
probably have no value. Nifedipine and calc i u m chan n el
This i s the common form o f acne a n d begins d u ring
blockers are effective for severe disease.
puberty. Other types arise fro m exposure to hydroca rbo n derivatives, phenols, steroids and androgenic hormones.
Findings that appear to be important incl ude elevated levels
: ' KEY
of sebum and free fatty acids in sebaceo us gla nds associated
with hai r follicles, the presence of pro prionibacterium
ames,
dennal
inflammation
and
increased
levels
of
androgenic hormones. These factors consp i re t o prod uce
inflammatory papules and pustules on the face, back and chest, which progress in severe cases to the development of
nodules a nd cysts. Reso l ution may be incomplete and leave a legacy of macules and scarring. Diet, skin care, a ntibiotics,
synthetic
retino i ds
and
ultravio let
l ight
a re
used
to
POI N-TS
",� . Rhindphyma ]s an "-lmusual and- late . : �"' " manifestation -of ros aceq. hap p eni ng solely in -
_"
men. _
"
� ;
' : Deiula-tological dise ase b?-volvi ng_ the n ose
: " " 'may -'prese�_t- as erythema ; p usJwes, scahng or .
'thi�kenin g , � u't is
always part of "a more
Wid-est)f(�a:d cutaneo u s rea
m oderate the condition. Following the active phase o f
ct}on. _
c"
..
disease, permanent scarring can b e lessened with dermab
rasion techniques or laser therapy.
Best cl i n ica l practice Fac i a l rashes
./ A com prehensive d rug h i sto ry s h o uld b e so ugh t as to pical use of facial, nasal or o ph thalmic med i cations
i
I
Rashes ra rely if ever involve the face alone. P ityri asis versicolour is a skin eruption fo llowi ng sun exposure with
i
!
�-
can produce a localized contact dermatitis.
1716 I
PART 1 3 TH E NOSE AN D PARANASAL SI N U SES
Defi c i e n ci es i n cu rrent know l ed g e a n d a reas fo r fu tu re resea rch
10.
G ra h a m J H , H e l w i g EB. Cuta neous pre m a l i g n a nt lesions. I n : M onta g n a W, Dobson RL (eds). Advances in biology of skin, vol. VII, Carcinogenesis. New York: Perg a m o n , 1 9 66:
277.
>- With the i n crea si n g i nvolve m e n t of
11 .
oto rh i n o l a ry n g o l og ists i n fac i a l d iseases, the s u rgeon m ust d evelop the know l ed g e, experi e n ce and a b i l i ty to ma n a g e such pathol ogy.
su rvey. International Journal of Cancer. 1993 ; 53 : 585-90. 12.
>- S u rg ical exc ision of n asa l a n d fa cia l lesions m ust be d i rected at resecti n g d isease, m a i nta i n i ng fu nction
Journal o f Dermatology. 1 99 1 ; 3 0 : 715-7.
14.
be re moved. This is st i l l not a d eq uately resea rched for
Ko CB, Wa lton S, Keczkes K, B u ry H P, N i cholson C. The e m e rg i n g e p i d e m i c of skin cancer. British Journal of
m a l ig n a n t m e l a n o m a .
Dermatology. 1994; 1 30 : 269-72.
15.
Rosso S, Za n etti R , M a rt i n ez C, To rmo MJ, Sch ra u b S,
may be e m p l oyed and these shou l d be ta i l o red to the
Sa ncho-G a r n i e r H et 01. The m u lticentre south E u ropean
type of d isease and to t h e pati ent.
study ' H e l ios' I I . Differe n t s u n expos u re patterns i n the
» So l a r expos u re i n d u ces a spectru m of skin lesions of
aeti o l ogy of basa l ce l l a n d sq u a m ous ce l l carc i n o m a s of
va ry i n g severity that a re i n creasi n g in freq u e n cy, a n d e m p h asis shou l d a l so be p l aced on prevention.
)0
Cza rn ecki D, M e e h a n C, O ' B ri e n T, Lea hy S, N ash C. The c h a n g i n g face of ski n ca ncer in Austra l i a . International
> The n a t u re of the lesion d ictates the extent of
>- F o r m a l i g n a n t co nd itions va rious treatment m o d a l ities
Cotra n RS. M etastasisi ng basa l ce l l carc i n o m a s. Cancer. 1 9 6 1 ; 1 4 : 103 6-40.
1 3.
a n d preservi ng a esthetic i n teg rity. resection a n d the m a rg i n of hea lthy tissue that m ust
M a rks R, Sta p l es M, G i les CG. Tre nds in n o n - m e l a nocytic skin ca n ce r t reated in Austra l ia : the second n a t i o n a l
the ski n . British Journal of Cancer. 1 9 9 6 ; 73 : 1447-54. 1 6.
In fa cia l p l astic s u rg e ry, surg i c a l exce l l e n ce req u i res the knowledge a n d expe ri e n ce that e n compasses a ra n g e of spec i a l ities i n c l u d i n g oto rh i n o l a ry n g o l ogy,
H o g a n DJ , To T, G ra n L, Wong D, La ne PR. R i sk factors for basa l ce l l ca rci n o m a . International Journal of Dermatology. 1989 ; 2 8 : 591 -4.
17.
dermatol ogy, oncology a n d p l astic s u rg e ry.
G a i l a n i M R , Sta h l e-Backd a h l M, Leffel l DJ , G ly n n M , Za p h i ropou l os PG, Press m a n C et 01. T h e ro l e o f t h e h u m a n h o m o l o g u e o f D rosoph i l a patched i n spora d ic basa l ce l l ca rc i n om as. Nature Genetics. 1 9 9 6 ; 1 3 : 78-81.
18.
R oe n i g k R K, Ratz J L, B a i l i n PL, Whee l a n d RG. Trends i n the p resentation a n d treatment of basa l ce l l carc i n o m a s.
REFERENCES
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Noble WC (ed .). The skin m icroflora and m icrobial skin
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ca rc i n o m a . Archives o f Dermatology. 1 9 87 ; 1 5 :
1 41 a n d 177.
340-4.
Wa l ley J, Porter J. Chemoprophyla xis in tu bercu l osis a n d
20.
m a l ig n a n t tra n sform ation in g i a nt pig me nted n aevi.
Watson JM, M e redith SK, W h itm ore-Overton E, B a n n iste r
Scandinavian Journal of Plastic and Reconstructive
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Surgery. 1977; 1 1 : 1 63-7.
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P. The n u m be r and d istri bution of be n i g n m e l a nocytic
d iseases and vascu l itis in the nasa l m u cosa. I n : Rya n TJ
n aevi in a hea lthy B ritish population. British Journal of
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Dermatology. 1 9 8 5 ; 1 1 3 : 1 67-74.
22.
Roo k A, Champion RH. Keratoacanthoma. M o n og ra p h 1 0. M a rks R , Fo ley P , G ood m a n G , H a g e B H , Sel wood TS.
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of the extrem ities: a c l i n i copath o l o g i c study usi n g levels
co nse rvative m a n a g e m e nt. British Journal of Dermatology.
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Roberts D L. I n cidence of non-melanoma s k i n ca ncer i n Dermatology. 1990; 1 2 2 : 3 9 9 -403.
t ra nsm itted i nfecti o n . Lancet. 1 9 9 0 ; 3 3 5 : 1 2 3 -8. 25.
Moore PS, Cha ng Y. Detection of herpes vi rus- l i ke
M a rks R, Sta ples M, G i les GG. Trends in n o n - m e l a n ocytic
seq u e n ces in Ka posi's sarcoma in patie nts w i t h a n d
skin ca n ce r t reated in Austra l i a : The seco nd nation a l
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B e ra l V, Pete rm a n TA, Berke l m a n R L, Jaffe H W. Ka pos i 's sa rco ma a m o n g persons with AI DS - a sexua l ly
West G l a m org a n , S o u t h Wa les. British Journal of 8.
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* 27.
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Kerd e l FA, M osch el la S L. Sa rco id osis ; a n u pdated review.
1717
S nyder 3 rd G G , M cCa rthy R E , Too m ey J M , Rothfi e l d N F.
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I
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Ja nsen T, P l ewig G. Rosa cea : c l a ssification a n d treat m ent.
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FU RTH ER READ I N G
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* 32. 33. 3 4.
* B u rget GC, M e n i ck FJ. Aesthetic reconstruction of the nose. St. Lou i s : Mosby-Yea r Book, 1 994.
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Wa l la ce DJ , H a h n BH (eds). Dubois' lupus eryth ematosus.
Wilkinson/Ebling textbook of dermatology. Oxfo rd : B l ackwe l l ,
P h i l a d e l p h i a : Lee a n d Feb i g e r, 1 99 3 .
1 988.
Love LA. l'J ew e nvi ro n m enta l a g e n ts associated w i t h
* Freed berg 1M, Eisen Al, Wolff K, Fra n k Austen K, G o l dsm ith LA,
l u pus- l i ke d isorders. Lupus. 1 994; 3 : 467-7 1 .
Katz S I et al. (eds). Fitzpa trick's Dermatology in general
Tuffa n e l l i D L, D u bois EL. Cuta neous m a n ifestations of
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syste m ic l u pus erythematosus. Archives of Dermatology. 1 9 64 ; 9 0 : 3 7 7-86.
1 35 The diag nosis and managem en t of fac ial pa i n
TI M J WOO LFO R D AN D N I C H O LAS S J O N ES
I n trod u cti o n
1 71 8
Te nsi o n -type he adache
1 724
Backgro u n d
1 71 8
M i dfa ci a l se g m e n t p a i n
1 72 5
H istory ta king i n faci a l p a i n
1 71 9
Atyp i c a l faci a l p a i n
1 72 7
R h i n olog ical pa i n
1 720
Key points
1 727
De n t a l pa i n
1 7 21
Best c l i nical pract ice
1 7 27
Vascu l a r p a i n
1 722
Defi ciencies i n c u rrent know ledge a n d a reas fo r fu t u r e
N e u ra l gias
1 7 24
Pa i n caused by t u m ou rs
1 724
1 7 28
resea rc h
1 728
References
This chapter is based u p o n a Medline search using the key words facial pain, sinusitis, paranasal sinuses, migraine, cl uster headache, neu ralgia a n d focu sin g on diagnosis, sin us s urgery and management.
I NTRO D U CTI O N
facial p ain and headaches are usually caused by sinusitis. The fact that there is an ENT sign in outpatients does not
Patients
with
facial
pain
are
frequently
refer red
to
limit the p resenting conditions to this sp ecialty. If all cases
otorhinolaryngologists. Most patients arrive in the clinic
of facial pain are assumed to be sinogenic, those with
with an i nitial diagnosis of si nusitis, although in reality
other conditions
few of these patients have si nogenic pain. This chap ter
ment and many patients
aims to assist the reader in the accu rate diagnosis of facial
inappropriate surgery.
p ain and the management of this co ndit ion.
will not receive correct medical treat will continue to be subjected to
The majority of p ainful stimuli from the face are transmitted to the spinal tract of the brain stem via afferents in the trigeminal nerve. Pain afferents from the
BACKG ROU N D
VIIIth, IXth and Xth cranial nerve also relay in the spinal
Reaching the co rrect diagnosis i n patients with facial pain
poorly localized ache because the afferen t nerves inner
is challenging because many patients come with fixed
vating them are unmyelinated. Facial skin is supplied by
tract. Facial pain fro m deep structures tends to be a dull ,
A
ideas about the cause of their pain. The majo rity are
myelinated
convinced they have sinusitis, a not unreasonable view
neurophysiological m odel has been proposed by Olesen I
because this diagnosis has o ften been co nfirmed by their
to explain the interaction of the various nociceptive
general practitioner o r other specialists. A proportion of
n erves
that
p roduce
a
sharper
inputs causing tension headaches and migraine
pain .
and this
patients have already undergone unsuccessful nasal or
can use full¥ be extended to help in the understanding and
sinus surgery and this reflects the widely held view that
diagnosis of fa cial pain. This theory describes central
Chapter 135 The diagnosis and management of facial pain I 1719
sensitization of the trigeminal nucleus by myofascial, vascular or supraspinal input. It is postulated that an imbalance between these various inputs causes pain. Psychological influences that reduce supraspinal inhibition of the trigeminal caudal nucleus may either increase pain from established disease or provoke pain in the absence of disease. [H/*] To add to this, surgery, trauma and inflammation may promote nociceptive stimulus of the trigeminal caudal nucleus and initiate pain. To manage patients with facial pain effectively, the psychological aspects of this condition must be considered, and in some patients these may be an important factor. A good example is a patient with facial pain who has previously sustained a nasal injury during an assault, without resolution of the psychological insult. The pain is more likely to persist if there are ongoing compensation or legal issues that are outstanding. Similar problems can arise after rhinoplastic or other sinonasal surgery, particularly where the patient is dissatisfied with the outcome. For some patients facial pain is an expression of their emotional distress or anxiety, and in some patients their continuing pain may enable them to obtain attention or secondary gain. The pain is very real to the patient and an empathetic approach is essential. [H/*]
•
•
•
HISTORY TAKING IN FACIAL PAIN In common with many areas of medicine, the key to a correct diagnosis in patients with facial pain is taking an accurate history. It may not be possible to reach a definitive diagnosis at the first visit, and retaking the history at a subsequent consultation with the patient's diary of their symptoms will often clarify the situation. In making a diagnosis it is helpful to classify facial pain into broad categories, namely rhinological pain, dental pain, vascular pain, neuralgias, pain caused by tumours, midfacial segment pain and atypical facial pain. Although these groups mix both anatomical and pathological criteria, a structured approach to history taking remains a key ingredient to making a diagnosis. A practical approach will be described, stressing the need to think beyond the sinuses. It is useful to have a mental algorithm to plan questions and to use these to work through a diagnostic checklist of possible conditions. 2 Below is a guide to general history taking, with more detail given in the sections relating to each of the specific conditions. In reality, many patients do not fit neatly into one category and judgement without the benefit of a firm base of evidence is required as to which treatment offers the best chance of success. • Where is the pain and does it radiate anywhere? Asking the patient to point to where the pain is most severe is usefuL Often this will differ from
•
•
information contained in the referral letter. So-called 'sinus' pain may be headache or pain from the cervical spine or temporomandibular joint (TMJ). Bilateral facial pain is commonly midfacial segment pain. Sinogenic pain may be unilateral or bilateral, whereas migrainous pain and TMJ dysfunction tend to be unilateral. The manner in which a patient outlines their pain, and the gestures used, can inform the examiner about the emotional significance of the symptom. Is the pain continuous or intermittent? Pain described as continuous or present on a daily basis is unlikely to be sino genic or migrainous in origin, and more likely to represent midfacial segment pain or atypical facial pain. Migraine often happens with increased frequency premenstrually, and cluster headaches do indeed cluster, with patients often having weeks or months of remission. Pain that is constant, predominantly unilateral, and particularly if it is progressive, can be due to a tumour and this possibility must be considered. Character of the pain? Vascular pain tends to be throbbing in nature, with cluster headaches being particularly severe. Midfacial segment pain is often described as pressure or a band -like pain. Trigeminal neuralgia causes a stabbing pain that is initiated by a trigger point. What precipitates or is associated with the pain? Sino genic pain is associated with the rhinological symptoms of nasal obstruction and infected catarrh, and tends to be worse with upper respiratory tract infections. Vascular pain may have a preceding aura and is often associated with nausea. Trigger factors, such as certain foods, withdrawal of stress and sleep disruption, are well recognized. Cluster headaches are frequently triggered by alcohol and wake the patient. The pain of TMJ dysfunction is exacerbated by chewing and trigeminal neuralgia provoked by trigger points. What relieves the pain? Patients with facial pain due to sinusitis generally respond to medical treatment such as antibiotics. Although midfacial segment pain initially responds to simple analgesics, patients with this condition often report that these drugs are unhelpful by the time they are referred for a specialist opinion. Patients with migraine will retreat to a darkened room and lie down to help cope with t~eir symptoms. What effect does the pain have on daily life? Patients with atypical facial pain often describe their pain in dramatic detail as severe and unrelenting despite sleeping well and living a relatively normal life. In contrast, some patients with this condition are unable to work and blame the pain for a breakdown in a close relationship. Severe crippling pain that wakes the patient, often a man, is typical of cluster headache. [H/*]
1720 I
PART 13 THE NOSE AND PARANASAL SINUSES
RHINOLOGICAL PAIN Sinusitis The majority of patients who present to an otorhinolaryngology clinic with facial pain and headaches believe they have 'sinus trouble'. Chronic sinusitis can cause facial pain, particularly during an acute exacerbation, although this is overdiagnosed. The symptoms of acute sinusitis are well recognized. Typically, there is nasal obstruction, infected catarrh and facial pain of variable intensity in association with an upper respiratory tract infection. Chronic sinusitis is however often painless, with pain only present during acute exacerbations. This pain is often a unilateral dull ache around the medial canthus of the eye, although there may be more severe facial pain with maxillary toothache. An increase in severity of the pain on bending forward is traditionally thought to be diagnostic of sinusitis but this is nonspecific as many types of facial pain and headache are made worse by this action. The key points in the history of sino genic pain are an exacerbation of pain during an upper respiratory tract infection, an association with rhinological symptoms and a response to medical treatment. Examination of the face is often normal in patients with chronic sinusitis. Facial swelling is usually due to another pathology such as dental sepsis or, more rarely, malignancy. Nasendoscopy is mandatory in the diagnosis of sinusitis. A normal nasal cavity, showing no evidence of middle meatal mucopus or inflammatory changes makes a diagnosis of sino genic pain most unlikely, particularly if the patient is currently in pain or had pain within the past few days. Even the presence of inflammatory changes or infection does not indicate with any certainty that the pain is sinogenic, and all findings must be considered in conjunction with the history. On occasion it is useful to review the patient and repeat the nasendoscopy when they have pain to clarify the diagnosis. Figure 135.1 shows normal middle meatus viewed endoscopically. It is extremely unlikely that this patient's facial pain would be due to paranasal sinus disease. Figure 135.2 shows middle meatal sepsis viewed endoscopically. The issue of imaging continues to cause controversy. Plain sinus x-rays are used to confirm a diagnosis of acute bacterial sinusitis; however, the poor sensitivity and specificity of sinus x-rays make them redundant in the diagnosis of chronic sinusitis. 3 ,4 Interpretation of the appearance of the sinuses on computed tomography (CT) scans must also be treated with caution. Approximately 30 percent of asymptomatic patients will demonstrate mucosal thickening in one or more sinuses on CT scanning. The presence of this finding is certainly not an indication that pain is sinogenic in origin or that surgery is indicated. 5,6 Several other clinical observations suggest that a diagnosis of sinusitis causing chronic facial pain should
Figure 135.1
Normal middle meatus viewed endoscopically.
Middle meatal sepsis viewed endoscopically. This patient could well have facial pain. Figure 135.2
only be made after careful consideration. Chronic rhinosinusitis is common in young children and invariably resolves as the immune system matures. Children very rarely complain of facial pain, even in the presence of florid rhinosinusitis. One must also remember that rhinological symptoms are common, affecting perhaps one-fifth of the adult population. These patients suffer from rhinosinusitis due to various conditions including allergic rhinitis and conditions associated with nasal polyps. It is again notable that the vast majority do not complain ~f significant pain? Headaches are also common in the general population and linking these with unrelated
Chapter 135 The diagnosis and management of facial pain
nasal symptoms can lead to an incorrect diagnosis of sinusitis. Vascular pain is frequently associated with autonomic rhinological symptoms, such as congestion and rhinorrhoea, leading to diagnostic confusion. 8 The management of rhinosinusitis is considered in Chapter 117, Surgical management of rhinosinusitis however, in the current context it is important to stress that surgery should only be considered in the minority of patients where there is good evidence they have sino genic pain and when medical treatment has failed. It is interesting to note that many patients who undergo inappropriate surgery for nonsinogenic pain experience temporary relief from their symptoms, although the pain normally returns. In some patients, surgery does not significantly affect the pain and in a few the pain is made far worse. 8 , 9 Patients whose pain is increased by surgery are subsequently particularly difficult to manage with medical treatment. [***1**1*]
I 1721
produce a sharp, well-localized pain often caused by a lost or cracked filling. Once the periodontium is involved the pain becomes localized to the area of the affected tooth, which throbs and is tender to percussion. [**]
Phantom tooth pain This pain follows a dental extraction although on enquiry there is often a history of some pain that preceded the extraction. Although necrotic bone and neural elements have been found in some patients with this syndrome, the majority of cases represent a form of atypical facial pain. A dental extraction has often been performed following pressure from the patient who is convinced they have diseased teeth. Such patients may eventually find their way to otorhinolaryngology clinics for the management of 'sinus pain', and unfortunately, many subsequently undergo equally inappropriate sinus surgery. [*]
Pain after trauma or surgery Temporomandibular joint dysfunction A small minority of patient's who have sustained nasal trauma or have undergone surgery continue to experience pain long after the direct effect of the injury or surgery have settled. 8,9 There is usually little abnormality on examination and different theories exist about whether the alteration in the neurological pathway is central or peripheraL These patients often suffer from psychological distress following injury or are dissatisfied with the result of their surgery. This problem seems to be particularly common following cases of assault, and ongoing litigation may have a bearing on how symptoms are reported. Caution is required in the management of such patients, especially if further surgery is being considered. Correction of cosmetic abnormalities may not alleviate the pain and the psychological status of such patients must be assessed carefully. These patients often fall into the category of atypical facial pain (see later under Atypical facial pain) and should be managed accordingly. [**1*]
DENTAL PAIN
The pain of TMJ dysfunction may be localized to the joint or extend over the periauricular area extending to the temporoparietal and cervical regions. Temporomandibular joint dysfunction may also present with deep otalgia. 10 In the majority of cases the pain is unilateral and while chewing often exacerbates the symptoms, clicking is a nonspecific sign. Poor dental occlusion with a crossbite or poorly fitting dentures may be implicated in TMJ dysfunction. Examination reveals a tender TMJ on direct palpation or lateral jaw movement. The muscles surrounding the joint also may be tender, and pain caused by palpation of the lateral pterygoid muscle insertion at the posterior end of the upper buccal sulcus is said to be a specific sign of TMJ dysfunction. In practice, the majority of patients with TMJ dysfunction diagnosed in an otorhinolaryngology clinic are best managed by oral and maxillofacial surgeons. Treatment involves correction of aggravating factors and resting the joint by avoiding yawning and prolonged chewing. Occlusal devices such as bite-raising appliances often help. [**]
Painful teeth While many patients attending oral and maxillofacial surgery clinics have facial pain originating from the teeth, patients with pain attributable to this cause are rare in otorhinolaryngology. Usually the diagnosis is clear as the offending tooth is painful to percussion. However, pain originating from the dental pulp may produce poorly localized pain causing misdiagnosis. This pain rarely crosses the midline but can radiate to surrounding structures and, in particular, the opposite jaw (e.g. maxilla to mandible). In contrast, dentino-enamel defects
Myofascial pain This condition is five times more common in postmenopausal women and has a strong association with stress. It has many features in common with TMJ dysfunction. A widespread, poorly defined aching in the neck, jaw and ear with tender points in the sternomastoid and trapezoid muscles may be initiated by malocclusion or poor deltopectoral posture. Treatment is along similar lines to TMJ dysfunction. [**]
1722 I
PART 13 THE NOSE AND PARANASAL SINUSES
VASCULAR PAIN Migraine Migraine is a common condition affecting approximately 6 percent of men and 18 percent of women. 11 The classical variety accounts for 25 percent of migraine cases and there is often a family history of the condition. In classical migraine an aura precedes the onset of headache and this may include visual disturbances, such as fortification, scotomata (blind spots within the field of vision) or visual field defects. The aura may also include unusual tastes and aromas. The headache is usually a throbbing, unilateral pain although rarely it may be bilateral and constant. Even if the pain is not typically migrainous, patients will normally have nausea, photophobia or phonophobia (sensitivity to sound).12 Figure 135.3 shows the features of migraine. As the name suggests, common migraine happens more frequently than classical migraine, accounting for 75 percent of cases. Patients with common migraine have the same throbbing headache and nausea but do not experience the visual aura or other neurological symptoms. Migraine can last up to 72 hours.13 Migraine attacks can be induced by a number of trigger factors including various foods, sleep disturbance and withdrawal of stress (,Saturday morning headaches') and premenstruation. Not infrequently there is an association of migrainous headaches with a woman's menstrual cycle and this finding may point to the aetiology of the pain. Management of migraine involves avoidance of trigger factors and medical treatment aimed either at the acute
episode or prophylactic treatment. Simple treatment in the acute phase includes aspirin and antiemetics. Serotonin agonists, such as sumatriptan and rizatriptan, are frequently effective in treating acute attacks. Betablockers or pizotifen are usually the first-line treatment for prophylaxis provided there are no contraindications to their use. Prophylactic treatment is considered if symptoms happen more than three times a month with a duration of more than 48 hours. 13, 14 Referral to a neurologist is recommended for refractory cases. [****/***] [Grade B]
Cluster headache Cluster headache typically affects men between 30 and 50 years old. The term cluster headache is something of a misnomer as the pain is commonly frontal, temp9ral, extends over the cheek or even into the teeth. Frequently, there is lacrimation, rhinorrhoea and nasal obstruction, symptoms that have led to misdiagnosis of sinusitis. A temporary Horner's syndrome has been described on the side of the pain. IS, 16 Patients describe a distressing, throbbing, unilateral pain that wakes them. In extreme cases patients feel like 'banging their head against a wall'. The pain may last for 15 minutes up to two hours. Clusters of attacks often continue for several weeks followed by months or years of remission. Alcohol should be avoided during a cluster period and treatment is along the same lines as migraine with triptans for acute attacks and pizotifen to prevent recurrent clusters. Figure 135.4 shows the features of cluster headache. [****/***] [Grade B]
Piercing
Supraorbital Facial Frontal Parietal
Photophobia Pallor or flushing
Occipital Temporal
Figure 135.3
The features of migraine.
Chapter 135 The diagnosis and management of facial pain
I 1723
diagnostic biopsy if there is a strong clinical suspicion that the condition is present. [***] [Grade C] Burning
o
Piercing
Red eye Watery eye Dry/runny nose
Ptosis
Unilateral Figure 135.4
The features of cluster headache.
Paroxysmal hemicrania This uncommon condition happens almost exclusively in women and causes multiple attacks of excruciating pain in the frontal, temporal or ocular regions. The unilateral pain has several similarities to cluster headaches, lasting 15-30 minutes and happening several times a day. The autonomic symptoms of lacrimation, nasal congestion and rhinorrhoea may cause diagnostic confusion. 16, 17 The first-line treatment is with indomethacin which is usually effective; indeed, chronic paroxysmal hemicrania was originally classified on the basis of a response to this drug. More recently, the overlap between cluster headaches and chronic paroxysmal hemicrania has been recognized with reports of chronic paroxysmal hemicrania responding to sumatriptan. 18 ,19 [***] [Grade B]
Temporal arteritis Although patients with this condition rarely present to an otorhinolaryngology clinic, rapid diagnosis is essential to avoid progression of the disease with involvement of the ophthalmic artery and visual loss. The majority of patients with temporal arteritis are women aged over 50 years with fever, malaise and severe temporal pain. Examination shows the temporal artery to be thickened and exquisitely tender. Investigation reveals an elevated erthrocyte sedimentation rate. The diagnosis is confirmed on histological examination of an arterial biopsy that reveals intimal hyperplasia and fragmentation of the internal elastic lamina. Steroids in high doses (60 mg prednisolone daily) should be commenced prior to a
Siuder's neuralgia and 'contact point pain' In 1908, Sluder20 first described a collective group of neuralgic, motor, sensory and gustatory symptoms and signs including facial pain. His hypothesis was that these clinical findings were caused by inflammation of the sphenopalatine ganglion. This condition is now considered to be of vascular origin, hence inclusion in this section. Sluder named this clinical presentation 'sphenopalatine ganglion neuralgia', although, interestingly, he did not record a case with a combination of all the features he described. In the years that have followed many have accepted 'Sluder's neuralgia' as a discrete clinical entity. Some have also extended his theory of sphenopalatine inflammation to include mucosal contact with the lateral nasal wall as a cause for facial pain, despite the fact that Sluder did not describe the presence of contact points. Sluder recommended that pain should be treated with topical treatment of the sphenopalatine ganglion using cocaine or formaldehyde, followed by an injection of phenol if this failed. He described a variable response to treatment, and blamed the recurrence of pain on disease causing further inflammation of the sphenopalatine ganglion.21 In recent years attempts have been made to manage Sluder's type syndrome with topical, surgical or stereotactic radiotherapy treatment aimed at specific ablation of the sphenopalatine ganglion. 22 , 23, 24 The success of these various treatments has been mixed with many patients only gaining limited or short-term relief. [**/*] A review of the literature also reveals many publications claiming successful treatment of facial pain by surgical correction of contact points pressing on the lateral wall of the nasal cavity. Many of these publications have questionable methodology, with small numbers of patients and various clinical presentations being included. Most report short follow-up periods and no control group. The routine use of the nasendoscope, not available to Sluder and the previous generation of rhinologists, frequently reveals nasal cavity mucosal contact points in the pain-free patient. There is also now research evidence that questions the whole concept of mucosal contact points causing pain. 25 ,26 The finding that mucosa-tomucosa contact within the nasal cavity does not cause pain is not unduly surprising as there is nowhere else in the body where mucosal contact has this effect. [***/**] Septal surgery has also been reported to help headaches in the absence of contact points,27 but few rhinologists would attribute pain to this cause. No pathological theory can be offered to explain this outcome although the placebo effect of surgery is well recognized, as is cognitive dissonance,z8 One possible
1724 I PART 13 THE NOSE AND PARANASAL SINUSES explanation for this is that surgery transiently alters neurological input into the trigeminal caudal nucleus, thereby temporarily relieving pain. This neuroplasticity is further modified by the emotional and psychological stimuli that inevitably surround surgery, particularly where relief of pain is the main objective. [*] The clinical syndrome described by Sluder has several autonomic features in common with vascular pain described previously in this section (see above under Vascular pain), particularly cluster headache. Sluder's neuralgia is now classified as cluster headache. 29 [*]
NEURALGIAS Trigeminal neuralgia The characteristic presentation of trigeminal neuralgia with paroxysms of severe lancinating pain induced by a specific trigger point is well recognized. In more than one-third of sufferers, the pain arises in both the maxillary and mandibular divisions, while in one-fifth it is confined to the maxillary division. In a small number of patients (3 percent) only the ophthalmic division is affected. Typical trigger points are the lips and nasolabial folds, but pain may also be triggered by touching the gingivae. A flush may be seen over the face, but there are no sensory disturbances in primary trigeminal neuralgia. Remissions are common but the condition can also increase in severity. Patients with trigeminal neuralgia, and particularly younger patients, should undergo magnetic resonance imaging to exclude any other pathology such as disseminating sclerosis. The association of disseminating sclerosis with trigeminal neuralgia is well established. Disseminating sclerosis is identified in 2-4 percent of patients with trigeminal neuralgia and in a small proportion of these patients trigeminal neuralgia is the first manifestation of the disease. Patients with multiple sclerosis are younger than the general trigeminal neuralgia population and the pain is more frequently bilateraL 30 Tumours such as posterior fossa meningiomas or neuromas are found in 2 percent of patients presenting with typical trigeminal neuralgia, reinforcing the need for imaging to exclude such pathology.31 Carbamazepine remains the first-line medical treatment, with gabapentin now being employed more frequently. In cases refractory to medical treatment, referral to specialist centres for consideration of other treatment modalities such as microvascular decompression or stereotactic radiotherapy may be appropriate. 32 [****/***]
Glossopharyngeal neuralgia This very rare neuralgia is characterized by a severe lancinating pain in the tongue base, tonsillar fossa and
posterior pharynx. It may be precipitated by swallowing or yawning and the bouts may last for weeks with a tendency to recur. Treatment is along similar lines to trigeminal neuralgia with imaging to exclude any other pathology, including multiple sclerosis. Drug treatment is used initially, with surgery reserved for refractory cases. 33 [***]
Postherpetic neuralgia This is pain following a herpes zoster infection, and is defined as pain recurring or continuing at the site of shingles after the onset of the rash. Up to 50 percent of elderly patients who have had shingles may develop postherpetic neuralgia, although fortunately, most recover during the first year. Antiviral agents greatly relieve the pain of acute shingles, and there is evidence they reduce the risk of subsequent postherpetic neuralgia. 34 Various medical treatments may be helpful, in particular, tricyclic antidepressants, carbamazepine or gabapentin. Referral to a pain clinic is often appropriate for what can be a particularly distressing condition. [**** /***]
PAIN CAUSED BY TUMOURS Although tumours rarely present with facial pain, constant, progressive pain, particularly if associated with other suspicious symptoms or neurological signs should alert the clinician. A past history of malignancy may raise the possibility of metastases. A thorough examination and appropriate imaging is mandatory to exclude the possibility of a tumour. Some lesions, such as a neuroma, can have a long natural history and pain may have been present for several years. Patients with carcinoma of the paranasal sinuses often present with advanced disease. Unilateral blood-stained mucus is a common early presentation. Proptosis, epiphora, facial paraesthesia or swelling and a loose tooth or ill-fitting denture may represent more advanced disease. Pain is usually a late feature.
TENSION-TYPE HEADACHE This is typically described as a feeling of tightness, pressure or constriction, which varies in intensity, frequency and duration, and may be at the vertex or forehead, eyes or temple, and there is often an occipital component. It often lasts many hours and analgesics are of little or no benefit although many patients continue to take them, often in large quantities. It is usually present on waking. Figure 135.5 shows the characteristics of tension-type headache. The subgroup that is referred to an otorhinolaryngologist often have chronic tension-type headache with continuous symptoms or headaches that
Chapter 135 The diagnosis and management of facial pain I
Tender spots
Bilateral pressure/aching
_?-~~~~\,
Q( fdif>, ~
.
1725
,1j//1444~,
,~"
(--. ~)
Figure 135.5
Occipital
are continuous or last for more than 15 days a month. It does not worsen with routine physical activity, and rarely interferes with the patient getting to sleep. Hyperaesthesia of the skin or muscles of the forehead often arises, giving the patient the impression they have rhinosinusitis, as they know their sinuses lie under the forehead. It most often responds to low-dose amitriptyline, but propranolol, sodium valproate, gabapentin or a change in lifestyle may bring successful relief of symptoms. Amitriptyline should be given for six weeks before judging its effect, and should be continued for six months if it has helped. 3s , 36, 37 [****] The starting dose is 10 mg, and after six weeks if pain is not controlled this can be increased to 20 mg (and rarely 50 mg are needed). Patients need to be warned of the sedative effects even at this low dose, but they can be reassured that tolerance usually develops after the first few days. It is our practice to inform patients that amitriptyline is also used in higher doses for other conditions such as depression, but that it is not being given for this reason and its effect is unrelated to its analgesic properties, which would take effect much more quickly and normally require 75 mg. It is often reassuring for patients to know that the dose used for depression is some seven or more times the dose used in tension-type headache and that other antidepressants do not help this condition. In a proportion of patients there are migrainous features, and a trip tan may help acute exacerbations as up to 50 percent of patients have an overlap between tension-type headache and migraine. 1 It may be that the underlying pathology is similar. The aetiology of this type of pain is uncertain but Olesen's theory,I outlined at the beginning of this chapter (see above under Background), provides one of the best models and integrates the effects of myofascial afferents, the activation of peripheral nocioceptors and their convergence on the caudal nucleus of trigeminal, along with qualitative changes in the central nervous
The characteristics of tension-type
headache.
system. 38 ,39 There is also a suggestion that there is a downregulation of central inhibition from supraspinal impulses due to psychological stress and emotional disturbances. Another factor in those who have had a peripheral injury or inflammation is that these may induce neuroplastic changes in the trigeminal brainstem sensory nuclear complex and produce central sensitization. 40 This theory can also account for the superadded potentiation by nociceptors on top of the peripheral/ central sensitization that may be happening in this condition.
MIDFACIAl SEGMENT PAIN Many patients previously labelled as having atypical facial pain appear to have a specific clinical syndrome that is very similar to tension-type headache except that their symmetrical facial pain involves the midface and retroorbital region (Figure 135.6).41 It is not unusual for them also to have tension-type headache although they often fail to volunteer that they have symptoms involving the forehead as well. The quality of their pain and all its characteristics are identical to those mentioned in tension-type headache including the hyperaesthesia of the skin and soft tissues in the area affected. It is not uncommon for patients to say that their cheeks or periorbital skin is swollen although no abnormality can be seen. In these patients psychological factors are far less apparent than in atypical facial pain yet they have a relatively high prevalence of irritable bowel syndrome and fibromyalgia. Various names have been given to this condition including tension-type facial pain and midfacial segment pain. The authors favour the term 'midfacial segment pain' as it avoids having to explain to the patient why the term 'tension' is being used!
1726 I PART
Figure 135.6
13 THE NOSE AND PARANASAL SINUSES
Facial map of the patterns of distribution of midfacial segment pain.
Midfacial segment pain is a common cause of facial pain, and in the experience of the authors, the commonest single category of patient presenting to an otorhinolaryngology clinic. Midfacial segment pain may be considered as the facial version of tension-type headache and the two conditions frequently overlap.29,42 These patients are often misdiagnosed as having sino genic pain and may have undergone previous sinus surgery. Unlike many patients with atypical facial pain, although rather demoralized with their pain, patients with midfacial segment pain are generally functioning well in their everyday lives. There is rarely a history of depression. Typically, there is a bilateral band -like ache or pressure that can be frontal, periorbital or maxillary. The pain lasts
for many hours and on a daily basis. It is often present on waking, although it does not interfere with the patient getting to sleep. The pain can reduce during periods away from work such as weekends or while on holiday. To complicate matters, although not typically accompanied by rhinological symptoms, this type of pain can begin with a genuine episode of sinusitis. An upper respiratory tract infection or hayfever with rhinological symptoms can exacerbate the pain. A few patients also experience episodes of migrainous-type pain against a background of a more constant band-like pain. Many patients describe a gradual reduction in efficacy of simple analgesics. These drugs rna)' have been initially helpful but are eventually of no benefit.
Chapter 135 The diagnosis and management of facial pain
Examination often relieves a degree of tenderness or hyperaesthesia over the skin and soft tissues of the affected area. Nasendoscopy is performed and it is helpful, and by showing normal mucosa helps to reassure the patient they do not have sinusitis. After explanation and reassurance many patients are happy to 'live' with their symptoms rather than take medication with a possible side-effect profile. Lifestyle changes, including alterations to work routines or taking exercise can help break the cycle of pain. Some patients find alternative approaches, such as acupuncture, helpful. As described above the first-line prophylactic treatment of tension headache is low-dose amitriptyline43 ,44 and a similar regime will often help patients with midfacial segment pain. Assuming there are no contraindications to prescription, 10 mg of amitriptyline should be taken at night for six weeks. If the patient fails to respond, it is reasonable to double the dose for a further six weeks. Patients are generally advised to take medication for a full six months after their symptoms have been controlled. Second-line treatment includes propanolol, particularly if the pain has occasional migrainous features or carbamazepine if the pain has a neuropathic quality, possibly after injury or surgery. Recently, gabapentin has also proved useful as a second-line drug. [***1*]
ATYPICAL FACIAL PAIN This is very much a diagnosis of exclusion and care must be taken in reaching this conclusion, even when the patient has received previous opinions and no pathology has been identified. The history is often vague and inconsistent with widespread pain extending from the face onto other areas of the head and neck. The pain may move from one part of the face to another between different consultations, and other symptoms, such as 'mucus moving' in the sinuses, are often described. A number of patients have such completely fixed ideas about their condition that they will not be convinced otherwise whatever the weight of evidence to the contrary. Pain is often described in dramatic terms in conjunction with an excess of other unpleasant life events. Many of these patients have a history of other pain syndromes and their extensive records show minimal progress despite various medications. They have often undergone previous sinus or dental surgery and may be resentful about their treatment. It is not uncommon for such patients to give a history of nasal trauma. Many patients with atypical facial pain exhibit significant psychological disturbance or a history of depression and are unable to function normally as a result of their pain. Some project a pessimistic view of treatment, almost giving the impression they do not wish to be rid of the pain that plays such a central role in their lives. A comprehensive examination (including nasendoscopy) is essential to identify significant pathology before the patient is labelled as having atypical pain. The
I 1727
management of such patients is challenging and confrontation is nearly always counterproductive. A good starting point is to reassure the patient that you recognize that they have genuine pain and an empathetic consultation with an explanation should be conducted. Drug treatment revolves around a gradual build-up to the higher analgesic and antidepressant levels of amitriptyline (75-100 mg) at night. The second-line treatment includes gabapentin and carbamazepine. Patients should sympathetically be made aware that psychological factors may playa role in their condition and referral to a clinical psychologist or psychiatrist may be helpful. Referral to a pain clinic is often appropriate. [**/*]
KEY. POINTS • History taking istlie.keytoaccurate diagnosis ill patients with fa.cial pain. • Sinusitis isariue cause of chronic facial pain and mostpatienisWithfacial pain.' aonot . wardllitsllrgery. • Sinogenicpain Ismtermittel1tahdassociated with rhin()logiCaY symptoms. • SinUS'lnUcusa1thi~~el1ingoIiac=Tsc~hldoes
n?t indicate.thatpainiscsi~og~ni~.
• Vascular 'pain,'.s\Jcl1 • asmi?rain~.andc1uster • ·. headaches, can cause rhinoirhoeaa1.1dnasal congestion. • Many patients with. chronic facial pain benefit from the apprQpriate'n~l,lrological' medication~
A carefully taken history is key to accurate diagnosis, with recognition that the majority of patients will not have sinogenic pain. Examination should include nasendoscopy, which is particularly useful if the patient is currently in pain. In such circumstances, a normal nasendoscopy makes the diagnosis of sinogenic pain extremely unlikely. Sinus x-rays are not helpful in the diagnosis and management of chronic facial pain and sinusitis. Computed tomography scans should not be routinely performed because sinus mucosal thickening is common in asymptomatic patients and management based only on scan findings will result in unnecessary surgery. Given that the majority of patients presenting with facial pain will not have sinusitis, surgery is very rarely indicated in the treatment of chronic facial pain.
1728 I PART 13 THE NOSE AND PARANASAL SINUSES ./ Familiarity with the various medications available to treat nonsinogenic facial pain and liaison with other specialties, such as neurology, maxillofacial surgery and clinical psychology will benefit patients.
7. 8.
9.
10.
Deficiencies in current knowledge and areas for future research Further basic science research into the fundamental pathogenesis of rhinosinusitis is needed to increase our understanding of mucosal disease, including the potential of such inflammation to cause pain. Continued research into the neurophysiology of headache and facial pain is required, in particular, tension-type pain. Credible models have been proposed which help our understanding, but are they correct? ,.. Low-dose amitriptyline has been shown to help tension-type headache and midfacial segment pain. A randomized controlled study is required to test the efficacy of this treatment in midfacial segment pain. ,.. Psychological aspects of facial pain are well recognized. Well-designed studies are required into the usefulness of various psychotherapeutic techniques, particularly with regard to the selection of patients who will benefit.
11.
* 12. 13. 14.
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Fahy C, Jones NS. Nasal polyposis and facial pain. Clinical Otolaryngology. 2001; 26: 510-3. Khan 0, Majumdar S, Jones NS. Facial pain after sinus surgery and trauma. Clinical Otolaryngology. 2002; 27: 171-4. Jones NS, Cooney TR. Facial pain and sinonasal surgery. Rhinology. 2003; 41: 193-200. Bumann A, Lotzmann U. TMJ disorders and oro facial pain. New York: Thieme, 2002: 1-378. Lipton RB, Stewart WF. Migraine in the United States: A review of epidemiology and health care use. Neurology. 1993; 43: 6-10. Goadsby PJ, Oelson J. Diagnosis and management of migraine. British Medical Journal. 1996; 312: 1279-83. Daudia AT, Jones NS. Facial migraine in a rhinological setting. Clinical Otolaryngology. 2002; 27: 251-5. Silberstein SO, Goadsby PJ, Lipton RB. Management of migraine: An algorithmic approach. Neurology. 2000; 55: 46-52. Goadsby PJ. Cluster headaches: new perspectives. Cephalgia. 1999; 19: 39-41. Fuad F, Jones NS. Paroxysmal hemicrania and cluster headache: two disrete entities or is there an overlap? Clinical Otolaryngology. 2002; 27: 472-9. Antonaci F, Sjaastad O. Chronic paroxysmal hemicrania. A review of clinical manifestations. Headache. 1989; 29: 648-56. Pascual J. A case of chronic paroxysmal hemicrania responding to subcutaneous sumatriptan. Letters, correspondence, book reviews. Journal of Neurology Neurosurgery and Psychiatry. 1998; 65: 407. Evers S, Husstedt I. Efficacy of sumatriptan in chronic paroxysmal hemicrania. Letter to the editor. Headache. 1998; 38: 630-1. Sluder G. The role of the sphenopalatine (or Meckel's) ganglion in nasal headaches. New York Medical Journal. 1908; 87: 989-90. Sluder G. Etiology, diagnosis, prognosis and treatment of sphenopalatine ganglion neuralgia. Journal of the American Medical Association. 1913; LXI: 1202-06. Puig CM, Driscoll CLW, Kern EB. Sluder's sphenopalatine ganglion neuralgia. Treatment with 88% phenol. American Journal of Rhinology. 1998; 12: 113-8. Pollock BE, Kondzioloka D. Stereotactic radiosurgical treatment of sphenopalatine neuralgia. Journal of Neurosurgery. 1997; 87: 450-3. Cepero R, Miller RH, Bressler KL. Long term results of sphenopalatine ganglion neuronectomy for facial pain. American Journal of Otolaryngology. 1987; 8: 171-4. Abu-Bakra M, Jones NS. The prevalence of nasal contact points in a population with facial pain and .a control population. Journal of Laryngology and Otology. 2001; 115: 629-32. Abu-Bakra M, Jones NS. Does stimulation of the nasal muoosa cause referred pain to the face? Clinical Otolaryngology. 2001; 26: 403-32.
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29. Jones NS. The classification and diagnosis of facial pain. Hospital Medicine. 2001; 62: 598-606. 30. Hooge CF, Redekop WP. Trigeminal neuralgia in multiple sclerosis. Neurology. 1995; 45: 1294-6. 31. Cheng TMW, Cascino TL, Onofrio BM. Comprehensive
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Cerbo R, Barbanti P, Fabbrini G, Pascali MP, Catarci T. Amitriptyline is effective in chronic but not episodic tension-type headache. Headache. 1998; 38: 453-7.
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136 Medical negligence In rhinology MAURICE HAWTHORNE
Introduction Inadequate standard of care prior to referral to an otolaryngologist Inadequate presurgical management Interpretation of radiological investigations interpretation of histological investigations Failure to consider conservative treatment Consent
1730 1730 1731 1731 1731 1732 1732
Incompetent surgical technique Intraoperative monitoring Postoperative monitoring Inadequate conservative treatment Key points Best clinical practice References
1732 1734 1735 1735 1735 1736 1736
This data in chapter are supported by a PubMed search using the key words medical negligence, rhinology, sinus surgery, complications and risk. In addition, a manual search of Clinical Risk and the Journal of the Medical Defence Union was undertaken. There are virtually no published series of medical negligence cases in the field of rhinology. At best, the practice that might be considered acceptable by the profession is determined by expert opinion. Therefore, the evidence base of this chapter is level 4.
INTRODUCTION In the field of rhinology, damage caused by the surgeon has the potential of being considerably greater than any possible damage caused by leaving disease untreated. Damage occurs primarily to orbital structures, cranial nerves, the cavernous sinus and the brain. Delayed diagnosis or inadequate surgery for malignant skin lesions can lead to excessive and unnecessary cosmetic deformity. Failure to identify a patient with dysmorphophobia can lead to the surgeon himself being physically attacked and possibly even murdered.
INADEQUATE STANDARD OF CARE PRIOR TO REFERRAL TO AN OTOLARYNGOLOGIST Negligence in general practice in relation to rhinological disease is unusual. It appears to occur mainly due to a
failure in recognizing the significance of certain symptoms or signs. One of the most common areas is in failure to arrange timely treatment for a nasal fracture. In most practices, the best opportunity in effectively manipulating a nasal fracture is within the first 21 days of the injury. Failure to undertake timely treatment may lead to the necessity of performing a formal septorhinoplasty. The consequence of this is a longer period off work than would be necessary, as well as additional pain and suffering such as periorbital bruising. A delayed referral can rarely be defended and usually the best outcome is to seek a speedy settlement. There are exceptions and one of the most important is the cartilaginous injury of the nasal tip or septum when simple manipulation does not give the best results and a septorhinoplasty is indicated as first-line treatment. A delay in referral of sinusitis is also a common area that leads' to litigation. The general practitioner ( GP) usually fails to realize when a sinus infection has spread
Chapter 136 Medical negligence in rhinology
beyond the sinus and is involving the orbit, bone, meninges or soft tissues. The most common examples of this are orbital and forehead swelling. It is only the onset of symptoms in relation to brain abscess, meningitis, blindness or severe orbital swelling that leads to a speedy referraL The significance of unilateral nasal symptoms, such as discharge, may be ignored by the GP and so a delay in diagnosis of a tumour or foreign body occurs. In general practice, common errors that lead to litigation include: • delay in referral of nasal fractures; • delay in referral of complicated sinusitis; • failure to realize the significance of unilateral nasal obstruction. Sadly, it is not just the GP who may fall into the situation of delaying a diagnosis. Inexperienced senior house officers within the specialty, accident and emergency doctors, and occasionally other specialists within hospital practice, may all find themselves at the centre of litigation arising from these relatively common areas of negligence.
INADEQUATE PRESURGICAL MANAGEMENT Failure to investigate significant symptoms arises from time to time. Wegener's granulomatosis is a condition that regularly goes unrecognized. Often it may be mistaken for atrophic rhinitis or even industrial rhinitis, and the patient treated symptomatically, without adequate investigation. It is only when other systems are involved, such as the renal or respiratory system, that adequate investigations are triggered and the condition identified. Clearly if the condition has progressed to frank renal failure requiring dialysis before diagnosis has been made, then the patient may have a valuable claim. It is common to find that other conditions, such as scleritis, flitting arthropathy or skin lesions are not linked to the nasal symptoms. However, occasionally circumstances arise in which the investigations for this condition, such as a raised plasma viscosity or erythrocyte sedimentation rate (ESR) , which are usually positive, are within the normal range. Occasionally even the AN CA test is negative, and where adequate investigations have been undertaken but the diagnosis has been delayed, a reasonable defence can usually be mounted. From time to time, a post-nasal space carcinoma may present as a neck lump to another specialist. Although the malignant nature of the neck lump is identified, occasionally the primary site is missed. The ear, nose and throat (ENT) expert may be asked to comment on such a delay. It is of course inappropriate for him to deal with issues of liability concerning delay in diagnosis by another specialist, but it would not be unreasonable for him to comment on how the delay may affect the prognosis of the patient. Similarly, a restriction in eye movement may indicate early involvement of orbital contents or a cranial nerve by a sinus malignancy. Clinical examination may not reveal
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an obvious restriction in movement, due to the partial nature of the malignant process. Sudden onset of double vision, without an obvious cause such as head injury, or orbital displacement should never be ignored, and requires thorough investigation to exclude a pathological cause requiring treatment.
INTERPRETATION OF RADIOLOGICAL INVESTIGATIONS In many small district general hospitals, there is no radiologist with a special interest in ENT radiology. Consequently, the experienced consultant ENT surgeon may be just as competent at reading radiological films as the specialist radiologist. In all departments it is wise that both the clinician and the radiologist assess the radiological films within the clinical context of the patient's disease. From time to time, a difference of opinion may arise, and a failure to address this difference of opinion can lead to a delay in diagnosis, with a significant impact on prognosis for the patient. Where films have been discussed, and a difference of opinion continues, then it is advisable that a further opinion is sought from a radiologist with a special interest in the field. Nowadays, films can often be easily transferred electronically and the vagaries of the postal system do not have to be endured. Where there is a difference of opinion between the clinician and the radiologist, most patients would expect the radiological investigation to be repeated after some weeks. Although the radiologist, and indeed the clinician, may have some concerns about the increased dosage of x-rays necessitated by repeat films, where there is a possibility of malignancy, the patient will see this risk as being trivial, and would be much more concerned about obtaining peace of mind about what they see as a real and existing problem, compared to some theoretical risk of developing a malignancy in the future. Therefore, the wise clinician should argue for a repeat investigation. In the field of endoscopic sinus surgery, whether it is functional, diagnostic or treating an iatrogenic complication, it is essential to have a complete demonstration of the radiological anatomy by computed tomography (CT) scan. The nose should be scanned from its rostral extremity as far back as the basilar artery. In addition, it is essential that the window setting is such as to maximize the bony detail and also a second series should be saved with window settings to give some soft tissue information.
INTERPRETATION OF HISTOLOGICAL INVESTIGATIONS Much of what has been said above on radiological investigations also applies to histopathological investigations. The wise otolaryngologist will be well aware of the pitfalls that can arise. These are especially true in salivary
1732 I PART 13 THE NOSE AND PARANASAL SINUSES gland and nasal neoplasia. Also, fine needle aspiration cytology needs to be carefully considered in the light of the clinical picture and if a lesion deemed benign on cytological examination does not appear to be behaving clinically as such, rebiopsy should be undertaken speedily.
FAILURE TO CONSIDER CONSERVATIVE TREATMENT This issue appears to arise more commonly in private practice. It is not uncommon for the patient who has had a mishap following sinus surgery to state that conservative options for treatment, such as oral steroids and antibiotics in the case of nasal polyposis, had never been discussed, but that an immediate recommendation for surgery had been made by the practitioner. In the case of simple, benign, nasal polyposis in a fit individual, there is rarely any defence for not discussing the possibility of a course of oral steroids, with or without antibiotics. If there is doubt as to the nature of the polyps, a simple biopsy can be undertaken, followed by conservative treatment, rather than an attempt to radically clear the disease, as first-line treatment. In those patients with nasal obstruction due to enlarged inferior turbinates, first-line treatment should normally be conservative. Adequate investigation to identify the presence of any allergy and then treatment either by allergen avoidance or topical steroid treatment would usually be first-line treatment. If the general practitioner has already undertaken this in an adequate and thorough manner, it may be reasonable to proceed with an offer of surgery. However, a significant complication occurring following turbinate surgery in the patient who has not been offered an initial trial of conservative treatment can be very difficult to defend.
CONSENT Issues of consent on their own are rare in relation to sinus surgery and they are much more common when coupled with allegations of incompetent surgical technique. However, it is in the field of turbinectomy, particularly in the adolescent and young adult, that issues of consent arise. Torrential haemorrhage following inferior turbinectomy is not uncommon, probably happening in most surgeons' practice, with an incidence of between 1 in 60 and 1 in 200 cases. It does appear to be more common where a posterior turbinectomy has been undertaken, rather than removal of the anterior end of the interior turbinates. Nevertheless, torrential haemorrhage can happen in any form of turbinate surgery. When this occurs, and the patient has undergone the usual treatment to arrest the haemorrhage and correct the blood loss, an allegation of permanent psychological damage may arise, accompanied by the allegation that they were not warned of the risk and had they been, then they w~uld have refused consent for the surgery. In taking consent, the
wise surgeon must assess the personality of the patient and ask himself whether they would have the mental fortitude to withstand the psychological trauma which can accompany a severe nasal haemorrhage, particularly as it may appear life-threatening to the patient and their family. If the patient, despite warning of such haemorrhage, still wishes to proceed with the surgery, then it should be carefully annotated in the notes that the warning has been given and understood. Since the introduction of functional endoscopic sinus surgery on a wide basis, between 1988 and 1992, consent for these procedures seems, on the whole, to be well annotated in the notes, particularly from the point of view of the risks of injury to orbital contents and breach of the dura. However, where contention may arise, it is not that the patient was warned of these anatomical risks, but that they did not understand the consequences of these risks on their day-to-day life, or that should such risks occur, that secondary complications may supervene. One patient, an intelligent banker, freely admitted that he had been warned of the risk of cerebrospinal fluid leaking from his nose, but was adamant that he had been given no warning that this could lead to meningitis and subsequent intellectual impairment, which had occurred in his particular circumstances. However, the claimant may find it difficult to establish in court that, had they been fully warned, they would not have gone on to subject themselves to the surgical procedure. The landmark Australian case, Rogers v Whitaker, l in which it was felt the risk of sympathetic ophthalmitis, with a risk of approximately 1 in 30,000, should have been explained to a patient, has not found favour in the English courts. The risk of blindness as the result of submucosal diathermy, or the use of adrenalin-containing local anaesthetic in rhinological surgery, is somewhat similar. In one case, a young woman woke up following a general anaesthetic for a submucosal diathermy and had totally lost sight in one eye. Thorough investigation did not reveal any evidence of direct trauma to orbital or retroorbital structures, and a literature search revealed that this can happen despite competent surgical technique. On the Bolam principle, as virtually no ear, nose and throat surgeon practising in the United Kingdom would warn of this risk, her case would fail and therefore her solicitor advised that she should not pursue the issue. A Legal Aid Certificate was not granted to test the principle that such a loss was so catastrophic that, despite its rarity, it should have been warned of and that any reasonable patient would expect that this issue be mentioned.
INCOMPETENT SURGICAL TECHNIQUE Just because a recognized complication happens, it does not automatically mean that surgical technique has been below a 'satisfactory standard. A complication such as damage to the medial rectus muscle in endoscopic sinus
Chapter 136 Medical negligence in rhinology
surgery2 may occur, despite all care being taken by the surgeon. On the other hand, it may occur as a result of a 'gung ho' or slapdash technique, in which due respect and identification of the relevant surgical landmarks has not been attempted. For the claimant, it can be difficult, if not impossible, to prove that the damage has occurred because of the latter surgical technique, rather than the former. It would indeed be rare for a claimant to successfully identify a witness, present at the time of the surgery, who was willing to testify in court as to incompetent technique practised by the surgeon. Increasingly, video is used in theatre and, in the case of endoscopic sinus surgery, operating via camera is a common technique. If the surgery is recorded and the tapes kept until it is established there is no significant postoperative complication, the recording may be available to both parties in which an adverse outcome to the surgery has developed. For example, in one case, a trainee undertook a difficult nasal polypectomy endoscopically. The procedure was recorded and a breach of the anterior cranial fossa, and how it was acquired, could be clearly seen on the video. In this particular instance there was a dehiscence of the cribriform plate, with absence of bone in the anterior cranial fossa. The repair was also filmed. An explanation was given to the patient, who was quite satisfied. However his children, who lived some distance away, attended the hospital some days later. One child, a nurse in a maxillofacial surgical department, clearly felt that causing a cerebrospinal fluid (CSF) leak had to be negligent. Fortunately the video material was available, which was immediately shown to the family and carefully explained. This diffused the aggression and was successful in preventing litigation. Occasionally, massive injury can be sustained in which the degree of damage is so gross that basic surgical technique has to have been ignored, or not understood. For example, in one case where the patient failed to regain consciousness from the anaesthetic following intranasal surgery. On arrival at the intensive care unit, a 2 x 1 x 1 cm piece of cerebral cortex was retrieved from the oropharynx and subsequently an extensive resection of the anterior cranial fossa was identified, and the nose contained a huge herniation of the brain. The neuroradiological expert in the case felt that there was clear evidence of instrument tracks within the substance of the frontal lobes of the brain, suggesting that instruments had been passed repeatedly into this brain substance. In this particular case, preoperative CT scans did not reveal any evidence of a congenital abnormality of the anterior skull base. Not surprisingly the surgeon's insurers sought a settlement early on in the process of the case. Where the evidence is strong that the lack of standard of care would suggest a flagrant disregard for safety, or recklessness in performing the surgical technique, then the public may need to be protected by requesting the General Medical Council for a competency assessment.
I 1733
Frontal sinus trephine may lead to supratrochlear nerve damage and indeed supraorbital nerve damage. Where there is significant oedema in the surgical area, most surgeons could understand how the supraorbital nerve might be stretched by retractors, or indeed cut. However, in a simple drainage procedure, there can be no excuse for extending the incision so far laterally as to divide the supraorbital nerve. The Lynch-Howarth procedure gives wider access to the frontal and ethmoid sinuses. In extensive disease it may be necessary to sacrifice the supraorbital and the supratrochlear nerve. This should be anticipated before the surgery and the patient warned. In addition, the patient should be warned of the possibility of double vision postoperatively due to the detachment of the trochlea. Resting cheek retractors against the supraorbital rim in a Caldwell-Luc procedure, or similar surgery, can lead to a neuropraxia of the supraorbital nerve. This usually recovers, however, it is a well-recognized risk and adequate precautions can usually be taken to prevent it happening. On the other hand, infraorbital nerve neuropraxia in Caldwell-Luc surgery can be inflicted despite all care being taken, and does not indicate de facto substandard technique. A major saddle deformity of the supra tip area, following septal surgery, causes such a deformity that it can be difficult to prevent the angry and embittered patient from seeking redress. If the complication has occurred as the result of a postoperative septal abscess, and the patient has been warned of the possibility when consent was taken, then sympathetic handling can usually prevent the patient seeking redress through the help of a solicitor. A careful explanation that infection had destroyed the septal cartilage may suffice. However, most patients will ask immediately why they were not given antibiotics at the time of the original surgery. An explanation such as, 'It is not usual practice', will frequently earn the retort from the patient 'Well don't you think it should be'. A sympathetic explanation, couched in easy to understand terms, about bacterial resistance and the natural ability of the nasal area to defend itself against infection, is much more likely to be successfully accepted than a patronising comment such as 'We don't routinely give antibiotics: The patient clearly will require reassurance that an effective attempt to repair the damage will be undertaken. Rarely the saddle could be due to a failure to recognize and diagnose disorders such as Wegener's granulomatosis, sarcoidosis or relapsing polychondritis. 3 The wise surgeon, when presented with such an unexpected outcome, should take the appropriate tests to exclude such disorders. Clearly the presence of an alternative explanation for a septal collapse or perforation may present an opportunity for a defence. Septal perforation is another common complication, especially in submucous resection of the nasal septum that causes such symptoms that a patient may seek compensation. It should always be mentioned when septal surgery is being offered. The presence of a perforation
j
1734 I PART 13 THE NOSE AND PARANASAL SINUSES does not automatically imply a substandard technique; it is more likely to be an indicator of a severely fractured nasal septum or the presence of another disease, such as atrophic rhinitis or a granulomatous disease. The circumstances of a submucosal resection, in which the surgeon has made an error of judgement and resected too much cartilage, are likely to be much more difficult for the patient to accept. Once more, recognition of the patient's concern is the key to good management. In addition to offering surgery to correct the deformity, it is important to recognize that the patient may no longer have confidence in the surgeon, or indeed even in the hospital in which they have been treated, and so a prompt offer of transfer to another department and another surgeon may assuage the patient's anger. An allegation of inadequate primary resection of a tumour, either malignant or benign, usually follows the unexpected diagnosis of a recurrence. This may seem surprising to the profession, but sadly a combination of belief in modern surgical techniques, plus the confident statement from the operating surgeon that 'all the tumour has been removed', can lead to an accusation of incompetent technique. Clearly, a confident statement on tumour resection is meant to reassure the patient and improve their psychological well-being. However, there is no excuse to take on a patronising role, supported by frank lies. It is important that the patient is told the exact situation, as best as can be determined, and if the outcome for the future appears to be bleak, then such bad news needs to be adequately supported with appropriate psychological therapy. It is possible that any psychological damage may be looked upon leniently by the courts, and appropriately rewarded, especially when the major defence to the bulk of the claim is that 'the patient would have died anyway'. On the subject of failure to diagnose a recurrence, a claim may arise where a patient has been lost to follow up and only represents with an extensive recurrence. Such cases may have a prospect of being successful where the patient can establish that had there been a regular examination and inspection of the nose and sinuses, with the draining lymph nodes, that a recurrence would have been easily identified at an early stage. It is therefore important that health trusts have a robust system of tracking down those patients who fail to attend for their expected appointment. Trusts should be seen to communicate with the GP in order to establish whether the address that they have is correct, and furthermore to inform the GP that the patient has not attended and request the GP to investigate the reasons why. Failure to do so may be difficult to defend, unless the trust can establish that they have emphasized to the patient the importance of regular follow up and examination following treatment for the tumour. There is considerable merit in a letter being sent to the patient, giving details of the diagnosis, treatment and the planned follow-up care, for the purposes of identifying early
recurrence of disease. It is not uncommon for an expert to examine a claimant's notes and identify frequent nonattendance in out-patient departments of various specialties. However, the claimant usually alleges that they failed to receive the appointment in the mail. Although the treating physician may have a healthy scepticism of such allegations, it must be borne in mind that many people live in multiple occupancy dwellings in which security of mail may indeed be in doubt. As such, where follow up is important, it is advisable that the GP is asked to investigate for repeated failures to attend. In circumstances where resection margins are being monitored by frozen section examination during the surgery, it is vital that all specimens are sent. Thus, when a report says that the tumour is at the margin of resection, on one specimen it is useful to have a subsequent specimen indicating that there is a clearance. Obviously, where the tumour is up to, but not invading, a nerve sheath, the surgeon may have to exercise clinical judgement and decide whether to resect such a nerve sheath or not. These points should be carefully noted in the records. Thus, a histological report which indicates that the margin of resection is up to the edge of the tumour can be seen to have been acted upon appropriately. Prior to the 1980s, it was very common practice to undertake a 'proof puncture' of the maxillary antra. This would often be done at the time of a tonsillectomy or adenotonsillectomy, in older children and young adults. It was considered a legitimate investigation to detect the possibility of chronic sinus infection. Many surgeons advocated its routine use, even in the absence of any sinus or nasal symptoms. Such an invasive procedure, which carries the risk of damage to unerupted secondary dentition, the inferior orbital nerve and the orbital contents, in the absence of sinus symptoms, can no longer be justified without taking a formal consent for the procedure and offering alternative methods of investigation. In addition, several cases have arisen due to misunderstanding of the term 'examination under anaesthesia'. Some claimants who have sustained complications as a result of such procedures have asserted that they only gave consent for the surgeon to look, but not to biopsy. A typical examination would be obtaining consent for examination of the post-nasal space in a child or adult with glue ear, and then proceeding to perform an adenoidectomy having identified a significant pad of lymphoid tissue in the post-nasal space, the damage occurring usually being a secondary haemorrhage. It is important therefore, in taking consent, to include the potential risks that may arise for any additional procedure, usually a biopsy of an excisional or incisional nature.
INTRAOPERATIVE MONITORING This term usually invokes thoughts of nerve monitoring in the context of ENT surgery, but it is still particularly
-_----.i
Chapter 136 Medical negligence in rhinology
important in rhinological surgery, although the monitoring may be purely visual in nature. In endoscopic sinus surgery, it is the orbital contents which are at risk. Clues to a significant intraorbital incursion can be obtained by careful observation of both eyes during the procedure. This may not be possible by the operating surgeon, as it is likely that he will be observing the operating field either indirectly through a camera or directly through an eyepiece. However, an operating assistant, such as a scrub nurse or other colleague, should be in a position to observe both orbits and watch for the tell-tale signs of a complication arising. These may include a sudden movement of the globe of the eye, the development of proptosis or subconjunctival haemorrhage. Although in the early parts of the procedure it is important to protect the cornea from damage, at points in the surgery in which the eye may be in a critical, vulnerable, state, it is permissible for the eyelid to be opened and the globe observed for brief periods. Early identification of an incursion into the orbit is essential to reduce the risk of damage. Equally, in the recovery area, postoperative observation of the orbits and eyes is essential, particularly if a significant retrobulbar haemorrhage is to be identified, monitored and, if necessary, treated before permanent damage to the eyesight occurs.
POSTOPERATIVE MONITORING Even though frontal sinus infection has been adequately drained at surgery, the patient still has the potential of developing an intracranial complication, though this is now much less. It is likely that the infection has spread through the venous system prior to the actual drainage of the sinuses and so the intracranial symptoms usually commence 24-48 hours after surgery. Complaint of severe headache which is progressive, along with drowsiness, confusion or disinhibition, should alert the wary to the onset of a frontal lobe infection. Usually the patient should be on an antibiotic with a high ability to cross the blood-brain barrier, but if this is not the case, then with the onset of these symptoms the antibiotic will need to be changed. Inadequate monitoring in the postoperative period may also lead to delay in detection of a cerebrospinal fluid leak. Although these may be blatantly obvious when there is a striking flow of clear fluid from the nose and the patient has an accompanying headache, the occasional case may be intermittent. In one case, the patient reattended the hospital on three occasions complaining of watery nasal discharge, which was ignored. No investigations were undertaken, other than admission and observation on the ward, on one occasion only for 48 hours. On the final attendance at hospital the patient presente-d with a small bottle containing a sample of the CSF and symptoms of frank meningitis. The confusing issue is that nasal discharge which may be watery in nature is not uncommon following sinus surgery, or indeed may
I 1735
be related to the underlying sinus disorder. It is quite likely that minor CSF leaks are probably more common than is actually realized, but fortunately they close spontaneously without any secondary damage.
INADEQUATE CONSERVATIVE TREATMENT The usual practice is to treat the frontal and ethmoidal sinusitis with decongestants and antibiotics which is often successful. However, if there is a failure to respond or there is evidence of the infection beyond the sinus, then drainage of the sinus is required. Failure to recognize that the infection has spread beyond the sinus can lead to orbital abscess and intracranial infection. Within the hospital setting, spread of the infection should be recognized within 24 hours of the first signs or symptoms of this complication developing. If the infection spreads beyond the frontal sinus, then infection of the bony walls of the sinus can be inferred, as well as thrombosis of the venous channels through the bone. This infection is difficult to eradicate and requires prolonged use of antibiotics in the order of 8-12 weeks. When a patient presents with marked swelling of the soft tissues of the forehead, perhaps with a subperiosteal abscess, there may be an initial settling of the symptoms with a two-week course of antibiotics. The dramatic improvement in the patient's condition may lull either doctor and/or patient into a false sense of security and the antibiotic course is terminated as a result. Then, weeks later, the features of chronic osteomyelitis develop or even secondary intracranial sepsis. It is indefensible not to give a prolonged course of antibiotics where there is a significant risk of osteomyelitis. 4
KEY POINTS • Wegener's granulomatosis is a condition that regularly goes unrecognized. • Issues of consent on their own are rare in relation to sinus surgery. • Where contention may arise, is not that the patient was warned of anatomical risks, but, that they did not understand the consequences of these risks on their day-today life, or that, should such risks occur, secondary complications may supervene. • Just because a recognized complication occurs, it does not automatically mean that surgical technique has been below a satisfactory standard. • Infraorbital nerve neuropraxia in Caldwell-Luc surgery can occur despite all care being taken and does not indicate de facto substandard technique.
1736 I PART 13
THE NOSE AND PARANASAL SINUSES
REFERENCES if Sudden onset of double vision should never be ignored. It is wise that both the clinician and the radiologist assess the radiological films, within the clinical context of the patient's disease.
1. 2.
anatomy by CT scan. If a lesion deemed benign on cytology does not appear to be behaving clinically as such, rebiopsy should be undertaken speedily. In the case of simple, benign, nasal polyposis, there is rarely any defence for not discussing the possibility of a course of oral steroids, with or without antibiotics. Where there is evidence of a flagrant disregard for safety or recklessness in performing a surgical technique, then the public may need to be protected by requesting the General Medical Council for a competency assessment. A postoperative saddle could, rarely, be due to a failure to recognize and diagnose disorders such as Wegener's granulomatosis or sarcoidosis. In such an event, the appropriate tests to exclude such disorders should be taken. Where an adverse outcome of treatment has occurred, prompt offer of transfer to another department and another surgeon may assuage the patient's anger. Trusts shou Id have a robust system of tracki ng down those patients who fail to attend for their expected appointment.
Johnston MN, Jones NS. The complications of endoscopic sinus surgery. Clinical Risk. 2002; 8: 133-6.
3.
Morrison AW 'Silence in court': Twenty one years of otolaryngology litigation. Journal of Laryngology and
In the field of endoscopic sinus surgery, it is essential to have a complete demonstration of the radiological
Rogers v. Whitaker [1993] 4 Medical Law Reports, High Court of Australia 79.
Otology. 1990; 104: 162-5. 4.
Hawthorne M. Clinical negligence in rhinological surgery.
Clinical Risk. 2003; 9: 44-8.
PART
14
THE NECK EDITED BY JOHN HIBBERT
137 Surgical anatomy of the neck
1739
Chris R Jennings
138 Examination and imaging of the neck Sheila C Rankin and John Hibbert
1754
139 Neck trauma
1766
Johannes J Fagan and Andrew J Nicol
140 Benign neck disease: infections and swellings Peter Clarke
1777
137 Surgical anatomy of the neck CHRIS R JENNINGS Introduction Developmental anatomy Surface anatomy Triangles Fascia I layers Neck spaces Muscles Cervi~al
lymphatics
1739 1739 1740 1741 1743 1743 1745 1746
Major blood vessels Nerves Summary Key points Deficiencies in current knowledge and areas for future research Further reading
1749 1750 1752 1752 1753 1753
This chapter is based on anatomical and surgical texts and is supported by a Medline search using the key words head and neck anatomy. The anatomical evidence is supported by cadaver dissection studies. The clinical evidence is also observational.
INTRODUCTION Surgeons should master surgical anatomy of the neck before embarking on any neck dissection. The aim of this chapter is to outline the clinically important areas of neck anatomy. The upper border of the neck is the floor of the mouth anteriorly and the skull base posteriorly. The lower border is the upper border of the first rib and body of the first thoracic vertebra. The development of the neck helps in understanding the anatomy and will be discussed, while an appreciation of surface anatomy is important for neck examination and will be included in this chapter. The triangles of the neck, fascial boundaries, neck spaces, cervical lymphatics, muscles, vessels and nerves will be discussed in turn with particular points of surgical importance emphasized. It is not the intention of this chapter to be an operative surgery text and operations will not be discussed in detail.
DEVELOPMENTAL ANATOMY The ~~f the neck is derived from cervical dermatomes, Whic;se from the second to the sixth cervical
~
'-
segments. The sternocleidomastoid, strap muscles and trapezius originate from cervical myotomes. The viscera in the neck and structures innervated by the cranial nerves have their embryological origins in the branchial apparatus. The six branchial arches form at four weeks gestation and each has a principal nerve and vessel. The vascular anatomy changes unrecognizably from the embryo. The neural anatomy forms in an identifiable pattern. Each arch has a principal or trematic nerve. The branches to the previous arch are called pretrematic and to the following arch are post-trematic. Between the arches are the pharyngeal pouches. The contribution of each to the neck structures will be considered in turn. The first arch structures form the upper border of the neck. The mandible is derived from Meckel's cartilage which is the cartilage formed by the chondrofication of the first arch mesenchyme (embryological connective tissue). The mylohyoid, anterior belly of digastric are also first arch derivatives and the trematic nerve is the mandibular branch of the trigeminal nerve. The first pouch forms ear structures only. The bone structures of the second arch are formed from Reichart's cartilage, which represents chondrofication of the second arch mesenchyme. They are the styloid
1740 I PART 14 THE NECK
Anterior to this is the angle and ascending ramus of the mandible and between these two lies the parotid gland.
process, lesser cornu and upper body of the hyoid bone. The muscles are the platysma, posterior belly of digastric and stylohyoid. The trematic nerve is the facial nerve. The second pouch contributes only to ear-related structures. The third arch contributes the greater cornu and the inferior body of the hyoid bone and contributes to the hypobranchial eminence, which forms the cartilage of the epiglottis. It forms only one muscle in the neck, the stylopharyngeus. The trematic nerve of the third arch is the glossopharyngeal nerve. The third pouch gives origin to the thymus gland from its ventral aspect and the inferior parathyroid (parathyroid III) gland from the posterior aspect. The descent of the thymus draws down the parathyroid III so that it lies inferior to parathyroid IV. Arches four, five and six merge to form one, with the fifth arch being completely absorbed. The third and fourth arches fuse forming a transitory sinus between the two, called the cervical sinus. If this persists it runs in the lower neck, between the internal and external carotid arteries to the apex of the piriform fossa. If such a tract is found in the lower neck, a cervical sinus must be excluded by a sino gram. The fourth and six arches form the cartilages and muscles of the larynx and the muscles of the pharynx. The trematic nerves are the superior laryngeal branch and the recurrent laryngeal nerves of the vagus. The fourth pouch gives rise to the superior parathyroid gland (parathyroid IV), while the fifth pouch forms the ultimobranchial body from which the parafollicular cells or C-cells develop. The sixth pouch gives the intrinsic muscles of the larynx. The branchial arch derivatives are summarized in Table 137.1, and the brancial pouches in Table 137.2.
Mandible This represents the upper border of the neck. The superficial lobe of the submandibular gland can be palpated just inferior to the lower border of the inferior ramus of the mandible.
Hyoid The body and greater cornu of the hyoid bone are important bony landmarks in the neck. The body is in the midline and the greater cornu is just inferior to the angle of the mandible. The greater cornu acts as a guide to the lower extent of the course of the marginal mandibular branch of the facial nerve and it divides node levels II and III.
Thyroid cartilage Just inferior to the body of the hyoid is the thyroid cartilage. The thyrohyoid membrane links the two. This cartilage can be moved over the cricoid cartilage when the resulting crepitus is a sign of normality.
Cricoid cartilage This can be palpated inferior to the thyroid cartilage in the midline. Between the two is the cricothyroid membrane. This has a spring-like feel and is the site of emergency tracheotomy. The cricoid is at the level of the sixth cervical vertebra and represents the boundary between larynx and trachea, and the pharynx and oesophagus.
SURFACE ANATOMY Mastoid
Trachea
When examining the neck, this is as good a place to start as any, as it represents the origin of the sternocleidomastoid muscle. Anterior and inferior to the mastoid process, the transverse process of the atlas can be palpated.
Table 137.1
The cervical trachea can be palpated just inferior to the cricoid cartilage.
Summary of branchial arch derivatives.
Arch First Second Third Fourth and sixth
Muscles
Nerves
Skeletal structures
Mylohyoid digastric (anterior belly) Stylohyoid digastric (posterior belly) platysma Stylopharyngeus
V1 VII
Cricothyroid constrictors of the pharynx Intrinsic muscles of the larynx
x (Superior laryngeal)
Mandible Styloid process Hyoid (lesser cornu + upper body) Hyoid (greater cornu + lower body) epiglottis Laryngeal cartilages
IX
(Recurrent laryngeal)
Chapter 137 Surgical anatomy of the neck I 1741
Table 137.2 Pouch
Summary of branchial pouches.
Contribution to the neck stn.lCture
First and second
No neck structures
Third
Inferior parathyroid gland (parathyroid III) thymus Superior parathyroid gland (parathyroid IV)
Fourth
Accessory nerve
Thyroid gland The isthmus can be palpated overlying the trachea between the second and fourth rings. The thyroid lobes lie deep to the sternocleidomastoid muscles and cannot be palpated unless enlarged.
Sternocleidomastoid This muscle arises from the mastoid process and divides into a tendinous sternal head and a fan-shaped clavicular head. Between and deep to the two heads is the internal jugular vein. It divides the neck into anterior and posterior triangles, the posterior border is the anterior border of the posterior triangle and the anterior border is the posterior border of the anterior triangle. On its deep surface is the carotid sheath, which includes the carotid arteries, the internal jugular vein, the vagus nerve and the jugu ar chai 0 lymph nodes. This accounts for 80 perce of lymph nodes in the neck. The jugular chain of nodes is more easily palpated by tilting the head to the side that is being examined. This relieves the tension on the muscle and allows the deep surface to be accessed.
Trapezius This very large muscle can be palpated posterior to the sternocleidomastoid. Elevating the shoulder against resistance makes it more prominent. It should be remembered that the muscle extends out of the neck and into the chest down to the level of the 12th thoracic vertebra.
Marginal mandibular branch of the facial nerve This has a variable course, but it can be accurately located at the point where it crosses the mandible. It crosses with the facial artery, which can be palpated anterior to the masseter muscle. The lower limit of the nerve is the greater cornu of the hyoid, so that incisions below this should not damage the nerve.
This nerve runs through the sternocleidomastoid and in this part of its course is well protected. It exits the posterior border of the sternocleidomastoid at the junction of the upper and middle third about 1 cm above Erb's point. This is the point at which the cervical plexus emerges from the posterior border of the muscle. The nerve then courses across the roof of the posterior triangle and enters the trapezius at the junction of its middle and lower thirds in the neck.
Carotid artery This can be best palpated at the carotid bifurcation. This is between the angle of the mandible and the greater cornu of the hyoid bone. It follows a line from the sternoclavicular joint to midway between the angle of the mandible and mastoid tip.
Root of the neck The manubrium, sternoclavicular joints and the clavicles form the surface landmarks of the root of the neck. The superior surface of the manubrium is the jugular notch and above this is the suprasternal fossa or Burn's space. Laterally, the clavicles articulate with the acromium forming the anterior boundary of the root of the neck.
TRIANGLES It is difficult to readily compartmentalize anatomically all of the structures in the neck. To make this easier, the neck has been classically divided into triangles (see Figure 137.1). The sternocleidomastoid divides the neck into anterior and posterior triangles; the muscle itself is in neither triangle. The submental, submandibular, carotid and muscular triangles divide the anterior triangles.
Anterior triangle The boundaries of this triangle are sternocleidomastoid, the inferior ramus of the mandible and the midline. The contents of the triangle are summarized in Table 137.3.
SUBMENTAL
The boundaries are the anterior belly of the digastric, midline and hyoid bone. It contains lymph nodes and the submental salivary gland.
1742 I PART 14 THE NECK
Stylohyoid muscle Digastric muscle (posterior belly)
Sternocleidomastoid ------'-<:~~ ---;~---
Omohyoid muscle
~ Submandibular triangle
.&. Submental triangle
jugular vein Note the posterior triangle only extends to the posterior border of the sternomastoid muscle Occipital triangle } = Posterior triangle + Subclavian triangle Submental triangle Submandib+ular triangle + Carotid triangle
£.
Carotid triangle
~
Muscular triangle
£.
Occipital triangle
A
Subclavian triangle
)
= Anterior triangle
+ Muscular triangle
Figure 137.1
Triangles of the neck.
SUBMANDIBULAR
MUSCULAR
The boundaries are the inferior margin of the mandible and the anterior and posterior bellies of the digastric muscle. The deep boundary consists of the stylohyoid and mylohyoid muscles. The submandibular triangle contains the submandibular salivary gland, deep fascia, lymph nodes, anterior facial vein, facial artery and the marginal mandibular branch of the facial nerve.
The boundaries are the lower anterior border sternocleidomastoid' anterior belly omohyoid, the hyoid bone and the midline. It contains the lower carotid sheath, the infrahyoid strap muscles, upper aero digestive tract, the thyroid and parathyroid glands.
Posterior triangle CAROTID
The boundaries are the anterior border sternocleidomastoid, posterior belly digastric and the superior belly of omohyoid. It contains the upper carotid sheath and lymph nodes. Table 137.3
The posterior triangle can be divided into two by the omohyoid, which forms the lateral neck triangle and the subclavian triangle. The contents of the triangle are summarized in Table 137.4.
Summary of the contents of the anterior triangle.
Muscles Digastric
Stylohyoid and mylohyoid Superior belly of the omohyoid Strap muscles
Vessels
Nerves
External carotid artery and branches (except posterior auricular) Internal and anterior jugular vein and tributaries
Internal and external laryngeal Thyroid and larynx nerves Nerve to mylohyoid Hypoglossal nerve
Viscera
Submental and submandibular glands
Other Jugular chain of lymph nodes
Chapter 137 Surgical anatomy of the neck I
Table 137.4 Muscles
Summary of the contents of the posterior triangle. Vessels
Nerves
Other
Occipital, transverse
Cervical and
Lymph
1743
Deep cervical fascia SUPERFICIAL OR INVESTING LAYER
Omohyoid
cervical,
brachial
suprascapular and
plexus
nodes
subclavian arteries Transverse cervical, suprascapular and external jugular veins
LATERAL NECK TRIANGLE
The boundaries are the posterior border of the sternocleidomastoid, the anterior border of the trapezius and the superior border of the inferior belly of the omohyoid muscle. It contains the cervical plexus, fibrofatty tissue, lymph nodes and the accessory nerve.
SUBCLAVIAN TRIANGLE
The boundaries are the lower border of the inferior belly of omohyoid, the clavicle and the posterior border sternocleidomastoid. The contents are fibrofatty tissue, the scalene muscles, the brachial plexus and the subclavian ves Is, including the thyrocervical trunk. Also included are Sibson's suprapleural fascia and the pleura. The trape ·us us Ie covers the cervico-occipital region and represents t e posterior neck. This area is rarely involved in head and neck surgery so will not be considered in detaiL
This arises from the ligamentum nuchae and the spinous processes of the cervical vertebrae and invests the entire neck. It splits to enclose the trapezius, the omohyoid, sternocleidomastoid, the strap muscles and the parotid gland. The superior attachment is to the external occipital protuberance, the superior nuchal lines, the mastoid tip and the zygomatic arch. The splitting of this fascial layer around the parotid forms a deep layer, which fuses with the fascia around the internal carotid artery. It also forms the stylomandibular ligament. Anteriorly this is attached to the hyoid. The inferior attachments are the acromium, the clavicle and the sternum.
CAROTI D SH EATH
This is derived from the superficial layer of deep cervical fascia medial to the sterncleidomastoid muscle. It contains 80 percent of the lymph nodes of the neck, the carotid arteries, the internal jugular vein, as well as the vagus nerve.
MIDDLE LAYER. OR PRETRACHEAL OR VISCERAL FASCIA
This is derived from the superior layer of the deep cervical fascia, passes deep to the strap muscles and encircles the trachea, thyroid and the oesophagus. Movement of the hyoid and strap muscles during swallowing elevates the fascia so that thyroid lumps characteristically move on deglutition.
DEEP LAYER OR PREVERTEBRAL FASCIA
FASCIAL LAYERS The identification of fascia and fascial planes allows dissection to be performed quickly and relatively blood1essly. The neck has a superficial and deep fascia (see Figure 137.2). The deep fascia has three layers, a superficial layer, middle or visceral layer and a deep layer. Fascia is investing fibrous tissue related to muscles and major neck structures. The major fascial layers are described in this section.
Superficial cervical fascia This is a thin layer that invests the platysma muscle. It is closely associated with adipose tissue. This fascia is penetrated by the blood vessels that supply the neck skin. The subplatysmal flap therefore protects the blood supply to the skin.
This arises from the ligamentum nuchae and the spinous processes of the cervical vertebrae. It splits to enclose the postvertebral muscles, passes laterally around the scalene muscles and then forms a layer over the vertebrae. It forms the floor of the posterior triangles and allows the pharynx to glide during deglutition.
NECK SPACES Knowledge of these potential neck spaces is important in the understanding of the spread of infection and tumours in the neck. They contain only loose areolar fascia. The various neck spaces are described in this section.
Submental space This is a midline space that lies between the anterior bellies of the digastric muscles.
1744 I PART 14 THE NECK Ligamentum nuchae
Multifidus
Semispinalis cervicis Semispinalis capitis Levator scapulae Posterior primary ramusofC6 Scalenus medius
Prevertebral fascia
Scalenus anterior and phrenic nerve
Retropharyngeal space
Roof of posterior triangle
Recurrent laryngeal nerve Carotid sheath and vagus nerve
External jugular vein
Internal jugular vein
Level IV lymph node Pretracheal fascia Thyroid gland Plane for modified or Sternomastoid radical neck dissection
Infrahyroid muscles Parathyroid gland
Figure 137.2
Investing layer
Pretracheal fascia
Fascial layers of the neck.
Submandibular space
This lies between the tonsil and superior constrictor. It communicates through the fibres of the superior constrictor with retropharyngeal and parapharyngeal spaces.
the greater cornu of the hyoid bone (see Figure 137.3). It is bounded medially by the superior constrictor and laterally by the pterygoid muscles, the mandible and deep lobe of the parotid gland. The parapharyngeal space is divided by the styloid process and its attachments into the prestyloid and poststyloid spaces. The prestyloid space contains ectopic salivary tissue, while the poststyloid contains carotid arteries, internal jugular vein, cranial nerves 9-12, cervical sympathetic chain and lymph nodes. The parapharyngeal space contains a fat pad, which is located centrally. The radiological displacement pattern of this fat pad is useful for diagnosing lesions in this area. Prestyloid and lateral lesions will displace the fat posteromedially, while poststyloid lesions will displace this fat anteriorly.
Parapharyngeal space
Retropharyngeal space
This space is the most complex and clinically most important space. It is shaped like an inverted pyramid, the top of which is the base of skull and the inferior part is
This sits between the two parapharyngeal spaces and is continuous with both. Its superior boundary is the skull base, while the anterior boundary is the musculature of
The superficial boundary is the submandibular gland and digastric muscle, the deep boundary is the mylohyoid muscle. It communicates with the floor of mouth around the posterior border of the mylohyoid.
Peritonsilar space
Chapter 137 Surgical anatomy of the neck
I 1745
Parotid fascia Parapharyngeal space Deep lobe of parotid extending to parapharyngeal space Styloid process Carotid sheath
Medial pterygoid muscle Palatal muscles Superior constrictor Retropharyngeal space
Posterior belly of digastric
Parapharyngeal and retropharyngeal neck spaces.
Figure 137.3
the pharynx (see Figure 137.3). The posterior limit is the prevertebral fascia and the contents are only lymph nodes. It continues inferiorly behind the oesophagus and eventually communicates with the posterior mediastinum.
Pretracheal space This lies anterior and lateral to t e thyroid cartilage and deep to the strap muscles. It contam e elphian node and communicates with the superior medi stinum.
Prevertebral This is the potential space that lies between the cervical vertebrae and anterior longitudinal ligament posteriorly and the prevertebral fascia anteriorly. It extends down to the third thoracic vertebra where the fasica is bound to the vertebra. The prevetebral fascia is thin and infections in this space can rupture directly through into the posterior mediastinum.
clavicle. The sternal head is a thick tendon, which inserts into the anterior and lateral surface of the manubrium. The clavicular head is muscular and inserts into the medial third of the clavicle. The superior attachment is attached, to the lateral aspect of the mastoid tip, as well as the lateral half of the superior nuchal line. The muscle is functionally two with the clavicular fibres being mainly attached to the mastoid and the sternal head to the superior nuchal line. The muscle combines a cruciate and spiralized arrangement of fibres. This gives a complex action, which tilts the head to the shoulder on the same side, rotates the head to the opposite side and assists longus coli in neck flexion. The motor nerve supply is the spinal accessory motor and the anterior rami of C234 segments provides sensory and proprioceptive function. Its blood supply comes from the superior and inferior ends of the muscle with anastamoses in the middle of the muscle. The superior pedicle is from the branches of the occipital artery and the inferior pedicle is derived from the superior thyroid vessels.
Trapezius MUSCLES Knowledge of the relevant muscles is essential for understanding the surgical anatomy of the neck.. A description of each of the muscles follows.
Sternocleidomastoid This is the most prominent and important muscle in the neck in relation to surgery so is worth learning in some detail. Its inferior attachment is onto the sternum and
The size of this muscle is often underestimated. It has a wide origin from the medial third of the superior nuchal line, the ligamentum nuchae down to the seventh cervical vertebra, and all the spinous processes and interspinal ligaments down to the 12th thoracic vertebra. The superior fibres insert into the clavicle and acromium and the inferior fibres from the thoracic vertebrae insert into the spine of the scapular. The action of this muscle is to rotate the scapular so that the glenoid fossa points up. The trapezius is the major antigravity muscle of the shoulder girdle; it is antagonized by all the muscles that move the scapular and the large muscles of
1746 I PART 14 THE NECK the axillary folds. Paralysis of the trapezius is a common consequence of surgical damage to the accessory nerve in the posterior triangle leading to malrotation of the scapular and traction on the brachial plexus, which leads to severe chronic neck pain. The motor nerve supply is the spinal part of the accessory nerve from roots Cl to C6. Proprioceptive information occurs via branches from the cervical plexus, some motor fibres also innervate the trapezius through the cervical plexus.
Omohyoid This is one of the strap muscles but because of its unusual course and importance as a surgical landmark is worth considering on its own. The proximal attachment is to the hyoid bone just lateral to the attachment of sternohyoid. As it courses inferiorly, it diverges laterally, runs deep to the sternomastoid and crosses the internal jugular vein at which point it becomes a tendon. It is a useful landmark for the internal jugular vein. Lateral to the internal jugular vein the inferior muscle belly develops, runs across the posterior triangle and inserts into the suprascapular ligament and the lateral acromium. Embryologically, its distal insertion is to the medial clavicle and it migrates laterally until the adult position is reached. The nerve supply is the ansa cervicalis, the function of this muscle is obscure.
Digastric This is another muscle important to the head and neck surgeon. It arises from the digastric ridge, which is on the medial aspect of the mastoid tip. The posterior belly runs anteroinferiorly and becomes a tendon, which runs through a sling that is attached to the lesser cornu of the hyoid. Movement of this tendon is lubricated by a synovial sheath. The anterior belly then runs anterosuperiorly to insert into the digastric fossa on the inner surface of the mandible. This muscle encloses the digastric triangle, forms a landmark for the main trunk of the facial nerve and represents a deep boundary of dissection for safe avoidance of the hypoglossal nerve. It elevates the hyoid during swallowing and assists the lateral pterygoid in opening the mouth. The posterior belly is supplied by the facial nerve, and the anterior belly receives a branch from the nerve to mylohyoid, from the mandibular division of the trigeminal nerve, reflecting its first and second branchial arch embryology.
Strap muscles This group of muscles comprises the sternohyoid, omohyoid, thyrohyoid and sternothyroid muscles. They
move the larynx and depress the mandible. They are supplied segmentally from Cl, 2 and 3 via the ansa cervicalis. The strap muscles are retracted to access the trachea and thyroid gland and also form the anterior boundaries of the neck levels.
Prevertebral muscles The prevertebral muscles are a group of weak neck flexors that are bound down by the important prevertebral fascia. They are longus capitis anterior, longus capitis lateralis, longus capitis and longus colli. Because they are deep in their entire course to the prevertebral fascia, they are relatively unimportant and will not be described further. The scalene muscles are important landmarks for the head and neck surgeon. They are associated with the root of the neck, an area frequented in radical neck dissections. Scalenus anterior arises from the anterior tubercles of the transverse processes of the third and sixth cervical vertebrae, morphologically a continuation of longus colli. It inserts into the scalene tubercle of the first rib. It carries with it a prolongation of the prevertebral fascia. Over the scalenus anterior muscle runs the phrenic nerve, it is recognized because it is the only neck structure that runs from lateral to medial as it courses inferior to supply the diaphragm. The transverse cervical, ascending cervical and the suprascapular artery also cross the muscle. They are important landmarks for the deep extent of a neck dissection. The subclavian vein contacts the attachment of the muscle to the first rib. Posteriorly lies the subclavian artery and medially the common carotid artery, the inferior thyroid artery and the thoracic duct. The scalenus medius runs behind the scalenus anterior. Lateral to the scalenus anterior and emerging anterior to the medius are the roots of the brachial plexus. These too can be at risk during a neck dissection and must be avoided.
CERVICAL LYMPHATICS The cervical lymphatics are divided into superficial and deep. The superficial perforate the cervical fascia and drain into the deep. When cancer is involved, they will require skin resection for removal in an extended neck dissection. The deep lymphatic vessels and nodes are most densely associated with fascial condensations. This means they are most commonly found around blood vessels, nerves and muscles. The deep lymphatics drain the mucosa of the mouth, oropharynx, nasopharynx, larynx and hypopharynx. The groups of deep nodes are described below and shown in Figure 137.4.
Chapter 137 Surgical anatomy of the neck
I 1747
Lymph node groups: A, submental nodes; B, submandibular nodes; C, upper deep cervical nodes; D, middle deep cervical nodes; E, lower deep cervical nodes; F, posterior triangle nodes; G, paralaryngeal nodes; H, paratracheal nodes; I, parotid nodes; J, suboccipital nodes. Figure 137.4
Submental group These nodes are situated in the midline, inferior to the mandible and between the anterior bellies of the digastric muscles. They drain the anterior floor of the mouth.
Submandibular These nodes are divided into six groups. They are preglandular, prevascular, retrovascular, retroglandular, intraglandular and deep nodes. These nodes can best be described as those related to the submandibular gland and those related to the facial vessels. Cancers of the floor of mouth, tongue and buccal cavity metastasize much more commonly to the perivascular nodes, which should be cleared in a neck dissection.
Jugular chain Eighty percent of lymph nodes in the neck are closely associated with the internal jugular vein. The lymphatic channels are found within the loose areolar tissue that exists around the internal jugular vein and within the carotid sheath. The nodes occur anterior posterior and lateral to the vein. The most superior segment of the vein extends from the skull base to the level of the carotid bifurcation which
coincides with the level at which the greater cornu of the hyoid bone crosses the internal jugular vein. At the most superior extent of the vein, it runs deep to the digastric muscle. Nodes found here are referred to as the jugulodigastric nodes. They are the first echelon node for the drainage of the posterior faucial region, especially the palatine tonsiL Between the upper and middle jugular nodes lie the junctional nodes. They represent a lymphatic anastamosis of the submandibular nodes, the retropharyngeal nodes and the jugular chain of nodes. The middle jugular nodes are found between the carotid bifurcation and the level at which the omohyoid tendon crosses the internal jugular vein. They are first echelon nodes for the larynx midhypopharynx and upper thyroid gland. The lower jugular nodes are those between the tendon of omohyoid and down to the thoracic inlet. They are sometimes referred to as the prescalene group of nodes. They form an important confluence between the mediastinal node group, the axillary group and the neck. This communication can be a reason why neck nodes may appear secondary to disease outside the neck.
Posterior nodes The posterior triangle contains lymph nodes that are arranged into two groups: those that are found along the
1748 I PART 14 THE NECK accessory nerve and those related to the thyrocervical vessels. The nodes along the accessory are the first echelon for the nasopharynx and second echelon for the areas drained by the anterior neck nodes are. related to the thyrocervical vessels.
Lymph node levels The most widely accepted system for describing the lymph nodes in the neck originates from the Memorial Sloan Kettering Hospital, New York and was adopted by the American Academy of Otolaryngology Head and Neck Surgery (AAOHNS) in 1991. It is a system designed by surgeons and radiologists rather than anatomists, and divides the neck into six levels, of which I to V are paired in the lateral neck, and level VI describes midline neck nodes from hyoid to sternal notch (Figure 137.5). The system has been further classified by the Head and Neck Cancer Committee of the American Academy of Otolaryngology Head and Neck Surgery to include subzones, which will also be described. The reason for this added complexity was to more accurately differentiate node
Figure 137.5 Lymph node levels: I, submental and submandibular nodes; II, upper jugular group of nodes; III, middle jugular nodes; IV, lower jugular group of nodes; V, posterior triangle group of nodes; VI, anterior or central group of nodes.
groups that drain different but contiguous structures (Figure 137.6).
LEVEL I
This level refers to the submental and submandibular nodes and drains the lip, oral cavity and tongue. Subzone la refers to the submental nodes and subzone Ib to the submandibular nodes. Subzone la drains anterior floor of mouth, lower lip and ventral tongue, whereas subzone Ib drains other sub sites in the oral cavity.
LEVEL II
This forms the upper jugular group of nodes and drains the oropharynx, larynx, hypopharynx and parotid. The course of the spinal accessory nerve divides this level into two subzones. Level IIa lies anteroinferior to the spinal accessory nerve and lIb posterosuperior. The lIb subzone is also known as the submuscular recess. It is a clinically useful anatomical differentiation because positive level IIa disease mandates lIb dissection, however elective dissection for laryngeal and hypopharyngeal malignancy can exclude level lIb.
Figure 137.6 Neck node level zones and subzones: la, submental nodes; Ib, submandibular nodes; lIa, upper jugular nodes anterior to the accessory nerve; lib, upper jugular nodes posterior to the accessory nerve; III, middle jugular nodes; IV, lower jugular nodes; Va, posterior nodes superior to omohyoid; Vb, poster.ior nodes inferior to omohyoid; VI, midline nodes; VII, superior mediastinal nodes.
Chapter 137 Surgical anatomy of the neck'
LEVEL III
This refers to the middle jugular nodes and drains the larynx and pharynx. Level III is not further subdivided by the new nomenclature because, despite being the largest of the jugular levels, there is little variation in its draining area.
LEVEL IV
Level IV refers to the lower jugular group of nodes. This is a small area, which again drains the larynx and hypopharynx. Attempts have been made to subdivide this area but have not been successful owing to its small size.
LEVEL V
This is the posterior triangle group of nodes and drains the other lymphatic regions in the neck. It has been divided into sub zones. The Va lies superior to the inferior belly of the omohyoid muscle and the Vb level is inferior to the omohyoid muscle. The Va area contains the chain of nodes along the accessory nerve, which drain the nasopharynx. The Vb level contains nodes related to the thyrocervical trunk which drains the thyroid gland.
LEVEL VI
This is the anterior or central group of nodes. This includes the paratracheal, perithyroidal and Delphian nodes.
LEVEL VII
This corresponds to the superior mediastinal tissues. It is not recognized by most American texts.
MAJOR BLOOD VESSELS Common carotid artery This arises from the brachiocephalic artery on the right and the arch of the aorta on the left. It usually has no branches, but may give off the vertebral, superior thyroid, laryngeal branches of the superior thyroid, the ascending pharyngeal, inferior thyroid or the occipital artery. Its surface markings are the sternoclavicular joint, the tubercle of lateral process of C6 (Chassaignac's tubercle) and it bifurcates at the level of the greater cornu of the hyoid. The important relations are the internal jugular vein where it runs medial and deep, while the vagus nerve runs between the two in the carotid sheath. The sympathetic trunk runs deep to the sheath. It is the most
1749
important vascular structure in the neck, though owing to its size is rarely damaged.
Internal and external carotid Both of these originate at the common carotid bifurcation artery. This division is usually at the level of the hyoid bone, although it may be higher but rarely lower. At the point of division, the vessel dilates to form the carotid sinus. This may be confined to the origin of the internal carotid. Histologically, the media here is thinner and the adventitia thicker. Stretch receptors are innervated by the glossopharyngeal nerve and are the main baroreceptors. Deep to the bifurcation is the carotid body, which is reddish-brown in colour and measures 6 x 3 mm and features glomus cells containing dopamine and are innervated to the glossopharyngeal nerve. The internal carotid runs from the upper border of thyroid cartilage to the carotid canal in petrous temporal bone passing deep to the posterior belly of the digastric muscle. It is normally straight and unbranched, though in 15 percent of cases it may be coiled or kinked. Knowledge of its relations are important. The internal jugular vein lies anterolateral through almost the entire course of the internal carotid. Posteriorly lies the superior cervical sympathetic ganglion, the sympathetic chain and superior laryngeal nerve. Medially lies the wall of pharynx, with loose connective tissue, pharyngeal veins, ascending pharyngeal artery and the superior laryngeal nerve. The sternocleidomastoid is anterolateral throughout its course. The other important lateral relations of the internal carotid artery are the hypoglossal nerve, the superior root of the ansa cervicalis, as well as the lingual and facial veins. The external carotid artery originates with the internal carotid artery. In children, it is much narrower than the internal carotid, but in the adult the two are about the same size. It courses in a straight line from the greater cornu of the hyoid to a point between the mastoid and ascending ramus of the mandible. It terminates in the substance of the deep parotid gland, the terminal branches are the superficial temporal and maxillary artery. They supply the deep face, the nose and scalp. The diameter rapidly diminishes as the artery gives off its branches. Before entering the deep surface of the parotid gland, the artery gives off six branches (Table 137.5). They are from the anterior surface, the superior thyroid, lingual and facial arteries, which supply the thyroid, tongue, superficial face and nose. The deep branch is the ascending pharyngeal. This arises just above the bifurcation of the common carotid and is not usually seen during a neck dissection. It supplies the hypopharynx and oropharynx, skull base and posterior fossa dura through perforating branches. The posterior branches are the occipital, posterior auricular and run superficial to the internal jugular vein. Along with the superior thyroid
1750 I PART 14 THE NECK Table 137.5
Branches of the external carotid artery.
Table 137.6
Important relations of the internal jugular vein.
Irnportantrelation Anterior
Posterior Deep Terminal
Superior thyroid Lingual Facial Occipital Posterior auricular Ascending pharyngeal Superficial temporal Maxillary
branches, they supply the sternocleidomastoid and contribute to the external ear and occiput. Ligation of the external carotid artery is a common procedure to control head and neck haemorrhage. It is vital to recognize the external carotid artery and avoid the internal carotid. This is done by position, the external is anterior and superficial to the internal carotid artery. The external carotid artery also can be identified by recognizing more than one branch.
Sternocleidomastoid Common and internal carotid arteries Vagus nerve Crossed by:
Lateral Anteromedial Medial Posterior belly of digastric Superior belly of omohyoid
jugular vein. Superior to the digastric is the parotid, the styloid process and the accessory nerve, the postauricular and occipital arteries are lateral relations. Between the digastric and omohyoid is the inferior root of the ansa cervicalis. The deep cervical nodes of levels II, III and IV are mostly on the superficial surface of the vein. At the base of the skull, the internal carotid is separated by the lower four cranial nerves from the deep surface of the vessel.
External jugular vein Internal jugular vein The surface anatomy of the internal jugular vein in the neck is the lobule of ear to the medial end of the clavicle, running deep to the sternal and clavicular heads of the sternocleidomastoid. The internal jugular vein is a continuation of the sigmoid sinus and is a thin-walled capitance vessel. It exits the skull in the posterior compartment of the jugular foramen. At its origin exists the superior bulb, which is deep to the posterior floor of the tympanic cavity. The vein runs in the carotid sheath and joins the subclavian vein to form the brachiocephalic vein at the sternal end of the clavicle. At its termination the internal jugular vein has an inferior bulb, which is the only part of the vessel that contains valves. The tributaries begin with the inferior petrosal vein, which joins ~the superior bulb; other tributaries include the facial, lingual, pharyngeal, superior and middle thyroid veins. The thoracic lymphatic duct joins the vein at the intersection with the subclavian vein in Chassaignac's triangle, which is formed by the longus colli, scalenus anterior with the subclavian artery at the base, the apex is formed by the tubercle of the sixth thoracic vertebra (Chassaignac's tubercle). The posterior relations of the internal jugular vein are the prevertebral muscles, the transverse process of atlas, the phrenic nerve and the thyrocervical trunk. The medial relations are the vagus nerve, the common and internal carotid arteries while the sternocleidomastoid lies superficially along its entire course (Table 137.6). The posterior belly of digastric and superior belly of omohyoid are important surgical landmarks, which cross the internal
This vein along with the posterior external jugular vein and the anterior jugular vein forms a variable superficial system of veins, which drains blood from the face and scalp. It enters the subclavian vein where there are valves at the entrance with a further set of veins at 4 cm proximaL These are inefficient and do not prevent reflux of blood. The external jugular vein has a node, the external jugular node, which drains the parotid gland and is important in malignancy.
NERVES The knowledge of the major nerves in the neck is essential when operating in the area if damage and subsequent palsies are to be avoided. The major neural structures in the neck are described below.
Marginal mandibular branch of the facial nerve This nerve runs inferior to the angle of the mandible, it dips down into the neck and runs superficial to the submandibular triangle. The nerve runs just deep to the platysma and is superficial to the deep fascia. It runs inferior to the greater cornu of the hyoid bone, which is the inferior landmark of its course. It curves upwards and crosses the mandible for a second time close to the facial artery and vein. It lies deep to the depressor anguli oris, which it stlpplies. It also supplies risorius and the muscles of the lower lip. The lip is also attached to platysma and
Chapter 137 Surgical anatomy of the neck
asymmetry may result following division of the muscle or the cervical branch of the facial nerve.
Glossopharyngeal This is the trematic nerve of the third pharyngeal arch. It exits the skull at the anterior compartment of the jugular foramen. It has an inferior ganglion in the neck, which contains cell bodies of the sensory fibres. It passes down on the internal carotid artery then curves anteriorly around the stylopharyngeus, deep to the hyoglossus and reaches the tongue. Its branches are the tympanic or Jacobson's nerve, which supplies sensation to the middle ear and parasympathetic supply to the parotid gland from the inferior salivary nucleus via the tympanic plexus. It has a motor branch that supplies the stylopharyngeus. The carotid sinus is innervated by a branch of the glossopharyngeal nerve. It takes baroreceptor and chemoreceptor information to the brainstem. Pharyngeal branches join the pharyngeal plexus, which is probably sensory on the posterolateral surface of the middle constrictor. The tonsillar branches supply sensation to the tonsil mucous membrane, which is used to clinically test the nerve. Lingual branches supply the posterior third of tongue with taste, sensation and secretomotor fibres. Its surgical importance is as a conduit for referred pain from the neck to the ear, its contribution to the pharyngeal plexus and as a carotid body innervation. It rarely features in surgical dissections.
Vagus This is the trematic nerve of the fourth branchial arch and exits the skull base through the middle compartment of the jugular foramen. Beneath the skull base, the nerve dilates to form the inferior ganglion, which contains the afferent cell bodies. Below the ganglion, the vagus receives a branch from the accessory nerve. The vagus runs in the carotid sheath between the internal jugular vein and the internal and common carotid artery. Its branches are the: • • • • • •
auricular branch; carotid body branches; pharyngeal branches; superior laryngeal branches; cardiac branches; recurrent laryngeal branches.
The auricular branch, or Arnold's nerve, runs between the mastoid and the tympanic plate to supply tympanic membrane and ear canal skin and contributes to referred pain from the neck to the ear. A small carotid body branch supplements the glossopharyngeal branch. The pharyngeal branch slopes across the internal carotid· and joins the pharyngeal plexus on the middle constrictor. The contribution to the pharyngeal plexus
I 1751
derives from the accessory nerve and supplies motor innervation to the constrictors and soft palate. The superior laryngeal nerve leaves the vagus high in the neck, runs deep to the internal carotid and divides at the level of the hyoid into external and internal laryngeal nerves. There are two cardiac branches on each side, which leave the vagus low in the neck and form the cardiac plexus. The recurrent laryngeal nerve branches low in the neck. The left hooks around the ligamentum arteriosum and arch of aorta and then runs cranially in the tracheooesophageal groove. The right is more variable than the left and usually runs around the subclavian artery before coursing medially towards the tracheo-oesophageal groove. Though this may vary occasionally the nerve is nonrecurrent on the right in 2 percent of cases. The relationship that the recurrent laryngeal nerves have with the inferior thyroid artery and its branches is of major surgical significance during thyroidectomy. It may run deep, through or superficial to the inferior thyroid artery and its branches. The common landmark for it is as the inferior side of Beahr's triangle, with the other sides being the common carotid artery and inferior thyroid vessels. It supplies the trachea, oesophagus hypopharynx and enters the larynx above the cricothyroid joint.
Spinal accessory The accessory nerve is formed in the posterior cranial fossa by the union of spinal and cranial parts. The spinal part is formed from rootlets that emerge from the upper five cervical segments. They unite into two trunks, one on each side that run on the denticulate ligament lateral to the vertebral arteries. They run into the posterior fossa via the foramen magnum. After uniting with the cranial root, the nerve emerges from the skull base through the middle compartment of the jugular foramen, lateral to the vagus nerve. The cranial component peels off and joins the vagus just inferior to the inferior ganglion. The spinal accessory runs in contact with the internal jugular vein, inferior to the lateral mass of the atlas and passes into the sternocleidomastoid. It supplies motor input only to the sternocleidomastoid muscle from the C2 and C3 roots. The accessory nerve exits the muscle at the junction of the upper and middle thirds of the posterior border, a point known as Erb's point. It runs across the posterior triangle between the deep and superficial layers of the deep cervical fascia. The nerve enters the trapezius at the junction of its lower and middle thirds. It frequently divides before entering the muscle. The trapezius muscle is supplied from C3 and C4 roots.
Hypoglossal This nerve exits the skull through the anterior condylar, or hypoglossal canal, in the occipital bone. The nerve
1752 I PART 14 THE NECK courses around the inferior vagal ganglion then runs inferior around the internal carotid and then the external carotid artery to pass below the posterior belly of the digastric. It then runs around the stylomastoid branch of the occipital artery, the external carotid and the lingual artery and inferior to the greater horn of the hyoid bone. It then courses upwards deep to hyoglossus and divides to supply all the intrinsic muscles of the tongue and all the external muscles, except the palatoglossus. It is entirely a motor nerve and it is vital to recognize the hypoglossal nerve and preserve it during head and neck procedures. It is at its most vulnerable at the greater cornu of the hyoid. The nerve gives the upper root of the ansa cervicalis, which is called the descendens hypoglossi. It passes between the internal jugular vein and the internal carotid artery and runs on the internal jugular vein. The fibres are derived from the C1 nerve root and supply the strap muscles.
Cervical plexus This is a plexus of nerves formed from the anterior rami of the upper four cervical nerves. It lies on scalenus medius and is deep to the prevertebral fascia. The muscular branches of the cervical plexus are a loop from C1 to the hypoglossal nerve which then becomes descendens hypoglossi and the superior root of the ansa cervicalis, and the inferior root of the ansa cervicalis, which is formed from the union of branches from the C2 and C3 roots. The C2 and C3 roots give branches to the sternocleidomastoid and the C3 and C4 give branches that supply the trapezius. These branches are mainly proprioceptive with the efferent branches to these important muscles being channelled through the spinal accessory nerve. However, some efferent fibres come directly from the cervical plexus. The phrenic nerve is the most important muscular branch of the cervical plexus. It is the only motor supply to the ipsilateral diaphragm. It is also sensory to the central tendon of the diaphragm, the pericardium and the pleura. It is formed mainly by C4 fibres. It runs over the scalenus anterior, from its lateral to medial borders as it progresses inferiorly, and is recognized during a neck dissection by its lateral to medial course. It passes deep to the subclavian vein. Some fibres supplement the phrenic nerve from the nerve to subclavius via the accessory phrenic nerve. The cervical plexus gives four cutaneous branches. They supply the front and side of the neck, the external ear the parotid gland and fascia. They emerge from behind the sternocleidomastoid at Erb's point, which is at the junction of the upper and middle third of the posterior border of the muscle. They fan out to supply the neck. The branches are the lesser occipital, greater auricular, transverse cervical and supraclavicular nerves.
Cervical sympathetic trunk This runs over the neck of the first rib and ascends to terminate in the superior ganglion, which lies just anterior to the lateral mass of the atlas. The inferior ganglion is at the level of the first rib, sometimes fused with the highest thoracic ganglion to form the stellate ganglion. The trunk runs superficial to the prevertebral fascia. The preganglionic fibres of the trunk are all myelinated and the postganglionic fibres exit the ganglia to supply the vessels in the head and neck. The eye and the salivary gland are unmyelinated. The head and neck derive their supply from thoracic levels 1-3. Interruption of the cervical sympathetic trunk leads to Horner's syndrome. This consists of ptosis, anhydrosis, meiosis, blocked nose and an itchy scalp.
SUMMARY The anatomy of the head and neck is complex and the purpose of this chapter is to highlight important areas of which the surgeon needs to be aware. In distinction to most other areas of otolaryngology, head and neck surgery anatomical knowledge per se has not advanced greatly in the last 50 years. However, computer-based audiovisual advances have broken the monopoly of books and cadaveric dissection as the sole source of anatomical information, and would be recommended in appreciating three-dimensional anatomy. Operation planning requires knowledge gleaned from books. However, surgical experience with a senior tutor and cadaver dissection are as important as any surgical text in learning the anatomy of the neck.
KEY POINTS • knowledge. of the development of the neck helps in understanding its anatomy. • Surface anatomy must be considered when planning incisions. • The triangles help in learning neck anatomy. • The sternocleidomastoid is in no-man's-land, i.e. it forms the borders, but not the contents of any triangle. • The fascia around the trapezius, sternocleidomastoid and digastric muscles form dissection tunnels which surgically unlock the neck. • The platysma is enveloped by a superficial layer of cervical fascia,. which guarantees the blood supply to the skin. • The parapharyngeal space is the most important to master. • The· facial, accessory and hypoglossal nerves must be learnt.
/
Chapter 137 Surgical anatomy of the neck
I 1753
Lindburg R. Distribution of cervical lymph node metastases
Deficiencies in current knowledge and areas for future research
from squamous cell carcinoma of the upper respiratory and digestive tracts. Cancer. 1972; 29: 1446-9.
In the future, the need for detailed anatomical
Robbins KT. Classification of neck dissection, current concepts
knowledge may be largely replaced by advanced
and future considerations. Otolaryngologic Clinics of North
scanning, particularly magnetic imaging. This may
America. 1998; 31: 639-55.
provide highly individual information exactly detailing the courses of nerves.
Shah JP. Patterns of lymph node metastases from squamous carcinomas of the upper aerodigestive tract. American Journal of Surgery. 1990; 160: 405-9. Watkinson JC, Gaze MN, Wilson JA. Metastatic neck disease. In: Watkinson JC, Gaze MN, Wilson JA (eds). Stell and
FURTHER READING Agur AMR. Grants atlas of anatomy, 9th edn. Williams and Wilkins, 1991. Kauman PM, 500 KC. Motor innervation of the trapezius muscle: a histochemical study. Head and Neck. 1996; 18: 254-8. Last RJ. Anatomy regional and applied, 8th edn. Edinburgh: Churchill Livingstone, 1990.
Maran's head and neck surgery, 4th edn. London: Arnold, 2000. Watkinson JC, Gaze MN, Wilson JA. Tumours of the thyroid and parathyroid glands. In: Watkinson JC, Gaze MN, Wilson JA (eds). Stell and Maran's head and neck surgery, 4th edn. London: Arnold, 2000. Williams PL, Warwick R. Gray's anatomy, 36th edn. Edinburgh: Churchill Livingstone, 1985.
138 Examination and imaging of the neck
SHEILA C RANKIN AND JOHN HIBBERT
Introduction
1754
Best c lini cal pract ice
Imaging tech n iq u es
1755
Deficiencies in current knowledge and areas for future
Cross-sectional anatomy
1756
Cervical lymph node assessment
1759
Key points
1763
1763 1764
research
1764
References
The data in this chapter are supported by a Medline search using the key words positron emission tomography, computed tomography, magnetic resonance imaging, ultrasound and cervical lymphadenopathy.
INTRODUCTION
clavicles and manubrium for inspection. It is usual to palpate the neck while standing behind the patient so that
Examination of the neck is an essential part of the assessment
of
a
patient
with
an
otolaryngological
complaint or disorder. The patient with a lum p in the
both sides can be palpated simultaneously and compared. Each examiner should have a scheme for examination so that all regions are carefully palpated.
neck may have a primary tumour of which they are
If the patient has an obvious swelling it is logical to
unaware; thus, examination of the upper aerodigestive
palpate this first, but the rest of the neck should always be examined as well. The examination routine may always be
tract is essential. Examination begins with history taking and in many patients the diagnosis may be obvious even before the
the same or it
m ay
differ according to the clinical
indication. This means that in a patient with a thyroid
examined. In the case of a patient with the
problem, the thyroid region is palpated first and the rest
primary complaint of a lump in the neck, a history of
of the neck afterwards. In a patient whose neck is
associated complaints such as sore throat, hoarseness,
examined as part of treatment follow-up, the jugular chain of lymph nodes may be the starting point for the
patient is
dysphagia and ear ache must be established before the neck is examined. Once a history is taken, the upper
palpation. Whatever method an individual clinician uses,
aerodigestive tract is usually examined before the neck. It
the whole of the neck should be examined in a logical
is important to determine whether the neck lump is
sequence.
tender before palpating the region.
If palpation begins in the jugulodigastric region, it
Examination begins with inspection from the front
should proceed inferiorly along the anterior border of the
and one should ask the patient where they feel the
sternomastoid muscle, eventually reaching th e manu
sweUing
is. This is important both initially and for
patients who are being followed up after treatment of, for example, a p rima ry
tumour in the upper aerodigestive
tract. The neck should be exposed to the level of the
brium. At this point it may be sensible to palpate the larynx and thyroid gland. The present authors find it advantageous to ask the patient to swallow so that the thyroid gland is elevated and easier to palpate as it rises
1755
Chapter 138 Examination and imaging of the neck I
under
the
fingers.
Next the supraclavicular fossa
is
palpated, passing then into the posterior triangle and
moving upwards as far as the mastoid tip. Now the parotid region and then submandibular triangle and
5 and 20 MHz) transducers. The usual frequency is
5-12.5 MHz that has an axial resolution of 0.5 mm and a
lateral resolution of 1 mm or less. The use of higher frequencies
(15-20 MHz) improves spatial resolution,
submental area are palpated eventually returning to the
allowing nearly microscopic resolution of very small
jugulodigastric region and anterior triangle which should
areas, but has very limited depth penetration.
same
A systematic examination would include the thyroid
clinical situation,
gland, so the frequency and gain can be optimized and
examination of the neck may include asking the patient
then the vessels, salivary glands, floor of the mouth and
always
be
palpated
more
than
once
examination. Depending upon the
in
the
to protrude the tongue (thyroglossal cyst), may include
cervical lymph nodes can be examined. A limitation of
bimanual palpation through the floor of the mouth
ultrasound is that it is operator dependent and the deep
(submandibular gland) and examination of the facial and
structures cannot be identified. Ultrasound-guided fine
other cranial nerves.
needle cytology allows the accurate and rapid diagnosis of
Although examination of the neck is essential in
face and neck masses.
benign disorders, it is most important in the primary assessment and follow-up of patients with malignant disease of the head and neck. Clinical examination alone
Computed tomography
has variable reliability and is enhanced by radiological examination in the assessment of both benign and
Computed tomography is a quick, widely available and
malignant disease. Normal structures in the neck which
relatively cheap method of imaging the face and neck. The
the
patient lies supine with the head in a neutral position so
transverse process of the atlas, the carotid bifurcation,
may
be
mistaken
for
an
abnormality
include
that the hard palate is perpendicular to the tabletop. The
the submandibular salivary gland and the greater cornu of
scan plane is parallel to the inferior orbitomeatal line.
the hyoid bone. Some patients have necks which are very
Intravenous
difficult to palpate and assess and in these, radiological
differentiation of nodes from vessels and an 18 cm field
contrast
medium
is
used
to
aid
the
assessment is essential. In the assessment of patients with
of view will improve spatial resolution. If there is excessive
primary head and neck cancer, assessment of regional
artefact from dental amalgam, angling the gantry so that
lymph
nodes
is
very
important
and
it
almost
it is parallel to the teeth may be helpful. In single slice
Clinical
spiral technology, 3 mm collimation with a pitch of one
is
mandatory to assess the neck radiologically.
examination of the neck in this situation has a false
and a reconstruction every 2 mm is used. Multislice spiral
positive rate of between 20 and 30 percentl,2 and a false
techniques allow faster acquisition with improved utiliza
negative rate of 30-40 percent.3 There is no doubt that the
tion of contrast medium and thinner collimation, leading
sensitivity and specificity of neck examination can be
to improved spatial resolution and excellent reformatted
improved by radiological examination.4,5 This is parti
images
cularly important in the initial assessment of a patient
associated with dental amalgam and will allow excellent
with head and neck cancer, but in the follow-up patient if
coronal and sagittal images to be produced.
there is any doubt about the presence of metastastic nodes
excellent for evaluating bone destruction, whereas MRI
then radiological assessment is equally important.
is better for intracranial or dural extension.
that
may
overcome
some
of
the
problems CT is
The radiological methods for imaging the face and neck include ultrasound (US) including colour Doppler with or without the addition of guided fine needle cytology,
Magnetic resonance imaging
computed tomography (CT), magnetic resonance imaging (Mru) including the use of contrast agents, and positron
Magnetic resonance imaging (MRI) has superior soft
emission tomography
tissue
(PET). All these methods have
recognized advantages and limitations.
resolution
with
improved
demonstration
of
tumour-muscle interfaces compared to CT. There is less image degradation by dental amalgam and direct axial, coronal and sagittal images can be produced for the
IMAGING TECHNIQUES Ultrasound
assessment of intracranial and perineural involvement. It is superior to CT for imaging the base of the skull, salivary
glands,
oral
cavity
and
nasopharynx:.
It
is
probably no better than CT for the assessment of lymph nodes or the larynx. No radiation is involved and the
High-resolution B-mode ultrasound is an inexpensive
gadolinium-based
and rapid method of examining the neck and is used to assess palpable abnormalities and guide biopsies.6
characterization, unlike the contrast medium used for CT, is not nephrotoxic. The disadvantages of MRI include
The optimal examination of the superficial structures
the long acquisition time of the scans with consequent
of the face and neck requires high-resolution (between
degradation
of
contrast
the
images
medium
due
to
used
for
motion
lesion
artefact
-j---�--,----
1756 I from
PART 14 THE NECK
breathing,
swallowing
and
vascular
pulsations.
acquisition time and thus increased patient throughput
Claustrophobia and the contraindications due to the use
and
of a strong magnetic field including the presence of
350 MBq of I8-FDG is injected intravenously and after
(2)
there
is
excellent
anatomic
coregistration.
cochlear implants, cardiac pacemakers, aneurysm clips
approximately one hour for the tracer to be taken up, the
and any metal within the eye are also a problem. It is
images are acquired. These are usually taken from head to
more expensive than CT and is not as widely available.
pelvis. Standardized uptake values (SUV) can be calcu
High-resolution axial TIWand T2W images using 3 or
lated (SUV
4 mm thickness with a I-mm interslice gap are required.
of ROI/injected
If gadolinium is administered, TIW fat suppression
tumour and can be corrected for partial volume effect.
=
activity in region of interest (ROI)/volume activity/weight
of
sequences are obtained after contrast medium to improve
Coronal,
the
together with the scans from the multislice CT.
visualization
of
enhancing
tumour
against
the
transaxial and sagittal
patient)
for
each
slices are displayed,
adjacent fat. T2W or T2* sequences are used to assess cartilage involvement. Coronal scans are also obtained for the assessment of tumour extent, particularly intracranial involvement, and coronal and sagittal scans are used for assessing lesions of the tongue or skull base.
CROSS-SECTIONAL ANATOMY The complex anatomy of the head and neck may be difficult to appreciate from the two-dimensional axial
Positron emission tomography Positron emission tomography
(PET) is an imaging
technique that can map functional and metabolic activity before any structural changes have taken place. PET scanning
using
either
2-I8-fluoro-2-deoxy-D-glucose
(18-FDG) or llC-methionine can differentiate malignant from normal tissue based on enhanced glycolysis or amino acid metabolism by tumour cells, and can thus identify tumours in normal-sized lymph nodes, differ entiating sinus malignancy from secretions and fibrosis from tumours. PET appears to be the best imaging
images of CT or MRI and the advantages of coronal and sagittal images cannot be underestimated. The head used to be divided into the nasopharynx, oropharynx and oral cavity. This was
useful when staging
squamous
cell
carcinoma but not so useful when defining the origin of other
lesions
or
explaining
the
spread
of
disease.
Radiologists use the deep cervical fascia to divide the head and neck into spaces.
10, 11, 12
The deep cervical fascia
consists of three layers: the superficial (investing), middle (buccopharyngeal) and the deep (prevertebral) fascia. The spaces of the suprahyoid neck defined by these layers are as follows.
method for assessing recurrent tumour, although there are problems with false-positives due to inflammation.7 It is also possible to quantify uptake in absolute units, a factor that may increase sensitivity when monitoring metabolic changes after treatment, with a reduction in uptake correlating with tumour regression and a high initial uptake predicting a poorer outcome.8 A further advantage of PET is the ability to perform whole body scanning to identify synchronous primary tumours, distant metastases and identify the site of the primary in . patients who present with cervical node metastases?,9 Positron emission tomography has limited spatial resolution that is not as good as CT or MRI, but
Parapharyngeal space The parapharyngeal space (PPS) lies centrally within the head and neck and extends from the skull base to the cornu of the hyoid. Its medial margin is the middle layer of the fascia, laterally is the superficial layer and posterior is the anterior part of the carotid sheath. It contains fat, the internal maxillary and ascending pharyngeal arteries and a venous plexus. The importance of this space is not its contents but how masses from other spaces impact upon it indicating the origin of a mass.
coregistration of images can be performed to improve anatomical localization. There is increased uptake of I8-FDG in infection, and low-grade tumours may have
Pharyngeal mucosal space
similar uptake ratios to infection. A major limitation of PET is lack of availability and expense. Patients are fasted for six hours prior to the PET examination. Transmission scans are acquired in addition
The pharyngeal mucosal space (PMS) lies on the airway side of the mi�dle layer of the fascia. Superiorly, the fascia merges with the aponeurosis of the superior constrictor
to emission scans so an attenuation corrected image can
muscle attaching it to the skull base. It contains mucosa,
the transmission scans, but the more recent introduction
ghi.hds, the superior and middle constrictor muscles, the
be generated. Some cameras use 68 germanium rods for
of combined PET/CT scanners has resulted in the use of the CT scan to generate the transmission map. These combined systems, which are now the only systems available, have two advantages: (1) there is a decrease in
lymphoid tissue, adenoids and tonsils, minor salivary levator palati muscles and the cartilage of the Eustachian tube. Lesions arising in this space displace the pharyngeal space laterally and can therefore be differentiated from deep lobe parotid tumours.
Chapter
I
138 Examination and imaging of the neck
1757
Masses in this space include salivary gland tumours arising in minor salivary glands. These represent 9 percent of all salivary gland tumours, although they have a greater tendency to be malignant
(65 percent), as the smaller the
gland the more likely the mass will be malignant. Benign salivary gland tumours tend to be well-defined low attenuation masses on CT, which are hyperintense on T2W,
whereas malignant lesions tend
to be poorly
defined, and infiltrating with regular enhancement and irregular cystic or necrotic areas
(Figure 138.1).
Masticator space This is enclosed in two layers of investing fascia (super ficial). The medial fascia runs along the pterygoid muscles to the skull base, including the foramen ovale, and the lateral fascia runs superiorly over the temporalis muscle. It contains the muscles of mastication including the temporalis, masseter and pterygoid muscles and the mandible. It also contains the branches of the trigeminal
(V3)
nerve, allowing intracranial perineural spread to
tumour into Meckel's cave via the foramen ovale. Masses in
this
space
cause
posterior
displacement
of
the
parapharyngeal space.
Parotid space The superficial layer of fascia splits to encompass the parotid space and it extends from the external auditory canal to the angle of the mandible. The contents include the parotid gland, the facial nerve, external carotid artery and retromandibular vein and intraparotid lymph nodes. Masses in this space displace the parapharyngeal space medially
(Figure 138.2).
Carotid space All three layers of the fascia form the carotid space and it contains the common or internal carotid artery. the internal jugular vein (lying posterolateral to the artery), the
IXth,
Xth,
XIth
and
XIlth
cranial
nerves,
the
sympathetic plexus and lymph nodes. Masses in this space cause anterior displacement of the parapharyngeal space with
anterolateral displacement of
the
styloid
process.
Retropharyngeal space Figure 138.1
This space is formed between the middle and deep layer of deep cervical fascia with the constrictor muscles lying anterior and prevertebral muscles being posterior. It extends from the skull base to T4, thus allowing infection and tumour to pass into the mediastinum from the space.
Pharyngeal mucosal mass arising in accessory
salivary tissue. The parapharyngeal fat space is displaced laterally (arrow) . so the mass must arise in the pharyngeal mucosal space.
(a)
T1 W sequence pre-contrast medium;
post-gadolinium showing enhancement of the mass. sequence.
(c)
(b)
T1 W
T2W
1758
I PART 14 THE NECK
Perivertebral space The deep layer of fascia passes from one transverse process to the other encircling the spine and enclosing the paraspinal muscles. It extends from the skull base to the level of the fourth thoracic vertebra and contains the prevertebral and scalene muscles, the brachial plexus, the vertebral artery and vein and the vertebral bodies. Masses in this space, which usually originate from the vertebral bodies, displace the prevertebral muscles anteriorly.
Oral cavity This lies anterior to the oropharynx, being separated by the anterior tonsillar pillars and the soft palate tongue is
The
.
d ivided into the oral tongue (anterior two
thirds) and the tongue base (posterior one-third) which lies in the oropharynx.
Sublingual space This lies within the oral tongue with the mylohyoid muscles lateral and inferior and the genioglossus and geniohyoid muscles medi ally. It contains part of the hyoglossus muscle, the lingual nerve, the IXth and XIth cranial nerves, the
lingual artery and vein, the sublingual gland and the deep portion of the submandibular gland and duct.
Masses found in this space include dermoids, which are unilocular masses with contents that are of mixed density and may contain fat, and epidermoids, which are of
fl uid
signal
or
attenuation.
Dermoids
are
more
common in the submandibular space.
Submandibular space This space is infero l ateral to the mylohyoid and superior to the hyoid bone. The superficial layer of fascia encircles it and
it
is
de ep cervical
in continuity with the
sublingual and the parapharyngeal spaces. The contents include the anterior belly of the
digastric muscle, the
submandibular gland, the submandibular and submental Figure 138.2
Deep lobe parotid tumour (arrowheads). The
parapharyngeal fat space is displaced medially (white arrow)
(a)
indicating this mass must a rise in the pa rotid space. sequence.
(b)
T1 W
TlW following gadolinium. There is minimal
lymph nodes, the facial artery and vein and part of the hypoglossal nerve (XII). Lesions arising in this space include the branchial cleft cyst. This usually presents in young
adults and classically l ies anterior and medial to the
sternocleidomastoid,
enhancement of the tumour.
posterior
to
the
submandibular
salivary gland It is a well-defined low attenuation (fluid .
density) lesion on CT with a smooth wall . If it has become
infected it may have a thick enhancing wall with high It contains fat and lymph nodes, although there are no
attenuation contents and may be confused with malig
nodes in this space below the level of the hyoid Masses in
nant lymph nodes or an abscess. On MRI, it is usually
from
high signal on T2W and low signal on Tl W sequences,
.
this
space
displace
the
parapharyngeal
space
posterior medi al to anterior-lateral; the styloid process -
is not usually displaced unless the mass is very large.
although the signal intensity will vary depending on the protein level within the cyst
(Figur.e 138.3).
.
"
�
- '- -'-" '
Chapter 138 Examination and imaging of the
n eck
I 1759
assessment of lymph nodes,14 and one study comparing MRI and physical examination found the sensitivity and specificity were 75 and 97 percent for physical examina tion and 73 and 95 percent for MRL1s
[****1
A commonly used lymph node classification is that of the American Joint
Committee
on
Cancer and the
American Academy of Otolaryngology - Head and Neck Surgery.16 Som et al.17 have proposed an image-based lymph node classification that is similar and is based on easily identified cross-sectional imaging landmarks and this, combined with clinical palpation, should provide the best classification of nodes. The
majority of
normal
cervical
nodes
measure
2-5 mm (axial diameter) apart from the jugulodigastric and jugulo-omohyoid nodes that measure 8-10 mm in axial diameter and 10-15 mm in length. Reactive nodes are found in virtually all patients, particularly involving the submandibular and lateral cervical nodes. They occur in response to previous inflammatory disease with an increase in histiocytes in the lymph node sinus. The nodes Figure 138.3
usually measure less than 8 mm in axial diameter and
Branchial cleft cyst.
10-15 mm in length and are oval, smooth in outline with rounded ends.
The infrahyoid neck is usually taught as triangles.
In acute inflammatory disease, the nodes are enlarged,
However, these are difficult to orientate on axial imaging
but
and the concept of fascial planes can be extended into the
metastases in the neck are secondary to squamous cell
infrahyoid neck. These fascial planes are not visualized on
carcinoma in 80 percent of cases and they are enlarged
they
are
still
oval
with
rounded
poles.
Nodal
and rounded. The imaging characteristics for different
cr or MR, but do limit the spread of the disease.
The deep cervical fascia is divided into three layers: the
modalities are described below.
superficial layer that encircles the neck completely from hyoid bone to sternum and clavicle, the middle (visceral) layer which encircles the larynx, trachea, thyroid, para
Ultrasound
thyroid glands, the oesophagus and paratracheal nodes and the deep layer which encircles the prevertebral and
Normal nodes are echogenic and similar to the surround
paraspinal muscles, the scalene muscles and the vertebral
ing fat and difficult to visualize, requiring high frequency
bodies.
(13 MHz) probes. Pathological nodes tend to be larger and have decreased echogenicity due either to tumour infiltration, hyperplasia of lymphoid follicles or swelling
CERVICAL LYMPH NODE ASSESSMENT
of histiocytes in the sinus. Power Doppler sonography may help in the differentiation of metastatic from reactive
Clinical palpation is a good method for the staging of
lymphadenopathy. 18
lymph nodes in head and neck malignancy, but the deep
ultrasound increases the conspicuity of the intranodal
The
use
of
contrast
agents
in
nodes may not be palpable. Radiological staging methods
vessels in the nodal hilus. Using Doppler sonography,
(US, CT, MRI and PET) have therefore assumed greater
central linear or hilar increased perfusion may be seen.
importance, but the indications remain controversial
Inflammatory nodes are markedly hypoechoic and the
since the reliability of these techniques is variable. The
hilus may not be seen. The nodes are often 20-25 mm in
results of a meta-analysis of CT versus physical examina
length, but length does not differentiate between benign
tion have shown that CT is more sensitive, specific and
and metastatic nodes and the ratio between the transverse
accurate than physical examination, but the difference
and longitudinal diameter (short-to-Iong axis ratio) is
was not significant. The sensitivity of CT was 83 percent
more accurate. On Doppler sonography, there may be
(physical examination 74 percent), specificity 83 percent
marked increase in vascularity but with preservation of
(physical
the vascular architecture. There is a wide spectrum of
percent
examination (physical
81
percent)
examination
and
accuracy
Overall
changes in tuberculous nodes and they may be large,
physical examination identified 75 percent of pathological
round and hypoechoic or cystic, necrotic nodes with
77
percent).
83
nodes, but if both modalities were used the detection rate rose to 91 percent.13 Althouh MRI has superior soft tissue resolution to CT, it may be no better than CT for the
blurred outlines. Nodes (Hodgkin
involved and
with
sarcoidosis
non-Hodgkin)
and
appear
lymphoma
very
similar.
___ �
_-1� - ��---
1760
I PART 14 THE NECK
Multiple nodal groups are involved, so the nodes may be conglomerate. Individual nodes are round or oval and if
contact is greater than 3.5 em or circumferential contact of more than 150°.
very large may be markedly hypoechoic. They may
contain tiny echogenic foci. If rapid growth occurs, there may
extranodal
be
extension
causing
flattening
or
Computed tomography
deformity of the nodes. On Doppler sonography, there is
increased
perfusion
with
preservation
of
normal
On CT, normal lymph nodes are well defined round or
architecture, similar to the changes in inflammatory nodes.14 Nodal metastases are often secondary to
oval structures of similar attenuation to muscle. They
squamous cell carcinoma and are usually hyperechoic
contrast medium and the fatty hilus may be seen.
but may be inhomogeneously echogenic with loss of the echogenic hilus. Extranodal spread occurs in squamous cell carcinoma and the outlines become indistinct and there is central necrosis with liquid areas within the node. Thyroid carcinoma metastases may not enlarge nodes as the nodes are infiltrated peripherally. Small areas of punctate calcification may be seen (psammoma bodies)
in metastases
thyroid
cancers .
from papillary and medullary
The
use
of
colour-coded
duplex
sonography may be helpful as these metastases have increased
vascularity
and
this
can
be
demonstrated
in lymph node metastases as small as 3 mm. The nodes are hypoechoic with an increased number of vessels in relation to the
nodal size and
almost
cystic in
appearance. The sensitivity of ultrasound in the diagnosis of nodal metastases varies from 75 to 92 percent with a specificity 19. 20, 21,22 The specificity is reduced of 63 to 91 percent. because of the difficulty in differentiating between the enlarged nodes of reactive hyperplasia and metastatic
enhance slightly more than muscle following intravenous Size is used to determine normal nodes in both CT and MRI if the nodes are homogeneous and clearly demar cated. Nodes greater than 1 em, except the jugulodigastric nodes which may be up to 1.5 em in length, are considered abnormal. Alternatively an axial diameter of 11 mm is used for the jugulodigastric nodes and 10 mm elsewhere. Groups
of
smaller
nodes
are
also
suspicious
with
numerous nodes 8-15 mm in length or 8-9 mm in axial diameter suggestive of malignancy. The shape of the node may also be helpful and some authors use the ratio of the length to the transverse diameter, with reactive nodes being oval with ratios greater than two, whereas malignant nodes tend to be rounded with a ratio less than twO?8 Tuberculous
lymphadenitis
(Figure 138.4) can be
unilateral or bilateral and usually involves the posterior triangle
or
internal
jugular
nodes.
The
nodes
are
homogeneous in the acute phase and enhance homo geneously,
but
develop
low attenuation centres
with
peripheral enhancement later. Despite the large area that
disease. The shape of the nodes is an important criterion for diagnosing metastatic disease, but there is overlap between echogenicity and shape in pathological nodes. The use of US-guided fine-needle aspiration has proved very helpful in histological differentiation. Nonpalpable nodes can be sampled and sensitivity rates of between 50 and 77 percent with 100 percent specificitlO' 23, 24 have been reported. Various patterns of perfusion have been described
on
Doppler
sonography.
These
included
peripheral increased perfusion, focal absence of perfusion, absence
of
central
vessels
and
chaotic
patterns
of
perfusion.25 The use of power Doppler increases the sensitivity (83 percent) and specificity (98 percent) for the detection of metastatic nodes compared to the use of size criteria
alone
percent)
(sensitivity
and if the
66
percent,
specificity
sensitivity improves to 92 percent with
specificity,26 although lower
figures
with
92
two criteria are combined, the other
the
LOa percent
authors27 have reported
combined
criteria
giving
a
sensitivity of 77 percent, specificity of 86 percent and accuracy of 82 percent.
[****/***]
Vascular infiltration by malignant nodes is uncommon occurring in about 5 percent of metastatic nodes and is well demonstrated by sonography. The normally echo genic wall of the carotid becomes hypoechoic and this has
Figure 138.4
been demonstrated in 90 percent of cases with vascular
contrast medium. The nodes are of low attenuation with an
invasion. Vascular invasion is more likely if the length of
enhancing periphery.
Tuberculous nodes.. CT following intravenous
Chapter 138 Examination and imaging of the neck
I 1761
may be involved, there is minimal if any infiltration of the adjacent
fat
planes
and
this
may
help
distinguish
tuberculous from malignant nodes. In the chronic phase they may calcify. Nodal staging is very important for the appropriate management
of
head
and
neck
tumours.
Clinically
negative, but tumour-positive nodes are detected in 7-19
approximately
percent
of
cases.
This
is
only
significant if it alters management or the stage of the disease. The diagnosis of squamous cell nodal disease on CT is based on the size, shape and presence of central necrosis. The most reliable indicator of malignancy is 'central necrosis' where the node has a low attenuation centre and this is irrespective of nodal size. Tumour deposits tend to infiltrate from the cortex into the medulla of the node, which becomes lower in attenuation due to a mixture of tumour necrosis, interstitial oedema, fibrosis and viable tumour. If the area of involvement is greater than 3 mm, it can be identified on contrast enhanced CT as a node with irregular enhancement of the periphery and a low attenuation centre. The differential diagnosis
of
these
apearances
includes
fatty
hilar
metaplasia (a response to chronic nodal infection) or a nodal
abscess,
and
differentiation
may
be
difficult.
Figure 138.5
Metastatic squamous cell cancer. Lymph nodes
irregular soft tissue stranding indicating extracapsular spread (arrows).
Contrast-enhanced CT can identify enlarged or necrotic nodes but normal
cannot differentiate minimal enlarged or
size
nodes
containing
micro metastases
from
attenuation seen in malignant nodes is not all due to necrosis and is made up of mixed components and
reactive nodes, unless there is extracapsular spread of
therefore has heterogeneous signal on both Tl and T2W
tumour or necrosis.
sequences. It may not be demonstrated on noncontrast
Extracapsular nodal spread of tumour indicates a poor
TIW sequences, although it is seen as focal areas of high
prognosis with a reduction in overall survival of 50
signal on T2W sequences. It is best shown using TIW
percent with a ten-fold increase in the risk of neck
contrast-enhanced sequences where there is central low
recurrence compared with patients without extracapsular
signal with peripheral enhancement. This enhancement
On CT, it is seen as an enhancing rim that is
may be better appreciated against the high signal of the
spread.
irregular and thickened with infiltration into the adjacent
surrounding fat if fat suppression sequences are used and
(Figure 138.5). This represents macroscopic spread.
this also improves the visualization of extracapsular
fat
Microscopic spread is found in 40 percent of nodes less
spread of tumour. The cystic nodes of papillary thyroid
than 2 cm, in 50 percent of nodes between 2 and 3 cm
carcinoma
rising to 75 percent of nodes greater than 3 cm in
sequences.
are
high
signal
on
both
Tl
and
T2W
The size of nodes is used as a criterion in both CT and
diameter. Nodal metastases from papillary thyroid tumours may
MRI, and the use of MRI has not really improved the
be homogeneous similar to reactive nodes, cystic or may
diagnostic accuracy for metastatic nodes. Using size, the
show intense enhancement after contrast medium and
false-negative and false-positive rate is between 10 and 20
may have punctate calcifications. Nodal calcification may
percent. If size and internal architecture are combined,
be seen in tuberculosis or sarcoid and also in mucin
there is an improved diagnostic accuracy. Using a size of
secreting tumours and treated lymphoma.
1 cm or abnormal architecture to indicate a positive node,
Curtin et al.29 found CT has a negative predictive value of
Magnetic resonance imaging
84 percent (MRI, 79 percent) and a positive predictive value of 50 percent (MRI, 52 percent). Changing the size criteria to 5 mm gave a negative predictive value for CT of
Normal nodes are of similar signal intensity to muscle on
94 percent with a lower positive predictive value of 44
TIW and slightly higher signal than muscle on T2W
percent. CT performed slightly better than MRI in this
sequences.
study.
They enhance slightly more than muscle
following intravenous contrast medium. -Reactive nodes are usually homogeneous low signal on
[***]
Recently, however, the use of superparamag
netic iron oxide
(SPIO) particles as lymphangiographic
agents in MRI has been developed and does offer
T1Wand high signal on T2W.
potential for improvement. The small iron oxide particles
on TIWand high signal on T2Wj
are injected intravenously and are taken up by the
1762 I
T
PART 14 THE NECK
reticuloendothelial system in normal or inflamed lymph
using this technique found a sensitivity of 86 percent and
nodes.
a specificity of 100 percent for metastatic nodes, although
These
nodes
show
signal
drop
off on
T2*
sequences, whereas metastatic nodes do not show this
micrometastases may be missed.
effect
et aI.31 found the incidence of micrometastases in patients
(Figure 138.6).
A recent study by Mack et aI.30
[***] Van den Brekel
with head and neck cancer was high (59 percent) and in 25 percent of patients only micrometastases were present. So although the use of MRI with SPIO particles may help in altering the extent of surgery, it is unlikely that it can be used to substitute for staging neck dissection.
Positron emission tomography Positron emission tomography is used to stage primary
squamous
cell
carcinoma
including
the
nodal
involvement and distant metastases and for the detection of recurrent tumour. The reported sensitivity for nodal detection is 80-96 percent with specificity of 90-94 percent19, 32, 33 and in a recent studr3 using PET-FDG, PET was superior to both MRI and CT for the detection
of cervical nodes metastases
(Figure 138.7).
The use of
positron emission tomography in patients with nodal metastases in contentious.
the neck and no
obvious primary
is
Greven et aI.34 suggested there was no
benefit because of a high false-positive rate (46 percent), whereas other authors35,36 found it helpful in patient management. Positron emission t.omography does appear to be the most sensitive method of detecting recurrent tumour, particularly following radiotherapy.37, 38,39 Other tracer techniques include the use of pentavalent dimercaptosuccinic
acid
(Tc-99m
(v)
DMSA)
and
indium-1ll-octreotide for imaging medullary thyroid carcinoma. Both of these techniques can identify the primary tumour, but the ability to identify nodal disease is limited. One study by Kurtaren et al.40 comparing the two techniques found indium-111-octreotide identifed 71 percent of the primary tumours (pentavalent DMSA, 58 percent),
but neither technique identified the nodal
metastases, all of which were less than 2 mm. Other studies41 have compared indium-1ll octreotide, FDG PET and pentavalent DMSA in the follow-up of patients
with suspected recurrence of medullary thyroid carcino ma and found FDG-PET was the most useful, and other autho rs have found the combination of indium-ll1octreotide with the anatomical imaging of CT or MRI to be advantageous.42
The use of technetium-99m-labelled antibodies carcinoma43 Figure 138.6 Patient with squamous cell cancer of the tongue with a palpable mass on the left side of the neck. (a) Axial T2*
for
nodal
has
also
metastases been
in
evaluated
monoclonal
squamous with
cell
similar
sensitivity and specificity to CT and MRI, but there was a high. false-negative rate due to failure to identify
showing the palpable mass in the parotid (black arrow) and node anterior to the jugular (white arrow). (b) Axial T2* following injection of ultra-small super paramagnetic iron oxide
micrometastases.
(USPIO) particles. Node in the parotid shows no signal change
they share with CT and MRI, and it us unlikely that any of
All the tracer techniques are limited in their ability to identify micrometastases in lymph nodes, a limitation
(malignant). Node anterior to jugular shows homogeneous signal
these imaging methods will replace neck dissection for the
drop out (benign).
adequate staging of nodal disease.
Chapter
Figure
1763
138 Examination and imaging of the neck I
138.7
Squamous cell carcinoma of the maxillary
antrum. Metastatic lymph nodes. (a) Axial CT of the face. Antral tumour with destruction of the anterior wall. (b) Axial CT of neck with an enhancing node lying anterior to the jugular vein (arrow). (c) Fused positron emission tomography and CT image of cervical node confirming enlarged node is metabolically active and not a reactive node.
KEY POINTS •
1-
Bistory and clini�al examination remain th e '
./ Patients with an undiagnosed neck mass should
patient with -a lump in the neck. CT scanning_ can improve the sensitivity and sp ecificity of diagnosing metastatic - neck -
./ In young patients imqging should be with ultrasound
most important part of the investigation of a
•
undergo imaging. initially. ,/' Patients with malignant disease should have nodal
- disease compared with clinical examination. •
Best clinic'al practice
imaging, although those with T1 tumours or tumours
Ultrasound.;guided fine needle aspiration
with a low prevalence of nodal metastases may not
cytology does not increase the sensitivity, but
is 100 percent specific.
require this. ,
\
__ , _._.J _____
_..
1764 I
PART 14 THE NECK
examination. Archives of Otolaryngology - Head and Neck
Deficiencies in current knowledge and areas for future research
Surgery. 1997; 123: 149-52. 14.
Sakai 0, Curtin HD, Romo LV, Som PM. Lymph node pathology. Benign proliferative, lymphoma, and metastatic
The aim of future research should be directed towards
disease. Radiologic Clinics of North America. 2000; 38:
the detection of low volume metastic disease. This includes evaluation of ultrasound-guided fine needle
979-98. 15.
Hao SP, I\lg SH. lVIagnetic resonance imaging versus
aspiration (FI\lA). other contrast agents with MRI, CT and
clinical palpation in evaluating cervical metastasis from
PET scanning and finally more specific labelled
head and neck cancer. Otolaryngology - Head and Neck
monoclonal antibody techniques.
Surgery. 2000; 123: 324-7. 16.
Flemming 10, Cooper JS, Henson DE, Hutter RV, Kennedy BJ, Murphy SP et 01. American Joint Committee on Cancer Staging manual, 5th edn. Philadelphia: Lippincott Raven, 1997.
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and neck lesions based on their space of origin. 1. The
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Yusa H, Yoshida H, Ueno E. Ultrasonographic criteria for
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van den Brekel MW, Castelijns JA, Stel HV, Golding RP,
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Merritt RM, Williams MF, James TH, Porubsky ES. Detection of cervical metastasis. A meta-analysis comparing computed tomography with physical
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SaKaguchi T, Yamashita Y, Katahira K, I\lishimura R, Baba Y, Arakawa A et 01. Differential diagnosis of small round
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cervical metastases by d u a l-head positro n e miss i o n tomogra phy. Oral Oncology. 1 99 9 ; 3 5 : 390-4. 3 6.
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D i e h l M, Risse JH, B ra ndt- M a i n z K, Dietle i n M, Bohus lavizki KH, Matheja P et 01. Fl u orine- 1 B
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fl uorod eoxyg I ucose positro n e missio n tomog ra phy in
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i ma g i ng moda l ities (CT, M R I , US) i n lymph node sta g i n g of head a nd neck cancer. European Journal of Nuclear Medicine.
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" . . .. --1 - --
139 Neck trauma
JOHANNES J FAGAN AND ANDREW J NICOL
Introducti on
1766
Exploration of the neck: General principles
1774
The trauma patient: General principles
1766
Summary
1774
Aetiological classification
1768
Key points
1774
Zones of the neck
1768
Deficiencies in current knowledge and areas for future
1768
cervical injuries
1774
research
Mandatory versus s elective exploration of penetrating
1775
References
1770
Specific injuries
The data in this chapter are supported by a Medline search using the
key words tralima, cervical, trachea, esophagus and
vascular.
INTRODUCTION
THE TRAUMA PATIENT: GENERAL PRINCIPLES
The issue dominating discussion on the management of
Primary survey (survival assessment)
penetrating neck trauma over the past few decades is whether penetrating neck injuries require mandatory exploration. There has been a distinctive paradigm shift from mandatory
exploration,
towards more selective,
conservative management based on clinical evaluation and specialized investigations. Introduction of cliagnostic
The primary survey is an initial assessment of factors that cause early deaths in trauma patients. It focuses on factors such as hypoxia, hypovolaemia, tension pneumothorax and head injury.
tools such as flexible endoscopy, high quality oesophago graphy, angiography and duplex Doppler have improved nonoperative evaluation of aerodigestive and vascular injuries. The realization that certain injuries may
be
AIRWAY AND CERVICAL SPINE PROTECTION The patient is examined for evidence of airway obstruction,
treated nonoperatively and given the management of
which may present as stridor and use of accessory muscles.
selected arterial injuries by endovascular techniques, has
A chin
further promoted the concept of selective. exploration of
A cervical collar or sandbags should be used to stabilize the
lift and jaw thrust procedure should be performed.
the neck. There has been an increased awareness of
neck until cervical spine injury is excluded. Patients with
carotid injuries in respect to blunt cervical trauma and the
Glasgow
need to study the carotid artery by means of angiography
intubation to protect the airway. Major facial fractures,
and/or
in particular mandibular
duplex
Doppler
in
patients
unexplained neurological signs.
presenting
with
coma scores
haematomas may
(GCS)
of
fractures,
<8
usually
require
and large cervical
compromise the airway.
[Grade C]
Chapter 139 Neck trauma
Patients with transcervical gunshot wounds may not have airway problems initially, but must be closely observed as airway obstruction can rapidly develop. [Grade D] An endotracheal tube may sometimes be inserted directly into the trachea through the site of a penetrating cervical injury. Cricothyroidotomy must be considered if intubation fails. It should be converted to a formal tracheostomy subse quently, as the small tube is difficult to keep clean and in order to prevent subglottic stenosis. [Grade D] BREATHING
The chest should be examined with respect to movement and air entry. Tension pneumothorax presents with hypoxia, restlessness, hyper-resonance to percussion, decreased air entry, contralateral tracheal shift and elevated jugular venous pressure. It is decompressed by needle thoracocentesis with a large bore needle placed through the second intercostal space in the midclavicular line, followed by insertion of a chest drain. A large haemothorax is identified by dullness to percussion and decreased air entry, and is also managed with an intercostal drain. These are clinical diagnoses of life threatening conditions and immediate intervention is mandated before x-rays are obtained. CIRCULATION AND PERFUSION
Two high-flow lines with 14-gauge cannulae are inserted in the antecubital fossae. The line should not be inserted on the side of massive bleeding from a vascular injury, for if there is a venous injury, the fluids delivered will be bled out. In the shocked patient, start with 2 L of crystalloid and proceed to emergency blood (0 negative) if the blood pressure does not improve and crossmatch blood. A shocked patient with warm peripheries may have neurogenic shock secondary to spinal cord injury. Active bleeding from a cervical wound may be controlled with a compressive dressing or digital pressure. Failing this, a large Foley catheter may be inserted into the wound, the bulb inflated and the catheter crossclamped to stop blood pouring through the catheter. This can be a very effective form of haemostasis, particularly with bleeding from the subclavian and cervical vessels. [Grade C] The patient should remain recumbent, or the neck wound must be covered with an occlusive dressing when the patient sits up, to prevent air embolism. DISABILITY
The GCS and pupil size are recorded, and power in the limbs assessed. EXPOSURE
All clothes are removed in order to avoid mIssmg associated injuries and the patient is kept warm.
I 1767
ADJUNCTS TO PRIMARY SURVEY
Adequate monitoring, including electrocardiogram (ECG), pulse oximetry and noninvasive blood pressure monitoring is instituted. A rectal examination to exclude a urethral injury should be performed prior to insertion of a urinary catheter. The haemoglobin level, blood glucose and arterial blood gas are checked. Essential x rays are requested. In the polytrauma patient this comprises cervical spine, chest x-ray (CXR) and pelvic x-rays. In a patient with isolated penetrating neck trauma, a cervical spine and CXR will suffice. Nonurgent x-rays should be requested only on completion of the secondary survey. Haemo- or pneumothorax, pneumomediastinum (tracheal or oesophageal injury) and widened media stinum should be excluded. The mediastinal width on a supine CXR should not exceed 8 cm. [Grade C] A widened mediastinum is suggestive of a major intrathor acic injury and must be investigated further. Cervical spine x-ray is used to exclude spinal column injury and prevertebral air (pharyngeal or oesophageal injury) .
Secondary survey A detailed head-to-foot examination of the patient should be conducted. In firearm injuries, the entrance and exit wounds must be noted and the tract of the projectile determined to identify which anatomical structures may have been injured. If an exit wound is not present, then x rays are obtained (anteroposterior and lateral) to locate the bullet so that the tract of the bullet can be determined. The cranial nerves should be examined and Horner's syndrome excluded. Note the presence of large cervical haematomas, subcutaneous emphysema, the jugular venous pressure, the presence of blood in the nasogastric tube and tenderness over the mandible. Wounds should not be probed as this may result in massive bleeding from an arterial injury. [Grade D] The peripheral pulses should be checked for discrepancy or absence. The distal carotid and superficial temporal artery pulses should be exam ined and bruits should be listened for. Again exclude a haemo/pneumothorax and listen to the heart sounds. The abdomen and pelvis should be examined, followed by a full neurological examination during which spinal cord and brachial plexus trauma are excluded. Note the presence of hemiplegia or Brown-Sequard syndrome (hemitransection of spinal cord). The patient should be log-rolled in order that the back can be examined for trauma.
HISTORY
Take a history with specific reference to the nature of the trauma. Enquire about symptoms related to oesophageal injury (haemoptysis, haematemesis, dysphagia and ody nophagia) and recurrent laryngeal nerve or laryngeal
1768
I PART 14 THE NECK
injury (dysphonia, stridor), Past medical and surgical history are documented, as well as the time of the patient's last meal.
Zone III
FURTHER INVESTIGATIONS
Any further x-rays that are required after the secondary
' Zon
survey are now completed. Special investigations such as angiography, computed tomography (CT) scan, ultra sound and gastrograffin/barium studies may now be performed in a haemodynamically stable patient.
FULL DOCUMENTATION
All injuries are documented and the patient is referred for definitive care.
1 Grade D]
Figure' 39.1
AETIOLOGICAL CLASSIFICATION Unlike stab wounds and low velocity gun shot wounds, close-range
shotgun,
rifle
and
bomb
injuries
cause
extensive soft tissue trauma: •
- stabs; - gun shot wound (GSW):
•
blast;
•
blunt.
low velocity;
•
high velocity;
•
shotgun;
cartilage to angle of mandible; zone III, angle of mandible to base of skull. Redrawn from Ref. 1, with permission.
MANDATORY VERSUS SELECflVE EXPLORATION OF PENETRATING CERVICAL INJURIES
penetrating:
•
Roon and Christensen classification, Zone I,
sternal notch/clavicle to cricoid cartilage; zone II, crico id
Before the Second World War, nonoperative treatment of penetrating neck injuries was associated with a mortality of
15-18 percent. 3 Following experience in the Second
World
War,
Bailey
proposed
early
exploration
1944. Coupled with the
introduction
and
of
antibiotics
tracheostomy,
exploration reduced the mortality rate to patients not explored immediately was
Roon and Christensen's classification) is most commonly used for description of the site of cervical trauma
(Figure 139.1). The neck contains three principal anatomic
components, i.e. vascular (carotid, vertebral and sub
clavian arteries; jugular and subclavian veins), digestive (pharynx and oesophagus) and respiratory (larynx and trachea). All three zones contain major vascular and aerodigestive structures. However, injuries to zones I and are
both
diagnostically
and
surgically
more
challenging, According
to
a
second
early
7 percent.4 In
1956, Fogelman and StewartS reported that mortality for 35 versus 6 percent
ZONES OF THE NECK
III
for
penetrating neck injuries in
classification
system
by
Monson,2 the transition between zones I and II is at the
for
those
who
concluded that
had
been
explored
promptly.
They
all penetrating neck wounds that violated
the platysma required surgical exploration. Mandatory exploration of the neck whenever the platysma muscle had been breached became common practice. Stone questioned
the
need for mandatory
civilian injuries in controversy
about
exploration
for
1963.6 Since that time there has been the
relative
merits
of mandatory
exploration versus selective exploration for low velocity gunshot and sharp penetrating wounds of the neck. The majority of trauma centres now advocate some form of selective conservative management. 7
sternal notch. Both retrospective and prospective studies and review articles continue to compare results of studies without
considering
differences
in
the
classification
Mandatory exploration
systems used.2 Although transcervical injuries are asso ciated with vascular or aero digestive injuries in
73-100
Proponents of mandatory exploration of stable patients
percent of patients,2 neither classification system takes
with low v�locity gun shot wounds and stab wounds that
cognizance of transcervical injuries.
breach the platysma muscle, consider that the risk of
(H]
Chapter
missing an unsuspected vascular or aerodigestive injury outweighs the morbidity and the cost of negative exploration. They point to the unreliability of clinical evaluation, that diagnostic studies do not have 100 percent sensitivity to detect oesophageal and vascular injuries, low morbidity associated with negative explora tion, additional time and effort associated with expectant observation, and the significant morbidity and mortality associated with delayed detection and repair of oesopha geal injury. Yet, vascular and oesophageal injuries can be missed when the neck is explored without the assistance of preoperative angiography, oesophagography and/or oesophagoscopy.
Selective exploration Protagonists of selective exploration quote the high rate (36-89 percent) of negative mandatory explorations,7, 8, 9 good sensitivity and specificity of special investigations such as angiography, Doppler, barium swallow, rigid oesophagoscopy and flexible laryngotracheobroncho scopy; expense of prolonged hospitalization for negative explorations; the fact that many injuries that are detected at mandatory exploration, such as thyroid, pharyngeal and certain venous injuries, may be treated conservatively; and that neck exploration leaves an unsightly scar. Negative exploration in centres practising selective exploration ranges between 9 and 62 percent.8, 9,10 The safety of selective conservative management of penetrating cervical injuries is apparent in the results of the four prospective studies summarized in Table 139.l. Mortality in the studies by Campbell and Robbsll and Ngakane et al.12 was not attributable to cervical injury, but was due to associated trauma. With a selective approach, severe active bleeding, hypovolaemic shock not responding to resuscitation, a rapidly expanding haematoma, a large blowing wound and major haemoptysis are indications for emergency surgery. The remaining patients are assessed clinically and appropriate radiological and endoscopic investigations are undertaken if there is a suspicion of visceral injury. While the importance of early diagnosis of occult vascular injuries is debatable, delayed diagnosis of oesophageal perforations is accompanied by increased Table
139.1
139 Neck trauma
I 1769
4 morb·d· 1 Ity and morta 1·Ity.1 3' 1 Because of concerns about reliability of physical assessment alone, some protagonists of selective exploration advocate mandatory oesophageal and vascular studies, while others have employed active observation with special investigations only if the clinical examination is equivocal.
ACTIVE OBSERVATION WITH SELECTIVE SPECIAL INVESTIGATIONS
Demetriades et aC reported in a prospective study of 335 penetrating neck injuries that a combination of clinical and selective investigations yielded a specificity of 85 percent and sensitivity of 100 percent to identify clinically significant vascular and aerodigestive tract injuries. They advocate emergency exploration for the absolute indica tions for neck exploration noted previously, but do not consider soft signs such as shock responding to resuscitation, minor active bleeding, haematoma, dys pnoea, subcutaneous emphysema, hoarseness, dysphagia or minor haematemesis to be absolute indications for exploration. These patients are assessed individually, taking into account the direction of the injury tract and the severity of the signs. If the tract courses away from the larynx, trachea, oesophagus and carotid sheath, then no further investigations are undertaken. If the tract is directed towards the midline, then contrast oesophago graphy and/or endoscopy is carried out. CXR is requested for suspicion of chest pathology. Only 38 percent of patients with surgical emphysema required exploration. They conclude that selection for exploration can be decided on the basis of careful initial and repeated clinical examinations.7 Hall et al.3 supported this approach in a report on the safety of active observation of children with penetrating injuries in zone II. Although transcervical gunshots are twice as likely to have visceral/vascular injury as gunshots that do not cross the midline (79 versus 31 percent, p 0.02), 80 percent may be safely managed nonoperatively by active observation with selective special investigations.1s Evaluation of the neck with spiral CT scanning shows promise.16 When a CT scan in the stable patient reveals that the trajectory courses away from vital structures, then employment of invasive studies would seem superfluous (Figure 139.2). [***J =
Selective conservative management of penetrating cervical injuries.
Series '
(0J0)
Negaliveexp [orations (010)
Observed (Old)
Mortality (Old)
77
62
15
29
0
108
24
0
82
1.2
20
15
-No. patientS' O
Narrod and Moore1 Campbell and
Explored
Robbs11
2 Ngakane et 01.1 Demetriades et
ae
109 335
97
1.8
80
0
_i
_____
�__
1770 I
PART 14 THE NECK
Cervical trauma
Active observation
Emergency surgery Severe active bleeding Shock not responding to fluid resuscitation Expanding haematoma Large blowing wound Major haemoptysis
Clinically normal
Clinical suspicion
Angiogram
Oesophagogram Oesophagoscopy
Bronchoscopy Laryngoscopy
Large haematoma
Odynophagia
Tension pneumothorax
Pulse deficit
Dysphagia
Persistent air leak
Bruit
Saliva leak from wound
Pneumomediastinum
Widened mediastinum
Blood in NGT
Subcutaneous emphysema
High velocity injury
Haematemesis
Dysphonia
Stroke
Subcutaneous emphysema Prevertebral air on lateral C-spine Pneumomediastinum
Figure 139.2
Selective surgical exploration algorithm.
SPECIFIC INJURIES Pharyngeal injuries Hypopharyngeal injury should be suspected in penetrat ing injuries in zone II, particularly in the presence of dysphagia, odynophagia, voice change, haemoptysis, haematemesis and surgical emphysema. Flexible naso pharyngoscopy may reveal oedema, blood in the pharynx, or the perforation may be visible if located in the upper part of the hypopharynx. Oesophagography is unreliable, while direct pharyngoscopy should reveal all the in juries. I7 In a retrospective study of 47 hypopharyngeal injuries, Stanley et al. I8 reported no complications in supraarytenoid segment injuries, as opposed to a 22 percent complication rate for infraarytenoid hypophar yngeal injuries. They conclude that upper segment injuries can be managed nonoperatively as it is capacious, has a low intralumenal pressure and is enveloped by both the middle and inferior constrictor muscles. The lower segment funnels into the cricopharyngeus segment and is less capacious, has higher intralumenal pressure and is surrounded only by the inferior constrictor muscle and should be managed like oesophageal injuries by explora tion, repair and drainage.I8 [**] [Grade C]
Oesophageal injury Symptoms of penetrating InJuries of the oesophagus include dysphagia, haematemesis and odynophagia.
Clinical findings include surgical emphysema and salivary leak. Evidence of retropharyngeal air, retropharyngeal oedema, haematoma, tracheal deviation and pneumome diastinum may be revealed by x-ray.
ACCURACY OF DIAGI'JOSIS OF OESOPHAGEAL INJURY
Clinical evaluation has a sensitivity of 80 percent (50 for stabs, 100 percent for GSWs), a specificity of 64 percent and accuracy of 72 percent. I3 Sensitivity of barium swallow has been reported as between 48 and 100 percent, and of oesophagoscopy, between 40-90 percent. I9, 20 In a prospective study, Weigelt et al. 13 reported that barium swallow had 89 percent sensitivity, 100 percent specificity and accuracy of 94 percent (anteroposterior and lateral views with cineradiography); flexible oesophagoscopy was unreliable, particularly in the proximal oesophagus, as the mucosa cannot be effaced as with rigid oesophagoscopy; rigid oesophagoscopy had a sensitivity of 89 percent, specificity of 95 percent and accuracy of 94 percent; and a combination of oesophagography and oesophagoscopy had a sensitivity of 100 percent. Wood et al.21 reported sensitivity of oesophagography of 100 percent and specificity of 96 percent, and cautioned that oesophageal and vascular injuries can be missed on neck exploration. 2 However, Flowers et al.2 and Srinivasan et al.23 have more recently reported sensitivities of 100 percent, and specificities of 96 percent and 92.4 percent, respectively, for flexible oesophagoscopy to detect the presence of penetrating injury of the oesophagus. Because gastro graffin, if aspirated, may induce serious pulmonary
Chapter 1 39 Neck trauma
problems, it should not be used in trauma patients. [***] [Grade D]
IMPORTANCE OF TREATMENT DELAY
Early recognition and treatment of oesophageal perfora tion is the key to a favourable outcome. Missed oesophageal injury has high morbidity and mortality. Delayed intervention of > 12 hours for iatrogenic oesophageal injury has a mortality rate of 40 percent as opposed to 9 percent for < 12 hours.13 In a retrospective multicentre study, Asensio et al.14 compared the outcome of patients undergoing diagnostic studies, with patients taken straight to the operating theatre. The study revealed a significantly increased oesophageal complication rate (41 versus 19 percent) and length of intensive care unit (lCU) stay with patients having diagnostic studies. They concluded that time delays in instituting active manage ment incurred by investigations associated with selective exploration can lead to increased morbidity and mortal ity. This report does not distinguish between the cervical and thoracic oesophagus. Whether their conclusion applies to isolated cervical oesophageal injury is therefore open to question, particularly in view of reports of the successful outcome of small cervical oesophageal injuries treated conservatively. However, centres practising selec tive management of penetrating neck injuries should make rapid diagnosis and definitive repair a priority. [***] [Grade C]
11771
SURGICAL TECHNIQUE
The majority of oesophageal Injuries can be repaired primarily. The remainder can be repaired by resection and anastomosis, or managed by drainage alone. Intravenous antibiotics and enteral or parenteral nutrition should be instituted. Adequate drainage, suction or dependent, is important as even with a technically sound repair, 13 percent develop fistulae.9 If part of the oesophagus has been blown away, if mediastinitis or sepsis is already present, or if oesophageal injury extends into the chest, then a lateral cervical oesophagostomy may be required. [Grade C] There is no evidence to favour a double or single layer repair. Local muscle flaps, such as strap or sternocleidomastoid muscle, can be used to buttress the repair or used as an interposition between an oesophageal injury and a vascular or tracheal repair.25 Barium swallow is undertaken on day 5-7, as 50 percent of postoperative oesophageal fistulae are asymptomatic and detected only on contrast study.9 Should a fistula or sinus be present, the drain is retained. [**]
COMPLICATIONS OF OESOPHAGEAL INJURY
Oesophagocutaneous fistulae develop in 9-28 percent of oesophageal trauma.25 They are more common with gunshot wounds, but generally close spontaneously. Oesophagotracheal fistulae need to be repaired with interposition of a muscle flap. More serious complica tions include abscess formation, mediastinitis, septicae mia and death. [**]
DO ALL OESOPHAGEAL I"'JURIES NEED TO BE EXPLORED?
Recommended treatment of oesophageal injuries varies from observation to simple repair of the wall, with or without drainage of deep neck spaces, to primary diversion of flow of saliva to the skin by means of partial or total exteriorization procedures. Wound site, size, mechanism of injury, time delay until presentation, associated injuries, availability of and expertise with diagnostic tests such as oesophagography and oesophago scopy, and availability of theatre time all play a role in determining the management of oesophageal injuries. All high velocity injuries should be explored. The manage ment of stab wounds and low velocity GSW s is more contentious. Generally it is recommended that if barium swallow is positive or equivocal, treatment should proceed to rigid oesophagoscopy; if positive, then the oesophagus is explored. [Grade D] However, Ngakane et al.12 concluded from a prospective study of penetrating visceral injuries of the neck, that should oesophagography reveal minimal leakage of contrast, then patients can be managed conservatively; oesophagography is repeated on day 5, before commencing oral feeding. Similar favour able outcomes of small cervical oesophageal perforations treated conservatively have been reported by MandaI et al.24 and others. [***]
�--
Tracheal injury Cervical tracheal injuries are relatively uncommon and are frequently associated with oesophageal, vascular or spinal injuries. The initial priority is to secure an airway. The trachea can sometimes be readily intubated through a blowing wound in the neck. Tracheotomy is appropriate in the presence of laryngeal trauma to protect the injured larynx, when it is not possible to safely pass an endotracheal tube, or in the presence of quadriplegia necessitating ventilatory support. Earlier teaching that nasotracheal or orotracheal intubation should be avoided as it may aggravate an existing tracheal injury or cause a false passage, appears to have been overcautious.26 Distal tracheobronchial disruptions can be bypassed under vision ,with an introducer passed through a rigid bronchoscope, or by intubating over a flexible bronchoscope. Symptoms of tracheal injury include a blowing wound, surgical emphysema, haemoptysis and hoarseness. CXR may reveal surgical emphysema and pneumomediasti num. Tracheobronchoscopy can be useful to assess the injury, but the diagnosis is usually readily apparent on exploring the neck for associated injuries.
1772 I
PART 14 THE NECK
Minor tracheal injuries in patients not otherwise requiring cervical exploration can be managed expec tantly. In cases of marked surgical emphysema, a tracheotomy might expedite recovery. Tracheal repair is achieved with interrupted sutures. When there is an associated oesophageal or vascular injury, then the repair can be bolstered with a muscle flap. Tracheotomy or an endotracheal tube may, in selected cases, be used to protect the tracheal repair. [*] [Grade C]
Vascular injury The common carotid artery is the most frequently injured vessel, accounting for 22 percent of vascular injuries?7 Hard signs of vascular injury are an expanding haema toma, external haemorrhage, absent or diminished distal pulses, ischaemia, neurological deficit or coma. Current debate centres on evaluation of the asymptomatic patient and optimum treatment of vascular trauma. The majority of published series are small, retrospective and from single centres.
CLINICAL EVALUATION
The reported accuracy of clinical evaluation varies widely. Sclafani et al.28 reported a specificity of 80 percent and sensitivity of 61 percent, and Meyer et al?9 reported an accuracy of 68 percent.7 Demetriades et al.30 reported a sensitivity of 100 percent for clinical detection of significant vascular injury. The widely disparate results may reflect shortcomings of retrospective data collection and the lack of emphasis placed on clinical decision making in centres with a bias towards routine angio graphy or exploration.
INVESTIGATIONS
The gold standard investigation is four-vessel arch angiography with selective catheterization. Angiography has the following benefits: identification of the site of injury; identification of subclinical vascular injury, including vertebral artery trauma; provision of a road map for the surgeon; delineation of the extent of crossover circulation through the Circle of Willis; and identification of injuries amenable to endovascular intervention. Vascular injuries in zone II are readily exposed and with zone II penetrating injuries, the chance of detecting an asymptomatic arterial injury by angio graphy is less than 1 percent, which approaches the complication rate of angiography? With penetrating injuries in zone II, angiography may therefore be employed selectively for patients, with clinical suspicion of a vascular injury or when the tract of a gunshot wound passes close to vascular structures. Vascular injuries in zones I and III can be difficult to assess clinically. Surgical
exposure and control are more challenging. Hence, preoperative angiography of suspected vascular injuries in zones I and III is generally recommended. Demetriades et al.30 reported that colour-flow duplex Doppler (CFD) imaging, when combined with clinical examination, had a sensitivity of 91 percent and specificity of 99 percent to detect vascular injury. CFD only missed an intimal tear, which did not require treatment.30 CFD, however, requires trained personnel, is not always readily available and is best avoided if there is a suspected cervical column injury. The origins of cervical arteries from the aortic arch and the arteries close to the skull base, as well as the vertebral arteries, may not be well demonstrated and it is difficult to identify individual branches of the external carotid artery.
CAROTID REVASCULARIZATION VERSUS LIGATION
With the introduction of vascular surgical techniques during the Korean War, primary repair of carotid artery injuries was recommended. In 1973, Bradley31 concluded from two autopsy studies which revealed haemorrhagic infarction of the brain, that revascularization should not be attempted in patients with severe neurological deficits. Fear about converting an ischaemic into a haemorrhagic infarct by reperfusion and worsening the neurological outcome has since been a major concern to vascular surgeons, and has fuelled the dilemma of ligation versus reperfusion. In 1978, Liekwig and Greenfield32 showed that patients with severe neurological deficits just short of coma had significantly better results with reperfusion. This was supported by Brown et al.33 in 1982 who showed that revascularization in patients with preoperative coma (lack of meaningful response to verbal or noxious stimuli) was indicated when ischaemia had only been present for a short period of time prior to surgery (Figure 139.3).
PSEUDOANEURYSMS AND INTIMAL INJURY
Pseudoaneurysms (focal, eccentric widening of the lumen extending beyond the arterial wall), intimal defects and intimal flaps, have been managed conservatively.34, 35 Studies are small and the safety of a conservative approach, particularly with respect to the carotid artery, has not been confirmed. Clearly, the risk of surgery should not exceed the risk of complications developing from the arterial defect. Patients managed conservatively should be followed with arteriography to confirm that the lesion does not increase in size.
Vertebral artery injury With the increased availability of angiography, vertebral artery injury is being recognized more frequently.36 Patients may present with acute bleeding or with late
Chapter 139 Neck trauma I
1773
Suspected carotid injury
Unstable patient
Stable patient
Active bleeding
Pulse deficit
Expanding haematoma
Bruit
Unresponsive shock
Pulsatile haematoma
Angiogram
Reperfuse
Carotid artery injury
Reperfuse
Ligate
Coma <4-6 hours
Coma >4--6 hours
No ischaernic infarct
Ischaemic infarct
Distal flow
Brain oedema Complete distal occlusion Inaccessible high injury
Figure 139.3
Recommended protocol for carotid ligation versus reperfusion.
complications of thrombosis, false aneurysm formation, bleeding,
arteriovenous fistula
and
stroke.
Torrential
bleeding may be encountered from a lacerated vertebral artery. Arteriovenous
fistulae may present with a bruit,
thrill, haematoma, neurological deficits or cardiac failure. A neurological deficit is
seldom acquired in the presence
of a normal contralateral vertebral artery and intact collateral circulation.37 Mortality from isolated vertebral artery
trauma ranges from 5 to 17 percent, but increases associated inju ry of the carotid artery.38 The majority of vertebral artery injuries can be managed by angiographic embolization. If the injury is discovered at emergency surgery, the vessel should be ligated. This is fairly simple if the injury is located at a point before the vertebral artery enters the foramen to 50 percent if there is an
transversarium at the level of the sixth cervical vertebra. Once inside the vertebral canal, ligation may be achieved
Figure 139.4
with ligaclips. Alternatively, bone
caroticojugular fistula following stab wound at skull base.
wax:
should be
used to
False a neurysm of internal carotid artery, with
tamponade bleeding and followed with angiographic . embolization. [Grade C]
and
139.5), Bleeding from branches of the external
carotid artery can be controlled by embolization. ENDOVASCULAR TECHNIQUE
Endovascular techniques
are playing an increasing role in the treatment of both ac u te and late manifestations of vascular trauma, particularly at the skull base. False aneurysms and arteriovenous fistulae can be treated with covered stents, or by trapping the lesion proximally and distally with balloons or coils, once good crosstlow in the Circle of Willis has been demonstrated (Figures 139.4
VENOUS INJURlES
The external
jugular vein may be ligated if injured. The vein may be repaired by lateral venor
internal jugula r
rhaphy or ligated. Should both internal jugular veins have been injured, then at least one ve i n should be repaired to prevent sequelae of raised intracranial pressure such as blindness, syndrome of inappropriate antidiuretic
1774
I PART
14 THE
NECK
•
Exposure: - chest and face for zones I and III injuries, to permit additional surgical exposure if required; - contralateral groin and lower leg to permit harvesting of saphenous vein for grafting.
•
Approach: - localized injury: horizontal skin crease incision, subplatymal flaps; - wider exploration: long incision along anterior border of sternocleidomastoid muscle.
•
Additional exposure: - zone I: divide omohyoid muscle; bilateral exploration: apron flap; - zone III: anterior dislocation of the mandible.
SUMMARY Figure
139.4),
139.5
Trapped false aneurysm and fistula (Figure
Management of penetrating injuries of the neck remains
wi th coils inserted by endovascular technique.
controversial for the following reasons: paucity of well designed,
large,
prospective
studies;
the
uncommon
hormone secretion (SIADH) and even death. A remnant
occurrence of oesophageal injuries; the variable levels of
of the contralateral internal jugular vein or saphenous
radiological and surgical expertise at trauma centres confronted with cervical injuries; the wide spectrum of
vein can be used should a graft be required. [H 1
the site and severity of injuries and of aetiological agents; and the lack of a uniform classification system when
Chylous injury Patients with
zone
reporting neck injuries. I
injuries
can
rarely
develop
a
chylothorax due to injury to the thoracic duct or right lymphatic duct. Although one can attempt a diet of medium-chain triglycerides, Worthington et
al.39 re
ported that conservative treatment is uniformly unsuc cessful and advocate early ligation via thoracotomy. [H]
Neurological injury
......
-_
......
-... .... . -.. ... .... _ ...
.......
_----
_-----
•
Properly executed, se)cctive management of penetrating inj uries of the neck is as safe as
•
Trauma
mandatory exploration.
centr�s need
to design their
in accordance with their investigative and therapeutic ca pabili t ies.
manag,ement protocols Significant brachial
nerve injury should be repaired
electively within 24-72 hours unless the neck is explored
" '\'
for other reasons. [Grade D)
EXPLORATION OF THE NECK: GENERAL PRINCIPLES •
Intravenous infusion lines, suction, blood in theatre.
•
General anaesthesia: Crash induction with cricoid
•
Airway:
pressure. - nasotracheal/orotracheal intubation; _
•
cricothyroidotomy or tracheotomy.
Position: _
_
supine; neck extended, turned to opposite side) if no C spine injury.
Deficiencies in curre nt knowledge and areas for future research » Significance of delayed repair of cervical oesophageal inj ury.
).- CT scan for initial evaluation of penetrating cervical inj ury.
> MRI scan for initial evaluation of penetrating cervical injury.
>- Endbvascular intervention for vascular trauma.
; '.. -
Chapter 139 Neck trauma
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I 1775
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2.
Roon AJ, Christensen 1\1. Evaluation and treatment of
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RS, Krevsky B. Role of flexible endoscopy in the evaluation of possible esophageal trauma after
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Narrod JA, Moore EE. Selective management of
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Kantarovsky A, John KD et 01. lVIanagement of penetrating
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Campbell FC, Robbs N. Penetrating injuries of the neck: A
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27.
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Ngakane H, Muckart DJJ, Luvuno FM. Penetrating visceral injuries of the neck: Results of a conservative
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The role of angiography in penetrating neck trauma.
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Journal of Trauma. 1991; 31: 557-63.
Weigelt JA, Thai ER, Snyder III WHo Diagnosis of
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Asensio JA, Chahwan S, Forno W, MacKersie R, Wall M,
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Lake J et 01. Penetrating esophageal injuries: Multicenter study of the American Association for the Surgery of
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Demetriades D, Theodorou D, Cornwall E, Asensio J,
Surgery. 1995; 130: 971-5.
31.
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M et 01. Computed tomography in the evaluation of
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Brown IVlF, Graham JM, Feliciano DV, Mattox KL, Beall AC, De Bakey ME. Carotid artery injuries. American Journal of
Fetterman BL, Shindo ML, Stanley RB, Armstrong WB, Rice Laryngoscope. 1995; 105: 8-13.
Liekwig WG, Greenfield U. Management of penetrating carotid artery injury. Annals of Surgery. 1978; 188:
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Demetriades E, Theodorou D, Cornwell III E, Weaver F, Yellin A, Velhamos G et 01. Penetrating injuries of the neck
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Meyer JP, Barret JA, Schuler JJ, Glanigan DP. Mandatory vs selective exploration for penetrating neck trauma.
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Sclafani SJ, Cavaliere G, Atweh N, Duncan AO, Scalea T.
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* 11.
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Flowers JL, Graham SM, Ugarte IVIA, Sartor WM, Rodriguez
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Wood J, Fabian TC, Mangiante EC. Penetrating neck
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*
Dunbar L, Adkins RB, Waterhouse G. Penetrating injuries to the neck. Selective management. American Surgeon.
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Bishara RA, Pasch AR, Douglas DD, Schuler JJ, Lim LT,
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Stain S, Yellin AE, Weaver FA, Pentecost MJ. Selective
Stanley RB, Armstrong WB, Fetterman BL, Shindo ML.
management of nonocclusive arterial injuries. Archives of
Management of external penetrating injuries into the
Surgery. 1989; 124: 1136-41.
1776 I 35.
PART 14 THE NECK
Frykberg ER, Crump JM, Vines FS, McLellan GL. Dennis JW,
and management. Journal of Trauma. 1987;
Brunner RG et al. A reassessment of the role of
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36.
McLaughlin OJ, Modic M, Masaryk T, Pratt 0, Huang D. A
A prospective study. Journal of Trauma. 1989; 29:
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1041-52.
to the vertebral artery. Vascular Surgery. 1998;
Meier DE, Brink BE, Fry WJ. Vertebral artery trauma -
639-46.
acute recognition and treatment. Archives of Surgery. 37.
38.
27:
39.
32:
Worthington MG, de Groot M, Gunning AJ, Von Oppel UO.
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Isolated thoracic duct injury after penetrating
Golueke PJ, Sclafani E, Phillips T, Goldstein A, Scalea T,
chest trauma. Annals of Thoracic Surgery. 1995; 60:
Duncan A. Vertebral artery injury - diagnosis
272-4.
140 Benign neck disease: infections and swellings PETER CLARKE
Introduction Cystic lesions Lateral cervical cysts and branchial abnormalities Benign tumours Infections Deep neck space abscesses Conclusion
1777 1777 1779 1782 1783 1785 1786
Key points Best clinical practice Deficiencies in current knowledge and areas for future research References Further reading
1787 1787 1787 1787 1788
A PubMed search revealed only reviews and case reports. Searches for the following were undertaken: branchial cysts, branchiogenic carcinoma, lateral cervical cysts, thyroglossal cysts, dermoid cysts, bronchial cysts, lymphangiomata, cystic hygroma and thymic cysts. A search combining 'neck' and 'cervical' and the following was also undertaken: TB, HIV, AIDS, infectious mononucleosis, cat scratch disease, toxoplasmosis, brucellosis, Kikuchi's disease, actinomycosis, necrotizing fasciitis, abscess and infection. There are no Cochrane Reviews, and no level II or I evidence for the management of these conditions. Management recommendations are supported only by retrospective reviews and expert opinion. [Grade D]
INTRODUCTION
i
\
I
L_
Benign neck swellings may be nodal or cystic, lateral or central, neoplastic, inflammatory or congenital. Thyroid and salivary gland swelling will be considered elsewhere. Maisel 1 suggests that 80 percent of nonthyroid neck masses are neoplastic. Of these, 80 percent are metastatic and three-quarters are from primaries above the clavicle. , Although the statement above might be prefaced by a suggestion that this applies to masses over 2 em in diameter in those over 35 years of age, it is a useful rule of thumb - especially for those not regularly seeing patients with neck masses. This compares with 90 percent of neck masses in children representing benign conditions of which 55 percent were congenital. 2 [**/*] Neck masses are often enlarged lymph nodes, which may be reactive to either local or generalized infection. Nodal swellings may be suppurative or nonsuppurative. Pus may also spread from a local focus of suppuration related to, for example, the tonsil or a tooth. Swellings
may also be related to cystic structures, the most common of which are branchial cysts and thyroglossal cysts. These may present as infections or become infected. Benign tumours, particularly neurogenic tumours may present as neck swellings. Initial investigation should include history, physical examination and fine needle aspiration for cytology or microbiology and culture. This, with knowledge of the anatomy and physiology should allow an accurate diagnosis in most cases. Ultrasound scanning, computed tomography (CT) and magnetic resonance (MR) images will often be helpful in difficult cases.
CYSTIC LESIONS Thyroglossal cysts Most authors suggest these are the most common cystic lesions in the neck. Up to 50 percent will present in
1778
I PART 14 THE NECK
30 percent presenting before ten
present suprahyoid and just over 10 percent related to the
years of age. There is an equal male-to-female incidence
thyroid. Because of the hyoid attachments, these masses
(Figure 140.1).
move both on swallowing and protrusion of the tongue.
Embryology
may result in the development of a sinus from the cyst to
adulthood, with over
Cysts may become infected and incision and drainage the skin.
During the development of the branchial apparatus in a four- to five-week-old embryo, the thyroid enJage arises in an invagination of endoderm in the floor of the pharynx and develops caudally, with the descent of the great vessels. It enJarges and becomes bilobed, coming to rest at the root of the neck as the thyroid gland by the end of the seventh week. T he tract that is left usually atrophies and disappears, although the caudal end often remains as a
Pathology Thyroglossal cysts are usually lined by columnar epithe lium with small glands frequently containing thyroid colloid.
Decalcification of the hyoid bone
will often
confirm that the tract passes through it. 4
pyramidal lobe. Failure of the tract to involute may leave epithelial remnants or an open area of duct, which may expand into a cyst
because
of an accumulation
of
secretions. The hyoid bone, developing later, may entrap a portion of the thyroid duct or draw it caudally, leaving the duct dorsal to the bone.3
The diagnosis is clinical and may be confirmed with a fine needle
aspirate
if
the
mass
is
suprahyoid
to
help
differentiate it from a dermoid cyst or submental lymph node.
Clinical features
Further
investigations
are
not
necessary
for
diagnosis, but should be undertaken to ensure that a
Most present as midline masses 2-3 cm in diameter just inferior to the hyoid bone
Management
(Figure 140.1).
A quarter
normal thyroid gland is present. Ultrasound scanning is accurate,
cost-effective
investigation
of
and
choice
would
and
is
seem
the
to
most
be
the
common
investigation undertaken in the UK. Radionuclide scan ning may be reserved for patients with normal thyroid glands that cannot be localized. Thyroglossal cysts should be treated surgically. An infected cyst may be aspirated for microbiological culture and to avoid incision into the cyst. A horiwntal skin crease incision is made over the cyst and skin flaps raised superiorly and inferiorly. Care should be taken through out the dissection to avoid rupturing the cyst.
For
infrahyoid cysts, the sternohyoid and thyrohyoid muscles must be reflected laterally and stripped off the hyoid to reveal the cyst. The cyst is dissected from surrounding tissues up to the body of the hyoid. The hyoid is then divided with heavy scissors just medial to the lesser horns on both sides. A cuff of suprahyoid and intrinsic tongue muscles is then taken with the body of the hyoid. A specific tract is often not found, but if a convincing tract is seen, this should be followed into the musculature of the tongue base and removed. There is no need to resect epithelium of the tongue base. Sistrunk described this operation in
1920.5 Recurrence rates are significantly less
after Sistrunk's operation than after simple cyst excision. If a sinus is present, an ellipse of skin around the sinus is removed in continuity. Surgery for recurrent cysts should include excision of the hyoid and a cuff of tongue base muscle if the hyoid has not previously been excised, or excision of the cyst with a surrounding cuff of muscle if Sistrunk's operation has previously been performed. Figure 140.1
large thyroglossal cyst presenting in late
There have been a large number of case reports and
adulthood with symptoms of obstructive sleep apnoea. Elevation
small
of cyst on tongue protrusion demonstrated.
thyroglossal cyst. Up to
S'eries
of
thyroid
carcinoma
presenting
in
a
90 percent of these are papillary.
2-8% Vs 85%
1779
Chapter 140 Benign neck disease: infections and swellings I
6
A recent review from Slone Kettering suggests treatment
should be with Sistrunk's operation and thyroid suppres sion wit h thyroxine. Thyroidectomy and postoperative
Pharyngeal clefts
�.,-'
Ph�ry.,geat
Pharyngeal pouches
a rch es
radioactive iodine, although revealing malignancy in a quarter of patients, did not confer a survival advantage and they conclude that this should be reserved for high risk groups. [Grade D]
--="'-"---
1. Eustachian tube and middle ear cleft
LATERAL CERVICAL CYSTS AND BRANCHIAL ABNORMALITIES Lateral cervical or branchial cysts occur equally
in the
2'----1---.,.,
sexes and present most commonly in young adults,
3:----+-1---1
although they can occasionally present at any age. There is
3. Inferior parathyroid thymus
4----r+-�=:OO'�
debate about the precise aetiology of the cysts and fistulae and there may be a number of different aetiologies resulting in
r-----
.
�-
a similar clinical presentation.
4. Superior parathyroid u ttimobran chial body
Branchial fistulae Branchial
fistulae usually present in childhood as a
weeping defect along the anterior border of sternoclei domastoid, or occasionally as an acute infection.
Figure 140.2
Development of the pharyngeal ( branchial)
apparatus. The second arch grows over the third and fourth pharyngeal arches so burying the second, third and fourth pharyngeal clefts. The remnants of these clefts form the cervical sinus of His.
EMBRYOLOGY
ultimobranchial body
During the fourth week of intrauterine life, (or pharyngeal)
six branchial
(Figure 140.2) and hence extend
from the pharynx to the thyroid. The fact that fourth
arches develop as neural crest cells
branchial fistulae only seem to occur on the left would
fifth
suggest that the timing of the descent of the aorta allows a
migrate into the head and neck region. During the
week, the second branchial arch grows over the third and fourth branchial clefts which form a cervical sinus
(Figure
fistula to remain on the
left whilst descent of the
subclavian artery may obliterate potential fistulae on the
140.2). Failure of the cervical sinus to close may therefore
right. Although fistulae undoubtedly exist running from
potentially
the piriform fossa to the skin and are presumably related
communicate
with
the
second
branchial
pouch (and therefore the tonsil fossa), the third branchial
to the branchial apparatus, the exact mechanism of their
pouch in the area of the larynx or the fourth branchial
formation cannot be certain. Often described in the literature as fourth branchial pouch fistulae, they present
pouch opening in the piriform fossa.
on the left, often involve the thyroid gland and may present as a suppurative thyroiditis PRESENTATION
(Figure 140.4). They
usually present in children though may be asymptomatic
Clinically, second branchial cleft fistulae are the most
until adult life.
[** /*]
common. They have a cutaneous opening along the anterior border of the sternocleidomastoid, usually at the junction of the middle and lower thirds, and track up
MANAGEMENT
through the neck to rW1 between the internal and external
Fistulae may be investigated with a sinogram. Pharyngo
(Figure
scopy with careful examination of the tonsil fossa and
carotid arteries and end in the tonsillar fossa
140.3). Third and fourth branchial fistulae are more rare,
piriform
fossa
mucosa,
depending
on
presentation,
should be undertaken prior to excision.
opening low in the neck and ending in the piriform fossa.
Surgical excision should be started with an elliptical
The third arch fistula should pass over the hypoglossal
excision of the fistula opening. Dissection of the track can
nerve and the fourth arch fistula should run down into
be helped by careful injection of dye into the opening
the chest, running below the arch of the aorta on the left
before commencement. A second branchial fistula
or subclavian archway on the ri gh t. It is doubtful whether
need one or more further skin incisions to allow safe
these exist as clinical entities, however. A recent pape?
dissection to the carotid. Excision of the tonsil fossa
suggests that 'fourth branchial cleft fistulae' arise from the
opening or dissection in the fossa will allow excision in
_.�
will
-1 .�_.__-.
:.
-
1780
I PART 14 THE NECK
Figure 140.3
Second branchial cleft fistula.
between internal and external carotid.
(b)
(a)
Dissection followed up through neck and second incision to allow safe dissection
Opening of fistula in tonsil fossa demonstrated by appearance of dye.
Lateral cervical (or branchial) cysts The cervical sinus normally closes by six weeks leaving a cervical vesicle and it is this trapped ectoderm which) it is po stulated, forms the lateral cervical or branchial cysts commonly seen in young adults. There are a number of theories of origin for these lateral cervical cysts, which have a constant clinical pr esentation anterior to the upper third of sternocleido mastoid in young adults. They usuaHy appear fairly quickly often in relation to an upper respiratory tract infection. There is a slight left-sided predominance
.
All
three main theories of their aetiology have some merit. 8 Figure 140.4
Fourth branchial arch fistula. Young adult
presenting with anterior neck abscess and fistula
1.
Origin from a branchial pouch remnant:
A tract
from lateral cervical cysts running between the
communicating with left pyriform fossa. Lifetime history of
internal and external carotid would bolster this
intermittent weeping from small punctum in left neck.
theory and is sometimes described but often not proven histologically and may be a surgically
continuity
(Figure 140.3).
Removal of a fourth branchial
produced
arch fistula should include excision of the thyroid tissue
common
a g gregati on of tissue. Certainly, in with several eminent surgeons, the
as necessary to allow removal of the whole tract. Ligation
author has never seen a tract from a branchial
of the tract at the pharyngeal mucosa can then be
cyst. 'Detailed histological mapping of the
undertaken. [Grade D 1
cytokeratin profile of lateral cervical cysts and
Chapter mucosa from the tonsil fossa does, however, suggest an origin from this area. 9 2. Origin from the cervical sinus: This theory proposes the branchial cleft rather than pouch forms cysts. Overgrowth of the second arch produces the cervical sinus of His (Figure 140.2) which closes to leave the cervical vesicle, which, it is postulated, results in the lateral cervical cyst. This is an attractive theory embryologically, although does not fully explain why cysts usually do not appear clinically until the third or fourth decade and it might be expected that more cysts are found with tracts or sinuses running to the skin. 3. Origin from lymph node degeneration: Originally postulated in the nineteenth century, Kingl0 in 1949 studied a large number of cysts and concluded that cystic transformation of lymph nodes was the likely origin of lateral cervical cysts. Certainly most cysts have lymphoid tissue similar to lymph nodes in their walls and few, if any, have tracts to the skin or pharynx. It might be expected, however, if this theory were true that the position in the neck may be more variable.
140 Benign neck disease: infections and swellings
I 1781
infection, attempts should be made to aspirate the contents and treat the patient with intravenous antibiotics, though incision and drainage may be necessary. Imaging is not usually necessary to make the diagnosis. Lateral cervical cysts should be surgically removed. After a transverse skin crease incision over the cyst is made, dissection is followed along the anterior border of the sternocleidomastoid. Blunt dissection close to the cyst is usually simple and allows removal of the cyst. If there has been previous infection or the cyst is very adherent to local tissues, dissection should continue as for a neck dissection with identification of the spinal accessory nerve, carotid sheath and hypoglossal nerve with resection of the cyst and surrounding nodes and fibrous tissue. Proponents of a branchial sinus origin suggest looking for a cord or tract extending between the internal and external carotid and possibly examination of the tonsil fossa prior to excision of the cyst. If cysts have presented with acute infection and been treated with antibiotics, the cyst will occasionally not be apparent after resolution and unless radiology - either ultrasound scan or CT scan shows an obvious cyst, these cases can be treated expectantly. [Grade D]
Branchiogenic carcinoma PRESENTATION
In early adulthood, a cystic, often tender oval mass 4-6 cm in diameter anterior to the upper third of the sternocleidomastoid develops fairly quickly. A recent upper respiratory tract infection is often described. Swelling may be intermittent and occasionally the cyst is overtly infected with overlying erythema and pain at presentation. The main differential diagnosis is from reactive lymphadenopathy. In children, a dermoid cyst or rhabdomyosarcoma should also be considered. In young adults, lymphoma, tuberculosis (TB) or nerve sheath tumours need to be excluded. In patients over 35 years of age, a cervical metastasis from a head and neck primary must be excluded.
PATHOLOGY
Lateral cervical cysts are usually lined with squamous . epithelium with transitional type pseudo stratified epithelium. Cysts presenting in the younger age group are more likely to be lined with respiratory epithelium.
MANAGEMENT
The differential diagnosis can be simplified considerably by fine needle aspiration. Occasionally straw-coloured fluid is obtained, though more often, greasy yellow thick mucoid material is aspirated, probably representing recent inflammation. Should they present with acute
Opinion on the existence of this entity varies from the suggestion that it is underdiagnosed to denial of its existence. Following initial descriptions and the coining of the term 'branchiogenic carcinoma', it became clear that the majority of these cases were actually metastatic deposits from primary squamous cell carcinomas in the head and neck. In 1950, Martin et al. 11 therefore suggested that to diagnose a branchiogenic carcinoma, four criteria had to be met. 1. The cervical tumour occurs along the line extending from the tragus to the clavicle, along the anterior border of sternocleidomastoid. 2. The histological appearance must be consistent with an origin from tissue known to be present in branchial vestiges. 3. No primary source of the carcinoma should be discovered after at least five years of follow-up. 4. There is histologic demonstration of cancer arising in the wall of an epithelial-lined cyst. Even apparent fulfilment of these criteria, however, cannot exclude a metastatic squamous cell carcinoma. A cystic metastasis may have many similar features, histologically, to a branchial cyst and the addition of radiotherapy to the excision of these masses will treat small tonsil or tongue base tumours, so making even 12 adherence to Martin's criteria meaningless. Most metastatic nodes 'with unknown primary' are solid and most cystic nodes have primary tumours that
1782 I
PART 14 THE NECK
can be demonstrated in the tongue base or tonsil. Several 136
cases
of
cystic
squamous
cell
and about a
in the neck. They are uncommon
with only five cases per 3000 admissions to a pa(�(ll;atfllc
carcinoma,13 without an obvious primary site of origin
hospital and only account for four of 152
at initial diagnosis, have shown that in the vast majority a
of the neck. These lesions are COJngt�nltal, lyn1prlalllC stasis caused by congenital blockage
tumour can be found. Most are in but other sites found include
of a
There is no innate reason
and
lateral cervical cyst should not become
certainly there are case reports of tumours that fit Martin's criteria, but estimates
from
budding that arises from the lymphatic sacs. Capillary or simple
1.
lymphangiomas are comprised of capillary-like
that the incidence
if they
lyn1Pl1atllc vasculature and are usually
is in the
.... ,..,,' ...... .__ t-"rY'O'.b,..
of all head and neck carcinomas. 14
of 0.3
or
sequestration of the primitive embryonic endothelial
palate, sinuses and salivary
of
lymphatic
thyroid,
or oral
skin
and confined to the They are pale, small vesicle-like
lesions and no treatment is necessary. Cavernous
2. Cavernous
of dilated
lymphangiomas are lymphatic channels and These originate from ectoderm and mesoderm, and the head and neck is the most common site to find them. can
at any age, but the majority present in
patients aged under six years. Sex distribution is equal and
occur in the
tongue, cheeks and lips,
DERMOID CYSTS
fusion of the
along lines of
in the midline or lateral
facial processes to the submandibular
They occur in the sub-
cutaneous tissues and contain skin aplJenlaa.ges hair follicles, sebaceous
and sweat
wounds.
These account for 40 percent of lymphangiomas. hygromas are
3.
similar to cavernous lymphangiomas with thin-walled sinuses and cysts that are lined by flat endothelial cells and contain eosinophilic, acellular
fluid. In cystic hygromas, there
are larger
masses which may communicate
or be isolated.
so
differentiating them from epidermoid cysts. Dermoid cysts may also occur from implantation
diffuse swelling.
to
surgical excision is required
PRESENTATION Lymphangiomas occur predominately in the neck, often triangle where tissue planes are looser
in the
and is usually straightforward.
than in the lips, tongue and cheek. As these enlarge, they may involve the cheek,
BRONCHIAL CYSTS These are uncommon congenital lesions that can occur in the suprasternal notch, but are more common within the thoracic
or mediastinum. They are more common in
males and one-third are associated with a sinus. The cysts are lined by ciliated pseudostratified and tpe sinus with stratified squa-
columnar mous epithelium.
eXClSIOn is curative.
Cervical or plunging ranulae are considered glands
with
147, Non-neoplastic
gland diseases) and laryngocoeles are considered with the larynx
oral cavity and media
stinum or axina. In the neck they are fluctuant, soft,
88, Congenital disorders of the larynx,
trachea and bronchi).
they
diffuse masses with indistinct margins. transilluminateo The majority of lymphangiomas are may now be
at birth and
prenatally. It is extremely rare for
these to present after the age of two years, but recurrence after
treatment may occur after many years.
are usually asymptomatic, but are a distressing cosmetic problem.
hygroma and cavernous lymphangioma
either grow
or remain static and there have
also been many reports of involution. may, however, cause or airway largest
or infection
growth and symptoms of which may be
The
may also cause airway problems
without infection or bleeding.14[**I*]
MANAGEMENT Magnetic resonance imaging
(MRl) delineates the extent of
the lesion well and will facilitate accurate diagnosis and These benign lymphatic lesions can be divided into three morphological types:
cavernous and
One-third of cases are found in the oral cavity and cheek
pretreatment pi arming. Prenatal diagnosis may be made with ultra�ound assessed with
and potential airway compromise
MRl. There are case reports of
Chapter 140 Benign neck disease: infections and swellings
infants being treated ex utero to avoid airway problems at birth. In this country, the majority are not diagnosed until birth and treatment depends on the size and anatomical location of the lesion. Treatments used for lymphangioma include surgical excision and intralesional injections of such sclerosants as bleomycin, tetracycline and alcohol. Surgery is challenging and should be undertaken in specialist centres. With time and expertise, results can be excellent and surgery remains the treatment of choice. Resection is often limited to the neck initially and recurrence rates can be high and may occur rapidly or after many years. Surgical excision may be helped by the injection of tissue blue into the lymphatic spaces. A staging system has been used to predict surgical outcome (Table 140.1).15,16 Injection of sclerosants may lead to scarring and make subsequent surgery more difficult, but a new intralesional injection of OK-432 (picinabil) has shown promising results. It is thought to produce an inflammatory reaction leading to adhesions or to increased permeability of the endothelial lining, increasing the rate of drainage from the lesion. Pooled results from a group of series show marked shrinkage in 72 out of 116 children. It may be less effective in cavernous lymphangioma and lymphangioma with haemangiomatous elements. 17 [**1*]
I 1783
develop from lymph nodes, may develop in any of the cystic masses described above or may spread from local abscess formation around teeth, tonsil or from trauma. Tuberculosis, infectious mononucleosis, human immunodeficiency virus (HIV) infection, cat scratch fever and toxoplasmosis may all produce generalized cervical lymphadenopathy.
Tuberculosis Cervical lymphadenopathy is the most common head and neck manifestation ofTB and can occur in any age group, though most series suggest the most common presentation is in young adults. Most series suggest only 10-20 percent to have associated pulmonary disease or to have had a history of contact with TB. Up to half of these patients will have systemic symptoms. It has been suggested that the bacillus enters via the tonsils as tonsillectomy specimens will often show evidence of TB infection in these patients. Nodes tend to be tender and may have overlying erythema or occasionally a discharging sinus. Suspicion should be raised in immunocompromised patients, those from regions with high levels of TB, such as the Indian subcontinent and parts of the former Soviet Union, as well as parts of Africa. IS, 19 [**1*]
Paragangliomas and nerve sheath tumours These neoplasms of neural crest origin arise from the paraganglionic cells in the carotid body, vagal ganglia and jugulotympanum and, less commonly, other areas including the larynx, nose and orbit. Most present in the parapharyngeal space with swelling of the pharynx and fullness in the upper neck. These are considered in more detail in Chapter 191, Tumours of the parapharyngeal space.
INFECTIONS Infections may be suppurative or nonsuppurative and related to lymph nodes or neck spaces. Suppuration may
Stage 1 Stage 2 Stage 3 Stage 4 Stage 5
Unilateral infrahyoid disease Unilateral suprahyoid disease Unilateral infrahyoid and suprahyoid disease Bilateral suprahyoid disease Bilateral supra and infrahyoid disease
17 41 67 80 100
MANAGEMENT Ultrasound scanning of the nodes will often show multiple matted nodes most commonly in the upper deep jugular chain or supraclavicular region. A fine needle aspiration (FNA) should be undertaken and will often reveal mycobacteria. With an increased number of multiresistant strains of TB, however, an excision biopsy is often needed to establish sensitivities. 20 This may become less necessary as the application of DNA probes and polymerase chain reaction (PCR) becomes more widespread in the future. When FNA and PCR were used together, a specificity of 84 percent and sensitivity of 100 percent were found. 21 If possible, total excision of the node or nodes is suggested rather than incisional biopsy to reduce the chance of developing a discharging sinus. This may mean utilizing neck dissection techniques to undertake a selective neck dissection often with some excision of the sternocleidomastoid, which is commonly involved if the nodes are very inflamed and matted. Antituberculous chemotherapy should be started immediately after surgery and adjusted according to sensitivities. [**1*]
Infectious mononucleosis Although generally diagnosed and seen in the ear, nose and throat (ENT) setting due to the acute tonsillitis, generalized lymphadenopathy is often present. EpsteinBarr virus infection often occurs in childhood and usually
1784
I PART 14 THE NECK
results in a mild self-limiting illness characterized by
syndrome (AIDS) or a poor prognosis. Enlarging or
fever, pharyngitis, tonsillitis and lymphadenopathy. How
tender nodes are not typical of PGL and in a series of HIV
ever, in teenagers and young adults, it may present with
patients with enlarging or tender nodes none had PGL
significant tonsillar enlargement causing airway compro
and a diagnosis of TB was made in eight, opportunistic
mise and rarely death. Suppuration of lymph nodes can
nocardial
occasionally occur and awareness of the possibility of
metastatic carcinoma in one.25
infection
in
two,
lymphoma
in
one
and
splenic rupture is important. The enlarged tonsils have a characteristic grey fibrinous exudate and patients often have a typical 'hot potato' voice.
This is an infection caused by
MANAGEMENT
Bartonella henselae, a
fastidious Gram-negative bacillus acquired from exposure
Nasopharyngeal endoscopy may be a useful diagnostic tool showing the typical fibrinous membrane in the nasophar yngeal cavity of over 90 percent of patients with infectious mononucleosis
Cat scratch disease
and
none
of
patients
24
with
acute
tonsillitis?2 Diagnosis is made by Paul Bunnell monospot serology, detection of a viral capsid antigen-IgM or the presence of lymphocytosis with characteristic apoptotic lymphocytes present in 89 percent of blood smears of patients with acute infectious mononucleosis and only 4 percent of controls. Elevated liver function tests are usual. More recent quantitative polymerase chain reaction may allow prediction of fulminant infections. Treatment is supportive with hydration, if swallowing is a significant
to an infected kitten or cat, either directly or via cat fleas. Symptoms are of fever, arthralgia and lymphadenopathy. The presence of cat scratches or a history of a cat scratch should guide the diagnosis which is confirmed by indirect immunofluorescence antibody assay with high antibody titres
which
settle
over
several
weeks.
polymerase chain reaction RNA of
More
recent
Bartonella henselae
RNA has been used to confirm the diagnosis. The organism is sensitive to many antibiotics and so it is likely that many cases are never diagnosed. There is some evidence
that
azithromycin is
associated
with rapid
resolution, but many infections will settle without the 6 need for antibiotic therapy. 2
problem, and pain relief. Nonampicillin antibiotics are usually prescribed to prevent secondary bacterial infection. Upper airway compromise should be treated early with steroids and there are case reports of antiviral treatment with acyclovir or famcyclovir which may be of help. Tracheostomy should be avoided by the prompt use of steroids. Acute tonsillectomy has been advocated for upper airway obstruction. Only a small proportion of patients go on to have recurrent tonsillitis and so interval tonsillect omy is not indicated. A prospective cohort of 250 primary care patients with infectious mononucleosis or ordinary upper
respiratory
fatigue
syndrome
tract at
infections
two
months
suggested was
postviral
most
reliably
predicted by cervical lymphadenopathy and initial bed rest and at six months was predicted by a positive monospot test and lower physical fitness.23
Toxoplasmosis This is a parasitic infection with
Toxoplasma gondii which
may be asymptomatic or produce cervical lymphadeno pathy,
fever
and
malaise.
The
main
reservoir
for
toxoplasma in the UK is the cat, but transmission may also occur from cysts in undercooked meat. A fine needle aspiration will often show the microorganism on micro scopic examination.
Diagnosis can be confirmed by
serology. A retrospective review of 731 patients who had 'reactive
lymph
node
hyperplasia'
revealed
features
supporting a diagnosis of toxoplasmosis in 15 percent of cases.27 Treatment is not usually indicated.
[***1**] Brucellosis
HIV infection Persistent
The brucella group of pathogens occur in domesticated
generalized
lymphadenopathy
(PGL)
is
a
syndrome of diffuse lymphadenopathy involving two or more extrainguinal sites for greater than three months. It may be an early sign of HIV infection with up to 70 percent of patients infected developing diffuse lympha denopathy within the first few months after seroconver sion. Fine needle aspiration will usually show a reactive picture, so. excision biopsy of a node or panendoscopy is usually
not
undertaken,
indicated. will
Histology,
usually
show
if a
the
excision
reactive
is
in
patients
with
acquired
meat or dairy products or via direct contact through broken skin. An undulating fever, malaise and cervical lymphadenopathy in 20 percent of patients is typical. The diagnosis is confirmed serologically and treatment is with doxycycline and rifampicin for six weeks. Prevention by animal vaccination is the ideal.
Kikuchi's disease
follicular
hyperplasia.24 A lymphocyte depletion pattern may be seen
animals and brucellosis is caught from contaminated
immunodeficiency
Kikuchi's disease, previously known as subacute necrotiz ing lymphadenitis, has been increasingly recognized in the
Chapter 140 Beni gn neck disease: infections and swellings'
1785
West, having been described more commonly in Asia. It is
a histiocytic necrotizing lymphadenit is without granular cell
infiltration,
mainly
affecting
young
women.
It
presents with malaise, mild fever and painless posterior triangle cervical ly mphadenopathy The course is benign .
and resolves in weeks or months. There may be an association with systemic lupus erythematosus
(SLE)
which may develop subsequently up to three years later
.
Monitoring should therefore be considered. Fine needle
aspiration will usually be nonspecific, but diagnosis has been made with cytology. Excisional biopsy is usually required to rule out a lymphoma or TB. Histology shows areas of patchy necrosis and a paucity of neutrophils
.
Cervical necrotizing fasciitis This is a rare, but life-threatening, infection that causes progressive necrosis of the subcutaneous fat and fasciae and secondary necrosis of the overlying skin. It may complicate deep neck space infections or result directly from odontogenic or tonsillar infection. Streptococcus miIIeri or S. viridans and mixed anaerobes are commonly
found. The clinical picture is of cellulitis with dispropor tionate pain Reduced skin sensation may be a useful early .
sign of affected areas. CT may show oedema and air pockets in the deep and superficial neck spaces and necrotic
patches
of
skin
are
diagnos tic.
Untreated,
necrotizing fasciitis can be rapidly fatal and so early diagnosis and
aggressive
t reatment
with
intravenous
penicillin and metronidazole and surgical debridement of all necrotic areas are the keys to success
(Figure 140.5).
Skin that has not been affected should be preserved to reduce cosmetic deformity.
Actinomycosis Actinomycosis species are facultative anaerobes whose normal habitat is the oral cavity but they can cause a chronic lesion mimicking malignancy or TB, usually following surgery or trauma to the mouth. The anterior cervical triangle is most often affected and they present as a slow growing mass or as an abscess or group of abscesses with sinus tracts to the skin
(Figure 140.6). These
manifestations are probably polymicrobi al The organism .
is difficult to culture but the characteristic colonies,
Figure 140.5
NecrotiZing fasditis.
(a)
Gross oedema and
diagnostic collections of subcutaneous gas on CT. (b) Outcome following debridement and seconda ry skin grafting.
known as sulphur granules, are often seen histologically. Fine needle aspiration may also show sulphur granules. A
DEEP NECK SPACE ABSCESSES
two-month course of penicillin or cephalosporin and removal of carious teeth is usually curative. courses of
antibiotics
may be
necessary
Longer
in resistant
These
include
parapharyngeal
or
lateral
pharyngeal,
retropharyngeal and submandibular space abscesses and
cases. Infection with Nocardia species may give a similar
although less common than in the past, partially because
picture,
.
of better oral care and antibiotic treatment, may still
especially
in
immunocompromised
patients
Growth of the organism may therefore be important as
present as life threatening infections. Some series suggest
tr eatment should be with imipenem or sulphonamides for
there are slightly more men than women presenting with
Nocardia.28
these infections and the peak ages are in the third and
-
1786 I
PART 14 THE NECK
anterior to the superior half of the sternocleidomastoid. Submandibular space infections
will have localized swelling
below the mandible and may be associated with signifi cant oedema of the floor of the mouth, with elevation of the floor of mouth and tongue when it is described as Ludwig's angina. In this situation, airway compromise is significant and in one series, 75 percent of these patients required a 3o Airway co m promise is the most common
tracheostomy.
complication of deep neck space abscess, but internal jugular vein thrombosis characterized by spiking fevers, tenderness along the sternocleidomastoid and prostration, or mediastinitis are potential complications which should be anticipated.
[H/*]
MANAGEMENT
Antibiotics should be commenced before culture and sensitivities are available. Intravenous penicillin or amox ycillin with the addition of clavulanic acid or metronida zole to treat anaerobic bacteria should be the first choice. The history and examination should highlight the possibility of an abscess but investigations should include the assessment of the white cell count, inflammatory markers and radiologic assessment of the neck. A plain soft tissue lateral x-ray
will oft e n show a retropharyngeal
abscess but should be interpreted with caution in children and an orthopantomogram infection.
Ultrasound
(OPG) may show a tooth root or CT scanning will
scanning
usually delineate between cellulitis and abscess fonnation, Figure 140.6
Actinomycosis. Note multiple weeping punctae.
fourth decade. There is a dental origin in 40 percent of patients and other aetiologies are
tonsillitis with
or
without peritonsillar abscess, TB, intravenous drug abuse following injection into the internal jugular vein, man dibular fracture and foreign body ingestion. In up to 20 29 percent of cases, no obvious aetiological factor is found. Most bacterial cultures are polymicrobial and Streptococcus viridans is the most common organism isolated. Sta phy lococcus aureus and
Staphylococcus epidermidis are also
important. Anaerobes probably play a significant role in these abscesses, but are not always cultured.
but the possibility of false-negatives with either technique must be considered.
Needle aspiration under radiological Small loculated
control with either should be considered.
abscesses may be treated with intravenous antibiotics for 12-24 hours and drainage reserved for those that are 3l 32 , A signifi
not improving or with large collections.
cant abscess that cannot be substantially drained under imaging
control should be treated with surgical 33 Retropharyngeal abscesses or parapharyngeal
drainage.
abscesses medial to the carotid sheath may be drained intraorally though care must be taken not to rupture the abscess before the endotracheal tube is safely in the trachea.
Submandibular
and
most
parapharyngeal
abscesses are best drained externally.
If there is significant airway compromise, endotracheal incubation with gas induction is usually possible� Twenty
Clinical features
four to 48 hours of intubation may be necessary or the insertion of a tracheostomy following drainage will allow
in the
a return to the ward. Local anaesthetic tracheotomy
throat and neck, fever, a raised white cell count and raised
should be undertaken if the airway cannot be maintained
inflammatory markers. The clinical picture depends on the
for a gaseous induction.
T hese patients present acutely unwell with pain
[Hj*]
space affected. Retropharyngeal abscesses are more com mon in children and in adults are most commonly caused by TB of the spine. These may cause no neck swelling but
CONCLUSION
present with dysphagia, odynophagia and airway compro mise. The
m os t
common deep neck abscess is a lateral
pharyngeal (parapharyngeal) space infection which causes a diffuse, tender, indurated swelling which is usually
Any chapter on neck swellings should probably conclude with the advice to 'put a needle in' if there is any doubt or potential doubt about a diagnosis. In the presence of
Chapter 140 Benign neck disease: infections and swellings I
infection, this may also
be therapeutic, The addition of needle a pir a te is pr obably be t practice and the availability of this and a cyt ol ogist in a
s
ultrasound to the fine
one -stop clinic for neck
.I For deep neck space infections:
s
- start intravenous antibiotics immediately; - image and consider draining under ultrasound or
swellings is ideal and should be
CT control;
becoming commonplace,
- consider endotracheal intubation or tracheostomy
neck lump in the over 40-year-old must be treated metastatic squamous cell carcinoma from a head and
Any
as a
neck so
1787
early.
urce until another definite diagnosis is made. The
of branchial cys t in the over 40-year-old should be treated with caution and the pathologist asked to do m ultiple sections. Similarly, the diagnosis of carcinoma in a branchial cyst even if suppo rte d by histology should be treated with he al thy scepticism and a search for the
diagnosis
Deficiencies in current knowledge and areas for future research
primary.
Many of the conditions in this chapter are relatively rare and any prospective data collection or randomized trial of management options would therefore be very difficult unless multicentred or even national. For the majority of
'�i_ Thyro'glossal cysts may
�
'
,
"
-
present
at
·swallbwing. Excision I11l1st
i
th�'hYOtd. Branchial Cysts
of '� .
r
,
,(
-
"
"
•
are
any age,
author would hope to see the tertiary referral of cystic
midline, '�ssocjated "'lith the flyoid bone and
S9, move on - tons;ue protnlsion and ,
these conditions this is probably not practical. The
,
in the
oveI
include
3S
hygromas to a small number of surgeons so that progress in their management can be focused and
the body ','
controlled trials may be possible.
age group should /', .
be invesrigalted and treated as metastat ic ' ::"�' L � squamqw cell carc�f1��a:.�xcision should be ".' , undert�en',Qn�y �r f:ihe�n�d1e aspiration.� , panend��copY'�W:lth\ �Jopitd;, of the tongue ba�e-,,-�,,:.:,-:" :,' postn�al : space and: 'b iiatetabto'ilsillectomy. .-:�� ',, ' Inj'ectl9D-.'of bK�f!3ris',a'�prdm)sing new
..
It would be encouraging if a database of all cystic neck nodes with squamous carcinoma and no identifiable
I
primary could be developed to plan a trial of positron emission tomography (PET) scanning and bilateral tonsillectomy versus tonsil biopsy to prove best practice. A current European Organisation for Research and Treatment of Cancer (EORTC) trial may help decide whether the mucosal sites should be included in
",.: \
tre;1tinent for';Jymp�a-r�:gi0f!1�':' Where possibh�,;, ; :>:; s�rgical -resecti'6:n rema!h$"the_':;trcatment of�·l . ' , ' ,:",chpt�e. .,.
'fB
-lymphadenopathy
may be
atypical .J\1.ycobac/eria and
biopsy
radiotherapy fields when treating these tumours. A randomized trial of ultrasound-guided aspiration of neck abscesses versus open drainage versus antibiotics
c.aused by
therefore
alone may struggle to recruit sufficient patients as the
excision
author would predict there would be a large number of
-' I�
of the node may be required [or ,",", � - ,: 'I' ' culture and antimicrobial sensi-tivi!jes. '-. Many ea rly or sma Jll: deep neck space - infec ti ons cap be·treated with aspiration " ,.-i:"'-' under -ultrasound or CT c.ohtrol. together "'�'�.: ' , ' with intravenous antibiotics. " • Ludwig's angina has a high-1ncidence of "' · airway c�mpromise and sho.�� =
exclusions and would certainly need to be multicentred. A study looking at CT and ultrasound accuracy in the detection of pus in deep neck abscesses would be easy
"
L<>r l
be considered
ea r ...
ly.
' •
,
•
\
__ � .
and expertise.
--0
tia£��ostomy .• ,< �
to plan, but choice will often depend on local availability
_,_ .�-
_
......:;..:..\'....�.:.. .:: __.-�. " .
Best clinical practice
t
_:"_
REFERENCES 1.
Maisel RH. When your patient complains of a neck mass.
2.
Torsiglieri Jr AJ, Tom.
Geriatrics. 1980; 2: 103-8.
*
SD, Potsic WP. Paediatric neck masses: guidelines for
.I If history and examination does not lead to a clear
evaluation. International Journal of Pediatric
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Otorhinolaryngology. 1988; 16: 199-210.
3.
orientated embryology, 5th edn. Philadelphia: WB
,/ Lymphangiomas should be treated surgically in a specialist unit.
.I Fine needle aspiration and polymerase chain reaction should be utilized for the diagnosis of lB.
b
Moore KL, Persaud TVN. The developing human, clinically Saunders, 1993.
4.
Ellis PDM, Van Nostrand AWP. The applied anatomy of thyrog I ossa I tract remnants. Laryngoscope. 1977; 87: 765-70,
-
-
---.:..---
1788 I 5. 6.
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Sistrunk WE. The surgical treatment of cysts of the
22.
Keerl R. Nasopharyngeal endoscopy adds to reliability of
Patel SG, Escrig M, Shaha AR, Singh B, Shah JP.
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Golledge J, Ellis H. The aetiology of lateral cervical
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Regauer S, Gogg-Kamerer M, Braun H, Beham A. Lateral
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Scandinavica. 1997; 105: 623-30.
Otolaryngology and Head and Neck Surgery. 1992; 107:
King ESJ. The lateral Iympho-epithelial cyst of the neck
367-9.
(branchial cyst). Australian and New Zealand Journal of
27.
Conrad DA. Treatment of cat-scratch disease. Current
28.
Tuzuner N, Dogusoy G, Demirkesen C. Ozkan F, Altas K.
Opinion in Pediatrics. 2001; 13: 56-9.
Surgery. 1949; 19: 109.
12.
Martin H, Morfit HM. Erlich H. The case for branchiogenic cancer (malignant branchioma). Annals of Surgery. 1950;
Value of lymph node biopsy in the diagnosis of acquired
132: 867-87.
toxoplasmosis. Journal of Laryngology and Otology. 1996; 110: 348-52.
Soh KB. Branchiogenic carcinomas: do they exist? Journal of the Royal College of Surgeons of Edinburgh. 1998; 43: 1-5.
* 13.
29.
Thompson LD, Heffner DK. The clinical importance of
Actinomycosis of the posterior triangle: a case report and review of the literature. Journal of Laryngology and
Singh B, Balwally AN, Sundaram K, Har-EI G, Krgin B.
Otology. 1997; 111: 1082-5. 30.
Branchial cleft cyst carcinoma: myth or reality? Annals of Orvidas U, Kasperbauer JL. Pediatric lymphangiomas of the
Laryngology. 2001; 110: 1051-4.
* 31.
Laryngology. 2000; 109: 411-2. Hamoir M. Plouin-Gaudon I, Rombaux P, Francois G, Cornu
and Head and Neck Surgery. 1997; 116: 16-22. 32.
AS, Desuter G et al. Lymphatic malformations of the head
17.
Plaza Mayor G, Martinez-San Millan .I, Martinez-Vidal A. Is conservative treatment of deep neck space infections appropriate? Head and Neck. 2001; 23: 126-33.
and neck: a retrospective review and a support for staging. Head and Neck. 2001; 23: 326-37.
Gidley PW, Ghorayeb BY, Steirnberg CM. Contemporary management of deep neck space infections. Otolaryngology
head and neck. Annals of Otology, Rhinology, and 16.
Parhiscar A, Har-EI G. Deep neck abscess: a retrospective review of 210 cases. Annals of Otology, Rhinology, and
Otology, Rhinology, and Laryngology. 1998; 107: 519-24. 15.
Burns BV. al-Ayoubi A, Ray .I, Schofield JB, Shotton JC.
cystic squamous cell carcinomas in the neck: a study of 136 cases. Cancer. 1998; 82: 944-56. 14.
Burton F, Patete ML, Goodwin Jr WJ. Indications for open cervical node biopsy in HIV-positive patients.
Pathologica, Microbiologica, et Immunologica
11.
Mathur-Wagh U, Enlow RW. Spigland I, Winchester RJ, Sacks HS, Rorat E et al. Longitudinal study of persistent
Laryngology and Otology. 1994; 108: 653-9.
10.
White PD, Thomas .1M, Kangro HO, Bruce-Jones WD. Amess
.I, Crawford DH et al. Predictions and associations of
of the literature. International Journal of Pediatric
9.
Chan SC, Dawes PJ. The management of severe infectious
Nicollas R, Ducroz V, Garabedian EN, Triglia .1M. Fourth branchial pouch anomalies: a study of six cases and review
8.
Weber R, Hegenbarth V, Kaftan H, Krupe H, Jaspersen D.
thyroglossal tract. Annals of Surgery. 1920; 7 1: 121-2.
33.
Poe LB, Petro GR, Matta I. Percutaneous CT-guided
De Serres LM, Sie KCY. Richardson MA. Lymphatic
aspiration of deep neck abscess. AJNR American Journal of
malformations of the head and neck: a proposal for
Neuroradiology. 1996; 17: 1359-63.
staging. Archives of Otolaryngology - Head and Neck Surgery. 1995; 121: 577-82. 18.
Brewis C, Pracy JP, Albert DM. Treatment of lymphangiomas of the head and neck in children by
FURTHER READING
intralesional injection of OK-432 (Picibanil). Clinical Otolaryngology. 2000; 25: 130-4. 19.
neck. Facial Plastic Surgery Clinics of North America. 2001 ;
tuberculosis of the head and neck. British Journal of Oral
9: 131-45.
and Maxillofacial Surgery. 1996; 34:508-10.
* 20.
AI-Serhani AM. Mycobacterial infection of the head and neck: presentation and diagnosis. Laryngoscope. 2001; 111:2012-6.
21.
Enepekides DJ. Management of congenital anomalies of the
Penfold CN, Revington PJ. A review of 23 patients with
Morad NA. Tuberculous cervical lymphadenopathy; should antituberculous therapy be preceded by histological proof? Tropical Doctor. 2000; 30: 18-20.
Gidley PW, Ghorayeb BY, Stiernberg CM. Contemporary management of deep neck space infections. Otolaryngology and Head and Neck Surgery. 1997; 116: 16-22. McGuirt WF. The necK mass. Medical Clinics of North America. 1999; 83: 219-34. Soh KB. Branchiogenic carcinomas: do they exist? Journal of the Royal College of Surgeons of Edinburgh. 1998; 43: 1-5.
PART
15
THE UPPER DIGESTIVE TRACT EDITED BY JOHN HIBBERT
141 Anatomy of the mouth and dentition
1791
Barry KB Berkovitz
142 Benign oral and dental disease
1816
Crispian Scully and Jose-V Sebastian Bagan
143 Abnormalities of taste Steven M Bromley and Richard L Doty
1840
144 Salivary gland anatomy Graham J Cox
1852
145 Physiology of the salivary glands
1858
Roderick Cawsont and Michael Gleeson
146 lmaging of the salivary glands Nicole JM Freling
1871
147 Non-neoplastic salivary gland diseases
1898
Stephen R Porter
148 Cysts and tumours in and around the jaws, including sarcoma
1921
Mark McGurk, Anna Cassoni and Lisa Pitkin
149 Anatomy of the pharynx and oesophagus
1942
Nigel Beasley
150 Physiology of swallowing
1954
Paula Leslie and Stephen McHan well
151 Functional investigations of the upper gastrointestinal tract Lisa J Hirst
1964
152 Acute and chronic pharyngeal infection
1981
Marcelle Macnamara
153 Causes of dysphagia
2025
Elfy B Chevretton
154 Globus pharyngeus Petros D Karkos and Janet A Wilson
2037
155 Pharyngeal pouch
2043
Grant Bates
156 Oesophagal diseases Robert C Mason
2062
157 Neurological disease of the pharynx
2074
Robert J Sandersont, Paul Tierney and Richard Adamson
158 Dysphagia: management and intervention
2084
Alison Perry
159 Management and treatment of intractable aspiration Elfy B Chevretton
2094
141 Anatomy of the mouth and dentition
BARRY KB BERKOVITZ
I n troduct ion Palate Cheeks Lips Floor of the mouth Oropharynx Tongue Oral mucosa Muscles of the oral cavity
1 791 1 7 91 1 792 1 793 1 7 93 1 7 93 1 794 1 7 94 1 7 95
INTRODUCTION
Vascular supply and lymphatic drainage of the oral cavity Teeth Tissue spaces around the jaws The salivary glands Temporomandibular jo i nt Development of the face and palate Key points References Further reading
1 7 98 1 803 1 805 1 807 1 8 08 18 1 0 1 814 1 815 1 815
occupied mainly b y the tongue. The lateral walls of the mouth are defined by the cheeks and retromolar regions.
The importance of the mouth to the otolaryngologist is
Opening into the mouth are three pairs of major salivary
self-evident. It is the portal of entry for visual examina
glands
tion of the oropharynx, larynx and the opening of the
numerous minor salivary glands (labial, buccal, palatal,
Eustachian tube in the nasopharynx. It is also the portal
lingual).
(parotid, submandibular and sublingual) and
of entry for many of the surgical procedures undertaken in these regions. Malformations in the mouth, such as cleft palate, may have important consequences for the
PALATE
healthy functioning of the system. Infection or tumours from the mouth may spread to involve the ear, nose and
The palate is divisible into two regions: the hard palate in
throat. As an example, infection from maxillary teeth may
front and soft palate behind.
give referred pain to the nasal region, while infection from mandibular teeth may spread to the neck and result in severe (and sometimes fatal) respiratory embarrassment.
H a rd palate
Due to its close physical (and also evolutionary) relation ship to the ear, clinical conditions affecting the jaw joint
The skeleton of the hard palate is formed by the palatine
(temporomandibular joint) may need to be differentiated
processes of the maxillae and the horizontal plates of the
from those directly involving the ear.
palatine bones. The oral mucosa is bound tightly to the
The mouth can be subdivided into the vestibule
underlying periosteum. In its more lateral regions it also
(external to the teeth) and the oral cavity proper (internal
possesses a submucosa where the main neurovascular
to the teeth). The mouth extends from the lips and cheeks
bundles lie
(Figure 141.1).
externally to the anterior pillars of the fauces (palato
The periphery of the hard palate surrounding the
glossal arches) internally, where it continues into the
necks of the teeth is termed the gingiva and a zone
oropharynx:. The roof of the mouth is the palate and
similarly lacking submucosa runs anteroposteriorly in the
separates the oral and nasal cavities. The floor of the
midline as a narrow, low ridge, the palatine raphe. At the
mouth is formed by the mylohyoid muscles and is
anterior extremity of the raphe behind the incisor teeth is
_ . ..
..1_"--:'_
1792
I PART 15 THE UPPER DIGESTIVE TRACT
Fig ure 141.1
The hard palate. A, I ncisive papilla; B, palatine
raphe; C, palatine rugae; D, alveolus. Reprinted from Ref. 1 by permission from Elsevier.
Figure 141.2
Th e soft palate and oropharyngeal isthmus. A,
Palatoglossal fold; B, palatopharyngeal fold; C, palatine to n si l ; D,
a small prominence) the incisive papilla) that covers the
uvula. Reprinted from Ref. 1 by permission from Elsevier.
incisive fossa at the oral opening of the incisive canal. Radiating outwards from the palatine raphe in the anterior half of the hard palate are irregular transverse ridges or rugae. The pattern of rugae is unique for the individual. The submucosa in the posterior half of the hard palate contains minor mucous salivary glands. These secrete through numerous small ducts although) bilaterally) larger ducts collecting from many of these glands often open at the
paired
palatine
foveae.
These
are two sagittally
elongated depressions) sometimes a few millimetres deep) which flank the midline raphe at the posterior border of the hard palate. The upper nasal surface of the hard palate is the floor
The soft palate contains an aponeurosis) muscular tissue)
vessels)
nerves)
lymphoid tissue and
mucous
glands) while some taste buds are situated on its oral aspect. A thin) fibrous palatine aponeurosis is attached to the
posterior border of the hard palate. It represents the expanded tendons of the tensor veli palatini muscles and provides the fibrous skeleton of the soft palate that supports the palatine musculature. The aponeurosis is thick in the anterior two-thirds of the soft palate but very thin further back. All the other palatine muscles are attached to the aponeurosis.
of the nasal cavity and is covered by ciliated respiratory epithelium. The lower oral masticatory surface is covered by keratinized epithelium.
CHE EKS The cheeks are covered externally by skin and internally by
S o ft palate
mucous membrane (buccal mucosa) and have a muscular skeleton) the buccinator. Internally) the pink mucosa of the cheek adheres firmly to the buccinator muscle.
Few
The soft palate is a mobile flap suspended from the back
structural landmarks are visible. The parotid duct drains
of the hard palate) sloping down between the oral and
in the region of a small parotid papilla opposite the
nasal parts of the pharynx (Figure 141.2). The boundary
maxillary second molar tooth. A whitish line (the linea
between the hard and soft palate may be distinguished by
alba) may be seen at a position related to the occlusal
a change in colour) the soft palate being a darker red with
plane of the teeth) this hyperkeratinized line is presumably
a yellowish tint. In its relaxed and pendant position) its
the result of continuous mild trauma during biting. Yellow
anterior (oral) surface is concave) with a median raphe. Its
patches (Fordyce's spots) representing ectopic sebaceous
posterior aspect is convex and continuous with the nasal
glands may be evident on the internal surface of the cheek.
floor. A median conical process) the uvula, projects
Their numbers increase in puberty and in later life. Behind
downwards from its posterior border. Just behind and
the molar teeth, a fold of mucosa can be seen extending
medial to each upper alveolar process) in the lateral region
from the upper to the lower alveolus) especially when the
of the anterior part of the soft palate) a small bony
mouth is opened widely. This fold covers the pterygo
prominence can be felt. This is produced by the pterygoid
mandibular
hamulus) an extension of the medial pterygoid plate of
hamulus to the back of the mylohyoid line. The raphe
the sphenoid bone.
gives origin to the buccinator muscle from its anterior
raphe
that
extends
from
the
pterygoid
Ch apter
141
1793
An atomy of the mouth and dentition I
surface and the superior constrictor muscle from its posterior surface. The entrance to the pterygomandibular space lies lateral to the pterygomandibular raphe and medial to the ridge produced by the anterior border of the ramus of the mandible. Between the lips or cheeks and the teeth lies a slit-like space, the oral vestibule. Where the mucosa covering the alveolus of the jaw is reflected onto the lips and cheeks, a trough or sulcus is formed which is called the fornix vestibuli. With the teeth in occlusion, a space still exists behind the last molar tooth (retromolar region), allowing for the passage of fluids when the jaws are wired together following fractures. A variable number of sickle-shaped folds containing loose connective tissue run across the fornix vestibuli. The upper and lower labial frena (or frenula) are constant folds in the midline. Other folds may traverse the fornix near the canines or premolars.
Fi 9 u re
141.3
The ventral surface of the tong u e, rel ated to the
fl oor of the mouth. 1 , Ti p of tongue; 2, l ingual frenum; 3, s u bl i ngual p a p i l la; 4, s u bl ingual fold; 5, deep l ingual vein; 6, fim briated fold. Reprinted from Ref. 1 by per m ission from Elsevier.
The aperture of communication between the mouth
LIPS
and pharynx, the oropharyngeal isthmus, is situated
Like the cheeks, the lips are covered externally by skin and
between the soft palate above and the dorsum of the
internally by mucous membrane (labial mucosa) that is
tongue below, bounded on both sides by the palatoglossal
smooth and shiny and shows small elevations caused by underlying mucous glands. The lips have a muscular skeleton, the orbicularis oris muscle. The red zone of the lip (the vermilion) is a feature characteristic of man. In the upper lip, the vermilion
arches. Each palatoglossal arch runs downwards, laterally and forwards and contains the palatoglossus muscle with its covering mucous membrane. The approximation of the arches, to shut off the mouth from the oropharynx, is essential to deglutition.
protrudes externally in the midline to form the tubercle, above which is situated a grooved region termed the philtrum.
The
lower
lip
shows
a
slight
depression
corresponding to the tubercle.
Palatine tonsil The palatine tonsil is a mass of lymphoid tissue situated in the lateral wall of the oropharynx, where it lies within
FLOOR OF THE MOUTH
the tonsillar fossa between the diverging palatopharyngeal
This comprises a small horseshoe-shaped region beneath the tongue
(Figure 141.3). Near the base of the tongue in
the midline, a fold of tissue called the lingual frenum is seen to extend onto the inferior surface of the tongue. The sublingual papilla is a conspicuous centrally positioned protuberance at the base of the tongue. The submandib ular salivary ducts open into the mouth at this papilla. On either side of the sublingual papilla are the sublingual folds, beneath which lie the submandibular ducts and sublingual salivary glands. The muscle forming the floor of the mouth is the mylohyoid muscle.
and palatoglossal arches. It forms the anteroinferior part of
Waldeyer's
ring
of
lymphoid
tissue.
This
ring
surrounds the openings into the digestive and respiratory tracts and consists of the palatine and tubal tonsils laterally,
the
nasopharyngeal
tonsil
(adenoids)
and
smaller collections of lymphoid tissue in the intertonsillar intervals
posterosuperiorly,
and
the
lingual
tonsil
inferiorly. The medial (free) surface of the palatine tonsil projects into
the
oropharynx
and
usually
presents
a
pitted
appearance. These pits, 10-15 in number, lead into a system of blind-ending, often highly branching crypts, which extend through the whole thickness of the tonsil.
OROPHARYNX
The deep (lateral) aspect of the tonsil is covered by the
The oropharynx extends from the soft palate to the upper
easily separated throughout most of its extent from the
Figure 141.2). Its lateral wall
underlying superior constrictor muscle. An important
fibrous tissue of the tonsillar hemicapsule that can be border of the epiglottis (see
consists of the palatopharyngeal arch, with the palatine
and
tonsil lying between this arch and the palatoglossal arch
paratonsillar vein) descends from the soft palate lateral
sometimes
large
vein
(the
external palatine
or
anteriorly. The two arches are also known as the pillars of
to the tonsillar hemicapsule before piercing the phar
the fauces. The floor of the oropharynx is occupied by the
yngeal wall. Haemorrhage from this vessel can complicate
pharyngeal aspect of the tongue.
tonsillectomy.
1794
I PART
15 THE UPPER DIGESTIVE TRACT
The size of the tonsil varies greatly and at puberty may
palates above and has a tapered tip or apex touching the
be approximately 10-15 mm in transverse diameter and
incisor teeth, and a margin in contact with the gums and
approximately 20-25 mm in the vertical dimension. The
teeth. On each side, in front of the palatoglossal arch,
tonsil starts to atrophy at puberty so that, by old age, only
are four or five vertical folds, the foliate papillae.
a little tonsillar lymphoid tissue remains.
The dorsum has a longitudinal median sulcus and is papillated, the three remaining types of papillae repre senting the filiform, fungiform and circumvallate papil
TONGUE
lae. Of the papillae, all except the filiform papillae bear
The tongue is a highly muscular organ of deglutition, taste and speech. It is partly oral and partly pharyngeal in position. It has dorsal and ventral surfaces and a root and an apex. The curved dorsum of the tongue (Figure 141.4) shows an anterior, oral part facing upwards and a posterior, pharyngeal part facing posteriorly, the two being separated by a V-shaped groove, the sulcus terminalis. The sulcus terminalis runs anterolaterally towards the palatoglossal arches from a median depression, the foramen caecum, that indicates the site of the embryonic thyroid diverti culum that gives origin to the thyroid gland. The anterior two-thirds of the tongue anterior to the sulcus terminalis is related to the hard and soft
taste buds. The keratinized filiform papillae are the most numer ous. They are minute, conical or cylindrical projections, arranged
in diagonal rows extending
anterolaterally,
parallel with the sulcus terminalis, except at the lingual apex where they are transverse. They have a masticatory function, appearing to increase the friction between the tongue and food, facilitating the movement of particles by the tongue within the oral cavity. The fungiform papillae appear scattered on the lingual margin but also irregularly on the dorsal surface, where they may occasionally be numerous. They differ from filiform papillae by their larger size, rounded (mushroom) shape and deep red colour (due to their thin, nonkeratinized epithelium and highly vascular connective tissue core). The circumvallate papillae are cylindrical structures, 1-2 mm in diameter, varying in number from about 8 to 12 and form a V-shaped
row
immediately
in
front
of
the
sulcus
terminalis. Each papilla is circumscribed by a groove. The pharyngeal (postsulcal) third of the tongue lying behind the sulcus terminalis forms the base of the tongue and lies posterior to the palatoglossal arches. It forms the anterior wall of the oropharynx and its mucosa is 2
reflected on to the epiglottis posteriorly by a median and two lateral glossoepiglottic folds. The folds surround two depressions or valleculae. The pharyngeal part of the tongue has underlying lymphoid nodules that produce low surface elevations collectively termed the lingual tonsil. The ducts of small seromucous glands open on the apices of these elevations. The ventral inferior surface of the tongue (see Figure 141.3) is smooth, purplish and reflected on to the oral floor and gums. Anteriorly is a median mucosal fold, the
7
lingual frenum. Lateral to this fold on either side, a deep lingual vein is visible, and lateral to the vein is a fringed mucosal ridge, the plica fimbriata.
ORAL MUCOSA The lining of the mouth, the oral mucosa, is continuous with the skin at the vermilion of the lip and with the pharyngeal mucosa at the oropharyngeal isthmus. It Figure 141.4
The dorsum of the tongue. " Sulcus terminalis; posterior third (pharyngeal part); 3, lingual follicles; 4, pillars of fauces; 5, epiglottis; 6, vallecula defined by median and lateral glosso-epiglottic folds; 7, anterior two-thirds (palatine part); 8, circumvallate papillae; 9 , foramen caecum. Reprinted from Ref. 2 by kind permission of Informa Healthcare. 2,
varies in structure, appearance and function in different regions of the oral cavity. 1 It can be classified into masticatory, lining and specialized mucosae. Masticatory mucosa covers the gingivae (gums) and hard palate. Its epitheliu� is keratinized (often parakeratinized) and has a dense fibrous lamina propria. It is pink in colour. A
Chapter 1 41
Anatomy of the mouth and dentition I 1795
submucosa is absent from the gingivae and the midline
alveolar processes of the maxilla and mandible by the side
palatine ra phe, but is present over the rest of the hard
of the molar teeth. Behind, it arises from the anterior
palate ,
margin of the pterygomandibular r aphe (a thin band of
especially where
it contains m ucous
salivary
glands, and also the greater palatine nerves and vessels.
tendinous fibres passing between the hamulus of the
The masticatory mucosa is bo u nd firmly to underlying
med ial pter ygoid plate down to the posterior end of the
bone or to the necks of the teeth, forming in the gingivae
mylohyoid line of the mandible). Additionally, a few
and palatine raphe a mucoperiosteum.
fibres arise from a fine tendinous band that bridges the
internal surfaces of the lips
interval between the maxilla and the pterygoid hamulus.
and cheeks, floor of the mouth, soft palate, ventral surface
From these origins the fibres of buccinator pass forwards
of the tongue and the alveolar processes (excluding the
towards the angle of the mouth. Here,
gingivae). It is red in colour, having a nonkeratinized
decussate, those from below crossing to the upper part of
Lining mucosa covers the
the central fibres
stratified squamous epithelium overl ying a loosely fibrous
the mouth, those from above crossing to the lower part.
and elastic la m ina propria, and the submucosa conta ins
The highest and lowest fibres of buccinator continue
some fat deposits and collections of minor mucous glands. Gustatory mucosa covers the anterior two-thirds of the
forward
to
enter
their
corresponding
lips
without
decussation.
dorsum of the tongue. The vermilion (red zone) of the lip
The buccinator muscle compresses the cheek against
separates the skin from lini ng mucosa has been
the teeth and gums during mastication and assists the
that
regarded by some as being specialized, as it shares features
tongue in directing food between the teeth. When the
of bo th l ining and masticatory mucosa. The epithelium
cheeks have been distended
that attaches the tooth to the gingiva, the j unctional
it between the lips, for example when playing wind
epithelium, also has features that dis tinguish
it from all
inst ruments . The buccinator muscle is innervated by the
other stratified squamous epithelia (for example, internal
buccal branch of the facial nerve. Its arterial supply is
and external basal lamina) .
with air, the buccinators expel
derived from the facial and maxillary (buccal branch ) arteries .
MUSCLES OF THE ORAL CAVITY Mylohyoid muscle Buccinator muscle The main muscle forming the floor of the mouth is the
141.7). Immedi
The muscle of the cheek is the buccinator (Figure 141.5).
mylohyoi d muscle (Figures 1 41.6 and
Above and below it is attached to the outer surfaces of the
ately above it is the geniohyoid muscle. The mylohyoid
Figure 141 . 5 The buccinator muscle and the infratemporal fossa. '/ Lateral pterygoid muscle (two heads) ; 2/ bu ccal nerve; 3/ lingual nerve with accompanying branch from maxillary artery; 4, inferior alveolar nerve and artery; 5, mylohyoid nerve; 6, medial pterygoid muscle ( two heads) ; 7, maxillary artery; 8, buccinator muscle; 9, depressor anguli oris muscle. Reprinted from Ref. 2 by kind permission of Informa Healthcare.
_
.... .J _�_.
1796
I PART 15 THE U PPER DIGESTIVE TRACT
muscle
is
a
flat,
triangular
sheet
attached
to
the
mylohyoid line of the mandible. The posterior fibres pass medially and slightly downwards to the front of the body of the hyoid bone near its lower border. The middle and anterior fibres from each side decussate in a median fibrous raphe that stretches from the symphysis menti to the hyoid bone. The mylohyoid muscle elevates the floor of the mouth in the first stage of swallowing. It also aids in elevating the hyoid bone or depressing the mandible when the hyoid bone is fixed. The muscle is supplied by the mylohyoid branch of the inferior alveolar nerve and derives its blood supply from three sources: the lingual artery (sublingual branch), the maxillary artery (the mylohyoid branch of the
inferior
alveolar
artery)
and
the
facial
artery
(submental branch).
Ge niohyoid This narrow muscle lies above the medial part of the
(Figure 141.8
mylohyoid
and see also
Figure 141.6).
It
arises from the inferior genial tubercle (mental spine) on the back of the symphysis menti. It runs backwards and Figure 141.6
The floor of the mouth as seen in a median
sagittal section through the head. 1, Hard palate; 2, soft palate; 3, upper lip and superior part of orbiculari oris muscle; 4,
slightly downwards to attach to the anterior surface of the body of the hyoid bone. The geniohyoid muscle elevates the hyoid bone and
edentulous maxillary alveolar ridge; 5, lower lip with inferior
draws it forwards. When the hyoid bone is fixed, the
part of orbicularis oris muscle; 6, body of mandible; 7 , tongue;
geniohyoid muscle depresses the mandible. The muscle is
8, genioglossus muscle; 9, geniohyoid muscle; 10, mylohyoid muscle; 11, hyoid bone; 12, epiglottis: 13, valeculla. Reprinted
supplied by the first cervical spinal nerve, through the hypoglossal nerve. The blood supply is derived from the
from Ref. 2 by kind permission of Informa Healthcare.
lingual artery (sublingual branch).
Fig u re 141.7
Med ial view of the floor of mouth
showing deep part of the submandibular gland
(A)
passing around the free border of the mylohyoid muscle
(8). C,
Superficial part of submandibular
gland; D, submandibular duct wrapping around the lingual nerve (E); F, sublingual strand; G, bristle in opening of submandibular duct at the subling ua I pa pilla; H, branches of the lingua I nerve to the sublingual gland carrying •
parasympathetic nerve fibres. Reprinted from Ref. 1 by permission from Elsevier.
Chapter 1 41
Anatomy of the mouth and de ntition I 1797
Figure 1 41 .8 Muscles of the tongue and structures on the hyoglossus m uscle in the floor of the mouth. 1 , Li ng ua I nerve; 2, hypog lossa I nerve ; 3, submandibular duct (cutl ; 4, external carotid artery; 5, lingual artery; 6, glossopharyngeal nerve (cut) ; 7 , hyoglossus muscle; 8, styloglossus muscle; 9, geniohyoid muscle: 1 0, g enioglossus muscle. Reprinted from Ref. 1 by permission from Elsevier.
Muscles of the tongue
runs up to insert into the side of the tongue between the inferior longitudinal muscle medially and styloglossus
The muscles of the tongue comprise both extrinsic and intrins ic muscles,
the
former
extending
outside
the
laterally. The hyoglossus m uscle depresses the tongue. It is
tongue and moving it bodily, the latter lying who lly
innervated by the hypoglossal nerve. Its arterial supply is
within it and altering its shape.
derived fro m th e lingual (sublingual branch) and the
The extrinsic musculature is composed of fo u r pairs of muscles:
geniogloss us,
hyoglossus,
styloglossus
facial arteries (s ubmental branch).
and
palatogloss us.
STYLOGLOSSUS This muscle arises from near the apex of the styloid
GENIOGLOSSUS MUSCLE
process (an terolate ral aspect) and from the styloid end of
The genioglossus m uscle lies near the midline ( see
Figures
the stylomandibular ligament (a fibrous cord extending
141.6 and 141.8). It arises from the superior genial
from the tip of the styloid process to the lesser cornu of
tubercle ( men tal spine) behind the mandibular symphysis
the hyoid bone)
and above the origin of the geniohyoid muscle. From its
m uscle
origin, the fibres fan out as they pass backwards and
s u bstance of the tongue,
upwards. The inferior fibres are attached to the upper
hyoglossus.
anterior s u rface of the hyoid body near the midline.
The
runs
(Figure 141.8). From this origin, the
downwards an d forwards
styloglossus
muscle
to enter
the
decussating with fibres of acts
to pull
the
tongue
r ntermed iate fibres pass backwards into the posterior part
upwards and backwards. The muscle is supplied by the
of the tongue, and superior fibres ascend forwards to enter
hypoglossal nerve and derives its blood supply from the
the whole length of the ventral surface of the tongue from
sublingual branch of the lingual artery.
root to apex, intermingling with the intrinsic muscles. The genioglossus muscle brings abo ut the forward traction of the to ngue to protrude its apex from the mouth. Acting bilaterally, the two muscles depress the central part of the tongue, making it concave from s ide to side.
Acting unilaterally,
the muscle helps move the
tongue to the opposite side.
Genioglossus receives its
motor innervation from the hypoglossal nerve. Its blood supply is de rived from the lingual artery (sublingual branch) and the facial artery (submental branch).
PALATOGLOSSUS Although th i s muscle is most closely associated with the soft palate in function and innervation, it is described here with the other tongue muscles. The palatoglossus arises from the palatine aponeurosis and passes to the side of
the
tongue
within
the
palatoglossal arch. Acting
bilaterally, the muscles narrow the oropharyngeal isthmus and can also help raise the s i des of the tongue. Unlike the other tongue muscles, the palatoglossus is innervated, not
HYOGLOSSUS
by the hypoglossal nerve, but by the cranial portion of the accessory nerve through the pharyngeal plexus. Its blood
Thi s muscle arises from both the greater cornu and from
supply is derived from the ascending pharyngeal and
the front of the body of the hyoid bone (Figure 141.8). It
facial (ascending palatine) arteries.
1798 I
PART 1 5 TH E U PPER D I G ESTIVE TRACT
I N TRI N S I C MUSCLES OF THE TON G U E
These
comprise
four
inferior longitudinal,
groups:
the
superior
and
the transverse and the vertical
muscles.
VASCULAR SUPPLY AND LYMPHATIC DRAINAGE OF THE ORAL CAVITY Arteries
The superior longitudinal muscle forms a thin stratum of longitudinal and oblique fibres lying beneath the lining of the dorsum of the tongue. The inferior longitudinal muscle is a narrow band of muscle beneath the inferior surface between the genioglossus and hyoglossus muscles. The transverse muscle fibres pass laterally from the median fibrous septum to the submucous fibrous tissue at the lingual margin. The vertical muscle fibres extend from the dorsal to the ventral aspects of the tongue in the borders of its anterior part. When the superior and inferior longitudinal muscles contract, the tongue tends to shorten. In addition, the superior longitudinal fibres also pulls the apex and sides upwards to
make
the
dorsum concave,
while
the inferior longitudinal fibres pull the apex down to make
the
dorsum
convex.
The
transverse
contracts to narrow and elongate the
muscle
tongue
while
contraction of the vertical muscle makes the tongue flatter and wider. Acting alone or in pairs and in endless combination,
the
intrinsic
muscles
give
the
tongue
precise and highly varied mobility, important not only in alimentary function but also in speech. All intrinsic lingual muscles are supplied by the hypoglossal nerve and
derive
their
blood
supply
from
the
lingual
artery.
The main arteries to the teeth, palate and cheeks are derived chiefly from the maxillary artery, a terminal branch of the external carotid. The lips are mainly supplied by the superior and inferior labial branches of the facial artery. The floor of the mouth and tongue are supplied by the lingual arteries. The cheek is supplied by the buccal branch of the maxillary artery. Teeth in the lower jaw are supplied by the inferior alveolar (dental) artery, a branch of the maxillary artery (see
Figure 14l.5). It lies in the infratemporal fossa where
it gives off a mylohyoid branch before entering the mandibular foramen. The inferior alveolar artery then traverses the mandibular canal
(accompanied by the
inferior alveolar nerve) to supply the mandibular molars and premolars and divides into the incisive and mental branches below the premolar teeth. The incisive branch continues below the incisor teeth (which it supplies) to the midline. The mental artery leaves the mental foramen to supply the chin. Teeth in the upper jaw are supplied by the posterior, middle and anterior superior alveolar (dental) arteries that form a plexus of vessels. The posterior superior alveolar artery usually arises from the third part of the maxillary artery in the pterygopalatine fossa. It descends on the infratemporal surface of the maxilla to supply molar
MUSCLE OF THE LIPS
and
premolar
teeth,
adjacent
bone
and
the
maxillary sinus, and provides superficial branches that
The muscles surrounding the mouth and contributing to
continue over the alveolar process to supply the gingivae.
the lips are derived from two different sources. Neigh
The anterior superior alveolar artery arises from the
bouring muscles of facial expression converge on the
infraorbital
angle of the mouth and pass through into the lips. For
through
the upper lip, these are chiefly from the buccinator and
infraorbital groove and canal with the infraorbital nerve.
depressor
the
It curves through a fine canal (canalis sinuosus) to supply
buccinator, levator anguli oris and zygomaticus major.
the upper incisor and canine teeth and the mucous
anguli
oris,
and
for
the
lower
lip,
artery
the
that
inferior
enters
orbital
the
orbit
fissure
to
posteriorly run
in
the
In addition, an accessory muscle, incisivus labii super
membrane in the maxillary sinus. A middle superior
ioris, is present in the upper lip, arising from the floor of
alveolar artery is often present and supplies the premolar
the incisive fossa of the maxilla above the eminence of the
teeth.
lateral incisor tooth and running laterally within the
The gingival tissues derive their blood supply from the
upper lip to the modiolus (a zone of muscle intersection
maxillary and lingual arteries. In the lower jaw, the buccal
just beyond the corner of the mouth). A similar strip of
gingiva posteriorly is supplied by the buccal artery (a
muscle
is
present
in
the
lower
lip,
incisivus
labii
branch of the maxillary artery as it crosses the lateral
inferioris, arising from the floor of the incisive fossa of
pterygoId muscle) and by perforating branches from the
the mandible and running laterally within the lip to the
inferior alveolar artery. Anteriorly, the labial gingiva is
modiolus.
supplied by the mental artery and by perforating branches
The muscles of the mouth are capable of various
of the incisive artery. The lingual gingiva is supplied by
movements, including closing, protrusion and pursing of
perforating branches from the inferior alveolar artery and
the lips. The muscles are innervated by the facial nerve
by the lingual artery of the external carotid.
(buccal and mandibular branches) and derive their blood
In the upper jaw, the buccal gingiva around the molar
supply from the facial (superior and inferior labial),
and
maxillary (mental and infraorbital branches) and super
perforating branches from the posterior and middle
ficial temporal arteries.
superior alveolar arteries and by the buccal artery. The
premolar
teeth
are
supplied
by
gingival
and
Chapter 141
Anatomy of the mouth and dentition I 1799
labial gingiva of the anterior teeth is supplied by labial
The cheek is drained by the buccal vein that leads to
branches of the infraorbital artery and by perforating
the pterygoid venous plexus in the infratemporal fossa.
branches of the anterior superior alveolar artery. The
Venous blood from the lips is collected by the superior
palatal gingiva around the maxillary teeth is supplied
and inferior labial veins and drains into the facial vein.
primarily by branches of the greater palatine artery, a
The veins of the hard palate accompany the arteries and
branch of the third part of the maxillary artery in the
drain largely to the pterygoid plexus. Veins accompanying the superior
pterygopalatine fossa. The hard palate derives its blood supply principally from the greater palatine artery, a branch of the third part
alveolar
arteries
drain the upper jaw and teeth anteriorly into the facial vein, or posteriorly into the pterygoid venous plexus.
artery
Veins from the lower jaw and teeth collect into several
descends (with its accompanying nerve) in the palatine
inferior alveolar veins. Some of these veins drain through
canal. In the canal, it gives off two or three lesser palatine
the mental foramen to the facial vein, others via the
arteries that are transmitted through lesser palatine canals
mandibular foramen to the pterygoid venous plexus.
of the maxillary
artery.
The
greater
palatine
to supply the soft palate and tonsil (anastomosing with
No accurate description is available concerning the
the ascending palatine branch of the facial artery). The
venous drainage of the gingivae, although it may be
greater palatine artery emerges on to the oral surface of
assumed
the palate at the greater palatine foramen and runs in a
nasopalatine veins are involved. These veins run into
that
buccal,
lingual,
greater
palatine
and
curved groove near the alveolar border of the hard palate
the pterygoid plexuses (apart from the lingual veins,
to the incisive canal. It ascends this canal and anasto
which pass directly into the internal jugular veins).
moses with septal branches of the nasopalatine artery.
There are two sets of veins draining the tongue. The
The tongue and floor of mouth are supplied mainly by
deep lingual vein begins near the apex of the tongue and
the lingual artery that arises in the neck from the external
runs back on its ventral surface (see
carotid artery (see
a sublingual vein from the sublingual salivary gland, to
Figure 141.8). It reaches the floor of
Figure 141.3). It joins
the mouth by passing between the hyoglossus muscle and
form the vena comitans nervi hypoglossi. This then passes
the middle constrictor of the pharynx. Near the tip of the
backwards with the hypoglossal nerve and joins the
tongue, the lingual artery anastomoses with its fellow. The
lingual, facial or internal jugular vein. Dorsal lingual veins
branches of the lingual artery in the floor of the mouth
drain the dorsum and sides of the tongue and join the
are the dorsal lingual branches, the sublingual artery and
lingual veins accompanying the lingual artery. They drain
the deep lingual artery.
into the internal jugular in the region of the hyoid bone.
The dorsal lingual arteries (usually two or three) arise medial to the hyoglossus muscle and ascend to the posterior part of the dorsum of the tongue. They supply
Lymph drainage
the mucous membrane of the dorsum of the tongue, the palatoglossal arch, soft palate, tonsil and epiglottis.
The principal sites of drainage of lymphatic vessels from
The sublingual artery arises from the lingual artery at
orodental tissues are the submental, submandibular and
the anterior margin of hyoglossus. It passes forward
jugulodigastric lymph nodes. However, the manner of
between the genioglossus and mylohyoid muscles to the
drainage is so variable that there is no precise and
sublingual gland. It also provides a branch that enters a
accurate description.
small
foramen
(lingual
foramen)
on
the
mandible,
The cheek, upper lip and lateral parts of the lower lip
situated in the midline on the posterior aspect of the
drain to the submandibular nodes. The central part of the
symphysis, immediately above the genial tubercles.
lower lip drains to the submental nodes.
The deep lingual artery is the terminal part of the
The lymph vessels from the teeth usually run directly
lingual artery and is found on the inferior surface of the
into the submandibular lymph nodes on the same side.
tongue near the lingual frenum.
Lymph from the mandibular incisors, however, drains
In addition to the lingual artery, the tonsillar and
into the submental lymph nodes. Occasionally, lymph
ascending palatine branches of the facial and ascending
from the molars may pass directly into the jugulodigastric
pharyngeal arteries also supply tissue in the root of the
group of nodes.
tongue. In the region of the valleculae, epiglottic branches
The
lingual
and
palatal
group
of
gingivae
nodes,
drain
either
into
the
of the superior laryngeal artery anastomose with the
jugulodigastric
directly
inferior dorsal branches of the lingual artery.
indirectly through the submandibular nodes. Lymphatics
or
from the bulk of the palate terminate in the jugulodigas tric group of nodes.
Veins
The lymphatics from the tongue drain to three main regions: marginal, central and dorsal. The anterior region
As with veins elsewhere in the body, the pattern of
of the tongue drains into the marginal and central vessels
IS
and, behind the circumvallate papillae, the posterior part
drainage for the mouth and associated structures variable and only a generalized account will be given.
of the tongue drains into the dorsal lymph vessels. Of
_
1
______..•__
1800 I
PART 1 5 THE UPPER DIGESTIVE TRACT
Innervation
particular clinical importance is appreciating that more central
regions
may
drain
both
ipsilaterally
and
contralaterally. Marginal lymph vessels of the tongue that arise from
The
the apex of the tongue and the lingual frenum area descend under the mucosa to widely distributed nodes. •
derives
its
sensory
mandibular, facial and hypoglossal nerves. The salivary the facial and glossopharyngeal nerves. The innervation of the oral musculature is shown in Table 141.1.
pass to both sides. Some vessels drain to submandibular nodes.
mouth
glands are supplied by secretomotor fibres derived from
efferent vessels of submental nodes that are median
Some vessels end in jugulodigastric nodes, one vessel
the
supply the tongue, including special taste sensation. The
under the frenulum to end in the contralateral nodes,
•
lining
muscles of the mouth are supplied chiefly by the
Some vessels enter the submental nodes and also pass to the jugulo-omohyoid nodes. Vessels may cross
•
mucosa
innervation chiefly from the maxillary and mandibular divisions of the trigeminal nerve. Additional nerves
SEN SORY S U PPLY
often reaching the jugulo-omohyoid node.
Cheeks, lips and palate The sensory supply to the cheek is derived from the buccal branch of the mandibular nerve (see Figure
Vessels from the lateral margin of the tongue may drain into the submandibular nodes while others end in the jugulodigastric or jugulo-omohyoid nodes. Vessels from
141.5). This nerve arises from the anterior division of
the posterior part of the lingual margin traverse the
the mandibular nerve within the infratemporal fossa. Initially deep to the lateral pterygoid muscle, it emerges
pharyngeal wall to the jugulodigastric lymph nodes.
between the two heads of the muscle and runs forwards to
Vessels draining the central region of the tongue may
supply the mucosa of the cheeks.
drain to either or both sides into the deep cervical nodes, jugulo-omohyoid
The upper lip is supplied by the infraorbital branch of
nodes. Some pierce the mylohyoid muscle to enter the
the maxillary nerve (Figure 141.9). Running along the
submandibular nodes.
floor of the orbit in the infraorbital canal, it enters the
especially
the
jugdlodigastric
and
Vessels draining the dorsum of the tongue in the
face at the infraorbital foramen, where its labial branch
region of the circumvallate papillae and behind them run
runs downwards to supply the upper lip. The mental
posteroinferiorly. Those near the median plane may pass
nerve is a terminal branch of the inferior alveolar nerve
to either or both sides, draining to the jugdlodigastric and
and exits the mandible at the mental foramen to supply
jugulo-omohyoid lymph nodes.
the lower lip (see Figure 141.9).
Table 1 41.1
'Begion-" '. t
-.
Innervation of the oral musculature.
i;�"
Nerve
��
} }
Orbicularis oris
Facial
Cheeks
Buccinator
Facial
Tongue (intrinsic musculature)
Transverse
Lips
Longitudinal Vertical Tongue (extrinsic musculature)
GeniOglOSSUS Hyoglossus
Hypoglossal
Hypog lossa I
Styloglossus
Floor of mouth
Palatoglossus
Accessory (cranial part)
Mylohyoid
Mandibular division of trigeminal
Geniohyoid Palate
Tensor veli palatini Levator veli palatini Palatoglossus Palatopha ryngeus Musculus uvulae
Reprinted from Ref. 1 by permission from Elsevier.
)
Hypoglossal (CI fibres) Mandibular division of trigeminal
Accessory (cranial part)
Chapter 1 41 Ana tomy of the mouth and dentition I
1801
The sensory nerves to the palate are derived from the
palatine nerve descends through the greater palatine
greater and lesser palatine and nasopalatine branches of
canal, entering the hard palate at the greater palatine
the maxillary nerve (Figure 141.10) These nerves pass
foramen. It then passes forwards on the bony palate
through
towards the canine tooth) supplying the gums and the
the
pterygopalatine
ganglion.
The
greater
mucosa and glands of the hard
p alate (excluding the
anterior teeth). As it leaves the greater palatine canal, palatine branches are also distributed to the soft palate. The smaller lesser palatine nerves descend thro ugh the greater palatine canal to emerge through the inconspic uous lesser palatine foramina and give branches to the uvula) tonsil and soft palate.
Fibres conveying taste
impulses from the palate probably pass via the palatine nerves
to
the
pterygopalatine
ganglion
(see
Figure
141.10) and through it to t he nerve of the pterygoid canal and then the greater pet rosal nerve to reach the facial ganglion, where their somata are situated. Para sym p athetic
p ostganglionic secretomotor fibres run in the
facial nerve through its greater petrosal nerve to reach the pterygopalatine ganglion to be distributed in the palatine nerves) thereby reaching palatine mucous glands. The nasopalatine nerves (Figure 141.10) enter the palate at the incisive foramen to supply the anterior part of the hard palate behind the incisor teeth. There is an additional sensory component in the region of the pillars of the fauces derived from the glossopharyngeal nerve which is involved in the gag reflex (see Figure 141.8). The floor of the mouth is supplied by the lingual nerve (see Figures 141.5 and 141.9). This nerve arises from the posterior division
of
the
mandibular
nerve
in
the
infratemporal fossa.
Teeth and gingivae The regional supply to the teeth and gingivae is shown in Table 141.2. The posterior superior alveolar nerves supply Figure 1 4 1 .9
Infratemporal fossa showing mandi bula r nerve
branches . 1 , Auric ulotemporal nerve surro und ing middle meningeal artery ; 2, buccal nerve; 3, lingual nerve
G oined
the teeth in the upper jaw, while the inferior alveolar nerve supplies those in the lower jaw.
by
chorda tympani nerve); 4, inferior alveolar nerve; 5, mylohyoid
There are three superior alveolar (dental) nerves that arise from the maxillary nerve in the pterygopalatine fossa
nerve; 6, mental nerve; 7, sphenomandibular ligament; 8, medial
or in the infraorbital groove (canal) and these form a
pterygoid muscle; 9. infraorbital nerve. Reprinted from Ref. 1 by
plexus of nerves supplying all the upper teeth. The
permission from Elsevier.
posterior superior alveolar (dental) nerve leaves the maxillary nerve in the pterygopalatine fossa and runs
Figure 141.1 0
The pterygopalatine ganglion. 1,
I nternal carotid artery; 2, maxillary nerve; 3, nerve of pterygoid ca na I; 4, pterygopalati ne gang I ion; 5, greater palatine nerve; 6, lesser palatine nerve; 7, nasopalatine nerve d issected off from nasal septum ; 8, nasopalatine nerve at incisive fossa. Reprinted from Ref. 1 by permission from Elsevier.
I
;'
L·_ ..i..
""", ,,, , _____ __ _ _
.
1802 I
PART 1 5 THE UPPER D I GESTIVE TRACT
Nerve su p ply to the teeth and gingiva.
Table 1 41 .2
Maxilla
Nasopalatine nerve
Greater palatine nerve
Anterior su perior al veolar nerve
Middle su perior al veolar
Palatal gingiva Teeth
Posterior superior al veolar nerve
nerve I nfraorbital nerve
1
4
3
5
7
6
8
Tooth position
Buccal nerve and perforating branches of inferior alveolar nerve
Menta I nerve
Mandible
Buccal gingiva
Posterior superior alveolar nerve and buccal nerve
2
Buccal gingiva Teeth
Inferior alveolar nerve
I ncisive nerve
Lingual gingiva
Lingual nerve and perforating branches of inferior alveolar nerve Repri nted from Ref. 1 by permission from Elsevier.
anteroinferiorly to pierce the infratemporal surface of the
premolar teeth to supply the skin of the lower lip and
maxilla, descending under the mucosa of the maxillary
chin (see
Figure 141 .9).
sinus. After supplying the lining of the sinus, the nerve
The nerves supplying the gingiva in the upper jaw
divides into small branches that link up as the molar part
come from the maxillary nerve via its greater palatine,
of the superior dental plexus, supplying twigs to the
nasopalatine and anterior, middle and posterior superior
molar teeth. It also supplies a branch to the upper gingiva
alveolar branches. The mandibular nerve innervates the
and the adjoining part of the cheek.
gingiva in the lower jaw by its inferior alveolar, lingual
The variable middle superior alveolar (dental) nerve arises from the infraorbital nerve as it runs in the infraorbital groove, and passes downwards and forwards in the lateral wall of the maxillary sinus. It ends in small
and buccal branches (see
Table 141 .2).
The tong ue and floor of the mouth The sensory supply to the tongue involves both general
branches that unite with the superior dental plexus,
and taste afferents and reflects the embryological devel
supplying small rami to the upper premolar teeth.
opment of the structure. Thus, it can be considered in two
The anterior superior alveolar (dental) nerve leaves the
portions,
the
presulcal
(anterior
two-thirds)
and
a
lateral side of the infraorbital nerve near the midpoint of
postsulcal (posterior one-third). The nerve of general
its canal and traverses the canalis sinuosus in the anterior
sensation to the presulcal part is the lingual nerve,
wall of the maxillary sinus. Curving first under the
indicating the embryological derivation of this part from
infraorbital foramen, it passes medially towards the nose,
the first branchial arch. The lingual nerve also carries taste
turns downwards and divides into branches supplying the
sensation derived from the chorda tympani branch of the
incisor and canine teeth. It assists in the formation of the
facial nerve. The main nerve supplying general (and taste )
superior dental plexus.
sensation to the postsulcal part is the glossop haryngeal
The inferior alveolar (dental) nerve arises from the posterior
division
infratemporal
fossa
of
the
(see
mandibular
nerve
in
nerve, while an additional area in the region of the
the
valleculae is supplied by the internal laryngeal branch of
Figures 141 .5 and 141 .9).
the vagus nerve, indicating the embryological derivation
Emerging from beneath the lower head of the lateral
of the postsulcal part from the third and fourth branchial
pterygoid muscle, it descends to enter the mandibular
arches.
canal via the mandibular foramen (accompanied by the
The lingual nerve originates from the posterior trunk
inferior alveolar artery). Just before entering the man
of the mandibular nerve in the infratemporal fossa (see
dibular canal, the inferior alveolar nerve gives off a small
Figures 141.5, 141 . 8 and 141 .9. Here, it is joined by the
mylohyoid branch to supply the mylohyoid muscle and
chorda tympani branch of the facial nerve that supplies
the anterior belly of digastric.
taste to the
anterior two-thirds of the
tongue
and
In the mandibular canal, the inferior alveolar nerve
parasympathetic fibres that supply the submandibular
runs downward and forward, generally below the apices
and sublingual glands via the submandibular ganglion
of the cheek teeth until, below premolar teeth, it divides
(Figure 141 .9). Emerging from beneath the lower head of (Figure 141 .5), the lingual
into terminal incisive and mental branches. The incisive
the lateral pterygoid muscle
branch continues forward in a bony canal or in a
nerve passes forwards medial to the inferior alveolar nerve
plexiform arrangement, giving off branches to the first
and is closely applied to the periosteum of the medial
premolar, canine and incisor teeth, and the associated
surface of the mandible by the side of the roots of the
labial gingivae. The lower central incisor teeth may receive
third molar tooth
a bilateral
is at great risk during surgical removal of (impacted)
innervation,
fibres probably crossing
the
(Figure 141 .7). Here, the lingual nerve
midline within the periosteum to re-enter the bone via
lower third molars using a lingual approach. The lingual
numerous canals in the labial cortical plate.
nerve then passes medial to the mandibular origin of the
. The
mental
nerve
passes
upward,
backward
and
mylohyoid muscle, which carries it progressively away
outward to emerge from the mandible via the mental
from the' mandible. It passes downward and forward on
foramen between and just below the apices of the
the deep surface of the mylohyoid muscle and then runs
Chapter 1 41 A n a t o my of t h e m o u t h a n d d e nt iti o n I
below the subma nd ib u l a r du ct, which crosses it from medial to lateral ( F ig ure
141 .7). The nerve next cu rves
upward, forward and media]]y to en te r the tongue. The
lingual nerve is connected to
the submand ib ular
g ang l io n
1 803
a n d for w a rds between t h e mylohyoid a n d hyoglossus
m usc l es . Here, the hypoglo ssal nerve is situated below the
deep p art of the su bm a n d ib ular gl and , the submandibular duct and the l ingu al nerve. It then passes on to the lateral
by two or three branches and, at the anter i o r margin o f
aspect of the ge n i ogloss u s muscle, continuing fO lWa rds in
the hyoglossus , it forms co nnecting loo ps wi th twigs o f
i ts substance as fa r as the t ip of the tongue. The muscular branches from the hyp oglo ss al nerve are
the hypoglossal nerve. l i ngual
d is tr ib u ted to styloglo ssus , hyoglossus and genioglossus.
gingivae, the m ucosa of the floor of the mouth and the
Numerous slender rami ascend into the tongue to supply
anterior
its intri ns i c muscles .
Branches
of the lingual nerve supply the
two - thirds
(pres ulcal
part)
of
the
tongu e
( excluding the circ umvallate papillae, which a re suppl ied The glossopharyngeal nerve is present i n the neck where it passes around
posterior
the
The nerve to geniohyoid ( and to thyrohyo id) arises near th e posterior border of the hyo gloss us . It is derive d
by the gloss opharyngeal nerve ) .
styJ opharyngeus muscle, which it s u pplies
fro m fi bres of the
fi rst cervical sp inal
nerve .
border o f th e
( Figure 14 1.8).
It runs forwards on this m uscle and ei ther pierces the
TEETH
lowe r fibres of the s uperior cons t ri ct o r m uscle or passes between it and the middle constrictor to be d istrib u ted to the
p ostsuJcal
part
of
circumvallate p ap illa e) . It
the
( i n cl u d ing
tongue
the
co mm un i cates with the l i ng ual
nerve.
There
are
( p ri mary)
two
genera tio ns
dentit i o n
and
of teeth:
the
decid uous
the p e rm anen t
(secondary)
d entition. In the complete deciduous denti tion there are
20 teeth - five in each j aw qu a dra nt. In the co mplete
The senso ry sup ply to the valle cu l ae of the tongue ( t h e
perma nent de n t i tion there are 32 teeth - eight in each jaw
recess between t h e m edia n a nd lateral glossoepiglottic
q u a d r a nt . In both dentitions, there are three basic to oth
folds ) is derived from the internal laryngeal nerve. This
fo rms: incisiform, caninifonn and molarifo nn . I nc isi form
nerve is a branch of the s u p erior l aryngeal nerve and ,
teeth ( i nc isors ) are
p assing between the superi o r an d i n fer i o r constrictor
crowns.
muscles, pierces the thyro hyoid membrane. Fro m here,
tea ri ng teeth, having a single, s tout, p o inte d , cone-s h a p ed
branches ascend to supply the valleculae.
is
The p arasympathetic innervation o f the
li n g ual
nerve (Figure ] 4 1 .9) and
synapses in the submandib u l ar gangl i o n . Postgangl ionic fibres re-enter the lingual nerve symp athetic s upply to l i n g ual the to ngue thro u gh plexuses
to
teeth, having thin, blade-l i ke ( canines)
are
piercing
or
grinding teeth possessing
a num b er
of cusps separated by
fiss ures . Premolars are bicuspid teeth th at are pecuJ i ar to the
perma n en t
dentition
and
replace
the
deciduous
molars .
the gla nd s. The
g lands and vessels en ters
aro und
teeth
crown. Molari fo nn teeth ( mol ars and premolars ) are glands
derived from the chorda tympani b ranch o f the facial
nerve that joins th e lingual
c utting
Caniniform
its arteries, ari s ing
Pe r manent teeth
from the carotid plexus. There are two incisors, a cen tra! and a lateral, in each half jaw or qua drant
(Figures 141. 1 1 and 1 4 1 . 1 2). Viewed
from the front, the crowns are tra pezo id , the m axillary
MOTOR SU PPLY
incisors (particularly
The nerves sup ply i ng the b u cci na to r a nd o rbic u la ri s o ris
mandibular. They are surmo unted by the b i ting or incisal
muscles are derived fro m the facial nerve t hat exits the
edges. In side view their labial pro files are co nvex wh ile
the central) being larger than the
skull at the stylomasto id fo ramen and then passes into the
their lingual surfaces are concavo -co nvex (the co nvexity
substance o f the p arotid g l an d , where it divides into its
near th e cervical m a rgin being due to a low
term inal bran ches. The b uccinator is s upplied by its
ci ngu lum , pro m inent only on upper inciso rs ) . The roots
buccal bra n c h ( es)
of incisors are single and ro u nded in maxillary teeth, but
and the lips fro m the b uccal and
rid ge o r
mandibular branches. The nerve supplying the mylohyo id
flattened mesio distally in m andib ul ar teeth . The upper
nerve a nd is seen bra nch i ng fro m
lateral incisor may be congenitally absent or may have a
muscle is the mylohyoid
the inferior alveolar nerve j us t above the mandibular foramen The
m uscl es
reduced Conn (peg-shaped lateral inci so r ) . Behind each lateral inciso r is a canine tooth with a
(Table 1 41 . 1 ) . o f t h e t ongue
a re
supplied b y the
single cusp ( hence the American term cusp i d ) instead o f
hypoglo ssal nerve. These m uscles develop pri marily from
a n incisal edge . The maxillary canine is stou ter an d more
occipital so mites that migrate into the d evelo ping tongue
carrying their nerve s up p ly, t he hypoglossal nerve, with them . The hypoglossal nerve is seen i n the neck crossing
over the inte rnal and ex terna l ca rotid and then the loop of
the l ingual artery ( Fig ure
] 41 .8). It th en p asses
u pwards
po inted than the m and ib ul ar cani ne. The canine roo t is single and is the longes t o f any too th . Behind the canines are t w o premo lars, e a c h with a -buccal and lingual cusp (hence the term bicusp i d ). The o cclusal surfaces o f the maxillary p rem o l a rs are oval ( t he
1804 I
PART 1 5 T H E U PPER D I G ESTIVE TRACT
seco nd premolar, the ling ual cusp is more substantial co mpared with the first, and frequently presents as two cusps. Each lower premolar tooth generally has one root. Posterior to the p remolars are three molars whose size
decreases as one p asses backwards. Each has a large rhomboid (upper jaw) or rectang ular (lower jaw) occlusal surface with four or five cusps. The maxillary first molar has a cusp at each corner of its o cclusal surface and the mesiop alatal cusp is connected to the distobuccal by an obli que r i d ge.
A smaller cusplet or tubercle ( cusplet of
Carabelli) usually appears on the mesi op alatal cusp. The
to o th has three wi dely separated roots, two buccal an d one palatal. The smaller maxi l lary second molar has a re d uced distopalatal cusp. Its three roots are less divergent and two of them may be fuse d . The maxillary third m olar, the smallest, is very variable in fo rm. I t us u ally has three cusps ( the disto p alatal being absent ) and co mmonly the three r o o ts are fused. The mandibular first molar has three buccal and two lingual cusps on
i ts rectang ular o cclusal surface, the
smallest cusp being distal. It has two widely separate d
roots, one mesial and one distal . The smaller mandibular second molar is like the first but has o nly four cusps (lacking the distal cusp of the first molar) and its two Figure 1 41 . 1 1
Pe rm a n e n t d entition upper jaw. Re pri n ted from
Re f. 1 by permission from El sevier.
roots are closer to gether . The mandibular third molar is smaller still and, like the upper third mo lar, is var i able in form. I ts crown may resemble that of the lower first or second molar and its ro ots are frequently fused. The third molar is often imp acted against the second molar, with
p acki ng and i nflammation. Third molars
resultant fo o d
are frequently congenitally absent.
Deci d u o u s teeth The incisors, canine and premolars of the permanent dentition rep lace two deci d uo us incisors, a deciduous
canine and two deciduous molars in each j aw quadrant. The deciduous incisors and canin e are shaped like their successors
but
are
smaller
an d
whiter
and
become
extremely worn in older children. The deciduous second molars
resemble
permanent
ones
rather
than
their
successors, the p remolars . Each second deciduous molar F i g ure 1 41 . 1 2
Perm a n e n t dentition lower j aw. Repri n ted from
Ref. 1 by perm i ssion from Elsevier.
has a crown almost identical to that of their respective, adjacent first permanent molar. The upper first decidu ous
molar has a triangular occlusal surface (its roun ded ' ap ex '
being p ala t al) awl a fissure separates a d o uble buccal cusp
from the p alatal cusp. The lower first deciduous m o l ar is a mesiodistal fissure
long and narrow; its two bu ccal cusps are separated fro m
separati ng the two cusps. The maxillary first premolar
the two lingual cusps by a zigzagging mesiod istal fissure.
us u ally has two ro ots ( one buccat one palatal) . The
Like permanent molars, u pper deciduous molars have
long axis is buccopalatal)
with
maxillary second premolar usually has one root. The
three ro ots and lower deciduous m olars have two ro ots.
o cclusal surfaces of the man dib ular premolars are more
These roots diverge m o re than those of perm anent teeth,
circular or squarer than those of the uppers. The buccal cusp of the mandibular first p r emo l ar towers above the
very much reduce d li ngual cusp. In the mandib ular
as each developing - premolar tooth crown is accommo dated
dire ctly
p re decesso r.
under
The
the
roots
crown of
of
its
deciduous
deciduous teeth
are
Cha pter progressively resorbed by osteoclast-like cells ( odonto
1 805
1 4 1 Ana tomy o f the m outil a n d den titi o n I
TISS U E S PACES ARO U N D TH E JAWS
clasts) p rior to being shed. The most common cause of infection of the tissues associated with the mouth is dental caries ( tooth decay) .
As infection may spread from the teeth to the neck and
Eru pti o n
become life- threatening, a knowledge o f the tissue spaces
The first
d eciduous teeth t o erupt into
the mouth
appear at approximately six months a ft er birth and, by aro und the age o f three years, all the decid uous teeth have erupted. By six years of age, the first permanent teeth appear (lower incisors and first molars) and thence the deciduous teeth are exfoliated one by one as they are replaced
by their permanent successors.
A complete
permanent dentition is present when the third molars erupt at around the age of 18-2 1 years. Information on the sequence of development and eruption of teeth into the oral cavity may b e important in fo rensic medicine and archaeology in helping to age individuals. The data provided
in
Tables
1 4 1 .3
and
1 4 1 .4
concerning
the
chronology of tooth development are largely based on Euro p ean-derived populations and there is evidence o f
ethnic
variation.
When
a
permanent
tooth
erupts,
approximately two-thirds o f the root is formed and it takes approximately another three years for the ro ot to be completed. For deciduous teeth, root completion is more rapid . The developmental stages of initial calcification and crown completion are less affected by environmental influences than eruption, the timing of which may be mod ified by several factors such as early tooth loss and severe malnutrition.
Figures
141.13
and
1 4 1 . 14
show
the
panoramic
appearance of the dentition seen with orthopantomo grams at 5 and 1 1 years of age. For detailed info rmation concerning the structure and function o f teeth
the
reader is
referred
to
standard
textbooks. 1 Ta ble 1 41 . 3
Tooth
associated with the j aws is of considerable clinical , , ' 3 4 5 6 . unpor t ance. ' , , Th e tissue spaces are only potential spaces that are normally occupied by loose connective tissue. It is only when inflammatory p roducts destroy the loose connective tissue that a d efinable space is pro duced. The tissue spaces associated with the mouth are p rimarily defined by muscles (principally the mylohyoid, buccina tor, masseter, medial p terygoid, superior constrictor and orb icularis
oris
muscles).
Knowledge
of the
normal
position of the root apices in relation to some of these muscles is important fo r an appreciation of the treatment 7 of d ental abscesses. Because of the potential of inflammation associ ated with the tissues surround ing partially erupte d , impacted third molars (pericoronitis) , the spaces associated with this region are particularly important and, as they are interconnected, inflammation can spread to involve the tissue spaces of the neck. The submental and subman d ibular tissue spaces are located below the inferior bo rder of the mandible, beneath the mylohyoid muscle,
in the
suprahyoid region of the neck. The submental space lies beneath the chin in the midline, between the mylohyoid muscles and the investing layer of deep cervical fascia. It is bounded laterally by the two anterior bellies of th e digastric muscles. The submental space communicates posteriorly with
the two
submandibular spaces.
The
sub mand ibular space is situated between the anteri or and posterior bellies of the digastric muscle. It co mmunicates with the sublingual space around the posterior free border of the mylohyoid muscle .
Chro nology of the d ecid u o us d e n ti tions.
Crow'��-,C�lT!pl�ted . (mo ll �bl( '
First evidence of
calcification
f,�,
(months IU)
.{; �
' If
�ru p�j�n (mo nths)
R90t co,mp}eted (years)
_ .
-;:5?.t (,
Maxillary
�
A
3 -4
4
7
1 -2
B
41
5
8
1 1 over2-2
C
5
9
1 6-20
2 -3
D
5
6
1 2- 1 6
2-2
E
6-7
1 0- 1 2
21 -30
3
A
41
4
B
41
4J-2
6b2 7
C
5
9
1 6-20
D
5
6
1 2- 1 6
� � 2�- 3 2-2�
E
6
1 0- 1 2
21 -30
3
2
t
Mandibular 2 2
-
' U n le ss otherw i se i n d i ca ted a l l d a tes a re po st pa r t u m . l U, in utero. Th e teeth are i d e n t i fi ed a . Repri n ted from Ref. 1 by perm i ssio n from Elsevier.
!
1 -2 1 -2
cc o rd i ng
to the Zsigmo ndy System.
I • 1
.
' . _..._.__ ._·
1806 Table
I PART
1 5 THE UPPER DIG ESTIVE TRACT
1 41 .4
(years)
Root completed (years)
4-5 4-5 6-7 5-6 6-7 2r-3 7-8 1 2- 1 6
7-8 8-9 11-12 1 0- 1 1 1 0-1 2 6-7 1 2- 1 3 1 7-21
10 11 1 3- 1 5 1 2- 1 3 1 2-1 4 9-10 1 4- 1 6 1 8-25
4-5 4-5 6-7 5-6 6-7 2r-3 7-8 1 2- 1 6
6-7 7-8 9-10 1 0- 1 2 11 -1 2 6-7 1 2- 1 3 1 7-21
9 10 1 2- 1 4 1 2- 1 3 1 3- 1 4 9- 1 0 1 4- 1 5 1 8-25
Eruption
Tooth
Moxiffory
1 2 3 4 5 6
3-4 mon ths 1 0- 1 2 months 4- 5 months 1 t- 1 � years 2-2! yea rs
7
2r-3 years 7-9 years
B i rth
8 Mandibular
1 2 3 4 5 6 7 8
3 -4 months 3-4 months 4-5 months 1�-2 years 2t-2t years Bi rth
2!-3 years 8- 1 0 years
All d a tes a re post- partum. T h e teeth are i d en tified acco rd i ng t o the Zsigmo ndy Syste m . Rep r i n ted from Ref. 1 b y permission from Elsevier.
Teeth erupted
Max Mand.
ABCDE ABCDE
Teeth unerupted
Max Mand .
1 23 4 5 6 7
Fig u re 1 41 . 1 3 Orthopantomogram from patient aged five years. Reprinted from Ref. 1 by pe rm ission from Elsevier.
1 2 345 67
T h e subli ngua l space lies i n t h e flo or of the mouth,
because t h e fibres of the ma sseter muscle h ave multiple
above the mylohyo id muscles. It is continuous across the
i nsertions o n to mos t o f the lateral surface of the ramus.
midline
and
co mm unicates
with the subman dibular
Between the
med ial surface o f the
sp aces over the post eri or free borders of the mylohyoid
man d i b le
mu scles ( see Figure 1 4 1 .7) .
pterygomandib u l ar space.
The remaining tissue spaces in the region of the molar teeth a re illustra ted i n Figure 1 4 1 . 1 5 . The buccal space is loca ted i n the cheek, on the lateral s ide of the buccinator
th e
medial
p terygoid
ramus
muscle
o f the
lies the
Be h i nd the ramus o f the mand ible is located the paro t id space, in and arou nd t h e
p aro ti d gla nd .
The parapha ryngea l sp a ce is bo unded by the superior constrict o r of the pharynx a n d the medial surface of the
muscle. Between the
and
lateral surface of the
ramus
o f the
m ed i a l p terygoid mu scle. This space i s restricted to the
ma ndible and the masseter muscle is a series of sp aces
i n fra te m p o r al region of the head and the sup ra hyoi d
called the submasseteric spaces These sp aces are formed
region
'
.
of
th e
neck.
It
com m un i cates
wi th
the
.
-
C h a pter 1 41 A n atomy of the m o u th a n d dentition I
Teeth erupted
Teeth unerupted
Max Mand.
1 2 3 4 E6 1 2 34 E6
Figure 1 41 . 1 4
Max
5 78 578
aged 11 years. Repri n ted from Ref. 1 by
Mand.
1 807
Ortho pa ntom ogra m from patient
permission from E l sevier.
buccinator) and will have natural drainage. Where, for example, a cheek tooth drains b elow the buccinator (into the b u ccal space) or lingually b elow the mylohyoid ( into the submandibular space, especially when involving the second and third mandibular molars), surgical interven tion will be required to ensure drainage. As an example, direct spread may involve the submental space and the sublingual and submandibular spaces of both sides, giving rise to Ludwig's angina.
TH E SA LIVARY G LAN DS Salivary glands are compound, tubular, acinous, mero crine glands whose ducts open into the oral cavity. They secrete a fluid, the saliva that, among its many functions,
Fig u re 1 41 , 1 5
aids in the mastication, digestion and deglutition of S 9, 1 0 fo o d. '
Diagra m s h o w i n g the tissue spaces i n the
There are three pairs of major salivary glands: the
retrom a n d i bular reg ion. 1 , Vestibular su l cus; 2, peritons i l l a r
paro tid, the submandibular and the sublingual glands.
space ; 3, bucca l s pace , fi l l ed w i th bucca l p a d of fa t ; 4 ,
Numero u s
subm asseteric spaces; 5, pterygo m a n d i b u l a r space ; 6, pa ra p haryngeal s pace ; 7 , parot i d s pa ce ; 8, bucci nato r m uscl e; 9, masseter m u scl e ; 1 0, ra m u s of mandib l e ; 1 1 , su perior constrictor of pharynx; 1 2, med i a l pte ryg oid m uscl e : 1 3 , mylohyoid m uscle ;
1 4, retro pha ryngea I space ; 1 5, pterygoma ndibu l a r ra phe.
retropharyngeal
space,
which
itself extends
minor
salivary
glands
are
also
scattered
throughout the o ral mucosa. App roximately 0 . 5 L of saliva is secreted per day. Salivary flow rates are approximately 0 . 3 mL/min when unstimulated, rising to 1 . 5-2 mL/min when stimulated. D u ring sleep, salivary flow rate is negligible. In the
into
unstimulated state, the paro tid gland contrib u tes ap
the
proximately 2 0 percent, the submandibular gland ap
The peritonsillar space lies around the palatine tonsil
salivary glands the remainder. When stimulated, the
retrovisceral space in the lower part of the neck. between
the pillars
of the
fauces.
It is part
of the
intrapharyngeal space and is bo unded by the me dial surface of the superior constrictor of the pharynx and its m ucosa.
proximately 65 percent and the su blingual and minor parotid contribution rises to 50 percent.
1I
Pa roti d g l a n d
Most dental abscesses from lower teeth will drain
.
either into the m o u th lingually above the mylohyoid
The paro tid gland is the largest salivary gland . I t is a
muscle (sublingual space) or into the vestibule (above the
serous gland. The paro tid gland is situated in front of the
--
/ �. . -
j
--�-.
� ,.. -
1808 I
PART 1 5 TH E LI PPER D I G ESTIVE TRACT
external ear on the face and consequently will not be described further. The parotid duct runs through the
The postganglionic fibres are distributed to the sub mandibular and sublingual salivary glands.
cheek and drains into the mouth opposite the maxillary second permanent molar tooth. Its parasympathetic innervation is derived from the lesser petrosal branch of
S u b lingual gland
the glossopharyngeal nerve via the otic ganglion. The sublingual gland, the smallest of the main salivary glands, lies beneath the oral mucosa, which is raised as a
Su bmandibu lar gland
sublingual fold (see Figure 141. 3). The gland lies in
The submandibular gland is irregular in shape and
the mandible, close to the mandibular symphysis. It is
approximately the size of a walnut. It consists of a larger
narrow, flat, shaped like an almond and weighs 3-4 g. The
superficial and a smaller deep part, continuous with each other around the posterior border of the mylohyoid
gland
contact with the sublingual fossa on the lingual aspect of
is
seromucous
(but
predominantly
mucous).
Beneath the gland is the mylohyoid muscle, whilst behind
muscle (see Figure 141.7). It is partially enclosed between
it lies the deep part of the submandibular gland (see
two layers of deep cervical fascia extending from the
Figure 141.7). The genioglossus muscle lies medial to the
greater cornu of the hyoid bone. It is a mixed, but
sublingual gland, separated from it by the lingual nerve
predominantly serous, gland. The superficial part of the
and submandibular duct. The sublingual gland has 8-20
submandibular gland is situated in the digastric triangle.
excretory ducts. From the posterior part of the gland,
Above, it extends medial to the body of the mandible.
smaller sublingual ducts mostly open separately on the
Below, it usually overlaps the intermediate tendon of the
summit of the sublingual fold. From the anterior part of
digastric muscle and the insertion of the stylohyoid
the gland small rami sometimes form a major sublingual
muscle.
duct (Bartholin's duct) , opening with or near to the
The inferior surface, covered by skin, platysma and
orifice of the submandibular duct.
deep fascia, is crossed by the facial vein and the cervical branch of the facial nerve. The lateral surface is in relation with the submandibular fossa on the medial surface of the
Minor salivary glands
body of the mandible and the mandibular attachment of the medial pterygoid muscle. The medial (deep) surface is
The minor salivary glands of the mouth include the
related anteriorly to the mylohyoid muscle and poster
buccal, labial, lingual, palatal and palatoglossal glands.
iorly to the styloglossus muscle. In its intermediate part,
The buccal and labial glands contain both mucous and
the medial surface is related to the hyoglossus muscle,
serous elements. The palatal glands are mucous glands.
separated from it by the styloglossus muscle, the lingual
They are located in both the soft and hard palate. The
nerve, submandibular ganglion, hypoglossal nerve and
anterior and posterior lingual glands are mainly mucous.
deep lingual vein.
The anterior glands are embedded within muscle near the
The deep part of the submandibular gland lies between
ventral surface of the tongue and open by means of four
the mylohyoid muscle inferolaterally and the hyoglossus
or five ducts near the lingual frenum. The posterior
and styloglossus muscles medially. It extends forwards to
glands are located in the root of the tongue. Around the
the posterior end of the sublingual gland (see Figure 141.7).
circumvallate papillae are serous glands (of Von Ebner) .
The submandibular duct is approximately 5 cm long and emerges from the medial surface of the superficial
The palatoglossal glands are mucous glands and are located around the pharyngeal isthmus.
part of the gland behind the posterior border of the mylohyoid muscle. It passes through the deep part of the gland,
runs between the sublingual gland and the
TEMPOROMAND IBULAR JO INT
genioglossus muscle and opens in the floor of the mouth on the summit of the sublingual papilla at the side of the frenulum of the tongue. On the hyoglossus muscle it is
As the
temporomandibular
joint
is
closely
related
anatomically to the external acoustic meatus and clinical
crossed laterally by the lingual nerve, some of whose terminal branches ascend on its medial side (see Figures
that must be distinguished from those directly associated
141.7 and 141.8).
with the ear, the joint will be considered in this chapter.
The secretomotor supply to the submandibular gland
conditions of the joint may produce symptoms of pain
The
temporomandibular
(craniomandibular)
joint
is associated with the submandibular ganglion. This is a small, fusiform body that lies on the upper part of the
(glenoid) fossa articulating with the mandibular condyle.
hyoglossus muscle suspended from the lingual nerve. The
The shape of the mandibular fossa does not conform
motor, parasympathetic root conveys preganglionic fibres travelling in the facial, chorda tympani and lingual nerves
exactly to the shape of the mandibular condyle and this
(see Figure 141.9) to the ganglion, where they synapse.
divided by an articular disc into upper and lower
(TMJ) is a synovial joint. It is formed by the mandibular
may partly explain why, unusually, the joint cavity is
Ana to my of the mouth a n d dentiti on I 1 809
Ch apter 1 4 1
s u b a tm osp h e ri c, m asti ca t io n
1 4, 1 5
but
this
is
greatly
eleva ted
duri n g
.
Articu l a r disc The
art icul a r
disc
(meniscus)
is
of a
dense,
fib ro us
co nsisten cy and is moulded to the b ony j oint surfa ces above and below. Blood vessels are only evident a t the pe r i p hery of the articular disc, the bulk of its central p art
b ein g avascular. When viewed in sa gittal section, the upper su rface o f the disc is concavo-convex from before back wards and the lower surface i s concave. Viewed superiorly, the articuJ ar disc is somewhat rectangular or oval in o utl ine
Th e temporoma ndi b u l a r j o int s h o w i n g the a n d a ttachments of th e latera l pterygoid m uscle. A, Articu lar emine nce ; B, articu lar disc; C, m a nd ibular fossa ; D, condyle; E, u pper l a m i n a (fibro-e lastic) ; F, l ow e r l a m i n a (non elastic) ; G , ca psu l e of j o i n t ; H , l a t e ra l pteryg oid m uscle. Yel l ow layers indicate u pper a n d l ower joint cavities, black layers i n d icate u pper a n d l ower fi brous a rticular su rfaces. Redrawn by permission from Ref. 1 2. Fi g u re 1 4 1 . 1 6
a rt i c u l a r d i s c
compartments (Figure 1 4 1 . 1 6 ) . 6, 13 The temp orom a nd ib ular j o i n t a ll ows b oth glid ing ( upper j oint co mp ar tm en t )
a nd h inge ( l ower jo int comp artment) m ovem en t s . The
c ondyle
joins th e ram us thro u gh a thi n bony
proj ecti on t er med the neck of the condyl e a frequent si te ,
for a fr a ct u re of the mandible. A small depres s i on ( the
p terygo i d fovea) situ a ted on th e anterior s u rface of th e neck marks part of the a ttachment of the la teral p terygoid muscle. The articular su rface s o f the con d yl e are the
a n te rior and superi or s urfaces. During the period o f growth u p t o early teens, a layer of hyaline cartilage (co ndyl a r cartila g e ) lies immedi ately b e n ea th the fib rou s ar ticu la ting surface of the condyle .
.
The overall sh a p e of the articular disc is tho ught to provide a
self centring mechanism, which automatically acts to -
maintai n its correct relationship to the articular surface of the mandibular condyle during mandibular movem ents.
Wh ereas s o me regar d the functions of the articu la r disc as he lpin g to sp read th e j oin t forces and to stabilize the condyle oth ers see its function as pri marily destabilizing ,
t he co ndyl e and permitting it to move more freely.
16
The central ( i n termediate) zone o f t h e disc is t he th innest a nd the co l la g en fibres are crimped, perhap s
evidence tha t the disc is subj ec t ed to tensional, as well as co mpressi o n a l , fo rces .
17
The ma rgin of the articu l a r d is c
merges peri p h e rally with the j oi nt ca p s ul e. An teriorly, fibrous ba nds connect the disc to the anterior m a rgin o f the
a r tic u lar
eminence a bove, a nd to the anterior ma rgi n
of the co ndyle b elow. Media l ly and la tera ll y, the articular disc is atta ch ed to th e j o int capsule and, just below the medial and l a tera l p oles of the co ndyle
,
by t riang u lar
zones of co nnec tive t iss ue . Pos teri orly, the dis c is a ttached to the c a psule by a looser connective tissue, the retrodiscal tiss ue
(pad)
tha t
has
a
bil aminar
appearance.
T he
su p e r io r l a m ina is lo ose a nd possesses numerous vascular elements and elastin fibres. It attaches to the ant erio r m argin
of the squam o tympanic fissure.
The inferior
l a m ina is rela t i vely avascular, less extensible ( as it has few
The joint caps u l e
elastin fibres) and is a ttache d to the p os te rio r m argin o f the condyl e. The volume of the retrodiscal tissu e a pp ears
The
.
o f th e
above t o
to i ncrease fo u r to five times as a result of venous
mandibular fossa, extending anterior ly to j us t in fro n t
engorgement as the jaw is opened and the co ndyle moves
of the crest of the articular eminence and pos teri o rly to
downwards a nd fo rwards. The return of the articu lar disc
the squ amo tymp anic and pet ro ty mp anic fissu res. Bel ow,
to i t s o r i gin al p osi tio n m ay p os s ibly be aided by the elastic
the capsu l e is attached to the neck of the co ndyle. Being a
recoil o f the superior la m ella .
slack
cuff,
the
TMJ
is a tt ached
the
t hin
capsule
capsule
itself
does
not
limit
N u mero us stu dies have been undertaken t o determine
mandi bular movements and is too weak t o p rovide m u ch
t he p recise attachment of the l atera l p t erygoid muscle
support for the joint. The inne r sur fa ce of the fibrous caps ule is l i ned by a
synovi al membrane that is reflected over the ma rgi ns o f
p redis p osit i on t o
temporom an d i bu lar j oint
syn
dro me. Variations in the attachm en t a re seen . Th e
the ar ticular disc, but the membrane does not cover the
fi n dings indicate that, in the m aj ority of a r ticles (60
j oi n t .
p e rce nt ) , fibres from the superior head o f the l ateral p terygo id muscle are described as gaining a di rect
articu lar surfaces of the
The syn ovi a l me m b ran e
secre tes the synovial flui d , which occup ies the j o int
I·
with respect to the ar t icula r disc in t he hop e o f expla i n i ng any
cavities a nd lubricates the j o in t . Imp orta n t co mponents
att ach men t i n to the capsule of the
of the fluid are the p roteoglycans . At rest, th e hyd ros ta tic
medial a sp e ct of the
preSSure of the synovial fluid has been rep or ted as bei ng
( as well as to th e co ndyle) . In 30 p ercent
I· �- . .
� nterior
j oint and
to the
border o f the a rticular disc 0f
articles, only a
J
___ _
.-1 __ . _-
1810 I
PART 1 5 THE U PPER D I G ESTIVE TRACT
while in the remaining 10 percent of articles the superior
In nervation and vascu lature of the temporomandib u l ar joint
head of the lateral pterygoid muscle is attached only to 18 the condyle. Very rarely, some fibres from the inferior head of the lateral pterygoid may insert into the articular
Innervation for the joint is provided by the auriculotem poral, masseteric and deep temporal branches of the
few muscle fibres are described as inserting into the disc,
disc.
mandibular nerve. Of particular functional significance are the proprioceptive nerve endings important in the reflex control of mastication.
Ligaments of the temporomandibu lar joint The main ligament limiting lateral movement at the TMJ is the lateral ligament (temporomandibular ligament) , which cannot be readily separated from the capsule. It runs
downwards and
The vascular supply is derived from the superficial temporal artery and the
maxillary
artery
(anterior
tympanic and deep auricular branch). Other branches from neighbouring arteries may also contribute (e.g. deep temporal and transverse facial arteries) .
backwards from the articular
tubercle (a bony protrusion on the lateral surface of the articular eminence) to the lateral surface and posterior border of the neck of the mandibular condyle. 1 9 To help resist posterior movement of the mandibular condyle, the lateral ligament is reinforced by a horizontal band of fibres running from the articular eminence to the lateral surface of the condyle. As there is little evidence of a medial ligament, medial displacement of the TMJ is likely to be prevented by the lateral ligament of the opposite side. Accessory ligaments of the temporomandibular joint are the stylomandibular ligament, the sphenomandibular ligament and the pterygomandibular raphe. However, of
Condylar cartilage A secondary cartilage is present beneath the fibrous articular surface of the condyle until puberty. Unlike a primary cartilage, this secondary condylar cartilage has less extracellular matrix, the cartilage cells themselves do not undergo cell division and do not align themselves into columns. Although once thought to be a prime causative factor in controlling mandibular growth, the secondary condylar cartilage is now not thought to have any intrinsic
growth
potention.
The
condylar
cartilage
disappears around the age of 16 years.
these, the only one likely to have any significant influence upon mandibular movements is the sphenomandibular 0
ligament. 2
The stylomandibular ligament is merely a reinforced lamina of the deep cervical fascia that extends from the tip of the styloid process and from the stylohyoid ligament to the angle of the mandible. The pterygomandibular raphe is a thin band of tendinous fibres passing between the hamulus of the medial pterygoid plate and the posterior end of the mylohyoid line of the mandible. It gives origin anteriorly to the buccinator muscle and posteriorly to the superior constrictor muscle. The sphenomandibular ligament runs from the spine of the sphenoid bone to the lingula of the mandible. It represents the remnants of the perichondrium of the
DEVELOPMENT OF THE FACE AND PALATE As the neural plate of the embryo invaginates to form the neural tube, neural crest cells (ectomesenchyme) at the margins proliferate and migrate from this site to various parts of the body. There, interacting with the overlying epithelium
(epithelial/mesenchymal
interactions) ,
the
neural crest plays a significant role in normal develop ment, contributing to many systems, such as the nervous system, soft and hard connective tissues. In addition, the cells play a major role in tooth development and give rise to melanocytes.
cartilage of the embryonic first branchial arch. The sphenomandibular ligament is slack when the jaws are
Deve lopme nt of face
closed, but during jaw movement becomes tense at about the time when the condyle has passed in front of the lateral ligament. 2o
In a four-week-old embryo, the developing oral cavity
In addition to the above, an additional ligament, the retinacular ligament, has recently been described. This ligament is said to originate fom the articular eminence and insert into the fascia overlying the masseter muscle at the angle of the mandible. As the ligament is connected with the retrodiscal tissues, and contains an accompany ing vein, it may function in maintaining blood circulation during masticatory jaw movements.z1
(stomodeum) is present as a small, blind-ended pit bounded by five facial swellings (prominences) produced by proliferating zones of mesenchyme lying beneath the surface ectoderm. Much of the mesenchme is derived from neural crest cells. The five facial swellings are the single frontonasal and the paired maxillary and mandib ular processes (Figure 141. 17). The centrally positioned frontonasal process lies above, the two maxillary processes are located at the sides and the two mandibular processes lie below the mouth. The maxillary and mandibular
Ch a pter 1 41
Fig u re 1 41 . 1 7
Sca nn i ng electro n mic rog ra ph of the face at a n
equivalent fou r week stag e On t h e ra t). Frontal aspect. A, Fro ntonasa l process; B, mandibular processes ; C, maxil l a ry processes; 0, pericardial swe l ling. Repri nted from Ref. 1 by perm ission from Elsevier.
processes are derived from the first branchial arches. The facial processes are separated by grooves t ha t , in the co urse of normal development, become flattened out by the proliferative and migra tory activi ty of the underlying mesenchyme. Any disturba nce in this process affecting, for example, the number, migra tion a nd subsequent differentiation (or apoptosis) and pattern formation of these cells can produce congenital abnormalities such as cleft lip and palate.
An a t om y
of th e mouth a nd dentition . 1 8 1 1
At t h i s early stage of development, a membrane (the oropharyngeal membrane) separates the invagination representing the pri mitive oral cavity from the developing pharynx behind. The oropharyngeal membrane is bila minar, being composed of an outer ectodermal layer and an inner endodermal layer. This membrane soon breaks down to esta blish continu ity between the ectodermally lined oral cavity and the endodermally lined pharynx. Although not detectable in the adult, the demarcation zone between mucosa derived from ectoderm and endoderm corresponds to a region lying just behind the third permanent molar tooth. In a five-week-old embryo, localized thickenings of ectoderm on each side give rise to the optic and nasal placodes. These placodes wiJl invaginate to form the lens of the eye and the olfactory epithelium, respectively. The nasal placodes sink into the underlying mesenchyme, forming two blind-ended nasal pits. Proliferation of mesenchyme fro m the frontonasal process around the openings of the nasa l p its produces the medial and lateral nasal processes. The nasal pits continue to deepen until eventually they approach the roof o f the primitive oral cavity, being partitio ned from it by oronasal membranes (Figure 141.18). By the end of the fifth week, these membranes rupture to produce communications between the developing nasal and oral cavities. In the six-week-old embryo, the two mandibular processes fuse in t he midline to form the tissues of the lower jaw. Rarely, persistence of a midline groove in this region produces a mandibular cleft. The mandibular and maxillary p rocesses meet at the angle of the mouth {labial
(a) Sagitta l section through the deve l o p i n g n asa l A and o ra l B cavities to C. de�eloping ton gue 0, oronasa l mem bra ne; E. m a xill ary isthm us. Toluidi n e b l u e x 30. (b) Diagra m with similar labe l l ing. Repri nted from Ref. 1 by perm ission from Elsevier.
Fig u re 1 4 1 . 1 a
. I ----=---
1812 I
PART 1 5
THE UPPER D I GEST IVE TRACT
commissure ) , thus defining
its outline. Disturbances in
maxillary processes being sup plied by the maxillary nerve,
this develo p ment may give rise to macrostomia ( enlarged
the frontonasal process by the o phthalmic nerve. It is o f
oral orifice) or microstomia ( small oral orifice) , or rarely
interest t o no te that, in cases o f bilateral de ft lip, the
to an astomia (lack of an oral orifice) . From the corners of
iso l ated median segment of the lip is innervated by the
the mo uth, the maxillary processes grow inwards beneath
ophthalmic nerve, al t hough t h is dearly is a patho logi cal
the lateral nasal processes and to wards the medial nasal
condition. At presen t , too
p rocesses of the upper lip (Figure 1 4 1 . 1 9 ) . An apprecia
behaviour and any subsequent m ig ra tio n o f the mesench
l ittle is kn own abo ut the
tion of this arrangement helps explain the occurrence o f a
yme of t h e facial p rocesses a nd the acco mp anyi ng nerves
un ilateral or bila teral cleft lip (when the medial nasal and
a fter the i nitial fusion of th e maxillary and medial nasal
maxillary processes fail to merge successfully) and a
pro cesses. The muscles of the lip, like the other fa cial
median cle ft (when the two median nasal processes fail to
muscles, are derived from the mesenchyme of the second
me rge ) .
branchial arch, and are therefore innervated by th e facia l
T he severity of a cle ft may vary fro m a barely
imp erceptible groove to a co mplete cle ft. Between the
nerve .
merging maxillary and the lateral nasal process lies the naso - op t ic furrow. From each furrow a solid ectodermal rod of cells si nks below the s urface and can alizes to fo rm the n asolacrimal duct.
Persistence
Deve lopment of the pa late
o f the naso-o p t ic
furrow may produce an oblique facial cleft.
As we have seen at five weeks o f develo p ment, the nasal th e
p i t deepens and the nasal p lacode comes to lie in its roof
development of the upper lip. One interpretation is that
where it will form the olfacto ry epitheli um. The region of
th e m axillary processes meet the medial nasal processes,
t he fro nto nasal p rocess lying between the two nasal pits
Two
differin g
accounts
have
been
given
for
the latter thus forming the middle third of the up per l i p.
forms the primary nasal septu m , while the tissue beneath
is favoured by macroscopic observations o f
the p its a n d sep a rati ng them fro m the sto mo de u m fo rms
Thi s view
develo pment. The altern ative view states that t h e m ax
the p r i m ary palate . At this stage, the nasal pits are
the medial nasal processes,
co n fined o nly to the anteri o r extremity of the fu ture oral
m ergin g in the m idline to contribute all the tiss ue fo r the upper lip. This interpretation is based on the innerva t io n
co mmon oronasal cavity (Figure 141 .20a) . S ubsequent
illary processes overgrow
o f the fully formed upper lip (i.e. t h e infraorbital branch of the
maxillary division of the trigeminal nerve ) , the
cavity, the large regio n behi nd at this s tage fo rming a develo p ment is
d esigned
to extend the p rimary nasal
septu m and p ri mary p alate backwards by means of a secon dary nasal sep t u m and secondary pala te. D u ring the sixth week of development, a secondary nasal
sep tum
sto modeum
grows
behi nd
d o wn the
from
the
p rimary nasal
roof
of the
sep tum,
thus
div i ding the nasal aspect of the comm on oron asal c avity i nto two. In ad dition, a lateral p alatal shel f grows out fro m each maxillary p rocess b u t, d u e to t h e comparat ively la rge size of t he developing to ngue, is prevented fro m growing ho ri w ntall y and beco mes o riented more verti ca ll y ( Figures 1 4 1 .20b and 1 4 1 .2 1 ) . D u ri ng the eighth week o f develop ment, the tongue 'drops' and the vertically i ncli ned palatal shelves can now occupy
a
horizontal
positi o n
(Figures
141 .20c
and
1 4 1 .22 ) . The reaso n fo r the displacement of the tongue is no t
known. As
the to ngu e is attached to the
mand ible,
it has been su ggested that the descent of the tongue is
related to m andibular growth. Co nversely, reflex move ments of th e tongue and / o r a change in its shape may be impl icate d . On beco ming horizo ntal, the p alatal shelves co n t act each other (and the secon dary nasal sep tu m) in the midline to fonn the secondary palate . The shelves contact the primary pala te anteriorly so that the oral and Fi g u re 1 41 . 1 9
Scanning electron microg rap h of developing ra t upper jaw and lip at an equivalent stage to six weeks i n the human showing the merging maxillary and medial nasa l processes. A, Mandibu lar p rocess; B, maxillary process; C, l atera l nasa l process ; D, medial nasa l process ; E, naso-optic furrow ; F, primitive nasa l cavity. Reprinted from Ref. 1 by permission from Elsevier.
nasal cavities beco me completely separ ated from each other. A fter shel f contact, the medial edge epithel ia of the two
shelves
fuse to form a midline epitheJial seam .
Subsequently, this seam (to gether with the epitheliu m sep a rating the p alatal shelves from the secondary nasal sept u m ) degenerates, allowing conti nuity of mesenchy m e
.
Chapte r 141 Anatomy of the mouth a n d den tition I
Fi g u re 1 41 .21
1813
Coro n a l section th rough t h e h e a d a t a n
eq u iva lent stage of seven weeks i n tra u teri ne development i n t h e h u m a n show i n g t h e vertica l ly i ncl i n ed pa l ata l shelves (A) . B, Developing tong ue. M asso n 's trich rome x 3 0. Reprinted from Ref. 1 by permission from E lsevier.
Fi g u re 141 .22
Coro n a l section throug h deve l o p i ng o ro- nasa l
regions following contact of the palata l s h e lves (A) a n d secon d a ry n a s a l s e p t u m
(8).
C, M i d l i n e e p i th e l i a l seam ; 0 ,
developing bone o f maxilla. Masson's trich ro m e x 30. R e p ri nted
Fi g u re 1 41 .20 pa l ate
(a) .
Diag ra m show ing the d eve l o p m e nt of the
from Ref. 1 by permission from E lsevier.
By sixth week of i n tra uterine life; ( b) d u ri ng s ixth
week of i n tra uteri n e l ife a n d
(c).
At n i nth week of i n traute rine
l ife. A, latera l palata l she lves of secondary pa l ate : B, primary
b one
pa l ate ; C, primary nasal se ptu m ; 0, seco n d a ry n asa l sep tu m ;
perpendicular plate and appears in th e eighth week of
is
situated
in
the
region
fo rming
the
future
d evelopment. Incomplete ossification of the palate from
E , pri m itive n asa l cavities.
these centres defines the median and transverse palatine sutures. There does not appear to be a separate centre of 'to be established across the now intact and horizontal
ossification for the primary palate in man ( in other
secondary palate. Fusion
species
of the palatal processes is
complete by the 1 2th week of d evelopment. B ehind th e secondary nasal septum, the palatal shelves fuse to form the soft palate and uvula.
is
such
a
centre,
formin g
a
separate
The muscles of the palate are derived fro m the lower branchial
arches,
hence
their
nerve
supply
by
the
The hard palate ossifies intramembranously from fo ur
pharyngeal plexus. However. tensor veli palatini develops
centres of ossification, one in each developing maxilla and
from the first branchial arch, explaining its innervation by
one in each developing palatine b one. The maxillary
th e mandibular nerve.
ossification centre lies above the developing d eciduous
hr·
there
'premaxilla') .
As is
evident
from
the
description
above,
palate
canine tooth germ and appears in the eighth week of
formation is a complicated process. The palatal shelves
development. The centre of ossification for the palatine
must grow to the appropriate size; the palatal shelves
18 14 I
PART 1 5 TH E U PPER D I G ESTIVE TRACT
must elevate at the appropriate time on both sides; the
tissues across the midline. The signals that are responsible
medial edge epithelia of the palatal shelves must adhere to
for such a breakdown are not yet fully understood. As a
form a midline epithelial seam: the midline epithelial
breakdown of medial edge epithelium occurs in single
seam must degenerate to allow for the establishment of
isolated palatal shelves, the process does not depend
mesenchymal continuity across the midline. Any inter
specifically upon shelf contact.
ference or mistiming of these processes may contribute
Factors that may contribute to thinning and then
towards the formation of a cleft palate. Clefts of the
removing the epithelial seam include: growth of the palate
palate, like those of the lip, are multifactorial malforma
(in terms of oronasal height) and epithelial cell migration
tions, involving both genetic (polygenic) and environ
from the region of the seam on to the oral and nasal
mental factors. Recent research on palatogenesis has
aspects of the palate; programmed epithelial cell death
concentrated on two main events: palatal shelf elevation
(apoptosis); migration of epithelial cells from the epithelial
and the initial stage of fusion of the shelves.
seam
into
the
palatal
shelf mesenchyme
and
their
subsequent differentiation into mesenchymal cells (epithe 23 lial/mesenchymal transformation). As in other systems, it
PALATAL S H ELF ELEVATION
is thought that signals
This process, during which the palatal shelves move from
( e.g.
growth factors such as
epidermal growth factor and transforming growth factors)
the vertical to the horizontal position, is thought to occur
emanating from the underlying mesenchyme are ultimately
very rapidly (in terms of minutes and hours rather than
responsible for controlling epithelial degeneration.
days). Although it was once thought that extrinsic forces might be responsible (e.g. forces derived from the tongue or jaw movements), recent research has primarily focused
CLI N I CAL AN D AETIOLOG I CAL CO N S I D ERATI O N S
on the search for a force intrinsic to the palatal shelf.
Malformations
Systems which
appearance of clefts. The mildest form of cleft is that
have
at
one
time
or
another
been
o f palatogenesis
may
result
in
the
implicated include differential mitosis, contraction of
affecting the uvula, such a disturbance occurring relatively
connective tissue elements such as collagen or mesench
late
ymal cells, changes in vascularity or tissue fluid pressures.
occurring during the early phases of palatal fusion can
in
the
process
of palatal
fusion.
Disturbances
Particular attention has focused on the proposition that
result in a more extensive cleft involving most of the
the intrinsic shelf elevation force might develop as a result
secondary palate. Should the cleft involve the primary
of hydration of ground substance components (princi 22 In this
palate, it may extend to the right and/or left of the incisive
pally hyaluronan) in the shelf mesenchyme.
foramen to include the alveolus, passing between the
context, hyaluronan is a highly electrostatically charged,
lateral incisor and canine teeth. Cleft palate may be
open coil molecule that is capable of binding up to ten
associated with cleft lip, though the two conditions are
times its own weight in water. In support of the possible
independently determined.
Dental
malformations are
importance of hyaluronan in palatogenesis, research using
commonly associated with a cleft involving the alveolus.
organ culture systems have shown that the presence of
A submucous cleft describes a condition where the palatal
agents either leading to an alteration in hyaluronan
mucosa is intact, but the bone/musculature of the palate
content
is deficient beneath the mucosa.
or
size,
or
that
disrupt
glycosaminoglycan
substitution on proteoglycans, or that alter the balance of matrix molecules secreted via the Golgi complex and hyaluronan produced at the cell surface, all detrimentally 1 affect normal palatogenesis. In addition to hyaluronan, however, other matrix components (including proteogly cans) may also be important during shelf elevation.
KEY POI NTS •
mouth and dentition . is mandatory . for · all head and neck surgeons operating in this
FUSION OF TH E PALATAL S H ELVES
Following palatal shelf elevation, contact is made initially in the middle third of the palate and then extends both anteriorly and posteriorly. The two adjacent medial edge epithelium contact each other and adhere by means of a 'sticky' glycoprotein coating their surfaces. In addition, the epithelial cells develop desmosomes that form a
A detailed knowledge of the anatomy of the
area. •
the general ENT surgeon, the anatomy of: - the floor of mouth is irnportant when For
dealing with submandibular duct pathology or submandibular duct rerouting, . tongue tie, treatment of a ranula and biopsying suspicious . lesions;
medial epithelial seam. The adherence of the medial edge
the buccal mucosa is irnportant wheri
epithelia is site-specific as palatal epithelia will not fuse 22 with epithelia from other sites (e.g. the tongue).
biopsyil}g suspicious lesions;
For normal palatogenesis to proceed, the epithelial seam must be removed for consolidation of mesenchymal
dealing with parotid duct pathology and
- the hard palate is important when biopsying suspicious lesions;
C h a pte r 1 4 1 Anatomy of the mouth and dentition I
".' 1' -,' ' �':"
�e. �ft, p;alate is ,import,
palatal
lesions; ,
mastication and swallo wing and their dysfunctions.
;�)/;: ," ,
r. ,'
Frontiers of O ra l B i o l ogy S e ries, Vo l . 9. Base l : Karger, 1 99 8 :
;
palatine t09�i;I and lateral pha_ryIigiiil ,�') , ':
1 68-222.
·· . ••. \;�a�:��� :�f:'� �:;:1l1i �� ' ;t.cli , ;par�pharyt;tge�J 'abs��ss�'s , �s ' biqRs well 'as
Y ' o(suspicio�. lesiql!-�;' '/.- - , ', ,' '. , .> the tongUe� is:i�p'ortat;t when"-���essi�)i: , :, ncuroIogical fu nction a fter suspected, : .�, :
.
11.
Ferguson D B. Oral biosciences, 2 n d e d n . E d i n b u rg h :
12.
Osbou rn J . Fig u re 30. 1 0. I n : Sta n d ring S (ed.). Gray's
Ch u rchill Uvi ngstone , 1 998 : 1 1 7 - 5 7 .
.
anatomy: the anatomical basis of medicine and surgery,
' _
39th edn. Ed i n b u rg h : C h u rch i l l Livingston, 2004.
'
nerve damage or ch ord� :',� , " . �o. tympani loss, as well as fo r b iopsy g (' - '-'': suspicious lesions; '.:" .; < ", the salivary glands is important ; -'L . . ' unde.rstanding the principles of parot idectomy a nd subm andibular.;,g Hi:t,�� � . " i4,� \ . - -, . . excision; the temporomandibular joint i.s importa n t \,', " beca use of i t s c1o.'ie relationships to the ;�,,.l:;, e..x1ernal ear ca nal .
1 3.
hypoglossal
-
•
fo;i ·,·>J: : .
For t he genera l ENT surgeo n ,
the development of t he
is
' <"
helpful in u ndersta n d ing a wi de range o f
congenital head and neck abnormalit res cleft palate pat hologies i n part i c u l a r.
'\ .ci
and ..
:,
.��.
:1it.'f::':-)' " ,
H a wth orn R, Flata u A. Te m po ro m a ndibu l a r joint a n a tomy. I n : Norm a n J B, Bra m ley P (eds). A textbook and colour atlas of the temporomandibular join t. Lo ndon : Wolfe, 1 990 : 1 -5 1 .
1 4.
D ijkg raaf LC, De Bont LGM, Boeri ng
G,
Liem RSB. Fu ncti on,
b i ochem istry, a n d metabolism of the n o rm a l syn ovial m e m brane of the tem pe ro m a nd i b u l a r joint : A review of the l iterature. Journal of Oral and Maxillofacial Surgery. 1 996; 54: 95 - 1 00. 1 5.
N i tza n OW, M a h l e r Y, Si m k i n A. I ntra - a rt ic u l a r pressure measure m e n ts in pati e n ts with suddenly deve l o p i ng
lUldersnanding'L',:" � ;
face and pa,late
Thexton AJ , Cro m pto n AW. Swa l l o w i n g . I n : Li n de n R A (ed .). The scientific basis of ea ting. Toste and smell, salivation,
sut,getyJ§f ,sitoringi�'and'� for: <': :�, �: : ,
biopsying suspi�iQus
- the
1 0.
Eusta¢h4�1f 'ltt9�e-'p:�tpology,
1815
seve re ly l i m ited mouth o pe n i ng . Journal of Oral and Maxillofacial Surgery. 1 992 ; 50 : 1 038-42 . 1 6.
Osborn JW. The d isc of the h u man te m poro m a n d i b u l a r joint : design, fu n cti on ,a nd fa i l u re . Journal o f Oral Rehabilitation. 1 985; 1 2 : 2 79-93.
1 7.
Be rkovitz BKB. Co l l ag e n cri mping i n the i n tra-a rticular d isc a n d a rti cu l a r s u rfaces of the h u m a n te m poro m a ndibu l a r j oi nt. Archives of Oral Biology. 2000; 45 : 749-56.
R E F ER E N CES
1 8.
B e rti lsson 0, Strom D. A l i te rature survey of a h u ndred yea rs of a na to m ic and fu ncti onal l ateral pterygoid m uscle
1.
Be rkovitz BKB, H o l l a nd G R. M oxham BJ. Oral anatomy, histology and embryology, 3rd ed n . Lo n d on : M osby, 2002.
2.
researc h . Journal of Orofacial Pain. 1 99 5 ; 9: 1 7 -23. 1 9.
Be rkovitz B KB, M oxham BJ . Head and neck anatomy: a
Sato I , Shindo K, Ezure H , S h i m ada K. M orp hology of the l a te ral l ig a m e n t i n the h u ma n te m poro m a n d i b u l a r j oi nt.
clinical reference. Lo ndo n : D u n i tz, 2002.
Oral Surgery, Oral Medicine, Oral Pathology, Oral
3.
H o l l i nshead W H o Anatomy for surgeons: the head and
Radiology, and Endodontics. 1 99 6 ; 8 1 : 1 5 1 -6.
4.
G oldberg MH, Topazi a n RG. Odontog e n ic i nfecti ons and
neck, 3 rd edn. New Yo rk : H a rpe r and Row, 1 982.
20.
l i gam ents a ro u nd the te m poro m a n d i b ular joi nt. Journal of
deep fascia l space i n fections of de ntal o ri g i n . I n : To pazian RG, Goldberg M H (eds). Oral and maxillofacial infections, 5.
Osbo rn JW. I nte rn a l d e ra n g e m e n t a nd the accessory Oral Rehabilitation. 1 99 5 ; 2 2 : 7 3 1 -40.
21 .
Sh ira ishi Y, H ayakawa M, Ta n a ka S, Hosh i n o T. A new
3 rd ed n . Ph i l adelph i a : Sa u n d e rs, 1 994 : 1 89-2 50.
re ti nacu l a r l i g a ment and ve i n of the h u m a n
la ng J. Clinical anatomy of the masticatory apparatus and
t e m porom a n d i b ula r joi n t. Clinical Anatomy. 1 99 5 ; 8 : 208- 1 3.
peripharyngeal spaces. New York: Th i e m e Med ical Pu blishers, I n c, 1 995.
22.
Ferg uson M WJ . Palate deve l op me n t. I n : Thorogood P,
6.
la ngdon J D, Be rkovitz B KB, Moxham BJ (eds). Surgical
7.
To nge CH, Lu k e DA Denta l a n atom y : The spread of I n fecti o n . Den tal Update. 1 98 1 ; 8: 29 1 -301 .
mese n chyme after e m bryo n ic palata l she l ves fuse.
8.
G a rrett J R. Ekstrom J, A n d e rson LC (eds). Glandular
Developmental Biology. 1 98 9 ; 1 3 1 : 455- 74.
Ti ckle C (eds) . Cra n iofacial deve l o pm e n t. Development
anatomy of the infratemporal fossa. Lo ndo n : Du nitz, 2002.
1 99 8 ; 1 03 : 41 -60.
23.
Fi tch e tt JE, H ay ED. Medial edge e p i the l i u m transforms to
mechanisms of salivary secretion. Fron tiers of oral biology, Vo l u m e 1 0. Base l : Karger, 1 998. 9.
O rcha rdson R, Cad d e n SW. Mastication. I n : Li n d e n RA
FU RT H E R R EAD I N G
(eds). The scientific basis o f eating. Toste and smell, salivation, mastication and swallowing and their , dysfunctions. Frontiers of O ra l B i o l ogy Seri es, Vo l u m e 9. Base l : Ka rg er. 1 99 8 : 7 6- 1 2 1 .
Barker BCW, Davies PL. The a p p l ied anatomy of the pterygo m a n d i b u l a r space. British Journal o f Surgery. 1 97 2 ; 1 0 : 43 -55.
---- ..
) ,�-,- -:....::..-.
142 Benign oral and dental disease
CRISPIAN SCU LLY AND JOSE-V SEBASTIAN BAGAN
Introduction Disorders affecting the teeth Disorders of tooth eruption Disorders affecting the gingivae Disorders affecting the periodontium
1816 1816 1817 1818 1820
Disorders affecting the oral mucosa Inherited mucosal disorders Acquired mucosal disorders Oral soreness and pain Further reading
1822 1823 1825 1828 1837
The data in the chapter are supported by a Medline search using the key words oral, with specific disease entities, and focussing on diagnosis and management.
INTRODUCTION fermentation by dental bacterial plaque of dietary sugars Oral lesions are usually the reswt of local disease but may
to organic acids. Plaque is a complex biofilm that forms
be the early signs of systemic disease, and in some instances
on teeth, particularly below the contact areas, along the
may cause the main symptoms. It should be borne in mind
gingival margin and in pits and fissures. Fermentation of
that the professionals most experienced in treating oral
carbohydrates, principally sucrose, to acids such as lactic
diseases are dentally qualified; this is an important resource
acid results in tooth demineralization (decalcification)
for the practicing ear, nose and throat (ENT) community.
and then proteolysis - caries (dental decay). The main
The relevant clinicians should work towards constructive
causal organisms are viridans streptococci such as
relationships and perhaps draw up appropriate local referral
Strep. mutans, and Lactobacilli. Saliva protects against caries,
protocols based on the interests and expertise available so as
and xerostomia significantly predisposes to caries.
to offer the highest quality of care to all patients. This chapter is an overview only and is divided into a synopsis of the more common signs and symptoms affecting
Decalcification
produces
an
opaque
whitish
area
(white spot lesion) on the tooth, reversible if there is no' cavitation and if the diet is changed and fluoride is
specific oral tissues, and discussion of the benign disorders of
applied. If unhalted, the enamel breaks down to form a
the teeth and oral mucosa of most relevance to otorhinolar
cavity and the dentine is invaded. Once caries reaches the
yngology. Only the more classic oral lesions are illustrated.
dentine, stimulation thermally or with sweet/sour may elicit pain. Such dentinal pain may occur when dentine is exposed by caries
DISORDERS AFFECTING THE TEETH Dental caries
(or trauma, erosion or abrasion).
Dentinal pain subsides within seconds of removing the stimulus. Untreated, caries almost inevitably progresses to reach the dental pulp, which becomes inflamed (pulpitis) causing spontaneous pain and resulting in pulp necrosis and dental abscess, granuloma or cyst.
Most oral pain and most problems affecting the teeth are
Caries is largely preventable by lifestyle modification,
a consequence of dental caries. This arises from the
topical fluoride treatment and improved oral hygiene.
Chapter 142 B e n i g n o ra l a n d d e nt a l d isease I 1817
Diagnosis is clinical, supported by imaging. Restorative dental treatment is required if a cavity develops.
Peria pica l a bscess (denta l a bscess. odontogenic abscess) A dental abscess arises usually as a sequel of pulpitis caused by dental caries or trauma. A mixed bacterial flora is implicated, with anaerobes such as fusobacteria and bacteroides species important. T he tooth is dead (non vital) , but pain and facial swelling from inflammation in the jaw bone and surrounding tissues are characteristic. Once the abscess discharges beyond the periosteum, the acute pain usually resolves. Most dental abscesses produce a swelling on the buccal gingiva. However, abscesses on maxillary lateral incisors and first molars may present palatally. Rarely, abscesses - especially those of the lower incisors or molars - discharge extraorally. When the abscess discharges, swelling subsides but a chronic abscess remains, discharging from a sinus, until the causal dental infection is dealt with by the dentist. However, occasion ally a fascial space infection can follow and this may jeopardize the airway. A granuloma may later arise and occasionally develops into a cyst (periapical cyst) . This may be asymptomatic and a chance radiographic finding or may present as a swelling (usually in the labial sulcus) or may become infected. It should be treated by a dentist. Diagnosis is clinical, supported by imaging. Extrac tion or endodontic (root canal) therapy of the affected tooth removes the source of dental infection. A small periapical cyst may remain attached to, and be extracted with, the causal root or tooth, or resolve with endodontic therapy. A cyst left in situ after the root or tooth is removed may continue to expand and is termed a resi dual cyst.
DISO RDERS O F TOOTH ERUPTI O N Teething _
'Teething' is poorly understood, and the soreness and fever are often due to herpetic stomatitis.
Reta rded eru ption of teeth Most cases are of local aetiology (e.g. tooth impactions) . Systemic conditions, cytotoxic drugs and radiotherapy account for a few cases.
Extra teeth Extra ( supernumerary) teeth are uncommon and gen erally found in the premaxilla, and are usually of unknown cause. However, supernumerary teeth are common in cleidocranial dysplasia.
Missing teeth Missing teeth are often only apparently missing - simply because they are unerupted.
Denta l a p l asia (hypodontia. anodontia) Wisdom teeth (third molars) , second premolars and upper lateral incisors are sometimes genetically absent. Absence of several teeth may indicate generalized conditions such as cleidocranial dysplasia, incontinentia pigmenti or ectodermal dysplasia.
Ma lformed and d i scol o u red teeth T here is a wide range of normal variation in tooth morphology and colour and few have teeth as white as advertising offers. Most dental discoloration is superficial and caused by smoking, foods and beverages, poor oral hygiene or medicines. Dental trauma, caries and restora tions may cause discolorativn. Fluoride may occasionally produce inconsequential minute white flecks but con centrations over 2 p.p.m. may produce fluorosis. Tetra cyclines given to a pregnant or lactating mother or a child under the age of 1 2 years, may cause significant brown intrinsic tooth staining (Table 142.1 and Figure 142.1). Teeth may be malformed genetically, as in peg-shaped teeth (Figure 142.2), or because of trauma, infection, radiotherapy, drugs or cytotoxic therapy. Neonatal jaundice can produce greenish teeth.
Prematu re eru pti on of teeth
Amelogenesi s i m perfecta
Erupted teeth may rarely be present at birth (natal teeth) or appear within the first few weeks ( neonatal teeth ) , particularly i n the mandibular central incisor region. Such teeth occasionally cause ulceration of the infant's tongue or mother's nipple but usually can be safely left in situ.
Amelogenesis imperfecta is a genetically determined disorder of enamel formation, an autosomal dominant which affects both dentitions, producing defects ranging from a localized pitting defect to a general diminution of enamel formation in which teeth are smaller, mottled and brown-yellow-white in appearance.
1 818 I
PART 15 THE UPPER DIGESTIVE TRACT
Causes of discoloration of teeth.
Table 142.1
�:· �����,��':��� ;.·a"::: /.�':,:;
.''-"�'�
,
�, .
_'/,
'�Jn:iinsic'- -,',
' .-
Trauma Caries Restorative materials, e.g.
Poor oral hygiene Beverages/food Drugs, e.g. iron, chi orhexid ine, sweetened medication Habits, e.g. from smoking or betel chewing
amalgam Pink spot (internal resorption) Drugs - mainly tetracyclines Fluorosis Dentinogenesis imperfecta Amelogenesis imperfecta Porphyria Jaundice in neonate or infant
Figure 142.3
Dentinogenesis imperfecta.
Ectodermal dysplasia There are many types of ectodermal dysplasia and in most, oral abnormalities are common, especially missing teeth (hypodontia) and abnormally shaped teeth.
Syp hilis Congenital syphilis is rare. Dental defects are typically Hutchinson's incisors (teeth w i th a barrel- or screwdriver shape). Such incisors, along with neural deafness and interstitial keratitis, are combined in Hutchinson's triad. The molars may also be hypoplastic (Moon's molars or
Tooth staining.
Figu r e 142.1
mulberry molars).
Loosening and early loss of teeth Teeth are lost early mainly because of trauma, dental caries or destructive periodontal disease Various
systemic
conditions
such
as
( periodontitis) diabetes,
.
and
immune defects such as human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) predispose to accelerated periodontitis
(Table 142.2).
D ISORDERS AFFECTI N G THE G I N G IVAE Figure 142.2
Peg-shaped tooth.
Bleeding Bleeding from the gingival margins is' not seen
Dentinogenesis imperfecta
gingivae
(gums)
are
healthy.
However,
if the
bleeding
is
common, usually from chronic gingivitis, a consequence Dentinogenesis imperfecta is an autosomal dominant condition
in
wh i ch
the
dentine
is
abnormal
and
of the accumulation of dental bacterial plaque because of inadequate oral hygiene
(Table 142.3). Chronic
gi ng ivitis
(Figure
is extremely common and affects over 90 percent of
142.3) and the enamel easily chips and wears and the
adults. The accumulation of plaque because of inadequate
translucent, the teeth appear grey, blue or brown
roots are short and fracture easily. Periapical infection is
oral hygiehe produces nonspecific chronic inflammation
not uncommon.
which is painless but may bleed. The gingival margins are
Chapter 142 Ben i gn o ra l a n d d e n ta l d isease I 1 8 1 9
Table 142.2
Pat h o l o g i ca l ca u ses of loose n i n g a n d e a rly loss o f t h e teeth.
Loca I causes Tra u m a
System it causes
Others
Disord e rs with some i m m u n e defi cit:
Acrodyn i a
Peri odontitis
Down syn d ro m e
Neoplasms
Di abetes m e l l itus
Eos i n o p hi l i c g ra n u l o m a
Le u ko p e n ia o r l e u kocyte defects
HIV
disease
J u ve n i l e periodon titis R a pid ly p rog ressive p e riodo ntitis P a p i l l on-Lefevre syn d ro m e Hypo p h os p h atasia Eh l e rs-Da n l os synd rom e (type
Table 142.3
VIII)
Ca u ses of g i n g iva l b l e ed i n g .
Local
Blisters
Systemic
Ch ro n i c g i n g ivitis
Any co n d ition ca u s i n g exa c e rbation
Chro n i c period o n titis
Le u ka e m i a
Acu te n ecrot i z i n g
H u m a n i m m u nod efici e n cy v i r u s
Blisters on the gingivae may result from burns, viral infections or vesiculobullous disorders.
of g i n g ivitis (e.g. p reg n a n cy)
g i n g ivitis An g ioma/te l ang i ectasia
i nfection O t h e r cau ses of p u rp u ra Ciotti ng defects Dru gs, e.g. a n ti coa g u l a nts Scu rvy
slightly red and swollen. If untreated, it may progress to periodontitis and tooth loss. Dental advice on improved oral hygiene is needed. T he tendency to chronic gingivitis is increased in immune defects and slightly increased by oral contra ceptives and pregnancy. Acute necrotizing ulcerative gingivitis (ANUG) may also cause bleeding. Uncommon except in lower socio economic classes, this is typically an infection of adolescents and young adults, especially in institutions, armed forces, etc .. ANUG is a noncontagious anaerobic infection associated with overwhelming proliferation of Borrelia vincentii and fusiform bacteria. Predisposing factors include smoking, viral respiratory infections and immune defects such as HIV/AIDS. Characteristic features are severe soreness, profuse gingival bleeding, halitosis and a bad taste. Interdental papillae are ulcerated with necrotic slough and unpleasant halit osis. Malaise, fever and/or cervical lymph node enlargement (unlike herpetic stomatitis) are rare. Can crum oris (noma) is a rare complication (see under Cancrum oris (noma) ) . Diagnosis is usually clinical. Management is by oral debridement, metronidazole (penicillin if pregnant) and oral hygiene. Gingival haemorrhage may also be seen in some vascular or platelet disorders, for example leukaemia.
Periodontal breakdown Accelerated periodontitis can be particularly seen in a number of genetic conditions such as Down's syndrome, Papillon-Lefevre syndrome and neutropenia, eosinophilic granuloma, hypophosphatasia, and diabetes mellitus, HIV/AIDS and other immune defects.
Pigmentation Gingival pigmentation is common in dark-skinned races (Figure 142.4). Other common causes include amalgam tattoo and melanotic macules. Smoking, tobacco and betel chewing, and drugs such as hydroxychloroquinine and minocycline, may also cause hyperpigmentation. Addison's disease, Kaposi's sarcoma and melanoma are uncommon causes (Table 142.4).
Redness Chronic gingivitis is the usual cause of gingival redness and is usually restricted to the gingival margins and interdental papillae. More widespread gingival erythema in children is usually caused by herpetic stomatitis but, in adults, desquamative gingivitis ( typically seen in lichen planus or pemphigoid) or occasionally allergic responses are responsible. Localized red areas may represent erythroplasia, carcinoma, Kaposi's sarcoma, candidiasis, lichen planus or lupus erythematosus� Irradiation-induced mucositis is a further cause of a red, sore mouth.
_.L.
1820
I PART 15 THE UPPER DIGESTIVE TRACT
Ulcers Ulcers are sometimes self-induced (artefactual). Neo plasms, herpesviruses, acute ulcerative (necrotizing) gingi vitis (ANUG) and other bacterial infections (e.g. syphilis, tuberculosis) and mycoses (deep mycoses) are other causes of ulceration. Aphthae rarely involve the gingiva.
White patches
Telangiectasia may be a manifestation of hereditary haemorrhagic telangiectasia, primary biliary cirrhosis, systemic sclerosis, or may follow radiotherapy. Haeman giomas are usually isolated but may occasionally be part of a syndrome.
The causes of white patches are summarized in Table 142.6. Thrush (acute candidiasis) produces gingival white patches. Leukoplakia is often associated with friction or smoking, occasionally with syphilis, candidiasis, use of sanguinarine or chronic renal failure, but most cases are idiopathic. Lichen planus and lupus erythematosus may present as white lesions. Rarely, lichenoid lesions are associated with various drugs, liver disease or graft versus-host disease (GVHD). Inherited causes of white patches, such as white sponge naevus and dyskeratosis congenita, are rare.
Swelling
DISORDERS AFFECTING THE PERI ODONTI U M
Localized gingival swellings (epulides) may be of local aetiology (irritation) or can be manifestations of pregnancy, a neoplasm or systemic disease (Table 142.5). Generalized gingival swelling is most commonly seen in chronic gingivitis, or caused by drugs such as phenytoin, cyclosporin and calcium channel blockers (Figure 142.5) and is occasionally hereditary (hereditary gingival fibromatosis). Gingival swelling may also be seen in herpetic stomatitis, leukaemia, Crohn's disease, orofacial granulomatosis, sarcoidosis, amyloidosis, scurvy, lipoid proteinosis, mucopolysaccharidoses and other disorders.
Loosen ing of teeth
Figure 142.4
T.able 142.4
Racial pigmentation.
Chronic periodontitis (inflammation of the gingiva and periodontal membrane) is the most common reason for loosening of teeth, but accelerated periodontitis which can have a genetic basis or be related to immune defects, is also an important cause. Trauma, and occasionally neoplasms, may be responsible for loosening of teeth. Chronic periodontitis may be a sequel of gingivitis but smoking is also a risk factor. T he gingiva detaches from the tooth neck, the periodontal membrane and alveolar bone are damaged, and an abnormal gap (pocket)
Causes of oral hyperpigmentation.
Localized pigmentations Kaposi's sarcoma
Gen���fzi ed' &:'�
I
Addison's disease
Malignant melanoma
Drugs, e.g. phenothiazines, antimalarials, minocycline, contraceptives
Melanotic macules
Ectopic ACTH (e.g. bronchogenic carcinoma)
Naevi
Heavy metals
Syndromes:
Syndromes:
Complex of myxomas, spotty pigmentation and endocrine overactivity
Albright's Nelson's
Laugier-H unzi ker
Malignant acanthosis nigricans
Peutz-Jegher's
Racial
Tattoos (amalgam or graphite)
: -
Localized irritation, e.g. smoking Other rare causes, e.g. haemochromatosis, generalized neurofibromatosis, incontinentia pigmenti
�J
�I
1821
Chapter 142 Benign oral and dental disease I
Table
142 . 5
Table
Causes of gingival swelling.
White gingival lesions.
142.6
Localized
Local Chroni c gingivi tis Hyperplastic gingivitis due to mouth breathing
Systemic
Hereditary gingival fibromatosis and associated syndromes Drugs: Phenytoin Cyclosporin Calcium-chnnel blockers Pregnancy Sarcoidosis o rofaciaI granu lomatosis Crohn's disease Leukaemia Wegener's granulomatosis Scurvy Amyloidosis Mucopolysaccharidoses Mucol! pidosis Lipoid prote inosi s JuveniIe hyaline fibromatosis Hypoplasminogenaem ia
Candidias is lichen planus Lupus erythematosus Papillomas (some) Syphilitic keratosis Chronic renal failure Inherited lesions (e.g. wh ite-sponge naevus)
Frictional keratosis Smoker's keratosis Id iopathic keratosis Carcinoma Burns Skin grafts
Abscesses Cysts Pyogenic granuloma Neoplasms and warts (various) Pregnancy Sarcoidosis OrofaciaI granulomatosis Crohn's disease Wegener's granuIomatosis AmylOidosis Neoplasms (various)
Chronic periodontitis.
Figure 142.6
Periodontal attention is required. Management com prises
improved
oral
hygiene
but,
since
the plaque
accumulates within periodontal pockets below the gum line, surgical removal of the pocket wall and removal of diseased
tissue
may
be
needed
to
facilitate
future
cleansing. Attempts to regenerate lost periodontal tissue (such as guided tissue regeneration) may be indicated. Systemic antibiotics have no place in treatment.
Acute pericoronitis Inflammation of the operculum over an erupting or Figure 142.5
impacted tooth is common, especially surrounding the
Drug�induced gingival swelling.
lower
third molar and
swelling and halitosis,
lymphadenitis, and develops between the tooth and gum. The tooth may slowly loosen and eventually be lost
(Figure 142.6).
Chronic periodontitis is typically seen in ad u lts
is
painless but may be associated with bleeding, halitosis
presents
trismus, regional
swollen, red and often ulcerated
operculum. Diagnosis
,
a
with pain,
sometimes fever and
microbiology
is clinical, supported by imaging and in
some
instances.
Debridement
and
antimicrobials may be indicated. T he offending tooth
and a fo ul taste. Debris and pus may be expressed from
may
the pockets (pyorrhoea), and there may be i n cre asi ng
resolved. Trauma from an opposing tooth should be
tooth mobility.
relieved.
need
extractidn
after
the
acute
condition
has
1822
I PART 15 THE U P PER DIGESTIVE TRACT
Cancrum oris (noma)
Table 142.7
In malnourished) debilitated or severely immunocom
Main causes of mouth ulcers associated with
:tst�"!ic d �s��se..
promised patients) ANUG may extend with gangrenous
��,£�<��(�.; ·':�:.c���;
necrosis (cancrum oris, noma). Anaerobes, particularly
Microbial disease
.J
' . ' .'""1'
(> :...- �
Herpetic stomatitis
bacteroides porphyromonas species, have been impli
Chickenpox
cated, and the condition is especially seen in resource
Herpes zoster
poor areas such as the developing world, or war zones.
Hand, foot and mouth disease
Diagnosis is clinical supported by microbiology in some
Herpangina
instances. Debridement and antimicrobials are indicated.
Infectious mononucleosis
Reconstructive surgery is needed in severe cases.
HIV disease Tuberculosis Syphilis
D I SO RDERS AFFECTI N G THE ORAL MUCOSA
Rarely fungal infections Malignant neoplasms Erosive lichen planus and chronic
Cutaneous disease
Blisters
ulcerative stomatitis Pemphigus
The causes of ulcers include:
Pemphigoid
•
local causes (e.g. trauma);
Erythema multiforme
•
recurrent aphthae (and Beh�et's syndrome);
Dermatitis herpetiformis and linear
•
malignant neoplasms;
•
ulcers associated with systemic disease;
IgA disease
•
iatrogenic causes;
•
disorders of uncertain pathogenesis.
Epidermolysis bulIosa Other dermatoses Anaemia
Blood disorders
Leukaemia
Vesicles may be seen in viral infections, especially in
Neutropenia
herpes simplex stomatitis, chickenpox, herpangina and hand) foot and mouth disease. Blisters may result from burns or vesiculobullous disorders such as pemphigoid
Other white cell dyscrasias G astrointestinal disease
Crohn's disease
and pemphigus. Mucocoeles produce isolated blisters) typically in the lower labial mucosa. Mucocoeles typically remain intact but most other mouth vesicles and blisters break down rapidly to form ulcers, see also
Coeliac disease Ulcerative colitis
Rheumatic diseases
Lupus erythematosus 8eh«;et's syndrome
Table 142.7.
Sweet's syndrome Reiter's disease Iatrogenic causes
Pigmentation
Drugs Cytotoxic and other agents Acrodynia
Mucosal pigmentation is most usually seen in dark skinned races (but may be seen in white people). Other common causes include amalgam tattoo and melanotic
Radiotherapy Disorders of uncertain
Angina bullosa haemorrhagica
pathogenesis
macules. Addison's disease, Kaposi's sarcoma, melanoma)
Hypereosinophilic syndrome Eosinophilic ulcer
pigmentary incontinence and other causes may need to be
Necrotizing sialometaplasia
excluded.
Redness
Atrophic areas are common in lichen planus. Lingual depapillation in deficiencies of iron) folate or vitamin B12
Red lesions may be inflammatory or represent erythro
may
plasia, atrophy, petechiae, telangiectasia, haemangiomas
geographical tongue may also produce red patches.
or neoplasms. simplex stomatitis, lichen planus or mucous membrane Mucositis
can
readily
be
induced
by
irradiation or chemotherapy. Erythroplasia usually represents carcinoma in situ or worse.
a
red
tongue)
termed
glossitis)
the
Oral petechiae are usually caused by trauma or suction
Candidiasis is a common cause as are primary herpes pemphigoid.
produce
but can be a manifestation of thrombocytopenia and may be
seen
in
infectious
mononucleosis,
rubella,
HIV
infection or leukaemia. Telangiectasia may be seen in hereditary haemorrhagic telangiect<1sia,
primary
biliary
cirrhosis
sclerosis, or may follow radiotherapy.
or
systemic
Chapter
Haemangiomas are usually isolated but may occasion ally be part of a wider syndrome. Carcinoma, Kaposi's sarcoma and Wegener's granulo matosis are some neoplasms that may have a red appearance. Pyogenic granulomas, Crohn's disease, or o facial granulomatosis and sarcoidosis may cause red swellings.
142 B e ni g n o ra l a n d d e n ta l disease I
1 823
MELANOTIC MACULE
The melanotic macule is an acquired, solitary, small, flat, brown to brown-black, asymptomatic, benign lesion, unchanging in character, similar to ephelis and lentigo. Melanotic macules are seen in up to 3 percent of normal people. Melanotic macules are best excised to exclude melanoma.
Swel lings Mucosal swelling may be seen after trauma, infection, in pyogenic granulomas, Crohn's disease, oro facial granulo matosis, sarcoidosis, angioedema, Wegener's granuloma tosis, amyloidosis and other disorders.
U lcers Ulcers are often caused by trauma or recurrent aphthae (see below under Recurrent aphthous stomatitis) . Malig nant neoplasms, drugs, irradiation, infections or disorders of blood, gastrointestinal tract or skin, also produce mouth ulcers (see list above under Blisters and Table 142.7).
NAEVI
Pigmented naevi are much less common in the oral mucosa than in the skin. Approximately half are of. the intradermal ( intramucosal) type; one third are blue naevi, many others are compound naevi and some are junctional. They are usually brown, macular, do not change rapidly in size or colour and are painless. There is no evidence that most naevi, except junctional naevi, progress to melanoma. However, they may resemble melanomas and if early detection of thin oral melanomas is to be achieved, all pigmented oral cavity lesions should be excised for histology. This is particularly important if the lesions are raised or nodular. PEUTZ-JEGH ER'S SYN DROM E
White patches White patches can be caused by debris, burns, infections (candidiasis, hairy leukoplakia) , skin diseases (lichen planus mainly) , carcinoma, drugs, friction or smoking, but many cases are idiopathic (Table 142.6). Lichen planus and lupus erythematosus may present as white lesions. Inherited causes are rare.
Peutz-Jegher's syndrome is an autosomal dominant trait characterized by hamartomatous intestinal polyposis and mucocutaneous melanotic pigmentation. Those affected have discrete, brown to bluish black macules mainly around the mouth, nose and eyes. There is a slightly increased risk of gastrointestinal carcinoma and carcino mas of the pancreas, breast and reproductive organs. Ruby and argon lasers have been used to treat the skin pigmentation.
I N H E RITED MUCOSAL DISORD ERS Red lesions Blisters VASCU LAR ANOMALI ES EPI DERMOLYSIS BU LLOSA
Epidermolysis bullosa (EB) is characterized by blisters which develop where there is trauma, and rupture to . produce ulcers, often with eventual scarring. Oral lesions are fairly common in the dystrophic and lethal forms of EB. There is a predisposition to oral squamous cell carcinoma, mainly in the Hallopeau-Siemens type. Dental hypoplasia and other defects and delayed tooth eruption may also be a feature.
Hereditary haemorrhagic telangiectasia
Osler-Rendu-Weber syndrome is characterized by multi ple telangiectasia on the lips, perioral skin, oral and nasal mucosae, as well as the gastrointestinal tract. Occasion ally, there are colonic or hepatic complications. Oral hemorrhage can be controlled by cryotherapy, cautery, infrared coagulation or Nd-YAg laser.
HAEMANGI OMA
Pig mented lesions Most oral hyperpigmentation is racial (Figure 142.4) and is most obvious in the anterior labial gingivae and palatal mucosae and is usually symmetrically distributed.
Haemangiomas are usually deep red or blue-purple, blanch on pressure and are fluctuant to palpation. Most are small and of no c�nsequence and seen in isolation, but a few may be multiple and/or part of a wider syndrome such as Maffucci, Sturge-Weber or Dandy-Walker
1824
I
PART
15
THE UPPER DIGESTIVE TRACT
�
syndromes, or other cranial f� ssa mal ormations. Hae . mangiomas are prone to excessIve bleedmg lf damaged. Lesions suspected of being haemangiomatous should be aspirated. Kaposi's sarcoma and epithelioid angioma tosis should be excluded. Oral haemangiomas are left alone unless causing symptoms when, if small, they are best treated with cryosurgery or laser, or if large by ligation or embolization of feeding vessels.
FORDYCE SPOTS (FORDYCE'S GRANULES) Fordyce spots are common. They are sebaceous glands which appear as yellowish small grains seen beneath the buccal or labial mucosa, usually inside the commissures
(Figure 142.7), and sometimes in the retromolar regions and upper lip. Fordyce spots are totally benign, although the occasional patient or physician becomes concerned about them or misdiagnoses them as thrush or lichen planus. No treatment is indicated, other than reassurance .
Swellings WH ITE-SPONGE NAEVUS (CANNON'S DISEASE; PACHYDERMIA ORAUS; WHITE FOLD E D GI NGIVOSTOMATOSI S)
H EREDITARY ANGlO-OEDEMA (HAN E; Cl ESTERASE I NHI BITOR D EFICI ENCy) HANE mimics allergic angio-oedema, but minor trauma
triggers more pronounced oedema of the lips, mouth, face and neck region, the extremities and gastrointestinal tract. Oedema may persist for hours and even days. Obstruction of the airway is a constant threat with
a
mortality as high as 30 percent in some families. In most
Cl esterase levels are reduced, the plasma C4 level falls but the C3 levels are normal. Cl esterase
cases the plasma
concentrates are the best treatment.
autosomal dominant trait, and related to defects in keratins 4 and 13. Painless, shaggy or folded white lesions typically affect the buccal mucosa bilaterally but may al�o . involve other areas) the upper respiratory tract, gemtalta and anus. Family history and clinical examination are usually adequate to differentiate this from other more common causes of white lesions. Reassurance is all that is required.
FOCAL DERMAL HYPOPLASIA (GOLTZ-GORUN SYN D ROME)
LYMPHANGIOMA Lymphangiomas are usually solitary and affect the tongue predominantly.
This is a rare benign familial disorder inherited as an
Occasionally, they are associated with
cystic hygroma. Small lymphangiomas need no treatment. Larger lesions may require excision although cryotherapy can be useful.
Focal dennal hypoplasia is a rare, presumably X-linked, genodermatosis causing anomalies of meso ectodermal tissues, with abnormalities of eyes, skin, musculoskeletal system and central nervous system. dental
anomalies
(hypodontia,
Oral papillomas,
enamel
defects
and
taurodontism) and occasional cleft lip and palate are the main oral features.
UNGUAL THYRO I D Although approximately 10 percent of cadaver tongues contain thyroid tissue, clinical presentation is much less common. Typically, there is an asymptomatic smooth surfaced lump in the midline of the base of tongue, between the sulcus terminalis and epiglottis. Occasionally,
Ulcers Epidermolysis bullosa
IS
cause of ulceration.
a lingual thyroid may produce dysphagia, cough, pain or rarely airways obstruction. Not
all lingual thyroid tissue is MRl
functional, and function tends to decline with age.
and Tc-99 m pertechnetate scintiscanning is important to ensure the presence of normal thyroid tissue in the neck before considering treatment of a lingual thyroid by surgery or radioiodine. Where thyroid-stimulating hormone levels are high, thyroid hormone supplements are indicated. Malignant change
is rare in
lingual
thyroids
though follicular
carcinomas have been recorded.
White or yellow lesions There are a number of genetically determined white lesions but most are rare.
Figure 142.7
Fordyce spots.
the most common inherited
Chapter 142 Benign oral and dental disease I
1 825
ACQUIRED MUCOSAL D I SORDERS Blisters Mucocoeles produce isolated blisters, typically in the lower labial mucosa. Superficial extravasation mucocoeles of the minor salivary glands in the palate, buccal mucosa or labial mucosa are not uncommon, especially associated with oral lichen planus. Blisters may result from burns or vesiculobuUous disorders such as pemphigoid and pemphigus or angina bullosa haemorrhagica (see list above under Blisters and
Table 142.7).
Vesicles may be seen in viral infections,
especially
herpes
in
simplex
stomatitis,
chickenpox,
herpangina and hand, foot and mouth disease. Recurrent herpes labialis is the most common cause of lip blisters: acyclovir has been the standard treatment used as a 5 percent
cream,
but
pencyclovir
1
percent
cream
Figure 142.8 •
Brown hairy tongue.
chewing betel may cause superficial brownish-red discolouration and predisposes to submucous fibrosis
is
and cancer;
reportedly more effective.
•
drugs (such as chlorhexidine, iron salts, griseofulvin, crack cocaine, minocycline, bismuth subsalicylate,
Pigmented lesions
lansoprazole and hormone replacement therapy (HRT»
cause superficial staining. Drugs which cause
FURRED, BROWN AND BLACK HAIRY TONGUE
intrinsic staining include antimalarials, minocycline,
The tongue may be coated with off-wrute debris in febrile
busulphan and gold.
and other illnesses, particularly in the edentulous, those on a soft, nonabrasive diet, xerostomia, poor oral hygiene or fasting.
LOCALIZED HYPERPIGMENTED LESIONS
Localized hyperpigmented lesions are usually due to
The tongue is often discoloured due to superficial
pigmentary incontinence, amalgam tattoos or naevi, but
staining from foods, drinks or habits such as tobacco or
melanomas and Kaposi's sarcoma must be excluded.
betel use (the teeth are also usually discoloured). Various
Amalgam
medicaments such as chlorhexi.dine or iron can also cause
pigmentation, usually seen in the mandibular gingiva,
tattoos
are
common
causes of
blue-black
a black or brown superficial staining of the tongue (and
close to the teeth
teeth). Occasionally, a brown, hairy tongue may be caused
apicectomy.
by drugs that induce xerostomia, lansoprazole or anti
diagnosis.
microbial therapy
melanoma but otherwise these innocuous lesions can be
(Figure 142.8).
The condition typically improves if patients avoid
(Figure 142.9), or
Radiography Biopsy
may
may be
help
in the scar of an
to
indica ted
confirm the to
exclude
a
left alone.
habits or drugs that stain the tongue, increase their oral hygiene, brush the tongue with a toothbrush, use sodium bicarbonate mouthwashes, chew gum or suck a peach
PURPURA
stone. Topical tretinoin may be effective.
Purpura may cause brown or red lesions.
G EN ERAUZED HYPERPIG M ENTATION
Red lesions
Generalized oral mucosal hyperpigmentation is usually - racial in origin and only occasionally has a systemic cause such as Addison's disease
(Table 142.4).
ERYTH ROPLASIA
Other causes
include:
Benign migratory glossitis (lingual erythema migrans; geographical tongue)
•
•
foods, beverages (such as beetroot, red wine, coffee
Geographical tongue is a common condition affecting
and tea) or confectionery (such as liquorice) which
approximately
cause superficial staining;
characterized
1-2 by
percent of the map-like
atrophic
population. red
areas
It
is
with
smoking tobacco is now a fairly common cause
surrounding borders; of increased thickness of filiform
(smoker's melanosis) which may cause extrinsic
papillae
discolouration but can also cause intrinsic
to day and even within a few hours. Geographical tongue
pigmentary incontinence;
may be asymptomatic or cause a sore tongue. This is a
(Figure 142.10). The patterns change from day
1826 I PART
15 THE UPPER DIGESTIVE TRACT
appliance, usually a complete upper denture and, despite its name, is not often sore. Dentures worn throughout the night, or with a dry mouth, favour development of this infection with
Candida and bacterial species There is an .
accumulation of microbial plaque on and in the fittin g surface of the denture and the underlying mucosa. When candida is involved in denture-related stoma titis,
the
denture
more
common
stomatitis',
terms
'Candida-associated
'denture-induced
candidiasis'
or
'chronic atrophic candidiasis' are used. Denture-related stomatitis is not exclusively associated
with
candida
as
bacterial
however and, occasionally, other factors such
infection, or mechanical irritation may be at play. Complications are uncommon, but include:
Amalgam tattoo.
Figure 142.9
• •
angular stomatitis; papillary hyperplasia in the vault of the palate.
Any underlying systemic disease should be treated where possible. Since the denture fitting surface is. infested, usually
with Candida albicans, this must be disinfected
and plaque must be removed regularly. Dentures should be left out of the mouth at night and stored in an antiseptic such as chlorhexidine or hypochlorite. The mucosal infection is eradicated by brushing the palate and using antifungals (usually topically) for four weeks.
Acute candidiasis Acute oral candidiasis may complicate long-term cortico steroid
or
antibiotic
therapy,
producing
widespread
erythema and soreness, sometimes with thrush. Figure 142.10
Geogra phi cal tong ue.
HIV-associated
benign, inflammatory condition of unknown cause, but many patients with a fissured tongue (scrotal tongue) also have erythema migrans. A positive family history may be obtainable.
HLA
findings have
been
equivocal
with
reports of associations with B15 and DR7. Some patients have atopic allergies such as hayfever and a few relate the oral lesions to a particular food, for example cheese, or to stress. Clinical examination usually suffices to differentiate the condition from lichen planus, candidiasis or defi ciency
glossitis.
occasionally
be
Blood
and
necessary
to
urine
examination
exclude
anaemia
may and
diabetes. In those with no systemic disorder, no effective treatment is available except reassurance. Similar oral lesions may be seen
candidiasis
Candida infections in and around the mouth have HIV epidemic has spread, and now other species (especially C. krusei) and antifungal increased greatly as the
resistance are clinical realities. The combination of oral and oesophageal candidiasis is particularly prevalent in HIV-infected patients. There may be transmission of
Candida species from
HIV -infected persons and new
species are being recognized. The clinical presentation is of erythematous areas generally on the dorsum of the tongue, palate or buccal mucosa. Lesions on the dorsum of the tongue present as depapillated areas. Lesions in the
palate
may
have
a
'fingerprint'
configuration.
There can be an associated angular stomatitis which is a well-recognized
feature of
T-cell
immunodeficiencies.
Antifungal therapy is indicated.
in Reiter's syndrome and generalized
pustular psoriasis.
CAND I DIASIS Denture-related sto ma titis (denture sore mouth) This is the most common form of mild, chronic, oral candidiasis. It occurs only beneath a denture or other
MEDIAN RHOMBOID GLOSSITIS (CENTRAL PAPILLARY ATROPHY OF TH E TON GUE) This is an uncommon red, depapillated, rhomboidal area in the centre line of the dorsum of tongue, anterior to the sulcus tenninalis, thought to be associated wit h candi diasis.
Multiple oral lesions may occasionally be present,
especialiy.a 'kissing' lesion in the palatal vault. Smoking,
Chapter den ture
wea ring
and,
occasionally,
immune
defects
Med ian rh o mboid glossitis is us u ally diagnosed on grou nds,
since some
a l tho ugh biopsy
1827
Denture-induced stomat i t is should be treated with a n antifungal. Miconazole may b e a preferabl e t rea tment for
i nclu ding HIV a nd diabetes p redispose. clin ical
142 B e n i g n o ra l a n d d e n ta l d i sease .
may be
indicated
candidiasis (cream applied locaUy, toget h er with the oral gel )
as
it has some Gram-positive bacteriosta t i c action.
l esions are nodu lar and m ay s imulate a
New dentures wh i ch restore facial con to u r may help. Any
ne oplasm both cl inically and h istopatho l ogically. It may
staphylococcal infection s h o u l d be treated with fusid ic
respond to cessation of smoking and use of antifungals.
acid o in tment or cream.
ANG U LA R C H EI LITIS (ANG U LA R STOMATITIS)
Swelli ngs
Angular che i l i t is is a fa i rly co mmon a cu te or chronic inflam m a t ion of the skin a nd contigu o us l abial m ucous
Lumps range from simple anatomical va riants such as
membrane a t the angles o f the mo uth, bila teral ly. Most
unerupted teeth , to i nflammatory) cystic) neo p l astic
cases are i n ad u l ts and due to mechan ical and/or infective
other disorders
and
(Table 1 42.8 ) .
causes but, i n ch i l d ren, n u t ri t ional or i m m u ne defects are more prominent ca uses . Mech a n ical pa tients who
fac t o rs do
may
contrihute
not wear
a
in
edentulous
denture o r who
have
i nadeq uate dentu res and, also as a no rmal conseq uence of the ageing process, p ro d uce an keep
the
small
Nutritio nal
area
of sk in
deficiencies,
in
constantly
p a r t icular
macerated.
deficiencies
of
riboflavi n, fola te, i ro n and general p ro tein malnu trition, a
Most intraoral abscesses are o dontogen ic in o ngrn and discharge in the mo uth but they
can
cause diagnosti c
ohlique curved fold and
may pro d u ce smooth, shiny, red l ips assoc i ated with angular s tomatitis,
ABSCESSES
comb i natio n called che i l osis. Crohn's
disease or oro fac ial gra n u lom atosis may be fo und in
Table
1 .
��.8
Swe l l i ng s i n the mouth.
Type [9f swel l i ng' ; .� "'":..: �_ , :
s
_
,
_
-
-_
N o rma l a n atomical features
some. Immune defici ency such as d i abe tes a nd H IV infect ion may p resent with angu l ar stoma t i tis.
Fo l i a te or other l i ng u a l pa p i l lae
Candida o r
stap hylo cocci are isolated fr o m most pat ients.
Pteryg oid h a m u l us Stense n's pa p i l lae U n e ru pted teeth
Deve l o p m e n ta I
Angular cheil itis presents as a ro ugh ly triangular area
H a e m a n g i o ma Lym p h a ng ioma
of erythema and o edema a t one, o r more commo nly both,
Tori
angles o f the mouth
H e red ita ry g i n g iva l fi b ro m a tosis
(Figure 1 42. 1 1 ). Linear fur rows or
fissures radiating fro m the an gl e of the mouth ( rhagades) are
N e u rofibro m a tosis
seen in the more severe forms, especially in denture
Cysts
wearers. Diagnosis is usually
0 bvio us
Candida sho uld b e so ught
O d ontomes
from clin ical exa m i nat i o n .
in the lesions
I n fl a m m atory
and beneath the
Pyog e n ic g ra n u l oma
denture.
C ro h n ' s disease
Dentures should be kep t out of the m o u th at n ight and stored
Abscess
Pu lse g ra n u l o m a
in a candidacidal solution such as hyp ochlori te .
Sarco i d osis W e g e n e r's g ra n u l o m a Orofa c i a l g ra n u l o m a tosis Tra u matic
E p u lis Fibroe p i t h e l i a l polyp Dentu re- i n d uced g ra n u l o m a M u coco e l e Hern i ation of b u cca l fat p a d
I n fe ctive
Va rious pa p i l lom atous lesio n s
Cystic
Cysts (e.g. d e n ta l cysts)
B l oo d dyscrasias
Le u ka e m i a , lym p h oma a n d mye l o m a
Be n i g n neoplasms
Va rious
M a l i g n a nt n e o p l asms
Pri ma ry and secon dary
O t h ers
Ang io-oe d e ma Amyl o i d osis F i b ro-osseous d iseases
Fig ure 1 42 . 11
Angula r stomat i t i s.
Aca n th osis n i g ricans
1 828 I PART
1 5 TH E U PP E R D I G ESTIVE TRACT
difficulties if they discharge on the face. Drainage and antimicrobials are indicated. Dental attention is required. A NG lO-OEDEMA
Oral swelling in acquired angio-oedema is of acute onset, may affect the lips, tongue or other areas. Local anaesthetics or more commonly angiotensin-converting enzyme (ACE) inhibitors may cause angio-oedema, which may respond to a sympathomimetic agent such as epinephrine or antihistamines. D ENTU RE- I N D UCED HYPERPLASIA (DENTU R E G RAN U LOMA, EPU LIS FISSU RATUM)
This is an elongated fibroepithelial enlargement seen where a denture flange is overextended and appears as a firm, leaf-like, painless swelling which should be excised and examined histologically, if modification of the denture does not induce regression. FOLIATE PAPI LLITIS
The foliate lingual papillae may become inflamed and swell and, because of their location on the tongue, may give undue concern about malignancy. The condition resolves spontaneously. ORAL CROH N'S DISEASE AN D OROFACIAL G RANU LOMATOSIS
Crohn's disease can affect the mouth. Ulcers classically involve the buccal sulcus where they appear as linear ulcers, often with granulomatous masses flanking them. Mucosal lesions also include thickening and folding of the mucosa to produce a 'cobblestone' type of appearance and mucosal tags. Purple granulomatous enlargements may appear on the gingiva. The lips or face may swell and there may be splitting of the lips and angular stomatitis. Some patients develop similar oral lesions because of an adverse reaction to food additives such as cinnamal dehyde or benzoates, butylated hydroxyinosole or dodecyl gallate (in margarine) , menthol (in peppermint oil) or to cobalt. The term orofacial granulomatosis (OFG) is preferred in some centres. It is unclear where in the spectrum of Crohn's disease/sarcoidosis/allergy/infection these latter lesions ( and related conditions such as Melkersson-Rosenthal syndrome and granulomatous cheilitis) lie. Investigation of the gastrointestinal tract is mandatory. Chest radiography, serum ACE and a gallium scan may be required to exclude sarcoidosis. Patch tests may be indicated to exclude reactions to various fo od stuffs or additives. Elimination diets may be warranted if allergy is suspected. Topical or intralesional corticosteroids may effectively control the oral lesions. Clofazimine appears to help the majority of patients by clearing granulomas.
SARCOIDOSIS
Isolated nodules, gingival lesions, facial or labial swelling and salivary gland involvement are the main oral or perioral lesions of sarcoidosis. MACROGLOSSIA
The tongue may be congenitally enlarged where there is a haemangioma or lymphangioma, or in Down's syndrome or Beckwith-Wiedemann syndrome. It may also enlarge in angio-oedema, gigantism, acromegaly or amyloidosis. In primary amyloidosis, the tongue is enlarged and firm with yellowish submucosal nodules, lumps or petechiae. Sec ondary amyloidoses rarely involves the mouth, except in the case of multiple myeloma or haemodialysis-associated amyloid, which may occasionally produce oral nodules. ORAL PAPI LLOMAS AN D CONDYLOMAS
Papillomas and condylomas are warty lesions caused by human papillomaviruses (HPV), which can appear any where in the mouth, but are most common in the palate. They should be examined histologically to establish a correct diagnosis. ORAL ALLERGY SYN DROM E
Oral allergy syndrome is the combination of oral pruritus, irritation and swelling of the lips, tongue, palate and throat, sometimes associated with other allergic features such as rhino conjunctivitis, asthma, urticaria-angio oedema and anaphylactic shock, precipitated mainly by fresh foods such as fruits and vegetables, sometimes by pollens because of cross-reacting allergens. It may respond to antihistamines or to a sympathomimetic agent.
O RAL SO REN ESS AN D PAI N Most oral pain results from odontogenic infections. Neurological, vascular and referred causes are less common. Psychogenic pain is all too frequent and this is discussed below. Chronic oral soreness may be particularly caused by ulceration, or by atrophy, geographical tongue ( see above under Benign migratory glossitis) , lichen planus (see below under Lichen planus) , or deficiency states.
Deficiency glossitis Glossitis may be related to deficiency of iron, folate or vitamin B12, and is associated with angular stomatitis and/or ulcers. In many, the tongue can become sore but may appear clinically completely normal and such patients' complaints are liable to be mislabelled as psychogenic. A full blood p icture and assays of iron, •
Chapter 142 Benign o ra l and d enta l disease I 1 829
folate and vitamin B12 are indicated. The cause of any deficiency should be sought before replacement treatment is given.
Bu rning mouth synd rome (ora l dysaesthesia ; glossopyrosis ; glossodynia) This most frequently affects middle-aged and elderly women and is often a medically unexplained symptom (MUS) but may be a neuropathy. Burning mouth syndrome ( BMS) may be seen in diabetes, deficiency states and with drugs (e.g. angiotensin-converting enzyme inhibitors, protease inhibitors, cytotoxic agents, clonaze pam). A monosymptomatic hypochondriasis, or an underlying anxiety about cancer or other disease with perhaps excessive tongue activity, appear to be the basis for the complaint in many patients (Table 142.9) . Although the tongue is most frequently involved, the patient may also occasionally complain of burning lips, gums or palate. The burning is usually bilateral and relieved by eating and drinking. Once organic disease has been excluded, reassurance and, occasionally, psychologi cal treatment, antidepressants or psychiatric care, are indicated.
Atypical facia l pa in The International Headache Society defines atypical facial pain as 'facial pain not fulfilling other criteria': therefore it is a diagnosis reached by the exclusion of organic disease. Atypical facial pain is a constant chronic orofacial discomfort or pain, often of a dull boring or burning type and ill-defined location in which there is: • •
a total lack of objective signs; a negative result from all investigations;
Table 142.9
C a u ses of b u rn in g m o u t h .
Local
�. , ;� �: :�� ���S;��i C,
Can d i d i asis
Psychogen i c : Cancero p h obia Anxiety states Hypochond ri asis Defi c i ency states : Pern i cious an a e m i a and oth e r vita min B d eficiencies Fol ate d efi ci ency I ron d efici ency
G eog ra phical ton g u e
Di abetes
Li c h en p l an u s
Drugs (e.g. ca ptopri l)
Ora l s ub m u cous fibrosis Dentu res
•
no clear explanation as to cause; poor response to treatment.
It falls into the category of MUS, most of which have a psychogenic basis. Atypical facial pain is not uncommon. Patients are often middle-aged or older and more than 70 percent of patients are women. The four main groups of patient appearing to suffer from this type of psychogenic pain are those who have: 1 . extreme stress but are otherwise normal individuals; 2. personality traits such as hypochondriasis; 3. neuroses, often depression; 4. psychoses. Clinical features include a constant chronic discomfort or pain, often of a deep, dull boring or burning type and mainly in the upper jaw. The location of pain is unrelated to anatomical distribution of trigeminal nerve innerva tion, the pain is poorly localized, and sometimes crosses the midline to involve the other side or moves to another site. Pain persists for most or all of the day but does not waken the patient from sleep. There is no tenderness or swelling in the area, nor any obvious odontogenic or other local cause for the pain. There is a total lack of objective physical ( including neurological) signs and all blood investigations and radiographic studies are negative. There are often multiple oral and/or other psycho genic-related complaints and a high level of utilization of health care services. There have often already been multiple consultations and attempts at treatment. This is a clinical diagnosis though careful examination of the mouth, peri-oral structures, and cranial nerves, and imaging (tooth/jaw/sinus radiography and MR/CT scan) to exclude organic disease are important. Attempts at relieving pain by dental treatment are usually unsuccess ful. The pain reduction achieved with antidepressants exceeds that produced by placebos. Cognitive-behavioural therapy or a specialist referral may be indicated.
. ..
D e p ress i on
Oth e r infections
•
Trigem inal neu ralgia (idiopathic trige m i na l neu ralgia ; benign pa roxys m a l trigem i na l neu ralgia ; tic dolou reuxJ Trigeminal neuralgia (TN) causes episodes of unilateral intense, stabbing, electric shock-like pain in the jaw or the face. TN onset is mainly in the 50-70 year age group. The cause is unclear, but one hypothesis is that there may be compression around the trigeminal root in the posterior cranial fossa, possibly due to a cerebral blood vessel becoming atherosclerotic, and therefore less flexible with age, and then pressing on the roots of the trigeminal nerve causing neuronal discharge. TN has the following main characteristics (Interna tional Headache Society) : paroxysmal attacks of facial or
1830
I
PART
15
THE UPPER DIGESTIVE TRACT
frontal pain which lasts a few seconds to less than two minutes. The p ain also has the following features: •
•
• •
•
• • •
distribution along one or more divisions of the trigeminal nerve; sudden intense, sharp superficial, stabbing or burning in quality; pain intensity severe; precipitation from trigger areas or by activities such as eating, talking, washing the face or cleaning t he teeth; between paroxysms, the patient is entirely asymptoma tic; no neurological deficit; a ttacks are stereotyped in the individual patient; exclusion of other causes of facial pain by history, physical examination and special investigations when necessary.
Severe orofacial pain suggestive of TN but with physical signs such as facial s ensory or motor impairment can result from cerebrovascular disease, multiple sclerosis, infections s uch as HIV infection, or space-o ccupying lesions such as neoplasms. These must therefore be excluded. Medical treatment is used successfully for most patients, typically using anticonvulsa nts. Carbamazepine is the main anticonvulsant used; other choices which may be effective include phenytoin, baclofen, gabapentin, oxcarbazine, valproate, clonazepam, lamotrigine or antidepressants. Some p atients report having reduced or relieved pain by means of alternative medical therapies such as acupuncture, chiropractic adjustment, self-hypnosis or meditation. Should medication be ineffective or if it produces undesirable side effects, neurosurgical proce dures are available. U l cers Most ukers have a local cause such as trauma. Many are recurrent aphthae. However, the causes of mouth ulcers are diverse (see Table 142.7), partly because lesions such as vesicles rapidly break down in the mouth as a result of trauma, moisture and infection. Single ulcers, if persis tent, may be neoplastic or due to a chronic infection. Other persistent ulcers may be due to systemic disease, and some are iatrogenic ( radiotherapy, chemotherapy, drugs) . Any patient with a single ulcer lasting mo re than two to three weeks should be rega rded with suspicion and further investigated, usually by biopsy - it may be a neoplasm or other serious disorder.
cause heal spontaneo usly within 7- 1 4 days if the cause is removed. Maintenance of good oral hygiene and the use of hot saline mouth baths and 0.2 percent aqueous chlorhexidine gluconate mouthwashes aid heal ing. A 0 . 1 percent benzydamine mouthwash may provide relief. Patients should be reviewed within three weeks to ensu re healing has occurred.
RECU RRENT APHTHOUS STOMATITIS (APHTHAE; CAN KER SOR ES) Recurrent aphthous stomatItIs (RAS) is a common condition characterized by recurring episodes of ulcers, da ting typically from childhood or adolescen ce. Aphthae typically are small, round or ovoid ulcers with a circumscribed margin, erythematous halo and a yellow or grey flOOf, each lasting from one to approximately four weeks before healing (Figure 142. 12) . There are three main clinical types: most common are minor aphtho us 80% ulcers which account for 80 percent. Some 1 0 p ercent of patients have m ajor ap hthous ulcers, and a further 1 0 10% percent suffer from a herpetiform type of ulceration (see 10% l ist under Blisters, Table 142.7 and Figure 142. 1 3 ) . T h e aetiology of RAS is not clear though there i s a genetic basis in some patients. Other aetiological factors include stress, trauma and cessation of tobacco smoking. A m inority (approximately 1 0-20 percent ) have an underlying haematological abnormality, usuaUy a low serum iron or ferritin, or deficiency of folate or vitamin B 1 2 . Up to 3 percent of patients have coeliac disease. Ulcers similar to aphthae are also seen in Beh�et's syndrome, Sweet's syndrome, HIV i nfection cyclical neu tropenia and other immunodeficiencies and, ra rely, in children in association with fever and pharyngitis (periodic fever, aphthous stomati tis, pharyngitis and cervical adenitis (PFAPA) ) . Diagnosis i s based o n history and clinical features (Tables 142.10 and 142. 1 1 ) ; no specific tests are available. Fortunately, the natural history is of eventual remission in
MOUTH U LC ERS OF LOCAL AETIOLOGY Accidental biting, other trauma or burns may cause ulceration. The possibility o f abuse or self-mutilation should always be borne in mind. Most ulcers o f local
Fig u re 1 42. 1 2
Aphthae.
Ch a pter 1 42 Benign ora l a nd dental disease I 1 83 1 most patients. Predisposing factors should b e sought and corrected. Go o d oral hygiene shoul d be maintai ned: chlorhexidine or triclosan mo uthwashes help achieve this and reduce ulcer duration. Ulcer pain can usually be reduced, and the time to healing reduced, wi th hydro cortisone
hemisuccinate
pellets
( Corlan ) ,
2 . 5 mg
or
triamcinolone aceto nide i n carboxymethyl cellulose paste (Adcortyl in orobase), used fo ur times daily, or failing the success of these, a stronger topical corticosteroid (e.g. betamethasone) beclomethasone, sone)
or
systemic
fiuticasone,
corticosteroid.
mometa
Thalidomide
can
frequently induce remission, but its teratogenic effects and the risk of neuropathy must be considered.
Fig u re 1 42 . 1 3
B E H C; ET'S SYN D R O M E (ADAMANTJADES SYN DROME)
Recu rrent aphthae.
Beh�et's
syndrome
( BS)
is a systemic disorder often
characterized by the association of recurrent aphthous sto matitis with genital ulceration and eye disease ( espe Ta b l e 1 42 . 1 0
Systemic and other factors occasiona l ly
assod�te� w ith recu ��e_nt aph�hous stomatitis. :
..
,};
disease is most common in the eastern Mediterranean
1 0-20% of patients with RAS have
Haematinic deficiency
defidencies of i ron, fol ic acid or vita min 8 1 2 Gastrointestina I
Malabsorption states (pern icious anaemia, coel iac disease a nd Crohn's
d isease
disease) may preci pita te RAS in a sma l l minority In some wome n, RAS are clearly related
Endocrine factors
to a fa l l in progestogens in the luteal phase of the menstrual cycle A few patie nts have an i mmune defect
I m m u nodeficie ncy
such as H IV disease Other factors
Tra u ma , ce rtain foods, stress and
Beh�et's synd rome
Association of RAS with ocula r lesions;
cessation of smoking may play a part gen ita l ulcers and multisystem disease Sweet's syndrome
Ta b l e 1 42 . 1 1
Pa i nfu l red-brown plaques and nod ules
M a_ i n featu res o f RAS. . - , . ; .... -"..., _ �..
1
...r
�
�
__
(Table 142. 12).
There is a genetic background and associations with HLA- B 5 (Bw5 1 split), HLA- B 5 1 or its B I O I allele. The
�q���_� �� ,� \ _:
: Fa�t?r
cially irido cyclitis and retinal vasculitis)
countries and in eastern Asia, along the Silk Route taken by Marco Polo. Many of the features of BS
(erythema no dosum,
arthralgia, uveitis ) are common to established immune complex disease and indeed, circulating immune co m plexes ( usually antigen-antibody complexes) a n d vascu litis are found. Most p atients are men, usually in their third or fo urth decade. B S is usually diagnosed on clinical grounds though findings of HLA-B 5 1 0 1 and antibodies to cardiolipin and neutrophil cytoplasm are supportive. Disease activity may be assessed by serum levels of acute phase p ro teins or antibodies
to
intermediate
filaments,
or
erythrocyte
sedimentation rate. Patients with suspected BS sho uld be referred early fo r specialist advice. Treatment includes mainly colchicine or corticostero ids) azathio pri ne) cyclosporin, chlorambucil, cyclophosphamide, dapsone, interferon-alpha, levamisole or thalidomide.
_ (, C.":- i:.' ·· '"'f,.."
- , ; ·, ;':_: -?,· Mj�Qr a,pht���' : - , :
Age of onset U l cer size
Ch i l d hood or adolescence
Ch i l d hood or adolescence
Young adult
2-4 mm
May be 1 0 mm or larger
I n itia lly tiny but u l cers coa lesce
Nu mber of u l ce rs
Up to approxi mately six
Up to approxi mately six
1 0- 1 00
Sites affected
Mai nly vestibu le, labi a l , b uccal mucosa
Any site
Any site but often ventru m of tongue
and floor of mouth ; rarely dorsum of Du ra tion of each ulcer Other
±t
ton g ue, g i ngiva or pa late Up to ten days
\
Up to one month May heal with scarring
Up to one month Affect mai n ly women
1 832 I PART Table
1 42. 1 2
1 5 T H E U PPER D I G ESTIVE TRACT
B e h� et's syn d rome.
Features
Incidence . (P/o)
Major O ra l
Aphthae
90- 1 00
G e n ital
U l cers
64- 88
N e u ro-ocu l a r
I ridocyclitis
1 0-90
Reti n a l va scu l itis O ptic atrophy Syn d ro m es rese mbling disse m i n ated scl erosis, pseudob u lba r pa lsy or n e u rosyphi l i s M e n i n g o e n c e p h a l itis Others Dermatological
Pust u l es
48-88
Eryth e m a nodos u m Pathergy
M i nor Protei n u ria Haematu ria Th romboph l ebitis An e u rys ms Arth ra l g i a s
MALIG NANT N EOPLASMS
Rec u rrent intraoral herpes simplex infection
Any solitary mouth ulcer lasting more than two to three weeks should be biopsied to exclude malignancy or other serious condition.
Chronic ulcers, often with a raised, white border, and sometimes with a dendritic appearance, may occasionally affect apparently healthy individuals, especially at sites of trauma, for example following a local anaesthetic. Persistent lesions may be seen in immunodeficient patients. Acyclovir or other antivirals may be indicated.
I nfective diseases VI RA L I N FECTI ONS Herpes s i mp lex stomatitis
Herpes simplex virus (HSV) - l causes primary herpetic stomatitis ( and the secondary infection of recurrent herpes labialis) . There are no precise distinctions nowa days, presumably with more frequent orogenital and oroanal sexual practices, and oral infection with HSV-2 is also frequently seen. Cases of primary herpetic stomatitis are now seen occasionally in adults. Many infections with HSV occur in childhood and are subclinical and, where there is disease, it varies greatly in severity. In many it is trivial and misdiagnosed or passed off as 'teething'. More typically it presents with malaise, anorexia, irritability and fever, anterior cervical lymphadenopathy and a diffuse, purple, boggy gingivitis with multiple vesicles followed by scattered ulcers 1-3 mm in diameter. A full blood picture, white cell count and differential, and viral studies may therefore be required. Specific antiviral agents are most useful in early disease and immunocompromised patients.
Herpes loster (shingles)
The pain of trigeminal zoster may simulate toothache and precede, accompany and follow the rash. Post-herpetic neuralgia may persist for months or years. The rash is restricted to a dermatome, is unilateral and associated with ulcers in the distribution of the involved nerve. There is ulceration of one side of the tongue, floor of the mouth, lower labial and buccal mucosa if the mandibular . division is involved. One side of the palate, the upper gingiva and buccal sulcus are involved in maxillary zoster. An underlying immune defect, such as HIVIAIDS or malignancy, should be excluded, though most cases are related simply to lesser problems in advanced age. Antivirals can be useful. Analgesics are indicated, but amytriptyline and fluphenazine may also be needed. See also Chapter 1 52, Acute and chronic pharyngeal infection. Epstein-Barr viru s i nfections
Epstein-Barr virus ( EBV) is responsible for infect ious mononucleosis, producing particularly lymphadeno pathy, sore throat, fever, malaise and rashes. There may be
Cha pter
oral ulceration or pericoronitis. Similar syndromes may be caused by cytomegalovirus (CMV), human herpesvirus 6 (HHV-6), toxoplasmosis and HIY. Diagnosis is usually confirmed by heterophil antibodies (Paul-Bunnell or Monospot tests) . No specific treatment is available, but supportive care is important. EBV is commonly found in the mouths of immuno compromised patients, and is implicated in oral hairy leukoplakia, oral ulceration and some oral lymphomas. See also Chapter 1 52, Acute and chronic pharyngeal infection. Enteroviruses
Coxsackie viruses can cause the clinical syndrome of herpangina (malaise, anorexia, irritability, low fever, slightly enlarged and tender anterior cervical lymph nodes and mouth ulcers, predominantly on the soft palate) or hand, foot and mouth disease (similar but with mouth ulcers and skin vesicles) . There may be a contact history. It is possible to culture Coxsackie viruses in suckling mice if absolutely necessary. The conditions are self-limiting, and treatment is supportive only. BACTERIAL I N FEC-nONS Acute n ecrotizin g (u l cerative) gingivitis and n oma
Syphilis
Oral ulcers may be seen in primary syphilis ( a primary hard or Hunterian chancre); in secondary syphilis (mucous patches and snailtrack ulcers) ; or in tertiary syphilis (a localized granuloma - gumma) . Exudate from a lesion suspected of being syphilis should be examined for treponemes by dark-ground microscopy but, since the diagnosis can be confused by oral commensal treponemes, lesions should first be thoroughly swabbed then gently scraped with a sterile spatula; and the scraping examined immediately by dark-ground microscopy. Serology is indicated. Biopsy is not usually needed. Antimicrobial Ta�e
�
�
142 B e i g n o ra l a
e n ta l d i sease I
1 833
therapy is indicated. See also Chapter 1 52, Acute and chronic pharyngeal infection.
Tuberculosis
Oral lesions are not common in pulmonary tuberculosis but chronic ulceration, usually of the dorsum of the tongue, may be seen. The typical oral lesion is an irregular ulcer with a granulating floor. Usually the ulcers are painless and resemble an oral squamous cell carcinoma. Atypical mycobacteria are not uncommonly involved. Diagnosis and management are discussed in Chapter 1 52, Acute and chronic pharyngeal infection. FU NGAL I N FECTIONS
Candidiasis rarely produces ulcers. However, the deep mycoses, which are usually seen in the West only in immunocompromised or debilitated patients, including those with AIDS, may produce ulcers (Table 142. 1 3 ) . Rhinocerebral mucormycosis typically commences i n the nasal cavity or paranasal sinuses and invades the palate to produce black necrotic ulceration. Most cases are seen in diabetics or in immunocompromised patients. Biopsy and radiography are required for diagnosis. Treatment is surgical debridement together with amphotericin intra venously and/or triazoles. Other deep mycoses tend to present with chronic lumps or ulcers, often in people with pulmonary lesions, and frequently clinically mimic carcinoma. They should be biopsied and most respond to amphotericin or triazoles. See also Chapter 1 52, Acute and chronic pharyngeal infection.
Haemato l ogica l d iseases DEFICI ENCY STATES
Low iron, folate or vitamin Bl2 levels may predispose to aphthae.
R a re orofa ci a l fu n g a l i nfectio � s.
142 . 1 3
In{ettibn' ; . , ; , .
Aspe rg i l l osis
-, Oral ·, man Ifestations Asp e rg i l l o m a R h i n ocere b ra l type ca uses p a l ata l n ecrosi s D isse m i nated i n i rn m u n ocorn p rorn ised patie nts
B l a stomycosis N orth American
O ra l u l ce rs, or s u p p u rati n g g ra n u l omas
South Ame rica n (pa racocc i d io idomycosis)
O ra l u l cers and Iy rn p h a d e n opathy
Cocci d ioid omycosis
R a re l y ora l u l cers
Cryptococcosis
O ra l u l ce rs
H isto p l asmosis
Lu m ps or u l ce rs
Phycomycosis (mu cormycosis, zygomycosis)
An tra l i nv o l ve m e n t w ith p a l a ta l u l ceration in i m m u n oco m p rom ised pati e n ts -
Sporotri c h osis
O ra l l esions ra re
especi a l ly d i a betics
1 834
I PART 1 5 THE U P PER D I G ESTIVE TRACT
LEU KOPEN IAS White - cell
AND
Para neop lastic pem ph i g u s
AGRA N U LOCYTOSIS and HIV
dyscrasias
infectio n
compl icated by ulceration. See also
Chapter
are
often
1 5 2 , Ac u t e
a nd chro nic pharyngeal infection .
P araneo pl ast ic pemphigus (PNP ) , usually associated with lyrnp ho p ro l i fe rative diseas e or thymo ma, o ften p resents
with o ral lesio n s which may be the sote manifestat ion . D i rect im munofluorescence is positive fo r IgG b o th in the epidermal intercellular spaces and along the basement
Gastr o i ntesti n a l d iso rde rs
membrane zo ne. Indirect immunofluorescence is s imi l arly positive i n a
CRO H N 'S DIS EASE AND OROFACIAL GRAN U LOMATOSIS
Pyosto matiti s
PV p attern . There is often only a part ial
respo nse to corticosteroids. Recent t herapeu tic adva n ces include
vegeta ns
th e use
of anti-CD20
monoclonal
an ti body
(rituxim ab ) and mycop h enolate .
Pustules and ulcers m ay be seen i n ulce rative coli tis (see above
u nder
O ral
C ro h n 's
disease
and
o ro faci a l
gran u lomatosi s ) .
S u bepith e l i a l i m m u n e b u l l o us d i seases A spectrum o f immune-mediated subep i t heli al bullous d iseases can p resent with o ral blisters and/o r erosio ns,
Dermatolog ica l d iseases
and
with immune dep osits zone.
at the epithelial basement
m embrane
PEMPHIGUS
M u co us membrane pe m p h i g o i d
Pem p h i g u s vu l g a ris
Mucous memb rane p em p h igo i d (MMP) is t h e main
The oral mucosa is almos t invariably involved in pemph igus vulgaris (PV) a n d o ral lesions are commonJy t h e presenting feature (Figure 142. 14). B ull ae appear o n
condition, and involves the oral m ucosa in m o re than o ne-third o f cases, commonly causing gingiva l lesio ns, u s u ally des qu amative gi ngiv itis , w hich is characterized by
any part o f the oral mucosa including the p alate, but so
eryt h emato us ,
r apidly break that they are rarely seen, a nd usually the
B ullae tend t o pe rsist fo r l onger than t hose o f pemp h igus.
patient
A b iopsy is required for d iagnosis . Serum autoa ntibodies
p resents
with
la rge,
painful,
pers istent r e d lesions. The Nikolsky sign
i rregu l ar
and
is often positive .
D iagn osis shouJd be co nfi rm ed by bio psy and im mune studies . A biop sy o f perilesional mucosa shouJd be taken
nosis
and
monito ring
of disease
with
azathiop rine,
to epithelial b asement memb rane m ay be detected i n a few patients but many
h ave immun e deposits ( m a inJy
IgG) at the ep ithelial b asement membrane zone. Sera of
main
antibo d ies against epiligrin, h ave an asso ci ated i nte rn al
h elp diag The
is largely based on systemic immun os up p ress i on using corticosteroids,
(Figure 1 42. 1 5 ) .
3 . Treatme n t
activity.
in p emphig us vulgaris is desmoglein
sore gingivae
MMP sele c tively and speci fica Uy b i nd h um an alpha-6 integrin, which appears to be a ta rget antigen . A small mino rity of patients, m a i n ly those with
fo r p araffi n section s and immunostaining a nd serum collected for a uto antibody titres which can an tigen
glazed,
dapsone,
meth o
patients with oral
to
m alignancy which should be excluded.
Top ical corticosteroids us ually
h elp i f the l es ions are an
trexate, cyclophosp hamide, gold o r cyclospor i n . Myco
restricted to the oral mucosa; and azath ioprine m ay be
p henolate mofetil offers
t he h ope of rel a t ively safer imm unosuppressio n with no n eph ro toxici ty or h ep ato
alt e r n at ive . Systemic corticosteroid s m ay occasio nally be requ ired bu t tetr acycl i nes
toxicity.
may help . Dapso n e may b e useful .
Figure 1 42 . 1 4
Pe mph ig us.
Figure 1 42 . 1 5
with or without nicotinamide
Desq u a m a t ive g i ngivitis.
Chapter 1 42 B e n i g n o ra l a n d d e n t a l d isease I
Erythema m u lti forme
Erythema multiforme (EM) appears to be an immuno logical hypersensitivity reaction. There may be a genetic predisposition with associations of recurrent erythema multiforme with HLA-B I 5 (B62 ) , HLA-B35, HLA-A33 , HLA-DR53 and HLA-DQB l *030 1 , and HLA D Q3 with HAEM (herpes-associated EM) , the reaction being triggered by: • •
•
•
infective agents, particularly HSV; drugs such as sulphonamides (e.g. co-trimoxazole) , cephalosporins, aminopenicillins, quinolones, barbiturates, oxicam nonsteroidal antiinflammatory drugs (NSAID) and many others; food additives or chemicals such as benzoates, nitrobenzene, perfumes, terpenes; immune conditions such as BCG or hepatitis B immunization, and others.
Most patients (70 percent) with either minor or major forms have oral lesions which begin as erythematous areas which blister and break down to irregular, extensive, painful erosions with extensive surrounding erythema. The labial mucosa is often involved, and a serosanguinous exudate leads to crusting of the swollen lips. The diagnosis can be difficult and there are no specific diagnostic tests for EM. It may be helpful to undertake serology for Mycoplasma pneumoniae or HSV. Biopsy of perilesional tissue, with histological and immunostaining examination are essential if a specific diagnosis is required. Supportive care is important; a liquid diet and intravenous fluid therapy may be necessary. The use of corticosteroids is controversial but minor EM may respond to topical corticosteroids. Major EM should be treated with systemic corticosteroids and/ or azathioprine or other immunomodulatory drugs. Antimicrobials may be indicated - acyclovir in HSV associated erythema multiforme (HAEM) related to HSV, tetracycline in erythema multiforme related to Mycoplasma pneumoniae.
I m m u ne defects H IV
Oral ulceration in patients infected with HIV may be due to any of the causes of mouth ulceration, including aphthous-like ulcers. However, it is particularly important to exclude infections, mainly herpesviruses, and neo plasms. There are also occasional examples of ulcers due to less common infections such as mycobacteria, syphilis, histoplasma, cryptococcus, leishmaniasis and others. Malignant disease (mainly Kaposi's sarcoma or non Hodgkin's lymphoma) may result in lumps which can ulcerate. Aphthous-like ulcers in HIV are often of the major type and frequently affect the fauces: they may
1 835
respond to local treatment or, failing that, thalidomide. Other mouth ulcers should be treated as appropriate.
Iatrogenic cond itions
-------
M U COSITIS
Mucositis (mucosal barrier injury) is the widespread erythema, ulceration and soreness which commonly complicates chemo-, radio- or chemoradiotherapy. Mucositis appears from 3 to 1 5 days after treatment, earlier after chemo- than after radiotherapy. Mucositis invariably follows external beam radio therapy involving the orofacial tissues, and total body irradiation. Up to 90 percent of patients on chemotherapy develop mucositis. Oral mucositis is particularly severe after haemopoietic stem cell transplant (HSCT) , because of radiation damage and myeloablation. Mucositis typically presents with pain which can be so intense as to interfere with eating, and significantly affect the quality of life, with ulceration and sometimes bleeding. The impaired mucosal barrier predisposes to life-threatening septic complications. Diagnosis is clinical and it is helpful to score the degree of mucositis to monitor therapy. Management aims to relieve pain, hasten healing and prevent infectious complications. Pain relief is usually with opioids given by patient-controlled analgesia and benzy damine can aid relief. Oral cooling with ice chips ameliorates chemotherapy-induced mucositis. Reliable data for other treatments are unavailable. Monitoring microbial colonization and the institution of antiviral prophylaxis and antifungal prophylaxis, to avoid colonization and superinfection, is particularly important in patients with low neutrophil counts. Invasive fungal infections of the oral cavity can be associated with systemic fungal infection and are indications for the use of liposomal amphotericin B. DRUG-IN DUCED U LCERS
A wide range of drugs can occasionally induce mouth ulcers, by a variety of effects. Oral ulcers are regularly produced by cytotoxic agents. Oral use of caustics, or agents such as cocaine can cause erosions or ulcers. Aphthous-like ulcers may follow the use of the cardio active agent, nicorandil. Oral ulcers of a lichenoid type may follow exposure to NSAIDs and other agents (see below under Lichen planus) . Erythema multiforme or toxic epidermal necrolysis may follow the use of a range of drugs (see below under Erythema multiforme) . Drug induced ulcers usually resolve in 10- 1 4 days if the offending drug can be identified and withdrawn.
W h ite lesions Acquired white lesions in the mouth are usually innocuous keratoses or caused by cheek biting or
PART
1 836 I
1 5 TH E U PPER D I G ESTIVE TRACT
chem i cal b urns, but in fections, dermato ses ( usu ally lichen
fo rms , to develop carcinoma
planus ) , neoplastic d iso rd ers and o t her co nditions must
percent over ten years.
be excl uded ( see discussed
Table 142.6 ) .
earlier
(see
Co nge ni tal lesions were
above under White
or
yellow
Biopsy with immunofluo rescence is often indicated to exclude keratosis, strat ifi ed
lesions) .
- po ss ibly a risk of up to 5
chronic
ulcera tive
epithelium -specific
sto m at i tis
an tin uclear
with
ant ibo dies,
lichen sclero su s, lupus erythematosus , malig nancy and C H EEK B I T I N G
Cheek
b iting
( M O RS I CATI O causes
other disorders .
BUCCARUM)
a whitish,
Predisposing factors should be corrected and symp
shredded appearance
usually of the buccal or lower labial mucosa at the
to ms controlled with topical medication, usu ally top ical corticosteroids o r topical tacrolimus.
ocd usal line ( a djacent to where the tee t h meet) . The habit is most common in tense or anxious individuals who may also s how b ruxism, mandibular pai n dysfunction or o ther fea tu res of psychogenic d isorders. The lesion is
o ral
ben ign but may simulate whi te - sponge naevus ( see above
LU PUS ERYTHEMATOSUS
Lupus m ay present with white lesions or u lcers.
under White-sponge naevus) . CAN D I D IASIS B U R NS
Candida albicans is an oral co m mensal
Chemical
b urns
( d ue,
for
exa mple,
to
holdin g
mou thwashes in the mouth or drugs against the buccal mucosa ) , or burns caused by heat, cold or irradiation, can cause wh i te s loughing lesions of the mucosa. Such lesio ns typically h eal spon tan eously
within one to three weeks.
in up to 50
percent of the h ealthy population , mo re in ciga rette smo kers .
Candida resides particularly on t he posterior
dorsum of the tongue. Carriage and in fection a re likely to result such
from xerostomia, local disturbances in sal iva ry flo ra as occurs during broad -spectrum antimicrobial
treatment, or immune defects. O f the several clinical presentatio ns of oral candidiasis, only thrush, c a ndidal leukoplakia
LI C H EN P LAN U S
O ral lichen pla nus
( L P ) i s probably approxim ately eight
times more common than cu taneous fo rms. The o ral mucosa may be involved alone or in asso ciation with lesions on skin or other mu cosa.
Most lichen pla nus is
idio pa th ic but si gnificantly greater anxiety and depression are o bserved than in controls. Some lichenoid lesio n s may be related to den t al m aterials, GVHD, drug use (e.g. NSAl Ds) , d iabetes o r liver disease. The common l esions are bilateral white
lesions in the
buccal andlo r li ngual mucos a. They may be reticular, papul ar) plaque-like o r erosive
(Figure 142. 16) .
LP may
also produce a desquamative gingivitis. There app ears to be
a
pred isposi tion,
par ticularly in
the
nonreticular
and
chronic
mucocutaneous
cand idiasis
present as white lesions: the o ther types - acute and chro nic atrophic candidiasis - a re red
(Table 1 42. 1 4 ) .
Thrush syn. acute pseudomembranous candid iasis Healthy neo na tes, who h ave y e t t o develop imm unity t o
Candida species, may develop th rush.
In o t h e r patien ts ,
predisposing facto rs include a n tibio tic or co rticosteroid use, xeros to m ia and severe T- cell immune defects (e.g. i n organ transplantatio n, leukae mia o r HIV d isease ) . The soft, creamy patches of thrus h, which resem ble milk curds, can be wiped o ff the o ral mucosa with gauze, leaving an area of erythema
(Figure 142. 1 7) .
Chron ic ca ndid i asis Lo ng- st anding
o ral
candidiasis
p rod uce
may
to ugh)
( chron ic hype rpl astic candidiasis or candidal leukopl akias ) which can have a m alignant adherent white pa tches
potential. In only a few patien ts with t h is type of chronic oral candi d iasi s can ei ther a local cause o r und erlying immune defect be identified. Chro nic mucocu tan eo us candidiasis syndromes are rare. The
diagnosis
o f o ral
t h rush
is
usually
cl inical .
Suspected candidal leukoplakia should be hiopsied , bo th to distinguish it from also
o ther non -candidal pl aques an d
because of possible dysplas ia. Although candidal
hyphae
and
a
neu t rophil
infil trate
m ay be
seen o n
haema toxyli n and eosin s ta i ning , pe riodic acid-Schiff (PAS) will de monstrate the purple s ta in ing of the hyphae . Possible p redispos ing causes sho uld be looked fo r Figu re 1 42 . 1 6
Lichen p i a n u s.
and
treated.
To p ical
polyenes
such
as
nysta ti n
or
Cha pter 142 Be n i g n oral a n d d e nta l d isea se I
Tab l e 1 42 . 14
1 837
Ora I ca n d i d i asis.
�.T���s�·" rif:"c"a hdid·i asiS "
Us u a l age
Acute pse u d o m e m bra nous ca n d i d i a sis (th ru s h ) d
Any
Dry m o u t h , a n ti m i cro b i a l s corti coste roid, l e u ka e m i a ,
Ac ute atro p h i c ca n d i d i a s i s (' a n t i b i o t i c m o u th ' ;
Any
B road-spectru m a n ti b i otics or cort i costero i d s
,
' -.-,;-::.. -- - -
at
Pred isposing factorsb
o n set
h u m a n i m m u n o defi c i e n cy v i r u s
(H IV)
a ntibiotic sore m o u th) Eryth emato u s ca n d i d i a sis
Any
H IV espe c i a l l y
Chro n ic atro p h ic ca n d i d iasis ( d e n tu re-re l a ted
Ad u l ts
D e n t u re-weari n g , especia l ly a t n i g h t
Usu a l ly m i d d l e-a g ed or e l d e rly
Tobacco s m o ki n g , d e n tu re wea ri n g , i m m u n e defect
stomati tis) Chro n i c hyperplastic c a n d i d iasis (ca n d ida I leu kop l a kiaj3 Med i a n rho m bo i d g l oss i t i s
Th i rd or later d ecades
Tobacco sm o k i n g , d e nt u re weari n g ,
Ang u l a r c h e i litis
Th i rd or l a te r decades
De ntu re weari n g ,
Chro n i c m ucocuta neous ca n d i d i a s is3
Usua l ly first decade
Often i m m u n e d efect; ra rely e n d o c r i n o p a t h y
H IV
H I V, d i a be tes, vita m i n defi c i e n cy
a W h i te lesi ons. b l m m u n e defects ca n predispose to any fo rm .
F i g u r e 142. 1 7
F i g u re 142. 1 8
T h rush.
H a i ry l eu ko p l a k i a .
KO PLl K'S SPOTS
ampho tericin, o r imid azoles such as m ico n azole are often indica ted b u t , in H IV i n fect io n a nd ch ro n i c candidiasis, fluco nazo le o r other azo l es may be required.
H A I RY LEU K O P LA K I A
White specks may be seen i n the b u cca l mucosa i n early measles.
FU RTH ER READ I N G
(HL) is s e e n i n severe imm une defects, i n fection a nd occas iona l ly in the appar
Hairy le ukoplakia especially H IV ently
immunocompe tent .
EBV
is
present
in
hairy
leukoplakia especia lly in the upper epithel i um and the H L is a wh ite p a tch, usu ally seen on the parakerati mu cosa
on
the
ton gue,
frequently
bilaterally
(Figure 142. 1 8 ) . The lesions a re co rrugated or have
a
shaggy or h a i ry a p p ea ra nce, a re mostly symptomless, and, u nl i ke some oral keratoses, have no known malignant p otential. It really needs no t rea tment but
a c la ssifi cation a nd ca t a l o g u e for t h e 2 1 st centu ry. Oral
Diseases. 2003 ; 9 : 1 9 - 2 3 . B a g a n J , M u z i o LL, Scu l ly C . M ucous m e m b ra n e pem p h i g oid . Oral
lesion regresses on trea tment with a ntivu-als. nized
Al d red MJ, Sava ri raya n R , C rawford PJ. Amelogen esis i m pe rfecta :
in HIV-infected
Diseases. 200 5 ; 11 : 1 9 7 - 2 1 8 . B a g a n N, J i me n ez Y, Sa n c h is J M , Poveda R, Mi l i a n MA, M u ri l l o J
et 01. Pro l i ferative verru co u s l e u kop l a kia : h i g h i n cide nce of g i n g iva l sq u a mo u s c e l l ca rci n o ma . Journal of Or,a l Pa thology and Medicine. 2 003 ; 3 2 : 3 7 9-8 2. Bagan N, M u ri l l o J , Poveda R, Gava l d a C, J i m e nez Y, Scu l ly C.
indivi duals may occasio na lly improve sp o n taneously or
Pro l i fe ra t ive ve rru co us l e u ko p l a k i a : u n u s ua l locations of o r a l
with ant iretroviral agents, acyclovir o r ganciclovir.
s q u a m o u s ce l l carc i n o mas, a n d fi e l d cance riza t i o n as s h ow n
/ _ -- -.
_
"
1 838 I PART
1 5 T H E U PPER D I G ESTIVE TRACT
by the a pp e a ra n ce of m u lt i p l e OSCCs. Oral Oncology. 2004 ;
m a n a g e m e n t a n d m a l ig n a n t tra n sform ation. Oral Surgery,
40 : 440-3.
Oral Medicine, Oral Pa thology, Oral Radiology, and
Bazrafs h a n i MR, H aj e e r A H , O i l ie r WE, Thorn h i l l M H . Po lymorp h i s m s i n t h e I L- 1 0 a n d I L- 1 2 g e n e c l uste r a n d r i s k of d eve l o p i n g recu rre n t a p hthous sto m a titis. Oral Diseases. 2003 ; 9 : 287-9 1 . B l ack M, M i g n og n a M D, Scu l ly C. Pe m ph i g u s vu l g a ris. Oral Diseases. 200 5 ; 1 1 : 1 1 9-30. Bozzo L, A l m e i d a 0, Scu l ly C, A l d red M . Fa m i l i a l g i n g iva l fi b ro m atos i s ; re port of a n exte n sive fou r g e n e ration ped i g ree.
Endodon tics. 2005; 1 00 : 1 64-78. M a n fred i M, M cCu l l o u g h MJ, Vescovi P, AI - Ka a ra w i ZM, Porter SR. U pdate o n d i a betes m e l l itus a n d re l a ted ora l d iseases. Oral Diseases. 2004 ; 1 0 : 1 87-200. Ma rko pou l os A, A l b a n i d o u - Fa r m a k i E, Kayavis I. Act i n ic c h e i l it i s : c l i n i ca l a n d pathologic cha ra cte ri stics i n 65 cases. Oral Diseases. 2004 ; 1 0 : 2 1 2-6. Meyle J , G o n z a l e s J R. I nfl u e n ces of syste m ic d iseases on
Oral Surgery, Oral Medicinal, Oral Pathology. 1 99 4 ; 7 8 :
p e riodontitis i n c h i l d re n and a d o l esce n ts. Periodontology.
452-4.
2000. 200 1 ; 2 6 : 92 - 1 1 2.
C h a l l acom be SJ , Setterfi e l d J, S h i rl a w P, H a rm a n K, Scu l ly C, B l a c k M M . I m m u n o d i a g nosis of p e m p h ig us a n d m u cous m e m b ra n e p e m p h ig o i d . Acta Odon tologica Scandinavica. 200 1 ; 59 : 2 2 6-34. Gonza lez- M o l e s M, Scu l ly C. Ves i c u l o - e rosive ora l m u cosa l d isease. lVI a n a g e m e n t w ith topical corticoste roi d s : 1 . Fundamental Principles and Specific Agen ts Available Journal of Dental Research. 200 5 ; 84: 294-30 1 . Gonza l ez-Moles lVI , Scu l ly C. Ves i cu l o- e rosive o ra l m u cosa l d isease. lVI a n a g e m e nt w i t h to pica l corticoste roi d s : 2. Protoco ls, m o n itori n g o f effects a n d a dve rse reactions, and t h e fut u re . Journal of Dental Research. 200 5 ; 8 4 : 302-8. Gorl i n RJ . Se l e cted ectod e rm a l dys p l as ias. Birth De fects. 1 98 8 ; 2 4 : 1 23-48. Haya - Fe r n a n d ez IVIC, Bag a n JV, M u ri l l o-Cortes J , Poveda- Roda R , Ca l a b u ig C . The preva l e nce o f ora l l e u ko p l a ki a i n 1 3 8 patie n ts with o ra l sq u a m o u s ce l l carci n o m a . Oral Diseases. 2004 ; 1 0 : 346-8. H i l l FJ , W i n t e r GB. T h e teeth in d e rmatolog i c a l d iseases. I n : C h a m pi o n R H (ed.). Recent advances in dermatology. Lo n d o n : Livi n gsto n e , 1 98 6 : 1 03-26. I to FA, de An d ra d e C R , Va rgas PA, J o rg e J, Lopes MA. Pri m a ry t u b e rc u l osis of t h e o ra l cavity. Oral Diseases. 200 5 ; 1 1 : 50-3 . Katz J, S h e n k m a n A, Stavropou l os F, M e l z e r E. O ra l s i g n s a n d
M eyle J. Le u kocyte a d hesion defi c i e n cy a n d p re p u be rtal periodon titis. Periodontology. 2000. 1 994; 6: 26-36. Moen K, B e rte l s e n LT, H e l l e m S, J o nsson R , B ru n J G . Sal iva ry g l a n d a n d tem poro m a n d i b u l a r j o i n t i nvolve m e nt i n rh e u m atoid a rt h riti s : re l ation t o d i sease a ctivity. Oral Diseases. 200 5 ; 1 1 : 27-34. M u m cu G , Ci m i l l i H , S u r H , H ayra n 0, Ata l ay T. Preva l e n ce a n d d i stri bution o f ora l l e s i o n s : a cross-sect i o n a l study i n Tu rkey. Oral Diseases. 200 5 ; 1 1 : 8 1 - 7 . N i ko l ov 0, Laza revska B , Arsovski T. H e red ita ry p a l m o - p l a n ta r keratoderma U n n a -Th ost w ith pe riodontitis. God Med Fak Skopje. 1 97 6 ; 2 2 : 41 5-24. N u n ez- M a rti J M , Bag a n JV, Scu l ly C, Pe n a rrocha M. Le p rosy : d e n ta l a n d p e riodonta l status of t h e a nterior m a xi l l a i n 7 6 patie nts. Oral Diseases. 2004 ; 1 0 : 1 9- 2 1 . O g d e n G R . Ta u rodontism i n d e rm ato l o g i c d isease. International Journal of Dermatology. 1 98 8 ; 2 7 : 360-4. Pe n te n e ro M , Ca rrozzo M , Pa g a n o M , G a l l i a n o 0, B roccol etti R, Scu l ly C, G a n d olfo S. O ra l m u cosa l dys p l astic l e s i o n s a n d ea rly s q u a m o u s ce l l ca rci n o m a s : u n d e rd ia g n os is from i n cisi o n a l b i o psy. Oral Diseases. 2003 ; 9 : 68-72. Scu l ly C, Bagan JV, Black M , Ca rrozzo M , Eisen 0, Escu d i e r M et al. Epith e l i a l b i o l ogy. Oral Diseases. 2005; 1 1 : 58- 7 1 . Scu l ly C, We l b u ry R, Fla itz C, Al m e i d a O PD . A color atlas of
sym pto m s i n re l a t i o n t o d isease activi ty a n d site of
ora facial health and disease in children and adolescents.
i nvolve m e n t in pati e n ts with i nfl a m m atory bowe l d isease.
Lon d o n : D u n itz, 2001 .
Oral Diseases. 2003 ; 9: 34-40. La ka ris G, Scu l ly C. Periodontal manifestations of local and systemic disease. H e i d e l be rg : Spri n g e r M e d i ca l Pu b l i s h e rs, 2002. Leto u r n e a u Y, Pe russe R, B u i t h i e u H . O ra l m a n ifestatio n s of
Scu l ly C. ABC of oral h ealth. Lon d o n : B ritish M e d i ca l J o u rn a l B oo ks, 2000. Scu l ly C. D ru g effects on sa l iva ry g l a n d s : d ry m o u t h . Oral Diseases. 2003 ; 9 : 1 65-76. Scu l ly C, Bey l i M , Fei rrero M , F ica rra G , G i l l Y, G riffiths M e t al.
Eh l e rs-Da n l os syn d ro m e . Journal. (Canadian Dental
U pd ate on o ra l l ic h e n p l a n u s : aetiopa t h og e n es is a n d
Association). 2001 ; 67 : 3 30-4.
m a n a g e m e nt. Critical Reviews i n Oral Biology a n d Medicine.
Lev i n LS. D e n ta l a n d o ra l a b n orma l it i es in sel ected e ctod e rm a l dys p l a s i a syn d romes. Birth Defects. 1 988 ; 2 4 : 205-27. Lod i G , Scu l ly C, Ca rrozzo M , G riffiths M, S L1 g e rm a n PB, Thon g p rasom K. Curre n t controve rsies in ora l l i c h e n p l a n u s : report o f a n i nternati o n a l con s e n s u s m eeti n g . Part 1 . Vira l i nfections a n d etiopathoge n esis. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodon tics. 200 5 ; 1 00 : 40-5 1 . Lod i G, Scu l ly C, Ca rrozzo M, G riffiths M, S L1 g e rm a n PB, Th o n g p rasom K. Cu rre n t con trovers i es i n ora l l i ch e n p l a n u s : re port o f a n i n te rnati o n a l co n s e n s u s m e eti n g . Part 2. C l i n ica l
1 998 ; 9 : 8 6- 1 22. Scu l ly C, Ca rrozzo M , G a n dolfo S, Pui atti P, M o n te i l R. U pdate o n m u cous m e m b ra n e p e m p h igoid (a n i m m u n e m e d i ated s u b e pith e l i a l b l isteri n g d isease) ; a h eterog e n eous e n tity. Oral Surgery, Oral Medicine, Oral Pathology. 1 99 9 ; 8 8 : 56-68. Scu l ly C, Eisen 0, Ca rrozzo IVI. lVI a n a g e m e nt of o ra l l i c h e n p l a n us. American Journal of Clinical Dermatology. 2000 ; 1 : 287-306. Scu l ly C. Handbook of Oral Diseases; Diagnosis and Management. Lon don : D u n itz, 1 999. Scu l ly C, Fti n t SR, Porter SR, M oos K. Oral and m axillofacial diseases. Lo n d o n : Taylor a n d Fra n cis, 2004.
Chapter
Seow WK. E n a m e l hypo p l a s i a in t h e p ri m a ry d e ntiti o n : a review. Journal o f Den tistry for Childen. 1 99 1 ; 58 : 441 -52. Spe i g h t P M , Ba rrett AW. Sa l iva ry g l a n d t u m o u rs. Oral Diseases. 2002 ; 8 : 2 29-40. Ste wa rt RE, H o l l iste r OW, R i m o i n DL e t al. A new va ri a n t of E h l e rs-Da n l os syn d rom e : an a utosom a l d o m i n a n t d isord e r of
1 42 B e n i g n ora l a n d d e nta l d isease I
1 839
fra g i l e ski n , a b n o rma l sca rri n g a n d g e n eral ized periodontitis. Birth Defects. 1 9 7 7 ; 1 3: 85-93. S u resh L, Radfa r L. O ra l sarcoid osis : a review of l itera t u re. Oral Diseases. 2005 ; 11 : 1 3 8-45. Va rgas PA, M a u a d
T,
B o h m G M , Sa l d iva PH, A l m e id a O P. Pa rotid
g l a n d i nvolve m e n t in a dva nced AI DS. Oral Diseases. 2003 ; 9 : 55-61 .
1 43 Abnor m a I ities of taste
STEV E N M B RO M LEY A N D R I C H A R D L D OTY
I ntroduction
1 840
Key poi nts
1 849
Anatomy and physiology
1 841
Best cli n i ca l practice
1 849
Classification of g ustatory disorders
1 842
Deficiencies in cu rrent knowledge and areas for future
Cl i nica l assessment of taste function
1 843
Causes of g u statory dysfu nction
1 844
Acknowledgments
1 849
Treatment and management of taste problems
1 848
References
1 849
1 849
research
The data in this chapter are supported by searches of Medline) Psych Info and MedLine using the key word smell, plus any particular diseases.
common in the general p o pulation. One survey estimates
I NTRO D U CTI O N
that more than
1.1
million Americans
(0.6 percent)
suffer
The act o f eating is a prerequisite for life, and because of ) the ability to taste) it is among life s finest pleasures. In
from some kind o f taste disturbance.5 When malfunc
fact, the sense of taste, along with its sister sense o f smell,
patterns of consumption in some individuals so markedly
tioning, the taste system can alter fo o d choices and
permits the sampling of an otherwise largely ignored but
that
robust chemical environment. All living things, fro m
immunity can occur.6 In people who are diabetic o r
weight
loss,
malnutrition
and
even
impaired
bacteria to humans, monitor the intake of chemical
suffer from hypertension) taste l o s s can b e very danger
nutrients. Even human neonates, j ust a few hours old,
o us, as there is a tendency to compensate for the loss by
display relatively consistent, quality-specific, facial ex
adding additional salt or sugar to fo od.
pressions in response to the oral presentation of sweet
Patients present with taste problems in a variety o f ways,
substances ( facial relaxati on, sucking movements) , sour
including: ( a) perceived loss or diminutio n of function; (b)
substances ( facial grimaces) and bitter substances ( tongue
the distortion o f everyday flavours; ( c) persistent abnormal
protrusions) facial grimaces) . 1 In addition to its obvio us
taste sensations in the absence of taste stimuli; and ( d)
hedonic and sensory functions, which aid in determining
syndromes of pain with or without taste triggers. This
the quality of sampled fo o dstuffs (thereby helping to
range of taste complaints confronting a physician largely
distinguish good toxins )
2
tasting
reflects a wide gamut of diseases and disorders. In this
t he sense of taste triggers ingestive and digestive
tasting nutrients
fro m bad
chapter) we examine such maladies and review important
reflexes that alter the secretion of o ral) gastric) pancreatic
aspects of the anatomy and physiology of the gustatory
and intestinal juices)3 and reinforces the ingestive process
system. Additio nally) we describe practical means
by . enhancing feelings o f pleasure and satiety.4
quantitatively evaluating this system in the clinic, and
The value of gustation is generally unrecognized by physicians) even tho ugh taste problems are relatively
for
p resent examples of common types of gustatory dysfunc tion and approaches to their management and treatment.
Chapter 143 Abnormalities of taste
ANATOMY AND PHYSIOLOGY Peripheral structures Approximately 4600 goblet-shaped taste buds are found within the oral cavity, each with a taste pore that opens into the bud's centre, termed the taste pit. [****] Most are found within the fungiform, foliate and vallate papillae on the tongue's surface (Figure 143.1); others are present at the base of the tongue, within the tongue-cheek margin, the soft palate, the pharynx, the larynx, the epiglottis, the uvula and the first third of the oesophagus. Each bud contains 50 to 150 slender epithelial cells arranged in a manner similar to the segments of a grapefruit, as well as supporting cells and basal cells from which the other cell types arise. Microvillae, on which the taste receptors that interact with the tastants are located, project from these epithelial cells into the taste pit. Light, dark and intermediate cells can be identified within the walls and base of the taste bud based upon their ultrastructural appearance and the presence or lack of dense granules in their apical portion. Taste bud cells can replace themselves ('turn over') periodically, with a time course of around two weeks. A tastant initiates gustatory transduction in one of two ways: by activating receptors coupled to G-proteins that,
I 1841
in turn, are coupled to various second messenger systems (which occurs for sweet- and bitter-tasting substances) or by directly gating apical ion channels on the microvillae of taste bud cells (which occurs for sour- and salty-tasting agents).
Saliva's role in taste function Saliva, which is secreted into the mouth via the parotid, submandibular, sublingual and other salivary glands, contains numerous proteins and peptides and plays an important role in the taste process (Table 143.1). Before taste stimuli enter the taste buds, they dissolve in or mix with saliva, altering their potency and concentration. When, for example, bitter-tasting, tannin-containing foods are ingested, the amount of proline-rich salivary proteins that bind tannins increases. 8 This decreases the concentration of tannins available to the taste buds and thereby increases the taste threshold to tannins. Importantly, saliva plays a key role in taste bud maintenance, and rinses away tastants and other materials that are introduced into the mouth, decreasing their tendency to linger in the oral cavity. In rats, removal of the submandibular and sublingual salivary glands results in the disappearance of the taste buds within the fungiform papillae, a phenomenon that is reversed by adding epidermal growth factor to their drinking water. 9 [****]
Taste buds are innervated by several cranial nerves Taste buds are innervated by branches of either the facial (eN VII), the glossopharyngeal (eN IX) or the vagus (eN X) nerves. eN VII supplies the buds within the fungiform and filiform papillae on the anterior two-thirds of the tongue (via the chorda tympani nerve), as well as those of the soft palate (via the lesser palatine nerve branch of the greater petrosal nerve). The geniculate ganglion contains the cell bodies of these afferent gustatory fibres. Proximal to the tongue, a segment of the eN VII taste fibres is shared with the lingual nerve (eN V3 ). eN IX via its lingualtonsillar branch, supplies the taste buds of the circumvallate papillae and most of those of the foliate papillae within the posterior third of the tongue. Taste buds within the nasopharynx are innervated by its pharyngeal branch. The nerve cell bodies of these visceral gustatory afferent fibres are located immediately outside the jugular foramen in the petrosal ganglion. eN X innervates the taste buds on the epiglottis, aryepiglottal folds and oesophagus.
Figure 143.1
Diagram of the human tongue showing regions
Central gustatory structures
of different papillae. Taste buds are found on the fungiform, foliate and circumvallate (vallate) papillae. Reprinted from Ref. 7 by permission of Lippincott, Williams 8: Wilkins.
The first gustatory relay station within the central nervous system (eNS) is the nucleus tractus solitarius (NTS),
1842 I PART 15 THE UPPER DIGESTIVE TRACT Table 143.1
Proteins and peptides found in whole saliva of mammals.
Jlroteinsand peptidesfound in whole saliva of mammals N-Acetyl-D-glucosaminidase Agglutinagen A Agglutinagen B Agglutinagen C Albumin Aldolase Amylase family Angiotensin II Anticomplementary factor Antileukoprotease Biopterin Bone marrow colony-stimulating factor Calmodulin Carbonic anhydrase Cathepsin Collagenase Cystatin family Elastase Endothelial growth-stimulating factor Esterase Esterase B Esteropeptidase Reprinted from Ref. 8. Copyright
©
Ferritin Fibronectin Fucosyltransferase Gastrin Glucagon Glutamine-glutamic acid protein family Granulocytosis-inducing factor 6-Hyd roxym ethyl pte ri n IgA IgG IgM Kallikrein Lactoferrin Lactoperoxidase Lethal factor Lingual lipase Lysozyme Mesodermal growth factor Metalloprotease Monopterin Mucins Neopterin
Nerve growth factor Neural tube growth factor Parotid glycoprotein family Peroxidase Plasminogen activator Platelet-activating factor Proline-rich proteins Prostaglandins Pterin Renin Sialomucin Sialotonin Somatostatin Statherin Tissue plasminogen activator Tonin Transferrin VEG protein Vitamin B-binding proteins Wound contraction factor Xanthopterin
1995, Doty RL.
which receives all of the peripheral gustatory fibres (Figure 143.2). This brains tern structure extends from the rostrolateral medulla caudally along the ventral border of the vestibular nuclei. Reflexive connections, via the interneurons of the reticular formation, are present between the NTS and cranial nuclei that control (a) muscles of facial expression, (b) preabsorptive insulin release and (c) oral behaviours such as chewing, licking, salivation and swallowing. Projections from the NTS ascend ipsilaterally to higher centres within the central tegmental tract. Most cross to the contralateral side within the brainstem, forming their synapses within the parvicellular division of the ventroposteromedial thalamic nucleus (termed the thalamic taste nucleus (TTN)).l1 From the TTN, fibres then project to the primary taste cortex, which is located deep in the frontoparietal operculum and adjacent parainsular cortex near somatosensory centres related to oral sensation and motor centres related to the control of jaw and tongue movement. 12 Tastants activate insular and perisylvian regions, including the frontal operculum, superior temporal gyrus (opercular part), and inferior parts of pre- and postcentral gyrus. A secondary cortical taste region is located in the caudomediallcaudolateral orbitofrontal cortex, extending several millimetres in front of the primary taste cortex. The cortical regions that process taste information also contain neurons responsive to touch and temperature. The orbitofrontal cortex, which has been linked to emotion,
feeding and social behaviour, processes not only taste information, but visual, auditory and olfactory information as well,13, 14 suggesting that the superior insula is bilaterally innervated, whereas the inferior insula seems to have lateralized input. Right-handed subjects exhibit relatively more left inferior insula activation, whereas the reverse is true for left-handed subjects. IS Elevated citric acid recognition thresholds have been reported in patients who have undergone right anterior temporal lobe resection, but not in those who have undergone left anterior temporal lobe resection, whose thresholds were similar to those of controls. IS Positron emission tomography (PET) studies suggest that orally-presented citric acid increases regional cerebral blood flow (rCBF) bilaterally in· the caudolateral orbitofrontal cortex. Relatively more activation is seen, however, in the right anteromedial temporal lobe and in the right caudomedial orbitofrontal cortex relative to their left hemisphere counterparts. IS
CLASSIFICATION OF GUSTATORY DISORDERS Although several schemes are available for classifying gustatory disorders, the following is most commonly employed: • ageusia - inability to detect qualitative gustatory sensatitms, i.e. absence of taste; • hypogeusia - decreased sensitivity to tastants;
Chapter 143 Abnormalities of taste
I 1843
Figure 143.2 Drawing of the human brain, with the presumed afferent limb of the taste system superimposed. nst, nucleus of the solitary tract; pbn, parabrachial nucleus; VPMpc, ventroposteromedial nucleus of the thalamus, pars parvocellularis; ins., insula; op, operculum. CN VI, IX and X enter the nucleus tractus solitarius in the order shown. © 2003 from Handbook of olfaction and gustation, 2nd edn by Rolls ET, Scott TR.1O Reproduced by permission of Routledge! Taylor 8: Francis Group, LLC .
• dysgeusia - distortion in the perception of a normal taste (for example, the presence of an unpleasant taste when a normally pleasant taste is perceived; in the absence of an identifiable stimulus, this is often termed phantogeusia); • gustatory agnosia - inability to recognize a taste sensation, even though the taste processing, language and general intellectual functions are intact.
irritate taste buds, a history of gastrointestinal problems should be sought. The fact that a number of drugs, including antibiotics, antihypertensives and lipid-lowering agents, produce significant taste disturbances requires a thorough assessment of medication use, as noted in detail below under Medications.
Physical examination and imaging CLINICAL ASSESSMENT OF TASTE FUNCTION History Obtaining a clinical history for taste dysfunction is similar to that for olfactory dysfunction. The physician should distinguish altered sweet, sour, bitter and salty perception from alterations in the perception of such sensations as chocolate, lemon, chicken, spaghetti, etc., as the latter largely reflect retronasal stimulation of CN 1. Most 'taste' complaints reflect loss or .distortions of olfactory function. Problems with chewing, salivation, swallowing or speech, or the presence of oral pain or burning, dryness of the mouth, periodontal disease or foul breath odour should be noted. A careful determination of a history of dental procedures, radiation exposure, medication usage and bruxism should be made, along with balance or hearing problems (since previous ear infections or surgery can damage the chorda tympani nerve and produce taste loss or distortions). Since acid reflux can damage or
Since dysgeusia may result from exudates commonly found in gingivitis or pyorrhoea, particular attention should be directed to the teeth and gunls during the evaluation of the oral cavity. Inspection of dental appliances (for example, fillings, bridges) should be made, along with that of the mucosal surfaces, which may show signs of scarring, inflammation or atrophy. Candidiasis, lichen planus and leukoplakia can sometimes be established from the presence of a whitish lingual plaque on the mucosal surface. Local causes of glossitis include: (a) burns; (b) mechanical trauma (for example, tongue biting, jagged teeth, ill-fitting dentures); and (c) irritation (for example, that due to excessive use of alcohol, tobacco, OT liberating mouthwashes or peroxides). Systemic causes include, in addition to vitamin and mineral deficiencies (for example, B vitamins, zinc, iron), such dermatological syndromes as Behcet's syndrome, lichen planus, erythema multiforme, aphthous lesions, pemphigus and syphilis. Masses, as well as neoplastic lesions or collections deep in the tongue's musculature, can be identified by palpation. Neurologically, the gross integrity of CN VII, IX and X can
1844 I PART 15 THE UPPER DIGESTIVE TRACT be assessed by screening for deficits in nongustatory functions of these nerves (for example, facial musculature, swallow, salivation, gag, voice production).
Quantitative gustatory testing Since whole-mouth tests are insensitive to even complete dysfunction of one or several of the nerves that innervate the tongue, regional or localized taste testing is needed to establish the function of each of the nerves innervating specific taste bud fields. Two general approaches to the presentation of stimuli can be employed. In the case of chemical testing, liquids containing tastants are presented to selected regions of the tongue or oral cavity via pipettes, Q-tips or filter paper discs. In electrical testing (also termed electrogustometry), low levels of electrical current are presented to taste bud fields via small electrodes. Electrogustometry is more practical in clinical settings than chemogustometry, since in the latter case considerably more time are needed to prepare stimuli, to present stimuli and then rinse stimuli from the oral cavity. In chemical testing, stimuli representing each of the four basic tastes are commonly administered to each side of the anterior (CN VII) and posterior (CN IX) tongue, with rinsing and expectoration following. Thus, a minimum of 16 trials (four tastants x four tongue regions), as well as 16 rinses and expectorations, are required to provide a single trial of a tastant representing a single concentration of each of the major taste qualities within the back and front hemilingual surfaces. If a paired blank in a forcedchoice trial (for example, water) is to be presented, then an additional 16 trials are needed. A valid taste test requires a considerable number of trials since multiple stimuli are required to produce reliable responses. The regional test employed at our centre uses a micropipette to present 1511L aliquots of a single concentration of each of four suprathreshold tastants (sucrose, citric acid, sodium chloride, caffeine), equated in viscosity, to left and right anterior and posterior lingual regions on each side of the tongue. A rinse is presented after each stimulus presentation, resulting in the presentation of a total of 96 taste stimuli and 96 rinses.
CAUSES OF GUSTATORY DYSFUNCTION Despite the fact that cases of total loss or markedly diminished whole-mouth gustation have been reported in the literature, they are rare. This reflects, in large part, the fact that taste buds are innervated by several cranial nerves, necessitating simultaneous damage to multiple pathways. Thus, less than 4 percent of 585 patients studied at the University of Pennsylvania who were complaining of both smell and taste disturbance had verifiable whole-mouth gustatory dysfunction, and even that dysfunction was limited. 16 All, however, had
olfactory decrements. [***] Hence, when whole-mouth loss is observed in the absence of overt damage to large regions of the tongue, it is most likely due to systemic metabolic problems, drugs or central lesions. In contrast to total taste loss, regional deficits in taste dysfunction are relatively common. Such deficits appear to increase with age. Thus, when sensitivity to three relatively low concentrations of NaCl was measured on the tongue tip and 3 cm posterior to the tongue tip in 12 young (20-29 years of age) and 12 elderly (70-79 years of age) individuals, the elderly performed at chance levels. [****] In contrast, the young typically detected the stimuli, exhibiting - as expected - more sensitivity on the tongue tip than on the more posterior stimulation site, and an increase in detection performance as stimulus concentration increased. 17 Regional taste deficits often go unrecognized by patients. For example, patients who have had one chorda tympani nerve severed in middle ear surgery are often unaware of the hemilingual anterior sensory deficit. Unfortunately, while the severed nerve can often be repaired at the time of surgery by anastomosis or approximation of the proximal and distal stumps,18 this is frequently not done because of the lack of recognition of the dysfunction by the patient. Such lack of recognition reflects, in part, the redundant neural innervation of the taste buds, as well as compensatory mechanisms. However, regional losses are now recognized as having the propensity for altering sensitivity in other parts of the tongue, and may even induce some forms of dysgeusia. Thus, anaesthetizing or traumatizing the chorda tympani (CN VII) unilaterally reportedly enhances taste sensitivity on the rear of the tongue (CN IX), particularly on the side contralateral to that of the anaesthesia or lesion,l9 and apparently in some cases produces a dysgeusic condition. Anaesthetizing one chorda tympani nerve reportedly increases the perceived intensity of bitter substances, such as quinine, applied to taste fields innervated by the contralateral glossopharyngeal nerve?O In contrast, perceived intensity of NaCl applied to an area innervated by the ipsilateral glossopharyngeal nerve is decreased. When both chorda tympani nerves are anaesthetized, the taste of quinine is intensified and the taste of NaCl diminished in areas innervated by the glossopharyngeal on both sides of the tongue. In approximately 40 percent of subjects, a phantom taste, usually localized to the posterior tongue contralateral to the anaesthesia, appears in the absence of stimulation. The phantom taste is eliminated when the region of origin is anaesthetized. Such phantoms are suggested to arise because of the release of inhibition normally present between the central projection areas of the different taste nerves?O The implication is that when individual taste nerves incur damage, other taste nerves may be activated in ways that induce dysgeusic or hypergeusic sensations. A number of diseases and disorders have been reported to be accompanied by at least some degree of taste
Chapter 143 Abnormalities of taste
dysfunction. Often local infections disturb or impair taste, including those of: • • • •
the teeth and periodontal tissue; the salivary glands; surfaces of the tongue, mouth and oropharynx; the middle ear.
In some cases, such infections release bad-tasting materials into the mouth (for example, gingivitis, sialadenitis, oral infections). Although it would seem reasonable to expect that quelling a bacterial infection through the use of antibiotics would be effective, some antibiotics may, in and of themselves, have detrimental consequences on taste function. 21 Other causes of taste impairment include: (a) transport problems of taste chemicals to the taste buds (for example, those caused by excessive chronic dryness of the oral cavity or damage to taste pores from a burn); (b) destruction or loss of taste buds themselves (for example, due to radiotherapy of the oral cavity); (c) damage to one or more neural pathways innervating the taste buds (for example, from Bell's palsy, trauma, dental or surgical procedures); and (d) damage or compromise of central neural structures (for example, from tumours, epilepsy, stroke). Additionally, dissimilar metal in fillings or other oral appliances can produce subtle electrical currents that, in turn, are noticed directly or alter taste function. 22 Disorders of particular importance to the otolaryngologist that produce taste disturbances are listed in detail below.
Bell's palsy Taste loss is common in Bell's palsy, although often the loss is not recognized by the patient until formal taste testing. Moreover, the taste-salivary reflex can be compromised in this disorder, resulting, for example, in salivation when a gustatory stimulus, such as a weak acid, stimulates the taste receptors on the anterior tongue. It should be recognized that regeneration of eN VII after a Bell's palsy may be abnormal. For example, novel innervation to nearby structures can produce synkinesis of the facial musculature when chewing, or tearing of the ipsilateral eye while eating ('crocodile tears'). Recurrent Bell's palsy can result in permanent facial weakness, and may be associated with lingua plicata (furrowed tongue) or recurrent facial .oedema. The taste loss of Bell's palsy presumably reflects lesions somewhere in the neural pathway extending from the pons to the taste buds (i.e. within the nervus intermedius or chorda tympani portions of the facial nerve, or within the geniculate ganglion), whereas the compromised salivary reflex presumably reflects damage to a relay from the nucleus of the solitary tract to the parasympathetic fibres innervating the salivary glands. It is often assumed that taste dysfunction due to this disorder resolves completely over time, although the empirical basis of this assumption is weak. The severity of the taste loss early in the disorder has been used as an index of prognosis.
I 1845
Ramsey-Hunt syndrome occurs from active infection of the geniculate ganglion, for example by Herpes zoster oticus, and is characterized by pain and the formation of vesicles in the external auditory canal and/or soft palate. Bartoshuk obtained regional (including palate) suprathreshold intensity ratings for sweet, sour, bitter and salty tasting stimuli in a patient with this disorder at regular intervals across a nearly 600-day period. 7 The malady involved both eN V and eN IX on the left side. Approximately three months after the onset of symptoms, no taste function was present on the entire left side. At 400 days post -onset, all taste qualities were perceived on the left rear and palate regions, but only sweetness could be perceived on the left front. Full taste recovery of the anterior tongue was still not present by the end of the nearly 600-day-long testing period.
Carcinoma Various neoplasms can influence taste function, particularly those within or near the gustatory pathways (for example, middle ear cholesteatomas and jugular foramen tumours). In some cases, taste dysfunction, even taste loss, is induced by radiotherapy or other forms of treatment, contributing to the associated anorexia. It is important to recognize, however, that conditioned taste aversions commonly occur in patients undergoing chemo- or radiation therapy for other forms of cancer throughout the body. In effect, malaise from the therapy becomes conditioned to the taste of foodstuffs, even if the malaise occurs hours after the intake of the food. In some cases, such conditioned aversions are transient, but in other cases they can be relatively long lasting and can lead to generalized anorexia and cachexia. A strategy for minimizing such aversions is to have the patient consume a novel food immediately before the initiation of therapy. Somehow subsequent conditioned aversions become focused primarily on the novel food, protecting against the formation of conditioned aversions to preferred food items. 23
Diabetes There is considerable evidence that diabetes can adversely influence the ability to taste. Most studies suggest that diabetics have elevated glucose taste thresholds, and there is evidence that both chemical and electrical taste thresholds increase as the disease's neuropathy progresses. 24 Some studies suggest that there may be a progressive loss of taste sensitivity, beginning with glucose and extending to other sweeteners and then to salty stimuli and subsequentlyall stimuli. Interestingly, the glucose insensitivity of diabetes may reflect the tendency of persons with noninsulin dependent diabetes mellitus (NIDDM) to exhibit a general and presumably hereditary deficit in glucose recognition. NIDDM patients show a mitigated
1846 I PART 15 THE UPPER DIGESTIVE TRACT first-phase insulin release to glucose infusions, whereas insulin release is normal to nonglucose stimuli, including arginine, isoproterenol, tolbutamide and secretin. 24 There is evidence that reduced glucose sensitivity precedes the diabetic state. Thus, several authors have noted that a subgroup of healthy first-degree relatives of adult-onset diabetics are less sensitive to glucose, whether tested using threshold and suprathreshold procedures. 25 , 26 [****] Interestingly, the proportion of such relatives that exhibit glucose-related taste insensitivity is the same as the proportion of those who go on to develop frank diabetes. Although it would seem likely that the glucose-insensitive relatives are the ones who eventually develop diabetes, this has not been empirically tested.
Epilepsy Taste perception can be altered by the lesions in the brain that develop as a result of seizure activity, and occasionally gustatory auras appear. Like olfactory auras, gustatory auras typically represent seizure activity within the temporal lobes, but sometimes epileptiform activity in the orbitofrontal lobes can also elicit such auras. 27 ,28 Aetiologies vary and identifiable causes include mesial temporal sclerosis, tumours, vascular malformations, infections (for example, tuberculosis, herpes simplex) and Rasmussen's encephalitis. Sensations have been reported to include 'peculiar', 'rotten', 'sweet', 'like a cigarette', 'like rotten apples' and 'like vomitus', although many of these 'tastes' probably represent smell sensations erroneously categorized as tastes by both the patients and their physicians (for review, see Ref. 29 ). Usually, taste auras produced by simple partial seizures are quelled by antiseizure medications, although this may not be true in some cases of intractable epilepsy. Surgery employed in intractable cases (for example, temporal lobe resection) successfully eliminates most gustatory auras. 28
Head or facial trauma Post-traumatic ageusia is much less common than posttraumatic anosmia, with solitary ageusia of one or more primary taste modalities occurring in less than 1 percent of people with major head injury. 16 However, the prognosis for post-traumatic ageusia is far better than for post-traumatic anosmia, and recovery from ageusia usually occurs in most patients over a period of a few weeks to months. Post-traumatic taste dysfunction can reflect various factors. Trauma-induced injury to the middle ear, such as that encountered with temporal bone fractures, can potentially produce both ipsilateral impairment of taste and salivary function (by damaging the chorda tympani nerve and preganglionic parasympathetic fibres). Since the chorda tympani-lingual nerve carries both taste and touch information, trauma to the jaw (for
example, from a blow) or to the mouth (for example, from aggressive dental procedures or difficult orotracheal intubation) can produce numbness and taste loss over the anterior two-thirds of the ipsilateral tongue. Taste may be more severely altered than fine-touch, since the chorda tympani fibres of the conjoined nerve are more superficial and posterolateral, and hence more susceptible to partial transection or pressure on the side of the nerve. 30 Early administration of steroids may minimize damage due to inflammatory processes in some such cases. A rare clinical syndrome of post-traumatic gustatory neuralgia can be produced by isolated damage to the auriculotemporal nerve CATN). This syndrome is recognized as taste-initiated, episodic, paroxysmal lancinating facial pain (often electric shock-like) in the cutaneous distribution of the auriculotemporal nerve. Post -traumatic abnormalities involving this nerve, such as sweating and flushing in this same region of the ATN following a taste stimulus, is termed Frey's syndrome. 31 This syndrome is said to be elicited not only by tastes, but by the smell of foods and even emotional excitement. 32 Among its causes are head trauma, parotid gland surgery, temporomandibular joint (TMJ) surgery, carotid endarterectomy, orthognathic surgery, oncological surgery, viral illness and local infection. 32 , 33, 34
Hypothyroidism Hypothyroidism is associated with taste dysfunction, although the nature of this association is not clear. Most investigators have found no influences of hypothyroidism on taste threshold sensitivity for basic tastants. 35, 36, 37 Deems et al. 16 found that while hypothyroid patients complained more frequently of taste loss than euthyroid patients, their taste thresholds for citric acid, NaCl, and sucrose were within normal limits. In contrast, McConnell et al. 38 reported that hypothyroid patients exhibited heightened taste and smell thresholds to a range of tastants and odourants that reverted to normal following administration of thyroxine. Recently, Uchiyama et al. 39 described a 74-year-old male patient with significant t~ste loss of at least ten weeks' duration who regained function following the initiation of thyroxine replacement therapy. Since the latter two studies employed drops of stimuli in their tests, it is possible that they are detection regional deficits that go undetected by the use of whole-mouth procedures. Nonetheless, while hypothyroid rats show significant alterations in preferences to several of the basic tastants, they do not exhibit hyposensitivity.40
Iatrogenic causes A number of surgical procedures have been associated with taste' dysfunction. Ear surgery, including tympanoplasty, mastoidectomy and stapedectomy, can damage CN
Chapter 143 Abnormalities of taste
VII. 19,41,42 The chorda tympani nerve fibres are often stretched or sectioned during surgery for otosclerosis, resulting in taste loss or dysgeusia. Such aberrations can last long after the operation. 43 Damage to the glossopharyngeal nerve is not uncommon as a result of tonsillect0my' bronchoscopy or laryngoscopy,44, 45, 46 reflecting the close proximity of the muscle layer of the palatine tonsillar bed to the lingual branch of CN IX. Third molar extraction, a very routine dental procedure, can compromise the lingual nerve and its coexisting chorda tympani fibres, as they lie in close proximity to the mandibular third molars. Such damage is very common; recently the taste function of 17 patients was quantitatively evaluated before third molar extraction, and at one month and six months thereafter. 43 Measurable taste deficits were found in most of these patients that persisted for at least six months after surgery, even though complaints of the deficits were rare. [****] Patients with the most deeply impacted teeth exhibited the most severe loss. The chorda tympani nerve may also be injured by the injection of local anaesthesia, either by direct contact with the needle or as a result of neurotoxic effects of the anaesthetic agent (typically lidocaine and epinephrine) .43,47 As noted above under Causes of gustatory dysfunction, there is some suggestion that hypergeusia and some phantom tastes may be induced by CN VII or CN IX nerve damage. 2o While it is generally assumed that most cases of iatrogenic damage to nerves subserving gustatory function resolve spontaneously over time (reflecting the ability of nerves to regenerate), the limited data available suggest that complete recovery is, in fact, the exception. 43
Medications Medications appear to produce taste disturbances more frequently than olfactory disturbances. Over 250 medications have been noted in the literature to alter the sense of taste, including antimitotic drugs, antirheumatic drugs, antibiotic drugs, antilipid drugs, psychotropic drugs and drugs with sulphhydryl groups, such as penicillamine and captopril?2,48 Angiotensin-converting enzyme (ACE) inhibitors are commonly associated with taste disturbance, such as hypogeusia, or excessive metallic, bitter or sour dysgeusic tastes. 22 Psychotropic medications, such as amytriptyline, clomipramine, desimpramine, imipramine, doxepin and trifluoperazine, as well as protease inhibitors used in the treatment of HIV and AIDS, not only have a taste of their own, but can significantly alter the intensity of other tastants, such as salt and sugar. 48, 49 Drug-induced taste disorders can, in some instances, be reversed by discontinuance of the offending drug, by employing alternative medications or by changing drug dosage. However, many pharmacological agents appear to induce long-term alterations in taste that may take months to disappear even after discontinuance of the drug. In situations where xerostomia and excessive dryness occurs
I 1847
as a result of a drug, a physician can offer artificial saliva (for example, Xerolube) to improve comfort, particularly if alternative medications are not available and drug dose cannot be decreased. However, if specific salivary proteins are needed for taste bud maintenance, saliva substitutes may not completely alleviate the chronic effects of lack of saliva on the taste buds.
Multiple sclerosis As in the case of olfaction, multiple sclerosis (MS) can produce taste disturbances if, in fact, the demyelination is present in taste-related pathways. 50 There is some evidence that MS-related taste loss may be related to taste quality, with deficits occurring primarily for bitter, or possibly salty, tasting stimuli. 51
Stroke Gustatory disturbance can occur secondary to cerebrovascular accidents (either ischaemic or haemorrhagic). In some cases, such dysfunction is accompanied by lesions within the gustatory pathways that can be discerned by MRI. 52 Trauma-related damage to brainstem structures that subserve taste may produce dysgeusia, although usually not without noticeable impairment of other cranial nerves or long tracts. Brainstem areas involved in taste that are susceptible to injury include the tractus solitarius and its nucleus (where injury produces ipsilateral ageusia) and the pontine tegmentum which involves both gustatory lemnisci (where injury produces bilateral ageusia). Ageusia can result from bilateral injury to the thalamus, although unilateral lesions above the brains tern are believed not to cause complete loss of function since, at that level, multiple regions presumably become involved in taste processing. An example of a stroke-related ischaemia in a region of the upper medulla near the right nucleus tractus solitarius that produced altered taste ability is shown in Figure 143.3. This patient reported a localized complaint of dysgeusia on the right. Taste identification scores were lower on the right than on the left CN VII and CN IX lingual fields. Gustation may also be affected by injury to cortical association areas outside of the primary gustatory pathways. The concept of left unilateral neglect, typically resulting from contralateral injury to the right hemisphere (for example, parietal lobe, thalamus, basal ganglia), appears to exist for taste in a manner similar to the visual, auditory, tactile and olfactory sensory systems. 53 In fact, a specific syndrome of buccal hemineglect may exist in which patients neglect mouth and food products in the left half of the mouth and are unable to initiate chewing and swallowing when food is in this location. 54 This syndrome can result in choking or a socially embarrassing tendency to drool and reg-blrgitate unnoticed food.
1848 I PART 15 THE UPPER DIGESTIVE TRACT 70
~-----------------------------------.
60
t5
~
o ()
c
50
Q)
2 Q) 0..
40
30
Left •
Figure 143.3
Right Anterior
•
Posterior
Identification scores on a regional taste test
showing relative decrement on right side of tongue. From a 65-year-old woman with a history of ministrokes who developed a persistent salty/metallic dysgeusia and soreness on the right side of the tongue following a severe two-day bout of emesis accompanied by marked dehydration and increased blood pressure but unaccompanied by fever.
Other conditions There are numerous other causes of gustatory disturbance for which limited data are available, including familial dysautonomia (a genetic disorder with lack of taste buds and papillae), myaesthenia gravis and Guillain-Barre syndrome. Chronic renal failure and end-stage liver disease have been associated with alterations in taste function and, in some circumstances, transplantation may improve detection thresholds. 55 While certain tastes may induce a migraine,56 it is not clear whether the prodrome or acute headache phase associated with migraine involves definable gustatory phenomena, as is seen with olfaction.
TREATMENT AND MANAGEMENT OF TASTE PROBLEMS Treatment is available for many taste problems, depending upon their aetiology. Dysfunction related to gastrointestinal reflux disease (GERD) often resolves following medical control of the reflux. Infections and inflammation of oral and perioral structures can be treated with antibiotics or antiinflammatory medications (for example, nystatin mouthwashes for Candida infections). Replacing fillings and dental prostheses or appliances that are made of different types of metals with homogeneous materials can eliminate 'metallic' tastes or 'funny feelings' due to small electric currents generated between the metals. Improvement of diet or supplementation of vitamins or minerals may improve changes in taste function secondary to some vitamin (for example, B3 , B12 , C) and mineral (for example, zinc, copper, iron) deficiencies. Medication-induced taste problems are, in many cases, reversible by discontinuing the medication, employing alternative drugs, or changing the dose regimen. Some drugs themselves taste bad and induce a similar taste only when being taken. However, other drugs may alter receptor function or damage elements of the taste pathways. In the latter case, return of normal function may take longer than the half-life of the agent would predict. Diminished taste function associated with poor oral hygiene or smoking can be reversed, to some degree, by improved hygienic measures or cessation of smoking. Taste distortions associated with hypothyroidism, liver disease, end-stage renal failure and other metabolic disorders usually resolve with proper hormonal supplementation, transplantation or dialysis. Dysgeusia following radiation or chemotherapy often spontaneously resolves over time. Eating a novel food at the time of the initiation of such therapy may focus conditioned aversions onto the novel food and minimize or eliminate the conditioning of nausea to normal foods during this period. Spontaneous resolution of taste problems due to Bell's palsy or radiation-induced xerostomia can occur, although in some cases, long-term, even permanent, dysfunction can remain. In some circumstances, cholinergic agents that promote salivation (for example, pilocarpine), artificial saliva (for example, Xerolube) or flavour enhancers improve comfort, increase palatability of foods and encourage food intake. Unfortunately, artificial saliva is no substitute for real saliva, which contains numerous growth factors and other chemicals essential for proper taste bud maintenance. It should be noted that some dysgeusic symptoms are acutely amenable to selected specialized mouthwashes. For example, symptomatic relief of some dysgeusias occurs following the use of a chlorhexidine mouthwash (0.12 percent for three minutes twice a day).57, 58 Additionally, topical dyclonine mouthwash may be of some benefit in selected cases, particularly ones associated with burning
r
Chapter 143 Abnormalities of taste
sensations. 59 Some studies have reported that tricyclic antidepressants are effective in treating burning mouth syndrome, apparently independently of their psychiatric effects. Fortunately, most cases of idiopathic dysgeusias . h'III two years. 60 spontaneous1y reso1ve WIt While often disregarded, the astute physician or oral medicine practitioner should inform patients of the chemosensory side effects that can occur as a result of nasal, aural or oral surgical procedures, including dental extractions (particularly third molar), middle ear operations and anaesthetic injections. Failure to notify patients of these possible, albeit remote, complications can lead to unnecessary litigation and the attendant problems for the physician and his institution. In summary, there are numerous therapeutic avenues available for the management of taste dysfunction. Acknowledging the presence and implications of a taste disturbance, in addition to providing therapeutic alternatives, can often be of significant psychological benefit to the patient.
medications that can produce taste dysfunction (e.g. antimitotics, antirheumatics, antibiotics, antilipids, psychotropics, ACE inhibitors, antifungal drugs). ./ Inspect oral cavity for signs of poor oral health, xerostomia, scarring, infection, inflammation or atrophy. ./ Obtain complete blood work up to rule out vitamin and mineral deficiencies, hypothyroidism, kidney or liver disease. ./ Initiate appropriate therapy, such as drug discontinuance or substitution, diet/vitamin supplementation, treatment of infection, reflux or inflammation.
Deficiencies in current knowledge and areas for future research
»
»
»
»
./ Rule out presence of smell loss using a standardized smell test, since most such complaints reflect CN I deficits (see Chapter 131, Abnormalities of smell). ./ Ask whether the sweetness of sugar, saltiness of potato chips, sourness of grapefruit juice or bitterness of tonic water can be discerned. If so, if the problem is not one of sensory distortion then CN I dysfunction is most likely. When possible, quantitatively assess regional taste function with electrogustometry or chemical stimuli . ./ Establish potential antecedent events such as recent dental work, a viral infection, ear problems, gastric reflux and short- or long-term use of
I 1849
The physiological basis of taste dysfunction and associated disorders, such as burning mouth syndrome, are poorly understood. Moreover, the efficacy of various treatments has not been determined in double-blind studies. A practical understanding of the influences of viruses and other agents on the peripheral taste nerves, and their capacity and time-course of regeneration, is sorely needed. The degree to which restoration of taste bud function following damage from radiation and other treatments should be established in people across a wide age range. One of the more perplexing problems facing the clinician is the influence of drugs on taste function. Today, for example, it is not clear whether primarily peripheral or central factors are involved. Studies elucidating the mechanisms of drug-induced hypogeusia and dysgeusia, and ways of mitigating the adverse effects, are therefore needed .
ACKNOWLEDGMENTS This paper was supported, in part, by grants PO 1 DC 00161, R01 DC 04278, R01 DC 02974 and R01 AG 27496 from the National Institutes of Health, Bethesda, MD USA (RL Doty, principal investigator).
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Schiffman SS, Wedral E. Contribution of taste and smell 1996; 7: 106-20.
11.
Kveton JF, Bartoshuk LM. The effect of unilateral chorda tympani damage on taste. Laryngoscope. 1994; 104:
losses to the wasting syndrome. Aging and Nutrition.
10.
19awa H,
Physiology and Behavior. 1993; 53: 553-63. Hoffman HJ, Ishii EK, Macturk RH. Age-related changes in
(NHIS). Annals of the New York Academy of Sciences.
9.
1.
Ohtsubo T et 01. Incidence of regeneration of the chorda
supplement to the National Health Interview Survey
8.
Saito T, Shibamori Y, Manabe Y, Yamagishi
high-carbohydrate and a high-fat meal in humans.
States adult population. Results of the 1994 disability
7.
Matsuda T, Doty RL. Regional taste sensitivity to NaCI: stimulation. Chemical Senses. 1995; 20: 283-90.
Warwick ZS, Hall WG, Pappas TN, Schiffman SS. Taste and
the prevalence of smell/taste problems among the United
6.
Surgery. 1991; 117: 519-28. relationship to subject age, tongue locus and area of
smell sensations enhance the satiating effect of both a
5.
Deems DA, Doty RL, Settle RG, Moore-Gillon V, Shaman P, Mester AF et 01. Smell and taste disorders, a study of 750
Doty RL (ed.). Handbook of olfaction and gustation. New
Neurologique. 1923; 2: 97. Posttraumatic gustatory neuralgia: a clinical model of
Chapter 143 Abnormalities of taste
33. 34.
35.
36.
37.
38.
39.
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41. 42.
* 43. 44.
45.
trigeminal neuropathic pain. Journal of Orofacial Pain. 1998; 12: 287-92. Truax BT. Gustatory pain: a complication of carotid endarterectomy. Neurology. 1989; 39: 1258-60. Sharav Y, Benoliel R, Schnarch A, Greenberg L. Idiopathic trigeminal pain associated with gustatory stimuli. Pain. 1991; 44: 171-2. Lewitt MS, Laing DG, Panhuber H, Corbett A, Carter IN. Sensory perception and hypothyroidism. Chemical Senses. 1989; 14: 537-46. Pittman JA, Beschi RJ. Taste thresholds in hyper- and hypothyroidism. Journal of Clinical Endocrinology and Metabolism. 1967; 27: 895-6. Facchini F, Pettener D, Rimondi A, Sichimbaeva K, Riva P, Salvi P et al. Taste sensitivity to PTC and thyroid function (FT4 and TSH) in high- and low-altitude Kirghiz populations in the Pamir. Human Biology. 1997; 69: 97-106. McConnell RJ, Menendez CE, Smith FR, Henkin RI, Rivlin RS. Defects of taste and smell in patients with hypothyroidism. American Journal of Medicine. 1975; 59: 354-64. Uchiyama F, Fukuyama J, Kamei T. [Defect of taste in a patient with hypothyroidism]. [Japanese]. Rinsho Shinkeigaku-Clinical Neurology. 1992; 32: 547-9. Brosvic GM, Doty RL, Rowe MM, Harron A, Kolodiy N. Influences of hypothyroidism on the taste detection performance of rats: a signal detection analysis. Behavioral Neuroscience. 1992; 106: 992-8. Bull TR. Taste and the chorda tympani. Journal of Laryngology and Otology. 1965; 79: 479-93. Moon CN, Pullen EW. Effects of chorda tympani section during middle ear surgery. Laryngoscope. 1963; 73: 392-405. Shafer DM, Frank ME, Gent JF, Fischer ME. Gustatory function after third molar extraction. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology and Endodontics. 1999; 87: 419-28. Tomita H, Ohtuka K. Taste disturbance after tonsillectomy. Acta Oto-Laryngologica Supplement. 2002; 546: 164-72. Donati F, Pfammatter JP, Mauderli M, Vassella F. Neurologische Komplikationen nach Tonsillektomie. Schweizerische Medizinische Wochenschrift. 1991; 121: 1612-7.
46.
47. 48.
49.
50.
51.
52. 53.
54.
* 55. 56. 57.
58.
59.
* 60.
I 1851
Arnhold-Schneider M, Bernemann D. Uber die Haufigkeit von Geschmacksstorungen nach Tonsillektomie. HND. 1987; 35: 195-8. Nickel AA. Regional anesthesia. Oral and Maxillofacial Surgery Clinics of North America. 1993; 5: 17-24. Schiffman SS, Graham BG, Suggs MS, Sattely-Miller EA. Effect of psychotropic drugs on taste responses in young and elderly persons. Annals of the New York Academy of Sciences. 1998; 855: 732-7. Schiffman SS, Zervakis J, Heffron S, Heald AE. Effect of protease inhibitors on the sense of taste. Nutrition. 1999; 15: 767-72. Combarros 0, Miro J, Berciano J. Ageusia associated with thalamic plaque in multiple sclerosis. European Neurology. 1994; 34: 344-6. Catalanotto FA, Dore-Duffy P, Donaldson JO, Testa M, Peterson M, Ostrom KM. Quality-specific taste changes in multiple sclerosis. Annals of Neurology. 1984; 16: 611-5. Onoda K, Ikeda M. Gustatory disturbance due to cerebrovascular disorder. Laryngoscope. 1999; 109: 123-8. Bellas DN, Novelly RA, Eskenazi B, Wasserstein J. The nature of unilateral neglect in the olfactory sensory system. Neuropsychologia. 1988; 26: 45-52. Andre JM, Beis JM, Morin N, Paysant J. Buccal hemineglect. Archives of Neurology. 2000; 57: 1734-41. Bloomfeld RS, Graham BG, Schiffman SS, Killenberg PG. Alerations of chemosensory function in end-stage liver disease. Physiology and Behavior:. 1999; 66: 203-7. Blau IN, Solomon F. Smell and other sensory disturbances in migraine. Journal of Neurology. 1985; 232: 275-6. Helms JA, Della-Fera MA, Mott AE, Frank ME. Effects of chlorhexidine on human taste perception. Archives of Oral Biology. 1995; 40: 913-20. Lang NP, Catalanotto FA, Knopfli RU, Antczak AA. Qualityspecific taste impairment following the application of chlorhexidine digluconate mouth rinses. Journal of Clinical Periodontology. 1988; 15: 43-8. Formaker BK, Mott AE, Frank ME. The effects of topical anesthesia on oral burning in burning rr.outh syndrome. Annals of the New York Academy of Sciences. 1998; 855: 776-80. Deems DA, Yen DM, Kreshak A, Doty RL. Spontaneous resolution of dysgeusia. Archives of Otolaryngology Head and Neck Surgery. 1996; 122: 961-3.
144 Salivary gland anatomy GRAHAM J COX
Embryogenesis and ultrastructure Microscopic anatomy The parotid gland The parotid duct Facial nerve
1852 1852 1853 1854 1854
The submandibular glands The submandibular duct The sublingual glands Key points References
1856 1856 1856 1857 1857
This data in this chapter are supported by information and references derived from major anatomical and surgical texts. Although the recent literature was searched using standard strategies, this was unproductive. A search using the standard search engines (key words salivary gland anatomy) revealed only one recent relevant paper, thus most of the factual information has been derived from historical factual observation and description (level 3 and 4 evidence).
EMBRYOGENESIS AND ULTRASTRUCTURE
MICROSCOPIC ANATOMY
The salivary glands share a common embryological development, whether they are the major named glands or the minor mucosal salivary glands. The major glands lie distant to the oral mucosa, and are connected to the mucosa by excretory ducts. The minor glands lie within the mucosa or submucosa of the oral cavity and oropharynx and either open directly onto the surface of the mucosa or are connected to it via short excretory ducts. All of the major salivary glands are derived from oral cavity epithelium, which proliferates and burrows into the surrounding mesenchyme to form a solid cord. Extensive branching occurs during embyogenesis to form the acini of the glands, and a lumen develops within the main trunk to form the excretory duct. As the parotid gland burrows caudally, it entraps mesenchymal structures, which later develop into the facial nerve and lymph nodes. Some of the minor salivary glands develop from endoderm caudal to the stomodeal plate, but all of the major glands are derived from ectoderm. The parotid glands are the first to develop in the fourth week of embryogenesis, followed by the submandibular glands at six weeks and the sublingual glands at eight weeks.
The basic secretory unit is the acinus, comprising secretory cells arranged in a sphere surrounding a duct. The acini in major salivary glands are arranged into lobules and lobes within the glands. Each lobule has a single excretory duct. The lobules are linked by dense fibrous tissue containing excretory ducts, vessels, lymphatics, nerve fibres and ganglia to form lobes. The secretory cells are pyramidal with narrow luminal apices. Their broader bases rest on a basement membrane surrounded by stellate contractile myoepithelial cells. The acinar ducts coalesce into intercalated ducts and subsequent striated ducts composed of columnar cells, before uniting into the main excretory duct of the gland. The secretory cells are described as being of three types. Cells containing small granules are serous and secrete salivary proteins and enzymes. Mucin-producing cells are cylindrical in shape and contain larger granules producing mucoproteins. Seromucinous cells have an intermediate ultrastructure. It is likely that the morphological description is an oversimplification and the products of these cells form an almost continuous series, from serous secretions' with negligible amounts of protein-associated acidic carbohydrates, to mucous secretions rich in them.
Chapter 144 Salivary gland anatomy
THE PAROTID GLAND Clinical anatomy The parotid glands are the largest of the salivary glands. They resemble a three-sided pyramid, are wedge shaped in coronal section and enveloped by the investing layer of deep cervical fascia (Figures 144.1 and 144.2). Each gland has an average weight of 25 g. The parotid gland is irregularly lobulated and lies below the external auditory canal, filling the space between the mandible anteriorly and the sternocleidomastiod muscle posteriorly. It extends anteriorly onto the masseter muscle. The pars accessoria is a separate part of the gland lying on the masseter between the parotid duct below and the arch of the zygoma above. The superficial surface is concave and is covered by superficial fascia, the posterior border of platysma and skin. Superficial parotid lymph nodes and facial branches of the great auricular nerve overlie this surface. The great auricular nerve is derived from the cervical plexus, and provides sensory sensation for the lower two thirds of the pinna. The superior surface is concave and lies adjacent to the cartilagenous external auditory canal and the temporomandibular joint. The auriculotemporal nerve lies in the capsule adjacent to the neck of the mandible. The apex of the gland lies on the posterior belly of the digastric muscle. The anteromedial surface lies on the posterior border of the ascending ramus of the mandible and the medial pterygoid muscle. The facial nerve enters the gland on this surface. The posteromedial surface is indented by the external carotid artery before it penetrates this surface of the gland. It lies on the mastoid process, the posterior belly of the digastric, the sternocleidomastoid muscle and the styloid process. The medial aspect
I 1853
may project as far medially as to be in contact with the lateral wall of the pharynx. As the gland develops from the buccal cavity, it grows backwards towards the ear. It encloses part of the external carotid artery, which divides into the maxillary artery and superficial temporal artery within the gland. The maxillary artery emerges from the anteromedial surface. The transverse facial artery branches from the superficial temporal artery before the latter emerges from the superior surface. Superficial to the arteries lie the corresponding maxillary and superficial temporal veins, uniting to form
Zygomatic arch
Superficial temporal artery
Superficial temporal vein
Pinna
Dotted outline of parotid gland
Facial nerve
Styloid process
Parotid _A~• •I duct
Digastric
Masseter - - - - + - 1
External carotid artery
Figure 144.2
Sternomastoid
Greater auricular nerve
Retromandibular vein
The parotid gland is outlined to show its
relationship to adjacent structures, associated vessels and nerves.
Masseter muscle Ascending ramus of mandible Parotid gland Medial pterygoid muscle Retromandibular vein Pharynx Posterior belly of digastric muscle Stemocleidomastoid muscle
Figure 144.1
Axial MR scan showing
the relationships of the wedge shaped parotid gland, and its division into superficial and deep lobes by the retromandibular vein.
1854 I PART 15 THE UPPER DIGESTIVE TRACT the retromandibular vein. The posterior facial vein enters the anterior border of the gland adjacent to the mandibular branch of the facial nerve, to traverse the gland and join with the retromandibular vein. Emerging from the apex of the gland, the retromandibular vein unites with the posterior auricular vein to form the external jugular vein. An anterior branch of the retromandibular vein joins the common facial vein before entering the internal jugular vein. Radiologically, the retromandibular vein is a useful landmark for the facial nerve, which traverses the gland, superficial to the vein. The facial nerve enters high on the posteromedial surface and divides into two main temporal and cervical divisions, each passing anteriorly through the gland, before emerging from the anteromedial surface in its terminal branches. The facial nerve is said to divide the gland into a deep and superficial lobe. This concept is helpful clinically, but is not anatomically based. The intraparotid lymph nodes usually have a distinct capsule and are part of the mucosaassociated lymph nodes. Most are found lying within the gland lying superficial to the retromandibular vein.
The capsule The gland is enclosed by deep cervical fascia, which splits to surround the gland forming the capsule. The fascial envelope is continuous anteriorly with the fascia covering the masseter muscle, and posteriorly with fascia enveloping sternocleidomastoid muscle. Deep to the gland it is attached to the styloid process, tympanic plate and mandible, forming the strong and unyielding stylomandibular ligament, before blending with the carotid sheath. This fascial layer is largely tough and inelastic, but thins anteriorly. Inflammatory oedema or pus within the gland is largely constrained by the capsule, leading to severe pain occurring in advance of overt enlargement of the gland. The relatively thin fascia covering the apex of the gland can lead to the spread of sepsis into the parapharyngeal space. The capsule also can determine the position and expansion of tumours arising within the gland. The majority of tumours arise in the superficial lobe and expand towards the superficial surface of the gland, whereas some deep lobe tumours are constrained by the stylomandibular ligament and expand into the parapharyngeal space, distorting the lateral pharyngeal wall. Tumours originating adjacent to the stylomandibular ligament may be restrained by this structure and the posterior aspect of the mandibular ramus to form a dumb bell-shaped mass.
THE PAROTID DUCT The parotid duct is lined by low cuboidal epithilium, surrounded by a smooth muscle and fibrous tissue wall. Its course begins within the gland by the confluence of the main intraparotid ducts, and the duct emerges from the anterior border of the gland. It is approximately 5 cm in
length. Running anteriorly, overlying the masseter, it receives the duct of the accessory gland before turning medially at the anterior margin of masseter. It lies below the transverse facial artery, and between the upper and lower buccal branches of the facial nerve. It pierces buccinator before running obliquely between buccinator and the oral mucosa to emerge on a small papilla opposite the second upper molar tooth.
FACIAL NERVE A comprehensive review of the course and branching pattern of the facial nerve has been made by Cawson and Gleeson. 1,2 This review outlines the variability of the course of the intraparotid facial nerve, and correctly emphasizes its clinical and surgical importance. In most cases, the facial nerve emerges from the stylomastoid foramen as a single trunk (Figure 144.3). In rare cases, the nerve may emerge as a double trunk. Katz and Catalan0 3 found three patients with such a variation in a study of 100 parotidectomies. Similar anomalies are well documented in the intratemporal course of the nerve, often associated with other congenital abnormalities. Unless recognized, this abnormality could potentially result in inadvertent nerve damage during parotid surgery, and its existence should be especially considered in patients with congenital abnormalities of the pinna or with congenital hearing loss. The single trunk divides within the substance of the parotid gland into upper zygomaticotemporal and lower cervicofacial divisions. Each division then further subdivides to form five branches: temporal, zygomatic, buccal, mandibular and cervical, supplying the muscles of facial expression. The branching pattern within the parotid gland is also variable, and a number of classifications have been described. Katz and Catalano 3 described five patterns of branching. 1. Type 1 (25 percent). There are no anastamotic links between the main branches, but in two subtypes there is splitting and reunion of the zygomatic and mandibular branches. 2. Type 2 (14 percent). The buccal branch subdivides and fuses with the zygomatic branch. 3. Type 3 (44 percent). There are major anastamotic links from the buccal branch to other major branches. 4. Type 4 (14 percent). There is complex branching and anastamotic links between the two divisions. 5. Type 5 (3 percent). The facial nerve trunk divides before leaving the stylomastoid foramen. An understanding of the variability of the course of the facial ne'rve and the common branching patterns IS essential for those undertaking parotid surgery. 4
Chapter 144 Salivary gland anatomy
Figure 144.3
I 1855
Intraparotid branching patterns of the facial nerve. (a) and (b) Type 1: in this type there is splitting and subsequent
reunion of the zygomatic or mandibular branches. (e) Type 2: in this type subdivisions of the buccal branch fuse with the zygomatic branch peripherally. (d), (e) and (f) Type 3: in this type there are major communications between the buccal branch and others. (9) and (h) Type 4: there are complex branching and anastomotic patterns between the major divisions in this type. (i) Type 5: in this type the facial nerve leave the skull as more than one trunk. B, Buccal branch; C: cervical branch; M, mandibular branch; T, temporal branch; Z, zygomatic branch.
Autonomic nerve supply Preganglionic secretomotor fibres are carried from the inferior salivary nucleus to th~ otic ganglion via the glossopharyngeal nerve, tympanic plexus and lesser
petrosal nerve. Post -ganglionic fibres are carried to the parotid gland via the auriculotemporal nerve. The sympathetic supply is from the superior salivary nucleus, carried by the sympathetic plexus surrounding the carotid vessels.
-----......---------------1856 I PART 15 THE UPPER DIGESTIVE TRACT
Vessels and nerves The external carotid artery gives off branches within the gland and the venous drainage is via the retromandibular vein into the external jugular vein and via the facial vein into the internal jugular vein. There are a few intraparotid lymph nodes within the substance of the gland, into and through which lymph drains to the superficial and deep cervical lymph nodes. 5 The efferent innervation is parasympathetic via the tympanic branch of the glossopharyngeal nerve, relaying in the otic ganglion and then reaching the gland via the auriculotemporal nerve. Sympathetic innervation is via the sympathetic fibres of the external carotid plexus. Secretomotor fibres are also derived from the chorda tympani.
THE SUBMANDIBULAR GLANDS The submandibular glands consist of a larger superficial part and a smaller deep part wrapped around the posterior border of mylohyoid. Each is irregular in shape and about the size of a walnut. The superficial part is covered by a fibrous capsule, derived from the deep cervical fascia. The capsule runs from the greater cornu of the hyoid bone, splits to enclose the gland before blending with the periostium of the mandible along the mylohyoid line medially, and the lower border of the body of the mandible laterally. The superficial part of the gland lies within the submandibular triangle. It extends from the anterior belly of the digastric anteriorly to the stylomandibular ligament posteriorly. The lower border of the gland overlies the digastric tendon. The medial surface lies on the surface of mylohyoid anteriorly, with the nerve to mylohyoid and submental vessels; and posteriorly is related to the stylohyoid ligament, styloglossus, the pharynx and the glossopharyngeal nerve. The intermediate part of the medial surface overlies hyoglossus, the lingual nerve with its submandibular ganglion, hypoglossal nerve, stylohyoid and posterior belly of the digastric. The lateral surface lies adjacent to the body of the mandible in the mandibular fossa and the origin of the medial pterygoid. The facial artery enters or deeply grooves the gland posteriorly, after emerging from deep to the superior margin of the posterior belly of the digastric. It initially lies deep to the gland before turning anterolaterally to emerge between the gland and the lower border of the mandible. The inferior surface is covered by skin, platysma and deep cervical fascia and is related to the cervical branch of the facial nerve. The deep part of the gland lies within the floor of the mouth, lying on the mylohyoid, lateral to the hyoglossus and styloglossus. Anteriorly, it lies adjacent to the
posterior end of the sublingual gland, and posteriorly wraps around the posterior free edge of mylohyoid to join the superficial lobe. It lies between the lingual nerve above and the hypoglossal nerve below.
THE SUBMANDIBULAR DUCT Like the parotid duct, the submandibular duct is approximately 5 cm long. It is formed by the coalescence of numerous ducts within the superficial part of the gland before emerging from the medial surface of this part of the gland, traversing the deep part before running anteriorly along the floor of the mouth between mylohyoid and hyoglossus. It emerges on the summit of the sublingual papilla adjacent to the lingual frenulum after passing between the sublingual gland and genioglossus. Whilst running forwards on hyoglossus, it lies between the hypoglossal and lingual nerves. The lingual nerve crosses the duct laterally at the anterior edge of hyoglossus before branches of the nerve emerge on the medial surface of the duct.
Vessels and nerves The blood supply is from the facial and lingual arteries and the venous drainage into the corresponding veins. The submandibular lymph nodes lie adjacent at the medial aspect and anterior end of the superficial part and sometimes within the gland itself. Lymphatics drain into the deep cervical group, particularly the juguloomohyoid nodes. The nerve supply is via the submandibular ganglion, which receives autonomic fibres from the chorda tympani, the lingual nerve and sympathetic trunk.
THE SUBLINGUAL GLANDS The sublingual glands are the smallest of the paired named salivary glands. Almond-shaped, they lie beneath the mucosa of the floor of the mouth, adjacent to the symphysis menti, in the sublingual fossa of the lingual surface of the mandible. Each weighs approximately 4 g. They lie on mylohyoid under the cover of the overlying oral mucosa. Posteriorly, they contact the deep part of the submandibular gland, medially, they are separated from the genioglossus by the lingual nerve and submandibular duct. Most of the small excretory ducts open directly on the summit of the sublingual fold, but some may open into the submandibular duct itself.
Vessels and nerves The blood supply is via the sublingual and submental vessels. Innervation is similar to the submandibular
Chapter 144 Salivary gland anatomy I 1857
gland, by the chorda tympani, lingual nerve and sympathetic plexus, with the parasympathetic relay in the submandibular ganglion.
REFERENCES
*
1.
Cawson R, Gleeson M. Anatomy and physiology of the salivary glands. In: Kerr AG (ed.). Scott-Brown's Otolaryngology, 6th edn. London: Butterworth Heinemann, 1997.
2.
.• Th.e intraparotidportionof the fa.cialn~rV"e ·l1a~ a variable branching pattern. . . ·.>The.anatomyofthe .• fascial . . capsules'()£the salivaryglandsinfluenc~s thespreadQf salivary gland. djsease.
Davis RA, Anson BJ, Budinger JM, Kurth RE. Surgical anatomy of the facial nerve and parotid gland based on a study of 350 cervicofacial halves. Surgery, Gynaecology and Obstetrics. 1956; 102: 385-412.
3.
Katz AD, Catalano P. The clinical significance of the various anastamotic branches of the facial nerve. Archives
c.
of Otolaryngology - Head and Neck Surgery. 1987; 113: 959-62. 4.
Ragbir M, Dunaway OJ, Chippindale AJ, Latimer J, Mohammed F, McLean NR. Prediction and position of the intraparotid portion of the facial nerve on MRI and CT. British Journal of Plastic Surgery. 2002; 55: 376-9.
5.
McKean ME, Lee K, McGregor IA. The distribution of lymph nodes in and around the parotid gland: an anatomical study. British Journal of Plastic Surgery. 1985; 38: 1-5.
-
145 Physiology of the salivary glands RODERICK CAWSONt AND MICHAEL GLEESON
Introduction
Salivary
Collection of
1858
Salivary assays Key poin ts
1861
References
1858
secretion
saliva
Sia lochemistry
in diagnos is
1867 1869 1869
1863
The data in this chapter are supported by a Medline search using the term saliva and focusing on chemistry, drug effects, immunology, physiology and secretion.
INTRODUCTION
both viruses and bacteria can be detected and monitored from salivary samples as can drug and hormone levels.
It would not be unreasonable to say that in the past most
There is little doubt that our knowledge of saliva, its
surgeons' interest in salivary glands has been limited to
function, production and modulation
will grow (Table
145.1).
The next generation of surgeons will require a
recurrent infections. Yet disturbances of salivary gland
much
more
function or inability to cope with normal salivary flow
physiology which this chapter attempts to address.
the treatment of primary tumours, duct obstruction and
thorough
knowledge
of
salivary
gland
can have a devastating effect on the quality of life, not only for our patients but that of their relatives. For example,
the
dry
mouth
of patients with
Sjogren's
SALIVARY SECRETION
syndrome can lead them to despair, while drooling secondary to cerebral palsy may make them a social outcast and precipitate placement in institutional care. Over the past decade there has been an explosion of
The amount of saliva secreted and, to a large extent, its composition, is normally controlled by the autonomic nervous system. Other factors can also interfere with
the biotechnology of diagnostic tests. Clinical practice is
glandular
in the process of change. A wide variety of tests, once
autonomic responses, dehydration and disease or destruc
function,
for example,
drugs which affect
almost exclusively confined to the examination of blood
tion of salivary gland parenchyma.
and urine, can now be undertaken as precisely and accurately on other body fluids, such as sweat, tears and
saliva. While the collection of saliva may lack the drama
Autonomic control of salivary secretion
of venepuncture, the sincerity of sweat or the emotional appeal of tears, it is, at the least, readily accessible. 1
Samples can be reliably collected by the patient at home or in the workplace and, unlike blood, samples do not clot or carry the risk of needle-stick injury. Antibodies to
Extensive animal experimentation has been undertaken to establish the effects of autonomic stimulation on salivary flow.2 Normal reflex secretion of saliva depends on centrally coordinated parasympathetic and sympathetic
-
�
,
Chapte r 145 Physiology of the salivary glands I
Table 145.1
1859
The major functions of saliva.
Function Protective functions Lu b rication
M ucins, proline-rich g l ycoproteins, water
Antimicrobial
Amylase, complement, defensins, lysozyme, lactoferrin, lactoperoxidase, mucins, cystatins, histatins, pro l ine-rich glycoproteins, secretory leukocyte protease inhibitor, statherin, th rombospondin
Growth factors
EGF, TGF -ct, TGF-�, F GF, I GF-l and I GF - 2 , N GF
M ucosal integrity
M u cins, el ect rolytes and water
Lavage/cleansing
Water
Buffering
Bicarbonate, phosphate ions, proteins
Reminera I ization
Calcium, phosphate, statherin, anionic proline-rich proteins
Food
and
speech-related functions
Food preparation
Water, mucins
Digestion
Amyl ase, lipase, ribonuclease, proteases, water mucins
Taste
Water, g u stin
Speech
Water, mucins
EGF, epidermal growth factor; FGF, fibroblast growth factor; IGFl and IGF2, insulin-like growth factor; NGF, nerve growth factor; TGF-Cl, transforming growth factor-alpha; TGF-�, transforming growth factor-beta.
activity. Parasympathetic activity evokes most of the fluid
secreted by causing variable degrees of exocytosis from the
secretory cells and vasodilatation within the gland. It also induces contraction of the myoepithelial cells. Sympa
thetic stimulation of the salivary glands tends to be more
binding and probably conveys the functional specificity to
a G protein. Binding of a neurotransmitter to a receptor greatly strengthens the ability of a receptor to associate
with a G protein. The association with a G protein
stimulates replacement of GDP by GTP at the nucleotide
intermittent and is also directed at the cells that receive
binding site and promotes dissociation of the hetero
composition of saliva by increasing exocytosis from
subunit
parasympathetic impulses. certain cells.
It tends to modulate the
Some sympathetic
fibres exercise tonic
effects on blood vessels; these fibres are likely to be under
separate central control and not involved directly in the
reflex secretory pathway.
trimer into a free can
cr
then
subunit and a �'Y complex. The
activate
the
appropriate
cr
receptor
molecule. Activation continues until the GTP is broken down
into
GDP
activity in the
cr
by endogenous
enzymic
(GTPase)
subunit. The GDP bound to the
cr
subunit then unites with the �'Y complex to regenerate the
heterotrimeric molecule. There is also some evidence to suggest that the �'Y complex, or even the � subunit alone,
Mechanisms of salivary secretion
may be able to activate some receptor molecules directly.
The best recognized signal transduction processes in The mechanisms of saliva secretion have been reviewed in 3 detail by Baum, who emphasized that much of the
information presented below comes from the study of rat salivary glands. Little is known of the mechanisms of
salivary glands are first, generation of cAMP as a result of
� adrenergic receptor stimulation and second, formation
of 1,4,5-inositol triphosphate (IP3 ) after acetylcholine receptor stimulation. The latter leads to calcium ion
human salivary secretion, but such data as exist generally
mobilization and, as a consequence, fluid secretion.
described,
intermediary
.conform to the broad principles discussed here. As Baum saliva
is
produced
only
in
response
to
neurotransmitter stimulation. Neurotransmitters prob
ably bind to specific receptors in the basolateral region of
the acini.
Noradrenaline binds
to both
cr-
and
�
The specific mechanism by which cAMP acts as an
Typically,
in
cAMP
protein elicits
exocytosis
a
remains
response by
unclear.
activation
of
cAMP-dependent protein kinase and protein phosphor
ylation.
In rat salivary glands,
�-adrenergic receptor
adrenergic receptors, while acetylcholine binds to choli
stimulation leads to a rise in cAMP levels, activation of
nucleotide-binding regulatory protein (G protein) for
several cellular proteins and thus, amylase or glycoprotein
nergic receptors. These receptors depend on guanine transduction of the neurotransmitter stimuli. The G
the A kinase, phosphorylation or dephosphorylation of secretion
by
the
parotid
leads to protein secretion. Kinetic analyses suggest that
cr
of
cr,
�
and
'Y
subunit is the site of guanine nucleotide
of
rat
glands,
subunits. The
molecules consisting
treatment
submandibular
respectively.
heterotrimeric
Indeed,
or
proteins that carry the stimuli into the acinar cells are
parotid
and
submandibular gland cells with cAMP analogues also
1860 I
PART 1 5 TH E U P P ER DIGESTIVE TRACT
the 24-26 kDa species protein is the most probable
contains. The acinar cells are water permeable and derive
protein exocytosis is unknown. Moreover, the role of a
carried by the duct system which is impermeable to water.
protein secretion has become somewhat controversial. ++ It is well established that Ca plays a central role in
electrolytes. Most of the sodium and chloride ions are
candidate for phosphorylation although its function in
kinase-dependent phosphorylation in rat parotid gland
fluid secretion by acinar cells in response to acetylcholine
fluid from the surrounding blood vessels. The fluid is During passage through the ducts, there is exchange of
removed, but some potassium and bicarbonate ions as well as a little protein, are added.
receptor stimulation. Activation of this receptor leads to
fluid-related signal transduction via coupling to a G protein often designated G • The latter is probably a p member of the Gq/ll family which is known to couple to phospholipase C. Activation of phospholipase C results in hydrolysis of a minor membrane phospholipid, phospha
tidylinositol 4,5-bisphosphate, and formation of second
Mechanisms of primary fluid secretion in salivary acini As in all secretory epithelia, fluid transport in salivary
gland cells is
thought to be
driven osmotically by
messengers
transepithelial salt gradients. Turner4 has explained that
but diacylglycerol can promote activation of protein kinase
three mechanisms for primary salivary fluid secretion.
IP3 and diacylglycerol. IP3 is the main ++ mediator of Ca mobilization and thus of fluid secretion, C and lead to stimulation of a minor exocytic pathway.
IP3 binds to a receptor protein located on an ++ intracellular Ca storage pool that is probably related
to, or part of, the endoplasmic reticulum. The IP3 ++ receptor also functions as a Ca release channel and ++ allows stored Ca to move down a concentration ++ gradient into the cytoplasm. These Ca levels quicldy rise approximately ten-fold as a consequence of acet
ylcholine receptor stimulation. This reaction triggers a ++ cascade of events which include sustained Ca entry and
activation of specific ion transport pathways. Generation
of fluid in the acinar lumen is the final result, by mechanisms discussed in detail by Turner.4 ++ ++ Extracellular Ca and entry of Ca sustain high
levels of salivary fluid secretion over long periods. However, ++ mechanisms of Ca entry into acinar cells which are
studies on rat and rabbit salivary glands have suggested
Unexpectedly, these mechanisms do not appear to be
alternative explanations for salivary fluid secretion, but
appear to operate concurrently within the same gland or
possibly within the same acinar cells.
The first mechanism, of which the other two can be
regarded as variations, is that fluid secretion depends on the
combined
systems, namely: 1. an Na
+
-K
+
action
of
four
membrane
transport
-2CI- cotransporter that is located in
the basolateral membrane of the acinar cells; ++ + 2. a basolateral Ca -activated K channel;
3. an apical conductive pathway for CI- which is ++ presumably a Ca -activated CI - channel; + + 4. the Na IK ATPase.
+ In the resting state, both K and CI- are concentrated in
nonexcitable and not voltage activated, are poorly under ++ stood. Possible mechanisms for Ca entry into acinar cells ++ include a direct receptor-gated Ca channel, a G protein ++ activated Ca channel and a second messenger-activated ++ Ca channel. However, there is little evidence for the
the acinar cell above electrochemical equilibrium, with + + + being concentrated by Na IK ATPase and CI - by + + Na -K -2CI- cotransporter. As discussed under Me
activated by the synergistic action of IP3 and its metabolite 1, 3, 4,5-inositol tetrakisphosphate (IP4)'
and CI- conductance allow KCI to flow out of the. cell
involvement of the first two of these mechanisms and only ++ a few reports have suggested that Ca entry may be
Currently,
the
most favoured explanation of the ++ mechanism of Ca entry is one termed 'capacitative ++ ++ Ca entry'. This suggests that depletion of the Ca
storage pool provides the driving force for sustained ++ Ca entry. Support for this theory comes from studies ++ that have shown that graded depletion of the Ca store ++ have led to similarly graded Ca entry.
Use of nonreceptor activation by, for example ++ thapsigargin, to deplete the Ca store also leads to ++ entry. Although the exact mechanism by which Ca ++ ++ depIetl· On 0 f Ca stores causes Ca entry IS . uncertam, .
it is clear that it can be modulated by extracellular pH and ++ . cytopIasml. C Ca Acinar cells are responsible for production of the fluid
component of saliva and most of the proteins that it
K
chanisms of salivary secretion, secretagogue stimulation ++ leads to a rise in intracellular Ca concentration and, in ++ + turn, opening of the basolateral Ca -activated K + channel and the apical CI- channel. Increases in K and this results in accumulation of CI- ions and their
associated negative electrical charge in the acinar lumen. + As a consequence, electrical attraction causes Na to leak
from the interstitium through the tight junctions to
follow Cl. The resulting osmotic gradient for NaCI causes
transepithelial movement of water from the interstitium to the lumen. Continued influence of an agonist results in
a transepithelial chloride flux and concomitant fluid + + secretion. This is sustained by CI- entry via the Na -K 2CI- cotransporter and exit via the apical CI - channel.
Removal
of
intracellular
the
stimulus
is
followed
by
a
fall
in
calcium concentration to resting levels, + closure of the K and CI- channels and return of the
cell to its resting state.
The second mechanism is similar except that the + + basolateral Na -K -2CI- cotransporter is replaced by a
Chapter 145 Physiology of the salivary glands.
CI- IHC03 exchanger acting in parallel with an Na++ I H+ exchanger. A faU in intraceUular chloride concentra tion as a result of secretagogue KCI loss, thus leads to entry of more CI- in exchange for HC03 -. Acidification
1861
Depression and anxiety states are often associated with
a
dry mouth.
Busfield and Wechsler6 measured the rate of
salivary secretion in 42 untreated depressed patients and
found it to be decreased in comparison with nonde
of the cytoplasm that results from this bicarbonate loss is
pressed
buffered by the Na
correlation was found between the degree of xerostomia
++ IH+
exchanger, which uses the
hospital
patients
and
healthy
controls.
No
extracellular-to-intracellular sodium gradient generated
and the assessed severity of depression, nor was there any
by
difference found in secretion rates in
+ Na+ IK
ATPase, to drive protons out of the cell.
Unlike the first two mechanisms in which chloride is
Busfield
et
al?
between the
a
different
later study by categories
of
the secreted ion, the third involves acinar bicarbonate
depression or between those who complained of dry
secretion. In this last mechanism, CO2 enters the acinar
mouth and those who do not. The fact that decreased
cell across the basolateral membrane and is converted to
salivary flow is associated with sympathetic overactivity,
HC03 - plus a proton, by intracell ular carbonic anhy drase. HC03 - is lost across the apical membrane via an
as in anxiety states, or caused by sympathomimetic drugs
anion channel which is possibly the same as that involved
that the sympathetic supply to the salivary glands is
in chloride secretion. The proton is expelled by the
inhibitory in humans. However, sympathetic inhibitory
basolateral
fibres have not been found and, until they are, the
+ Na ++ IH
exchanger.
and can be relieved by �-blockers would seem to suggest
generally
accepted
hypothesis for the
mechanism
of
anxiety-induced xerostomia is that of central inhibition from higher centres which act on the salivary nuclei in the
Factors affecting salivary flow
brainstem and suppress reflex activity.
Even in the absence of parenchymal salivary gland disease, function can be abnonnal and, when diminished, result in
xerostomia. Although xerostomia is usually a complaint of late middle-aged women, it should not be assumed that ageing itself causes deterioration of salivary gland function. Several studies have been carried out and have yielded somewhat conflicting results. Ship et aI.s found that nom1al
postmenopausal women, the main group thought to be at
risk, had no deterioration of salivary gland function. In clinical practice, drugs are the most common cause of decreased salivary gland function. Tricyclic antidepres sants and phenothiazine neuroleptics are among the most
Drying of the mouth is virtually inevitable in dehydra tion and, as such, is a consequence of haemorrhage, diarrhoea, chronic vomiting, polyuria secondary to diabetes mellitus, restricted fluid intake or overdose of diuretics. A detailed discussion of the salivary gland diseases that cause xerostomia is outside the scope of this chapter. Nevertheless, it is
worth noting some of the more
common conditions, if only for further reference, namely: autoimmune sialadenitis, human immunodeficiency virus
(HIV)
infection,
radiation
damage,
graft-versus-host
disease, sarcoidosis, iron overload, amyloidosis and type
V
hyperlipoproteinaemia.
troublesome as they have particularly strong antimus carinic effects and are generally used over long periods. Formerly, ganglion-blocking drugs had the same effect,
COLLECTION OF SALIVA
but are now generally regarded as obsolete for the routine management of hypertension. A list of commonly used drugs that affect salivary flow is shown in
Table 145.2
Table
145.2.
Saliva may need to be collected to determine the flow rate, to confirm or discard a clinical complaint of xerostomia
Drugs liable ,to 53use xerost?mia.
Drugs with antimu5carini,c activi,ty Atropine and analogues (hyoscine, ipratropium, etc . )
Tricyclic antidepressives
'Cold cures' and decongestants containing ephedrine or phenylpropylamine
Monoamine oxidase inhibitors
B ronchod ilators (isoprenaline, orci prenaline, etc.)
Phenothiazines and related neuroleptics
Appetite suppressants, particularly amphetamines
Orphenadrine, benzhexol and related anti-Parkinsonian agents Antihistamines Ganglion blockers and clonidine Antiemetics (antihistamines, hyoscine and phenothiazin es)
and diethylpropion
1862 I
PART 15 TH E LI P P E R DIGESTIVE TRACT
or to provide a sample for assays of any type. Many
methods have been devised and may be summarized as follows: •
unstimulated flow of whole (mixed) saliva;
•
stimulated flow of whole saliva;
•
SPITIING AND DRAINAGE METHODS
The patient is put into a comfortable sitting position with the head inclined forward and encouraged to spit at one
minute intervals or to allow saliva to drain out of the mouth into a funnel draining into a sterile collecting vessel.
stimulated or unstimulated flow from individual glands.
SUCTION
This method requires the equipment associated with a
dental chair. The patient is put into a similar position as
Salivary stimuli
before to allow saliva to collect into the anterior floor of Over the years, a variety of stimulants to salivary secretion
have been used.
These are either systemic or local
sialagogues. The main systemic sialagogue that has been
the mouth. A saliva ejector is placed behind the lower
incisor teeth and the secretion is trapped in a bottle
intervening between the ejector and the drainage system.
used is the parasympathomimetic, pilocarpine. Although
effective, pilocarpine does not precisely reproduce the
balance of
sympathetic and parasympathetic activity
ABSORBENT DEVICES
responsible for normal secretion. One consequence is
Preweighed cotton wool rolls are placed under the tongue
ents, particularly sodium and potassium. Pilocarpine can also cause systemic cholinergic effects such as colic,
This method allows quantitation only. More recently, ® proprietary devices such as OraSure have been intro
troublesome.
analysis. Its use has been reported by Thieme et
that it can alter the concentrations of normal constitu
diarrhoea, bradycardia and sweating,
which may be
Local sialagogues are convenient and generally more
satisfactory. A good example is 5 percent citric acid
for a two-minute period then taken out and reweighed.
duced to simplify saliva collection and preserve it for
a1.9 who
collected saliva for determination of measles, mumps and
rubella immunization status. OraSure is a cotton-fibre
solution, which is a potent sialagogue and does not
pad which can absorb 1 mL of oral fluid. In manufacture,
Five drops of this solution can be dropped from a pipette
mounted on a plastic handle. In clinical practice, it is
interfere with the composition of the final specimen.
or disposable syringe onto the dorsum of the tongue.
This may be used as a preliminary measure before collecting unstimulated saliva.
The purpose of
this
it is saturated with hypertonic saline solution, dried and
placed between the gingiva and buccal mucosa for two
minutes, then withdrawn and placed in an antiseptic
transport medium. In the laboratory, the saliva specimen
manoeuvre is to flush out stagnant secretions that
is recovered by centrifugation.
tongue and saliva is collected for 15 minutes to eliminate
system for gathering oral fluid, it must be appreciated that
confuse the analysis. Thus, citric acid is applied to the
rest transients.
Stimulated or unstimulated saliva can then be collected
While there appear to be advantages to the OraSure
by virtue of the filtering effect of the cotton-fibre pad, it does not collect whole saliva. Cordeiro et
al.10 found that
for periods of 15-30 minutes as necessary. The results
the levels of IgG in OraSure oral fluid were three to four
necessarily comparable because individuals with a vigor
two to four times higher. They suggested that the cotton
obtained
by
different
sialometric
methods
are
not
ous secretory response to one stimulus do not necessarily have a similar response to another.
times higher than those of saliva and amylase levels were
fibre pad might promote passage of crevicular gingival exudate and stimulate secretion of amylase as a result of the pad's buffer solution. However, North et
Collection of mixed whole saliva There is a variety of methods for collecting saliva from individual glands or collecting mixed whole saliva. Many
al.ll found
that the OraSure system provided a reliable index of tobacco usage by means of continuous salivary assay.
Collection of parotid gland saliva
of these methods require specially made equipment and 8 are mainly suitable for research purposes. Navesh has
Pure parotid saliva can be collected by cannulating the
follows:
cup.
reviewed the methods for collecting saliva, which are as
parotid duct with a polythene catheter or using a suction Catheterization of the duct allows collection of
uncontaminated saliva, but is uncomfortable for the
•
spitting;
•
drainage;
the most widely used devices are the Carlson-Crittenden
cotton wool rolls.
parotid papilla. Each cup consists of a central chamber
• •
suction;
patient and the tube has to be held in place. For suction,
or Lashley cups, the centre of which are placed over the
Chapter 145 Physiology of the salivary glands I
into which the saliva flows and an outer chamber to which suction is applied to cause the cup to adhere to the buccal mucosa
(Figure 145.1).
all salivary glands, including the minor
glands, make a greater contribution to the amount of saliva
produced under normal conditions. Stimulated parotid flow is unsatisfactory because of difficulties that some
patients have with the collection devices and because the
Collection of submandibular gland saliva
variety of stimulants used have caused confusion as to what
Particularly in the past, submandibular gland saliva was collected by catheterizing the submandibular duct after dilatation.
the total activity of
1863
This technique is neither very simple nor
comfortable for the patient. Segregator appliances must be purpose-made to fit the patient's mouth and function in the same way as the Carlson-Crittenden cup. The device, which fits the anterior floor of the mouth, has a central collecting chamber, isolated by a surrounding ridge from the outer suction chambers.
is meant by abnormal flow rates. Speight et
al.13 found that
a whole unstimulated salivary flow rate of 0.1 mLlmin or
less was 81 percent predictive of Sjogren's syndrome if other causes of xerostomia could be excluded. Saliva was collected
by encouraging the patients to spit gently or drool into a beaker for 15 minutes. Although controversy persists about
methods of saliva collection and whether or not sialagogues should be used, there is a growing body of opinion that
collection of unstimulated mixed saliva best reflects the normal resting state. The European Community Study Group on Diagnostic Criteria for Sjogren's Syndrome14 have
Advantages and disadvantages of the different methods The choice of method depends on the type of investiga tion being carried out. If, for example, the aim is to investigate viral shedding from the parotid gland then catheterization of the duct has to be carried out or a Carlson-Crittenden cup used. Mandel12 listed the variations in concentrations of sodium, potassium, calcium, magnesium, bicarbonate and phosphate in the secretions of individual glands and whole saliva. However, overall, his findings suggest that collection of whole saliva is satisfactory for such chemical measurements. For straightforward measurement of salivary flow rate for confirmation of the diagnosis of Sjogren's syndrome, for example, the simple spitting method for unstimulated saliva
also concluded that collection of whole unstimulated saliva is the best method for confirming the degree of xerostomia.
Radioisotope salivary function tests Various isotopes have been used to visualize a number of organs and their ability to concentrate a particular isotope can be used to indicate function. 99mTc pertechnicate has been used for the study of salivary gland function and, with scintigraphy, an objective measure of its uptake, concentration and excretion can be made
(Figure 145.2).
This method of investigation has the advantage that both the parotids and submandibular glands can be studied at the same time. Although available for some time, this method of investigation has met with little clinical enthusiasm.
over a period of 10 or 15 minutes, requires minimal equip
ment and is satisfactory. In the past it was thought that since the parotid glands were predominantly affected by this disease, it was necessary to collect parotid saliva. However,
SIALOCHEMISTRY Normal The composition of saliva changes in disease states, particularly those causing xerostomia, and these changes have been reviewed by Mandel.l It must be emphasized that most studies on the composition of saliva have been based on relatively few subjects and may therefore be biased. Differences in laboratory methods may also result in discrepancies in the results which are not in fact real. Other complications are the presence of enzymes which are probably of bacterial origin. The composition of saliva in health provides a baseline for variations resulting from disease or drug administration. Unfortunately, even in healthy people, many variables, such
Figure 145.1
A Lashly collecting cup. The cup consists of
a
central chamber into which the saliva flows and an outer
as those listed in
Ta b le s 145.2 and 145.3, can affect the
composition of saliva. The major constituents of saliva are
Table 145.4,
chamber to which suction is applied so that it adheres to the
shown in
buccal mucosa.
made, these figures should be accepted with caution.
but in view of the comments already
1864
I PART' 5 THE UPPER DIGESTIVE TRACT
=
80 Lemon given here
J,
60
u c 0 0 C) (/)
I J
(j)
C
\ ......
.---'
\ ...
I
Q. (/)
Left parotid .\
40
::J
8 Right submandibular
20
o�------�--� 3.75
(b) Figure'45.2
7.5
11.3
15.0
Minutes
(a) 99rrrrc pertechnicate s tudy undertaken in a pat ient with early Sjogren's syndrome. There is poor tracer accumulat ion
in the right parot i d gland (arrowed) when compared to the left parotid (b) Following the administration of lemon drops. there is a brisk .
discharge of ac tivity from the left parotid gland and the right submandibular gland, but less response from the left submandibular gland.
Diseased states
of the most valuable diagnostic tests. Neither involves either exposure to x-rays or scintigraphy. A low resting
Changes in the concentration of inorganic ions have been 12 documented in the conditions listed in Table 145.5. Changes in the concentration of the organic components
have been found in the conditions listed in Three
diseases that
have
been
studied
Table in
145.6.
terms
of
sialochemistry in particular detail are Sjogren's syndrome, cystic fibrosis and coeliac disease.
SJOGREN'S SYNDROME
salivary flow rate and stimulated flow rate are typical of Sjogren's syndrome, cut off values of 0. 1 mLimin for resting whole
saliva and 0.5 mLimin for stimu
lated saliva have been considered diagnostic of gland hypofunction.
IS
Mandell has noted that salivary function changes, in addition to a lowered secretion rate include: •
raised sodium and chloride but lowered phosphate;
•
raised titres of immunoglobulin (Ig)A, IgG,
firming the diagnosis of Sjogren's syndrome because of
•
raised
the great variability in the abnormalities that may be
•
raised kallikrein concentrations;
detected. The problem is well illustrated by the neces
•
a 20-fold elevation in the concentration of
•
increased concentrations of inflammatory mediators,
lactoferrin and albumin;
Considerable difficulties are sometimes found in con
group concluded in its report that unstimulated whole saliva flow rate and minor salivary gland biopsy are two
microglobulin;
phospholipids;
sity to institute the European Community Study Group on Diagnostic Criteria for Sjogren's Syndrome.14 The
P2
e.g. eic6sanoids, PGE2, thromboxane B2 and interleukin.
Chapter 145 Physiology of the salivary glands I
Table 145.3
1865
Variables affecting the composition of saliva.
Flow rate Saliva specifically collected from the major glands differs in composition from whole saliva which includes that
Source
secreted by the minor glands Diurnal variation Duration and type of stimulus Rest transients
The concentration of a molecule. such as potassium. may vary according to whether the saliva sample is taken
Age and gender differences
Findings on differences in salivary flow and hence salivary composition, according to the age or gender of the
shortly after stimulation or after the Aow has been allowed to continue for several minutes subjects have been conflicting. Findings that, for example, salivary flow rates are lower in older women than men could conceivably be biased by the presence of unsuspected Sjogren's disease among women Plasma levels
The concentration of many molecules in saliva is related to and varies with their plasma levels
Diet
Findings suggesting that a predominantly carbohydrate diet, for example, leads to higher concentrations of salivary amylase or that high protein diets lead to higher concentrations of salivary amylase have not been widely confirmed or are conflicting
Drugs
Any drug that affects salivary flow rates can affect the concentration of salivary constituents that are Aow
Hormonal effects
Mineralocorticosteroids affect both plasma and salivary concentrations of molecules such as sodium and
dependent. Important drugs that affect salivary now rates are shown in Table 145.2 bicarbonate. It has also been suggested that the concentration of some salivary constituents such as calcium and sodium may fall and potassium levels rise at the time of ovulation
Table 145.4
Composition o � mixed saliva.
.Subs'��nc� '.
� � -: -�-.-'
.
.
�
:"-t::
'_Unstimulat�d ; �
. �-.
Stimulated
r
. � � . ....
.of:..
Mean ..±.s;d.:
Protein (giL)
Range 1.4-6.4
'. Mean.±. 2.8
1.8-4.2
Lysozyme (mg/Ll
108.9 ± 29.1
3.7-625
Carbonic anhydrase (KILl
2100
IgA (mg/L)
194.0
IgG (mg/Ll
14.4
IgM (mg/Ll
2.1
Amylase (giLl
0.38 ±0.08
Histamine (mg/Ll
0.15
Glucose (mmol/LJ
0.55±0.048
Urea (mmol/Ll
3.22 ± 2.5
2.33-12.5
Creatinine (mg/Lj
0.09
0.04-0.18
Cholesterol (mg/L)
0.2
0.07-1.3
Sodium (mmol/Ll
6.2 ± 0.46
26.4± 11.8
Potassium (mmol/Ll
21.6± 1.2
19.7 ± 3.9
0.11-0.18 0.056
0.02-0.17
2.17
0.1-4.8
Calcium (mmoI/L)
1.56± 0.06.
1.48 ± 0.04
Magnesium (mmoI/L)
0.21 ±0.01
0.15±0.04
Phosphate (mmol/L)
6.2
Chloride (mmol/L)
17.4± 1.4
Iodide (IlmoI/L)
0.8
0-3
Fluoride (Ilmol/Ll
15±0.68
0.5-3
29.0 ±8.8 1-3 0.56± 0.25
0.25-1.2
Parotid gland lysozyme was also found to be raised in
CYSTIC FIBROSIS
co'uld indicate whether labial gland biopsy or other tests
clinical effects on salivary gland function are
primary but not in secondary Sj ogren's syndrome. Such changes could be useful for screening.16, 17 These indices were
indicated but) perhaps more importantly) be used
for monitoring disease progress.
is affected the minimal, b ut there are signifi c an t changes in salivary composition. In particular, there are dramatic elevations in sa l ivar y Although all exocrine gland function
,
1866
•
PART 15 THE UPPER DIGESTIVE TRACT
Table 145.5
Changes in the concentration of ��organic ions, ,
Changes in the concentration of inorganic ions.
Condition
Raised Na +, K + , Ca++ and p+ levels Raised Na + , Ca++ , Mg + + and CI- levels Raised Na + , CI- and P + in parotid gland saliva Raised Na + , Ca ++ and P + levels. Mandel12 suggested that the combined Ca++ and P + concentrations formed a useful diagnostic index Depressed Na + but raised K + levels. Mandel12 suggested that the product Na + /K + could form a useful diagnostic index Depressed Na + levels Raised K + levels Raised Ca++ levels Raised Ca++ levels Depressed HC03 - levels Possibly raised Na + levels Raised Na + and K + levels, Mandel12 suggested that the product, Na + x K + , could form a useful diagnostic index
Sialadenitis Radiation damage Sjogren's syndrome Cystic fibrosis Aldosteronism Hypertension Alcoholic cirrhosis Hyperparathyroidism Diabetes mellitus Chro nie pancreatitis Psychiatric illness Digitalis intoxication
Table 145.6
Conditions affecting the composition of saliva. -
Conditi n o
�
�,,; ;:.
Sjogren's syndrome Cystic fibrosis Cirrhosis Hyperparathyroidism Diabetes mellitus Sarcoidosis
· >�,o.:"
��ct on composition of
.. �'
S��-li��!:�:"
-'"',
; .�;,
Raised total protein and �2 microglobulin levels in parotid gland saliva Raised total proteins, amylase, lysozyme in submandibular gland saliva and glycoproteins in parotid gland saliva Raised total protein and amylase in parotid gland saliva Raised total protein Raised total protein, IgA, IgG and IgM and raised glucose levels Depressed amylase and lysozyme levels
protein and cakium concentrations. The complexmg of
Antibacterial substances in saliva
these substances leads to obvious turbidity of t he saliva. This is such
as
to obstruct the excretory ducts of the
minor salivary glands and to cause the build up of calculus around teeth. Their greatly depressed secretion rate can be measured in the accessible labial glands with a
capillary tube.
Unfortunately, saliva cannot be used to detect or diagnose cystic fibrosis in affected patients or carriers of the disease. Screening for carriers can only be detected by
DNA analysis and even this is hampered by the number of mutations in the cystic fibrosis gene.
The
function
of
substances
such
as
lysozyme
and
lactoferrin secreted by the salivary epithelium and which have antibacterial act iv it y in vitro is unclear. Molecules such
as
these can be shown to have antibacterial activity
in vitro. Other factors which might affect bacterial activit y in
t he oral cavity are the pH and buffering capacity of
saliva and its content of immunoglobulins. Despite the presence of these substances, t he oral cavity supports a flourishing population of microbes including a
great variety of pathogens. Dental caries is usually also active on a high sugar diet and periodontal disease is likely to progress unless a high standard of oral hygiene is
COELIAC DISEASE
m ain t ai ne d. Despite great efforts to show protection
This condition'
is characterized by the malabsorption of gluten in the small intestine. Antibodies (IgA-AGA) to
against these diseases by saliva, the findings have been
gliadin) a major component of gluten, are produced and
have harmful effects by promoting adhesion of bacteria to
detectable in both serum and saliva. Measurement of this
the
antibody in saliva has been used as a screening test for
substances are difficult to substantiate in
coeliac disease but lacks the sensitivity of its serological counterpart.
18
Salivary tests are probably better employed
to monitor compliance with a gluten-free diet.19,
20
unconvincing. Moreover) salivary mucins for example, may teeth.
That
aside)
putative
effects
of
protective
h umans because
of the difficulty of performing the critical experiments. It is clear that the oral cavity has a high level of local
immunity.
The
large
bony
wounds
resulting
from
Chapter 145 Ph ysiology of the salivary g l ands I
extraction of teeth normally heal rapidly despite con
tamination
by
the
vast
and
pathogenic
flora
that
1867
3 4 discussed by Ferguson.2 Read2 has discussed the current status of salivary oestrogen and androgen measurement.
proliferates in periodontal pockets, but this fortunate
An
outcome is likely to result from local tissue immunity
hormone measurements is cast by the problems of salivary
Another factor which may affect the nature of the
salivary concentration of this hormone is only about 0.1
rather than from salivary components.
bacterial flora of the mouth is bacterial competition for
nutrients in their individual, ecological niches. However, the bacterial flora of the mouth is undoubtedly affected by
informative
light
on
the
limitations
dehydroepiandrosterone sulphate assay
of
salivary
(DHA-S).
The
percent of that in plasma and is a poor predictor of plasma levels in an individual or a particular plasma sample. The
inconsistencies arise from the fact that the concentration
low salivary flow rates which, in particular, promote
in parotid fluid is particularly low. Most salivary DHA-S
species. Nevertheless, xerostomia does not appear to
The fall in DHA-S concentrations with high salivary flow
The only aspect of saliva production that can be
concentrations of DHA-S in saliva depend largely on the
cariogenic
activity
and the
proliferation
of
Candida
promote periodontal disease.
probably therefore comes from blood in gingival exudate.
rates helps to confirm this possibility. If this is the case,
reliably related to protection against infection is that of
degree of contamination and, as has been shown, are
Candida albicans
and the method of saliva collection. Read concluded that
the overall flow rate. In conditions of xerostomia, the oral bacterial flora changes and in particular
and staphylococci are likely to flourish. Dental caries
activity and mucosal infections are thus promoted. From
the clinical viewpoint, therefore, the main contribution of
affected by the oral conditions in the person being tested
salivary assays for testosterone in men, androstenedione
and oestriol in particular, were valuable, but considered
that the value of salivary testosterone and oestradiol in
saliva to defence against infection appears to be the largely
women remained unproven.
the gastric acid.
salivary progesterone assay and their interpretation, and
mechanical effect of its flow washing down microbes into
reviewed the utility of these assays for clinical purposes,
particularly for the diagnosis and treatment of infertility.
Salivary progesterone levels are valid indicators of plasma
SALIVARY ASSAYS IN DIAGNOSIS Saliva is undoubtedly a valid medium for many diagnostic assays. Collection of saliva is noninvasive, painless and
obviates the risk of needle-stick injuries. Nevertheless,
most
Ellison25 has considered certain technical aspects of
clinicians are
unused
to
practised in collecting blood,
collecting
saliva
but
which can usually be
achieved more quickly. Moreover, most laboratories use
equipment for handling blood and are unused to dealing with saliva with its mucins and other constituents or
levels
and
Ellison
concluded
that
their
assay
was
particularly valuable because of the ease of obtaining
serial samples from the same individual. On a shorter
timescale, salivary monitoring could provide samples at short intervals for characterization of pulsatile progester
one patterns without the inconvenience and expense of
hospitalization. The ability to adapt salivary progesterone
monitoring under field conditions has also made possible
basic research on a wide scale into human reproductive
contaminants which may affect the assays. With regard to
biology. Ellison's concerns were the need for standardized
mention the possibility of using saliva.
analysis, recognized reference ranges and statistics on
drug
assays,
few
current
pharmacology
texts
even
laboratory procedures, methods of data reduction and
diagnostic efficiency. Furthermore, the low absolute levels
of steroids in saliva placed a premium on an unusually
Malignancy screening
high level, of quality control in the laboratory.
In recent years peptides and proteins associated with
social behaviour. Assay of testosterone in saliva provides a
Testosterone is a hormone that may, in addition, affect
malignancy have been detected in saliva. p53, a tumour
valuable method for field studies. Dabbs26 has summar
defensin-1 can be detected in the saliva of patients with oral
testosterone levels both between and within individuals.
suppressor protein, and increased levels of the peptide squamous cell carcinoma.21 Similarly, raised levels of the tumour marker c-erbB-2 and cancer antigen 15-3 (CA153) found in the saliva of women with breast carcinoma
offer the potential of relatively simple screening tests.22
ized the preliminary findings on differences in salivary Studies on individual differences are being carried out in
relation to violent and antisocial behaviour, occupational
achievement and everyday behaviour. Studies on chan
ging testosterone levels have been undertaken on winning sports contests,
Hormone monitoring Lipid-soluble, unconjugated steroids pass readily into
saliva and their concentrations are proportional to the concentrations of free, unbound steroids in plasma as
winning
nonathletic
events,
winning
political contests, 'winning' games of sex and vicarious
winning (sports spectators). Broadly speaking, it appeared
that salivary testosterone levels fell in losers and were unchanged or rose in winners according to the impor
tance of the victory. While animal studies confirmed
elevations of testosterone with real or anticipated sexual
1 868
• PART 1 5 TH E U PPER D I G ESTIVE TRACT
activity, there were considerable difficulties in obtaining
samples at appropriate times in humans. However, it
appeared that testosterone levels were higher on evenings when there was sexual activity, particularly in women, and low in its absence. Studies o n salivary testosterone levels und er conditions of abuse, depression and suicide are also in pro gress.
D rug m o n ito ri n g Jusko and Milsap27 have discussed the p harmacokinetics of drug distribution in saliva. They showed that the primary properties of a drug which determined its entry into saliva were molecular size, lipid so lubility, pKa and protein binding. However, salivary flow rates, the time o f sampling and disease states which altered saliva composi tion could also affect the results. Drugs that are not ionizable or not ionized within the pH range o f saliva are most suited to salivary mo nitoring. Haeckef8 has summarized some of the reasons fo r the failure to use saliva to any great extent for therapeutic drug monitoring as follows. •
Ta ble 1 45,7
D rugs that ca n be mon itored by sal ivary a n a lysi s, Recreationsl d rugs
Therapeutic drugs
Am phe tami nes
Antipyrine Caffei ne
B a r bitu rates
Ca rba mazepine
B e nzod iaze p i n es
Cisplatin
Coca ine
Cyclospori n e
Ethanol
Diazepam
Marij u a n a
Digoxon
N ico ti ne
Ethosux i m i d e
Opioids
Irinoteca n
Phencycl i d i n e
Lithium M ethadone Oxyprenalol Paraceta mol Phe nytoin Prim idone Proca i n a m i d e Quinine
Su I p h a n i l a m i d e Th eophyl l i n e
To l b utam ide
Blo o d h as to be sampled for other electrolytes anyway.
•
There are technical difficulties with sampling saliva.
•
There are existing di fficulties with the interpretation of salivary drug concentrations.
The remaining
applications for saliva sampling were
therefore:
VI RAL H E PATITIS
In view o f the hazard to surgeons, a simple method of detecting car riers o f hep atitis viruses has o bvious benefits.
•
when sampling at home is required;
•
special cases where the sample is taken only fo r the monitoring o f a par ticular drug;
•
M i cro b i a l a nti gens and a ntibod i es
circumstances where the sample volume is critical, as for example in newborns.
The
presence
of h epatitis
B
antigen
in
saliva
was
dem onstrated by Bro dersen et al. 3 1 Shikata et al.32 were
able to detect the hepatitis B surface antigen (HBsAg) and the core antigen in hepatocytes, but could not detect it in parotid gland parenchymal cells. However, in the patient
Nevertheless, if a constant saliva/plasma ratio can be established, use o f saliva for therapeutic drug monitoring becomes a clinically useful possibility and Siegel29 has pointe d out that the saliva/plasm a ratios
for at least
1 70
drugs have been established experimentally. Drugs which can be m o nitored in saliva include digitalis, phenytoin, primidone, ethosuximide, carbamazepine, theophylline,
with the highest serum titre of H BsAg, immu noreactivity was detected in the vascular wall and luminal fluid of the p arotid gland. P iacentini et al. 33 have reported high
sensitivity and specificity in the diagnosis of hepatlt,is
A, B
and C using the OraSure collection system, and that the samples had titres of antibodies to viral hepatitis that were similar to those of the serum.
caffeine, lithium, methadone, cyclosporine, marij uana, cocaine and alcohol A
related
(Table 145.7 ) .
u s e for salivary drug monitoring i s fo r
H IV I N FECTI O N
detection of drugs of abuse as described by Cone,30 who
M alamud34 has made a strong plea for u s e o f saliva a s a
reviewed the findings for alco hol , amphetamines, b a rbi
diagnostic fluid for the detection of antibodies to HIV,
turates, benzo diazepines, caffeine, cocaine, inhalants s uch
among other purposes. For the detection of carriage of
as general anaesthetic agents, as well as solvents, LSD,
antib o dies t o
marijuana, op io ids, phencyclidine and tob acco . The use
method and presents enorm o us advantages. It removes
of saliva for the detection of illicit drug use is particularly
the
attractive. The commo n recreational drugs appear in th e saliva at the sam e time as serum.
From
a forensic
standpoint it is not the concentration of these drugs that matters, it is their presence that is important.
risk
HIY, saliva testing is a simple noninvasive
of needle-stick
injuries
and
the
emotional
connotations o f blo o d sampling in this alarming disease. Salivary sampling has special advantages when investi gating
�h i1dren
Archibald
et
because of the great ease of collection. aI.35
have
described
the
p ractical
Chapter
applica tions fo r sal iva tes t i ng fo r p er ina tal HIV dia g
n osis. Only a m i no rity of infants
born to
HIV- p o sitive
mothers d evelop
but
the neona tal
H I V in fection,
in
R E FERE N CES *
1.
perio d usually carry pass ive ly tra ns ferred a n t ibo d ies to 2.
.
the value of an IgA-specific Wes tern blot assay, A rch ibald et al. 36 collected blo o d and saliva fro m 95 i nfan t s and
4.
24-35. 5.
percen t for infants over 1 2 mo n t hs T h e earliest a g e fo r .
detection of ser u m
IgA
antibod ies to HIV is
b elieved to
be two m onths. Sal ivary I gA an t ibod ies were det ect ed by
al. 3 6 in an infected infant a t six months, but had been nega t ive a t fo ur months . Relia b l e sa li va ry
Archibald et
6.
detection of HIV infection in the i m me d i a te neonatal perio d awai ts more sens itive metho ds, However, i f t hese can be fo u n d
,
saliva s amp l ing fo r antibod ies to HIV,
does not re q uire skille d personnel, avoids the need fo r re pea ted vene metho d .
punctures co u nt ries
and
Saliva
is
collectio n
ideal
fo r
studies
in
develop i ng
Ship JA, Patton LL. Tylenda CA. An assessment of salivary gland function in healthy premenopausal and postmenopausal females. Journal of Gerontology. 1 991 ; 4 6 : M11-3. Busfield BJ, Wechsler H. Studies of salivation in depression. Archives of General Psych iatry. 1 961 ; 4 : 1 0-5.
7.
part icularly for infants and chil dren, is a pote n t ia l ly valuable
Baum J B . Principles of saliva secretion. Annals of the Ne w 694: 1 7-23. Turner RJ. Mechanisms of secretion by saliva ry glands. Annals of the Ne w York Academy of Sciences. 1993; 694 :
for de tecti ng antibo dies to HIV gp 1 60 a nt igens was 50 1 2 mon ths old and 9 7 . 3
Humphrey SP, Williamson Rl A review of saliva : normal composition, flow a nd function. Journal of Pros thetic
York Academy of Sciences. 1993;
buccal sulcus. The total se nsit ivi ty o f the sal ivary assay percent of infants less than
Journal of Oral
Den tistry. 2001 ; 8 5 : 162 -9. 3.
children born to HIV-infected women. Sal iva sa mples
fro m infa nts were co l lected by ge nt le aspi ra t io n from t h e
Mandel ID. The diagnostiC uses of saliva.
Pathology and Medicine. 1990; 1 9 : 119-25.
,
HN from t he moth er. However, it is believed th a t IgA and fgM ant ibo d ies do no t cross t h e pla cent a To assess
1 45 Physiology o f t h e saliva ry glands . 1869
Busfield BJ, Wechsler H, Ba rnum WJ. Stu dies of salivation in de pression. Archives of General Psychiatry. 1961 ; 5 : 7 6-81.
8.
Navesh M. Methods for collecting saliva.
Annals of the
Ne w York Academy of Sciences. 1 993 ; 694 : 7 2-7. 9.
.
Thieme TR, Piacentini 5, Davidson S, Steingart K. Determi nation of measles, mumps and rubella immunization status using oral flu i d samples. Journal
of
th e A merican Medical Association. 1994 ; 2 7 2 : 219-2"
MONITORING OF I M M U N IZATION STATUS Thieme et
mumps
1 0.
al.9 h ave used sa liva ry sa mp l i ng fo r measles
and
,
rubella immunization st atus . SaJ iva was
collected using the OraSure system. Antibo dies in oral fluid
specimens
correla ted
with
and
sp ecificity to
the following
an d
1 00
respective ly;
percent,
levels degree: mum ps,
Academy of Sciences. 1993; 694 : 330-1. 11.
o f sensi t ivi ty measles,
97
94
94
an d
percent, resp ectively; and rubella , 9 6 a n d 98 percent,
13.
KEY PO I NTS
•
Ii
•
I
499-502.
Drug thera p y is t he most common cause o f decreased sal i vary tlow. Dry mo u t h is a com mon man i festatio n of a u ro i m m u n e d isease. l·B V infec t ron, sa rcoidos i s i ron overload,
Vitali C, Moutosopou los HM, Bombardieri S, and The European Community Study Group. Diagnostic criteria for Sjogren's syndrome. Annals of the Rheumatic Diseases.
1 5.
Sreebny L, Zh u WHo Whole saliva and the diagnosis of Sjogren's syndrome : an evaluation of pa tients who complain of dry mouth and dry eyes. Part 1: screening tes t .
1 6.
Tishler M, Varon I, Raz A, Meyer FA, Varon M. Salivary eicosanoid concentration in patients with Sjogren's syndrome. Annals of th e Rheumatic Diseases. 1996 ; 5 5 :
17.
Tish ler M, Yaron I, Sh irazi I, Varon M. Salivary interleukin-6 levels in patients with Sjogren's syndrome. Arthritis and Rh euma tism. 1 99 6 ; 3 9 : S68.
1994 : 5 3 : 637-47
L
t ype V hype rllipoprotci naem ia.
flow rate and labial biopsr a rc t he two mos� reliable tests for Sjdgren's syndrome. Salivary as ays , :i1tave a sigll ificant ro le to play ;i�" ., . ' · 'in th@ mQQitori�g of d ru g tJiLc ra py,c de{e c�ti? g�, . : Unst i m u t att:od whole s a l iv a ry
•t����4�:�11;t;reSf��, fo.r Gf��+;·: ;?�fy'/ · ..
I
,
__
Ma ndel ID. Sialochemistry in diseases and clinical situations affecting saliva ry glands. Critical Reviews in Clinical Labora tory Sciences. 1 980 ; 1 2 : 321-66. Speight PM, Kaul A, Melson R D. Measurement of whole unstimulated saliva ry flow in t h e diqgnosis of Sjogren's syn drome. A nnals of the Rh eumatic Diseases. 1 992 ; 51 :
14.
,
•
North LM, Gaudette N D, Cordeiro M L. Fitchen J H, Davidson S L. Hida hl MS. Detection of cotinine in oral fluid recovered with the OraSureR collection system. Annals of the New York Academy of Scien ces. 1993; 694 : 332-3.
* 12.
respectively.
•
Cordeiro ML, T urpi n CS , McAdams SA A compa rative stu dy of saliva and OraSure R oral fluid. Annals of the New York
.-
Gerodontology. 1 99 6 ; 1 3 : 35-43.
2 02-4.
1870 1 8.
I PART 1 5 T H E LI P P E R DI GESTIVE TRACT
27.
Rujner J, Scha J, Barra E, Gregorek H, Madal inski K, and serum I gA anti-endomysi um antibodies as a screening test for celiac disease. Acta Paediatrica.
1 9.
1 996; 8 5 : 8 1 4-7.
Sciences. 28.
of Sciences.
G, Smith P M . Sal ivary and serum antibodies to g l iadin in and Medicine. 20.
Siegel IA. The ro l e of sal iva in dru g monitoring. Annals of
30.
Cone EJ . Saliva test i ll g for dru g s of ab use. A nnals of the
31 .
Brodersen M, Stegmann S, Klein KH , TrUlzsch D, Reshsch P.
the Ne w York Academy of Sciences. Ne w York Academy of Sciences.
Williams J . Salivary I gA anti g l iadin antibody as a marker
1 99 2 ;
6 7 : 7 24-7. P53
antibodies in the saliva of patients with s q u amous cell
h uman parotid gland. Oral Surgery, Oral Medicine, and Oral Pathology.
Strekfus C, Bigler L, Tucci M , Thigpen JT. A pre l im inary receptor, cathepsin-D and
33.
p53 in saliva among women
with breast carcinoma. Cancer In vestigation.
of the New York Academy of Sciences.
Ferguson DB. Current diagnostic u ses of saliva. Journal of
34.
1 987 ; 6 6 : 420-4. 35.
estrogens and androgens. Annals of the Ne w York
I I I ) in sal i va of acq uired immunodeficiency syndrome
E l l ison PT. M eas urements of salivary progesterone. Annals
1 986; 67: 83 1 -4. 3 6.
Dabbs Jr. J M . Sal ivary testosterone measurements in behavioral studies. Annals of the Ne w York Academy of Sciences.
(A I DS) patients and in persons at risk for A I DS. Blood.
1 993 ; 694:
1 61 -76.
1 993 ; 694: 1 77-83.
1 99 2 ; 3 0 5 : 207-8.
Archibald DW, Zon L . Groopman J E, McLane M F, Essex M . Antibodies to human T- Iym photrophic virus type I I I (HTLV-
1 993 ; 694 : 1 46-59.
of the Ne w York Academy of Sciences.
M alam u d D. Sal i va as a diagnostic flu id. Second now to blood? British Medical Journal.
Read GF. Status report on measu rement of salivary Academy of Sciences.
26.
1 993 ; 694:
334-6.
Dental Research.
25.
1 98 5 ; 59 : 58-62.
Piacentini SC, Thieme TR, Bel l er M , Davidson S L . Diagnosis of hepatitis A, B and C u s ing oral sam p l es. Annals
2000 ; 1 8 :
1 01 -9.
24.
Shikata H , Su zuki K , H enmi A, Ll s h iyama H , Ucida T, Utsumi
I\J et al. Local i zation of hepatitis B surface antigen in the
1 99 8 ; 7 8 : 390- 1 .
study on CA 1 5-3, c-erb B-2, epidermal growth factor
23.
1 993 ; 694 : 9 1 - 1 27.
1 974; 1 3 : 675-6. 32.
carcinoma of the oral cavity. International Journal of 22.
1 993 ; 694: 86-90.
Salivary H BAg detected by radioimm unoassay. Lancet.
Tavasso l i M, Brunei N, Maher R, Johnson N W, Soussi T.
Cancer.
1 993 ; 694: 1 28-42.
29.
1 98 9 ; 1 8 : 578-8 1 .
H akeem V, Fifield R, al- Bayaty H F, A l dred MJ, Walker DM, for cel iac disease. Archives of Disease i n Childhood.
21 .
1 993 ; 694: 36-47.
Haeckel R. Factors infl u encing the saliva/plasma concentration of dru gs. Annals of the Ne w York Academy
al- Bayaty H F, Aldred MJ, Wal ker DM , Newcombe RG, Swift the diagnosis of celiac disease. Journal of Oral Pathology
J u s ko WJ , Milsap R L. Pharmacokinetic principles of drug distrib ution in sal iva. Annals of the Ne w York Academy of
Wozniewicz B. Serum and sal ivary antig l iadin antibodies
Archibal d DW, Farley JJ, H ebert CA, H ines SE, Nair P, Johnson J P. Practical applications for saliva in perinatal H IV diagnosis. A nnals of the Ne w York Academy of Science.
1 993 ; 694: 1 95-201 .
r
146
:
Imaging of the salivary glands
NICOLE JM FREUNG
I n trod uctio n Imaging techniques Non-neoplastic disease Neoplastic disease Imaging sal ivary disease in children
1871 1872 1878 1882 1886
Best c l i nica l practice Deficiencies in current knowledge and areas for future research Acknowledgements References
1887 1887 1887 1896
The data in this chapter are supported by a PubMed search using the key words salivary gland disease - imaging; US-guided FNAC - salivary disease. Only publications in the English language have been included.
INTRODUCTION
patients. Imaging-guided fine needle aspiration cytology
Imaging of the salivary glands has evolved into a highly
radiological suspicion of infectious or neoplastic disease.
(FNAC) is an elegant way to confirm a clinical and sophisticated use of high-resolution digital techniques,
Awareness of the increasing costs of medical imaging will
for example ultrasonography (US), magnetic resonance
influence the decision as to which imaging technique has
imaging
(MRI),
digital
contrast-enhanced
subtraction
computed
sialography
tomography
and
to be ordered in which specific situation.3
[*J
(CE-CT).
These new techniques have replaced many conventional radiographic modalities during the last few years.
Normal anatomy - parotid gland
There are instances in which imaging seems to be superfluous: some ENT surgeons will diagnose a small
The normal anatomy of the major salivary glands is best
tumour within the superficial lobe of the parotid gland
demonstrated on magnetic resonance
without imaging. They will argue that any small, well
tomography
circumscribed parotid tumour should be removed by
recognized in the adult patient due to its fatty content
superficial parotidectomy, regardless of histology. 1, 2 On
(Figure 146.1).
the
other
hand,
planning
surgical
or
radiotherapy
(CT)
(MR) and
computed
images. The parotid gland is easily
The superficial lobe is seen
between the external
treatment for a large malignant parotid tumour will
auditory canal and the angle of the mandible, lateral to
seldom be carried out without imaging.
the masseter muscle. The deep lobe is medial to the
Imaging may help in acute submandibular inflamma
mandible extending towards the prestyloid parapharyn
tion to differentiate between lymphadenitis and sialadeni
geal space, best seen on axial (transverse) images. The
tis, to depict an abscess and to demonstrate deep extension
parotid duct courses anteriorly over the masseter muscle
into the neck. In chronic recurrent disease, imaging may
and pierces the buccinator muscle to end in the mucosa of
help
the mouth at the level of the second upper molar.
to detect
complications,
for example
malignant
lymphoma in patients with Sjogren's disease or in HIV +
Accessory parotid glands may be found along the parotid
1872
I PART 15
THE UPPER DIGESTIVE TRACT
Parotid duct Masseter muscle Medial pterygoid muscle Parapharyngeal space Deep lobe parotid gland Mandible Retromandibular vein Supetiicial lobe parotid gland
Sternocleidomastoid muscle
F[gure 146.1 (a) SET2, transverse 3T normal anatomy parotid gland; (b) SET1 coronal 3T normal anatomy parotid gland. Superficial (long arrow) and deep (short arrow) lobe parotid gland. r
duct, and these may undergo the same disease processes as the major glands (Figure 146.2).
hand-held transducer is a transmitter of the ultrasound beam and also a receiver of the reflected ultrasound from
The submandibular glands fold over the
posterior
the body. Due to the different reflecting properties of
border of the mylohyoid muscle and have a deep part in the posterior floor of the mouth and a superficial part
tissues, a grey-scale image can be obtained displaying 4 anatomical structures and disease. US is a dynamic
within the submandibular space
examination in which a continuous flow of information is
(Figure 146.2). The
submandibular duct courses from the deep part over the
displayed on a screen. The transducer can be turned in
floor of the mouth to end with a steep bend in the mucosa
every direction in the search for the best possible view of
of the anterior floor of the mouth next to the
frenulwn of
the tongue. The submandibular glands do not contain fat
the
lesion.
Due
to
the
relatively
small
size
of
the
transducer, US provides a kind of keyhole image (Figure
and therefore have a less high signal intensity on SE T 1-
146.3). The advantages and disadvantages of US are
weighted images compared to the parotids in adult patients.
summarized in Table 146.1. It can be difficult to obtain an image of the lesion in combination with surgically important anatomical refer
IMAGING TECHNIQUES
ences, for example in the case of a large lesion. Images represent a very limited part of the dynamic examination.
Ultrasound
They may be difficult to understand by those who were
us is a technique in which a high frequency (7-10 MHz)
accurate information when performed by an experienced
sound
beam - is
transmitted
into
the
patient.
The
not present at the examination. Nonetheless, US provides sonographer.5
Chapter 1 46 I maging of the salivary g la nds I 1873 Figure 146.2
(a) SET2, 3T normal a n atomy submandibular (doub le a rrows) and subling ua l glands (long th in arrows), The submandibular gland folds over the posterior border of the mylohyoid muscle (thin arrows). The stylohyoid muscle (arrowheads) is media l from both the submandibular and the subl i ngual glands. The fat between the mandib le and the submandibul a r gland (sm a l l thick a rrow) must be recognized in t h e norma l situation. When oblitera ted, t h i s m a y signify subtle disease (tumour i n filtration). Note also the different s i g nal from the parotid glands (long th ick arrow). due to fatty changes i n t h e adult i ndividuals, compared to t h e signal of the submandibular and sub l ingual glands; (b) SEn, 3T coronal normal anatomy submandibular g lands. The submandibula r gland (arrows) is lateral from the mylohyoid muscle (small arrows)) i n its submandibula r extension; (c) SEn, corona l 3T normal anatomy subl ingual glands (sma l l arrows). The sublingua l glands a re situated anterior within floor of the mouth, medial to the mandible (long thin a rrow),
Figure 146.3 (a) US of normal paroti d g land (short arrows) and mandi ble [long thin a rrow). (b) US of normal submandibular g land (sm a l l a rrows), posteriorly folding over mylohyoid muscle (long thin arrows).
�--
Table 146.1
Comparison of imag ing techniques.
Technique us
MRI
CE-CT
Conventional sialography
Salivary gland
scintigraphy Advantages
Quick exami nation
Excellent soft tissue contrast
Quick
Quick
Widely available
Multiplanar capabilities
Widely avai lable
Widely available
l\Jo harm for the patient Possible in noncooperative patients US-guided FNAC
No radiation
Most sensitive for radiopaque Excellent depiction of extra- and intraglandular ducts calculi Large anatomical range easy to depict
Less dental artefacts
l\Joninvasive
Disadvantages No information Not w idely available behind bone or air No depiction of deep Long exami nation time (30-45 m i nutes) facia I spaces Operator dependent Motion artefacts
Wel l tolerated
2D and 3D reconstructions from axial i mages Rad iation dose
Invasive exam ination (retrograde contrast injection )
Artefacts from dental restorations Iodinated contrast: renal
Com plications: bleeding; traumatic perforation; rupture Radiation burden ( low) duct No i nformation proximal to com p lete obstruction
Easy to perform
function? allergy? thyroid? Contra i ndications: pacemaker; claustrophobia; noncooperation of patient
Quantification of function Quantification of obstruction Reproducible
Indirect information on parenchymal disease 4-15% unsuccessful cannulation submandibular duct Excellent patient cooperation needed for subtraction Contraindications: acute sialadenitis; contrast al lergy; thyroid disease; uncooperative patient
No morphological presentation
Chapter 146 Imaging of the salivary glands. 1875
A drawback of US is that bone and air reflect the sound beam completely. Behind bone, no information can be gathered. This
limits the examination of deep structures
The
strong
(1.5 tesla) magnetic field and Tl- and
T2-weighted pulse sequences yield excellent contrast of the
and abnormal soft tissues and osseous in the body. Sometimes, an intravenous
normal
in the face and neck. To prevent air slipping in between
structures
the skin and
contrast injection of gadolinium may further enhance
the transducer,
gel is applied
at the
contrast between normal and abnormal tissues or demon
examination area. The
dynamic
character
makes
it
easy
to
follow
strate subtle changes along nerves or vessels or intracra
percutaneous needles into the tissue to obtain guided
nial
biopsies of the most suspicious areas.
images in every desired plane without the need to move
Bloodflow assessed
and
within large and small vessels can be Doppler
spectra
Doppler ultrasonography.
analysed
with
colour
[*J
structures.
provide
(Figure 146.4).
suppression techniques
are
used
after
intra
venous contrast in areas where the disease process is surrounded by fat (orbit, skull base). Fat suppression reduces the
MRI was introduced in the early 1980s. The advantages
(a)
capabilities
the patient. MRI is an excellent modality to depict the soft different planes
Magnetic resonance imaging
Figure 146.4
multi planar
tissues of the face, neck and skull base in multiple Fat
and cUsadvantages ofMRl are summarized in
The
Table 146.1.
the
high signal
conspicuity
of
from
subtle
fat thereby
enhancement
increasing
of a
lesion
(Figure 146.4).
SET1. Most lesions present with a low signal, comparable to muscle, on Tl-weighted sequences;
(b)
SET2.
Intermediate signal intensity of the lesion (arrow). Intermediate or low signal is seen in benign as well as malignant lesions. The lesion is w ell-defined. Sharp demarcation does not exclude malignant nature;
(c)
SET1 after i.v. gadolinium. Enhancement of the larger lesion
{arrow}. Homogeneous enhancement of a small lesion can be seen in benign as well as malignant lesions;
(d)
SETl after gadolinium
with fat suppression technique. Better appreciation of contrast enhancement of the lesion with fat suppression technique. Superficial parotidectomy was performed. Histology revealed a benign pleomorphic adenoma with a high degree of cellularity, whi ch explains the relatively low signal 'intensity on T2. These cellular pleomorphic adenomas have a higher incidence for becoming highly malignant carcinoma ex pleomorphic adenoma.
1876
I PART 15 THE UPPER DIGESTIVE TRACT
Due to the permanent strong magnetic field, ferro
magnetic devices cannot be near to the system. Electronic
Gadolinium has virtually no adverse effects) although sporadic allergic reactions are reported in the literature.
devices will be deregulated resulting in potentially lethal
There is no interaction with thyroid function. Reduced
complications (cardiac pacemakers), therefore MRI is
renal function is a relative contraindication to gadolinium.
contraindicated in patients
with a pacemaker. Other
electronic devices can be readjusted immediately follow ing the MR examination, for example insuline pumps,
The average examination time of MRI of the head and neck varies between 30 and 45 minutes. The
advantages
summarized in
ventriculoperitoneal drains.
and
disadvantages
of
MRI
are
Table 146.1.
Claustrophobia and noncooperation, due to pain or unconsciousness) is another contraindication due to MRI being extremely sensitive to motion artefacts. Routinely) SE Tl- and SE T2-weighted images are obtained
in
axial
and
coronal
planes.
Post-contrast
(gadolinium) images with and without fat suppression are mandatory in malignant disease. Artefacts from dental restorations are local and seldom obscure parotid or submandibular abnormalities on MRI
(Figure 146.5).
MR sialography Magnetic resonance sialography (MRS) is a relatively new development in MR imaging, using heavily T2-weighted sequences. No intravenous or intraductal contrast en hancement is necessary to obtain images of the salivary ducts and intraglandular ductal system. MRS is based on the principle that stationary fluids are hyperintense on heavily T2-weighted images.6
NEW DEVELOPMENTS King and co-workers have published the first results of MR proton spectroscopy for differentiating ben ign from malignant disease.7 Although the results are promising, they refer to the small series and technical drawbacks (only large tumours of greater than
1 cm3 in size) ten
percent of examinations unsuccessfW due to motion artefacts) and conclude that more research is necessary to vaJidate MR spectroscopy as a strong diagnostic tool. Diffusion-weighted imaging has gained in interest in head
and neck radiology
recently.
To
the
author's
kn owledge there is no clinically relevant literature on the value of diffusion-weighted imaging and salivary gland tumours at this time
.
Computed tomography Computed tomography (CT), introduced in 1974) is a cross-sectional imaging technique using ionizing radiation. The advantages and disadvantages of CT are summarized
in Table 146.l. The table - with the patient in a comfortable supine position - is moved through the gantry, containing the x-ray beam. Slice thickness and distance between slices is determined by collimation of the beam
(1-5-10 mm) depending on the manufacturer)
and table speed. With a spiral CT scanner, thin slices (1-2
mm) can be obtained of a large volume. This provides excellent 2D and 3D reconstructions so that there is no need for direct coronal scans with the patient in an uncomfortable prone position. Coronal reconstructions from spiral scans are' not hampered by dental artefacts
because the axial scans can be chosen to stop above the Figure 146.5
(a) Dental artefacts (arrows) are less pronounced on MRI compared to (b) CT.
amalgam
(Figure 146.6),
Intravenous iodinated contrast medium is necessary to enhance
the
contrast between vessels,
other
normal
Chapter
146
Imaging of the salivary glands I 1877
structures and disease processes. Patients who are allergic
to contrast medium should be prepared according to local guidelines. Renal function should be checked as the contrast medium has an adverse effect on it. Anticipation of thyroid function tests or iodine-131 therapy is a contraindication to iodinated contrast medium. Serious artefacts in the parotid region may arise from dental restorations. These may obscure even medium sized tumours. The average duration of a CE-CT examination of the head and neck is 15-20 minutes. Because of the relatively large gantry opening and the short examination time) claustrophobia and noncooperation are lesser problems with CT than with MRI.
Conventional sialography After cannulation of the duct orifice) watery or oily iodinated contrast medium is injected in a retrograde manner into the parotid or submandibular duct and multiple radiographic images are obtained. At digital subtraction sialography, noncontrast images are super posed on contrast images to avoid bony and soft-tissue overprojection of the ducts. This results in a sharp outline of contrast-filled ducts on the radiographic films. The advantages and disadvantages of conventional sialography are summarized in
Table 146.1. The technique requ ires
good cooperation of the patient) who should not move between the pre- and post-injection images. Because of the intricate nature of the procedure, operator experience and patient cooperation are required. In
4-15 percent of
patients, unsuccessful cannulation of the duct is reported due to a small submandibular duct opening, papillary stenosis,
oedema
or
distal
obstruction.s
Retrograde
injection may displace infection from the distal duct more proximal or into the gland) resulting in aggravation of sialadenitis. The examination time is reported to be between 10 and 20 minutes. There are also disadvantages: retrograde sialography is contraindicated in patients with acute sialadenitis)
in the
case of a previous allergic reaction to contrast medium, interfering
with thyroid function tests and the radia
tion dose. Complications associated with the technique are bleeding) traumatic perforation or rupture of the duct.9 In the case of a complete obstruction no information is gleaned from the proximal duct and glandular parenchyma.
Plain radiographs
Figure
1 46.6
(a) Technique spiral CT: planning above/around
dental restorations to avoid artefacts in region of interest; (b) CE-CT normal parotid gland: superficial lobe (thick arrow) and deep lobe (thin arrow); (c) CE-CT normal CT-anatomy of the submandibular (arrows) and sublingual (arrowheads) glands.
Due
to the
increasing
availability
of
cross-sectional
imaging methods such as US and CT, the need for plain radiographs to demonstrate intraductal calculi is reduced. Plain scout films precede retrograde conventional sialo graphy to match for filling defects in the contrast-filled duct.
PART 15
1878 I
THE UPPER DIGESTIVE TRACT post-injection of the radionuclide. After the acquisition,
A disadvantage of plain films is that no other information about the ducts and the glandular aspect is
regions of interest are drawn
glea ned Approximately 15 percent of salivary stones are
submandibular glands. Salivary gland uptake and excre
.
over the parot id and
radiolucent and therefore will not be demonstrated on
tory function can be assessed visually on dynamic images
plain films, again, it adds to the radiation dose.
or (semi-) quantitatively on time-activity curves with
a
possibility of calculation of uptake and excretion percen tages of injected activity
146.7 and
Scintigraphic methods have been
Scintigraphy Pertechnetate
(Figures
146.8).10
replaced
by radio
graphic techniques in the diagnosis of space-occupying
t9mTc04)
is well known for its uptake by
salivary glands with a single intravenous injection and limited radiation dose. Based on its physicochemical correspondence to chloride, it concentrates in the salivary glands and is secreted along with saliva in the oral cavity. The advantage of salivary gland scintigraphy is that both parenchymal function and excretory function
of all
lesions
of the
salivary
glands.
Only
when patients
complain of vague symptoms related to the salivary glands without definitive objective signs of abnormality can salivary gland scintigraphy be a reliable alternative to
investigate functional disorders, omitting the need for any discomfort of sialography and excessive radiation exposure of CT.11
salivary glands can be quantified simultaneously with a single
intraveneous
injection
and
limited
radiation
burden. The patient is placed in the supine position with the head and neck
under
intravenous injection of
a gamma
camera .
After
80--100 MBq 99 Tc-pertechnetate,
NON-NEOPLASTIC DISEASE Calculous disease
sequential images of one minute each are acquired up to 30 minutes. Salivary stimulation is performed with oral
Intraductal stones cause acoustic shadowing if larger
lemon juice or lemon stick adm inistrati on
than 2-3 mm (Figure 146.9).
15
minutes
A
dilated parotid
Figure 1 46.7 Normal semiquantitative salivary gland scintigraphy. After injection' of 99myc-pertechnetate, accumu lation of tracer is observed in all salivary glands. Application of lemon stick induces rapid secretion of saliva without signs of obstruction.
or
Chapter
146
Imaging of the salivary glands I 1879
Fig ure 146.B Abnormal semiquantitative sa I iva ry gland scintig raphy. After injection of 99'""1"c-pertechnetate, accumulation of tracer is observed in all salivary glands except for the left parotid gland. Application of lemon stick induces rapid secretion of saliva without signs of obstruction in both submandibular glands. There is no response in the right parotid gland. This patient had bilateral parotid gland sialolithiasis with functional obstruction without parenchymal impairment in the right parotid and functional obstruction with subsequent parenchymal impairment in the left parotid gland. submandibular duct is well recognized as a hypoechoic, fluid-filled structure. Small s tones in nondilated ducts may go unnoticed due to lack of acoustic shadowing. Small stones within the intraglandular ducts may be
equally difficult to recognize with US.6, 9 US
has
specificity
a
good
(80--100
(80-94
sensitivity
[It>t*]
perc en t)
the submandibular and parotid duct.9,12
perlormed
techniques
situation
are
ductal strictures, kinks or other
preoperatively pla nned. 1 3
It
if
endoscopic
depends
on
surgical
the
local
if no ninvas i ve MRS or conventional subtraction
sialography can be carried out.
Recently, attention has been paid to MRS techniques.6, 8, 9
MRS is a rapidly evolving noninvasive
technique
to depict
the salivary ducts and intraglandular ductal system. The
dilated ducts and intraglandular ductules has a very high signal in heavil y TI weighted sequences. Reconstructed images may show subtle ductal abnormalities, for example stones, diverticula and strictures. fluid in
-
It
I
93-97
88-97
SenSItlvity for the diagnosis of cal
69-91
percent. It s specifi
percent, the positive predictive value is
percent and the negative predictive value is
91
percent.6, 9 Becker reports a sensitivity of ductal stenosis with
(n
=
9)
and w ithou t
specificity of
subtle ductal abnormalities, additional sialography should be
city is
and
percent) for diagnosing calculi within
Since US cannot depict
The reported
culous disease varies from
87-95 percent
93-98
(n
=
11) calculi of 100 percent and a
percent, a positive predictive value of
percent and a negative predictive value of
100
.
The advantage of MRS over conventional sialography
is that no retrograde injection of contrast is necessary. It can
be
performed
in
acute
sialadenitis
and
when
iodinated contrast is contr ai ndicated. Although MRS
shows excellent results for depicting calculous disease within the main ducts, its per form ance for intraglandular
calculi is less impressive. Its limited availability and costs
are drawbacks of the technique. US is the
first-choice examination for
evaluating
calculous disea se, and may serve to select patients who
need MRS.
1880 I
PART
15
Figure 146.9
THE UPPER DIGESTIVE TRACT
US: ductal dilatation (thick arrows) due to large
calculus (long arrows) within Stenson's duct.
Conventional digital subtraction sialography remains a widely available technique to detect calculi.14 Conven tional
sialography
depicts
calcified
and
noncalcified
stones and strictures as filling defects within the main or
intraglandular ducts. It may not be possible to insert
the cannula in the case of a distal obstruction. Proximal displacement
of
infected
calculi
by
retrograde
con
trast injection may aggravate sialadenitis by glandular
involvement.6 Noncontrast-enhanced CT is
an
excellent and fast
examination for detecting calcified stones in the parotid and submandibular ducts and glands
(Figure 146.10).
Figure 1 46. 10
(a)
Enlarged left submandibular gland (long
arrow): acute sialadenitis of the left submandibular gland
(al,
caused by a large calculus in the submandibular duct (b). Small arrows: normal right submandibular gland; arrow heads:
Radiolucent stones on plain radiographs may be radio
thickened platysma and inflammatory changes in subcutaneous
paque on CT. CT shows more calculi than are seen on
fat; thick small arrow: vallecula cyst.
plain films and this may influence treatment.1S In the case
submandibular duct (long arrow). Inflammatory changes in
of one distal calculus, a local excision may be attemp
ted, whereas multiple calculi often necessitate an excision
(b)
Large calculus in
subcutaneous fat. Reactive lymph node enlargement (small arrows) and thickening of the platysma (arrowheads).
of the duct and gland in chronic recurrent sialadenitis.
The intraglandular ducts are not seen with CT; CT
sialography has been outdated by other less invasive examinations.
In the case of a diffusely hypo echoic appearance of the gland, parenchymal infiltration rather than abscess formation is the cause and intravenous antibiotics will
Noncalculous disease
be given rather than surgical repeated when necessary
ACUTE SIALADENITIS
Acute swelling of the submandibular
treatment. US can be
(Figure 146.11).
CE-CT is needed for the evaluation of inflammatory gland
due
to
sialadenitis is no indication for imaging. Whenever there
is suspicion of an abscess, US is the first choice modality.
US can differentiate between a diffusely enlarged
submandibular gland and enlarged lymph nodes, which may be difficult by palpation only.
A circumscribed hypo- or anechoic fluctuating area
within the gland indicates an abscess.
lesions or abscesses of the deep facial compartments and the neck
(Figure 146.11 ).16
having a deep neck abscess,
In patients suspected of
US should not be performed.
The patient should be sent directly for CE-CT to assess
para- and' retropharyngeal and mediastinal extension of disease.
Chapter
1 46
Imaging of the salivary glands. 1881
Figure 1 46.11 (a) US of acute sialadenitis: swollen parotid gland and (b) duct enlargement (arrows). (c) CE-CT: acute sialadenitis R parotid gland (arrows). The gland is swollen and shows a higher density compared to the normal left gland. (d) The parotid duct is enlarged (arrows); (e) no cause of obstruction was demonstrated. (f) After i.v. antibiotics, spontaneous regression of symptoms, confirmed on US.
1882 I
PART 15
THE UPPER DIGESTIVE TRACT
Chronic sialadenitis: Sjogren's syndrome, HIV infection and cysts In
chronic
salivary
disease,
ultrasonography
is
the
imaging modality of first choice. Enlargement of the glands,
unilateral
or bilateral involvement and focal
changes within the parenchyma
all may be demonstrated.
MRI may show the same changes but its diagnostic potential is not superior to ultrasonography. In Sjogren's syndrome, a good correlation between US, MRI, sialography and histology is reported.17 Ultrasono graphy, which can
be performed repeatedly without any
discomfort to the patient, is suited to imaging follow-up for most patients with Sjogren's syndrome. When a changed echo pattern is noted, US-guided FNAC is indicated to confirm or exclude malignant changes. While ultrasonography is accurate in detecting submandibular lesions and lesions within the superficial lobe of the parotid gland, it does not offer decisive information regarding
large
or
deeply
located
lesions.
In
those
patients, MRI should be performed. In 5-10 percent of HIV+ patients, the parotid glands may be enlarged and contain multiple cystic lesions
(Figure 146.12). Histologically, these are benign epithelial lesions. The diagnosis may be confirmed by US-guided FNAC. In patients who are not known to be HN+, bilateral cysts in the parotid in combination with cervical 8 lymphadenopathy is very suggestive of HIV infection.1 Follow-up by US is indicated to detect changes due to malignant lymphoma or Kaposi's sarcoma. Again, US guided FNAC will confirm the diagnosis Simple
cysts
and
branchial
cleft
(Figure 146.12). cysts
are
rare.
Branchial cleft cysts may show an atypical ultrasound appearance, similar to a solid lesion, due to infection or blood or proteinaceous fluid. Preoperative confirmation by US-guided FNAC helps in differentiating a cystic from a solid lesion. Large cysts may be obliterated by injection of sclerosing agents (alcohol) under US guidance
(Figure 146.13).
Ranulas are well recognized on US as anechoic lesions within the floor of the mouth. Due to its watery contents, a ranula is very clearly seen on axial coronal T2-weighted MR images. The extension of a plunging ranula is accurately depicted on axial, coronal and sagittal images. Ranulas may be recognized on spiral axial CT and coronal reconstructions due to their low density compared to muscles
(Figure 146.14).
Figure 146.12 F, five years, HIV+ , recurrent parotit is. US: Benign Iymphoepithelial cysts in the parotid gland (small arrows) (a); in combination with bilatera I cervica I lymphadenopathy (arrows) (b).
Haemangiomas children.
are
the
most
common
tumours
in
[***]
Approximately 5 percent of all pleomorphic adenomas ' may become highly malignant tumours and therefore should be resected. Pleomorphic adenomas recur in less than 3 percent of patients after parotidectomy; however, recurrences
are
reported
in
up
to
50
percent
after
enucleation. Recurrent tumours may adhere to facial nerve branches and this makes resection a hazardous procedure. Pleomorphic adenomas have rounded or lobulated contours and often present a high signal intensity on SE T2-weighted MR images
NEOPLASTIC DISEASE
A pleomorphic adenoma characteristically presents as
Benign lesions
a lobulated lesion with high signal intensity on SE T2-
By far the most common benign parotid tumour in an adult patient is a pleomorphic adenoma, the second most common
is
adenolymphoma
(Figure 146.15). These are hypo
echoic and slightly inhomogeneous at ultrasonography.
or
Warthin's
tumour.
weighted images and inhomogeneous contrast enhance ment, reflecting the histological composition of cellular and
stromal
elements.
Tumours with
predominantly
cellular components, so-called type III-IV,19 make up
Chapter
146
Imaging of the salivary glands. 1883
Figure 146.13 SETl (a) tumour right parotid gland, superficial lobe (arrow); (b) High signal intensity on SET2; no enhancement after gadolinium (c) axial and (d) coronal, consistent with a simple cyst. FNA: parotid cyst. No evidence of Warthin's tumour. No malignant cells.
only
approximately
adenomas
and
15
present
percent with
a
of
all
pleomorphic
relatively
low
signal
Adenolymphoma is often recognized due to its cystic components. Haemosiderin deposits) a result of bleeding
intensity on SE T2-weighted images and therefore cannot
within these cysts) is incidentally seen as an area of very
be differentiated from other benign or malignant solid
low signal on T2-weighted images
twnours
(Figure 146.16)?O
Recurrent
pleomorphic
(Figure 146.17),
This particular feature is not seen in other benign or adenomas
are
very
well
identified on T2-weighted MR images due to their high signal intensity. MRI may show up to ten times more
malignant tumours and seems to be characteristic of l Warthin's twnour? Adenolymphomas occur virtually only within
the
recurrences than can be expected by palpation. Imaging)
parotid gland, may be multiple and bilateral and are
however, cannot assess the relationship with intraparotid
more common in elderly men. There is an extremely low
facial nerve branches. The present author believes that
risk of malignant changes and the tumour may be left in
preoperative
place in patients who are poor surgical candidates. The
MRI
seems warranted
in
patients with
residual or recurrent pleomorphic adenomas to provide
diagnosis may be suggested from US or MRl findings and
an accurate surgical roadmap.
confirmed by US-guided FNAC.22,23
1884
I PART 15 THE UPPER DIGESTIVE TRACT
used
in
daily
routine
to
evaluate
small)
superficial
MRI being reserved for staging malignant
tumours)
tumours and large lesions, not well depicted by US. Although US can differentiate solid from cystic lesions, the histological nature of lesions cannot be reliably predicted.24,25 Cytology can differentiate between inflam matory and neoplastic disease} but it may be difficult to differentiate between a benign or malignant tumour on cytology alone.26, 27
CE-CT is less well-suited because of less soft tissue contrast) but should be used when there is a contra indication to MRI.
Malignant tumours The
most
common
malignant
salivary
tumours
are
mucoepidermoid carcinoma, adenoid cystic carcinoma) acinic cell carcinoma, adenocarcinoma and squamous carcinoma.
Approximately 20
percent of
all parotid
tumours, half of the submandibular gland tumours and more
than
90
percent
of
sublingual
tumours
are
malignant. Malignant tumours may show the same imaging characteristics
as their benign counterparts. Imaging ) criteria like 'well-defined , 'homogeneous', 'high signal on T2 weighted images' are unreliable; approximately half of the malignant tumours in the series of Freling et al.21 ) did show these 'benign appearances. When infiltration into adjacent compartments and the subcutaneous fat was demonstrated) bony changes and perineural enhancement were seen}
obvious clinical findings of
tumour were present in Som
and
Biller28
a malignant
all patients (Figure 146.18).
reported
a
correlation
between
malignant grade and signal intensity on T2-weighted images in a small series of six patients. The high-grade malignant tumours weighted
images
(n
and
=
3)
showed a low signal on T2-
the
low-grade
lesions
(n
=
3)
containing more serous and mucoid material, showed a Figure 146.14
(a) SE T2
high signal on T2-weighted images. Although many have attempted to correlate imaging
axia l of a nonplunging ranula
(arrows) of the R sublingual gland.
(b) SE T2
coronal image does
features of salivary tumours to histology)25 radiological
not show extension of the saliva collection (arrow) into the
criteria
submandibular space.
differentiate between benign and malignant tumours?,21
per se did not prove to be sufficiently reliable to
This means that FNAC or cutting-needle biopsy remain MRI is by far the best imaging technique for evaluating salivary tumours. Due to its multiplanar capabilities and superior soft tissue contrast, MRI delineates parotid tumours better than any other imaging method. Tumour delineation within the superficial and the deep lobe, extension into other compartments and solid and cystic or necrotic tumour components} are clearly shown. All the
information
needed
for
planning
treatment
is
obtained in a one-step examination.
Due to the limited availability of MRl scanners in
Europe, ultrasonography with or without FNAC
is often
the diagnostic tools to guide imaging and treatment
in a
patient presenting with a preauricular or submandibular mass lesion. Apart from assessing local tumour extension} contrast enhanced MRI has proven to be invaluable to show clinically silent tumour extension) for example along the cranial
nerves
and vessels
intracraniallj9,30
(Figure
146.19). Treatment failures can be reduced when this silent tumour extension is demonstrated before surgical and/or radiation treatment. Even small, well-defined nodules can be malignant tumours2,21 and some of these may show
Chapter 146
Imaging of the salivary glands I 1885
Figure 146.15
Classical pleomorphic adenoma. Tumour in superficial lobe of R parotid gland (arrow). Low signal on SET1 (a), high signal and lobulated aspect on SET2 (b); enhancement after i.v. gadolinium (c) and (d). Histology (superficial parotidectomy): pleomorphic adenoma.
the tumour and
clinically unnoticed perineural spread. Therefore, any
with parotid sialography displays the gland,
patient
the s urroundin g bone and muscles together. It is suggested
with
a
preoperative
diagnosis
salivary tumour should undergo
(Figure 146.20).
of
malignant
MRl for optimal staging
by Kosaka that this display surgeon to
For many years, MRl has been preferred to
CT for
evaluating mass lesions within the salivary glands.2B, 31 Its
will make it easier for the recognize the anatomical relationships. Cur
rently, the lack of soft-tissue contrast compared to MRI, the radiation dose and the need for iodinated intravenou s and
superior soft tissue contrast, in combination with multi
intraductal cont rast makes CT less well
planar imaging, demonstrates clearer anatomical detail
use in the evaluation of salivary tumou rs.
,
suited for routine
than CT. Where CT of the parotid glands is degraded by
With regard to salivary gland disease, sufficient bone
dental restorations, this seldom is a problem in MRI. CT
detail at the level of the skull base can be obtained with
is less accurate in depicting subtle perineural spread when
MRl.
skull base foramina still have a normal size. CT certainly
needed.
helps in staging malignant t umou rs if MRl is not available or contraindicated, but lacks the superior soft tissue contrast of MRI.
CT-guided patients
to
p e rin eural
Recently,32,33 CT for salivary tumours regained atten tion. Spiral CE-CT
Complementary CT
with
2D reconstructions or
3D CT
FNAC
may
demonstrate spread
for bone detail js seldom
from
be a
a
p erformed
skull salivary
base
in
lesion
gland
(or
selected to
be
other)
tumour. It is a safe technique that is well tolerated by the patient
(Figure 146.20).
1886 I
PART 15
THE UPPER DIGESTIVE TRACT
Figure 146.16 (a) US study of a well-defined solid parotid tumour (large arrows). Increased transmission of US (small arrows) is a characteristic feature of pleomorphic adenoma. (b) SE 11 u nenhanced axial image of a tumour in the left parotid gland (long arrow). Note the high signal intensity in the posterior part of the lesion (small arrows). (c) SE 11 coronal image of the same tumour (arrows). (d) SE T2 axial. Most of the tumour has a relatively low signal i n tensity (long arrow); the posterior part shows high signal intensity. This may be due to b lood, protein-rich contents or calcification. This p resentation is not characteristic for pleomorphic adenoma. Al l other histologies, including mal ignancy, shou ld be considered (continued over),
commonly are mucoepidermoid carcinomas and these are
IMAGING SALIVARY DISEASE IN CHILDREN
extremely rare. Most
Ultrasonography should be the initial imaging method
common are inflammatory lesions> due to acute viral or
Salivary
diseases
are
uncommon
in
children.
to analyse salivary abnormality in children. US can help
acute suppurative or recurrent acute or chronic sialade
differentiating intra- from extraglandular disease. Colour
nitis. Intraparotid lymphadenitis, for example in cat
Doppler US may help to recognize vascular lesions.34
scratch
disease>
may
occur.
Other
lesions
such
as
sialolithiasis or ranula may occur. Salivary gland neo plasms are rare. The most common benign neoplasms are haemangiomas and lymphangiomas. Incidentally> pleo morphic adenomas are seen. Malignant neoplasms most
(H/*]
MRI is necessary to demonstrate the extent of large haemangiomas and lymphangiomas (Figure 146.21). STIR and ISE T2 images in axial and coronal or sagittal planes most often display the lesions clearly.35 There is no need for intravenous contrast (gadolinium).
Chapter
146
I maging of the salivary gla nds I 1887
Evaluation of malignant sa livary tumours requ ires injection
contrast
intravenous
to
demo nstra te
silent
(Figures 1 46 . 2 1 and
perineural or perivascular spread
146.22). MRI
is
also
recommended
during
evaluation
of
treatment of malignant salivary tumours, and during fo llow-up after surgical resection and/or radiation therapy. Due to its excellent soft tissue contrast, the multiplanar images,
its
relative
harmlessness
reproducibility of the
and
examinatio ns,
the
excellent
residual
masses,
complications of treatment and/or recurrent tumo urs may be detected and documented In summ�ry, m o dality
to
(Figure 1 46.23) . .
ultra sonography is the first imaging
evaluate
a
preauricular
or
submandi
bular swelling in most clinical circumstances. Abscesses in
the
s ubm andibular
region
may
extend
in to
the
deep neck co mpartments and should be evalu ated by contrast- enhanced CT from skull b ase to the media stinum.
[*]
MRI i s the bes t examination t o evaluate malignant tu mours because MRI may clinically show wmoticed tumour extension along the cranial nerves and intracra nially. MRS i s a new, noninva sive technique to depict the paro tid a nd subm andibular duct without the need for intraveno u s or retrograde intraductal contrast injection which
is
reco mmended
fo r
evaluation
of
chronic
recurrent sialadenitis .
./
Best clinical practice recom mendations are summarized in Tabl e 146.2.
Defi c i e ncies i n cu rrent know led g e a n d a reas for fu t u re resea rch �
Figure 1 46 . 1 6 (contin ued) (e) SETl after i.v. gadolinium with fat suppression technique. I nhomogeneous enhancement of the tumour in the left parotid g la nd (arrow). No apparent enhancement in posterior part, which suggests, in combination with the other sequences, haemorrhage with in the tumour (small a rrows). (f) SETl after Lv. gadolinium shows no abnormal en hancement along the left facial nerve. (9) SETl after i.v. gadolinium. No abnormal enhancement along the third division of the trigeminal nerve either (arrows). Abnormal enhancement should be excluded in all patients, presenting with a suspicious malignant tumou r in the parotid (or other salivary) gland. Histology (parotidectomy) : ca rcinoma ex pleomorphic adenoma.
h ' .-
No imaging m ethod can replace histological diagnosis in tumou rs of the salivary gla nds. )- N ew MR tech niques : D W I spectroscopy for evaluation of salivary tu mou rs. � What has PET in com bination with CT or M R I in petto?
ACKNOW LEDGE M E NTS Due to the kind contribution of Dr Roel Bennink of the Department of N uclear Med icine of the AMC, Amster dam) this chapter has become a fa irly complete overview of radiolo gical and scintigraphic imaging fo r the evalua tion of sa liva ry disease.
.
1 -_ _
__
��_
1 888 I PART ' 5 TH E U PPER D I G ESTIVE TRACT
Fig u re 146. 1 7 E l derly fem a le patien t wi th a palpable lesion in the right su perficial pa rotid gla nd. (a) S E T 1 and (b) SET2 transverse i m ages show mu ltiple bilateral lesions within the superficial lobe of both parotid g l a nds (a rrows) . (e) SE T2 tra n sverse sca n. The l a rgest lesi on in the rig h t parotid gland shows a low signa l in tensity. The most l i ke ly diagnosi s in these c.i rcu msta nces is Warth i n 's tumour, wh ich is a lesion of th e elderly patien t and may occur as u n i l ateral a n d b i l a tera l as sol i ta ry or m ulti p le. (d) Coronal SET2 i mage with fa t sup pressi on shows two low sig n a l i n tensity lesions i n the l e ft pa rotid g land (sma l l a rrows) a n d one in the rig h t p a rotid gland (thick arrow). H i stology: W a rthi n's t u m o u r; (e) S ETl a fter i.v. gado l i niu m. No obvious en h a n cement of the lesions. Fa t su ppression seq u e n ces a fter i.v. g ado l i n i u m injecti o n wou l d have been of b e n e fi t to detect sl i ght e n ha nceme nt, but we re not carried out in this patient
Cha pter
1 4 6 Imaging of the sa liva ry g la nds I 1889
Fig u re 1 46.1 8 The patient is a n elderly ma le, presenti n g with a l eft prea uricula r swel l i ng and left facial nerve palsy. (a) SETl transverse image of a left pa rotid tu mou r (arrow). The tu mou r is u n i latera l , sol i tary, well defi ned, with low sign a l intensity. (b) S ET2 axial shows very low signal i n tensity of the lesion. The lesion is slightly in homogeneous. Extension i nto the deep lobe (arrow). Low signa l and deep lobe extension with facia l para lysis is very suspicious for ma l i g na nt tumour; (c) SETl after i.v. gado l i n i u m with fat suppression techn i q ue. M i ld e n ha ncement of the lesion. The low sig n a l intensity on T2 a nd extension in the d eep lobe, i n combination w ith the facial nerve pa lsy, is very suspicious for a ma l ig na n t lesion. Warthi n's tumour n orma l ly does not cause facia l nerve pa lsy. Corona l scans m ust be obta i ned to exclude p e ri n e u ra l enhancement a long the trigeminal and/or facia l nerves ; (d) SETl after i.v. gado l i n i u m w ith fat suppression tech nique. The tumour is located w i th i n the s u perficia l (long arrows) part and extends i nto the deep lob e (sho rt a rrow) ; (e) SET l after Lv. gadoli n i u m . No abnormal enhancement a long the th i rd d ivision of the trig e minal nerve (arrows) is shown. Neither w a s there a bnorma l en ha ncement a l o n g t h e facial ne rve ( n o t shown). Biopsy : m u coepidermoid carc i n oma.
1890
I
PART 1 5 THE UPPER
Fi g u re 1 46 . 1 9
(a)
,
D I G ESTIVE TRACT
a djacent compartments.
Ta ble
1 46.2
(d)
SETl coronal i mage. N o extension into
.
Indications i mag ing exa m i na tions, a su m m a ry.
MRI
CT
Convent j,on a l
MRS
s i a lography
. ' -�'/;.:.; .
+
Acute sialaden itis
+/
N eck abscess
+
Chronic siaiaden itis-
+
+
+
+
+
H IV +
+
Ben ign neoplasms
+
+/ +/ +/
Sia l adenitis i n chi ldren
+
Neoplasms i n ch i l d re n
+
i n it i a l exa m i natio n ; +
<: {. !:2,, : : .
/-,
-
+/ +
+/
-
+ /+ /+ /-
+
M a l i g n a n t neoplasms
SaHvary g l a nd sci nitlgraphy
+/
-
Sj o gre n ' s sy n d rome
.
(e)
SETl after i.v. gadol i n i u m . I n h o m ogeneous enha ncement with central necrosis (arrow) (conti n ued ov e r)
us
+
.
SET1 tra nsverse i mage. I I I -defined tumour in the l e ft parotid g l a n d (arrows) ; (b) SET2 tra nsverse i m a ge Low signal
i n tensity i n the i l l-defi n ed lesion. This i s very suspicious for a high g rade m a l i g nant tu mo u r ;
+
+
may be i n i tial exam in atio n or a dditional to US or US-FNAC;
- , no i n d i cation, except for contra i n d ications to MR\.
Ch a pter 1 46
I magi ng of the salivary g l ands I 1891
Fig u re 1 46. 1 9 (con tinued) (e) SET1 after i.v. gadolin ium. Abnormal perineural en hancement along the facial nerve: genicu late ganglion ; and (f) along the intracanalicu lar facial nerve, considered perineural tu mou r spread. (g) Coronal SE T1 after i.v. gadol inium shows abnormal en hancement along the descending facial nerve on the left (arrow). H i stology parotid tumour: mucoepidermoid carc i noma.
L
1892 I PART 1 5 TH E UPPER DIGESTIVE TRACT
Figure
1 46.20
Ma le,
42
yea rs. Pa i n a n d swa l l o w i n g disord e r
a n d palpa b l e lesio n l e ft pa roti d . No facia I pa I sy.
(a)
T u mou r, l e ft
paro t i d g la n d , exte n d i n g i n to deep l o b e ; sharp d e ma rca t i o ns ; low, i n homog en e o u s si g n a l on e n h a n ce m e n t
(c)
SET2 (b) ,
a nd after gad o l i n i u m
suggesti ng ma l i g na nt nat u re ;
(d)
a n d (e)
tumo u r does n o t exte n d a l o n g fa c i a l n e rve or i n to sty l o ma s toid fora me n . At s u rgery the fac i a l n e rve co u l d not be i d e n t i fi e d , the tumour a p p e a ri n g to o rig i n a te from the n e rve. H istology ( b i o psy) : schwa n n o mq.
�--
Chapter
1 46 I maging of the salivary glands I
1893
Fi 9 u re 1 46.21 Vascu la r ma Iformation of the right hemiface in a 1 4-year-old g i rl. (a) S E T2 axial shows the lesion a nte rior to the right parotid g land. The accessory g land is pushed latera l (sm a l l arrows) a nd the massete r muscle has been complete ly invaded by the lesion, compare to the normal left side (arrow). (b) Cauda l ly the lesion does not seem to involve the su bmand i bu lar (arrowhead) or sublingu a l (small arrows) g la n ds. The demarcations a re sharp. (c) Coronal S ET2 images seem to confi rm this fi nding. (d) After Lv. gado l i n i u m , i nhomogeneous e n h a ncement is seen without large vessels. No e rosion of the m a n d ible has occu rred . Diag nosis; low-flow vascula r ma l formation .
1 894
I PART 1 5 T H E U P P E R D I G ESTIVE TRACT
F i g u re 146.22 Malignant parotid tumour in a 1 3-month-old boy_ (a) SET 1 shows enla rgeme nt of the right pa rotid g land. (b) SET2 shows an i ntermed iate signal intensity of the tumour. (c) After Lv. gadolin i u m, the tumour enha nces i nho moge neously: (d) SET2 coro n a l i mages d o n o t s h o w i ntracra nial extension : and (e) there is no abnormal intracranial enhancement. Histo logy : sia loblastoma, a ra re, probably m a l i g n a nt, tum o u r with indolent but sometimes aggressive behaviour.
Chapter
Fig u re
146.23
146 I m a g i n g of the s a l iva ry g la n ds I
1895
Atro phy of the p a rot i d a nd s u b m a n d i b u l a r
g l a nds i n a 5 -year-o l d g i rl afte r exte r n a l b e a m ra dia t i o n thera py for p a ra ph a ry n g e a l rh a b d o m yosarcoma.
(a) SET1 ;
a n d ( b)
SET2
show vo l u m e loss of th e rig ht p a rotid g l a n d (arro w h e a ds) . Norm a l l eft s i d e (arrows). (c) Coro n a l
SET1
shows atrophy of the
r i g h t pa rot'ld a n d s u b m a n d i b u l a r g l a n d s (arrowhea d s, thick a rrow) d u e to ra d ia tion. N ote the l o w signal i n te n sity o f the l eft parotid g l a n d (arrows) , a n o rm a l fi n d i ng at t h i s yo u ng a g e. (d) After i .v. ga d o l i n i u m , a b n ormal e n h a nc e m e n t of the ri g h t masto i d c e l ls is s e e n a n d a sm a l l l e s i o n i n the ri g h t
PPS
(arrowsl. The a b norm a l e n h a n c e m e n t of t h e m asto i d c e l l s is d u e t o ra d i ation t reatm e n t a n d proba b l y a l so to t h e res i d ual tu m o u r ma ss i n t h e PPS (sma l l a rrow).
(e)
Th e coro n a l i m a ges a fter i .v.
co n tra s t and fa t s u p p re s s i o n rev e a l re s i d u a l tu m o u r exte n d i n g th rou g h the ova l fora m en a l ong the th i rd divisi o n of t h e tri g e m i n a l n e rve i n to the cavern o u s s i n u s (a rrowsl. Aga i n , the i m po rta nce of obta i n i n g coro n a l i.v. co ntra st is d e m o nst ra ted.
MR
i m a g e s before a n d/or after
1 896 I
PART
15
TH E U PPER D I G ESTIVE TRACT
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563-9.
147 Non-neoplastic sa I iva ry 9 la nd diseases
STEPHEN R PORTER
Introduction
1898
Best clinical practice
1905
Congenital salivary gland disease
1899
Other inflammatory disorders
1906
Key points
1899
Drug-associated salivary gland disease
1906
Infections of the salivary gland
1899
Key points
1907
Key points
1900
Sialosis
1907
HIV salivary gland disease
1900
Bulimia nervosa
1908 1908
Key points
1901
Pneumoparotitis (pneumosialadenitis, wind parotitis)
Best clinical practice
1901
Key points
1908
Hepatitis C virus infection
1901
Some disorders associated with xerostomia
1908
Suppurative sialadenitis (su ppurative parotitis)
1901
Key points
1909
Key points
1902
Best clinical practice
1909 1909
Best clinical practice
1902
Sjogren syndrome
Chronic non-specific sialadenitis
1903
Key points
1913
Key points
1903
Best clinical practice
1914
Best clinical practice
1903
Lymphoepithelial lesion
1914
Miculicz's disease and Miculicz syndrome
1914
1904
Excess salivation (sialorrhoea)
1914
Key points
1904
Key points
1914
Best clinical practice
1904
Best clinical practice
1914
Chronic sclerosing sialaden itis (Kuttner tumour)
1904
Some minor salivary gland disorders
1915
Xanthogranulamatous sialadenitis
1904
Deficiencies in current knowledge and areas for future
Recurrent parotitis of childhood Ouvenile recurrent parotitis)
Sia 101ithiasis
1904
Key points
1905
1916
research
1916
References
A literature search was performed using Medline, including the following search terms: non-neoplastic salivary disorders
and benign salivary disorders, as well as all the main subject headings. A few earlier references are included where they are
pertinent and only the relevant references have been cited.
INTRODUCTION
syndrome and drug-induced xerostomia.
A wide range of non-neoplastic disorders of the salivary
glands can arise
(Table 147.1)
although the more com
mon are mumps) acute suppurative sialadenitis, Sjogren
provides
an
overview
of
This chapter
non-neoplasti c disorders
of
the salivary glands) but also focusses on the common disorders . likely
to be
otorhinolaryngology.
of
relevance
to
specialists
of
Chapter Table 147.1
I
Xerostomia
Swelling
I
'
,'
�-
,
Drug-induced
Mumps Recurrent parotitis of childhood
Irradiation damage
Acute suppurative sialadenitis
HIV infection
Sarcoidosis
HCV disease
Chronic sialadentitis
BMT/GVHD
Sjogren syndrome
Cystic fibrosis
Sialosis
Amyloidosis
Pneumoparotitis
Sarcoidosis
Depression
bone marrow transplantation;
GVHD, graft-versus-host
disease;
HCV,
virus.
itt ·parncul;r.i �cqmi ap.p"ara·tus.. .x
�
. s�ij-Y�w ':gi�m-d.�I. foP.o,�s �that-of: x:et:ostqmia due · · '. 'to SJ6gre:nls' syndrome:l� -;
.
."
infections are the most common of the salivary glands, although very rarely other infectious agents can be involved. In addition, the salivary glands may be the site of asymptomatic viral infect.ion - particularly some of the herpes group (e.g. human herpesvirus 6, cytomegalovirus and perhaps disorders
of
8 (HHV-8)), while saliva can be a
for a wide range of infectious agents including hepatitis B virus, hepatitis C virus, HHV-8 and human vehicle
immunodeficiency virus.2,
3
than
of the salivary glands.
Of note, xerostomia is more likely with viral (e.g. hepatitis C virus and human immunodeficiency virus)
Salivary gland agenesis the major salivary glands is
extremely uncommon. There can be variation in the number of absent salivary glands and hence the degree of associated xerostomia, dysarthria and/or dysphagia varies accordingly. Lack of saliva predisposes to dental caries, gingival disease, candidosis and acute infective sialadeni tis, although in children rampant dental caries may
bacterial
infections that
The precise incidence of major salivary gland agenesis is difficult to establish due to the asymptoma tic nature of many affected individuals. A recent review suggested that there is a male to female ratio of 2: 1 of affected
infection can arise
in Table 147.2; however, as some of these are rare and/or have no specific salivary gland features, the present discu ssion will centre upon the more common
infections
Table
of the salivary glands.
147.2
Infections of the salivary glands. �,'
" ;<_-�": UncorTlI�'oil·; ,;. '
:.-
Salivary gland aplasia may occur in isolation or be associated with other ectodermal defects,
in particular
lacrimal apparatus abnormalities. Associations with hypo hidrotic ectodermal dysplasia,
lacnmal-auriculo-dento
ectodactyly-ectodermal
dysplasia-collecting
syndromes have been reported.
�-
�
'••
, j'.
\
>
' , .:, : '
, -., .
.. ..
glands follows that of xerostomia due to
Sjogren syndrome. 1
Mumps
Epstein-Barr virus (EBV)
Human immunodeficiency virus
Cytomegalovirus (CMV)
(HTLV-1)
associated salivary gland disease Hepatitis C virus-associated sialadenitis
Mycobacterium tuberculosis Non-tuberculous mycobacteria Arachna sp. Haemop hilus influenzae Treponema pallidum EikeneJla corrodens BartoneJla henselae CaffJdya anaerobia
KEY- POINTS e
La�k
Actinomycosis israeli;
" ' of saliva predisposes to de�tal ca�ies;
girigivai diseas�l candidosis and acute infective sialadeni tis,
although in
rampant dental caries
m�y
sign of underlying salivary
_
children be the 'only initial
ageri�sk
J...
Human T-Iymphocytic virus 1
Escherichia coli
The management of children with absence of salivary
"
Acute suppurative sialadenitis
individuals. Familial clustering of salivary gland agenesis has occasionally been reported.
The
in the salivary glands are
summarized
be the
initial sign of underlying salivary agenesis.
and
,
.. ��no..uh�lities. · Jhe ::� �.fl�g t:;mept� �f�htidreh:. -'-\rj t lt .abs'ep:ce of
human herpesvirus
CONGENITAL SALIVARY GLAND DISEASE
digital
m�Y'6"ccur in 'isolation
Viral and bacterial
Hyprochondriasis
only
•
�.e�fe'�t�)
infectious
Salivary gland agenesis
Agenesis of one or more
q.pl�:sia
1899
INFECTIONS OF THE SALIVARY GLAND
Dehydration (various causes)
C
SalivaTY gland
·.r or' De· ·associi.ted %ih'·other' ectodermal
,�.
,,�
Sjogren syndrome
BMT,
�'.
.'
. Symptom
hepatitis
- e.
Non-neoplastic disorders of the salivary glands. . , .;
147 Non-neoplastic salivary gland diseases I
Actinomycosis eriksonii Samonello enteritidis Salmonella cho/eraesuis Histoplasma sp. Candida sp. Cysticercosi S
1900
I
PART
15 THE LIPPER DIGESTIVE TRACT
lympha,denopathy andtarely sublingual
Mumps (epidemic parotitis)
sweUing,·-·',
Mumps is an acute generalized paramyxovirus infection
,.
of children and young adults. Mumps typically affects the structures
can
occur
including
the
pancreas,
afteripptdXiriiat�lyfourtofiv�
•
major salivary glands, although involvement of other
: tosiiminjsb.
MUmps'saliyaryswelling tends
d�Ys
.
"
�' '-',
.
Serious andIlotin#equent mlllllps , complications include orchitis and viral
testes,
ovaries, brain, breasts, liver, joints and heart.4 Mumps is transmitted via the droplet route and has an
incubation time of approximately 14-18 days. Patients present with initial pyrexia, chills and facial pain. The
parotids are typically bilaterally enlarged, although this may initially be unilateral. There is often swelling of the submandibular glands together with lymphadenopathy, giving rise to profound facial and neck swelling. Rarely,
sublingual swelling may be so profound as to cause elevation of the tongue and dysphagia and dysarthria. The salivary swelling tends to diminish after approximately four to five days and may precede more complicated aspects of the illness. Orchitis may develop approximately four to five days
HIV SALIVARY GLAND DISEASE Salivary gland disease can arise in 4-8 percent of adults and children with HIV infection. The principal clinical features are detailed in
Table 147.3. A variety of lesions
can underlie the salivary gland disease of HN infection and include bacterial sialadenitis, intraparotid lymphade nopathy, primary or metastatic non-Hodgkin's lympho ma or Kaposi's sarcoma.3 HIV
salivary
gland
involvement. Orchitis tends to arise in post-pubertal
are most frequently affected, often with profound bilateral
though
occasionally
there
can
be
bilateral
boys and rarely gives rise to serious long-standing disease. Mumps can give rise
to a lymphocytic or
viral
meningitis. This again commences a few days after the development of parotitis, although can occur in the absence of salivary gland disease. Other neurological manifestations include retrobulbar neuritis and encepha litis. Deafness is possible, but rare. Pancreatic infection may give rise to mild upper abdominal pain, but acute and long-term complications are unusual. Likewise, while cardiac, hepatic and joint infection can occur, they are rare and do not generally cause notable complications. The diagnosis of mumps is typically based upon the clinical
picture;
however,
it
may
detection of viral-specific IgG and
be
19A.
confirmed
by
Viral culture is
possible, but generally unnecessary as serological methods are highly sensitive. There is no specific treatment for mumps, analgesia and appropriate fluid intake being the mainstays of therapy. It has been suggested that corticosteroids may be effective for severe parotitis, but generally these are not
required unless the patients have other systemic symp toms, such as orchitis.
Mumps can generally be prevented with appropriate vaccination (mumps/measles/rubella (MMR». The asso ciation of MMR vaccination with inflammatory bowel disease and childhood autism seems unlikely. 5
recurrent
•
major
enlargement. Salivary gland disease tends to arise in late HIV infection, although occasionally can be the first manifestation. An increased male to female ratio of involvement has been reported, but this probably reflects the
epidemiology
of
the
patients
that
have
been
previously reported. HIV salivary gland disease may be associated
with
HLA-DRS,
and
is
part
of
a
more
generalized disorder termed diffuse infiltrated lymphocy tosis syndrome (DILS) characterized by CD8 +
T-cell
infiltration of the lungs, salivary glands and lacrimal glands.3 The clinical picture mimics that of Sjogren syndrome; however, there are distinct histopathological and serolo gical differences between the two disorders. Patients with HIV disease generally do not have anti-Ro or anti-La antibodies - but do have hypergammaglobulinaemia. The minor salivary gland histopathology is generally similar to that of Sjogren syndrome, being dominated by perivas cular, periacinar and periductal lymphocytic infiltrates, however, the majority of the infiltrating T cells are CD8 + Multicystic
lymphoepithelial
lesions
may also
.
occur,
although cystic change can also arise following intra glandular ductal obstruction by hyperplastic lymphoid tissue.
Table
147.3
Salivary gland disease in HIV infection.
CIinic(!I
feature
HIV salivary gland disease
Xerostomia
Kaposi's sarcoma
Salivary gland enlargement
Mumps presents with initial pyrexia, facial
Non-Hodgkin's lymphoma
submandibular glands, together with
Acute suppurative sialadenitis
pain, enlarged parotid glands, swelling of the
persistent
salivary gland enlargement and xerostomia. The parotids
Disease KEY POINTS
and/or
disorder
characterized
affected,
by
disease is a distinct
after the onset of parotitis, typically only one testicle is
Lymphadenqpathy
Chapter 147
Non-neoplastic salivary gland diseases I 1901
The diagnosis of HIV disease is similar to that of
Xerostomia is the predominant symptom of HCV
Sjogren syndrome. Fine needle aspiration biopsy may
associated salivary gland disease. L L Objective evidence of
be particularly useful as it allows rapid exclusion of 6
mal'Ignancy. There
is
reduced unstimulated whole sialometry has been ob
served little
information
regarding
the
specific
management of the condition. Clinical signs are usually non-progressive and hence therapy is only indicated if
in
13-33
percent,
although
some groups
of
patients with HCV disease seem to have normal salivary
flow rates - despite the presence of HCV T he
histopathological
features
of
in saliva.11
HCV-associated
xerostomia.
sialadentitis are similar, but not identical to those of
Antiretroviral therapy (ART) may cause at least some
Sjogren syndrome. In particular, there is a pericapillary
short-term resolution of the swelling. Other, less practical,
lymphocytic infiltrate within the salivary glands.
there
is
notable
cosmetic
deformity
or
suggested therapies are repeated aspiration, tetracycline sclerosis or surgical removal of an enlarged gland.7 External radiation (e.g.
8-10 Gy) can cause transient
Transgenic
mice
expressing
HCV
genes
develop
sialadenitis, thus confirming the notion that HCV gives rise to salivary gland disease.12 Nevertheless, the precise
improvement, although higher doses (e.g. 24 Gy) can
pathogenesis
cause resolution of disease for at least 24 months -
remains unclear, although susceptibility to HCV-related
without causing severe xerostomia.8
Xerostomia independent of salivary gland involvement
of
HCV-related
salivary
gland
disease
non-hepatic disease may be associated with a particular HLA haplotype.
may arise in HIV infection as a consequence of some
HCV infection may occasionally give rise to non
nucleoside analogue HIV reverse transcriptase inhibitors
Hodgkin's lymphoma and salivary disease akin to that
or protease inhibitors (see Xerostomia),9
of Sjogren syndrome, but there is no evidence to suggest that Sjogren syndrome is related to hepatitis C virus - -.;
•
HIV sahvary gland
disease,
a
SUPPURATIVE SIALADENITIS (SUPPURATIVE PAROTITIS)
distinc.t
disorder, characterizt:d by recurrent or persistent major
-: --: ��s'll�l�¥.;,;?f:;:the paf�t;4�X�ar}4 ;:�erost o m i a , � n
-
•
saJivary gland enlargement, <
Clinicaily, it
-
-
'"
infection. 13
-
Clinical features
-
munics Sjogren syndrome, but
there are serolQgicaJ and histological
differences.
Acute suppurative sialadenitis is an uncommon disorder characterized by painful swelling - usually of the parotid glands (suppurative parotitis), purulent discharge from the duct of the affected gland
(Figure 147.1), associated
.I
Treatment is indicated for notable cosmetic deformity or xerostomia. .I Antiretroviral therapy may cause some short-term resolution of the swelling. ./' O ther therapies are repeated aspiration, tetracycline sclerosis or surgical removal of an enlarged gland.7 .I External radiation (e.g. 8-10 Gy) may offer some benefit.s
HEPATITIS C VIRUS INFECTION Unlike the other hepatotropic hepatitis viruses, hepatitis
C virus (HCV) frequently gives rise to a wide spectrum of extrahepatic manifestations that include salivary gland disease. Hepatitis C virus-associated salivary gland disease arises in perhaps as many as 80 percent of infected patients.
10
Figure 147.1 Purulent discharge from the parotid duct in acute suppurative parotitis .
1902
I PART 15 THE UPPER DIGESTIVE TRACT
dysgeusia and cervical lymphadenopathy. When disease is
Complications
severe, there may be accompanying pyrexia, malaise and a risk of abscess formation and parapharyngeal
space
There is a risk of abscess formation as a consequence of
Acute suppurative sialadenitis can affect children and
likely with submandibular gland infection) or infection of
infection - including Ludwigs angina. adults. Prematurity may be a risk factor for disease
in
childhood, and sialadenitis can occur in newborns.14 The highest incidence of childhood disease seems to arise in children aged three to six years of age.IS Of interest, an aseptic sialadenitis has been observed in preterm children who are receiving long-term orogastric tube feeding. Immunodeficiency and concurrent illness may predispose to childhood
suppurative
parotitis.
In
adults,
long
standing xerostomia (e.g. Sjogren syndrome) and radio therapy-induced xerostomia are the most likely risk factors, although other predisposing factors may include poor oral hygiene, diabetes mellitus, HIV disease and the use of total parenteral nutrition. Ductal obstruction (e.g. sialolithiasis, malignancy or foreign bodies) and infection as a consequence of bacteraemia 16 may also predispose to acute suppurative sialadenitis. Coprophagia gave rise to recurrent
submandibular
sialadenitis
in one patient.
Rarely, infection may be acquired nosocomiaily.17 The causative organism of acute suppurative sialade nitis is often not found; however, facultative anaerobes, particularly Staphylococcus aureus and Streptococcus 18 viridans • 19 have frequently been reported to be of aetiological significance. In addition, Klebsiella and strict
duct ectasis, primary parenchymal involvement (most subcapsular lymph nodes.Is Parapharyngeal space infec tion and Ludwig's angina are also possible and, rarely, mediastinitis.22
Therapy Effective hydration and antibiotics are the mainstays of therapy of uncomplicated acute suppurative sialadenitis.23 Typically
employed antibiotics are anti-staphylococcal
penicillins (e.g. flucloxacillin, amoxycillin or Augmentin), cephalosporins
or
clindamycin,
although
the
precise
choice of antibiotic will often depend upon any likely causative organism that is identified. Other alternatives may
include
flurithromycin.
Intraductal
injection
Surgical drainage should of clinical
be considered if there is a lack
improvement after three to
five days of
antibiotic therapy, any (unlikely) facial nerve involve ment, any involvement of deep fascial spaces, or abscess formation within the parenchyma of the gland?3 Super ficial parotidectomy may be required if disease becomes 23,24
recurrent or chronic.
anaerobes such as bacteroides spp, Fusobacterium
nucle atum and Peptostreptococcus anaerobius have been isolated from
pus samples and may
thus be of aetiological
significance. The diagnosis of acute suppurative sialadenitis is usually straightforward - being based upon the history and clinical picture. Microbiological culture of pus, under both aerobic and anaerobic conditions, may reveal the causative agents, although specific relevant tests may be useful if a particular infection seems likely. The benefits of sialography for the diagnosis of acute suppurative sialadenitis remain unclear. Some authorities suggest that such investigation is contraindicated (prob ably when there is notable disease), while others suggest that it may resolve any causative ductal stricture.IS
KEY POINTS Acute suppurative sialadeni,tis presents with painful sweUing- usuaHy of the paroti.d gl-ands (suppurative p�roti,ti$), purulent discharge from the duct of the affected gland. dysgeusia, cervical lymphadenopathy, pvrexia, :. ;: ."'.. maJaise, pa r a pha rynge al abscess, as well as :� : Ludwig's angina in severe cases. ::�. �: Acute suppurative sialadenitis usually affects '.' . adults, although children may rarely be '. ,�" affected. •
Sialography may reveal areas of ductal stricture and sialectasis, the latter being most likely with recurrent disease. Scintiscanning is generally unhelpful, but may
sometimes reveal the underlying cause (e.g. poor salivary gland function). Ultrasound scanning can be useful, particularly if abscess formation is likely, as can magnetic resonance imaging.
There have been rare reports of acute sialadenitis associated with primary Mycobacterium ,tuberculosis, pre ex.isting
Mycobacterium
t u b erc ulos is and non-tuberculous
mycobacterial infection. Other rare infections have in 20 2I cluded Salmonella Sp.16 and Neisseria meningitidis. •
Table
147.2 indicates other possible bacterial infections of
the salivary glands.
of
antibiotics is unlikely to be of practical benefit.
Best clinical practice ./ The diagnosis of acute suppurative sialadenitis is primarily clinical. Mi crobiological culture of pus, under aerobic and anaerobic conditions may occaSionally be 'helpful.
.I The benefits of sialography for the diagnosis of acute suppurative sialadenitis remain unclear. It is probably contraindicated when there is active infection, but it may resolve any causative ductal stricture.1s It may reveal areas of ductal stricture and sial ectasis.
Chapter 147 Non-neoplastic salivary gland diseases
.I Scintiscanning is generally unhelpful, but may sometimes reveal the underlying cause (e.g. poor salivary gland function).
.I Ultrasound and magnetic resonance imaging can be useful, if abscess formation is suspected.
.I Effective hydration and antibiotics are the mainstays of therapy of uncomplicated acute suppurative 23 sialadenitis. Typical antibiotics may include flucloxacillin, amoxycillin (or Augmentin), cephalosporins or clindamycin.
.I Surgical drainage should be considered if there is a lack of clinical improvement after three to five days of antibiotics, facial nerve involvement, deep fascial space involvement, or abscess formation within the parenchyma of the gland?3 Superficial parotidectomy may be required if disease becomes recurrent or chronic.23. 24
CHRONIC NON-SPECIFIC SIALADENITIS Chronic non-specific sial adenitis is an uncommon disorder, usually of adulthood, characterized by recurrent andlor persistent enlargement of usually one major salivary gland. The parotids are more commonly affected than the submandibular glands. 25 Patients can have episodes of disease akin to acute suppurative sialadenitis. Affected patients are generally well and have no disease likely to cause sial adenitis (see under Sialolithiasis below), although they may have a history of recurrent parotitis of childhood or previous sialolithiasis. In most instances, chronic non-specific sialadenitis reflects abnormalities of the ductal system - the recurrent infection having caused or worsened any ductal strictures. Likely primary causes of this disorder are small sialoliths and, less commonly, external pressure and resultant ductal defects due to dentures,26 congenital ductal defects or radiotherapy-induced salivary gland damage. The strictures have a damming action, causing salivary stasis and liability to infection with resultant chronic, and possibly acute, inflammation. The investigation of chronic non-specific sialadenitis is similar to that of acute suppurative sialadenitis, although often microbiological examination of saliva will be unhelpful. Sialochemistry is not helpful. Sialography or ultrasonic scanning are the principal investigation methods of chronic non-specific sialadenitis. Sialography will almost always reveal strictures andlor associated distortion of the major ducts, although there can also be variable sialectasis. Computed tomography may reveal small causative sialoliths. Chronic non-specific sialadenitis has no specific histopathological features, although there may be duct dilatation (sometimes with squamous metaplasia), acinar atrophy, interstitial fibrosis and a periductal inflammatory infiltrate comprised predominantly of lymphocytes and sometimes plasma cells and eosinophils.
I 1903
The clinical course of the chronic non-specific sialadenitis is highly varied, about 50 percent of patients have eventual spontaneous resolution of symptoms after up to five years, but as many as 40 percent will have symptoms that warrant surgical intervention. 27 Although there is a recent report of parotid duct carcinoma arising within chronic sialadenitis,28 chronic non-specific sialadenitis does not have any notable malignant potential. The management of acute infection associated with chronic non-specific sial adenitis follows that of acute suppurative disease. In addition, sialagogues such as chewing gum, duct and glandular massage, improved oral hygiene and therapeutic sialography have been suggested to be useful, but there are no supporting data. 29 Unless the cause is likely to be a sialolith, subtotal or total surgical removal of the affected gland may be the only useful treatment,z4, 25, 30
KEY POINTS .' .C3~f:0nicnon-sp~cificsialadenitis ism lf~~~~mondisorder, usually of adulthood, Fh~r~cteriz~dcbl'l'ecurrentand/or. ~ersistent
·. ~~~~gement?f usu~llrone.major .salivary glal1a.;!hepar()ti~s.a~Tmore '90mIl1()n1y
affect.~~.th~n.thesubl11~l1dib~larc.~lands. ..Patients 9~llhaveepis9desakintoacute sl1ppurative.si~~deJ.1itis,·. but affected individ~als are'· 'o/ellandhave no systemic q.isease .·.likely.tocause;sialadenitis, although th~Y11layhave . ~ •. history of.recurrentparotitis ofch~
Investigations might include sialography, ultrasound to detect a collection or computed tomography scanning to delineate calculi. Treat acute episodes as for acute suppurative sialoadenits with hydration and appropriate antibiotics. Sialogogues, glandular massage and improved oral hygiene and therapeutic sialography seem logical, but there is no supporting evidence. Subtotal or total gland removal may be the only useful treatment for the chronic, non-infected state unless calculi can be identified.
1904
I PART 15 THE UPPER DIGESTIVE TRACT
RECURRENT PAROTITIS OF CHILDHOOD (JUVENILE RECURRENT PAROTITIS)
Recurrent parotitis of childhood is characterized by recurrent parotid inflammation usually associated with non-obstructive sialectasis of the parotid gland. Recurrent parotitis can arise at any age, but the usual age of onset is three to six years. Childhood onset disease is usually more common in males, but interestingly, adult onset disease normally arises in females. The disease is characterized by localized pain and swelling that may last up to 14 days. Fever and overlying erythema are common, and occasionally white mucopus can be expressed from the parotid duct. Recurrent parotitis of childhood tends to be unilateral rather than bilateral. The number of attacks vary from one to five per year, but some patients may have up to 20 episodes of swelling per year. The frequency of recurrence tends to peak between five and seven years of age, and up to 90 percent of patients have resolution of disease by puberty. Sialography and ultrasonic scans reveal sialectasis. Of note, this feature can also be observed in the non-affected glands of the opposite side. The precise aetiology of recurrent parotitis remains unclear, but certainly almost all affected patients are otherwise welL There is no evidence that viral infection underlies this disorder. Analgesia is the mainstay of therapy. Antibiotics do not shorten attacks. In general, the disease tends to resolve and there is no need for surgical intervention.31
Best clinical practice -
./ AnalgeSia IS the mainstay of therapy. Antibiotics do not shorten attacks. In general, the disease tends to resolve and there is no need for surgical intervention.
CHRONIC SCLEROSING SIALADENITIS (KUTINER TUMOUR)
Chronic sclerosing sialadenitis is a rare chronic inflam matory disorder of adults. The submandibular gland is commonly affected, although the parotids, sublingual glands and minor salivary glands can occasionally be affected. The disease manifests itself as a long-standing and generally asymptomatic swelling. The aetiology of chronic sclerosing sialadenitis is not known, although sialolith-induced salivary statis is most likely. The histopathology of chronic sclerosing sialadenitis includes a notable lymphocytic infiltrate, lymphoid follicle forma tion and extensive fibrosis with cirrhosis. 32. 33 There is a report of chronic sclerosing sialadenitis in a patient with idiopathic retroperitoneal fibrosis, suggesting perhaps that occasionally the salivary gland disease may have a similar (but unknown) aetiology as retroperitoneal fibrosis.34 The investigation of chronic sclerosing sialadenitis is similar to that of salivary gland malignancy. Surgical excision is the treatment of choice. XANTHOGRANULAMATOUS SIALADENITIS
I
•
�
Re irre:nt patotltis of childhood is -'--chanict�riied by- recurrent --l.1Ililate�al parotid infla�matibn usually associated with - -non-obstructive sialectasis of the parotid
. •
q
)"� ��f:��ai��c��;�f�nsetiS' thre�.t�;iJt'· - years The nu�ber' of attackS vari from- one to five per year, but up to 20 episodes may occur per year. The frequency of recurrence peaks between the ages of five and seven, and up to 90 percent of patients have resolution of disease by puberty. The dis�ase is characterized by localized pain and swelling that may last up to 14 days. -Fever and overlying erythema are common and occasionally white mucopus can be-expressed from the parotid . duct. .
Xanthogranulamatous sialadenitis is a very rare disorder manifesting itself as a solitary swelling within a major salivary gland.35 The investigation of this disorder is similar to that of a salivary gland malignancy. It has been suggested that xanthogranulamatous sialadenitis may reflect underlying non-Hodgkin's lymphoma,35 but there are few good data on this most rare disorder.
,
-
,
c·
es
.
SIALOLITHIASIS
.
•
Clinical features
Sialolithiasis is a common disorder characterized by the formation of a calculus (sialolith) usually within the ductal system of a gland. Sialoliths can arise in both the major and minor salivary glands - indeed a necropsy study revealed 1 percent of patients to have salivary calculi, although only a minority of patients develop sialolithia'sis.36 Sialoliths are more common in the sub mandibular glands (e.g. 83 percent of one sample) than
1905
Chapter 147 Non-neoplastic salivary gland diseases I
the
parotid
(10 percent) or sublingual (7 percent)
glands)37 are more common in females than males and
are much more likely in adults than in children.
Sialolithiasis presents as pain and swelling, typically
in the submandibular gland with gustation or eating.
remained
symptom-free up to
lithotripsy therapy,4S while
71
71
months following
percent of a second group
of patients reported no symptoms up to
96
piezo-electric lithotripsy. 46
months after
Lithotripsy can be undertaken without general anaes
The swelling is diffuse, develops rapidly and is often
thesia and adverse effects
generally non-tender and gradually resolves over a few
telangectasia and haemorrhage.47
suppurative sialadenitis or chronic non-specific sialade
ven to be of clinical relevance in the diagnosis and
associated with a burning-like local pain. The swelling is hours. Long-standing sialolithiasis may give rise to acute nitis (see under Chronic non-specific sialadenitis above).
The cause of sialolith formation remains unknown,
although it is suggested that development reflects a defect
of migration of autophagosomes through the ductal
system, or the calcification of mucous plugs.38,39 The
are minor and transient,
comprising mild local pain and swelling) cutaneous Endoscopic methods (sialoendoscopy) have also pro
treatment
of
sialolithiasis;48,49
indeed
. combined with lithotripsy. In a series of
this
154
can
procedures, it was possible to remove 82 percent of the calculi without notable complication, in addition sialo
dendoscopy was able to detect and remove radiolucent
calculi are composed of both organic and non-organic
sialoliths from the parotid, submandibular or sublingual
Calcium phosphate is the predominant salt of the calculi,
tion of stenotic ducts may also be possible,49 although
It is suggested that sialoliths may be associated with
technique for chronic sialadenitis.
material, the central medulla being the more organic. laid down as concentric shells of about diabetes
mellitus,
hypertension
10 � thickness.39
and/or
chronic
liver
glands.49 Sialoendoscopy with subsequent balloon dila
there remain no studies of the long-term benefits of this
disease and possibly nephrolithiasis,40 but not to water hardness.39
KEY
Investigations
• ..
i
Plain radiographs may reveal a sialolith - provided it is
large and radiopaque - however, as many as 30 percent of
•
sialoliths, particularly of the parotid glands, are radio
submandibular and sublingual glands. Panoral tomo
grams are not helpful in view of their tomographic
Sialolithiasis is a co.mmon disorder du·e to . formation of calculi "(sialoliths)", usually within · the ducta} 'system of a gland.
-Sialoliths are more common in the
sample)
than the parotid
sublingual
and radiolucent sialoliths) while sialography may also be
helpful, although technically difficult when examining the
�OINTS
.
. submandibular glands (e.g. 83 percent of one
lucent. Ultrasonic scanning can detect both radiopaque
(7
(10
percent) or
percent) glands/7 are more
( common in females than males and are much
. -.more.li; ' ' - �.,rrSialqlithiasis� res:erifs. ·�s
p
pijrt and, sw�llirig;:'
,"�.
typically in the submandibular glimd with
nature, although computed tomography and possibly
gustation or eating. The non-tender swellin:g'
magnetic resonance imaging may be of some benefit.
is 'diffuse, develops rapidly, is often assoCiat.ed
wIth a burning-like local pain and resolves over a few hours..
Treatment •
When small and accessible, it may be possible to express a sialolith
from
the
submandibular
palpation, and many sialoliths
can
duct
by
manual
Long-standing sialolithiasis may give rise to
acute suppurative sialadenitis or chrO'l'lic; non
specific sialadenitis� "
also be simply removed
surgically - if within the anterior segment of the . submandibular duct. This does) however, carry a risk of stricture fonnation.41 Surgical removal of an affected
gland may often be the only effective treatment for calculi 2 in the posterior aspect of the duct or within the gland.36, 4 In the past ten years, non-surgical piezo-electric,
electromagnetic, electrostatic or laser lithotripsy have
proven to be an effective means of removing salivary calculi. Lithotripsy may be aided by fluoroscopically
Lo
guided
basket
retrieval
of
fragments43
or
when the calculi are less than ng_term study found that
76
7 rom in
./ Investigations include plain radiographs, ultrasound, sialography and occasionally computed tomography scanning.
.! When small and accessible, manual expression of
a
possibly
stone' from the submandibular duct is often feasible.
diameter.44 One
the anterior segment of the submandibular duct, but
sialoendoscopy. Lithotripsy seems to be most effective
i
be
endoscopic
percent of treated patients
and many can also be removed surgically - if within this carries a risk of stricture formation.
1906
• PART 15 THE UPPER DIGESTIVE TRACT
DRUG-ASSOCIATED SALIVARY GLAND DISEASE
.I Surgical removal of an affected gland may often be the only effective treatment for calculi in the posterior aspect of the duct or within the
A wide range of drug-related salivary disorders can arise.
gland.
These predominantly compr ise swelling, xerostomia and
.I Lithotripsy may be aided by fluoroscopically guided
p ain (Table 147.4).53
basket retrieval of fragments or possibly sialoendoscopy. Lithotripsy is most effective for calculi less than 7 mm in diameter. Seventy-six percent of treated patients remained symptom-free
Salivary gland swelling
up to 71 months after lithotripsy therapy,45 while 71 percent of a second group of patients reported no
Painless, usually bilateral, salivary gland enlargement may
symptoms up to 96 months after piezo-electric
be an occasional side effect of phenylbutazone, clozapine,
lithotripsy.46
sulphadiazine,
cytosine
arabinoside
or
chlorhexidine.
Bilateral sialadenitis observed in one adult following naproxen therapy was thought to be allergic in origin as the affected patient also had a cutaneous rash. Recently, dozapine, a novel antipsychotic agent, was found to give
OTHER INFLAMMATORY DISORDERS
rise to transient salivary gland swelling. Mild acute sialadenitis
Chronic sarcoidosis can give rise to xerostomia and
(sometimes termed 'iodide
mumps') can arise in response to iodine-based contrast
salivary gland enlargement in up to 9 percent of affected
media (e.g. for angioplasty). This disorder tends to be
patients, this often occurring as part of Heertford's
transient. R adioactive iodine, used for the treatment of
syndrome.5o Repor t s of Crohn's disease affecting the
thyroid cancer, can cause transient sialadenitis, indeed
minor salivary glands51 are probably
sialadenitis is the most frequent non-thyroid complica
unexpected;
in
view of the widespread nature of oral lesions of the
tion
disorder,
however,
manifests itself as tran sient xerostomia and unilateral
seems to
be rare. Major salivary gland enlargement due
involvement of the major glands
or
of radioactive bilateral
salivary
iodine gland
therapy.
This
enlargement,
sialadenitis the
parotid
to Wegener's granulomatosis52 has been reported, but is
being
extremely rare.
develop wit h i n 24 hours of iodine therapy and resolve
Table 147.4
particularly
affected.54
The
cl i nical
Salivary gland manifestations of drug therapy. Salivary gland swelling,
' .;�jijgren
syndrome
Salivary gland pain
Sariva colourtd red
Atropine a nd analogues (antimuscarinics)
Anti-thyroid agents
Hydralazine
Bethanidine
Rifabutin
Tricyclic antidepressants
Chlorhexidi ne
levamisole
Bretylium
Rifampicin
Serotonin reuptake inhibitors (SRI)
Cimetidine
Practolol
Clonidine
Antihistamines
Clonidine
Procainamide
Cytotoxics
Antiemetics
GangIion-blocking
Sucralfate
Guanethidine
TranquiIIizers (antipsychotics)
insulin
Decongestants
Interferon
agents
Bronchodilators
Iodides
Appetite suppressants
Isoprenaline
Amphetamines
Methyldopa
Lithium
Nicardipine
Omeprazole
Nifedipine
H IV protease inh ibitors
N itrofurantoin
Disopyramide
Oxyphen butazone
Dideoxyinosine Didanosine
Phenothiazines . Phenylbutazone
Diuretics
Ritodrine
Interleukin-2
SuIphonamides
Retinoids O thers
features
Methyldopa
1907
Chapter 147 Non-neap lastic salivary 9 land diseases I
within a week, although occasionally they may
persis t
and cause permanent loss of function of one or more
gland.
The risk of radioactive
can
the
iodine-induced sial adenitis
be reduced by the use of lemon confectionery increased
salivary
flow
the
increasing
speed
of
carriage of radioactive iodine through the glands and hence reducing the extent of glandular radiation ex
posure. A detailed description of the impact of radio
active iodine upon the salivary glands can be found 54 elsewhere. s
Sialadenitis due to deposition of gold salts caused
alivary gland swelling in one patient.55
-
, --
-
,
"
-.I.,
-':.- Sa 1i���j�!���'d,_s��f1:iOg"-:- : - r._� /� ' � � ,
-,
-
. ". Mn�k�t;-��si�nt\ lJi:laH�Ial, -�a'h-il�ss-: sialadeniti�" '," -( may_ 'foUo�,' ph�rtylbut¥one; d�lorhexidine, , " ' :' \ -, ..� '- iodine-and". radio a<;:t �ve - iodmeusage.
:
.
"
--
-
.. .x,ero�tornia
500 drugs -can caus e .dry' mouth, but the
-; _ -,�,: 'Over,-.
> :_'-·'piin c-ipaJ me�han.i!sm o f- action to. cause
-' -'xerostomia 'is -antkholinergic and synlpath��)�imetic.
T�€refoFe,- tricy;dics,
benzodiaiepines; a t ropinics betablockers and ,
an�aniines ar�- �he Xerostomia
n
complaint of many elderly
people,56 probably as a consequence of a large number of
500) that can caus e xerostomia and the high
frequency of polyph armacy in the el derly. The principal
mechanisms of drug-induced xerostomia reflect anti
cholinergic or sympathomimetic actions, hence the drugs
most commonly implicated in xerostomia are tricyclic
ant idepressants benzodiazopines , atrop i nics beta block ers and
.
Salivary gland pain
Dry mouth is a commo drugs (over
most common culprits
,
antihistamines,
and thus
,
it is
common in
•
Salivary gland
due to sia losis '
'
,
.
, t ..
patients treated for hypertensive or mental illness
(Table 147.4).53 Wh ile often promoted as having less anti chol inergi c actions than the tri cyclics the selective serotonin reuptake inhibitors (SSRI) s till cause some dry mouth. Some other newer drug therapies in
e nlarg, enient
be asso cia te d with diabetes, hypothyroidism, malnutrition, hepatic cirrhosis. puberty, menopaus�, an,d ," i alltihyp,e_rte�siye medicatlqri. .' " ' • Treatrli'e'.nt�'is' ; ;:Q ften difficult with;'eildciq:ine ' . ' ,. . : e '. I ' .'. . ' and n;�;;ttI.s�- A�uses of. sia�osj's� beiti�.'", )".�' par �_iaUlat1y .:reSistrlUt, �ven- -if. {h'e :tihdetf0ng" . , ' : ! , " , ,.,; I >?2 - ':-q�sorde! -is - addtess-ed may
,
cluding omeprazole, anti-HIV protease inhibitors, the nucleoside ana logue HN reverse transcriptase inh ibitor didanosine,
trospium chloride,
eUiptinium,
and new generation antihistamines may induced xerostomia.53 Some
drugs
syndrome-like
can
give
rise
to
tramadol
all cause drug
primary
Sjogren
disease, including hydr al azine, busulfan,
quinidine sulphate and thiobendazole. However, this clini ca l
disease can be trans ient. In addition, affected high levels of immunological markers of Sjogren syndrome hence it seems unlikely patients may not have that this is true Sjogren
-
syndrome. 57
SIALOSIS Sialosis is an uncommon non-neoplas t ic and non inflammatory disorder giv ing rise to bil ater al non-painful enlargement of the major s al ivary glands. Sialosis tends to
arise in mid dl e to late life with peak incidence in the fifth
and sixth decades There is a sligh t female .
enlargemen t is
pro found (Figure 147.2). The enlargement
develops slowly and there may be some decrease in
s al ivary flow.
Altho ugh the precise aetiology is unknown, the under
lying patho genesis is thou ght to reflect a neuropathy.
t
There are disease associations with diabetes melli us
,- Salivary gland pain Salivar y
gland
number
of
pain
may
be
rarely
associated
with
gu anethidine th erapy and may be a side effect of a oth er
drugs
(e.g.
bethanide,
clonidine, me thyldopa and some cytotoxiCS).53
bretylium,
SALIVARY DISCOLOURATION
Discolouration of saliva may occur with rifampicin and
53
rifabutin therapy.
..
.. l
predominance .
The parotid glands are typica lly affected, indeed often the
Figure 147.2
Parotid enla r g e m e nt in sialosis .
,
1908
I PART 15 THE UPPER DIGESTIVE TRACT
hypothyroidism, malnutrition. alcoholic and other causes
instrumentalists, balloon and glass blowers. There are rare
of hepatic cirrhosis. puberty and menopause and reactions
reports of pneumoparotitis secondary to bicycle tyre
to antihypertensive medication. Rare associations with
inflation, dental procedures using air-powered equip
neurogenic disorders have also been described.
ment, cough associated with chronic obstructive airways
Sialosis is histopathologically characterized by acinar
disease, cystic fibrosis, whistling, nose blowing and the
cell hypertrophy, atrophy of striated ducts with oedema of
Valsalva
the
there is
pneumoparotitis may be self-induced, possibly reflecting
is often difficult. Manage
mental illness. There have been reports of pneumopar 6o otitis due to spirometry.
interstitial
connective tissue.
Ultimately
widespread fatty replacement of acini. The treatment of sialosis
manoeuvre
to
clear
the
ears.
Occasionally
ment is typically directed towards correcting any under
There is often no need for detailed investigation as the
lying systemic disorder, however, sialosis associated with
history is often suggestive of the cause. Sialography may
diabetes mellitus, other endocrine disorders or hepatic
demonstrate air bubbles within the ducts and may also
cirrhosis is often resistant to treatment. Rarely, surgical
show sialectasis if repeated episodes of pneumoparotitis
reduction of the parotid glands may be required; however,
have resulted
this clearly carries some risks. There is one report of
Ultrasound may also demonstrate air within the parotid
pilocarpine successfully resolving sialosis associated with 58
gland and duct, as may computed tomography. The
bulimia nervosa.
in infection and resultant sialadentitis.
management
of pneumoparotitis
is
relatively
straightforward. The avoidance of increases in intraoral pressures generally results in complete resolution of signs.
BULIMIA NERVOSA
There is virtually never any requirement for antibiotics as acute suppurative sialadenitis associated with pneumo
Salivary gland enlargement can arise in individuals with
parotitis is rare.
bulimia nervosa. The aetiology of increased salivary gland
,
size in bulimia nervosa remains unclear; however, it is suggested that binge
eating may result in functional
hypertrophy of the salivary glands. Alternatively. mild damage due to passage of fluid into the gland, autonomic neuropathy, endocrine disease or past alcohol use have also been suggested to cause this problem. Of note, the salivary gland enlargement may correlate with the frequency of bulimic symptoms and with levels of serum amylase. There presently remains no specific management
"��\KEy,: �p:6t�t�'>: ; ,".
:J
•
:
� �I::
"
...
.: -;� , ,
,
.'
�"
.
,
-�. "
..' '/.
" "
,,0
o� significant rise in intraoral a r l1 �·� ;· ,r.f1.�u�� ��o t�tis. pressu e Tay � , ,'�":.:.',c Marr�em;.ent mV9Jves . av,Ol�g- raised
;
_ ''
'
Any persi�tcnt
�
'c .
..
..� � .��!r�o
ral
�,���:�U!e.� ;,<.,:" :,,1 :''.f? '1!'���:
•
.
.
_
�
-
I ,7 • _ .
-:.
for a salivary gland enlargement associated with bulimia nervosa; however. cessation of vomiting
is generally
associated with resolution of the parotid swelling. Local application of heat, salivary substitutes and the use of cholinergics (including pilocarpine) may result tion
in
the
size
of
the
parotid
glands.
in reduc
Superficial
parotidectomy may rarely be required. 58, 59
SOME DISORDERS ASSOCIATED WITH XEROSTOMIA
Radiotherapy-associated salivary gland dysfu nction Radiotherapy of head and neck malignancies can cause
PN EUMO PAROTITIS (PNEU MOSIALADENITIS. WIND PAROTITIS)
profound xerostomia and salivary gland acinar destruc tion when the radiotherapy is directed through the major salivary glands. The degree of xerostomia clearly reflects
Pneumoparotitis is characterized by the presence of air
the duration and dose of radiotherapy. The xerostomia is
within the parotid gland due to the reflux of pressurized
irreversible and patients have oral symptoms akin to those
air from the mouth into the parotid duct. The swelling
of Sjogren syndrome (see Xerostomia)
1 (Figure 147.3).6
may be unilateral or bilateral, and tender or non-tender.
Irradiation that involves the salivary glands of doses
There may be crepitus and frothy saliva and air bubbles
about 52 Gy causes severe salivary dysfunction. Radio
may emanate from the parotid duct during massage of the
therapy techniques restrict unwanted irradiation to one
gland. The swelling of the parotid gland resolves over
side alone and can preserve contralateral salivary func
minutes to hours, although occasionally may take several
tion. Other sources of irradiation. such as radioactive
days to resolve. Rarely, air may escape from the parotid
iodine, may also cause salivary damage; however, this
gland giving rise to subcutaneous emphysema of the face
tends to be transient (see above under Salivary gland
and neck, mediastinum and possible pneumothorax. where
swelling). ' The results of open-label studies of orally administered
raised intraoral pressure is common - for example, wind
pilocarpine in small nwnbers of patients post-radiotherapy
Pneumoparotitis
is
most
likely
in
people
Chapter 147 Non-neoplastic salivary gland diseases I
1909
of primary Sjogren syndrome. The results of studies of patients
with radiotherapy-induced xerostomia have
sugges ted that acupuncture
may cause a sustainable
in sali vary flow rates. In tensity modulated radiotherapy (IMRT)
increase salivary
gland disease and
lessens
the resultant xerostomia.
Radioprotectants, such as amifostine, may also lessen the
frequency
xerostomia . 63
and
severity
of radiotherapy-induced
KEY POINTS •
Figure 147.3
Xerostomia in a patient receiving radiotherapy
Radiothcr3Py of head and neck malignancies profound xcro.-;tomia and salivary gland acinar destrucrion when the radiotherapy is directed through the major can cause
for an oral squamous cell carcinoma.
suggest that it might lessen the severity of radiotherapy
salivary
glanJs.
topical pilocarpine may reduce the frequency and severity
The degree of xerostomia dearly reflects the duration and dose of radiotherapy. The xerostomia is irreversible and patients have oral symptoms akin to those of
of
Sjl)greo's syndrome.
associated xerostomia?3.24 More recently, a number of double
blind
and
randomized
controlled
trials
have
conclusively established that oral and perhaps high-dose radiotherapy-induced
xerostomia
and
•
•
associated
symptoms. Clinical benefit associated with oral pilocarpine may not always reflect salivary function before radiotherapy or pilocarpine treatment. Clinical response can vary between patients and cannot be predicted from technetium-99m pertechnetate scintigraphy, although it is the
majority of patients
p ilocarpine
therapy.
es
will be identified during the first
The
ti mated
that
likely to have clinical benefit with
pilocarpine-induced
./ Dou ble bl i nd, randomized controlled trials have
12 weeks of
enhanced
established that oral and perhaps high-dose topical
salivary
pilocarpine may reduce the frequency and severity of
secretion may be possible for up to seven months
radiotherapy-induced xerostomia and associated
following radiotherapy and it has been suggested that
symptoms .
,
the administration of p iloca rpine before or during t he
.I Bethanechol and anethole may be of some benefit,
radiotherapy may lessen the severity of any radiotherapy induced
xerostomia
but there are limited supportive data.
.I Intensity modulated radiotherapy lessens the
.
Pilocarpine cannot increase the function of glands t hat
frequency and severity of radiotherapy-associated
are completely damaged by irradiation, but it does appear to enhance the function of minor salivary glands that may
xerostomia.
.I Radioprotectants, such as amifostine, may be of
be more resistant to the damaging effects of radiotherapy
advantage in preventing radiotherapy-induced
compared
xerostomia.
with
the major glands - indeed, by virtue of
their location, the minor mucous salivary glands of the
palate
and
elsewhere
may
escape
ra diotherapy.
the
full dose of
Bethanechol was found to increase the unstimulated and
stimulated
salivary flow
rates
of patients
with
xerostomia secondary to radiotherapy, although objective
changes in salivary flow rates did not always correlate
with sy mptomat ic irnproveme nt 62 It has been suggested .
that carbecholine may be of benefit in the treatment of radiotherapy-induced xerostomia, but good published
confi rmatory data are lacking.63
Sjo gren syndro me is the second most common auto immune
connective
tissue
disorder
characterized
by
due to profound lympho 64 the sal iva ry and lacrimal glands. can be c la ss ified as primary clisease
xerostomia and xerophthalmia cytic
infiltrat ion
into
Sjogren syndrome
in which there are only symptoms and signs affecting the
Anethole trithone may enhance pilocarpine-induced salivation in patients with radiotherapy-induced xerosto mia, although it may not be of benefit
SJOGREN SYNDROME
in the management
eye and
mouth, and secondary Sjogren syndrome in xerostomia xerophthalmia and associated
which there is
,
connective tissue disorder - most frequently rheumatoid
1910 I
PART 15 THE UPPER DIGESTIVE TRACT
Despite its frequency,
arthritis or systemic lupus erythematosus. This classifica
Sjogren syndrome probably
tion is possibly more simplistic as many patients with
remains underdiagnosed, possibly reflecting the generally
primary Sjogren's have a spectrum of other systemic, and
mild nature of the clinical signs. In addition, there is an
often autoimmune, disorders
increasingly wide range of other disorders that may give
Table 147.5
(Tables 147.5 and 147.6).65
Revised international classification criteria for Sjogren syndrome.
Classific�tion Ocular symptoms: a positive response to at least one of the following questions: Have you had daily, persistent, troublesome dry eyes for more than three months? Do you have a recurrent sensation of sand or gravel in the eyes? Do you use tear substitutes more than three times a day? II
Oral symptoms: a positive response to at least one of the following questions: Have you had a daily feeling of dry mouth for more than three months? Have you had recurrently or persistently swollen salivary glands as an adult? Do you frequently drink liquids to aid in swallowing dry food?
III
Ocular signs - that is, objective evidence of ocular involvement defined as a positive result for at least one of the following two tests:
(1) (2)
Schirmer's I test, performed without anaesthesia Rose bengal score or other ocular dye score
(�4
� 5 mm
in five minutes)
according to van Bijsterveld's scoring system)
IV Histopathology: In minor salivary glands (obtained through normal-appearing mucosa) focal lymphocytic sialoadenitis, evaluated by an expert histopathologist, with a focus score mucous acini and contain more than V
50
� 1,
defined as a number of lymphocytic foci (which are adjacent to normal-appearing
lymphocytes) per
4 mm2
of glandular tissue
Salivary gland involvement: objective evidence of salivary gland involvement defined by a positive result for at least one of the following diagnostic tests: Unstimulated whole salivary flow
� 1.5 rnL
in
15
minutes)
Parotid sialography showing the presence of diffuse sialectasias (punctate, cavitary or destructive Salivary scintigraphy showing delayed uptake, reduced concentration and/or delayed excretion of pattern), without evidence of obstruction in the major ducts tracer VI Autoantibodies: presence in the serum of the following autoantibodies: Antibodies to Ro(SSA) or La(SSB) antigens, or both Reprinted from Ref. 65, with permission.
Table 147.6 -
Revised internationaI rules for classification of Sjogren syndrome.
' Rev1sed:iJlte rnational rules for
clasSificatton
For primary Sjogren syndrome In patients without any potentially associated disease, primary Sjogren syndrome may be defined as follows: a. The presence of any four of the six items is indicative of primary disease, as long as either item IV (histopathology) or VI (serology) is positive b. The presence of any three of the four objective criteria items (that is, items III, IV, V, Vi) c. The classification tree procedure represents a valid alternative method for classification, although it should be more properly used in a clinical-epidemiological survey
For secondary Sjogren syndrome In patients with a potentially associated disease (for instance, another well-defined connective tissue disease), the presence of item I or item II, plus any two from among items III, IV and V may be considered as indicative of secondary disease
Exclusion criteria Past head and neck radiation treatment Hepatitis C infection Acquired immunodeficiency disease (AIDS) Pre-existing lymphoma Sarcoidosis Graft-versus-host disease Use of anticholinergic drugs (since a time shorter than four-fold the half-life of. the drug) Reprinted from Ref. 65, with permission.
Chapter 147 Non-neoplastic salivary gland diseases I
rise to
clinical features similar to those of
1911
Sjogren
syndrome - notably infection with HIV, HCV, human
T-Iymphocytic virus
(HTLV-l) and chronic graft
1
versus-host disease. Many asymptomatic persons have circulating antinuclear antibodies relevant to Sjogren syndrome, but these are generally present in low titre. The clinical manifestations of Sjogren syndrome are well detailed elsewhere.66 For the purposes of this text,
only the oral and salivary features of Sjogren syndrome
will be discussed.
The xerostomia of Sjogren syndrome can be profound,
giving rise to dysarthria and dysphagia. The oral dryness leads to retention of food on the teeth, mucosa and gingiva
and
thus
increases
the
frequency
of
caries
(particularly cervical disease) (Figure 147.4) and acute
gingivitis. Patients with Sjogren syndrome do not appear to have an increased predisposition to periodontitis per se.
There is an increased liability to candidal infection -
notably acute pseudomembranous candidosis, and med ian
rhomboid
glossitis,
chronic
atrophic
(denture-associated
stomatitis)
and
The
xerostomia
of
long-standing
candidosis
angular Sjogren
cheilitis. syndrome
increases the liability to acute suppurative parotitis (see under Suppurative sialadenitis
(suppurative parotitis)
above). The poor salivary output can lead to dysgeusia and loss of
taste
- many
affected
people
report
that
most
foodstuffs taste 'cardboard-like'. Affected patients may have intermittent swelling of the major salivary glands - notably the parotid glands, this often reflects non-specific inflammatory change within the glands. Solitary enlargement of a salivary gland may reflect chronic sialadentitis, acute suppurative parotitis, and
importantly,
mucosa-associated
lymphoid
tissue
(MALT) tumour (Figure 147.5).
There is an increased risk of lymphoma - approxi
mately 2-4 percent of patients with long-standing Sjogren syndrome lymphoma
developing within
a
one major
or
more
salivary
non-Hodgkin's gland.64,67
The
Figure 147.5
Parotid swelling due to MALT lymphoma in
Sjogren syndrome.
majority of these tumours are MALT tumours and indeed it
has
previously been
suggested
that
Sjogren
may
represent a preneoplastic disorder, although presently it is not possible to predict patient
liability to MALT
tumour development. The aetiology of Sjogren syndrome remains unknown. A viral aetiology - human retrovirus 5
-
was proposed,
but now seems unlikely, nevertheless a viral basis ca nnot be excluded as the salivary features of HTLV-l, HCV and HIV infection mimic those of Sjogren syndrome. To date, there is no evidence of a strong genetic basis for Sjogren syndrome.
Possible
aetiological
associations
between
silicone breast implants and Sjogren syndrome have not been confirmed. The pathogenesis of Sjogren syndrome remains unclear and is discussed in detail elsewhere.68
Investigation The investigation of Sjogren syndrome centres upon a Figure 147.4
Cervical caries secondary to long-standing
xerostomia in Sjogren syndrome.
series of clinical, radiological and immunological tests -
these are summarized in Tables 147.5 and 147.6.65
1912
PART
I
15 THE UPPER DIGESTIVE TRACT
reduced symptoms of xerostomia. This clinical benefit
Treatment
of orally administered pilocarpine has been confirmed in LOCAL
a large randomized, placebo-controlled, fixed-dose multi
AGENTS
centre trial. A dosage of 5 mg pilocarpine four times daily
Sal ivary substitutes
for at least
A number of synthetic salivary substitutes is av ail able for
to increasing whole saliva flow, pilocarpine can increase
the management of xerostomia; however, often these have a transient action and patients find them generally unsatis factory
- unless the xerostomia is mild.
Patients frequently
resort to sipping water. Sialogogues are thus likely to be
n salivary substitutes; however, more effective that can
even these
be of variable benefit in patients with profound salivary
gland obstructi on - as in severe radiotherapy-associated salivary gland dysfunction or Sjogren syndrome.
12 weeks is clinically beneficial. In addition
labial minor salivary gland secretion, perhaps suggesting th at many patients with Sjogren syndrome, at least, have some potential to benefit clinically from treatment
with
cholinergic agonists . 7o P ilocarpine therapy can also reduce the
frequency
of oral and ocular symptoms related to xerostomia and xerophthalmia. These data suggest that pilocarpine may be of benefit in the symptomatic management of Sjogren syndrome, but studies have not included p atients
with
Chewing gum
absolute xerostomia, who may have the most severe oral
Chewing gum may enh an ce salivary flow rates, bu t these
symptoms of long- standing oral dryness.
actions are likely to be tr ansient , fujI-denture wearers may be unable to use them - even when the manufacturers state that these agent s ar e suitable. The systemic management of l ong-standing xerostomia, as in Sjogren syndrome, is summarized in
Table 147.7.69
Double-blind studies in Sjogren syndrome suggest that cevimeline reduces symptoms of xerostomia, although the results of another study did not suggest that cevimeline was of benefit . 7 1 It has been suggested that the required daily frequency of use of cevimeline
SYSTEMIC AGENTS
(30 mg, three times
daily) may be less than that for pilocarpine (e.g. 5 mg,
Pilocarpine
four times daily). The adverse effects of cevimeline mirror
The results of
initial placebo - controlled studies of rela
tively small numbers of patients with Sjogren syndrome suggested that systemic pilocarpine increased salivary flow within two to three hours of administration and Table 147.7
Cevimeline
Sys temic therapies for lo ng- s tand i ng xerostomia.
Therapy
Disease
those of pilocarpine. Bethanechol Bethanechol , which has both muscarinic and nicotinic agonist actions, was suggested to be of potential use in the management of drug-induced xerostomia, but has never been obj ectively assessed. 72. 73 Pyri dostyg mine
Likely to be beneficial Pi loca rpi ne
Post-head and neck radiotherapy Sjogren syndrome Chronic graft-versus-host disease Drug- induced xerostomia
Betha necho I
Drug-induced xerostomia
Cevimeline
Sjogren syndrome
Interferon alpha
Sjogren syndrome
Ca rbachol ine
Post-head and neck radiotherapy?
Bromhexine
Sjogren syndrome?
Hydroxychloroquine
Sjogren syndrome?
Vitamin supplementation
Sjogren syndrome?
Acupuncture
Sjogren syndrome?
Electrostimu lation
Sjogren syndrome?
Evening primrose oil
Sjogren syndrome?
Unlikely to be of benefit Azathioprine
Sjogren syndrome
Ciclosporin
Sjogren syndrome
M e thotrexa te
Sjogren syndrome
Infliximab
Sjogren syndrome
E tane rcerpt
Sjogren syndrome
Rituximab
Sjogren syndrome
Available data , including those of a placebo-controlled
study,74 suggest that the cholinesterase inhibitor pyridos tygmine may be of benefit in the treatment of drug related xerostomia, although there are no data on the efficacy
of this agent
in the management of other
common disorders giving rise to xer ostomia . Bromhexine
Bromhexine (32-48 mg daily) may increase saliv ary and lacrimal flow in patients with Sjogren syndrome.7s,76 However, there are few published data on the p recise oral benefits of this therapy other than those of one study and the
results of an animal study that suggested that
bromhexine does not significantly alter the devel opment or severity of Sjogren syndrome-like disease?7 Interferon alpha Open label studies suggested that intramuscular
1
x
106 IU/week) and parenteral (3
x
106
( e .g .
IU three times
weekly) interferon alpha increase the lacrimal and salivary flow ot patients with pri mary and secondary Sjogren syndrome.78 Subsequent open and single-blinded studies
Chapter 147 Non-neoplastic salivary gland diseases I
also suggested that interferon alpha-containing lozenges
(ISO
IV interferon alpha three times daily) might reduce
the severity of xerostomia in primary and secondary Sjogren syndrome, clinical benefit being observed in some patients after nine weeks of therapy?9,80 A randomized
controlled study confirmed that therapy with interferon alpha lozenges
(ISO
IU three times daily) for 12 weeks
inhibitors
of
de
pyrimidine
novo
synthesis
1913
for
xerostomia remain unknown.64 Similarly, the in vivo potential benefits of gene therapy (utilizing
viral vectors
of aquaporin) remain unknown. Electrosti m u la ti o n
tended to increase unstimulated salivary flow, signifi
I t has been suggested that electrostimulation may increase
cantly increased stimulated whole salivary flow, lessened
salivary flow in some patients with Sjogren syndrome,94
associated oral symptoms and did not give rise to adverse
but good clinical evidence for such a claim is lacking.
side effects. A higher dosage of interferon than
150 IU
induced xerostomia95 and Sjogren syndrome,96 and may
Co rt i costero i ds
provide
While systemic corticosteroids may be beneficial tor the management of accompanying connective tissue disor ders, there are conflicting data of the precise benefits in reducing
the
It has been reported that acupuncture may be of
benefit in the management of xerostomia of radiation
does not impart any additional benefit.8l
oral
or
ocular
symptoms
of Sjogren
some
symptomatic
improvement
in
some
patients requiring palliative care.97
D ieta ry supplementation The
results
of
one
placebo-controlled
investigation
syndrome. The results of one randomized study suggested
suggested that a herbally
that prednisolone
supplements (LongoVital®) cause a prolonged increase
(30 mg on alternate days) was effec
tive,82 while a more recent investigation found that lower
in unstimulated salivary
doses
Bengal scores
of
prednisolone
were not
clinically
useful
-
although levels of relevant serological markers did fall.83
in
based agent with vitamin
flow and reduction in Rose
a group
of patients
with
Sjogren
syndrome. It has been suggested that evening primrose
Of interest, corticosteroid irrigation of the major glands
oil, rich in fatty acids important in inhibiting 2-series
(e.g. -with prednisolone 2 mg/mL saline) may be clinically
prostaglandins
useful by increasing salivary flow rates, particularly in
may enhance salivary s patients with Sjogren syndrome.9
flow
in some
patients with early disease.84
Hyd roxych I oroq u i n e
KEY POINTS
Hydroxychloroquine may be of some clinical benefit at doses of 6-7 mg/kglday, producing a reduction
in serum
Head and neck manifestations of Sjogren
IgG and IgM levels and C-reactive protein and erythro
syndrome in.clude:
cyte sedimentation rates and a fall in salivary levels of
•
interleukin-6
in Sjogren syndrome without causing
significant retinopathy.8s, 86, 87. 88 However, the clinical efficacy of hydroxychloroquine
appears
variable
and
benefit may only occur if the drug is prescribed for
•
periods greater than one year. Other
gLossrtis. chronic cmdidosis (denturc-assodatcd stoma�i.tis), as well a." angular cheilitis and
in subjective
a cute suppurativ(' parotitis; •
xerostomia, but did not produce any other relevant clinical improvement.90 Cyclophosphamide was reported , to be of benefit in the management of secondary Sjogren
Methotrexate does not seem to be of significant clinical newer immunosuppressive agents, such
as
•
infliximab,
etanercept and rituximab, do not seem to cause sympto rituximab
did
Inhibitors of chemokine function or receptors may ultimately prove to be helpful in the management of Sjogren syndrome, but at present the benefits of these and
L
int�rmiHent swelling of the major sativary glands notably the par ot id glands (lhis often reflects non-specific inflammatory change within ,th� gl�mds); solitary enlargement of a salivary gland may reflect chronic siafadentilis, acute supP1:lIativc parotitis, or i m por tantly mucosa-associated lymphoid tis-sue tumour (Figure 147.5); Increased risk of non-Hodgkin's Iym.phoma of the major s-alivarr glands, mainly MALT .
cause
resolution of the MALT of one patient.93
and loss of taste (many aff{'cted persons repo'ft most foodshlffs Mste
-
benefit in the treatment of primary Sjogren syndrome.92 use in the management of Sjogren syndrome. Likewise,
dysgeusia
'cardboard-like' ); •
syndrome in one young adult.91 Sulphasalazine was not of
although
-
atrophic
cyclosporin produced some improvement
improvement,
be profound, giving risc to dysarthria, d�phagi3\ increased frequcnqr of caries and acute gingivitis, but not periodontitis per se; increased liab i l it y to candidal infection and median rhomboid
i mmu n osuppressa nts
Azathioprine has not proved effective for the manage
matic
xerostomia which can
notably acute pseudomembranous candidosis.
ment of the xerostomia of Sjogren syndrome.89 Systemic
I
the
management of long-standing immunologically mediated
•
tumoUIS.
1914
• PART 1S THE UPPER DIGESTIVE TRACT
rather than hypersalivation. The common causes of
B-est clinical practice
drooling
include
cerebral palsy,
amylotropic
lateral
Treatment of xerostomia in Sjogren syndrome
disease. Persistent drooling leads to angular cheilitis,
sclerosis, traumatic brain injury, stroke and Parkinson's
excoriation of the lower facial skin and wetting of clothes .
./ Local agents, such as salivary substitutes and
There are no specific investigations for sialorrhoea,
chewing gum. are of limited transient value.
often the cause being established from the clinical history.
.I Systemic agents:
There are few controlled studies of possible treatment
- pilocarpine;
for excess salivation. Young adults with likely long-term
- cevimeline; - bethanechol;
1
- interferon alpha.
.I Other suggested treatments include
2 3
electrostimulation, acupu ncture and dietary supplements.
4 LYMPHOEPITHELIAL LESION Lymphoepithelial lesion is an uncommon disorder that
manifests as a recurrent or persistent swelling typically
of
the parotid gland. The submandibular gland may be affected in approximately 15 percent of individuals.
Generally, the swelling is non-painful.
illness, such as cerebral palsy, may benefit from surgical
relocation of the submandibular ducts together with removal of the sublingual glands. Likewise, the parotid
ducts may be relocated to pass out in the tonsillar fossa. Anticholinergic agents, such
as
transdermal scopola
mine or benztropine, have been suggested to be of long term benefit, but more recently intraglandular injection of
botulinum toxin has been found to be of value for the 01, 102 and chil treatment hypersalivation in adults 1
of
dren 103 with amyotropic lateral sclerosis, cerebral palsy,
5
Parkinson's disease and other causes of excess salivation.
Low dose radiotherapy (8-12.5 Gy) has been suggested
to be effective for excess salivation of patients with
amyotropic lateral sclerosis.
Affected patients do not have clinical features of
Sjogren syndrome nor features of other disorders likely to
give rise to xerostomia, although they do have an increased risk of non-Hodgkin's lymphoma. The histo
pathological diagnosis of benign lymphoepithelial lesions
is important as the clinical features mimic those of
salivary gland malignancy, and histopathologically there
can be some confusion with MALT lymphomas. Surgical
excision is the usual treatment of a benign lymphoe pithelial lesion.99
:�. �.·:·:'�Pl� ::c�,;ri�J,�-t����·� ." S f �d;�,? )i�i, i�� l����·i� ·;;':�� ': · t'. .,'. ( .c:ereQ{al,· palsY;)l,myoJropklatcr8.1 sdcr6si�».� � ':
�
S:�;:2��.���,r���;,n:,�:� .. •.
;:'"1C��C �:t�%��t
�P�rsisteIit ''dl:6&Jing-'lea9�,:,t((,, �l1-gu lar cheili �i$,:',.... " � " excoriation -'of the loweE'f<1c}aFskin and ,;':" �_l _'_�
�" C"
.
·,:' (�r�· *�tttrig, 9tclQihes:' �:,:�,::::� iI.·'�;,; �;. \, ,<:��.�:_.�:r. c�: :���st�J�a �ions for . ,� : I�(�--";t:p�}i�,, ii:�;,��:��B���fi . .: "�:" JJ:::}:,� ,',.;" ' '. slalqrrhoea, 9ffep. �he,{'1Jl.se' bemg established'''' ,. - - frC)!ri, 'th�_�liJlic'aI' hIstorY, , . .
'it
MICULlCZ'S DISEASE AND MICULlCZ SYNDROME
, _� '
-,
It
_
_
'
'
,
•
�"':
"
,
'
Miculicz's disease is a disorder characterized by multiple
-
�T.
.."
'.
_
,
,-
'.
lymphoepithelial lesions of the lacrimal and salivary
glands. It is probably a variant of Sjogren syndrome. Miculicz syndrome simply reflects other disorders char
acterized by lacrimal and salivary gland disease that
mimics Sjogren syndrome, but is associated with disorders such as sarcoidosis, lymphoma and other similar systemic disorders. The use the term 'Miculicz's disease' or (syndrome' often simply confuses the literature.100
of
Best clinical practice ./ Young adults with likely long-term illness, such as cerebral palsy, may benefit from surgical relocation of the submandibular ducts together with removal of the sublingual g l a nd s. Likewise, the parotid ducts may be relocated to pass out in the tonsillar fossa.
\1 Intraglandular injection of botulinum toxin has been found to be of application for the treatment of
EXCESS SALIVATION (SIALORRHOEA) Although excess salivation is uncommon, it can be distressing to both patients and carers. True excess salivation is extremely unusual, although may sometimes arise following drug therapy. The majority of patients with excess salivation have difficulties in salivary control
hypersalivation in adults and children with amylotropic lateral sclerosis, cerebral palsy, Parkinson's disease and other causes of excess salivation.
./ Transdermal scopolamine or benztropine may be
i
he pful.
Chapter 147 Non-neoplastic salivary gland diseases I
SO ME MINOR SALIVARY GLAND DISORDERS
aetiology affecting the minor salivary glands. It presents as a rapid-onset painful, non-ulcerated swelling of minor palatal
Mucocoeles
1915
salivary
glands.
Almost
all
reported
affected
patients have been men. Subacute necrotizing sialadenitis
Mucocoeles are probably the most common disorder of the minor salivary glands, typically presenting as single blue or translucent sessile swellings on the lower lip
tends to be self-limiting, symptoms and signs resolving within two weeks, and is not associated with necrotizing sialometaplasia.105, 106, 107
(Figure 147.6). Mucocoeles occur in both genders and in all age groups, the peak age of incidence being between 10 and 29 years. They are rare in infants, although they can occur in neonates. The lateral aspect of the lower lip is the most common site of occurrence of mucocoeles, but other common sites include the floor of the mouth and the ventral surface of the tongue. The usual clinical presentation is of a single, recurrent, fluctuant, painless, well-circumscribed bluish swelling which ruptures easily to release viscid salty mucus.
Occasionally, mucocoeles can be multiple or
develop suddenly at mealtimes. The majority of mucocoeles are of the extravasation type in which duct damage causes pooling of mucus in the adjacent connective tissue. Retention mucocoeles, the less common variant, arise after partial or complete obstruction of the excretory duct (e.g. a sialolith), leading to retention of glandular secretions and dilatation of the duct. Extravasation mucocoeles may be more frequent in young patients, whereas retention mucocoeles may occur most often in middle to late life.
0 1,2,3 4 5
Some mucocoeles may resolve spontaneously, but large, recurrent or unsightly mucocoeles often need to be surgically excised, or removed by laser or cryotherapy. Other
therapies of
less
well-proven efficacy
include
intralesional corticosteroid injections and gamma-linole nic acid (oil of evening primrose)J04
Subacute necrotizing sialadenitis Subacute necrotizing sialadenitis (SANS) is a rare non specific inflammatory disorder of adults of unknown
Necrotizing sialometaplasia Necrotizing sialometaplasia is an uncommon disorder that typically affects the minor salivary glands of the palate, although may rarely involve other minor salivary glands and, very unusually, the major salivary glands. It presents typically as a palatal swelling that breaks down to give rise to localized, irregular ulceration. Lesions can be large - up to 5 cm in diameter - and can give rise to local paraesthesia or anaesthesia; however, they generally heal within 4-90 days. Affected patients may have systemic features, such as pyrexia, chills and malaise. Despite the sometimes extensive area of ulcera tion, bony involvement is rare. Of
note,
it
may
be
clinically
and
histologically
confused with malignancies such as a squamous cell carcinoma, mucoepidermoid carcinoma or non-Hodg kin's lymphoma. Necrotizing sialometaplasia is character ized histopathologically by acinar necrosis with squamous metaplasia of the ductal epithelium. This latter feature underlies
the
possible
diagnostic
confusion
between
necrotizing sialometaplasia and squamous cell carcinoma. Necrotizing sialometaplasia is thought to arise from local ischaemia, possibly caused by direct trauma (e.g. from a denture), placement of dental local anaesthetics, cocaine use, radiotherapy, alcohol, tobacco smoking, upper respiratory tract infections, allergic disease, oral intubation and other surgical procedures or sickle cell disease. Necrotizing sialometaplasia is usually self-limiting; however, in view of the possible clinical similarity between necrotizing sialometaplasia and oral malignancy, careful histopathological
examination
of
biopsy
material
is
essential. Any likely causative factors should be identified 1 8 and removed. 0
Cheilitis glandularis Cheilitis glandularis (suppurative stomatitis glandularis) is a rare disorder that usually arises in adults manifesting as labial swelling and ulceration. The disease is localized almost
exclusively
to
the
lower
contact zone between the lips,
lip,
especially
the
although there have
been occasional reports of the condition affecting the upper lips and palate. Affected individuals usually have
L
swelling, Figure 147.6
Mucocoele of the lower lip.
eversion
and
protrusion
of
the
lower
lip
secondary to inflammation of the minor labial salivary
I . !.
___ .1"_ 0··__ __ _
1916
I PART 15 THE UPPER DIGESTIVE TRACT
glands
(Figure 147.7). The orifices of the minor salivary
Inclusion of salivary gland tissue
gland ducts are dilated and inflamed, and a mucopurulent secretion may be expelled from the ducts when the lip is compressed. The precise aetiology remains
unknown,
although
associations with syphilis and other more ill-defined bacterial infections, poor hygiene, tobacco use, actinic
Cyst-like areas of radiolucency are seen in the region of the angle of the mandible.
Such inclusions are also
possibly the origin of rare intraosseous salivary gland tumours.lll
exposure and emotional disturbance have been suggested. A genetic predisposition has also been proposed.
Cheilitis glandularis may be classified into three types based
upon
the
severity
of the
disease -
simplex,
superficial suppurative and deep suppurative. The last two types represent a stage where there is bacterial infection ,
being
clinically
characterized
by
increased
inflammation, suppuration and ulceration of the lip. The
deep
suppurative
type
has
also
been
termed
'cheilitis apostematosa' or 'myxadenitis labialis', while the superficial suppurative has also been termed (Baelz's disease'. The
histopathological
findings
are
non-specific,
but include local chronic sialadenitis and ductal dilata tion.
Dysplastic
epithelial
changes
may
has
been
reported,
cheilitis
There are many unknowns in the aetiology and treatment of non-neoplastic salivary gland disease. Perhaps the most relevant areas of investigation for the treatment of such disease are: .. establishment of the pathogenesis of HIV and HCV related sialadenitis;
� determination of the aetiology of Sjogren syndrome: )- development of wordwide prophylactic strategies for the prevention of radiotherapy-induced salivary gland
occasionally
occur, but although associated carcinoma of the lower lip
Deficiencies in current knowledge and areas for future research
glandularis
is
still
considered to be a benign disorder that should
disease; )- development of gene therapies to circumvent long term xerostomia of primary or secondary cause.
be
managed by conservative means.109 There are no detailed randomized studies of the treatment and surgery, but vermilionectomy
has been
suggested
to be effective.
However, albeit rarely, mucocoeles can occur following
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56.
57.
58.
59.
60.
61.
62.
63.
* 64. * 65.
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148 Cysts and tumours in and around the jaws, including sarcoma
MARK McGURK, ANNA CASSONI AND LISA PITKIN
Introduction Cys ts of the ja ws Odontogenic cysts Nonodontogenic cyst - fissura l cysts (epi th e l i um lined)
1921 1921 1922 1926
Mal ignant tumours arising in and aro und the jaws
1926 1927
References
Benign tumours of the jaws
Best clin ica I practice
1931 1939 1939
Deficiencies in cu rrent know ledge and areas for futu re
resea rch
Nonodonto gen i c cyst - pseudo bone cysts (nonepithel i u m l ined)
Key points
1939 1939
The da ta
in this chapter are supported by Medline searches from the PubMed online database using the following subject search headi ngs: malignant, odont ogen ic tumour, jaw tumours, jaw cysts, ameloblastoma, head and neck sarcoma, head
and neck cancer, head and neck neoplasms, therapy, ch emotherap y, radiotherapy and each of the tumour subtypes mentioned. The CDchrane Database was also consulted.
INTRODUCTION
are sarcomas and, of all s arcomas, 10 percent present in the head and neck. There are many histological subtypes
Cysts of the jaws are a frequent finding because epithelial
that evolve from either bone or from soft tissue and they
remnants persist in the bone after tooth formation -
vary in clinical agg ressiveness.
are
Rarely, malignan t tumours also develop from odonto
result of dental
genic tissue. The mos t common odontogenic tumour is
these are known as odontogenic cysts. 1, 2, 3 Apical cyst s
the most common (55
perce nt) and are
a
infection stimul ating the epithelial remnants to coalesce.
the ameloblastoma which has
Fissural cysts develop from epithelial residues at lines of
million population per annum. Squamous cell carcinoma
an
incidence of one per
fusion tha t result from folding of the branchial a rches
has been reported to develop from the lining of dental
during development of the face.
cysts but this is extremely unusual .4
Tumours of the jaws can arise primarily within the jaws or invade them from adjacent structures. The jaws
may also be the site of metastases, most commonly from the bronchus, breast, liver, thyroid or kidney. Sarcomas are uncommon malignancies that arise from mesenchy
CYSTS OF THE JAWS
mal tissue and develop in patients of all ages. They
Classification of jaw cysts
b ut
account for 1 percent of malig nant tumours in adult life, are rela tively more common in children and
Several classifications of jaw cysts have been proposed, but
adolescents. About 1 perce nt of head and neck tumours
that of'the World Health Organisation enjoys current use
1922 I
PART 1 5 THE UPPER DIGESTIVE TRACT
(Table 148.1). This scheme is based on the ongm of
Small apical cysts « 1 cm diameter) can be managed
the cyst epithelium: developmental cysts arise at lines of
nonsurgically in the first instance.6,7
epithelium and pseudocysts are nonepithelial and lined
tooth is controlled by root canal therapy. Resolution
fusion, odontogenic cysts from the remnants of enamel
only by connective tissue.
Normally
they
resolve spontaneously if the infection in the associated
cannot be guaranteed and progress of the cyst should be
monitored with serial radiographs. Surgical management
consists of either enucleation or marsupialization.
Mechanisms of cyst formati on Cysts are defined as pathological cavities that contain
Enucleation is the most appropriate treatment in the
majority of cases. The resultant haematoma may become
infected and prophylactic antibiotics are advisable. The
fluid, semi-fluid or gases not derived from pus. All
adjacent teeth should be monitored as these can become
epithelium. The proposed explanation for cyst formation
prone to fracture. This usually happens seven to ten days
Infection is one such stimulus and so it is not uncom
patient should be warned of the risk of fracture and
but solitary cysts and aneurysmal bone cysts are lined by is that a stimulus induces the epithelium to proliferate.
devitalized. Large cavities can leave the jaw weak and
after treatment when the bone is being remodelled. The
mon for cysts to form at the apex of infected teeth.
advised to eat a soft diet for two to three weeks.
that the central cells then eventually die leaving an
beneath vital teeth or large cysts develop in elderly
The proliferating cells form a ball - it is presumed
epithelium-lined sac filled with a high concentration of protein (the keratocyst being an exception), cholesterol,
hemosiderin and immunocompetent cells. Subsequent
positive hydrostatic pressure within the cyst, together
Marsupialization
is
advisable
when
cysts
burrow
individuals. The technique of marsupialization consists of
removing the root of the cyst and opening it into the oral
cavity. Decompression of the cyst stimulates bone growth
so that in time the cavity slowly decreases in size. After
with cytokines released from the epithelial cells, promote
about 1 2- 1 8 months, it may reach a size that can safely be
produces the characteristic radiographic appearance of
is the time taken for the bone to reform. During this
In keratocysts, where the epithelium is more active,
This is sometimes achieved by filling the defect with a
bone resorption.
This gradual and uniform pressure
a smooth, well-defined radiolucent area within the bone.
growth may not be uniform and multilocular lesions
dealt with by enucleation. The drawback to this technique period, the cavity must be kept open to the oral cavity.
plug attached to a dental plate.
can develop.
ODONTOGENIC CYSTS Principles of management of jaw cysts The majority of cysts are odontogenic in origin and often
an incidental finding on routine radiographic examina
tion of the jaws. The radicular cyst, which arises at the
apex of an infected tooth, is the most common and
accounts for usually 50 percent of cases. These cysts are
approximately 1 cm in diameter, smooth-sided, oval or pear-shaped and the adjacent tooth roots are intact. This
is an important feature as erosion of the roots is usually a
feature of malignancy. Most small, unilocular, odonto
genic cysts, apart from the keratocysts, can be safely
treated by enucleation.
Large cysts are more of a management problem. First, in dentate patients, they may scallop out the bone beneath a line of vital teeth and enucleation then runs the risk of devitalizing these teeth. Large cysts, particularly the
multilocular variety, may not be simple and must be
distinguished from neoplasms and keratocysts by open biopsy.
Essentially, there are three methods of managing bony
cysts:
1. observation; 2. enucleation; 3. marsupialization.
Odontogenic cysts develop from redundant epithelium left behind in the jaws as a result of tooth development.
Teeth
evolve
from
a
line
of thickened
epithelium
that develops along the surface of the mandibular and maxillary processes. This epithelial line slowly invaginates into the underlying mesenchyme. The trough that forms
then breaks into clusters of epithelial cells that by now are buried in the mandibular and maxillary processes of the jaws. These epithelial clusters ultimately produce 20 primary and 32 permanent teeth. There are 52 odonto genic structures within the embryonic tooth germ and many become redundant. This process of redundancy is important in the pathogenesis of cysts and tumours of the jaws.
The process of tooth formation has been classified into
stages (Figure 148.1). Initially, the mesenchyme starts to condense under the epithelial cap which itself is attached by a tenuous epithelial strand (dental lamina) to the oral mucosa (cap stage) . Later, the epithelium around the
margin of the cap migrates down the sides of the
mesenchyme creating the crown of the tooth (the 'bell
stage') . It then continues downward (root sheath of Hertwig) to define the shape of the root. These epithelial . cells of the root sheath and dental lamina splinter into
small nests and lie in the mesenchyme of the jaw
as
Chapter 148 Cysts and tumours in and around the jaws, including sarcoma I
Table 148.1 Tumour
1923
WHO histological classification of odontogenic tumours.
type
M aligna nt tumours Odontogenic carcinomas Metastasizing (malignant) ameloblastoma
9310/3
Ameloblastic carcinoma, primary type
9270/3
Ameloblastic carcinoma, secondary type (dedifferentiated), intraosseous
9270/3
Ameloblastic carcinoma, secondary type (dedifferentiated). peripheral
9270/3
Primary intraosseous squamous cell carcinoma, solid type
9270/3
Primary intraosseous squamous cell carcinoma derived from keratocystic odontogenic tumour
9270/3
Primary intraosseous squamous cell carcinoma derived from odontogenic cysts
9270/3
Clear cell odontogenic carcinoma
9341/3
Ghost cell odontogenic carcinoma
9302/3
Odontogenic sarcomas Ameloblastic fibrosarcoma
9330/3
Ameloblastic fibrodentino- and fibro-odontosarcoma
9290/3
Benign tumours Odontogenic epithelium with mature, fibrous stroma without odontogenic ectomesenchyme Ameloblastoma, solid/multicystic type
9310/0
Ameloblastoma, extraosseous/peripheral type
9310/0
Ameloblastoma, desmoplastic type
9310/0
Ameloblastoma, unicystic type
9310/0
Squamous odontogenic tumour
9312/0
Calcifying epithelial odontogenic tumour
9340/0
Adenomatoid odontogenic tumour
9300/0
Keratocystic odontogenic tumour
9270/0
Odontogenic epithelium with odontogenic ectomesenchyme, with or without hard tissue formation 9330/0
Ameloblastic fibroma Ameloblastic fibrodentinoma
9271/0
Ameloblastic fibro-odontoma
9290/0
Odontoma
9280/0
Odontoma, complex type
9282/0
Odontoma, compound type
9281/0
Odontomeloblastoma
9311/0
Calcifying cystic odontogenic tumour
9301/0
Dentinogenic ghost cell tumour
9302/0
Mesenchyme and/or odontogenic ectomesenchyme, with or without odontogenic epithelium Odontogenic fibroma
9321/0
Odontogenic myxoma/myxofibroma
9320/0
Cementoblastoma
9273/0
Bone-related lesions Ossifying fibroma
9262/0
Fibrous dysplasia Osseous dysplasias Central giant cell lesion (granuloma) Cherubism Aneurysmal bone cyst Simple bone cyst
Other tumours Melanotic neuroectodermal tumour of infancy
BACK
9363/0
Morphology code of the International Classification of Diseases for Oncology (lCD-O) and the System ized Nomenclature of M e d ic i ne (http;//snomed.org). Behaviour is coded /0 for benign tumours, and
/1
for borderline or uncertain behaviour. Reproduced from Ref. 5, with perm i ssion .
1924
I PART
15
THE UPPER DIGESTIVE TRACT
it can lie on the lateral surface of the root, presumably associated with a necrotic lateral root canal. Radicular cysts are lined by proliferative epithelium of the non keratinizing type with an intense inflammatory infiltrate. As
these
cysts
enlarge,
they
encroach
on
adjacent
structures, such as the antral lining or the inferior dental canal, but the cyst lining remains a distinct structure that can be peeled from nerves and antral mucosa.
Dentigerous cyst Dentigerous cysts develop from the epithelial sac that surrounds the crown of unerupted teeth Figure stage;
148.1 (b)
Pictures of dental bud as it is forming:
(a)
cap
the tooth needs to be greater than 4 mm to be recognized
bell stage.
as a dentigerous cyst, as the presence of the sac is a
residual odontogenic epithelium. They persist throughout the lifetime of the patient. It is these residual epithelial elements
that
(Figure 148.3).
By convention, the follicular space around the crown of
give
rise
to
the
different
types
of
odontogenic cysts and tumours that we now describe.
common phenomenon that helps the tooth erupt through the bone. Impacted wisdom teeth are the most common cause of these cysts again,
these
findings.
cysts
However,
(0.8 percent of impacted teeth). Once are
often
unlike
incidental
radicular
radiographic
cysts,
they
are
normally quite large and may on occasion fill the whole of
Radicular cyst
the
ramus
of
the
mandible.
The
nonintlamed
dentigerous cyst has an epithelial lining composed of two to three layers of cuboidal or ovoid epithelial cells.
Radicular cysts develop at the apex of an infected,
Enucleation is the treatment of choice, with removal of
nonvital tooth. If the tooth
the impacted tooth in most instances. Sometimes the
percent of cysts are of this origin.3 There is a bimodal
occlusion at a later date.
is removed and the cyst persists, it is called a residual cyst. Approximately 50
tooth can be left in place so that it can be brought into
incidence within the third and sixth decades of life and they are rarely seen in the primary dentition. These cysts are usually found on routine dental examination and are
Odontogenic keratocysts
symptomatic if the contents become infected. Large cysts can expand through the bone and are fluctuant to
These are characterized by an epithelial lining that is
palpation, giving the classical sign of eggshell cracking. As
parakeratinized and stratified. It is characterized by a
might be expected, the radicular cyst is usually situated at
basal layer of neatly arranged, palisaded, columnar and
the apex of a tooth
cuboidal cells, above which are several layers of squamous
Figure
148.2
(Figure 148.2), although occasionally
Radicular cyst associated with a carious lower
right fi rs t molar. Courtesy of Edward Odell.
Figure
148.3
Dentigerous cyst associated with an unerupted
lower left third molar. Courtesy of Edward Odell.
Chapter 1 48 Cysts and tumours in and around the jaws, including sarcoma I
epithelium. This lining has a high mitotic rate8 and rarely may become dysplastic and develop into squamous cell
1925
cyst remnants, the bone cavity should be deroofed to its maximum
diameter
to
ensure
adequate
access.
The
carcinoma. Unlike other odontogenic cysts, keratocysts
keratocyst has been reported to be associated with nevoid
have a high incidence of recurrence (up to
basal cell carcinoma (Gorlin-Goltz syndrome).
60 percent).9
Odontogenic keratocysts can be associated with erupted, unerupted teeth or nontooth-bearing areas of the jaw.
4- 10 percent of all odontogenic cysts and have an incidence of 3.5-5 per
Eruption cyst/dentigerous cyst
million populations per year.lO The peak incidence is the
The eruption cyst is a variant of the dentigerous cyst. It is
They
represent
approximately
second to fourth decade of life and the condition is twice
present in children as a fluctuant swelling overlying an
as common in the mandible as the maxilla, particularly in
erupting tooth. In reality, it is an expanded tooth follicle
the region of the third molar tooth.
and treatment, if required at all, consists of marsupializa
Odontogenic keratocysts normally present as large multilocular cysts, but this is not always the case. On
tion to expose the crown of the tooth. There are no implications to the health or development of the tooth.
occasion they can masquerade as large dentigerous cysts or, when small, are indistinguishable from other dental cysts. As with most jaw cysts, the keratocyst is asympto
Lateral periodontal cyst
matic and discovered as an incidental finding on radio graphic evaluation. These cysts are filled with keratinous
This is a developmental lesion that occurs on the lateral
debris (with the consistency of toothpaste) and this can
aspect of a tooth or between the roots. It is distinguished
become infected. The epithelial lining is not as inactive as
from a radicular cyst by the fact that the tooth is
that of other cysts and there is :a tendency for these cysts
vital. These lesions develop in the mandibular premolar
to expand
regions, but occasionally in the maxilla, mainly in the
through marrow spaces and
hence their
multilocular radiological appearance. Rarely, keratocysts
fifth
to seventh decade of life. Radiologically, they appear as a
resorb tooth roots and this makes them indistinguishable,
well-defined radiolucency on the lateral surface of a tooth
except by biopsy, from neoplasms. The presence of buccal
root. It is rare to find the lesion greater than
and lingual bone expansion is held by some to be an
diameter and treatment is by enucleation.
important
diagnostic
sign,
but
this
feature
is
1 cm in
not
restricted to keratocysts. The diagnosis should always be suspected in the presence of a large cyst, particularly if it
Botryoid odontogenic cyst
is multilocular and at the angle of the mandible. Radiologically, the margins of the cyst are well defined,
The botryoid odontogenic cyst is a polycystic form
smooth or scalloped. Displacement of adjacent teeth is
of lateral periodontal cyst. It is unclear whether this is
more common than resorption. If suspected, low protein
a distinct entity or a reflection of the propensity of
content
« 4 g)
in a fluid aspirate is highly suggestive of a
pathologists to subclassify these entities. The treatment
keratocyst. Nevertheless, it is prudent to undertake an
is by enucleation
open biopsy for occasionally an ameloblastoma (odonto
removed cysts tend to recur.
genic tumour) masquerades as a keratocyst.
or curettage,
though inadequately
An incision
in the retromolar area should be positioned in such a way that if the lesion proves to be a neoplasm the area could
Glandular odontogenic cyst
be excised easily. A small window of bone can be removed to expose the keratin-filled cyst. Treatment reputation
of
for
this
cyst
recurrence.
is
Glandular odontogenic cysts arise in the tooth-bearing over-shadowed
Large
cysts
by
its
respond
to
anterior part of the mandible, they are small
where healthy teeth would be compromised by enuclea
multilocular. The average age at the time of diagnosis is 50 years. Glandular odontogenic cysts have a tendency to
simply a biological phenomenon. Nowadays, this is not
recur and great care should be taken to eliminate every
the case as careful enucleation in conjunction with the
vestige by curettage or preferably enucleation.
Carnoy's
solution
(a
fixative)
reduces
10 percent.l1 If the cyst has
burrowed between molar teeth, these units normally have to be sacrificed in order to ensure adequate clearance. The inferior dental nerve is often found to lie
in the floor
Calcifying odontogenic cyst These cysts have variable histological features that include
during
columnar basal cells and ghost cells in the cyst lining. The
enucleation. However, the injury is usually transient in
ghost cells may calcify. While this lesion is a cyst, there is
nature. In terms of surgical technique, to avoid leaving
also a solid neoplastic variant. The condition is extremely
of' the cyst cavity and
.
« 1 cm) and
tion. In the past, high recurrence rates were accepted as
recurrence to less than
1
epithelium. The majority of these cysts are found in the
marsupialization and this treatment should be considered
application of
-�-
areas of the jaw. They are lined by cuboidal, columnar
is at risk of
injury
1926 I
PART 15 THE UPPER DIGESTIVE TRACT
rare and lesions are more common in the anterior part of the mouth and are usually closely associated with the dentition. Surgical enucleation is the treatment of choice and the diagnosis is usually made by the pathologist after treatment is completed.
Gingival cyst of adults The gingival cyst is a small swelling on the attached gingiva that arises from epithelial remnants. These cysts are frequently situated in
the
buccal aspect of the
mandible. They have no implications to the health of the gingiva or teeth and treatment is by excision.
Gingival cyst of infancy The
gingival cyst of infancy is a superficial microcyst
that
arises from embryonic rests located in the mucosa. It is a normal phenomenon and represents a swollen follicle over the crown of the erupting tooth, just before it breaches the
oral mucosa. This is usually an incidental finding In newborn infants and does not require treatment.
NONODONTOGENIC CYST - FISSURAL CYSTS (EPITHELIUM LI NED) Nasopalatine duct cyst Figure 1 48.4
This is a developmental cyst that arises from the epithe� the nasopalatine canal (Figure 148.4). The cyst may be associated with a salty dis�
lial remnants within
charge from behind the incisor teeth or be an incidental finding on radiographic examination. The radiographic appearance is that of an ovoid radiolucency in the midline of the premaxilla. It rarely exceeds 2 cm
in diameter.
These lesions are detected throughout life, but the mean age at presentation is
40 years. The cyst is lined by
(a) Periapical radiograph of a nasopalatine cyst; (b) large nasopalatine cyst presenting as a swelling in the labial sulcus. Panel a, courtesy of Edward Odell.
Surgical ciliated cysts The surgical ciliated cyst arises from the lining of the maxillary sinus following trauma or surgical intervention. Treatment is by simple enucleation.
pseudostratified columnar ciliated epithelium. Treatment consists of surgical enucleation normally by
ra i si n
g a
palatal flap to expose the nasopalatine canal.
NONODONTOGENIC CYST - PSEUDO BONE CYSTS (NONEPITHELIUM LINED)
Nasolabial cyst
The solitary bone cyst
The nasolabial or nasoalveolar cyst is a rare extraosseous lesion normally appearing beneath the
ala of the nose on
the maxillary alveolar process. Treatment consists of local surgical excision and it is important to distinguish this lesion from a minor salivary gland tumour.
Palatal cysts of infancy
The solitary bone cyst is an intraosseous cavity lined by an attenuated fibrovascular membrane that lacks an epithe� lium. These cysts account for about 2 percent of all jaw cysts. Other names given to the entity are traumatic bone cyst, haemorrhagic cyst, progressive and simple bone cysts. T hey are found in the mandible more often than the maxilla and the cyst is solitary and often quite large and nonexpansile. They have a well-demarcated and sometimes scalloped edge. It is difficult on clinical and
g
These are microcysts in the midpalatal raphe. In general,
radiolo ical examination to distinguish these cysts from
they require no treatment.
other entities before surgery. At surgery, the presence of a
Chapter 148 Cysts and tumours in and around the jaws, including sarcoma I 1927 cavity
filled
with
straw-coloured
fluid
is
virtually
make the odontogenic tumours a h ighly diverse group of
(Table 148.1).5 The most common odontogenic
diagnostic It is postulated that these cysts arise from a
lesions
traumatic, intraosseous haemorrhage with subse quent
t umour is the ameloblastoma. The remainin g odonto
.
bone
resorption.
Once
opened,
resolves spontaneously, though
the cavity in
nonnally
a few cases bone
genic tumours are rare pathological
grafting may be requ i red .
behaviour.
Lingual mandibular salivary gland defect
AMELOBLASTOMA
This is a develop mental concavity occasionaliy found on the lingual surface of the mandible. It usually contains salivary gland or fat Its main diagnostic feature is a well .
described bony radio lucency situated below the inferior dental canal
(Figure 148.5). Other names given to this
entity are Stafne's bone cyst or lateral b one cyst. It does not re quire treatmen t.
entities and do not
warrant extensive description of their appearance and
Five types of ameloblastomas have been described: a solid or multicystic variant, the uni cystic
variant (6 percent), (2
an unusual dermoplastic variant, a peripheral variant percent) and a malignant form.12
The ameloblastoma is a locally aggressive e pitheli al odontogenic neoplasm which very rarely m eta stasi zes
.
14
D•
The annual incidence is approximately one per million population
in the UK. In general, they are benign, slow
growing and locally i nvasive tumours. There have been a
Focal bone marrow defect Focal bone marrow defect is an asy mpto m atic radiolucent lesion of the jaws that contains bone marrow. This lesion is usually an incidental finding on routine dental radio graphs. There are few features that distinguish it from other entities and so it is usually curetted and the diagnosis made. Otherwise there would be no need for treatment.
few reported cases where metastases have developed after repeated
surgical
interventions.
Whether
the surg ical
interventions played a part in changing the biological
behaviour of the tumour is debatable. Ameloblastomas normally present in the third and fourth decades of life, but cases have been reported at almost any age from the second to the ninth decades of life. There is no gender bias. More than
80 percent of ameloblastomas develop in
the mandibular ramus or molar region. Ameloblastomas are treated by resection with a margin
BENIGN TUMOURS OF THE JAWS Odontogenic tumours and tumour-like les ions The com pl i ca ted embryological development of the jaws, togethe r with divergent patterns of cellular differentiation,
of normal tissue. The peripheral ameloblastoma presents as a smooth swelling on the gingiva and does not exhibit an
aggressive behaviour. It will respond to local excision.
The mu lticystic lesions spread
pref e rent i ally
thr o u gh
medullary bone and spare the dense co r ti c al plate. If the cortex is perforated, the perios teum us u ally forms a barrier to the tumour, as this is an osteophilic neoplasm. The propensity of the tumour to grow through medullary spaces suggests a I-cm margin of clearance is desirable
(Figure 148.6). If the lesion extends into connective tissue, any overlying soft tissue should also be removed Maxillary ameloblastomas require decisive treatment. They tend to be
.
IS
located in the posterior maxilla and if
managed inappropriately can spill into the infratemporal fossa and cases are recorded where the lesion has proved incurable. In general, follow up of ameloblastomas should be indefinite as recurrences can develop after
20 years or
more. A number of composite forms of ameloblastoma can develop such as the odonto-ameloblastoma, the amelo blastic fibroma and ameloblastic fibro-odontoma. These lesions behave in the same way as the more common forms of amelobl a s t o m a and should be treated as sllch. The
subclassification
has
no
treatment
consequence.
However, the unicystic variant merits separate considera tion for it seems to have a less aggressive growth pattern and behaviour. As a consequence, it can be treated more
Figure 148.5
Staphne's bone cyst in the body of the left
mandible. Courtesy of Edward Odell.
conserva tively.
16 17 ,
These ameloblastomas tend to deve
lop in a younger age group
with 75 percent presenting in
!-
1928 I PART
15 THE UPPER DIGESTIVE TRACT
the second and third decades of life. T he majority are in the mandible, again mainly in the molar and ramus areas. As the name would suggest, these tumours are unicystic and tend to be large, filling the angle of the mandible or the ramus. Tooth erosion is a suspicious sign. Paraesthesia is not a feature of ameloblastomas and they may be indistinguishable from large dentigerous cysts or kerato cysts. It is for this reason that a biopsy taken from large jaw cysts should be carefully examined for the presence of ameloblastic change.18 The unicystic ameloblastomas can be treated by enucleation supported by Carnoy's solution to reduce the risk of recurrence. Overall recurrence rates of
10-25 percent are reported after simple enucleation or 10 percent
curettage and this can be reduced to less than with the addition of Carnoy's solution.
CALCIFYING EPITHELIAL ODONTOGENIC TUMOUR Only
150 cases of this tumour have been described in the
literature. Twnours present as a slowly enlarging, painless mass. Initially, the lesion is radiolucent, mimicking a cyst or ameloblastoma, but with time radiopaque foci develop and a honeycomb or snow-like appearance is typical. It is a true n eoplasm with recurrence rates of 14 percent. Resection of the tumour with a margin of normal tissue is the treatment of choice.
ADENOMATOID ODONTOGENIC TUMOUR This is an uncommon benign neoplasm and its distinctive feature is duct-like spaces within an epithelial component. Unlike the other neoplasms, it tends to present in young adults in the anterior dentition as a well-defined soft tissue mass that radiologically appears as a unilocular radiolucency. Roots are seldom eroded, but frequently displaced. The thick capsule surrounding this lesion allows it to be enucleated. The risk of recurrence is 10w.19
SQUAMOUS ODONTOGENI C TUMOUR Another uncommon neoplasm that arises from cell rests in the periodontal membrane. It tends to present in the anterior
part
of
the
maxilla
and
can
be
treated
conservatively by local enucleation, but the treatment is always governed by its clinical presentation and beha viour. Those with an aggressive nature require wide resection. All odontogenic tumours should be treated with this principle in mind.
Figure 1 48.6
Mesenchymal tumours
Panoral radiographs of (a) a l arge
ame l obl astoma developin g at the angle of the left ma ndible;
(b)
a unicysti c ameloblastoma arisi n g in the lower right premol a r
ODONTOGENIC MYXOMA
region; and (c) amel oblastoma. Panels a and b, courtesy of
This tumour is thought to arise from undifferentiated
Edward Odell.
odontogenic mesenchyme in the tooth-bearing areas of
Chapter 148 Cysts
and tumours in and around the jaws, including sarcoma I 1929
both the mandible and the maxilla. It tends to affect young adults and is normally a unilocular or multilocular
radiolucency
found
coincidentally
on
routine dental
radiographs. The diagnosis is made by biopsy. These lesions tend to be gelatinous and local resection is necessary.
ODONTOMES These are hamartomas and not neoplasms. The com pound variety refers to formation of a recognizable tooth, whereas the complex form is a haphazard arrangement of tooth elements. These entities may be found at any time of life, but mostly in adolescence. They are asymptomatic
and, like so many other dental tumours, are seen on routine radiographs as a dense mass surrounded by a lucent zone. The presence of this capsule means that there is a definable margin between the lesion and the bone and therefore the odontoma is relatively easy to deliver surgically. There is no absolute indication to treat odontomes unless they are interfering with tooth eruption or position.
Nonodontogenic tumours of the jaws Figure 148.7
CT
scan of fibrous dysplasia fiIIi ng the maxilla.
This group of lesions includes a broad spectrum of entities, most of which are extremely uncommon. The generic term 'fibro-osseous lesion of bone' is widely used to denote a skeletal lesion where normal architecture is replaced by vascularized fibrous tissue. The definition encompasses several entities, namely fibrous dysplasia or ossifying fibroma, and juvenile or aggressive ossifying fibroma.
1 2
not
be
employed
as
there
is
a
sarcomatous transformation rate of about 0.4 percent which increases to over 40 percent following radio
therapy.22 As stated previously, the timing of treatment is lesions wanes as growth of the body ceases and where
This disorder presents in two forms. A localized solitary or mono-ostotic form is most conunon and accounts for
70 percent of patients. The remaining
Radiation should
dictated by the symptoms. The growth potential of these
c/f: expansion of bone and cosmetic deformity
FIBROUS DYSPLASIA
the maxilla or mandible can simply be paired down 20, 21 surgically or in children possibly treated medically.
30 percent are
multiple or polyostotic. Both types tend to be found in
possible surgical excision should be delayed as long as possible to avoid the likelihood of repeated interventions. This is not always possible because the swellings can be quite disfiguring.
the maxilla and mandible, but other bones of the facial skeleton
may
also
be
affected.
Polyostotic
fibrous
dysplasia can be associated with skin pigmentation and premature sexual
development in girls,
a condition
'known as Albright syndrome. Bony expansion caused by these
deformity.
The
radiological appearance is described as ground glass
lesions may
cause
a
cosmetic
with
no definable edge as the lesion simply merges with the surrounding bone
(Figure 148.7).
Without a biopsy, it is
impossible radiologically to distinguish these lesions from a range of other bony disorders, such as dermoblastic
OSSIFYING FIBROMA This condition presents in a similar way to fibrous dysplasia
with expansion of the bone and cosmetic
deformity, but it is more common in the mandible. It is a well-demarcated lesion
(Figure 148.8),
a feature that
distinguishes it from fibrous dysplasia on radiological
examination and also lends the lesion to simple surgical removal. The mass is normally divided with
a
burr and
the pieces then separate easily from the surrounding bone.
fibroma, osteosarcoma or osteomyelitis. Treatment de pends on the symptoms caused by the lesion and the age of the patient. A craniofacial resection may be required if
JUVEN I LE OSSIFYING FIBROMA
the lesion is encroaching on vital structures, such as the
This is a variant of ossifying fibroma that is found in
optic nerve, or displacing the globe. Bony enlargement of
the young
(5-15 years) and exhibits rapid growth over a
1930
I PART 15 THE UPPER DIGESTIVE TRACT
Figure 148.8
Orthopantomogram (OPG) of a
large ossifying fibroma in the angle of the right mandible. Courtesy of Edward Odell.
period of several weeks, rather than the typical slow
growth of the ossifying fibroma. The recurrence rate for
this lesion is approximately 50 percent.23 A conservative approach is still appropriate, bearing in mind the age of
the subject and the secondary deformities that attend radical surgery in the growth period.
of 3-84 years with a mean of approximately 40 years?4
Osteomas are the cause of sinus disease in 0.5-1 percent of patients. The frontal sinus is most frequently affected
where obstructed drainage can result in large muco
coeles?S In the external auditory meatus, cold water acts as a stimulus to induce exostoses, and other common sites are the lingual and palatal tori of the mouth. Mandibular
PERIAPICAL OSSEOUS (CEMENTAL) DYSPLASIA
This condition is the most common member of a group of 'cemento-osseous dysplasias' which are thought to arise
in the periodontal membrane. They are usually recog
nized as an incidental finding on radiographs. Initially, a radiolucent area is present at the apex of an otherwise
vital tooth and over a period of time this slowly calcifies.
The calcification is ill defined. Diagnosis is established
through follow up and no treatment is required. A
familial form of the disease, described as 'cemento
osseous dysplasia', has been reported. The condition is asymptomatic and has a predilection for black females.
It presents as a hard buccolingual expansion of the mandible that on radiographic examination appears as an
osteomas can
be part
of a triad of
premalignant intestinal polyps, skin lesions (epidermoid cysts, dermoids, lipomas) and osteomas that comprise Gardner syndrome, an autosomal dominant disorder.
Exostoses and osteomas are normally asymptomatic and
only require treatment if they become problematic or cause cosmetic deformities. These lesions have no malignant
potential and their growth rate can be exceedingly slow. A point to note is that what appears to be a simple bony exostosis of the scalp may represent the outward
and visible sign of a meningioma. Careful radiological evaluation is recommended for all
but the simplest
cases. Surgery is usually the treatment of choice and in
appropriate circumstances can be undertaken endoscopi cally or occasionally by radiofrequency ablation?6,27
ill-defined radiopaque mass with a ground glass appear
ance. The lesions tend to be multiple and in themselves present no real problem. However, this dense calcified
Giant cell lesions
tissue has a poor blood supply and if the mucosa is
breached, the lesion is prone to infection. Treatment
is therefore dictated by symptoms rather than the need to remove the lesion itself.
GIANT CELL GRANULOMA
It is unclear whether this lesion is a reactive or neoplastic
process and whether the nonaggressive and aggressive
variants represent a continuum of one disease or are two OSTEOMA/EXOSTOSIS
There is potential confusion between these two entItles which are not synonymous) even though the terms are
often used interchangeably. Exostoses are thought to be
developmental or reactive lesions, whereas osteomas are
distinct entities. In the majority of cases, the granuloma is
nonaggressive, asymptomatic and a coincidental finding
on a dental radiograph. In contrast, the aggressive variant is painful and there is evidence of erosion of cortical bone and teeth. This condition normally presents before the age of 30 years and is found equally commonly in- both
true neoplasms. Confusion arises because there is no
anterior and posterior aspects of the jaws. These lesions
The majority of osteomas that are found in the head
of hyperparathyroidism. A small nonaggressive lesion
auditory meatus and jaws. These lesions are found in
lesions may require resection with a margin of normal
evidence to support either point of view.
and neck region involve the paranasal sinuses, external patients of all ages. Cases have been reported in patients
have to be distinguished from the giant cell tumour
requires nothing more than simple curettage. Aggressive tissue.
Chapter 148 Cysts and tu m o u rs in and aro u nd the jaws. inc l u ding sarco ma I
193 1
CHERUBISM
AETIOLOGY AND PATHOGENESIS
This condition is histologically identical to giant cell
Sarcoma may be a feature of an inherited disease ( Table
granuloma but affects the four quadrants of the jaws in
148.4), as follows.
a symmetrical fashion. The disease is familial with a dominant mode of inheritance.28 Cherubism first mani
fests itself in early childhood and is progressive until puberty. The symmetrical enlargement of the maxilla results in ptosis of the lower eyelids and exposes the sclera producing the characteristic facies. Radiographi
cally, the lesion has a soap bubble appearance, teeth
are displaced and appear to be floating. The condition is
self-limiting
and
treatment
should
be
•
•
•
•
malignant peripheral nerve sheath tumours.
The following are considered to increase the risk of
developing sarcoma ( Table 148.5). •
are
a
Patients with neurofibromatosis type 1 have a 5-10 percent lifetime risk o f soft tissue sarcoma, especially
External beam radiotherapy. Malignant change in or
close to the irradiated field is well recognized. Both
ANEURYSMAL BONE CYSTS These
Retinoblastoma survivors have a greatly increase risk
of osteosarcoma.
where possible until growth ceases. The residual defor mity can be recontoured for cosmetic purposes. Radio
p53, increases the risk of rhabdomyosarcoma, breast cancer, brain tumours and leukaemia.
withheld
therapy is contraindicated.
Li-Fraumeni (a germline mutation of the tumour suppressor TP53 gene) .
blood-filled unilocular
or
multilocular
pseudocysts. Their aetiology and pathogenesis have not
yet been identified. They normally affect young adults and can evolve rapidly. These cysts have a radiolucent, 'blow
out' appearance on radiograph. Cysts are divided by fibrovascular septa and the contents are identical to giant
cell reparative granulomas.
As with
many
of these
odontogenic lesions of the jaws, diagnosis is made by biopsy. Treatment consists of curettage or enucleation, but recurrence is relatively common (25 percent) .29
soft tissue and bone sarcomas have been reported. •
Exposure to phenoxyherbicides, chlorophenols and
dioxins has been linked to increased risk of soft tissue sarcoma.
INVESTIGATION Investigation should include the following.
1. Imaging of the primary tumour is necessary to
define the extent of the tumour. It plays a central
role in the management of sarcoma and detecting distant metastases.
a. Plain radiographs and computed tomography
MALIGNANT TUMOURS ARISING IN AND AROUND THE JAWS
(CT) (with bone windows) show bone
destruction, while magnetic resonance imaging (MRI) defines soft tissue extension and marrow
Head and neck sarcomas
involvement.
b. Staging CT scans (3 mm cuts) of the thorax are
Head and neck sarcomas are rare, accounting for about
routinely employed for all types of sarcoma as
10 percent of all sarcomas. The rarity of these tumours
the lungs are the most common site of
has led to studies of pooled data over many years, during
have
which
diagnostic
and
therapeutic
metastases.
strategies
c. Isotope bone scans are indicated in the
evolved and the pathological classification has
following specific types: Ewing's,
changed. Although sarcomas are a heterogeneous mix of
neoplasms, they can be divided into two broad clinical groups - those arising in bone and those in soft tissue
( Table 148.2).30
.
Sarcomas show a biphasic age distribution, with 80-90
percent
presenting
in adult life.
Rhabdomyosarcoma
accounts for approximately 4-5 percent of all childhood malignancy. The most common primary bone tumours which develop in the head and neck are osteosarcoma,
chondrosarcoma, fibrosarcoma, malignant fibrous histio cytoma and Ewing's sarcoma (Table 148.3).
Lymph node metastases are generally uncommon and
only develop in 5-10 percent of cases. The one exception is . rhabdomyosarcoma.
Nodal
metastases
are
also
a
feature of synovial sarcoma, angiosarcoma and epithelioid
sarcoma. 32,33
rhabdomyosarcoma and osteosarcoma.
2. An image-guided tissue diagnosis (core biopsy) is recommended. This should be through an
approach that will cause minimal disruption of the tumour and surrounding structures. Fine needle aspiration biopsy rarely identifies the correct type of sarcoma and often underestimates the grade.34
3. Extensive haematological and biochemical
screening to test renal and cardiac function are part of the initial assessment. These tests are
repeated throughout the course of chemotherapy.
PRINCIPLES OF MANAGEMENT The
basic
principles
of
sarcoma
management
are
local control and prevention or treatment of recurrence.
/
_
. --
�-.
1932
I PART 1 5 T H E U PPER D I G ESTIVE TRACT
Tab le 1 48.2
Classification of soft tissue sarcomas.
Group F i b rous and myofibroblastic
TVp�
Su bty pes
Fibrosarcoma
Ad u l t type Infantile type I n fl a m ma tory type (infla m m a to ry myofi b roblastic tu mou r) Sclerosing e p i th e l i oi d type
Low-grade fi b ro myxoid sarcoma Fi b roh is t iocytic tu me u rs
Derm ato fi b rosa rc o m a protru b e ra ns3
Myxoid va riant Pi gmen ted va ri a nt Fibrosarcomatous va ri a n t
An g i e matoid(m a l i g n a n t h istiocytoma)3 M a l i g na nt h i st i o cy t o m a
Pl eomorphi c/storiform Myxoid vari a n t {myxofi b rosarcoma) G i a n t cel l varia nt I n flamma tory variant
Ad i pocytic tu m o u rs
We l l d ifferentiated (atypica l lipomate us)3
Lipom a - l i ke va ria n t Sclerosing varia n t I n fl a m matory variant Spi n d l e ce! l variant
Ded ifferentiated Myxoid/round cellb Pleomorphicc Smooth m u scle tumo u rs
Le io myesa rcomab
Conve ntiona l
Skeleta l muscle tumours
Rha bdomyosarcoma
E m b ryo n a l'
Epi the\ ioid Botryoid' Spindle cell Alve o l a r' P l eomorphicc Vasc u l a r tu m o u rs
Ang iosa rcoma'
Ep ithe l ioid vari ant
Ka posi's sarcoma Epithelioid haemangioe nd othe l i o m a Pe rivascu l a r tumours
Malig n a n t g l om u s M a l ig n a n t ha e m a n g i opericyto mad
Synovia l tu m o u rs
M a l i g n a n t tenosynovial g i a n t cel l tumou r
N e u roectoderm a l tum o u rs
M a l ignant p e r i p he ra l n erve sheath tu mour:
W i th h e terologous rhabd omyosarcoma (Triton tu mou r) W i th other mese nchy m a l heterology Epi the l ioid va ria nt
Malignant g ra n u l a r tu mouti C l e a r cel l sarcoma (m a l i g n a n t m e l a n oma of soft pa rts)h M a l i g nant m e l a n otic schwan noma M a l i g n a n t p e riphera l p ri m i tive neuroectode rmal tumour (Ew i n g's fa mily)' Extraskeletal cho n d ro-oseous tu m o u rs
Extraskel etal myxo id c h o n d rosarcomad Extraske l e ta l m esenchym a l c h o n d rosarcomac Extraskeletal osteosa rcomac
M isce I I aneo us
Alve o l a r soft p a rtb E pi the l i oidb Synovialh Desmoplastic small ce l l tumo u r Ectomesenchymoma Extrare n a l rh abdoid tumour M a l ig n a n t mesenchymomad
Troj a ni g ra d i n g is based on d e g re e of necrosi s ; m i to tic ind e x ; resemb l a nce to tissue o f o rigin. I n a d d i tion, some tumours by their nature fa l l i n to certa i n categories, i n d ica te d b y foo tnotes i n t h e above tab l e : 3 d efinition al ly low g ra d e ;
b not g radeable but often metastasize within 1 0-20 yea rs ; 'defi n itio n a l l y h i g h g rad e ; dvarying behaviour b u t g ra d i n g system defi ned ; evarying behaviour in w hich g rad i ng may be usefu l . Re produ ced w i t h pe rmission from Ref. 30.
Ch apter 1 48
Cysts and tu mours in and a ro u n d the jaws, i ncluding s a rcoma I 1933
Treatment is determined by tumour type, st age, anato
local infiltration, the resection must include
mical site and the age o f the patient. I t often involves
margin of normal tissue. Because of anatomical con
more than one therapeutic mo dali ty.35 In general, a wide,
a wide
straints in the head and neck, this principle is sometimes
en-bloc local resection is requi red t hat avoids transection
difficult
of the tumour. As sarcomas have a high propensity fo r
chemoradiotherapy can have significant functional
to
achieve.
It
sho uld
be
remembered
that
and
cosmetic consequences fo r children and these have to be Ta ble 1 48.3
H istological d istribution of head and n eck
sarcomas.
Incidence (%)
Osteosarcoma Ch ond rosarcoma Ma l ig n a nt fibrous h istiocytoma Fibrosarcoma Dermatofibrosa rcoma protrubera ns R h abdomyosa rcoma Leiomyosa rcom a Angiosarcoma H aemangioperi cytoma Neurogen ic sarcoma Li posarcoma Synovia l sarcoma Ewi ng's sarcoma Alveolar soft p a rt sarcom a Unclassifi ed from the
treatment fo r specific tumour types
will be covered under
their respective sections.
Type
Data
considered in treatment planning .36 The recommended
Loca l the ra py - s u r g e ry
1 4.8
For most sarco m as, surgery is the local treatment of first
6.4
choice. How radical the surgery should be depends on the tumo u r subtype and the likely effectiveness of chemo
11 .2 4.7
rad iation.
5.2
ra diotherapy can be very effective in controlling residual
In
some
s ubtypes
of sarcoma,
adj unctive
1 1 .0
microsco pic disease. However, it should be stated that, in general, s u rgical resection appears essential for long-term
2.4
co ntrol.
1 1 .2
1.9
Local therapy - rad i othera py
6.2 2.4
Sarcomas are relatively radioresistant. Radiotherapy is
3.6
most o ften u sed as an adjuvant to surgery or chemother
0.9
apy or both, aJ tho ugh it may be used as the sole radical local
0.7
MD Anderson Ca ncer Center, 1 9 70- 1 999 : 802
treatment when
the primary
is
no t considered
operable. When given with s urgery, it is usually given
17 . 6
cases?'
postop eratively. Radiotherapy
in combination with che
motherapy may achieve go o d lo cal control for p atients with rhabdomyosarcoma and to a lesser extent in those
Ta ble 1 48.4
Diagnostica l ly usefu l chromosomal a nd gene a bnorma l i ties in sa rcoma.
: Tumour
Synovia l sarcoma Ewing's/PNET Dermatofibrosarcom a Chondrosa rcoma: extraske letal myxoid
Ta ble 1 48.5
Chromosome abnormality
Molecular event
t (X;18)(p11 ;q l l ) t(11 .22), t(2 1 :22)
SYT-SSX fusi on EWS- FLI- 1 , EWSERG fusions CO LlA l -PDGFB fusion EWS-CH N
+
8 ri ng ch ro mosomes
t(9 :22)
with Ewing's sarcoma. There are no clinical trials that compare the effectiveness of treatment fo r high-grade sarcomas with radiotherapy alone as opposed to surgery. Syste m i c therapy
Chern a therapy Chemotherapy is o ften used fo r both intermediate- and high-grade so ft tissue sarcomas, either as adjuvant or neoadjuvant therapy. It is no t generally used
The ab ility of adjuvant chemotherapy to facilitate s u rgery o r to improve lo ng-term survival has not yet been established. The agents most commonly used are
Ri�k f�� ors a� d aetio logy for sa rcoma.
Ge:n·�t.¥ , '. '� .. . . .,; .: " ' :'
.
" . ; :, '
'Re l ev� nt to·-head: '-and'.ne'ck?'; · ,-::,. . , ' • .
- .
. ..
N e u rofibromatosis N F l Li-Fraumeni Reti noblastoma
M PNST increased Va rious sarcomas, bra i n and haem atolog ical m a l igna ncies I n creased risk of osteosa rcoma
G ard ner syndrome
PolYPOSis col i and soft tissue tu mours, espeCially fi bromatosis Previ ous rad iat i o n : both bone a nd soft tiss u e tumours U rethane, ethylene derivative, polycycl i c hyd roca rbons H IV and Ka posi
Environ menta l Carcinog ens Virus
in low-grade
sarcoma.
I
Yes Yes Yes, especia l ly if previous radioth erapy to reti noblastom a Yes Yes No Yes
1934 I PART
15 TH E U PPER D I G ESTIVE TRACT
doxorubicin and ifosfamide. The largest review to date of
the alveolar subtypes ( 15-20 percent of RMS) . Botryoid, a
no significant difference in five-year survival with only a
good prognosis, whereas the alveolar subtype has a worse
14 randomized trials of adjuvant chemotherapy showed
small reduction in the progression of disease. 37
[****]
These studies drew on data from other sites. However,
there is reason to believe that head and neck sarcomas
subgroup of the embryonal form, carries a particularly
prognosis ( Table 148.6).
adults is very rarely found in children.
may behave differently. The local relapse rate of head and
Prese n tation
lower than that for the extremity tumours that formed
site
neck sarcomas is considerably higher and the survival rate the majority of tumours studied in these trials.
Neoadjuvant chemotherapy, which has radically al
tered both local and distant control in tumours of the
paediatric and young adult type, has not been of overall
benefit in adult-type soft tissue sarcoma. However, it has been argued that it may be of value in head and neck
sarcoma
where
the
local relapse
rate
with
current
strategies is much higher (40-50 percent rather than
10-20 percent),38 but evidence from randomized studies
is lacking.
Chemotherapy regimens for soft tissue sarcoma are
in different combinations and intensity, depending on the prognosis for that particular tumour type. These proto alkylating
cyclophosphamide,
agents
such
actinomycin
as
D
ifosfamide
and
and
doxorubicin
and, more recently, etoposide. In some situations, the
platinum-based agents cisplatinum and carboplatin are
added or substituted. All these protocols are intensive and
often toxic and they should be administered in a specialist
centre.
determines
the
presenting
symptoms
and
also
influences the prognosis. Orbital tumours account for
10 percent, parameningeal (nasopharynx, nasal cavity,
paranasal sinuses, middle ear, mastoid, pterygoid fossa)
20 percent and other head and neck sites 10 percent. Orbital tumours present with proptosis and have rarely
spread at the time of presentation. Parameningeal sites carry a risk of intracranial spread and cerebrospinal fluid (CSF) involvement.
Initial staging involves full clinical examination and
usually prolonged. Multi-agent schedules are employed
use
Forty percent of RMS present in the head and neck. The
Staging
Chemo therapy regim ens
cols
39 The pleomorphic type seen in
The
principal
and
severe
acute
toxicity
is
neutropenic sepsis. Many of these agents cause alopecia (temporary) , fatigue and may adversely affect fertility.
The main late risks to organ function are to the heart (actinomycin and doxorubicin) and kidneys (the alkylat -
ing and platinum agents) .
imaging of the primary and regional lymph nodes,
together with a biopsy of the primary tumour. Particu
larly at parameningeal sites, both CT and MRI may be
necessary to define the extent of the tumour and positron emission tomography (PET) may contribute further in this respect. There has been a difference in approach to nodal staging in Europe and the USA (Tables 148.7, 148.8 and
148.9), with the latter until recently favouring
surgical assessment, while the former relies on clinical
and radiological examination only. Once the diagnosis has
been
made,
staging
is
completed
with
a
CT
examination of the lungs, bone scan, bone marrow aspirate and
trephine.
In those
with parameningeal
tumours, CSF analysis is necessary, as well as extensive
haematological and biochemical screens.
Principles of management Except for small, localized tumours where a complete excisional biopsy may be suitable, the initial treatment is
SPE C I FIC TUMOUR TYPES
by neoadjuvant chemotherapy. Different staging systems
have been used to plan an appropriate treatment strategy
Soft tissue sarco m a - rhabdomyosarco m a
Sarcomas of the soft tissue comprise some 8 percent of childhood tumours and
are a heterogeneous group.
Rhabdomyosarcoma (RMS) is the most common single
variety accounting for approximately 4-5 percent of all
childhood malignancy with an annual incidence of 5.3 per
million children under the age of 15 years. The median
for each patient. In general, a multimodal approach involving surgery, chemotherapy and radiotherapy is
necessary. 40
Table
1 48.6
Stag e d istri bution a nd prog nosis of
rhabdo myosarco m a .
Stage (Ofo)
age at diagnosis is about five years and boys are more frequently affected than girls.
I
II
II I
IV
(Ofo)
(Ofo)
(Ofo)
Overal l survival (Ofo)
Rhabdomyosarcoma is thought to arise from primitive
mesenchymal cells that would develop into striated muscle. It can be found virtually anywhere in the body, including those sites where striated
muscles are not
normally found. Two main forms of RMS have been distinguished
in
childhood,
the
embryonal
(which
accounts for approximately 80 percent of all RMS) and
O rb i t
70
25
3
2
90
Para m e n i ng e a l
10
65
20
5
60
N o n pa ra me n i n g e a l
40
40
15
5
75
Based on d9ta from the I nternational Society of Ped iatric Onco logy (Sl O P) M a l ignant Mesenchymal Tu mors Study 89 (MMT89) and the I nterg rou p Rhabdo myosa rcoma Study I I I (l RS- I I I).39
Chapter 1 48 Cysts a n d t u m o u rs in a n d a rou n d the jaws, i n c l u d i n g sa rcoma I
Table 1 48.7
I nternatio n a l Society of Pa ediatri c O n co l ogy (S l O P)
-
'-,
European studies omitting local therapy in patients who
achieve a complete response. This has been associated
sta g i n g system . Sta� e
1935
with a higher local relapse rate. However, the salvage rate
Descri�tioJ1
is high and the justification for this approach has been the lower overall long-term morbidity produced.
TO
No evi d e n ce of pri m a ry t u m o u r
Tl
Tu m o u r confi n ed t o o rg a n o r tissu e of o ri g i n
Tl a
S cm or l ess
Tl b
M o re t h a n S cm
T2
Tu m o u r i nvo lvi n g o n e or m o re co ntig uous o rg a n s
T2a
S cm or l ess
T2b
M o re t h a n S cm
NO
No evid e n ce of reg i o n a l nodes
N1
Evi d e n ce of reg i o n a l node i nvo lve m e n t
In
principle,
patients are treated with multidrug
regimens. Where local therapy is indicated, surgery, if
not mutilating, is preferred to radiotherapy because of concerns of late toxicity produced in young children. Surgery
is
conservative
NX
Node sta tus u n certa i n
MO
No evi d e n ce o f d i sta nt m etastases
Ml
Evi d e n ce of m etastases
rarely in
used
nature
in
orbital
when
tumours
undertaken
and
is
elsewhere.
Radiotherapy produces a high local control rate. Doses in excess of 55 Gy are rarely indicated and most current
protocols use doses of 45-55 Gy, depending on the site and response to chemotherapy.
Outcome In recent years, multimodality treatment has improved
Tab l e 1 48. 8 ,- - -
•
.- : 1
. "J
cure rates from 25 to approximately 70 percent. Alveolar
Stage g ro u p i n g . -
.�
subtype, age over ten years, large size and parameningeal
- ..i
sites are adverse prognostic features. [ ****]
TN M
Nod,es -�
Metastases
I
T l a , Tl b
NONX
MO
II
T2 a , T2b
NONX
MO
Prese n tation
III
Any T
I'l l
MO
About 33 percent of patients present with tumours of the
IV
Any T
Any N
Ml
�tag�
Soft tissue sa rco mas of a d u lt type
scalp or face, about 25 percent in the orbit or paranasal sinuses, 25 percent in the neck and the majority of the rest
in the upper aerodigestive tract (Table 148. 1 0 ) . Lymph Tab l e 1 48.9
Sta g e g rou p i n g : I n terg ro u p rhabdo myos a rcoma
study ( I RS).
further 1 percent developing them later. Lymph node
.' Group , pescri pti c>n
involvement develops almost exclusively in rhabdomyo sarcoma, synovial and epithelioid sarcomas.
Loca l i zed co m p l etely resected
a . Confi n ed to org a n of o ri g i n b . O u tside org a n o f o ri g i n c.
II
l'l ode n eg ative
Co m pro m ised resection
a . G ross ly resected ; m i crosco p i ca l ly pos i tive m a rg i n : node negative b.
Reg i o n a l d isease, exte nsion i nto oth e r org a n or nodes co m p l etely resected , w i t h o u t m i crosco pic res i d u e
c.
Reg i o n a l d isease g rossly resected, but with m icrosco p i c res id u u m
III
G ross m a crosco p i c d i sease
IV
Dista nt m etastases
About 45 percent of patents eventually develop distant
metastases and this risk is largely dependent on the grade of the tumour.
The most common site for distant
metastases is the lungs. Factors predictive of relapse,
other than tumour grade, are size over 5 cm, margin status and invasion of bone, skin or neurovascular structures. Negative margins have a 70-88 percent control
rate, positive or close margins 52 percent and gross
removal of local disease just 25 percent control rates. 4 1 , 42
Principles of man agement Usually,
initial
treatment of
soft
tissue
sarcoma
Table 1 48. 1 0
Anato m ica l site of head a n d neck s a rcom as.
S i te
Ofo 3 1 .0
S i n o nasa l t ract: a nterior/m ed i a l sku l l base
30.S
risk-adapted, intensifying chemotherapy schedules for
U p per a e ro d ig estive tract
1 8.0
Pa rotid and neck
1 9 .0
beyond the scope of this chapter. The two groups have
Other
tumours with a worse prognosis. A detailed description is differed in their emphasis on local therapy, with the
is
resection. The principles of surgery for sarcomas were
Sca l p a n d face
Both European and USA protocols are complex and
L
node metastases are uncommon with only 3-8 percent
having detectable nodes at the time of presentation and a
1 .S
Data from the MD An derson Cancer Center, 1 970- 1 99 9 : 802 cases? 1
1936 I
PART 1 5 TH E U PPER D I G ESTIVE TRACT
described first by Simon and Enneking4 3 and remain the basis of sarcoma management. En bloc excision is
metastases. Long-term survival may be achieved in those
with bone or bone marrow secondaries, but generally the
recommended as piecemeal resection is associated with a
prognosis is extremely poor.
as anything less is associated with a significant rate of relapse. 44 En bloc resection is often difficult in
Principles of management At the outset, four to six cycles of multiagent chemother
even complete macroscopic removal may be extremely
therapy planned. A resection is best, but radiotherapy can
high rate of relapse. A wide margin of resection is advised
the head and neck; margins are rarely wide enough and
apy is given. The patient is then reimaged and local
difficult.
be effective if surgery would be mutilating. Radiotherapy
relatively radioresistant. Most clinically detectable tumours
to chemotherapy is poor. Adjuvant chemotherapy con
are unlikely to be eradicated by radiation doses within
tinues to a total of 1 2-14 cycles, with reduced intensity
of
cyclophosphamide in combination with either actinomy
Adult-type soft tissue sarcomas are considered to be
normal tissue tolerance, but there is a considerable body evidence that shows it is capable
of destroying
microscopic disease. In current practice, adjuvant external
is given if the surgical margins are positive or the response
regimens using alkylating agents, ifosphamide and or
cin and doxorubicin. Etoposide has been added to more
beam radiotherapy often follows surgery and is usual in
recent regimes. 4 6
with positive or less than radical margins and in tumours
Pri m a ry bone sa rco m a s - osteosa rco m a
intermediate- and high-grade tumours, especially those greater than S cm in size.45, 4 6
[****]
Nonrandomized
Osteosarcoma i n the craniofacial region comprises some 5
radiotherapy (70-77 percent) than with surgery alone
from the most common osteosarcoma of the extremities.
50 Gy and surgery four to six weeks later produces fewer
of in-field or edge induction of osteosarcoma.
[***1**]
studies report higher control rates with the addition of
(45-55 percent). 4 7, 4 8 Preoperative radiotherapy with
side effects and has been associated with high control
rates and may offer a more promising approach.4 5
Pri m a ry bone sa rcomas - Ew i n g ' s fa m i ly of tu m o u rs
percent of all osteosarcomas and differs in several aspects
Radiotherapy, especially for retinoblastoma, carries a risk
Presen tation The median age of presentation is in the fourth decade of
life with a higher proportion being low-grade tumours
Primary bone sarcomas account for less than 3 percent of
and propensity for distant spread appears to be lower
adults and less than 5 percent in children. The Ewing's
subtypes can occur in the head and neck. Osteoblastic,
all head and neck benign and malignant tumours in
( 1 0-20 percent compared to 50-75 percent). Most
family of tumours arise primarily in bone, although soft
not otherwise specified ( NOS), is the most commonly
tissue presentation may be seen. They account for 10-15
reported osteosarcoma (75 percent) and chondroblastic
of five years and uncommon over 35 years. The peak age
telangictatic subtypes of osteosarcoma are uncommon.
percent of primary bone tumours are rare under the age
of presentation is between 10 and 20 years.
Presen tation The most common presenting features are pain and
swelling of the affected area. Fewer than 2 percent of this
group of tumours arise in the bones of the skulL Systemic
symptoms, such as fatigue, weight loss and fever, may develop and lymphatic spread is unusuaL Overall, about
20 percent of patients will have metastases at the time of
diagnosis, usually in the lungs, but sometimes in bone and bone marrow.
Prognosis and staging
the second ( 1 6 percent) . Fibroblastic, juxtacortical and Osteosarcoma arising in Paget's is relatively uncommon at this site and is most often seen in women over 65 years.
The majority arise in the mandible and maxilla. Most tumours measure 3-6 cm at presentation (Figure 148.9) . Grade is an important prognostic feature. Over 35
percent are low or intermediate grade, which is a higher proportion than in the limbs; mandibular tumours are more likely to be of lower grade than elsewhere and larger
tumours are more commonly high grade. Overall survival
rates are of the order of 60 percent with age over 60 years,
size over 6 cm, positive margins and nonmandibular sites
being associated with a poorer prognosis. Surgery is an essential part of treatment,
with long-term survival
Stage is determined by imaging, an isotope bone scan,
without surgery being of the order of 20 percent. As in
factors are: presence or absence of metastatic disease, site
have been associated with poorer survivaL
adjuvant chemotherapy. Unfortunately, the majority of
Principles of managemen t
marrow aspirate and trephine. Important prognostic of metastasis, tumour volume and response to neo
several other head and neck sarcomas, positive margins
[****1***1**]
patients have micrometastases at presentation. Survival
Before the routine use of adjuvant chemotherapy for
multimodality therapy, survival rates of 50-70 percent
a better overall outcome with survival between 23 and 60
after local therapy alone is only 10 percent. With modern
may be achieved in those without obvious secondaries,
but this decreases to 30 percent in those that have
extremity osteosarcoma (OS), head and neck OS had
percent, compared to 10-20 percent in the extremities.
Chemotherapy has improved the latter to over 60 percent,
Chapter 1 48 Cys ts
a n d tumours i n a n d a round the jaws, i n cl u d i n g sarcoma I 1937
Figure 1 4 8. 9 Chondroblastic oste osa rcom a , rig h t mandible. Large m a ss i nvolv i n g right body of mandib le, a n ter i orl y to midline a nd posteriorly to junc t ion of body and a n t e rior sur fa c e of ra m us. The m ass bu lges i n to the oral cav ity a n d fl oor of mou th, displacing tongue a nd laterally into the cheek, displacing the bucc i n a tor m uscle. (a) O PG ; (b) T1 coronal M R I ; (c) T1 axial M RI . but the effects i n OS o f the head and neck are u nclear,
plays a signi fic an t role. High":gra de spindle cell tumo urs of
fib ro us h istio cytoma
possibly due t o the h igher proportion of lower grade
bo ne, fibrosarcoma and malignant
turnours in t he head and neck . The similar prognosis o f
are generally treated as osteosarcomas.
p at i ents
t reated
wit h chemotherapy
or n o t may
be
Pr i m a ry bone sa rco m a s - c h o n d rosa rcoma
interp re t ed as s ugges t ing no advantage or a benefit as 49 50 the fo rmer gro up had worse pro gnostic fea t ures. ,
The most common age is the fifth to seventh decade.
I n sum mary, improved survival has been noted over
These are a group of tumours of varying behaviour. The
the last 20 yea rs , with curren t su rvival of the
ord er of 60 however, the survival
central types comprise conventional, dedifferentiated and
is lower at less than 40 percen t , presumably due to the
may also be extraskeletal and these su btypes a re myxo id
percen t . In a series o f children onl y
mesenchymal
and
clear
cell
types.
Chondrosarcoma
hig her proportion of high-grad e tumou rs. The ro l e o f
or arise in osteochondroma s or associated with a mult iple
chemothera py i s no t defined but may h ave a s urvival
exostosis syndrome .
high
Mesenchymal chond rosarco ma is an aggressive sub
grade d isease. Unl i ke th e case in extremity osteo s a rcoma,
type of chondrosarcoma, tending to develop in you ng
di sta nt metastases,
women . They may h ave a rapidly p ro gr essive co u rse.
be n e fi t in high - risk pa t ients , essenti ally those with where mo rtality is related p rimari l y to
i n head and neck osteosarco ma failure of local control
In
view
of this,
treatment
wi th
chemotherapy
and
.
1 - __.
_
1 938 I PART
1 5 TH E U PPER D I G ESTIVE TRACT
radiotherapy may be indicated, although there is no clear evidence of benefit.
The majority of cases in both adults and children are
low grade. Surgery is the treatment of choice, usually without adjuvant therapies.
In general, pain, paraesthesia, trismus and rapid onset
of malocclusion are not usual features of benign tumours and may indicate a malignant process.
Both chemotherapy and
radiotherapy have been used, but in insufficient numbers to allow comment on efficacy. Chondrosarcoma ( except
for the mesenchymal and dedifferentiated subtypes) is generally considered to be resistant to both these therapies.
MALIGNANT AMELOBLASTOMA AND AMELOBLASTIC CARCINOMA The
malignant
forms
of ameloblastoma
have been
classified into two subtypes according to clinical beha viour and histological features.
SURVEILLANCE IN SARCOMA
M a l i g na nt a m e l o b l asto m a (m etastasizi ng
The majority of tumour relapses develop within two
a m e l o b l a stoma)
years. There is little published on surveillance strategies
Distant metastatic lesions are present yet histologically
and
The interval between diagnosis of tumour and manifesta
specifically on head and neck sarcoma. Paediatric, Ewing's osteosarcoma
protocols
usually
include routine
imaging of the primary and sites at risk of secondary tumours, for at least two years with initially CT and then
chest radiographs for metastatic surveillance. There is no evidence-base
in
the
head
and
neck
sarcomas
on
surveillance strategies for soft tissue sarcoma. For such
resemble the primary benign-appearing ameloblastoma.
tion of metastases is long. The average interval is 12 years, although
the
development
of metastases
has
been
described up to 30 years after diagnosis. Metastases are typically found in the lung (88 percent) and the lymph
nodes (27 percent) . Distant metastases to bone, brain,
tumours Dverall, there is no survival benefit for regular
kidney, small intestine and liver have also been reported.
cross-sectional image at suitable intervals may be valuable
produce significant effective improvement; the response
CT or MRI of the primary site. A post-therapy baseline
where clinical assessment is difficult (as after extensive surgery or radiotherapy) and, where the tumour site is
not amenable to clinical examination, a programme of routine
images
for
the
first
two to three years
is
reasonable. Surveillance CT of the lungs does not improve outcome over well-performed chest radiographs. Chest
radiographs at intervals of three to six months over the
first five years are recommended with CT scan to clarify any abnormalities. 5 1 [ * ]
Treatment is unpredictable: chemotherapy does not
to radiotherapy is also variable. The treatment of choice tends to be surgical resection of pulmonary metastases
as it is considered the more likely option to offer a significant disease-free survival or cure.53
The a m e l ob l astic carci n o m a
This is a very rare tumour that is found primarily in the mandible and over a wide age range with no sex or race
predilection. The primary lesion shows dedifferentiation and
TREATMENT OF RELAPSE Chemosensitive tumours may be amenable to salvage
after local or distant relapse. Where isolated secondaries in the lung develop in osteosarcoma or adult-type soft tissue sarcoma, pulmonary metastectomy may be asso
ciated with survival of 40-50 percent at three years and
35-40 percent at five years. Where surgery is not possible,
chemotherapy may be used palliatively. Mean survival is 1 2-20 months.5 2
cytological
atypia
as
compared
with
a benign
ameloblastoma. Its presentation is variable, such as a
predominantly cystic lesion with benign clinical features or a large tissue mass with ulceration, bone resorption
and tooth mobility. The clinical course of ameloblastic
carcinoma is typically aggressive, with extensive local destruction. Direct extension of the tumour, lymph node involvement and metastasis to various sites have been
reported. 5 2
Wide local excision is the treatment of choice. Cervical
lymph node dissection should be considered when there is obvious lymphadenopathy.
Radiotherapy and chemo
therapy Seeii1 to be of limited value for the treatment
Mal ignant odontogenic tumours
of ameloblastic carcinomas. Close periodic reassessment
of the patient is mandatory.
Malignant odontogenic tumours ( MOT) represent 0-6. 1
percent of all odontogenic tumours. These percentages
are based on the small number of series published worldwide. Diagnosis of MOT may be complicated as
Squamous cel l cancer arising in odontogenic keratocysts
some benign odontogenic tumours (the benign amelo blastoma and calcifying epithelial odontogenic) are locally aggressive and relentless and may be confused with a malignant lesion.
Squamous cell carcinoma arising from malignant trans formation of an odontogenic keratocyst is extremely rare
with less than 60 cases reported in the world literature.
---�
Ch a pter 1 48 Cysts and t u m o u rs in a nd aro u n d t he jaws, incl u d i n g sa rco ma I
Wide local excision is important and the hi s t o l og ic al requirements for th is diagnosis are sp e c ifi c .
Best cl i n ic � 1 practice
...,
1939
,-
./ Surgery is ce n tra l to the t rea t m e nt of most
M etasta ti c t u mo u rs of th e j a w
sarcomas w i t h loca l co n trol havi ng a m ajor i m pact on s u rv iva l.
The most cemmon t umo u rs that me t as t as i ze t o. the j aw are carcinoma of the lun g and ade necarcinema of the
breas t, prosta te, kidney, thyro id an d liver. The mos t
j aws is the
comme n site within the
p o t er ior mandible.
s
The commen mode of p r es e n t a t i e n i s l oosening of the
teeth,
unil ate r
./ N eoadj uva n t chemoth erapy has im proved su rvival in osteosa rco m a , E w i n g ' s and rhabdo myosarcoma sign i fica n t ly,
./ H i gh q ua l i ty ca re of sarcoma req u i res: - ap p ropria te imagi n g ;
- bio psy, preferably i m a g e-g u i d ed a n d u n d e rtaken i n
al numbness of the chin and event ually
s u c h a w a y t h a t su bseq u e n t ra dical su rgery is n o t
ulceration ef the seft tissues. Treatment tends to i nvolve
com p rom ised ;
pallia tive chemetherapy and/er ra di o the rapy.
- m u l t i d i sc i p l i n a ry d i sc u ss i o n a n d m a n a g e m en t p l a n at the o u tse t ;
.
,
-
. ..;, ....
-
- t reat ment with i n a t ria l pro tocol where ava i lab l e ;
.
KEY PQI NTS ,
."
�:�j .:.; qyst�
are
.
-
' .
.
.
a .frequent occurrence in the
I '·
...
, ,
,...
'
ja\\;s
:,' because epithe1iaJ: rep)nants , persist i n t he
neoadj uva nt thera py, w h e. n ind icated, a d m i n iste red
'.
i n a speci a l ist ce ntre ; t i m e ly p l a n n i n g of loc a l th erapy co nsidering
;.
re spo nse to chemot h e ra py ; extent of su rg e ry
boO:e: -: :. " a ft er" tOoth for��ti(m".with the majodty of jaw .' ';�: ' .i ,. cysts-,�·eing: o.d()otogc rue; i n 0. ri gin. Not'maUy;:, .,,) ;. .
·
.' · ,�" theY'·�re a4 · .incidentaI fif}ding" fo:l.16,�� ng
. :�ra,e;i.iographic·.exa:tp.i'n'cltion. qf
,
the-"J aws
re q u i red (if a ny) t o dear tumou r- beari ng tissue ; ra di ose n sitivity of t u m o u r type a n d l i ke ly effectiveness as sale local the rapy or adjuvant to su rg e ry ; fu n c t i o n a l a n d cosmetic conseq u e n ces of
',' "
e i t h e r or both loca l moda l ities ; and the appro p r i a te
' ..:.,. ' 'c The corrip lic�'ted ,em,btYolO.gicaLd,6�elQPIriei}t. · · of the jaws} togeth er wi th different paH�rns " ?f cellular differentia t ion, make the , . odontogenk tumours a ' highlY,dj.veTse gtoti'p -- ' . 01 lesions. The most co'mnlon o.dQntbgenic':: , turrnour is the ameloblasto ma: ; . '-' . : ',£." ,� , �: y ,' ' --. .' , Osteoma and exostoses are two:., ·separat e en ti ties - exos t ose s are thought -to ·b� developmental or re�ctive,lesions�. whereas
su ppo rt services .
"
./ Fo l l ow up of a m e l o b l astomas s h o u l d be i n d e fin ite a s recu rren ces can deve l o p beyon d 20 ye a rs.
�
, :- '.osteomas are tru e '. ' The major i t y of
Defic i e n c i es i n cu rre n t know l e d g e a n d a reas fo r futu re resea rch
neoplasms. ' . "
osteomas are found in t he . head and .. neck regi on , inv<;>lving, ' , predominantly the paran-asal sinuses) ex t e r n al 1 ;:' caudit o, IY '.m.e atus . �d -jaws: :.'.: : ; ,': ':,¢- '- , ,' . ' ' Tutnoms of...ttte -'j.��s qp1 either ' �Tis� ::';'\ �':;l :):'�-." ' ,-, ,� , pri m a r ily ot tesiillt froq!' invasion, of tuirion!s that have dev;eloped '·in,·:a-dj���nt· ·stru��'res: ·
Fo r soft tissu e sarco ma of a d u l t type , a p pro pri ate
1 .
ma nagement stra teg i es have not bee n adeq u a tely
·
deve lo ped and a u s efu l evi d e n ce-base is l a cki ng.
. '.� .
,
·
,
). M ost p a t i e n ts u n dergo su rg e ry fi rst A h i g h proport i o n of t u m o u rs h ave pos i tive ma rg i ns a t surgery,
-
R a d i othe r a py is probably u su a l ly added for
.
Metastases,
·0
most
i n term ediate- a n d h i g h-g ra d e t u m o u rs and is us u a l l y
commocly trorr.i:;brorlchifS, ' kidney,-' may �lso' ,be'. " ,
posto p e r a tive a n d m a y redu ce, but d o e s n o t
breast, liver, thyroi.d', or
fo und in the jaws'. , Sarcomas are uncommon malignancies ·that
•
e l i m i nate, t h e adverse effect of m a rg i n pos i t ivi ty, ). For n o n m etasta t i c t u m o u rs , the rol e of chem othera py as neoadj uva nt or a dj uva n t is l a rgely u n k n o w n .
yinal tissue ,and are seen in
arise from mesench
all age groups. They cOl1lprise only 1 percent of malignant tWl101.irs' in 'adultS, but are . relatively more conu:npn in children. and adolescents., About ' 1 ' p ercent 'of head and :neck tumours are s arco mas and ahout lO · :peicent
of sarcomas present in the h�d, and neck., ' • ,
Rhabdomyosarcomas account- for a pp roximately 4-5 percent of all · childhood . malignancy.
Possi b i l i ties fo r i m p roved ma nage m e n t i n c l u d e bot h neoadj uva n t che motherapy a n d ra diot hera py.
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2.
PART 1 5 TH E U P P E R D I GESTIVE TRACT
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*
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f"J" "
Chapter 1 48 Cysts a n d tu m o u rs i n a n d a rou nd t h e jaws, i n c l u d i n g sa rcoma I
N eck S u rg eo n s Co m m ittee o n Resea rch . Head and Neck.
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149 Anatomy of the pharynx and oesophagus NIGEL BEASLEY
Introduction
1942
Anatomy of the oesophagus
1951
Embryology
1942
Key points
1952
Anatomy of the pharynx
1944
References
1953
INTRODUCTION The pharynx lies at the crossroads between the respiratory and digestive tracts controlling and diverting air, fluid and food on their appropriate course using propulsive waves of muscle contraction and a series of valves. The pharynx also plays an important role in the production of speech. Pharyngeal dysfunction due to surgery or neurological disorders may result in dysphagia, aspiration and speech problems, the devastating consequences of which are a testament to the success of this system in normal individuals.
covered by ectoderm externally and endoderm internally. They are separated externally by deep pharyngeal clefts and on the inside by depressions corresponding to the clefts, the pharyngeal pouches. There are five pairs of pharyngeal pouches, although the last is considered part of the fourth. Each has a ventral and dorsal section. The endodermal lining of the pouches gives rise to a number of structures as shown in Table 149.1. The mesoderm of each arch differentiates into the cartilage, muscle and vascular structures of that arch (see Table 149.2 and Figure 149.2). Table 149.2 shows which branchial arch gives rise to the skeletal components, cartilage, muscles and nerves, and is important in that
EMBRYOLOGY During the early stages of embryonic development, cephalocaudal and lateral folding result in the formation of an endodermally lined primitive gut. In its cephalic part this forms a blind ending tube, the foregut, which is separated from the ectodermally lined stomatodaeum by the buccopharyngeal membrane (Figure 149.1). This ruptures and the stomatodaeum becomes continuous with the foregut. The endodermal lining of the foregut differentiates to form many parts of the aero digestive tract including the pharynx and oesophagus ..
-----2
8
3
9
4
10
5
11
6
12 Figure 149.1
Saggital midline section of a 23-25 day embryo
to show the position of the foregut and stomatodaeum. 1,
Embryology of the pharynx
Tracheobronchial diverticulum; 2, foregut; 3, buccopharyngeal membrane; 4, Rathke's pouch; 5, stomatodaeum; 6, amniotic
The pharyngeal arches develop in the fifth week of embryonic life. They consist of a core of mesoderm
cavity; 7, ~eural tube; 8, mesocardium; 9, heart tube; 10, pericardial cavity; 11, septum transversum; 12, yolk sac.
Chapter 149 Anatomy of the pharynx and oesophagus
it provides the logical basis for understanding the anatomy of this region, in particular its nerve supply. Each arch receives an afferent and efferent nerve supply for the skin, muscles and endodermal lining of that arch (post -trematic nerve) and an additional nerve from the next arch (pretrematic nerve). The mesoderm of the second arch actively proliferates and moves downwards to overlap the third and fourth arches and clefts fusing with the epicardial ridge in the lower neck. The second, third and fourth clefts lose contact with the outside and form a temporary cavity lined with ectoderm, the cervical sinus. This usually disappears completely but may persist as a branchial cleft cyst. If the second arch fails to fuse with the epicardial ridge, a sinus will remain in contact with the skin. Occasionally, the mesoderm between the second pharyngeal cleft and pouch will break down leaving a sinus with an external opening on the skin of the neck and an internal opening in the tonsillar fossa.
Embryology of the oesophagus The oesophagus develops from the foregut below the primitive pharynx. At the upper end of the foregut the tracheobronchial diverticulum appears on the ventral wall around the fourth week. This becomes separated from the developing oesophagus by the tracheobronchial septum, which grows in from either side. The tracheobronchial
~""'~---9
rc:;,;;.t----10 -H----11 -r------12
------13
1
14
2------~~~~ 3--~
Table 149.1
Derivatives~ of the pharynge~1 pouches.
PoilcbDorsaLsectiorl'
I 1943
15
4----~---16
6----
VentralcseCtion:
5--------~~
1st
Middle ear and Eustachian
Obliterated
tube (with 2nd) 2nd
Dorsal pharyngeal wall -
Figure 149.2
Tonsil
4, fourth arch cartilage; 5, tracheal rings; 6, sixth arch cartilage;
nasopharynx and adenoid 3rd
Parathyroid - inferior
Thymus
4th
Parathyroid - superior
Ultimobranchial body C cells of thyroid
Table 149.2
1st
2nd
7, Meckel's cartilage; 8, malleus; 9, incus; 10, stapes; 11, styloid process; 12, stylohyoid ligament; 13, lesser horn and upper body of hyoid bone; 14, greater horn and lower body of hyoid bone; 15, thyroid cartilage; 16, cricoid cartilage.
Structures developing from the pharyngeal arches.
Dorsal-maxillary process
Muscles of mastication
Ventral-Meckel's cartilage
Anterior belly of digastric
Incus
Mylohyoid
Malleus
Tensor tympani
Sphenomandibular ligament
Tensor palati
Stapes
Stapedius
Styloid
Stylohyoid
Stylohyoid ligament
Posterior belly of digastric
Lesser horn and upper part
Auricular muscles
of hyoid 3rd
Derivatives of the pharyngeal arches. 1, First
arch cartilage; 2, second arch cartilage; 3, third arch cartilage;
Mandibular division of
Facial (VII)
Muscles of facial expression Glossopharyngeal (IX)
Thyroid
Cri cothyro i d
Vagus (X) and accessory (IX)
Cricoid
Levator palati
Arytenoids
Constrictors of pharynx
of hyoid 4th and 6th
Corniculate Cuneiform
Tympanic branch of IX (Jacobsen's nerve)
Stylopharyngeus
Lower part and greater horn
Chorda tympani
trigeminal (V3)
nerves
Not well defined in man
1944 I PART
15 THE UPPER DIGESTIVE TRACT
diverticulum goes on to form the larynx, trachea and bronchi. Oesophageal atresia and tracheooesophageal fistula are thought to result from spontaneous deviation of the oesophagotracheal septum posteriorly or other mechanical factors pushing the dorsal wall of the foregut anteriorly. The primitive oesophagus is at first a short tube extending from the tracheobronchial diverticulum to the fusiform dilatation of the foregut, which is to become the stomach. It extends down as the heart and lungs descend.
ANATOMY OF THE PHARYNX General description
~_--~
9
~~~~~~ ~~~---10 -+-t--¥rIYI---
12 13 14 15 16
1----r 2--------' \.-\--\r'~--
3
11
17
4----------~ 5---------------J~
NASOPHARYNX
6 7--------+~~~~
The posterosuperior wall of the nasopharynx is formed by the anteroinferior surface of the body of the sphenoid and basilar part of the occipital bone, the (basispehoid'. It contains the nasopharyngeal tonsil (the adenoids). The posterior wall extends down to the junction of the hard and soft palates and is formed by the pharyngobasilar fascia overlying the anterior arch of Cl (atlas). The inferior wall of the nasopharynx is formed by the superior surface of the soft palate and opens into the oropharynx. The cartilaginous lower end of the Eustachian tube opens into the lateral wall of the nasopharynx approximately 1 cm behind the inferior turbinate (see Figure 149.3). It forms an elevation shaped like a comma, with a shorter anterior limb and longer posterior limb. Behind and above this is the pharyngeal recess (fossa of Rosenmuller), which passes laterally above the edge of the superior constrictor. It is important to be able to recognize a normal Eustachian tube opening and the normal appearance of the fossa of Rosenmuller during endoscopic examination of the nasopharynx so that the area can be reliably biopsied to exclude a diagnosis of nasopharyngeal carcinoma. From the posterior edge of the Eustachian tube opening the salpingopharyngeal fold produced by the underlying salpingopharyngeus muscle passes downwards and fades out onto the upper surface onto the lateral pharyngeal walL A less well-defined fold passes from the anterior edge of the tubal opening onto the upper surface of the soft palate and is caused by the underlying levator palati muscle.
8----------~~
Figure 149.3
Sagittal section through the head showing the
nasal cavity, pharynx and larynx. 1, Epiglottis; 2, hyoid bone; 3, aryepiglottic fold; 4, vocal fold; 5, thyroid cartilage; 6, cricoid cartilage; 7, oesophagus; 8, thyroid isthmus; 9, nasopharyngeal tonsil (adenoid); 10, pharyngotympanic tube; 11, salpingopharyngeal fold; 12, nasopharynx; 13, palatoglossal fold; 14, palatine tonsil; 15, oropharynx; 16, palatopharyngeal fold; 17, hypopharynx.
downwards and a little backwards from the lower border of the soft palate to the side wall of the pharynx where it fades away. Beneath this is the palatopharyngeus muscle. In the space between the two folds lie the palatine tonsils. There is wide variation in the extent to which the tonsil is set back between the palatoglossal and palatopharyngeal folds which can give the impression that the tonsil itself is either very large or very small when in fact the volume of the tonsil may be the same. The posterior wall of the oropharynx is formed by the constrictor muscles and overlying mucous membrane. The superior wall is formed by the inferior surface of the soft palate and uvula. Below the oropharyngeal isthmus, the anterior wall is formed by the tongue base, behind the vallate papillae, and below this are the valleculae. These are separated in the midline by the median glossoepiglottic fold passing from the base of tongue to the lingual surface of the epiglottis. Laterally, each vallecula is bounded by the lateral glossoepiglottic fold.
OROPHARYNX The oropharynx extends from the junction of the hard and soft palates to the level of the floor of the vallecula. Anteriorly, it starts at the palatoglossal folds (anterior faucial pillar) formed by the underlying palatoglossus muscle passing from the undersurface of the palate to the side of the tongue. Just posterior to this, the palatopharyngeal fold (posterior faucial pillar) passes
HYPOPHARYNX The hypopharynx lies behind and to the sides of the inner part of the larynx. The posterior wall extends from the level of the floor of the vallecula to the level of the cricoarytenoid joint. It is formed by the constrictor muscles and overlying mucous membrane. The region
Chapter 149 Anatomy of the pharynx and oesophagus
below this, down to the inferior border of the cricoid cartilage, is called the postcricoid region and is bounded anteriorly by the posterior plate of the cricoid cartilage and encircled by the cricopharyngeus muscle which forms the upper oesophageal sphincter. Superiorly, the anterior wall of the hypopharynx is continuous with the laryngeal inlet. This is bounded anteriorly and superiorly by the upper part of the epiglottis, posteriorly by the elevations of the arytenoid cartilages and laterally by the aryepiglottic folds. To each side of the larynx lie the piriform fossa. These are bounded laterally by the thyroid cartilage and medially by the lateral surface of the aryepiglottic fold, the arytenoid and cricoid cartilages. They extend from the lateral glossoepiglottic fold to the upper end of the oesophagus.
I 1945
aponeurosis is attached to the posterior edge of the hard palate and to its inferior surface behind the palatine crest. Near the midline it splits to enclose the uvular muscle and all the other muscles of the soft palate are attached to it. The aponeurosis is thick and less mobile, anteriorly lying in a more horizontal plane than the thinner more mobile posterior part. From the base of the uvula on each side, the palatopharyngeal fold (posterior faucial pillar) sweeps down to the lateral wall of the oropharynx. More anteriorly the smaller palatoglossal fold (anterior faucial pillar) passes from the soft palate to the side of the tongue forming the oropharyngeal isthmus. The soft palate contains numerous mucous glands and lymphoid tissue, chiefly on the inferior aspect of the palatal aponeurosis and towards its posterior edge. The muscles acting on the soft palate are outlined in Table 149.3 and illustrated in Figures 149.4 and 149.5.
The soft palate The soft palate is a mobile flexible partition forming the floor of the nasopharynx and the roof of the oropharynx anteriorly. Its movement is controlled by two groups of muscular sphincters which pull the palate up and back to close the nasopharynx and down and forward to close the oropharyngeal isthmus. 11
STRUCTURE OF THE SOFT PALATE
2 - -_ _ _~~
The soft palate is formed by the expanded tendons of the tensor palati muscles which join in a median raphe called the palatine aponeurosis (see Figure 149.4). This
~~'h_'r---12
13
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:-----14 4
---15 ~------7"-=-----8
5
16
+--+---+-----9 +-----10
17
6
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18
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~!+t-Itf.!f--------12
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9 ---19 \~--------14
10 Figure 149.5
~-=-----15
Right lateral wall of the pharynx seen from
inside to show the muscles of the palate and pharyngeal wall. 1, Medial pterygoid plate; 2, tensor palati; 3, levator palati; 4,
Figure 149.4
The muscles acting on the left side of the soft
pterygomandibular raphe; 5, palatoglossus; 6, tonsillar branch of
palate from behind. 1, Pharyngotympanic tube; 2, levator palati;
facial artery; 7, glossopharyngeal nerve; 8, stylohyoid ligament;
3, tensor palati; 4, pterygoid hamulus; 5,
9, stylopharyngeus; 10, epiglottis; 11, phayngotympanic tube;
palatopharyngeus-posterior bundle; 6,
12, pharyngobasilar fascia; 13, salpingopharyngeus; 14, superior
palatopharyngeus-anterior bundle; 7, tonsillar fossa; 8, posterior
constrictor; 15, palatopharyngeal sphincter; 16,
nasal opening; 9, middle turbinate; 10, nasal septum; 11, inferior
palatopharyngeus-anterior bundle; 17, palatopharyngeus-
turbinate; 12, palatine aponeurosis; 13, uvular muscle; 14,
posterior bundle; 18, middle constrictor; 19, inferior
palatoglossus; 15, transverse intrinsic tongue muscle.
constrictor.
.L
Name Tensor palati
1. Scaphoid fossa of pterygoid process 2. Lateral lamina of the ET cartilage 3. Medial aspect of the spine of the sphenoid
Levator palati
1. Inferior surface of the petrous temporal bone immediately in front of the carotid canal 2. Inferior surface of the ET cartilage
Palatoglossus
Oral surface of the palatine aponeurosis
Palatopharyngeus
1. Anterior-posterior border of the hard palate and palatine aponeurosis
2. Posterior inferior surface of the soft palate
Uvular muscle
Midline of the palatine aponeurosis just behind the hard palate
Descends on the lateral surface of the medial pterygoid plate and converges to form a tendon which passes around the pterygoid hamulus, pierces the attachment of the buccinator to the pterygomandibular raphe and spreads out to form the palatine aponeurosis Descends forwards and medially over the upper edge of the superior constrictor piercing the pharyngobasilar fascia and descends in front of salpingopharyngeus to its insertion Passes anteroinferiorly and laterally in front of the tonsil forming the palatoglossal arch
Anterior bundle passes back between levator and tensor palati to unite with the posterior bundle and salpingopharyngeus before descending in the palatoglossal fold. Spreads out to form the inner vertical muscle layer of the pharynx Passes backwards and downwards
Median raphe
1. Tightens the soft palate and depresses it by flattening the arch 2. Opens the ET assisted by levator palati
Trigeminal (nerve to medial pterygoid)
Upper surface of the palatine aponeurosis between the anterior and posterior bundles of the palatopharyngeus •
1. Raises the soft palate up and back, closing the nasopharyngeal isthmus during deglutition 2. Assists in opening the ET
Pharyngeal plexus
Side of the tongue merging with intrinsic muscles of the tongue
Closes the oropharyngeal isthmus by approximating the palatoglossal arches and elevating the tongue against the soft palate 1. Pulls walls of the pharynx upward, forwards and medially to shorten the pharynx and elevate the larynx during deglutition 2. Approximates the palatopharyngeal arches towards the midline
Pharyngeal plexus
1. Shortens the uvu la 2. Bulk up the dorsal surface of the soft palate
Pharyngeal plexus
1. Posterior edge of the lamina of the thyroid cartilage
2. Side wall of the pharynx
Mucous membrane of the uvula
Pharyngeal plexus
Chapter 149 Anatomy of the pharynx and oesophagus I 1947
NERVE SUPPLY TO THE SOFT PALATE
All the muscles of the soft palate, except the tensor palati, are supplied by the pharyngeal plexus (cranial root of accessory and vagus) with an additional supply from the facial nerve (greater petrosal nerve). The tensor palati is supplied by the trigeminal nerve through the nerve to the medial pterygoid muscle. Sensation to the palate is provided by the maxillary division of the trigeminal nerve, through its greater and lesser palatine branches, and the pharyngeal branches of the glossopharyngeal nerve. Sympathetic fibres reach the palate on the blood vessels supplying it and are derived from the superior cervical ganglion. VASCULATURE OF THE SOFT PALATE
The palatine branch of the ascending pharyngeal artery curls over the upper edge of the superior constrictor to supply the palate. Additional supply is sometimes provided by the ascending palatine branch of the facial artery and the lesser palatine branches of the descending palatine branch of the maxillary artery. The venous drainage is to the pterygoid plexus and then through the facial veins. Lymphatics drain to the upper deep cervical nodes and to the retropharyngeal nodes.
The pharyngeal wall The pharyngeal wall consists of four layers which, from the inside out, are the mucous membrane lining, the pharyngobasilar fascia, the muscular layer and the buccopharyngeal fascia. MUCOUS MEMBRANE
The nasopharynx is lined by pseudostratified ciliated columnar epithelium, with goblet cells, down to the lower border of the soft palate. It is pierced by the ducts of minor salivary glands that lie in the submucosa. The oropharynx and hypopharynx are lined by a nonkeratinizing stratified squamous epithelium. Immediately beneath the epithelium there is a connective tissue lamina propria that contains a large amount of elastic tissue, which takes the place of the muscularis mucosa found in the oesophagus.
PHARYNGOBASILAR FASCIA
The pharyngobasilar fascia is a fibrous layer firmly attached superiorly to the basilar region of the occipital bone and petrous part of the temporal bone medial to the carotid canal. It bridges below the Eustachian tube and extends forwards to be attached to the posterior border of the medial pterygoid plate and the pterygomandibular raphe. Thepharyngobasilar fascia bridges the gap between the superior border of the superior constrictor and the base of
'rtf
the skulL In this region it is firmly united to the buccopharyngeal fascia forming a single layer. The fibrous layer diminishes in thickness as it descends. It is strengthened posteriorly by a strong fibrous band which is attached above to the pharyngeal tubercle on the undersurface of the basilar portion of the occipital bone and passes down as a median raphe, which gives attachment to the constrictors.
MUSCLE LAYER
The muscles of the pharyngeal wall are arranged into an inner longitudinal layer and outer circular layer. The inner layer is formed by three paired muscles: the stylopharyngeus, palatopharyngeus and salpingopharyngeus (Tables 149.3 and 149.4, Figures 149.5 and 149.6). The outer layer has three paired muscles: the superior, middle and inferior constrictors (Table 149.4, Figures 149.5, 149.6 and 149.7). Each of the constrictors is shaped like a fan, arising from the lateral wall of the pharynx and sweeping around to be inserted into the median raphe posteriorly. The muscles overlap each other from below upwards. Although they form an almost complete coat for the side and posterior walls of the pharynx, their attachments anteriorly separate the edges and it is through these intervals that structures pass from the exterior of the pharynx towards its lumen. During deglutition the longitudinal muscles elevate the larynx and shorten the pharynx while the constrictors contract in a coordinated way to propel the bolus through the oropharynx into the oesophagus. The inferior constrictor is made up of two muscle groups: the thyropharyngeus superiorly and the cricopharyngeus inferiorly. The fibres of the cricopharyngeus are continuous with the circular fibres of the upper oesophagus. Posteriorly, there is a small triangular interval between the upper end of the cricopharyngeus and the lower fibres of the thyropharyngeus, so-called 'Killian's dehiscence'.
BUCCOPHARYNGEAL FASCIA
The buccopharyngeal fascia is a thin fibrous coat of areolar tissue covering the pharyngeal constrictor muscles. It contains the pharyngeal plexus of nerves and veins. Posteriorly, it is loosely attached to the prevertebral facia and laterally to the styloid process, the muscles arising from the styloid and to the carotid sheath.
Structures related to the pharynx LATERAL RELATIONS OF THE CONSTRICTOR MUSCLES
The superior constrictor has, on its lateral surface, the lingual and inferior alveolar branches of the mandibular division of the trigeminal nerve, the ascending pharyngeal
Table 149.4
Muscles of the pharynx.
Superior constrictor
Pa latopharyngea I sph incter
Middle constrictor
Inferior constrictor thyropharyngeus
Inferior constrictor cricopharyngeus
1. Posterior border of the medial pterygoid plate and pterygoid hamulus 2. Pterygomandibular raphe 3. Posterior end of the mylohyoid line on the inner surface of the mandible Anterior and lateral part of the upper surface of the palatine aponeurosis
Fibres pass backward as a quadrilateral sheet
1. Posterior edge of the lower part of the stylohyoid ligament and lesser horn of the hyoid 2. Whole length of the upper border of the greater horn of the hyoid 1. Oblique line on the lateral surface of the lamina of the thyroid cartilage 2. Lateral surface of the cricoid cartilage and inferior horn of the thyroid cartilage Side of the cricoid cartilage
Fibres spread in a wide fan upwards and downwards
Blends with the internal surface of the superior constrictor near its upper border Whole length of the median pharyngeal raphe
Fibres pass backwards
Median pharyngeal raphe
Horizontally backwards encircling the pharyngo-oesophageal junction Descends passing between superior and middle constrictors. Fans out before insertion
Same place on the opposite cricoid cartilage
Stylopharyngeus
Medial side of the tip of the styloid process
Salpingopharyngeus
Posteroinferior corner of ET cartilage
See Refs 1, 2, 3.
1. Medial pharyngeal raphe
Contracts in a coordinated way to propel the food bolus
Pharyngeal plexus
Elevates the larynx and shortens the pharynx
Branch of the glossopharyngeal nerve
2. Pharyngeal tubercle on the basilar part of the occipital bone Fibres sweep backwards latera I to levator pa lati
Downwards and blends with palatopharyngeus
1. Merges with the constrictors and the lateral glossoepiglottic fold 2. Posterior border of the thyroid cartilage see palatopharyngeus
Pharyngeal plexus
Chapter 149 Anatomy of the pharynx and oesophagus
I 1949
18 2---\-'<--/lllt1
19
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20
2
21
3 4 5 6
~~~r----+-+---16
7
C~~_-/18
5 6
-------t-
-----\-i
22
7
23
8
24
8a
25
8
10
26
9
11
27
9
11 a
1r-\------>.,--17
19 ....J.-=o.,..,..,...,-N--,~---20 ~~~~#m~-----21
'--""'=+------22
10
28
12 13
29
14
30
~m\\\1~----23
11
24 ----1--------25
15
16 12-----------~~~~~~~~---------26
17
Figure 149.6
The pharynx from behind. 1, Pharyngotympanic
13-------------~
tube; 2, tensor palati; 3, levator palati; 4, stylohyoid ligament;
14 -----------tH-+-H+ttI11'r>-r.,.,....,.,.,.,....,.,crr(
5, stylopharyngeus muscle; 6, styloglossus muscle; 7, superior
15 _ _ _ _ _ _ _ _---JH+1I1111--....u.!.J.llJ.~
constrictor muscle; 8, medial pterygoid muscle; 8a, stylohyoid muscle; 9, posterior belly of the digastric; 10, greater horn of hyoid bone; 11, middle constrictor; 11 a, palatopharyngeus muscle; 12, superior horn of thyroid muscle; 13, inferior constrictor muscle - thyropharyngeus; 14, Killian's dehiscence; 15, inferior constrictor muscle - cricopharyngeus; 16, circular oesophageal muscle coat; 17, longitudinal oesophageal muscle coat; 18, facial nerve; 19, hypoglossal nerve; 20, pharyngobasilar fascia; 21, accessory nerve; 22, inferior ganglion of vagus nerve; 23, external carotid artery; 24, superior cervical sympathetic ganglion; 25, ascending pharyngeal artery; 26, internal jugular vein; 27, middle cervical sympathetic ganglion; 28, inferior thyroid artery; 29, inferior cervical ganglion; 30, right recurrent laryngeal nerve.
Figure 149.7
Lateral wall of the pharynx to show the
constrictor muscles and associated structures. 1, Tensor palati; 2, spine of sphenoid bone; 3, levator palati; 4, pterygoidhamulus; 5, superior constrictor; 6, stylopharyngeus; 7, glossopharyngeal nerve; 8, middle constrictor; 9, greater horn of hyoid bone; 10, lateral thyrohyoid ligament; 11, thyropharyngeal part of inferior constrictor; 12, Killian's dehiscence; 13, cricopharyngeus part of inferior constrictor; 14, right recurrent laryngeal nerve; 15, oesophagus; 16, buccinator; 17, pterygomandibular raphe; 18, styloglossus; 19, geniohyoid; 20, stylohyoid ligament; 21, lesser horn of hyoid bone; 22, thyrohyoid membrane; 23, internal laryngeal nerve; 24, superior laryngeal vessels; 25, oblique line on thyroid cartilage; 26, fascial bridge overcricothyroid muscle.
artery, ascending palatine branch of the facial artery, stylohyoid ligament, styloglossus and stylopharyngeus muscles and, more laterally, the medial pterygoid muscle inside the angle of the mandible (Figure 149.8). On the outer surface of the middle constrictor lie the lingual artery, hyoglossus muscle, hypoglossal nerve and the tendon of the posterior belly of the digastric. On the outer surface of the inferior constrictor lie the external laryngeal nerve, thyroid gland, sternothyroid, sternohyoid and omohyoid muscles. STRUCTURES PIERCING THE PHARYNX
The cartilaginous portion of the Eustachian tube and the tensor and levator palati pass through the pharyngobasilar
fascia to reach the lateral wall of the pharynx and palate, respectively. The palatine branch of the ascending pharyngeal artery curls over the upper edge of the superior constrictor. The stylopharyngeus enters the pharynx between the middle and superior constrictors, it then blends with the fibres of the palatopharyngeus. The stylopharyngeus is accompanied by the glossopharyngeal nerve which supplies it before passing forwards to the tongue. The internal laryngeal nerve and superior laryngeal nerve pierce the thyrohyoid membrane between the middle and inferior constrictors and come to lie submucosally on the lateral wall of the piriform fossa. The recurrent laryngeal nerve and inferior laryngeal artery
1950 I PART
15 THE UPPER DIGESTIVE TRACT
Figure 149.8 2--------/
Transverse section at the level of C2
showing the relations of the oropharynx including the parapharyngeal and retropharyngeal space. 1, Tongue; 2, cavity of oropharynx; 3, palatoglossus muscle; 4,
3----4 _ _ _ __
palatine tonsil; 5, palatopharyngeus muscle; 6, retropharyngeal space; 7, cervical sympathetic
5--------'
ganglion; 8, internal carotid artery; 9, vagus nerve; 10, hypog lossal nerve; 11, g lossopharyngea I nerve; 12, internal jugular vein; 13, accessory nerve; 14, external 1--+---15
carotid artery; 15, sternocleidomastoid muscle; 16, posterior belly of digrastic; 17, parotid gland; 18, stylohyoid muscle; 19, stylopharyngeus muscle; 20, styloglossus muscle; 21, parapharyngeal space; 22, medial pterygoid muscle; 23, masseter muscle.
pass between the cricopharyngeal part of the inferior constrictor and the oesophagus behind the articulation of the inferior horn of the thyroid cartilage with the cricoid cartilage. Understanding the position of the internal laryngeal nerve and superior laryngeal vessels is crucial to the safe surgical dissection of the upper pole of the thyroid gland. The close anatomical relationship of the recurrent laryngeal nerves, the carotid artery and the inferior thyroid artery, is described by an inverted rightangled triangle with the carotid artery forming the vertical side laterally, the inferior thyroid artery forming the horizontal base at the top passing from medial to lateral, and the recurrent laryngeal nerve forming the hypotenuse (or longest side) travelling from medial to lateral at a relatively shallow angle on the left and a more acute angle on the right. The nerves may sometimes pass superficially or deep to the inferior thyroid artery but the triangular relationship remains constant and is the only safe way of identifying the nerve.
POTENTIAL SPACES AROUND THE LARYNX
The retropharyngeal space lies between the prevertebral fascia and the buccopharyngeal fascia (Figure 149.8). The space is closed above by the base of the skull and on each side by the carotid sheath. Inferiorly, it is continuous with the superior mediastinum. The parapharyngeal space is lateral to the pharynx on each side and can be visualized as an inverted cone with its base under the temporal bone and its apex in the neck at the hyoid bone (Figure 149.8). Laterally, it is bounded by the fascia overlying the pterygoid muscles, the medial aspect of the deep lobe of the parotid gland and the ascending ramus of the mandible. Medially, the space abuts the fascia overlying the pharyngeal constrictors and the tensor and levator palatini. Anteriorly, it is bounded by the pterygomandibular raphe and the posterior wall is
formed by the posterior part of the carotid sheath and prevertebral fascia. The retropharyngeal and parapharyngeal space are filled with loose areolar tissue, fat and a number of lymph nodes. They communicate with each other and the submandibular spaces, which allows the spread of infection and tumour along fascial planes with little resistance.
Nerve supply of the pharynx The pharyngeal plexus is formed by the pharyngeal branches of the glossopharyngeal and vagus nerves with sympathetic fibres from the superior cervical ganglion. Many of the vagal fibres come from the cranial root of the accessory, which joins the vagus at its superior ganglion. The pharyngeal branches of the vagus supply all the muscles of the pharynx via the pharyngeal plexus, except the stylopharyngeus which is supplied by the glossopharyngeal nerve. The cricopharyngeus has an additional supply from the external laryngeal nerve and receives parasympathetic vagal fibres from the recurrent laryngeal nerve (relaxation) and postganglionic sympathetic fibres from the superior cervical ganglion (contraction). Sensation to the pharynx is provided by the pharyngeal plexus with the glossopharyngeal nerve supplying sensation to the upper part of the pharynx including the surface of the tonsil, which is also supplied by the lesser palatine branch of the maxillary nerve and posterior third of the tongue. The tongue in front of the valleculae and the valleculae themselves are supplied by the internal laryngeal nerve, a branch of the superior laryngeal nerve of the vagus. Sympathetic fibres reach the pharynx on the blood vessels supplying it and are derived from the superior cervical ganglion. Parasympathetic secretomotor supply
Chapter 149 Anatomy of the pharynx and oesophagus
to the minor salivary glands of the pharynx comes by way of the nasal palatine and pharyngeal branches of the pterygopalatine ganglion. These are derived from the nervus intermedius and pass through the facial nerve to the greater petrosal nerve and pterygopalatine ganglion.
Pharyngeal vasculature The ascending pharyngeal artery arises from the medial aspect of the external carotid artery just above its origin. It passes upwards behind the carotid sheath against the pharyngeal walL Branches go to the pharynx and the tonsiL Its palatine branch passes over the upper free edge of the superior constrictor to supply the inner aspect of the pharynx and soft palate. The pharynx receives an extra supply from the ascending palatine and tonsillar branches of the facial artery and the greater palatine and pterygoid branches of the maxillary artery. The veins of the pharynx are arranged in an internal submucous and external pharyngeal plexus with numerous communicating branches between the two plexuses and veins on the dorsum of the tongue, the superior laryngeal veins and the oesophageal veins. The pharyngeal plexus drains to the internal jugular vein and anterior facial veins, it also communicates with the pterygoid plexus. Lymphatics from the upper part of the pharynx drain first to the retropharyngeallymph nodes and then join the oropharynx in draining to the upper deep cervical nodes. The hypopharynx drains to the inferior deep cervical group and paratracheal nodes.
I 1951
which is separated from the wall of the oropharynx by loose areolar tissue. Laterally, the floor of the tonsillar fossa is formed by the pharyngobasilar fascia overlying in its upper part the superior constrictor and below the styloglossus muscle passing forward into the tongue. The glossopharyngeal nerve and stylohyoid ligament pass obliquely downwards and forwards beneath the lower edge of the superior constrictor in the lower part of the tonsillar fossa.
ANATOMY OF THE OESOPHAGUS General description The oesophagus extends from the lower border of the cricoid cartilage at the level of C6 to the cardiac orifice of the stomach at T11, a total distance of approximately 25 cm in adults. The diameter varies between 20 and 30 mm, stretching to allow the passage of a food bolus. In its course, it follows the curvature of the spine posteriorly and deviates to the left initially until it returns to the midline in the posterior mediastinum. A second bend to the left occurs as the oesophagus crosses the descending thoracic aorta to pierce the diaphragm. The oesophagus is the narrowest region in the digestive tract. It has three constrictions: at 15 cm from the incisors the cricopharyngeal sphincter, at 23 cm it is crossed by the aortic arch and left main bronchus and at 40 cm it pierces the diaphragm.
Oesophageal wall Lymphoid tissue of the pharynx The wall of the upper aero digestive tract contains a large amount of unencapsulated lymphoid tissue in the lamina propria, the so-called gut-associated lymphoid tissue (GALT). This is particularly prominent in the pharynx at the entrance to the upper aero digestive tract. The nasopharyngeal, tubal, palatine and lingual tonsils form a ring of GALT at the level of the oropharyngeal and nasopharyngeal isthmus, known as Waldeyer's ring. Lymphatic efferents leave this tissue and drain to regional lymph nodes.
THE PALATINE TONSIL
The palatine tonsil is located between the diverging palatopharyngeal and palatoglossal folds. A sulcus usually separates the tonsil from the base of the tongue, the tonsillolingual sulcus. The medial surface of the tonsil is characterized by numerous tonsillar crypts, which may penetrate nearly the whole thickness of the tonsiL The deep surface of the tonsil is covered by a fibrous capsule,
The oesophagus has four layers, from inside out: the mucous membrane, submucosa, muscular coat and an outer fibrous layer. It is lined by a nonkeratinizing stratified squamous epithelium continuous with that of the pharynx. Beneath this is the loose connective tissue of the lamina propria containing elastic fibres and GALT. The muscularis mucosa lies deep to this, becoming thicker as it descends. The submucosa loosely connects the mucous membrane and the muscular coat. It contains blood vessels, lymphatics, Meissner's plexus of postganglionic parasympathetic nerve fibres and minor mucous glands, which lubricate the oesophagus. The muscular coat has an outer longitudinal layer which is complete apart from a small dehiscence at the upper end where the fibres diverge from the midline posteriorly to form two longitudinal bundles which come around anteriorly and attach to the posterior lamina of the cricoid cartilage. The inner circular layer is continuous superiorly with the fibres of the cricopharyngeus and inferiorly with the oblique fibres of the stomach. The muscles of the upper third of the oesophagus are striated, while in the lower third they are smooth. There is a
1952 I PART 15 THE UPPER DIGESTIVE TRACT transitional zone in the middle third. The fibres of cricopharyngeus make up the upper oesophageal sphincter while at the lower end there is no anatomical sphincter. It is thought that a number of factors contribute to closure of the lower oesophagus including intrinsic muscle activity, the encircling fibres of the right crus of the diaphragm and oblique fibres of the stomach, the thoracoabdominal pressure gradient and the angle of the oesophagogastric junction. There is an external adventitia of dense connective tissue overlying the oesophagus. A condensation of this, the phreno-oesophageal ligament, attaches the oesophagus to the diaphragmatic opening.
Nerve supply to the oesophagus The striated muscle in the upper third of the oesophagus is supplied by the recurrent laryngeal nerve. The smooth muscle is supplied by parasympathetic fibres from the oesophageal branches of the vagus and recurrent laryngeal nerves. These fibres synapse in the ganglia of the submucosa (Meissner's plexus) and myenteric (Auerbach's) plexus, between the longitudinal and circular muscle layers. Sympathetic fibres are derived from the sympathetic trunk and come either directly from the cardiac plexus or around the blood vessels supplying the oesophagus. Afferent fibres run with the branches of the vagus and sympathetic nerves. The oesophageal mucosa is sensitive to heat and cold but insensitive to touch. Pain is poorly localized and probably caused by muscle spasm rather than direct stimuli.
Vasculature of the oesophagus The cervical oesophagus is supplied by the inferior thyroid artery and left subclavian artery. The thoracic part has a segmental supply directly from the descending aorta and branches of the bronchial and upper posterior intercostal arteries. The abdominal part is supplied by the left gastric artery, a branch of the coeliac artery, and the left inferior phrenic artery directly from the abdominal aorta. An extensive venous plexus lies on the outside of the oesophagus and drains in a segmental way to the inferior thyroid veins (systemic), azygos and hemiazygos veins (systemic) and left gastric vein (portal). The lower end of the oesophagus is an important area of portal systemic venous anastomosis. At the upper end of the oesophagus, longitudinal submucosal veins enter the pharyngeal and laryngeal plexuses. ~ Lymphatic plexuses lie in the mucous membrane and in the muscular coat. They drain by ascending or descending beneath the mucosa or by piercing the oesophagus. The cervical lymphatics drain to the lower
deep cervical and paratracheal nodes, the thoracic ones to posterior mediastinal and tracheobronchial nodes and abdominal ones to the left gastric nodes.
Relationships of the oesophagus The cervical oesophagus lies posterior to the trachea and anterior to the prevertebral fascia. The recurrent laryngeal nerves ascend on each side in the tracheo-oesophageal groove. The thoracic duct passes up and behind the left side of the oesophagus. In the superior mediastinum, the oesophagus lies slightly to the left of the midline and passes behind and to the right of the aortic arch. The left subclavian artery is immediately to the left of the oesophagus as it arises from the aortic arch. On the right is the azygos vein arching from posterior to anterior over the lung root to enter the superior vena cava. The mediastinal pleura is in contact with the oesophagus, separated on the right by the azygos vein and on the left by the aortic arch and left subclavian artery. At the level of the tracheal bifurcation the oesophagus is crossed anteriorly by the left main bronchus and immediately below by the right pulmonary artery. The fibrous pericardium overlying the left atrium comes into contact with the anterior surface of the oesophagus further down. The inferior tracheobronchial nodes lie between the bifurcation of the trachea and the oesophagus. The thoracic duct enters the thorax through the right side of the aortic opening in the diaphragm and runs up behind the right margin of the oesophagus until it crosses obliquely to lie behind the left side. The two hemiazygos veins lie between the oesophagus and the prevertebral fascia and then pass to join the azygos vein on the right. Inferiorly, near the diaphragm, the aorta passes behind the oesophagus as the latter curves toward the left and turns forwards to pass through the diaphragm. The left and right vagus nerves, having branched to form the cardiac and pulmonary plexuses, come together as the oesophageal plexus and form multiple nerve trunks that descend with the oesophagus through the diaphragm. The left vagal fibres usually lie on the anterior surface and those on the right posteriorly. After the oesophagus emerges from the right crus of the diaphragm slightly to the left of the midline, it lies in the oesophageal groove on the posterior surface of the left lobe of the liver. It curves sharply to the left to join the stomach at the cardia. This short abdominal section of the oesophagus is covered with peritoneum.
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Chapter 149 Anatomy of the pharynx and oesophagus
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REFERENCES 1.
Sadler T. Langman's medical embryology. 8th edn.
2.
Sinnatamby C. Last's anatomy. 10th edn. London: Churchill
3.
Williams P. Gray's anatomy. 38th edn. London: Churchill
Philadelphia: Lipincott Williams, 2000.
'''l1()~sspr~~d.of· infectidP'
·fas9ialplane~.'· .
I 1953
Livingstone, 1999. Livingstone, 1995.
150 Physiology of swallowing
PAULA LESLIE AND STEPHEN McHANWELL
Introduction
1954
What constitutes the normal swallow?
1961 1961
Structures involved in swallowing
1954
Key points
The sequence of events in the normal swallow
1956
Deficiencies in current knowledge and areas for future
Neural control
1958
Respiration and swallowing
1959
Age effects: presbyphagia
1961
research
1961
References
1961
The data in this chapter are supported by a Medline search using the key words deglutition, dysphagia, neural control, respiration age and focussing on the healthy, normal process.
INTRODUCTION
understanding of dysphagia. Neural control and the coordination of breathing and swallowing will also be
Swallowing requires the coordinated activity of muscles in
addressed.
three regions of the head and neck: the oral cavity, the pharynx and larynx, and the oesophagus. This complex sequence of motor behaviour is part reflex and partly
STRUCTURES INVOLVED IN SWALLOWING
under voluntary control. It has been extensively investi gated using a variety of techniques including radiography,
Swallowing involves the passage of a bolus of food or
ultrasound
liquid from the oral cavity to the stomach via the pharynx
and
electromyography
(EMG)
recording,
together with observations on individuals with dysphagia.
and
More recently, videotluoroscopy and endoscopy have
laryngeal vestibule
been
used to investigate swallowing,
particularly
oesophagus,
passing
over
the
entrance
to
the
(Figure 150.1). The basic musculature
its
of swallowing controls the jaw, the tongue , the degree of
disorders. Swallowing as a motor behaviour is so complex
constriction and length of the pharynx and closure of the
lhat some details have remained difficult to resolve. The
laryngeal inlet.
literature is often contradictory, particularly the earlier
The elevators and depressors of the jaw play a key role
studies based on inferential analysis of radiographic data.
in bolus preparation before the swallow is initiated by
Careful analysis of swallowing using newer techniques
grinding and reducing the food between the teeth. Bolus
shows that there is a surprising amount of variation
formation is also a function of the tongue, the intrinsic
between individuals and this needs to be borne in mind
muscles of which are mainly responsible for changing the
when assessing the swallow. This chapter current
state
of
knowledge
will survey the
concerning
the
normal
shape of the tongue and the extrinsic muscles altering its position in the mouth. The actions of these two groups of
anatomy and physiology of swallowing and what might
muscles ate not independent since changes in shape result
be considered as the limits of normality, essential to the
in changes in position and vice versa. For example,
Chapter
150 Physiology of swa liowi ng I
1955
the cricothyroid and cricoarytenoid joints. The larynx is suspended
from the
hyoid bone by the thyrohyoid
membrane and thyrohyoid muscle. When the suprahyoid and infrahyoid muscles move the hyoid bone, they also alter the height of the larynx. The epiglottis projects above the hyoid behind the posterior part of the tongue and is attached to the posterior aspect of the thyroid cartilage. Attached arytenoid
between
the
cartilages
epiglottis
posteriorly
anteriorly is
the
and
the
quadrangular
membrane, the superior margin of which forms the boundary of the laryngeal inlet. Within this superior border are the aryepiglottic muscles that control the inlet, Figure 150.1
together with the small thyroepiglotticus muscle that may
A mid-sagittal section of th e head and neck
help to depress the epiglottis to
showing the location of the maj or structures involved in
prevent aspiration.
Adduction of the vocal cords by the intrinsic muscles of
swallowing. A, Hard palate; B, soft pal a te ; C, nasopharynx: D,
pharyngeal isthmus; E, oro ph a rynx ; F, laryngoph arynx : G, cr icoi d cartilage; H, thyroid cartilage: I, hyoid bone; J, laryngeal inlet.
the larynx provides a second line of defence to the accidental ingestion of food or foreign objects. The oesophagus is a muscular tube continuous with the pharynx. It has a short cervical course before it enters the thorax where it lies posteriorly in the midline
flattening
the
tongue
by
the verticalis
muscles
will
protrude the tongue as its bulk is displaced, while
stomach.
downward movement of the tongue by the hyoglossus
The act of swallowing involves a crossing of the stream
muscle will tend to lower the sides of the tongue but not
of liquid and food with that of breathing and this occurs
its centre. The actions of the tongue and jaw muscles in
within the pharynx. This crossing of the alimentary and
bolus
ventilatory streams is
formation
are
aided
by
that
of
the
lips
in
an
evolutionary consequence of the
maintaining a seal, the buccinator muscle of the cheek
transition in vertebrates from sea to land living.
in returning food from the vestibule into the oral cavity
primitive vertebrates the pharynx is an apparatus for
In
and the soft palate in preventing nasal regurgitation and
simultaneously extracting dissolved oxygen from seawater
premature movement of material into the oropharynx.
at the gills and filter feeding on suspended particles. In
On leaving the oral cavity, food enters the pharynx, a
man, food and air are separated in the pharynx. A variety
midline tube approximately 15 cm long continuous with
of mechanisms have evolved to ensure that during normal
the oesophagus below and the nasal cavities above and the
swallowing no liquid or food can be aspirated into the
larynx which opens on its anterior wall. The anterior wall
lungs through the larynx. Aspiration can result in serious
of the pharynx is incomplete and composed of the
consequences such as asphyxiation caused by airway
posterior part of the tongue superiorly and the larynx
blockage or of occult aspiration with resultant complica
inferiorly. This leads to a natural division of the pharynx
tions. Swallowing has two components: the passage of the
into three regions: nasopharynx, oropharynx and lar
bolus from the oral cavity to the stomach and airway
yngopharynx, corresponding to those structures that lie
protection. These same mechanisms also serve to inhibit
anterior to the appropriate part of the pharyngeal tube.
the ingestion of air into the stomach.
The remainder of the pharynx is composed, like the whole
The traditional view is that biomechanical events such
of the gastrointestinal tract, of four layers: the outer
as movement of the posterior part of the tongue and
areolar, the muscular, the submucous and the inner
elevation of the hyoid bone and larynx, associated with
mucous membrane. The muscular layer is composed of
passing the bolus, are the leading events of the pharyngeal
circular and longitudinal muscles. The circular muscles
phase
are arranged as a triad, the superior, middle and inferior
videotluoroscopic investigations clearly show that the
of
swallowing.
However,
videoendoscopic
constrictors, with the latter being further subdivided into
airway protection mechanism is activated first.l.
2.3
and
[**1
a thyropharyngeus and cricopharyngeus part With the
The main sphincteric
exception of the cricopharyngeus, the constrictor muscles
airways are the soft palate,
are paired and attach to a posterior midline raphe. The
isthmus and those guarding the laryngeal aditus. Since
mechanisms protecting
the
guarding the pharyngeal
cricopharyngeus forms a distinct sphincter at the point
airway protective mechanisms are activated in advance of
where the laryngopharynx joins the oesophagus. There
those of passing the bolus, it is necessary to consider how
are two discrete longitudinal muscles on each side, the
palatopharyngeus and the stylopharyngeus.
..... j.
and descends, piercing the diaphragm and entering the
salphingo_P
swallowing is coordinated with ventilation. Ventilation is
always discussed as part of the normal process of speech
The larynx is a series of cartilages in the wall of the
production but swallowing also needs to be carefully
upper part of the trachea, the main cartilages being the
timed in relation to the respiratory phases and a failure in
thyroid, cricoid and arytenoid. These cartilages move at
this may be one cause of swallowing difficulties.
1956 I
PART 15 TH E UPPER DIGESTIVE TRACT
THE SEQUENCE OF EVENTS IN THE NORMAL SWALLOW
preparatory phase where the food is taken into the
In any land-living animal that does not normally swallow
when the bolus leaves the oral cavity to enter the pharynx
its food whole, different stages of swallowing can be
identified as having evolved in order to ensure that food is
mouth and broken down, and the oral phase proper
where the bolus is moved to the back of the tongue. From
until it passes into the oesophagus defines the pharyngeal
reflex
phase.
During
this phase the ventilatory
and
transported from the mouth to the stomach safely.4
alimentary streams cross and so it is important for
into three distinct phases: oral, pharyngeal and oesopha
as possible. The bolus is then moved past the protected
Swallowing is a continuous process split by convention geal. This evolutionary division is also convenient for
descriptive purposes.
Figure
150.2 illustrates the key
stages in the swallowing process as traditionally described.
In the oral phase, food enters the mouth where it is prepared for swallowing. During this phase it is mixed
survival that this reflex behaviour occurs as automatically
laryngeal inlet, through the pyriform fossae towards the
cricopharyngeal sphincter and into the oesophagus.
[*]
The timings of the stages of swallowing have been
extensively investigated. Once the food is of a suitable
consistency to swallow, transit from the mouth to the
with saliva before being formed into a bolus of a suitable
oropharynx takes one to two seconds, with up to a further
oesophagus.
cricopharyngeal sphincter. The bolus then passes through
consistency to permit transport through the pharynx and The
oral
phase may be
split
into the
second for the bolus to traverse the pharynx to the
the oesophagus to the stomach. The time
taken for
oesophageal transit has been estimated by a variety of techniques.
Using
scintigraphy,
healthy
oesophageal
clearance times for a single swallow of 99mTc sulphur
colloid is estimated as 10-15 seconds.5 In a scintigraphic study with improved spatial and temporal resolution,
Russell et al.6 estimated healthy oesophageal transit times
to be less than 15 seconds with a mean time of seven to
eight seconds. This agrees with earlier manometric and
electromyographic studies, although a shorter time of
three seconds was needed for liquids.4 In the preparatory stage, it is unclear what determines when the bolus
is to
be moved into the oropharynx. An important factor is
likely to be bolus consistency as sensed by mechano
receptors in the oral cavity. The sensory control of swallowing
[*** 1* ]
will be discussed below under Neural control.
Oral phase The oral preparatory phase is where food
is readied for
swallowing by reducing and mixing it with saliva by the
muscles of the jaw and oral
cavity. This can vary
in
duration considerably. The jaw is closed by the jaw
elevators, temporalis, masseter and medial pterygoid and chewing uses a combination of elevators and depressors.
The lips maintain
a
tight seal under the action of the
orbicularis oris while the buccinator is used to return
food from the vestibule during the process of mastication.
Throughout this phase the soft palate is lowered under the action of the palatoglossus and palatopharyngeus
which approximate the arches of the Figure 150.2
(a)
same name to the
dorsal aspect of the posterior part of the tongue. The
Oral and pharyngeal stages of a normal swal!ow:
oral phase, food is reduced and the bolus prepared;
(b)
bolus
is moved to the posterior part of the tongue; (c) bolus contacts the trigger points in the oropharynx and the pharyngeal phase is initiated; (d) bolus is moved past the closed larynx; enters the oesophagus.
(e)
bolus
airways remain open. Traditionally, the oral cavity was
thought to be sealed posteriorly though recent work
indicates that this may not always be the case.7
[**] muscle
The oral phase proper involves several distinct
actions. The tongue is moved by the action of the intrinsic muscles together with the genioglossus
which elevates the
Chapter
150 Physiology of swallowing
I 1957
tongue tip and blade of the tongue towards the hard
60 percent of liquid and 76 percent of solid swallows
palate. A prerequisite for this is mandibular elevation and
before the swallow is triggered. This calls into question
although the mouth does not have to be completely
the term 'premature spillage' as an indicator of dysphagia.
closed during swallowing, it is hard to swallow with the
It is often said that once the bolus of food has passed the
mouth more than a little open. The elevation of the
palatoglossal and palatopharyngeal arches then swallow
raising
ing becomes reflexive. While it is true that swallowing is
the hyoid bone. It is more effective to change the height
mandible assists the
suprahyoid
muscles
in
automatic once initiated, many people can voluntarily
of the hyoid bone if the mandible is fixed. The elevation
delay their swallowing up to a certain point. [**]
of the floor of the mouth is accompanied by lifting the
Lack of clarity exists around the precise temporal
tongue under the action of the stylohyoid. Simulta
relationships of subsequent events involving movement of
neously, the tongue is flattened and the bolus is moved
the food from the posterior part of the tongue into the
back by these muscles together with the superior long
oropharynx and airway protection. As the bolus is moved
itudinal and transversus muscles as the tongue fills the
into the oropharynx, a reflex closure of the glottis is
oral cavity. As the bolus reaches the back of the tongue,
initiated in which there are preparatory movements of the
now deeply grooved, the soft palate is elevated to protect
vocal folds and the laryngeal inlet prior to a full closure of
the nasopharynx from the entry of food and closes the
the larynx. These movements are even seen when the bolus 3 enters the oral cavity. A completely sealed larynx requires
airways. The soft palate is elevated by the levator and tensor veli palatini.
1
full adduction of the vocal folds and hence glottic closure
The formation of the bolus has often been regarded as
by medial movement of the arytenoid cartilages. Supra
a unitary event. A more rigorous analysis has suggested
glottically,
that the way in which food is prepared for swallowing
ventricular folds, tensing of the edges of the laryngeal opening and lowering of the epiglottis.9 The events causing
may involve repeated transport of chewed food between
there
needs
to
be
approximation
of
the
the oral cavity and the oropharyngeal surface of the
laryngeal closure occur as the larynx is elevated. Reflex
tongue, through the palatoglossal and palatopharyngeal
closure of the glottis is initiated and apnoea onset occurs
arches. Videofluorographic techniques
evidence that the bolus is progressively accumulated on
approximately 0.19 seconds prior to the elevation of the larynx.9 This coordination between swallowing and ventila
the oropharyngeal surface of the tongue through several
tion is another important airway protection mechanism by
have provided
cycles of upward and forward movement on the tongue ? surface. [**]
Pharyngeal phase
preventing simultaneous breathing and swallowing. [**] The bolus
enters the
pharyngeal space which is
widening as it is raised, resembling the engulfing of prey 4 10 by a snake. , This is partly due to the relaxation of the
Pumping action of tongue Hypopharyngeal suction
pharyngeal constrictors and partly to the anterior move ment of the pharynx as the hyoid bone is drawn forward
As the bolus is moved back by the tongue to enter the
under the elevating action of the suprahyoid muscles.
pharynx, a sequence of events is initiated that ensures that
Laryngeal elevation also occurs as the suprahyoid muscles
the airways are protected during bolus transport. Firstly,
move the hyoid bone anteriorly, contributing to phar
diaphragmatic contraction is inhibited making simulta
yngeal dilation. Raising the larynx narrows the laryngeal
neous breathing and swallowing impossible under normal 8 circumstances. At the same time, the soft palate is
epiglottis as the laryngeal cartilages move anteriorly. The
inlet and moves it towards the pharyngeal surface of the
elevated to ensure a sphincteric closure of the naso
interarytenoid, aryepiglottic and thyroepiglottic muscles
pharynx. Finally, the vocal cords start to close to protect
all help to close the margin of the laryngeal aditus in the
the airways. [*]
As the bolus enters the oropharynx and touches key trigger
points,
a
reflex
is
initiated
in
which
the
manner of a drawstring purse. [**/*]
The bolus moves into the oropharynx contacting the epiglottis which then moves downward. This movement
constrictors relax to dilate the pharynx, while the pharynx
is usually described as occurring in two distinct stages,
and larynx are raised by the longitudinal muscles. The
with the first bringing the epiglottis from a vertical to a
bolus is propelled over the epiglottis by the action of the
nearly horizontal position and the second moving the
constrictors contracting in sequence. The larynx is then
upper third of the epiglottis to below the horizontal to
closed by contraction of the muscles of the laryngeal inlet.
cover the narrowed laryngeal aditus. The precise con
The initiation of swallowing involves contact of the food
tribution of active and passive mechanisms to this two
with the faucial arches or with the mucosa overlying the
phase closure is unclear. Some authors state that both
posterior pharynx in the region that is innervated by the
actions occur passively due to movements of adjacent
glossopharyngeal nerve. Recent work involving simulta neous videofluoroscopy and endoscopy suggests that the
pre-epiglottic adipose fat pad, and within the ligamentous
structures and forces generated by compression of the
'trigger point' may be the 'summation of afferent signals
attachments of the epiglottis, or by a combination of the
for the entire oropharyngeal sensory field'. Bolus material
two.
is seen in the valleculae and even the pyriform sinuses in
ment
1
11, 12
is
Others claim that the second epiglottic move generated
actively
by
the
action
of
the
1958 I
PART 15 THE LIPPER DIGESTIVE TRACT
13
In favour of
central nervous system (CNS). In common with all
an entirely passive mechanism, it has been claimed that
complex motor behaviours, swallowing is organized and
thyroepiglottic and hyoepiglottic muscles.
these muscles are too sparse to generate adequate force
coordinated by a hierarchical series of structures within
and that some of their attachments are not consistent 12 with such an action. Throughout this stage of swallow
the brain. This extends from the motor neurones within the motor nuclei of the brainstem up to the cortex. The
As the food passes over the posterior part of the curved
although the importance of this has only been fully
epiglottis, it is diverted into the lateral food channels and
recognized recently. There are probably still some areas of
ing, respiration remains suspended. [***/**]
act of swallowing is regulated by sensory feedback,
the pyriform fossae. Early studies suggested that airway
the CNS involved in swallowing that remain to be
protection was further maintained by the bolus splitting
identified but there is a consensus as to the main regions
after passing the base of tongue, moving laterally through
involved. The initiation of swallowing can either be as a
the pyriform sinuses and rejoining to pass into the
voluntary act or a reflex as the result of stimulation of the
oesophagus. Recent evidence has shown that solids tend
appropriate mucosa in the oral cavity. This might occur
to go straight over the epiglottis, while liquids are
during saliva accumulation or by the presence of food or
diverted laterally. This is possibly a characteristic of bolus I properties rather than swallow biomechanics. Multiple
liquid. This emphasizes the fact that as swallowing is
swallowing post-bolus is often classed as a sign of
control is divided between two major regions of the brain:
impairment. This occurs in the healthy population even I4 with water, more so with older adults and with yoghurt,
the cerebral cortex and the brainstem. Studies have shown
a typical test substarice in the UK. Yoghurt is acidic which
voluntary
increases saliva flow and it is a sticky substance that
anatomical
requires effort to clear. I
S
[***/**]
partly a reflex activity and partly voluntary, its neural
that several regions of the cortex contribute to the control and
of
swallowing.
physiological
Due
to
the
relationships
close
between
swallowing, ventilation and mastication, there is extensive
The laryngeal inlet itself is never actually fully closed
overlap in the brainstem areas controlling these functions.
but should food enter the laryngeal vestibule the true and
There is an absolute requirement that neural control of
false folds guard the entrance to the airways and the true
these various processes ensures that they are coordinated.
vocal folds are adducted to prevent ingress of foreign bodies. The protective cough reflex can then be used to
The
voluntary
initiation
of
swallowing
involves
bilateral areas of the prefrontal, frontal and parietal cortices. Positron emission tomography (PET) of the
remove the object. The pharynx constricts behind the bolus as the
cortex following passive initiation of swallowing reveals
superior constrictor muscle contracts. The bolus is carried
activity in several regions. These include the face areas of
down the pharynx by a coordinated peristaltic wave in
both the primary sensory and motor cortex, as well as the
which the three constrictor muscles contract in the
prefrontal
appropriate sequence. The bolus leaves the oropharynx
anterior to the face region of the precentral gyrus in the
and enters the laryngopharynx passing over the closed
primary motor cortex, corresponding to Brodman's area
laryngeal aditus and arytenoid cartilages and entering the
6. Stimulation here produces swallowing activity in the
pyriform fossae in the lower part of the laryngopharynx.
appropriate muscles of the oral cavity, pharynx, palate 16 and larynx. [***]
The inferior constrictor then moves the bolus towards the
swallowing
areas
which
are
located
just
The inference from animal studies is that the control of
oesophagus.
swallowing is bilateral, but in man projections from the cortex appear more complex. Cortical projections to the
Oesophageal phase
muscles of the larynx, pharynx, palate and upper face are
The cricopharyngeus relaxes and the anterior superior
bilateral while projections to other muscles may be l? unilateral or bilateral. Within the cortex, evidence
movement of the laryngohyoid complex acts to open the
suggests that the frontal swallowing centre is organized
upper oesophageal sphincter. The bolus passes through
somatotopically with different regions controlling differ
the
ent stages of swallowing. This is substantiated by studies
sphincter
and
moves along the oesophagus by
peristalsis. The levator and tensor veli palatini relax lowering the soft palate. The laryngeal vestibule opens, the 3 hyoid drops and the vocal cords open. This opening of
employing
transcranial
magnetic
stimulation
of
the
frontal swallowing centre. IS These studies show that the lower precentral gyrus and posterior inferior frontal gyrus
the glottis at the very end of the oropharyngeal swallow
control the oral phase of swallowing. The pharyngeal and
sequence is part of the airway protection mechanism. [**]
oesophageal phases of swallowing are controlled from more rostromedial regions of the cortex within the anterior inferior and middle frontal gyri. In most people,
NEURAL CONTROL
swallowing control is asymmetrical with the projection healthy
from
one hemisphere being larger than the other, independent of handedness. It has been hypothesized
swallowing involves a number of different regions of the
that this explains both the prevalence of swallowing
Neural
control
of
the
complex
actlvIty
of
Chapter
150 Physiology of swallowing I
1959
problems following stroke and the recovery that occurs in
the medulla above the nucleus of the solitary tract. A
most patients over a period of weeks. Damage to the
second group lies more ventrally around the nucleus
hemisphere that is the source of the greater projection to
ambiguus. These two neuronal groups are sometimes
the swallowing structures in the brainstem would account
referred to as the lateral and medial medullary swallowing
for the initial difficulty. Recovery then occurs as the intact projection from the undamaged hemisphere is I reorganized. 9 [H*/H/*] Other cortical areas that have been implicated in
centres. A variety of evidence, much of it emanating from 21 supports the view that these two
the laboratory of Jean,
neuronal groups are vital in the control of swallowing. The dorsal group would
appear
to
be the site of
swallowing include the frontal operculum, orbitofrontal I8 cortex and the insula. The insula lies deep to the lateral
and is probably important in the sequencing of swallow
fissure and is covered by the operculae of the frontal,
ing. The ventral group distributes outputs to the various
parietal and temporal lobes and strokes here can induce 20 dysphagia. This suggests that cortical control of
not simply excitatory. In any reflex system, excitation of
convergence of sensory input from the various nuclei
cranial nerve motor nuclei. Outputs from this region are
swallowing is hierarchical with precentral areas of the
agonist muscles and their synergists will be accompanied
cortex being influenced by deeper and more caudal I8 [*H/H] centres.
by inhibitory outputs to the corresponding antagonist
muscles. [*]
The cortex is crucial in the voluntary initiation of
The correct sequencing of events for healthy swallow
swallowing and integration with movements of the face and associated structures. However, cortical structures are
ing is thought to be controlled by a central pattern 2I generator (CPG). CPGs are groups of neurones capable
not essential for a coordinated swallow which can occur
of generating outputs that will ensure the basic sequen
in the presence of significant brain damage in these
cing of a movement in time and space in terms of the
regions. There are important areas within the brainstem
muscle contractions needed for automatic movements 22 The
necessary for the control of swallowing and these are
such as swallowing, ventilation or locomotion.
located
Descending
action of many CPGs is based upon pacemaker-type
pathways project to these medullary swallowing centres
activity of a subset of neurones that is responsible for the 22 initiation of the rhythmic activity. In this respect,
particularly
within
the
medulla.
from the frontal swallowing areas within the cortex. These probably include pathways in both the dorsolateral and
swallowing is similar to ventilation and both these motor 23 Given
ventromedial descending systems through the ventral and
behaviours are linked to masticatory movements.
lateral corticobulbar tracts.
the close relationship between swallowing and ventilation,
Within the medulla there are a number of neurone
it seems to be inevitable that there will be central
groups involved in the control of swallowing. Swallowing
coordination of these processes. The idea of a central
is initiated by touch sensation or pressure from the liquid
mechanism coordinating and regulating respiration and 24 swallowing was first hypothesized over 15 years ago. The 25 exact neural organization is still unclear and is one of
or food within the posterior part of the oral cavity, epiglottis
or
oropharynx.
Thus the
nuclei
receiving
afferent input from these regions, which include the nucleus
tractus
solitarius
and
the
spinal
trigeminal
the many areas for further investigation for a fuller
H understanding of the control of swallowing. [ /*]
nucleus, are very important. Afferent input from the jaw, muscles of mastication, lips and tongue is also essential to the control of swallowing. The oral cavity
RES PIRATION AND SWALLOWING
contains an unusually high concentration of mechano receptors. These protect delicate tissues from the high
Respiration and swallowing are inextricably linked as they
forces generated during mastication, to trigger the reflex
use the same structures and thus the two processes must
and to sense the size and consistency of the bolus, also as
be finely coordinated. Efficient transport of food and
part of the trigger mechanism.
drink to the oesophagus has to co-occur with main
The efferent pathways from the medulla and pons to
tenance of a safe airway and prevention of material
the muscles involved in swallowing involve several cranial
entering the lower respiratory tract (Figure 150.3). There
motor nuclei. The most important are the nucleus larynx, the hypoglossal nucleus for the muscles of the
appears to be an individual swallowing respiration 15 pattern that matures in the teenage years and is 27 remarkably consistent thereafter. This may be subject
tongue and the motor nuclei of the trigeminal and facial
to a degree of peripheral modification by bolus char
ambiguus for the muscles of the palate, pharynx and
nerves for the muscles of the jaws and lips. In addition,
acteristics. The existence of such an individual pattern
motor neurones within the cervical spinal cord control
may present a risk for aspiration if it is disturbed. Disease
the muscles of the neck including the infrahyoid.
or injury may upset this delicate balance, whether due to
Between these input and output pathways are inter posed two main groups of neurones that appear to be
neurological insult or common otolaryngological condi 28 [H*/H/*] tions such as posterior laryngitis.
essential for the coordination and regulation of swallow
One of the difficulties in describing this relationship is
ing by the medulla. The first lies in the dorsal region of
that the defining characteristics and influencing factors of
1960
I PART 15 THE UPPER DIGESTIVE TRACT
suspended during pharyngeal transit of the bolus
150.4). and
is
(Figure
This is known as the period of swallow apnoea typically
less
than
one
second
in
length,
corresponding to the duration of the reflex part of the swallow in its pharyngeal phase.27, 30 The duration of swallow apnoea is dependent upon bolus volume and possibly bolus consistency.
[**]
In a study of 60 people, one of the largest to date, Hiss
et
a
l 33 reported that increasing the bolus volume over .
15 mL corresponded with increased swallow apnoea. The
effect of bolus consistency is less clear. There is evidence to
suggest
that
solids
increase
numbers are too small to swallow or saliva swallow
apnoea
but
sample
be unequivocal. 34 The 'dry'
is often used as a trial condition
but the actual volume cannot be controlled, which could introduce error and may even involve different physiol ogy.33 Gender effects are conflicting with men having Figure 150.3
longer durations due to differences in structure35 and
Aspiration into upper trachea. Reproduced by
women having longer durations linked to increased upper
permission of the BMJ Publishing Group from Ref. 26.
oesophageal opening.33
[***/**]
the swallowing ventilation pattern vary from one study to another. The problems with the literature in this area, as in all aspects of swallowing research are that: • • • •
there are few standard definitions;
Phase of respiration when swallowing occurs Swallowing tends to occur during the expiration phase of
investigation techniques vary;
respiration.
authors study different features;
Expiration occurs after 80-100 percent of
healthy swallows.35, 36 This is likely to be a protective
many studies are of small numbers.
mechanism: material left in the laryngeal vestibule post
For example the 'increase' in bolus volume in a study can vary widely; ranging from 1-5 mL29 to 0-20 mL.30 There are variations in the methods by which a bolus is administered, including giving free access to the test material, providing premeasured volumes but offered on a spoon or directly syringing material into the mouth. Swallowing may be 'to command' or when the participant 'feels ready'. Posture may be seated, standing or less often,
swallow
will be moved to the pharynx rather than sucked
into the lungs. Post-swallow inspiration is more common in populations with impaired swallowing. 15,37 There does not seem to be an effect of bolus volume or gender on the exhale-swallow-exhale pattern.33 The respiratory rhythm is reset after swallowing and there is a shift in the timing of all subsequent breaths post-swallow: type I phase resetting.38
supine. All of these influence the subsequent measured
[***/**] Apnoeic period
indices and care has to be taken when interpreting the results of studies spanning such wide methodological variation. Respiration monitoring techniques also vary. Measurement can be made of respiratory effort (plethys mography, pneumography), body movement (pneumo tachograph) or nasal airflow (thermistor or pressure transducer). Tarrant et
al.31 give a concise review of the
various techniques and concluded that nasal airflow devices are the most appropriate but that they may need
supplementation, for example, in the event of a mouth breather. Changes due to disease such as decreased pharyngeal patterns.32
sensation
may
mask
altered
respiratory
[*** /**/*]
Swallow apnoea Despite
these
principles
methodological
emerge.
Clearly,
caveats, ventilation
some has
general to
be
Figure 1 50.4
Swallow apnoea.
Normal reset pattern
Chapter 150 Physiology of swallowing I
Continuous versus single swallows
KEY POINTS
Much of the information on the swallowing respiration
•
pattern is based on single boluses of 1-20 mL. The few studies that have looked at larger volumes, such as 100 mL
•
of liquid, have found changes in the features of the swallowing respiration pattern.
1961
A greater number of
•
swallows occurs during the inspiratory phase and there is a plateau of the number of mouthfuls taken with an
•
increase in volume, possibly so as not to compromise occur as mouthfuls are swallowed.9 This puts considerable
•
strain on the system and could be interrupted with a drive to breathe in, a danger in patients at risk of aspiration or
•
with already compromised respiratory systems. This has a bearing on advising patients to use a straw to drink.
Healthy swallmving has a much wider range than previously thought. Neural control is divided betw'een the cortex and the braLnstem. Corti ca l control of swallowing is bilateral,
of parameters
one
hemisphere is usually
dominant. Airway protection is activated in advance of the pharyngeal stage of swallowing. I mpaircd respiration patterns will affect
swallowing
[**]
stepwise progression, it is
a cyclical and irregular process.
aJ:though
respiration.39 The larynx is held up and a long apnoea can
a
Swallowing is not
and
vice
versa.
AGE EFFECTS: PRESBYPHAGIA Deficiencies in current knowledge and areas for future research
From 1960 to 1990, the population of the US grew by approximately 40 percent with the number of people over 65 almost doubling and for those over 85 years there was
In five years time we would like to have a better
more than a 200 percent increase.40 There will be greater
understanding of and robust evidence for:
numbers of older people and correspondingly
� the process of swallowing a whole meal rather than
more
people at risk of age-related illnesses. As we age, processes
discrete controlled boluses;
slow down, there is a decrease in strength, coordination
).- the link between oral health and pneumonia rather
and sensation - particularly smell, which is a primary
than the red herring of aspiration and pneumonia;
factor in eating.41 Where the older person performs
»- long-term outcomes:
similar to a younger one, they are often working far
> muscle sequencing and timing;
harder, for example with lingual pressure.42 Reserve
). the role of the brainstem in swallowing;
capacity also diminishes, that extra ability called upon
> individual variation;
in times of high demand. Single swallow peak suction
>- what is normal?
pressure is the same for young and old but during forced repetitive swallows there are differences with the older person)
suggesting
less
reserve
capacity.14 Individual
features of the swallow may change with age but the current evidence base is small though growing.
[""*1*)
REFERENCES *
1.
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Dua KS, Ren J. Bardan E. Xie p. Shaker R. Coordination of deglutative glottal function and pharyngeal bolus transit during normal eating. Gastroenterology 1997; 112: 73-83,
Much of the data on the swallowing process come from observations
of populations
with
impaired
systems.
pathway
Studies of healthy groups are often of small numbers
2,
with young age ranges and many of the difficulties
swallowing
in art! linked to agt! or age-related diseases. As
Neck. 1995; 5: 394-402. 3,
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1478-84. *
4.
Miller A. Deglutition. Physiological Reviews. 1982; 62:
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Tolin R. Malmud
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�--
[**1
Shaker R. Dodds WJ, Dantas RO, Hogan WJ, Arndorfer RC. Coordination of deglutative glottic closure with
series of controlled volume/consistency
of eating a meaL7 When evaluating reports) the reader
Ohmae Y, Logemann JA, Kaiser P, Hanson DG, Kahrilas PJ. Timing of glottic closure during normal swallow, Head and
more information emerges, the performance envelope of
swallowing a
Queries received wisdom of 'premature
spillage' and illustrates consistency effect on bolus
129-84.
A comprehensive review of the early literature.
l
Reilley J, Fisher R. Esophageal
scintigra phy to qua ntitate esophagea I transit
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PART 15 THE UPPER DIGESTIVE TRACT
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Arshavsky Y, Deliagina T, Orlovsky G. Pattern generation.
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McFarland DH, Lund JP. Modification of mastication and
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Russell C, Hill L, Holmes E, Hull D, Gannon R, Pope C.
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24.
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Curtis JL, Langmore SE. Respiratory function and complications related to deglutition. In: Perlman AL,
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Schulze-Delrieu K (eds). Deglutition and its disorders.
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Martin BJW, Logemann JA, Shaker R, Dodds WJ.
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29.
volume, viscosity, and temperature in patients with
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Coordination of respiration and swallowing: effect of
during deglutition. A cineradiographic study.
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Physiology. 1992; 263: R624-30.
31.
aspects of swallowing in an elderly nondysphagic
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Leslie P, Drinnan M, Ford G, Wilson J. Swallow respiration 32.
Woolsey C, Erickson T, Gilson W. Localization in somatic
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determined by direct recording of evoked potentials and electrical stimulation. Journal of Neurosurgery. 1979; 51 :
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Dysphagia. 2001; 16: 128-35.
34.
swallowing: effects of bolus consistency and presentation
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14: 131-8.
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* 21.
Klahn MS, Perlman AL. Temporal and durational patterns associating respiration and swallowing. Dysphagia. 1999;
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20.
Preiksaitis HG, Mills CA. Coordination of breathing and
Hamdy S, Aziz Q, Rothwell J, Singh K, Barlow J, Hughes D health and disease. Nature Medicine. 1996; 2: 1217-23.
* 19.
Hiss SG, Treole K, Stuart A. Effects of age, gender, bolus
476-506. Stimulation of the human motor cortex through the scalp. 18.
Lazarus CL, Logemann JA, Rademaker AW, Kahrilas PJ, Pajak T, Lazar R et 01. Effects of bolus volume, viscosity,
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17.
Tarrant SCI Ellis RE, Flack FC, Selley WC. Comparative
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Preiksaitis HG, Mayrand S, Robins K, Daimant NE.
Ekberg 0, Sigurjonsson S. Movement of the epiglottis Gastrointestinal Radiology. 1982; 7: 101-7.
14.
Bisch EIVI, Logemann JA. Pharyngeal effects of bolus
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Shaker R, Hogan WJ. Reflex-mediated enhancement of airway protective mechanisms. The American Journal of
Negus V. The mechanism of swallowing. Journal of Fink B, Martin R, Rohrmann C. Biomechanics of the human
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11.
Leslie P et 01. Investigation and management of
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10.
Broussard DL, Altschuler SM. Central integration of swallow and airway-protective reflexes. American Journal
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8.
Nishino T, Yonezawa T, Honda Y. Effects of swallowing on
Hiiemae KM, Palmer JB. Food transport and bolus
36.
Selley WG, Flack FC, Ellis RE, Brooks WA. Respiratory
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Jean A. Brainstem control of swallowing: localization and organisation of the central pattern generator. In: Taylor A
1989; 18: 168-72. 37.
Hadjikoutis S, Pickersgill TP, Dawson K, Wiles CM.
(ed.). Neurophysiology of the jaws and teeth. London:
Abnorl'flal patterns of breathing during swallowing in
Macmillan Press, 1990. Brainstem control.
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Paydafar D, Gilbert RJ, Poppel CS, l\Jassab PF. Respiratory
41.
40.
1963
Mulligan C, Moreau K, Brandolini M, Livingstone B,
phase resetting and airflow changes induced by
Beaufrere B, Boirie Y. Alterations of sensory perceptions in
swallowing in humans. Journal of Physiology. 1995; 483:
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273-88. 39.
150 Physiology of swallowing I
Issa FG, Porostocky S. Effect of continuous swallowing on
42.
Robbins JA, Levine R, Wood J, Roecker E. Age effects on
respiration. Respiration Physiology. 1994; 95: 181-93.
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151 Functional investigations of the upper gastrointestinal tract LISA J HIRST
1977
Introduction
1964
Conclusion
Investigations
1965
Key points
1977
Radiology
1966
Best clinical practice
1977
Endoscopy
1968
Deficiencies in current knowledge and areas for future
Manometry
1970
Other investigations
1975
1978
research
1978
References
The data in this chapter are supported by Medline, EMBASE and CINAHL searches using the key words deglutition, swallowing, investigation and diagnostic tests; and MeSH deglutition, videofluoroscopy, manometry, ultrasound,
MRI,
nasendoscopy, FEES, respiration and pH monitoring. In addition, references were gained from attendance at the international meetings of the Dysphagia Research Society (DRS), a North American-based multidisciplinary society committed to the study of swallowing disorders.
INTRODUCTION Normal swallowing
3. Downward pharyngeal contraction movement
against the hyoid for pushing through the bolus tail. Relaxation and opening of the UOS must be timely and
The physiology of the normal swallow has been well
coordinated with the bolus flow for normal swallowing.
documented: Mendlesohn explains the mechanics and
Throughout, the bolus passes along the path of least
pressure changes within the swallowing tract that facilitate
resistance.
movement of a single liquid bolus. 1 Lip, cheek and tongue muscle control are necessary to ensure bolus control in the mouth, and maintain intraoral pressures for bolus movement during swallowing. The three main forces moving the bolus in a coordinated manner, independent from gravity, are:
Dysphagia Oropharyngeal
dysphagia
is
a
nonspecific
term
for
disorders of swallowing. Underlying aetiologies are of
1. Tongue thrust pushing force?
anatomical,
2. 'Pull' of the relatively lower (i.e. atmospheric)
origins. An impaired swallowing mechanism prevents
pressure
in the oesophagus as the upper
oesophageal sphincter (UOS) opens, termed
neurological,
muscular
or
psychological
complete and timely bolus transfer to the oesophagus, or causes a misdirected bolus, resulting in nasal reflux; bolus
'hypopharyngeal suction pump' by McConnel
spillage, pholing and residue; penetration and aspiration;
et
and
aI.3
oesophago-pharyngeal
regurgitation.
Poor
oral
Chapter 151
Functional investigations of the upper gastrointestinal tract I
are widely used
control, weak pharyngeal contraction, inadequate UOS
opening and incoordination between events all contribute
geal
to dys functi onal swallowing. The symptoms of dysphagia
1965
as instrumental assessments of oropharyn (Table 151.1). Manometry provides
dysphagia
additional information and evaluates the pressure changes
are varied including coughing, choking, chest infections
from pharyngeal and oesophageal muscle activity, parti patien ts with mot ility disorde rs. 14 All are
and slow, painful or effo r tful swallowing. Ultimately,
cularly in
patients may develop pneumonia, become dehydrated
complimen tary functional investigations.
and undernourished.
IS, 16
Throughout any investigation, common principles of good practice, such as those listed below, prevail. •
INVESTIGATIONS Bedside
clinical
instrumentation
assessments do
not
of
have
swallowing high
•
without
sensitivity
functioning, insight, perceptions, beliefs and compliance; fluctuation or deterioration in
12
However, functional investigations involving instru
medical and respiratory state or swallow function; signs of aspiration; fatigue level;
ability to maintain posture and position for safe
mentation provide detailed information about swallowing
feeding; and health, safety and infection control
function in t erms of anatomy and physiology, as well as
the symptoms of dysphagia such as the presence or
issues.
1 absence of aspiration , penetration, reflux and residue. 3 With
information
about the
•
flow),
dysphagia
decisions
an
can
for
accurate
inform
patient
diagnostic
treatmen t
safety
and
description
and
•
aspiration (below the level of the vocal folds), for example, using Rosenbek's penetration/aspiration 17, 18 scale.
Repeat
investigations allow evaluation of the effectiveness of treatment
over
time,
as
well
as
any
spontaneous
(modified
barium
swallow)
fibreoptic endoscopic evaluation of swallowing
Table 151.1
•
Assessing patients in their optimum or usual feeding
•
Awareness of multifactoral risks for developing
position.
improvement or deterioration. Videofluoroscopy
and
pneumonia.19
(FEES)
Comparison oF. �i�eofluoroscopy with FEES and manometry.
'\fFL' ,"
, Feature Equipment
Personnel
Accurate recording of p enetration (material entering
the larynx but remaining above the vocal folds) or
of
management
well-being,
Recording clinical observations, instructions, bolus
volumes and consistencies given.
physiology causing the
swallowing disorder, and the symptoms (in terms of
bolus
Awareness of adverse situations dur ing
assessment. For example, the patients cognitive
and
specificity to swallowing abnonnalities and aspiration, 4,5,6,7,8,9,10,11 and have poor interjudge and intrajudge reliabilit y.
A detailed history of onset and p rogression, specific
symptoms and relief strategies .
tid
.
I
Nasoendoscope camera, monitor,
X-ray screening facility, digital/
Catheter, com puterized
dig'ital/video-recorder with timer
video-recorder with timer and
multichannel recording
and microphone
microphone
device
Otolaryngologist, speech and la nguage therapist, and nurse
Radiologist and radiographer,
Gastroe nte ro logist (speech and language therapist)
otolaryngologist, speech and language therapist, and nurse
Hazard
Cross infection
Radiati on Ii mitati ons
Versatility
Portable, bedside use
X-ray department only
Portable
Oral stage
Only incomplete and indirect
Well seen
No
Pharyngeal stage
Direct assessment before and after
Well seen
Pressure readings
Cross infection
inferences swallowing, not during Oesophagal stage
Not consistently seen
Can be observed
Pressu re readings
Aspiration/penetration
Can detect occurrence
Accurate assessment
No
Pharyngeal sensation
Tested accurate Iy by FEESST
Only inferred
No
Range of boluses
All ranges of food and drink
Radio-opaq ue contrasts a Iter
Yes
viscosity, texture and taste of food/drink Fatigue effect
Easy to record
Limited by radiation and expense
Yes
Biofeedback
Good and simultaneous
Good
Limited use
-
!,
-----
1966 I •
•
•
PART 1 5 T H E UPPER DIGESTIVE TRACT
Challenging the swallow during assessment by increasing the speed and bolus volume if necessary (normals manage single bolus sizes up to 20-25 mL and swallow continuously at a speed of approximately 15 mL/second, unless elderly);20,21, 22 , 23 therefore, bolus volumes given during assessment should increase in size up to this if safe, and both single mouthful and continuous swallowing should be recorded. Sterilizing equipment from contamination of nasal mucus and blood, due to the semi-invasive nature of nasendoscopy and manometry. Access to gluteraldyhyde is necessary to comply with infection control policies and safe practice guidelines. A team approach, including speech and language therapists, radiologists, otolaryngologists, gastroenterologists, neurologists and psychiatrists, etc., as required.
RADIOLOGY There are two distinctly different barium swallows available for the evaluation of dysphagia: the traditional barium swallow, and video fluoroscopy (also called a modified barium swallow or dynamic swallowing study). Videofluoroscopy was originally described by Logemann24 as a diagnostic procedure for oropharyngeal dysphagia. Early reference to this technique was made late in the nineteenth century, soon after the discovery of x-rays?5 Later, cineradiography developed from single images, but was superseded in the 1980s by videofluoroscopy with a recording rate of up to 50 frames per second, and much lower radiation exposure?6 The method described by Logemann remains the accepted standard and is widely used. 24,27
Video fluoroscopy has an important role in detecting dysphagia in the absence of overt symptoms of dysphagia such as when silent aspiration occurs. It enables safe management of symptoms, planning of treatment based on the underlying physiological problem, and measure ment of the effectiveness of treatment.
PROCEDURE
Patients are assessed in a sitting position and boluses are given in increasing volume to minimize the risk of aspiration of large amounts of barium, often starting with 1 mL to coat oral structures. All consistencies are given (liquid, semi-solid and solid) using video fluoroscopic specific contrast materials that are commercially available. These are designed to optimize bolus visualization using standard viscosities and to minimize adherence and coating on mucosa. Some clinicians bake with barium to incorporate barium throughout a solid bolus, rather than on its surface (note that barium sulphate becomes toxic when cooked28) . Videofluoroscopy should include simul taneous viewing of the oral, pharyngeal and laryngeal areas, but the oral cavity may initially be sacrificed to gain a clear picture of the pharynx, larynx cervical trachea and upper oesophagus to determine the competence of the pharyngeal swallow. Images are recorded on videotape or digitally, in the lateral and anterior-posterior views for later analysis and interpretation. If dynamic measurements of distance and area are to be calculated, then a metal ring of known diameter (e.g. coin) is taped in the midline to the underside of the chin for calibration. Perlman and Schulze-Delrieu29 give a comprehensive account of the equipment and procedure, as well as an interpretation of observations and dysphagic character istics in the oral and pharyngeal stages of swallowing?9
Equipment Videofluoroscopy Video fluoroscopy is a dynamic fluoroscopic imaging procedure that enables visualization of the rapid and integrated movements of the oral cavity, pharynx, larynx, trachea and oesophagus required for eating, drinking and swallowing of food and liquids. It should be performed in the context of a multidisciplinary team. Video fluoroscopy is particularly advantageous for observing all stages of swallowing, estimating the amount of aspiration, and identifying structural or anatomical abnormalities as well as the physiological abnormalities causing dysphagia. The main points of information gained concern the symptoms of the dysphagia and the anatomy and physiology of the swallow and include: 1. the flow, misdirection and residue of the bolus; 2. the reaction to penetration or aspiration; 3. the oropharyngo-oesophageal muscle movements and timings of these.
Typical imaging equipment found in a modern radiology department is required, along with special commercially available seating, video fluoroscopy-specific contrast ma terials, and an ability to make high quality video or digital (including auditory) recordings with the capability for slow-motion and frame by frame analysis. Downloading the study onto a computer enables dynamic swallow study measurements. 30
ANALYSIS
Subjective interpretation of video fluoroscopy by experi enced clinicians provides descriptions about the bolus flow, reactions to a misdirected bolus and variations from the normal anatomy and physiology. Rating scales attempt to standardize observations over time or between clinicians, for parameters of oral transit, pharyngeal transit and laryngeal valving30 and for penetration and aspiration.17
Chapter 1 51 Fu nctional i nvesti g ati ons of the u p per g astro i n te stinal tract I 1967
Objective analyses of videofluoroscopy are called dynamic swallow study measurements30 or kinematics of swallowing.29 These involve capturing and manip ulat ing digital images with computer technology to make exact timing measures of bolus flow and movement of structures, as well as spatial measurements of distance and area against reference points. In-depth methodology is provided by Leonard and Kendall.30
ADVANTAGES • •
•
• •
•
All stages of the swallowing mechanism are seen. Estimates of volume, depth and clearance of aspiration can be made. The safety of any therapeutic or compensatory strategies can be evaluated. A full range of consistencies can be tested. Anatomical abnormalities can be detected (pouches, diverticulae, fistulae). Biofeedback to patients.
LIMITATIONS •
•
• •
•
•
•
Radiation exposure to the patient, especially for repeated or lengthy studies. However, three minutes of videofluoroscopy examination gives the equivalent radiation exposure as two cervical spine radiographs24 and scattered radiation exposure to the surroundings is within acceptable levels.31 High cost of equipment and involvement of several staff. Patient intolerance of procedure. Difficulties with seating some patients within the confined space. Properties of barium are designed to coat structures, so liquid and food containing barium does not behave in the same way as normal liquids or food. This can be minimized by using videofluoroscopy specific contrast materials. Limited or inferred information only is gained about mucosa and secretions, sensation, inter-bolus pressure, and details of glottic closure. Greater standardization of the procedure,32 with higher interjudge reliability between experienced clinicians,12 is required before it is truly a 'gold standard' technique.
CONTRAINDICATIONS •
•
Patients without a pharyngeal swallow, as aspiration of barium will almost certainly occur. Unsuitable patients (e.g. those who are unable to maintain a stable position, drowsy, uncooperative, nil by mouth for reasons other than dysphagia, have adverse reactions to contrast media, should avoid unnecessary exposure to radiation).
•
Caution needs to be taken when patients are suspected of large volume aspiration, or have a history of respiratory distress/arrest due to aspiration. If large volume aspiration is suspected, there should be a small volume « 5 mL) initial test swallow using water soluble contrast materials such as nonionic isotonic agents (e.g. Omnipaque or Gastromiro). Gastrograffin is contraindicated due to its hypertonic properties and risk of pulmonary oedema if aspirated.
RISKS •
•
Aspiration of barium can be assessed with a chest radiograph to document the pattern and extent of aspiration, before suction and physiotherapy. Repeated or prolonged radiation exposure.
Barium swallow If oropharyngeal dysphagia and aspiration are suspected, bolus sizes need to be kept small and the investigation should proceed cautiously, or a videofluoroscopy exam ination should be undertaken instead. The traditional barium swallow includes both static and dynamic components to identify intrinsic disease (tumours, diverticula, webs and dysmotility) and extrinsic disease (cervical osteophytes, enlarged thyroid gland). The oesophageal lumen is distended with liquid barium, or coated in thick barium and distended by gas to show intrinsic irregularities and extrinsic impres sions. Static imaging with plain radiographs provides information on structural abnormalities (e.g. Zenker's diverticulum, cervical osteophytes), but these static images have little else to contribute to the investigation of dysphagia.28 Oesophageal motility is assessed with multiple single swallows in different positions, including recumbent (unlike in a videofluoroscopy assessment of oropharyn geal dysphagia) , to assess peristalsis without the effect of gravity. Continuous and single swallows are observed separately as a second swallow obliterates peristalsis of the first. The oesophageal stage lasts for 8-20 seconds. Both the oral and pharyngeal stages should be assessed even if the complaint is only oesophageal as 35 percent of patients have simultaneous disorders of the pharynx and oesophagus29 and the level of the lesion does not necessarily correspond to the site of the patient's symptoms.33 Perlman et al.29 give a comprehensive account of the interpretation of observations and dysphagic characteristics in the oesophageal stages of swallowing. CT and MRI These techniques each show structural lesions, for example the intracranial disease causing neurogenic dysphagia?8 More recently, high speed MRI has been
_1
___ ____ _
1968 I
PART 1 5 THE UPPER DIGESTIVE TRACT
used for dynamic analysis of the pharyngeal phase of swallowing, where the oral, pharyngeal and laryngeal musculature can be evaluated during movement. How ever, this is experimental and costly, and patients need to be supine - which does not reflect the true physiology of swallowing.13 Some experimental work has been carried out with MRI looking at lingual deformation during swallowing.3 4
ENDOSCOPY Fibreoptic endoscopic evaluation of swallowing (FEES) is also called flexible endoscopic evaluation of swallow ing, and video endoscopic evaluation of swallowing (VEES). It has been called 'milk nasendoscopy',35 and was first described by Langmore et al. 3 6 Trans-nasal insertion of the nasendoscope provides assessment of pharyngeal and laryngeal anatomy and physiology at rest and in the pre- and post-swallow stages of dry (saliva) and bolus swallows, using normal food and drink. The extended technique of flexible fibreoptic endoscopic evaluation of swallowing with sensory testing (FEESST) quantitatively measures sensory loss in the supraglottic larynx and pharynx by sending air pulses of differing intensity, duration and frequency through an additional port in the endoscope.37 , 38, 39 FEESST instru mentation is an important development as reduced or absent laryngeal sensation found in endoscopy correlates with silent aspiration and thus the risk of aspiration pneumonia. 40, 41, 42 The technique of FEESST has been described by Aviv and Murral3 where the authors cover practical aspects of sensory testing including equipment require ments, procedures, the safety of FEESST and clinical case studies.
Fibreoptic endoscopic evaluation of swal l owing FEES is a routine investigation for diagnosis and manage ment decisions in the acute stages of the dysphagia, and for therapy with biofeedback in patients with persisting or progressive dysphagia. The assessment technique and interpretation of findings has been well described in detail by several authors.l3 , 29, 30, 3 6, 41, 44, 45,46, 47 Kidder et al. 48 clearly outlines both the practical and clinical reasons for choosing to investigate dysphagia with FEES.
applied to the nasal passages 49 (sparingly to avoid desensitizing the pharynx and larynx) , although it is not always necessary. 50, 51 Decongestant and lubrication allow easier insertion of the scope transnasally between the inferior turbinate and the floor of the nose. Four different views allow observation of anatomy and physiology during swallowing as follows: 1. Nasal passage for elevation of the dorsal side of the velum (Figure 151.1a). 2. Nasopharynx for nasal reflux and lateral and posterior pharyngeal walls (Figure 151.1b). 3. Oropharynx for base of tongue, epiglottis and larynx (Figure 151.1c). 4. Hypopharynx for pyriform fossae, vocal folds and upper trachea (Figure 151.1d). Dry and bolus swallows of coloured liquid and foo d (using foo d colouring), are given i n measured volumes.
Equipment The equipment includes a flexible nasendoscope, with camera for video or digital (including auditory) recording and slow motion playback facilities, with an additional colour monitor for immediate biofeedback with the patient. Developments include reducing the scope diameter, picture clarity and size, light source strength and portability. For FEESST, a specially designed scope and pulse generator are needed to deliver quantifiable air pulses.37, 38,39,43
ADVANTAGES •
•
•
•
•
•
•
PROCEDURE
The technique is straightforward but requires competent, experienced clinicians, with access to nursing staff, sterilization and standard resuscitation equipment. The patient sits upright, the nostrils are examined to detect any septal deviation, and topical anaesthesia is
•
•
Goo d views of any alterations in the anatomy and of muscular function in the nasopharynx, oropharynx and hypopharynx. Quantitative objective assessment of pharyngeal and laryngeal sensitivity with FEESST. Assessment of initiation and maintenance of airway protection. Visualization of secretions and any pooling of secretions, thus helping overall management. Ability to assess swallow without giving food or drink to those patients who are nil by mouth. Observation of swallowing with a range of normal food and drink. Lengthy or repeated assessments without radiation exposure. This enables assessment throughout a meal (to evaluate swallow fatigue, effective of cumulative bolus residue, delayed reaction to aspiration and effectiveness of coughing). Real time and repeated biofeedback to the patient for evaluating the effectiveness of therapeutic manoeuvres. Portable and easy implementation at the bedside and in the clinic.
Chapter 151 Functional investigations of the upper gastrointestinal tract I
1969
.'
(c) Figure 151.1
Nasendoscope positioned to view
(a)
dorsal side of velum; (b) nasopharynx; (c) oropharynx; and (d) hypopharynx/
laryngopharynx.
. / .._. ...- .---- .
1970 I
PART 15 THE UPPER D I GESTIVE TRACT
LIMITATIONS •
•
•
•
No view for evaluation of bolus management in the oral cavity. Loss of view (,whiteout') during the swallow due to pharyngeal constriction around the endoscope lens. Quantitative measures of structure displacement are not possible. Limited ability to estimate amount of aspirated material.
CONTRAINDICATIONS •
•
• •
• •
Unsuitable patients (e.g. those who are unable to maintain a stable position, drowsy, uncooperative) . Predisposition to risk factors (history of bronchospasm or laryngospasm, severe heart disease, recent respiratory distress, allergies) . Lack o f appropriate medical and nursing support. Physical obstruction to passing the scope (e.g. extreme deviation of septum, oedematous mucosa, hypersensitivity) . Obscured view (e.g. large epiglottis, thick secretions) . Maxillary and other supraglottic resections.
RISKS
The potential complications listed below are extremely rare, however, awareness of the risks is important for those performing FEES.35 •
•
•
•
•
Aspiration - suction equipment should be readily available, with small volumes of liquid and food being used until swallowing safety has been verified. Vasovagal responses of hypotension, bradycardia or cardiac dysrhythmia. These risks are minimized by local anaesthesia of the nasal mucosa and care manipulating the scope in the hypopharynx. Laryngospasm is less likely to occur in patients with pooling and aspiration of secretions who also have poor tactile sensitivity of the larynx, and who therefore usually need sensation testing. Probing of the hypopharynx and larynx should be cautious in those who swallow normally, are asymptomatic of aspiration, with an adequate cough reflex. Nose bleeds can be avoided by the use of topical decongestant and lubrication of the scope. Adverse reactions to the topical anaesthetic are rare, but clinicians should take an adequate case history, adhere to recommended doses and have resuscitation measures available.
MANOMETRY Manometry directly measures the amplitude and duration of contraction and relaxation pressures in the pharynx,
UOS, oesophagus and lower oesophageal sphincter (LOS). Measurements are taken at rest and during swallowing. 1 4 Oesophageal manometry The oesophageal peristaltic wave pressure rises slowly to approximately 50 mmHg, and falls rapidly. Secondary peristaltic waves arise locally in response to distension, needed for more solid bolus transportation. Tertiary oesophageal contractions are irregular, nonpropulsive contractions involving long segments of the oeso phagus.28 The 3 cm long LOS behaves like the UOS, but with a lower tonic (resting) contraction pressure of 10-30 mmHg relative to intragastric pressure. It remains closed except for relaxation when the bolus and peristaltic wave arrive, as swallowing induces inhibition of lower oeso phageal sphincter tone activity. The barrier formed by LOS tonic pressure is lower after meals and tighter at night. Similar to the UOS, measurement of the LOS tonic pressure is complicated by radial asymmetry and a respiratory pressure fluctuation. 52 Originally, water perfused catheters were used to measure oesophageal contractions, with patients in a reclined position. This equipment and methodology are inadequate for pharyngeal and upper oesophageal mano metry, where catheters with miniature strain gauge pressure transducer sensors are required. This is because of the differences in anatomy and physiology and the frequency of recordings, as explained under Limitations below. Pharyngeal manometry Pressure changes in the oropharynx and UOS are required for effective bolus transit and UOS opening during swallowing. UOS opening involves:1 4 •
• •
•
•
•
cricopharyngeal muscle relaxation, preceding opening by 0.1 second; hyoid and laryngeal elevation, pulling the U OS open; pharyngeal and tongue base pressure (up to 90 mmHg) on the bolus further pushing open the UOS; cricopharyngeal elasticity allowing the UOS to stretch open for larger boluses; closure of the UOS with increased pressure (90 mmHg) ; return to an UOS tonic (resting) pressure of approximately 45 mmHg.3 The UOS remains closed with increased tonic pressure with each inspiration to avoid aerophagy. 53
LIMITATIONS
Conventional pharyngeal manometry involves using a catheter with a limited number (three or four) of pressure
Chapter 151 Functional i nve stigations of the u p per gastrointestinal tract I 1971
sensors spanning the oropharynx and hypopharynx (including the VaS), in a unidirectional or multi directional orientation. However, conventional pharyn geal manometry, particularly when used in isolation, is susceptible to technical difficulties with accurate sensor placement, and inter- and intrasubject variation53 as
Table 151.2
Pro b l e m s with mano metric measurements.
Ariat()m'iC�IJ physiological. diffic,ulty Rad ial asym metry
•
•
•
•
•
radial asymmetry of the vas, as anterior-posterior pressures are two or three times greater than those recorded laterally54 because contraction of the cricopharyngeus muscle compresses the vas against the trachea into an oval slit-like aperture;14 , 29 longitudinal (axial) asymmetry of the vas, with larger anterior pressures closer to the pharynx and larger posterior pressures closer to the oesophagus, 55 especially in men; orad (upward) movement of the vas during swallowing due to laryngeal movement. Consequently the sensor may be left in the open oesophageal lumen without recording vas relaxation. To compensate, clinicians move the catheter during swallowing, or place the sensor just above the vas high pressure zone before swallowing;14 this ensures they find the correct vas waveform with a negative low-point, preceded and followed by an elevated pressure wave and clearing wave (an M-shaped waveform); sensitivity of vas to diameter size requires the smallest diameter catheter possible (e.g. 3 mm or less) to avoid inaccurate and increased vas tonic pressure readings; vas tonic pressure increases with stress and decreases during sleep; over 60 years of age, vas tonic pressures decline and pharyngeal pressures during swallowing increase as a result of reduced compliance of the vas, thus requiring greater force to push large boluses through a less stretchable sphincter.
Some of the problems associated with conventional manometry can be overcome with HRM, or with conventional catheters and sensors as described in Table 151.2. Variations in manometric readings are known to occur within and between patients, and some of the reasons for these are listed in Table 151.3.
High-resolution manometry High resolution manometry is a recent advance over conventional manometry for taking measurements of the oesophagus and upper and lower oesophageal sphinc ters.56 , 57 It has been made possible by the development of micro-manometric water-perfused assemblies and minia turized solid-state pressure sensors. The presence of closely spaced recording sensors in HRM (up to one pressure sensor per cm) provides several procedural advantages over conventional manometry. For example,
k L_
Circu mferential sensors as i n H R I VI ; or posterior orie ntation of sensors in
follows: •
TechniCal solution
ph arynx i n conve ntional manometry Axial asymmetry
H R M ; or exact positi o ni ng of sensors
Striated m u scle respo nse
Catheter as smal l and sti l l as possi b l e
and m o vement o f catheter Rapid seq u e nce of e vents due to striated m u scle
50 H z record i ng for freq u e ncy and catheter with strai n g au g e pressure sensors
UOS sensitivity to water
Catheter with strai n g auge pressure
H i g h am p l itude
Catheter with strai n g auge pressure
sensors co ntracti o ns i n UOS Orad m o vement in swallow
sensors HR M ; or co nventional manometry with extra sensor above UOS, or m o ve catheter d i stal ly d u ri ng swal low (aided by manofl u o roscopy)
Table 151.3
Pro b l e m s with mano metric measure m e nts.
Biological factor
Variati()n
O ver 60 years of age
R e d u ced UOS tonic pressure
M al e g e nder
I ncreased axi al sym m etry
I ncreased p h aryngeal contraction During sleep
Red u ced UOS tonic pressure
With stress
I ncreased UOS to nic pressure
it removes the need for the time-consuming station pull through procedure and facilitates the accurate positioning of the catheter. In the oesophagus and LOS, major clinical advantages of using HRM over conventional oesophageal manometry are described by Fox and Hebbard.56 They report that studies have shown that HRM detects segmental abnorm alities of oesophageal function and predicts the success of bolus transport more accurately than conventional oesophageal manometry, and identifies clinically impor tant abnormalities not detected by other investigations. For pharyngeal and vas measurements, a solid state high-resolution manometry catheter can have a total of 36 pressure sensing elements. Sensors are spaced at 1 cm intervals; with each sensor detecting pressure changes over a length of 2.5 mm and consisting of 12 circum fer entially dispersed smaller sensing elements. The pressure recorded at each axial location is the mean pressure measured from the 12 elements.
19721
PART 15 THE UPPER DI GESTIVE TRACT
Computer technology allows the large data set acquired by HRM to be analysed and presented in real time either as a conventional 'line plot' or as a 'spatiotemporal plot' (also referred to as a 'contour plot') . Concurrent video fluoroscopy images displayed in the same record as HRM allow simultaneous analysis.
Observations of bolus flow and timing of flow can be related to physiological movements, for example, differ ential diagnosis of reflux occurring with normal oeso phageal contractions, from reversed bolus direction due to retrograde peristalsis, or from bolus escape due to insufficient contact (or squeeze) pressures of the oeso phageal wall.
Manofluoroscopy PROCEDURE
Pharyngeal manometry is rarely the first or sole study used to evaluate swallowing function, because of the limitations described, particularly when using conventional mano metry. More information is provided when it is performed simultaneously with videofluoroscopy, termed mano fluoroscopy or videomanometry. Manofluoroscopy shows a simultaneous image with pressure readings so that clinicians gain information about bolus flow relative to anatomical movements. Radio-opaque metal housing around each pressure sensor gives accurate information about the placement and position of the sensors during movement to ensure, for example, that the UOS relaxation pressure is being measured during swallowing rather than the pressure in the oesophageal lumen.
ADVANTAGES
Manofluoroscopy aids clinical decisions about the need for medical procedures: •
•
•
•
•
•
It provides information to distinguish between UOS opening with and without relaxation of the cricopharyngeal musculature. Where adequate UOS relaxation is occurring, manofluoroscopy can help to differentiate between poor opening of the UOS secondary to weak pharyngeal and tongue forces; poor elevation of the hyoid; and decreased elasticity of the cricopharyngeus muscle. In patients with good UOS relaxation but with reduced tongue and pharyngeal pressures or reduced hyoid elevation and poor pulling forces, it would be inappropriate to treat with dilatation or myotomy, and these could increase the symptoms of dysphagia. Impairments of decreased elasticity, and impairments of relaxation and hypertonicity, may respond to cricopharyngeal myotomy which reduces the relative obstruction by surgically creating a state of permanent relaxation. Some studies also report improved dysphagia from dilatation in patients with high UOS resting pressures or incomplete UOS relaxation.14 Videofluoroscopy alone without manometry cannot make the above distinctions.
Abnormally high pressures can be explained more easily (e.g. 600 mmHg due to the epiglottis hitting a pharyngeal sensor during the epiglottic tilt mid-swallow58).
Standard methodology for oropharyngeal manometry is needed because of the technical and subject variables. To date, normal and dysphagic results are not directly or numerically comparable because of different equipment and procedures. Two main methodologies have predominated in conven tional manometry: those of the McConnel group3,59, 60, 61, 62 and those of the Castell group. 14, 63, 64, 65, 66, 67 However, there has been no agreed universal standard for method ology and equipment. Salassa et al. 68 have proposed catheter standards for pharyngeal manofluoroscopy, which aim to enable comparison of the same patient over time; to establish normal ranges for all parameters; and to evaluate abnormal results in relation to the diagnosis, treatment, outcome and effectiveness of treatments. His proposals are summarized below.
Equipment
Sensor type
Catheters with miniature strain gauge pressure transducer sensors, rather than water perfused catheters, are required for pharyngeal and UOS measurements for the following reasons. •
•
•
Striated muscle contractions are quicker in the oropharyngeal area, producing altering pressures of higher frequency and amplitude, compared with the slower smooth muscle contractions in the oesophagus. The pharyngeal pressure 'wave' travels at a speed of 9-25 cm per second (requiring a recording frequency of over 50 Hz), whereas the slower oesophageal wave travels at 4 cm per second (requiring a recording frequency of 5 Hz). 28 Patients can be tested in a normal upright position, unlike the supine position with water perfused catheters. Although less expensive, water perfused catheters are usually slower to set up and use, and they also introduce water into the pharynx, so causing unwanted swallows and poor tolerance.
Catheter •
The diameter should be small (3 mm or less) both for comfort and to avoid the reactive increase in UOS tonic pressure.
Chapter 15 1 Functional investigations of the upper gastrointestinal tr act I
•
A series of circumferential sensors usuall y require a
catheter (for example, in HRM the outer diameter has been described as 42 mm).57
larger diameter
However, larger diameter catheters cause more patient
discomfort and may raise UOS tonic
pressure values. • Catheters with fibreoptical 'sensors' are available, and the se provide circum ferential rea d ings witho ut increasing the catheter diameter. • An ovoid sha ped cat het er helps to maintain correct orientation, essential if it only has unidirectional sensors, to ensure the larger anterior- poster ior pressures can be recorded (as DOS radi a l pressures are asymmetri c al) . • Clear markings in ce n ti m etres, with the distal sensor marked at 0 em, ind i cates anterior and posterior orientation, and help s with the intersubject variation in pharyngeal l ength and DOS high pressure zone
1973
• A pressure transducer too high in the nasopharynx should be avoided in case the readings record the soft palate against the p osterior pharyngeal wall. A trans ducer too low in the pharyngeal area may cat ch a
•
pressure trough area thought to give poor readings
during swallowing, approximately 3-5 53 UOS ).
em
a b ove the
techniques of st ation p ull through (SPT) or (RPT) are used to position the catheters a ccurately. Each sensor passes the DOS in turn, and the method is described in full by Wil son s 3 (Figure 15104). • In HRM, the above procedural difficulties are overcome by the large number of circum ferentially placed and closely spaced sensors. The
rapid pull through
length.
Proximal
• Cath eters need to be 100 em long for oseophageal manometry, if req uired. • A short (4 em ) ma lleable section of the catheter should extend past the most distal sensor to enable easier naso-pharyngeal insertion, and also to allow some of the
cathete r to pass into the oesophagus to
provide catheter stability l at erally and horizontally during manometry recordings (see
Figure 151.2).
Sensor spacing and placement in conventional manometry • One sensor each sh o ul d be placed in three (or four) locations, which are level with the tongue bas e, hypophar ynx, UOS (and u pper cervical oesophagus); with 2 and 3 em between the sensors in the order stated above (Figure 151.3). • Unidirec ti onal i n-li ne sensors, or ie n tated poster i orly, capture readings of maximum a m pl it ude . The
Tongue base
advantage of circumferential sensors is that radial
asymmetries can be ave ra ged , and readings are not
Hypopharynx
affected by unwanted c h an ges in the o rienta tion of the catheter.
• Correct placement of the UOS sensor can be seen d uring swallowing by production of a waveform that has a negative nadir, preceded and followed by an
uos
elevated pressure wave and clearing wave.
Upper cervical oesophagus
Distal
Figure
151.2
Strain gauge pressure sensor catheter for
conventional oropharyngeal manometry.
Figure
151.3
Position of the pressure sensors in conventional
manometry.
, '--
-:.--
1974 I
PART 15 THE UPPER DIGESTIVE TRACT
Pi
-2 mm
P2
31
P3
Hg
mm Hg
-6 mm Hg
P4
-2 mm Hg
P5
-4mmHg
P6
-1 mm Hg
23
25
24
26
27
Min
28
29
Figure 151.4
Pressure readings seen during
SPT technique to identify position of UOS.
METHODOLOGY Salassa et
al.68 also suggest that methodology guidelines
are still needed in order to standardize: •
bolus volumes) consistencies and temperatures;
•
duration of swallow intervals;
•
single or multiple swallow analysis;
•
methods to obtain) and values of) pressure recordings to analyse;
•
comparable software analysis systems.
Recordings •
A computerized mulitchannel recording device is
used to collect) store and display the pressure readings) such as Albyn Medical
(Figure 151.5)
and Griffon software, or the digital swallowing workstation (Kay Elemetrics Corporation) USA). A channel is needed for each transducer pressure reading, and these are displayed in graph form with amplitude
(x
axis) against time (yaxis).
Computer recordings are accurate, quick and unbiased. Windows driven software is easier to use, and automatic data collation into a database gives faster analysis and interpretation. •
The frequency by which pressure reading data is recorded needs to be standardized. Wilson 53 suggests a minimum frequency of 50 Hz is needed to record accurately the rapid pressure changes within the fast pharyngeal swallowing mechanism.
•
Each laboratory needs to decide whether to average
all the readings taken at the UOS) and for this to be
a constant in recorded values over time and between
Figure 151.5 •
•
Regular calibration of the equipment is necessary before the equipment is used.
The measurement of UOS pressure is usually expressed relative to intrapharyngeal zero baseline,
patients.
Calibration
Albyn Medical recording system.
(equivalent to atmospheric pressure). •
Sensors are zeroed to an accurate baseline of atmospheric pressure) then a known pressure (e.g. 200 mmHg) is applied to calibrate) before readings
are taken.
Chapter 15 1 Functional investigations of the upper gastrointestinal tract I
INTERPRETATION AND CLINICAL RELEVANCE OF
CONTRAI N DICATIONS
MANOMETRY
P atien ts
suspected of ha ving a perfora ted gastrointestin al (GO tract. • Those l isted under Endoscopy above.
•
Neurogenic dysp hag ia includes swallowing disorders from a heterogeneous group of patients with a variety of underlying medical conditions. More studies of mano m etr y and HRM: a re needed in relation to each type of individual condition (e.g. the amplitude and t empo ral differences in swallowing in various types and at different stages of stroke). The complication of oral dysph agia and the conse quent dysfuncti on of important components of swallow ing, such as the tongue force (e.g. in motor neurone disease (MND)), make treatmen t options such as myotomy more l ikely to fail and increase the risk of aspira ti on (Figure 151.8). For effective bolus transport in the oesophagus, contact pressure must be at l east 30 mmHg lar ger t han bolus pressure 29 otherwise the bolus may move in the
ANALYSIS
(resting) pressures, and variations in pressure the pharynx, VOS and oesophagus during s wa llowing are the main measurements. Large numbers of swallows per subject are needed due to intra-subject variabili ty (Figure 151.6).53 Two types of pressure ca n be anal ysed and both are seen within one pressure wave sha p e (Figure 151.7): vos tonic
in
,
1. Bol us pressure on the sensors
as they are surrounded by fluid, also c alled intrabolus or lumin al or c av ity pressure, and usuaUy small in amp litude Contact pressure from con t rac tion of the lumen walls on the sensors during peristalsis or occlusion, also called squeeze pressure, and usually large in a mplitud e. This is the pressure usually analysed.
,
.
2.
1975
reverse direction. This is known as bolus escape, and is
as retrograde peristalsis where the sequence of contractions occur in the reverse direction.
not the same
OTHER INVESTIGATIONS
Measurements made inel ude:
• mmmum and mini mu m pres sures; • durati on o f contraction with th e sequence and relative timing of contraction s and relaxat ions
Respiration
,
oropharyngeal tract is the same an atom ical channel swallowing and breathing, resu lting in the need for deglutition apnoea and the potential risk of aspira tion Respiratory recordin gs can measure the duration and timing of degl utition apnoea, direction and rate of air flow and thus a more comple te picture of the physiology of swallowing.69 70 Co ntinuous recordi n gs of oxygen satura ti on by pulse oximetry have also been inv esti gate d as a possib le marker of aspiration w i th conflicting results.69,71.72,73,74
.
The
In the oesophagus, multiple swallows of one bolus calUlot be analysed as a series of single swallows as a second swallow inhibits the oesopha gea l per istaltic contraction of the first. Pressure readings should only be comp ared within one laboratory set up because of methodological and intra subject variation. Each laboratory should acquire its own bank of normal data, and use the same equi pm ent and proced ure for comparative use between patients and over time.
for
.
,
,
W
s:
P1
P2
M: q
WI e I I
[
e
I
1 mm Hg
wi
-
T: E:
Ri e
i
-2 mm Hg
P3
-1 mm Hg
P4
37 mm Hg
26mm Hg
65 mm Hg 1839 '
1849
1859 S
1869
1879
Rgure 151.6
Normal liquid bolus swallow,
using conventional manometry.
_.1- __ '__
1976
I PART 15 TH E LI PPER D I G ESTIVE TRACT
OJ I
E E
.f:;
� ::i (f) (f)
�
0...
I
Bolus I pressure
I II'
Cont(lct pressure
)
I Figure
15 1.7
B olu s a nd contact p re ssu res w ith i n
one contraction wa vefo rm.
Seconds
4 mm Hg
-6 mm Hg
O mm Hg
-1 4 mm Hg
Ul trasound The ultrasound transducer with high frequency sounds ( > 2 MHz) is placed sub mentally to produce dynamic images of the soft tissue in the oral cavity and parts of the oropharynx, and the motion of the hyoid can be tracked. It is noninvasive and risk free, but the quality of the tongue image, for measuring tongue movements, is not easy to interpret. 13 , 28 , 75 The pharyngeal stage of swallow ing cannot be viewed.
Oesophageal pH monitoring Prolonged (24-hour ambulatory) pH monitoring is the most reliable method of diagnosing gastro-oesophageal reflux, especially atypical presentations. However, the
invasive technique prevents some patients from under taking activities that provoke reflux during the investiga tion, so underestimating their problems? 6 The distal oesophageal pH probe is placed 5 cm above the LOS (position determined by manometry) and the proximal one below the UOS, 13 thus any reflux is measured along the entire length of the oesophagus.
Scintigraphy This procedure tracks movement of the bolus over time, and quantifies the residual bolus in the oropharynx, larynx and trachea, using radio nuclide material with liquid or food, and a gamma camera. 13 Although it detects aspiration and reflux, it does not have a significant advantage over other functional investigations as it does
Ch a pte r 1 51
not image a na t omy a nd physi olo gy, nor does it image the biom echanics of swallowing, and the cause o f aspiration cannot be determined . 28
Fu n cti o n a l i nvesti g at i o n s o f the u p per g astro i n testi n a l tract I
1 977
: �: , Oropharyngeal - .dys-phagia - is Ca llsep by ma ny -- , unde rlyi ng aetiologies, prodbdng :'i! wide ,, '. -::, mnge of symptoms, t herefore lit is irriportant . to have several con t ras t i ng yet complementary funct i o na l investigations fOol' ' such a heterogeneous gro up of p a t i e n t s . .' " . . . ' ; • Videofluo roscopy and FEES are diagnostic :" assess ments as tht-y ·can define the swaHow, . . , . . diso rder i n te rms of 3r:13'tomy a n d physiol6.gY ' . causing t h e probfLem, and the sym pt om s in ' terms of asp i ra t io n , pen et radonl reflux and . " , residue. Such i n fo rm at ion enables t reat ment " , to be directed a t the phys iological disord'er(s) while symp loms a re managed by
\
Li ngu al p ress u re recording Recently, th ree-bu l b linear manometric sensor arrays (Kay Elemetrics Wo rkstation) have been used to evalu ate the timing a nd pressure patte rns of the tongue during the oral phase of swallowing. The small st rain gauge press ure sensors a re attached to the palate) and most work to date
has been experimental. 7 7 ,
78
compe nsatory
strategies.
I n cont rast,
ilnd s'creeni ng t ests detect the presence of d ys p h a g ia and do not gai n non i ns t ru m c n tal
E l ectromyogra p hy S urface electromyography ( sEM G ) m eas ures th e ampli tude (voltage) o f swallowing m u scle activity ( fro m the submental muscle group) from electro des placed o n the throat, and is a method for identi fying th e onset of
suffic ient informa t i o n t o defi ne t h e disorder
of i t s p hys i o lo gy and a n a to m y and trea t ment at the un de rly iJlg
in terms t o plan
phys i o logi ca l d isorder.
swallowing only. Activity is recorded from any or all of
submental m uscl es d uri n g swallowing, and they are a c t i va t ion both within and
the
variable in their o rder of between subj ects.79
Best cl i nical practice ./ After ca reful h i story t a k i n g a n d eva l u a t i o n of
CO N CLU S I O N Ma no met ry,
sym ptom ato logy,
nasendoscopy
and
videofl uoroscopy
are
co mpli men ta ry procedures a nd, when used togeth er, they enhance o u r understanding of the pathophysiological
causing sym ptoms and inform managem ent 14 decis ions. Other techniq ues mentio ned are either at
process
experimental stages requiring more research-based d ata) or are for specific con d i t i ons related to dysphagi a .
80
choosi n g the most a p pro p ri a te
investi gation for a ny o n e pati e n t d e p e n d s on m a ny factors: - specifi c sym pto ms of dys p ha g i a ; - m e d i ca l co n d it i o n , cog n it ive fu n ct i on i n g , fa t i g u e l e v e l a n d m o b i l ity of patient; - i nvasive n a tu re of i n vestig ations a n d l i kely effect t h i s m ay have ; - ava i l a b i l i ty a n d cost of both e q u i p m e n t a n d 1 t ra i n ed /expe rie nced p rofess i o n a l s. 8
/ E a ch investi g a t i o n h as d iffere n t adva n ta g es a n d l i m itati ons, as l isted i n deta i l i n th e c h a pte r.
KEY POI NTS •
./ Some pa tie nts may req u i re severa l i nvesti g a t i o n s fo r a m ore co m p l ete pictu re b u t, in g e ne ra l , FEES a n d/or
the u pper GI
Func t. i onal i nvest �gations of
vi d e ofl u oroscopy a re th e fi rst c h oi ces fo r
t ract to i nvest igate orop ha ryngeal d ysphagia
o ro ph a ryn g e a l dysph agia, fol lowed by FEESST for
p roVide i n forma t io n about anatomy,
- c�
:
-
.
-
sensory d is o rd ers ; and m a n o metry for m o ti l i ty
m us c ula r function, mucosal sensatjon and bolus d i rection and flow, and t he
� �elatjonsh i p s between these, eQ..a i?liu.g aJ}alY$is
and dia gnosfs of t he
rea s o
n for and, '
,
d isord e rs a n d to ide ntify ca n d i d a tes for myotomy o r d i l atation. 1 5 B a ri u m co ntrast i d e ntifies a n ato m i ca l a n d _ --
symptoms of dys p h a g ia , for plan ning patient
manage m en t and decision maki ng, and for '" . �' , .- �;: . :.; ,. �valuating tre a tm e n t over t i me. .
>���, �·�:I)ctionaHnvest igati ons . using . ...", . , : :;' -..' �- , :, . ,: - . i '" -. <- '-'; ,� il�strumeJltation are more ' se'nsit'ive :�md . >' . , ' , '., - - - . - '·- :··:-$i; �cific 'th.a.1) Qedside cli n i ��� , ,� ss��smen�s .. or
-
;.- :
. - �
i'tnn ' -
:s-,geening ,t�s;t s, in a�cUlra.tely' cletecti'ng
p
-
penetr�tiop.> .
'
.
I.
.
"" _
s o m e m otor d isord e rs ; e n doscopy of th e oeso p hag u s for obstructions, gastroesophag ea l refl ux, ta king b i o psies for path o lo g i c i d e n tifi cation, the ra peutic d ilatation of a str i cture or remova l of fo re ign bodi es.
82
.I The two tec h niq u es of videofl u o rosco py a n d FEES a re eq u a l ly effective i n d iscri m i nati o n between 8 p e n etra t i o n and aspi ra t i o n 3 a n d i n g u i d i ng m a n a g e ment with resp ect to the o utco m e of p n e u mon ia. 40
. 1 - - .• - -
1978
I PART 1 5 T H E U PP E R D I G ESTIVE TRACT
Defici encies i n cu rrent know l ed g e a n d a reas for fu tu re resea rch
1 4.
Caste l l JA, Caste l l DO. Recent deve l o p ments i n the m a n o m etric assessment of upper eso p h a g e a l sph i n cter fu nctio n a n d dysfu ncti o n . Digestive Diseases. 1 99 7 ; 1 5 : 28-39.
Th e re needs to be fu rth e r deve l o p m ent of sta n d a rd
1 5.
p rocedu res a n d good i ntraj u d g e a n d i nterj u d g e re l ia b i l ity 1 2 32 fo r fu ncti o n a l i nvestig ations of dysp h a g i a . •
H i l a A, Caste l l J, Caste l l D. P h a ryngea l a n d u p per eso p h C1 g e a l sph i n cter m a n o m etry i n t h e eva l u ation of dysp h a g i a . Journal of Clin ical Gastroenterology. 2001 ; 3 3 : 3 55-6 1 .
1 6.
Schrote r- M o rasch H, B a rto l o m e G, Trop p m a n n 1\1, Zieg l e r W . Va l u es a n d l i m itations of p h a ryngo l a ryngoscopy
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Resea rch Soci ety m eeti n g ; Albeq uerque, N ew M exico,
eso p h a g ea l sph i n cter, eso p h a g us, and lower eso p h a g e a l
USA, 2001 . 78.
i n l i n g u a-palatal press u re patterns d u ri ng the ora l p h ase
Sa lassa J R, deVa u l t KR, McCo n n e l FMS. Proposed catheter
of swa l l ow i n g . Te nth An n u a l Dys p h g i a Resea rch Society m eeti n g ; Albequerq u e, l'Jew M exico, USA, 200 1 . 79.
fu n cti o n a l a n d d i a g n ostic test i n g of d e g l utition. I n :
H i rst L, Ford G, G i bson G, W i l son J. Swa l l ow-i n d u ced
Pe rl m a n AL, Sch u l ze- Del rieu K (eds). Deglutition and its
2002 ; 1 7 : 1 52-61 .
disorders, 1 st ed n. San Diego/Lond on : Si n g u l a r Pu b l i s h i n g G ro u p, I n c., 1 99 7 .
Sel l ey WG, Flack FC, El l is R E, Brooks WA. The Exeter 80.
Ekberg O. D i a g nostic aspects of dysp h a g i a . Acta Oto
81 .
Aviv J, Sata l off R, Cohen M, Sp itzer J, Ma G, B h aya n i R
Laryngologica-Supplementum. 2000 ; 543 : 2 2 5-8.
227-35.
72.
Col l i ns MJ, Bakheit AMO. Does pu lse oxi m etry re l i a bly d etect a s p i ration in dys p h a g i c stroke patients ? Stroke.
et al. Cost effectiven ess of two types of dys p h a g i a care i n
1 99 7 ; 2 8 : 1 7 73-5.
head a n d neck cancer: a pre l i m i n a ry report. Ear; Nose, and Throat Journal. 2001 ; 80: 553-6, 558.
Colodny N . Com pa rison of dysp h a g ics a n d no ndysphag ics on pu l se oxi metry d u ri n g ora l feed i n g . Dysphagia. 2000;
82.
74.
Medicine. 1 99 9 ; 1 05 : 1 3 1 -4, 1 41 - 2 , 1 45.
Se l l a rs C , D u n n et C, Ca rter R. A pre l i m i n a ry compa rison of vid oefl u o roscopy of swa l l ow a n d pu lse oxi m etry in the
M uj ica V, Co n kl i n J . When it's h a rd to swa l l ow. What to l ook for i n patients with dysp h a g i a . Postgraduate-
1 5 : 68-73. 73.
Coo per OS, Pe r l m a n AL. Electro myog ra phy i n t h e
a ltera tions i n breath i ng i n n o r m a l o l d e r peop l e. Dysphagia.
Dys p h a g i a Assessment Tech n iq u e. Dysphagia. 1 99 0 ; 4 : 71 .
Yokoya m a M , So n i es BC, M i c h i wa ki Y, M ich i K. Va riations
dystrophy. Dysphagia. 1 99 5 ; 1 0 : 22-6.
(vi d e o m a n o m etry). Dysphagia. 1 99 8 ; 1 3 : 1 05- 1 0.
70.
H i n d J , N icosia MA, Robbins JA. Va r i a b i l ity of l i n g u a l i so m etric pressu res in a d u l ts. Te nth An n u a l Dys p h a g i a
Caste l l JA, Caste l l DO, D u ra n ce a u CA, Topa rt P.
sta n d a rds for p h a ryngea l m a n ofl u o rogra phy 69.
Fass R , H e l l R, Sa m p l i n e r R, Pu l l i a m G, G raver E, H a rtz V
m a n o m etry of t h e p h a ryng oeso ph agea l seg m e n t.
s p h i ncte r i n patie nts with ocu l o p h a ryn g e a l m uscu l a r 68.
Casas M, Seo A, Ke nny D. Sonog ra p h i c exa m i n ation of the
Journal of Physiology. 1 99 0 ; 2 58 : G 1 7 3-8.
Dysphagia. 1 993 ; 8: 3 3 7 -8. 67 .
7 5.
83.
Co l o d ny I'J. Effects of a g e, gender, d isease, a n d
i d e ntificati o n o f a s p i ration i n dys p h a g i c patients.
m U ltisystem i nvolve m e n t on oxyg en saturation leve ls in
Dysphagia. 1 99 8 ; 1 3 : 8 2-6.
dysph a g ic pe rso ns. Dysphagia. 2 00 1 ; 1 6 : 48-57.
Za i d i N H , Sm ith HA, Ki n g SC, Pa rk C, O ' N e i l l PA, Co n n o l ly MJ. Oxygen d esatu rati o n on swa l l ow i n g as a pote n ti a l
152 Acute and chronic pharyngeal infection MARCELLE MACNAMARA
Acute pharyngitis
1982
Best clinical practice
Key points
1987
Specific viral pharyngitis
2002
Best clinical practice
1987
Key points
2005
Tonsillectomy
1988
Vesicular and bullous eruptions of the pharynx
2005
Key pOints
1996
Tonsi I pi ugs and pseudocysts
2005
2002
Best clinical practice
1996
Unilateral tonsillar enlargement
2005
Peritonsillar abcess ( quinsy )
1996
Ulceration of the tonsil
2006
Key points
1998
Oedema of the uvula
2006
Best clinical practice
1998
Nonspecific chronic pharyngitis
2006
Parapharyngea I abscess
1998
Specific chronic pharyngitis
2007
Key points
2000
Key points
2015
Deficiencies in current knowledge and areas for future
Best clinical practice
2000
Retropharyngea I abscess
2000
Key points
2002
2015
research
2016
References
ACUTE PHARYNG ITIS
The data in t his section are supported by a Medline search using the terms acute
pharyngit is, sore throat, acute tonsillitis,
streptococcal pharyngitis/sore throat, bacterial pharyngitis/sore throat, viral pharyngitis/sore throat, Cochrane database of systematic reviews and reviewing the references in the Scottish Intercollegiate Guideline Networkl for the
sore throat.
m an age m ent
of
TONSI LLECTOMY
The data in this section are supported by a Medline search using the key words tonsillectomy alone and with referral, indications,
techniques,
new
variant
complications.
Creutzfeldt-Jakob disease,
disposable
instruments,
postoperative
care
and
PERITONSI LLAR ABCESS (QU I NSy)
The data for this section were obtained by a Medline search using the key words peritonsillar abscess alone and with epidemiology, bacteriology, clinical features, differential diagnosis, investigation, treatment and complications. PARAPHARYN G EAL ABSCESS
The data for this section were obtained by a Medline search using the key words parapharyngeal abscess alone and in conjunction with epidemiology, bacteriology, clinical features, differential diagnosis, treatment and complications .
...
1 982 I
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TH E U PPER D I G ESTIVE TRACT
RETROPHARYNGEAL ABSCESS
The data for this section were obtained by a Medline search using the key words retropharyngeal abscess alone and in conjunction with epidemiology, bacteriology, clinical features, differential diagnosis, investigation, treatment and complications. SPECIFIC VI RAL PHARYNG ITIS: I NFECTIOU S MONONUCLEOSIS
The data for this section were obtained from a Medline search using the key words infectious mononucleosis, glandular fever and Epstein-Barr virus, both in isolation and in conjunction with, epidemiology, clinical features, systemic manifestations, associated tumours, serological diagnosis and treatment. SPECIFIC VI RAL PHARYNGITIS: CYTOMEGALOVIRUS I NFECTION
The data for this section were based on a Medline search using the key word cytomegalovirus infection, alone and in conjunction with, children, adults and immuno compro mise. CHRONI C PHARYNG ITIS
The data for this section are from a Medline search using the terms chronic pharyngitis/ nonspecific chronic pharyngitis or noninfectious chronic pharyngitis.
ACUTE PHARYN G ITIS Defi n ition
Acute pharyngitis is defined by its most predominant symptom, i.e. acute onset sore throat, and has a primarily infectious aetiology. The term is frequently used synony mously with acute tonsillitis; however, in reality, there is a spectrum of conditions, from acute inflammation localized primarily to the tonsils, often although not exclusively of bacterial origin, to acute pharyngitis implying generalized inflammation of the whole pharynx.
were interrelated and that illness behaviour may partly influence the tendency to seek care for less serious diseases. Sore throat may be the introductory topic to a wider agenda, which is often relevant to the reason for the consultation and may have a fundamental inf1uence upon decisions made. Prescribing antibiotics for sore throat in general practice enhances patient belief in antibiotics and increases the intention to consult for future episodes. [***] A patient information leaflet may be of value in the management of acute sore throat and may assist in managing future episodes at home without GP involvement.
E p i d e m i o l ogy Aeti ol ogy
Sore throat affects both sexes and all age groups, but is much more common in children in late autumn and early winter. Overall acute tonsillitis was the eighth most common general practitioner (GP) acute presentation in 1 996, with a rate of 32 per 1 000 patients per year. The rate was higher for females in all age bands. Most patients with sore throat either never or only rarely ( 1 / 1 8 episodes) see their GP. The overall incidence of sore throat in all age groups varies widely and different definitions make comparisons between figures difficult. The cost to the National Health Service (NHS) of GP consultations for sore throat, before any treatment or investigation, has been estimated at approximately £60 million per annum. The nonrandom nature of the distribution of 1 44 1 Dutch children visiting a G P suggested that symptoms
The causes of pharyngitis include viruses, isolated in approximately 40-60 percent of cases, and p rimary bacterial pathogens, which account for approximately 5-30 percent of cases. In approximately 30 percent of cases no pathogen is isolated. Group A beta-haemolytic streptococci (GABHS) are the commonest cause of bacterial pharyngitis and are spread via respiratory secretions through close contact. There is an incubation period of one to five days. The risk of contagion most probably depends on innoculum size and the virulence of the infecting strain, as a result of which, individuals are most infectious in the early stages of the disease. The role of individuals colonized with GABHS in the spread of disease is uncertain but carriers rarely spread the disease to close contacts. Data suggest
Chapter 152 Acute a nd c h ronic p h a ryngea l i nfection I 1983
that the disease cannot be spread via pets. More than 1 20 M -protein types of GABHS have been isolated, with serotypes 1 , 3, 5, 6, 1 8 , 1 9 and 24 associated with rheumatic fever (i.e. rheumatogenic forms) and others, such as serotypes 49, 55 and 57, associated with pyoderma and acute poststreptococcal glomerulonephritis. Neisseria gonorrhoeae and Haemophilus inJluenzae are uncommon, Corynebacterium diphtheria, Moraxella (Branham ella) catarrhalis, group C and G streptococci are rare and Corynebacterium haemolyticum extremely rare. Other, less common causes of pharyngitis include Chlamydia trachomatis and Mycoplasma pneumoniae. Unusual bacteria that could present with pharyngitis include Borrelia species, Francisella tularensis and Yersinia species. Other probable co-pathogens for pharyngitis in children include Staphylococcus aureus, H. inJluenzae, Branhamella catarrhalis, Bacteroides fragilis, Bacteroides oralis, Bacteroides melaninogenicus, Fusobacterium species
and Peptostreptococcus species. Viral causes of acute pharyngitis in order of frequency include rhinovirus, adenovirus (5 percent) , parainfluenza virus, Coxsackievirus « 5 percent) , coronavirus, echo virus, herpes simplex virus « 5 percent) , Epstein-Barr virus (EBV) (mononucleosis) , cytomegalovirus (CMV) and human immunodeficiency virus (HIV) infection. Another cause of pharyngitis is oral thrush due to candidal species, usually in patients who are immuno compromised. Noninfectious causes include dry air, allergy/post-nasal drip, chemical injury, gastro-oesopha geal reflux disease (GERD) , smoking, neoplasia and endotracheal intubation.
Patho phys i o l ogy
In infectious pharyngitis, bacteria or viruses may directly invade the pharyngeal mucosa, causing a local inflam matory response. Other viruses, such as rhinovirus, cause irritation of pharyngeal mucosa secondary to nasal secretion. Streptococcal infections are characterized by local invasion and release of extracellular toxins and proteases. In addition, M-protein fragments of certain serotypes of GABHS are similar to myocardial sarco lemma antigens and are linked to rheumatic fever and subsequent heart valve damage. Acute glomerulonephritis may result from antibody-antigen complex deposition in glomeruli.
Cl i n i ca l fi n d i ngs
The clinical differentiation of the pathogens of pharyngi tis is rarely possible and, in particular, there are no reliable clinical clues to GABHS. Some rare diseases are associated with specific features, such as the thick grey membrane of diphtheria, which is difficult to remove. A small but increasing number of cases are being reported and
therefore the distinct membrane and risk of upper airway obstruction should not be forgotten. The classical history of sore throat, fever, chills, malaise, headaches, anorexia, abdominal pains as well as a history of exposure to known carriers is not always present, but sore throat is present in all those old enough to recognize the symptom. There is no evidence that bacterial sore throats are more severe than viral ones or that the duration of the illn ess is significantly different in either case. The clinical picture in an individual sore throat is of limited assistance in distinguishing between a bacterial and a viral aetiology. Several studies have attempted to differentiate between these, based on symptom complexes including tonsillar exudate, anterior cervical lymphado pathy, absence of cough, pharyngeal erythema, level of pyrexia and pain, etc., but the results are conflicting and inconclusive. Studies on sensitivity and specificity suggest that reliance on clinical diagnosis will miss 25-50 percent of GABHS pharyngitis cases and that 20-40 percent of those with negative throat cultures will be labelled as having GABHS. [***] Although no single or combination of physical findings is specific for distinguishing GABHS from viral aetiologies, several features are suggestive: enlarged tonsils, pharyngeal erythema, tonsillar crypts containing necrotic or purulent exudates, soft palate petechiae, cervical lymphadenopathy, fever and scarlet fever rash (punctate erythematous macules with reddened flexor creases and circumoral pallor) , the so-called 'sandpaper' rash. Specific viral infections have characteristic features: conjunctivitis more commonly with adenovirus infec tions, viral pharyngitis usually is associated with sneezing, rhinorrhoea and cough; infectious mononucleosis typi cally is exudative and associated with extensive false membranes; finally, herpangina ( usually Coxsackievirus A or herpes virus) is associated with papulovesicular lesions. Concomitant vesicles on the hands and feet are associated with Coxsackievirus (hand, foot and mouth disease). Tonsillopharyngeallpalatal petechiae are seen III GABHS infections and infectious mononucleosis. A tonsillopharyngeal exudate may be seen in streptococcal infections, infectious mononucleosis and occasionally in M. pneumoniae, Chlamydia pneumoniae, Acinetobacter haemolyticus, adenovirus and herpesvirus infections. Therefore, exudate does not differentiate viral and bacterial causes. Tender anterior cervical lymphadenopathy is consis tent with streptococcal infection, while generalized adenopathy is consistent with infectious mononucleosis or the acute lymphoglandular syndrome of HIV infection. Murmurs should be documented in an acute episode of pharyngitis to monitor for potential rheumatic fever. Pharyngitis, together with lower respiratory tract infections, are more consistent with M. pneumoniae or C. pneumoniae, particularly when a persistent nonpro ductive cough is present.
1 984 I
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15 THE U PPER D I G ESTIVE TRACT
Differential diagnostic possibilities include diphtheria, gonorrhoea, rheumatic fever, infectious mononucleosis, herpes simplex, hand, foot and mouth disease, the candida croup, epiglottitis, tracheitis, peritonsillar abscess (PTA) , retropharyngeal and parapharyngeal abscess and mycoplasma pneumonia. Noninfectious causes of acute pharyngitis might include endotracheal intubation, smoke inhalation, in door heating sources and excessive air conditioning. Other problems to consider might include allergic rhinitis with post-nasal drip, GERD, airway obstruction, head and neck neoplasms and peritonsillar cellulitis.
I nvestig atio ns
Investigations are of limited practical value but may be of benefit in certain circumstances. Throat culture is described as the criterion (gold standard) diagnostic test for GABBS in the North American literature. Results can take up to 24 hours. Throat culture results are highly sensitive and specific for GABBS but can vary, depending on technique, sampling and media. A positive throat culture for GABBS makes the diagnosis of streptococcal sore throat likely but a negative culture does not rule out such a diagnosis. There are cases where streptococcus is isolated from sore throats but there is no serological evidence of infection. 2 There is also a high asymptomatic carrier rate of up to 40 percent for GABBS. 3 The flora of bacteria recovered from the surface of the tonsil correlates poorly with that deep in the tonsillar crypts, which is the most likely cause of infection. 4, 5 Symptoms also correlate poorly with results of throat swab culture. 6 Throat swabs are neither sensitive nor specific for serologically confirmed infection, increase costs considerably, may medicalize illness and alter few management decisions. Throat swabs should not routinely be carried out in sore throat? [**] Rapid antigen testing is commonly used in the USA to identify GABBS. The sensitivity of rapid antigen testing measured against throat swab culture is broad and varies between 6 1 and 95 percent, although specificity may be better at 88-100 percent. A UK study of 250 patients showed that the sensitivity of the test was 63 percent and specificity 9 1 .7 percent, compared with 74 and 58 percent respectively, for clinical assessment. Use of the test changed prescribing decisions very little. The test cost £4 and took ten minutes to report. 8 Rapid antigen testing should not routinely be carried out in sore throat. [**] Rapid antigen detection is not sensitive for group C and G streptococci or other bacterial pathogens. Leukocytosis is highly suggestive of bacterial infection. A peripheral smear may show atypical lymphocytes in infectious mononucleosis. Monospot is used as a screening test for the detection of EBV and is up to 95 percent sensitive in children
(less than 60 percent sensitivity in infants) . Other tests occasionally used include screening for gonococcal infection using a warm Thayer-Martin plate, viral culture in special media, Gram stain may be suggestive of the aetiology and streptococcal isolates may be immunologi cally typed.
Treatm ent
Suggested treatment includes simple analgesics, such as aspirin or paracetamol, and nonsteroidal antiinflamma tory drugs (NSAIDs). Several reports suggest that between two and three days after the start of treatment with NSAIDs there is slightly faster resolution of pain, fever, dysphagia, inflammation and lymphadenopathy com pared with either placebo or paracetamol. Taking account of the increased risks associated with NSAIDs, their routine use in the management of sore throat is not recommended. [****] There is little literature regarding the use of stronger analgesics for sore throat. There is no convincing evidence that analgesics other than paracetamol are routinely necessary in acute sore throat. Paracetamol is the drug of choice for analgesia in sore throat, taking account of the increased risks associated with other analgesics. One small study showed that benzydamine hydro chloride (Difflam) , as a gargle for sore throat, resulted in significantly greater relief of pain and dysphagia at 24 hours than placebo, but this requires confirmation. Corticosteroids are very occasionally prescribed in hospital patients with acute infectious mononucleosis when pain and swelling threaten the airway or where there is very severe dysphagia. A recent randomized controlled trial (RCT) suggests that a single dose of oral dexamethasone (0.6 mg/kg) in children with moderate to-severe sore throat resulted in significantly earlier onset of pain relief ( 9.2 versus 1 8.2 hours) and shorter duration of sore throat ( 30.43 versus 43.8 hours) . 9 A similar adult RCT in a GP setting showed that 60 mg oral prednisolone for one to two days resulted in significantly more rapid resolution of throat pain.10 [****]
ANTIBIOTICS
In sore throat In the UK, the significance of the presence of bacterial pathogens in cases of sore throat remains in doubt.11 It is therefore illogical to treat all sore throats with antibiotics, and there is a favourable outcome in the majority of cases even when antibiotics are withheld. An open study of prescribing strategy in over 700 patients randomized to antibiotic versus no prescription versus delayed prescrip tion for three days showed no difference in the main outcomes:12 [****] A recent assessment of Cochrane reviews suggests that for streptococcal tonsillitis the use of
Chapter 1 52 Acute a nd c h ronic p h a ryngeal i nfection I 1 985
antibiotics seems to be discretionary rather than prohibi ted or mandatory. This is because the benefit in terms of symptoms is only about 16 hours (number needed to treat (NNT) for benefit from two to seven at day 3 for pain) compared with placebo,13 and that serious compli cations, such as rheumatic fever and glomerulonephritis are now rare in developed countries; however, the latter is an area of debate as the American Infectious Disease Society recommends routine treatment. [****] Even if the sore throat persists, a throat swab to identify GABHS may not be helpful, as the poor specificity and sensitivity of throat swabs limit their usefulness. Nevertheless, RCTs of antibiotic therapy in patients with acute sore throat in whom GABHS has or has not been isolated (whether or not causative) have been reported. The limited information available is insufficient to support a recommendation on the routine use of antibiotics in acute sore throat. Patient and doctor education on the lack of benefit of antibiotics in routine management of sore throat can have a significant impact on the amount of antibiotics prescribed.14, 1 5 Most trials have compared penicillin with a variety of other antibiotics, notably cephalosporins. Although optimum elimination of GABHS is secured with in tramuscular long-acting penicillin, oral penicillin V given six-hourly for ten days is widely regarded as the gold standard treatment in such trials, with the advantages of cheapness and tolerability. Other more expensive anti biotics, mainly cephalosporins, have been shown to be statistically significantly more successful in eradicating the organism although the clinical advantage is much less clear. Some cephalosporins offer a more convenient dosage regimen but twice and three times daily dosage of oral penicillin V has also been shown to be effective in eliminating GABHS. A ten-day course of penicillin appears to be more effective than five days. There is no convincing evidence of advantage for any individual cephalosporin. There is evidence from two small American studies that erythromycin and metronidazole may provide symptomatic relief in nonstreptococcal sore throat. A recent UK study suggests that a cephalosporin may improve the rate of resolution of symptoms. However, there is no convincing evidence of benefit from antibiotic therapy as the primary treatment for sore throat. In an attempt to reduce prescribing antibiotics, delayed prescription, i.e. more than 48 hours after the onset of symptoms has been recommended. A recent Cochrane review (2004) has shown that for most upper respiratory tract (URT) symptoms there is no significant difference between the immediate and delayed antibiotic groups. Those patients with sore throat and fever showed more fever and vomiting but less diarrhoea in the delayed antibiotic group. Further trials to report symptom changes were recommended.1 5 In severe cases, where the GP is concerned about the clinical condition of the patient, antibiotics should not be
withheld. (Penicillin V, 500 mg, four times daily for ten days is the dosage used in the majority of studies.) Doctors need to be aware that infectious mononucleosis may present with severe sore throat with exudate and anterior cervical lymphadenopathy, and therefore should avoid prescription of ampicillin-based antibiotics, including co-amoxiclav, as first-line treatment.
In recurrent sore throat When sore throat recurs in patients who have received antibiotic treatment, the reasons may include inappropri ate antibiotic therapy, inadequate dose or duration of previous therapy, patient noncompliance/nonconcor dance, reinfection and local breakdown of penicillin by beta-Iactamase producing commensals. Benzathine peni cillin, cefuroxime and clindamycin have been shown to be superior to penicillin V in the management of children with this problem, and may reduce the frequency of episodes. There is no evidence to support a recommenda tion of the use of antibiotics in recurrent nonstrepto coccal sore throat. [****/**]
To prevent rheumatic fever and glomerulonephritis It has been argued that the primary clinical rationale for treating streptococcal pharyngitis with antibiotics is the prevention of rheumatic fever and other sequelae, and that outbreaks of rheumatic fever are still being reported in both children and adults in the USA.I6 This does not apply in the UK, and a small reduction in bacteriological failure rate has to be weighed against the considerable increase in cost when antibiotics other than penicillin are used. The incidence of rheumatic fever in the UK is extremely low and there is no support in the literature for the routine treatment of sore throat with penicillin to p revent the development of rheumatic fever.I7 Acute rheumatic fever remains a major problem in tropical regions, resource-poor countries and minority indigenous communities, with Aborigines in central and northern Australia showing some of the highest rates of both acute rheumatic fever and rheumatic heart disease in the world. Study of this latter group suggests that group C and G streptococcal organisms as well as the usual group A streptococcal infections may also have rheumatogenic strains. IS A recent metaanalysis of RCTs on the use of antibiotics for the primary prevention of acute rheumatic fever identified ten eligible trials ( n = 7665) carried out between 1 950 and 1 96 1 in which eight of ten populations were young male US soldiers. Metaanalysis revealed an overall protective effect of 70 percent (RR = 3.2 percent, 95 percent CI = 0.2 1-0.48) . The absolute risk reduction was 1 .67 percent with NNT of 53. They calculated that the marginal cost of preventing one case of rheumatic fever by a single i.m. injection of penicillin was $46.17 Similar considerations apply to the prevention of glomerulonephritis. 19 Most of the information on the prevention of acute rheumatism comes from studies performed on military personnel living in overcrowded
1 986 I
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THE LI PPER D I G ESTIVE TRACT
barracks immediately after the Second World War, when the incidence of rheumatic fever was exceptionally high. At that time penicillin, particularly benzathine penicillin, was shown to be an effective p rophylactic. There is no evidence that these results are applicable in modern Britain. Sore throat in the UK should not be treated with antibiotics specifically to prevent the development of rheumatic fever and acute glomerulonephritis. [****]
To prevent suppurative complications On pragmatic grounds, p atients with severe pustular tonsillitis are frequently treated with antibiotics both in general practice and in hospital. There is no evidence that the routine administration of antibiotics to individuals with sore throats will reduce the occurrence of suppura tive complications such as quinsy. The incidence of quinsy is very low, although it has risen over the last five years. There is no evidence that this is related to changes in the use of antibiotic therapy. The prevention of suppurative complications is not a specific indication for antibiotic therapy in sore throat. A Cochrane review showed that antibiotics for sore throat reduced the incidence of acute otitis media by about one quarter compared with placebo and acute sinusitis by about one-half.20
Choice in the USA Studies in the late 1 940s and 1950s showed that penicillin therapy for GABHS pharyngitis could prevent rheumatic heart disease. The American Heart Association has recommended penicillin therapy since 1 953, and this remains the p rimary treatment of choice to prevent rheumatic heart disease in the USA, but not in the UK. Initial studies using a five- to seven-day course showed a decline in the number of GABHS-positive follow-up throat cultures from 53 to 1 8 percent. Subsequent ten-day courses of penicillin proved to be the most beneficial in eradicating GABHS from the p harynx. The effectiveness of antimicrobial therapy in prevent ing poststreptococcal glomerulonephritis is less certain. The gold standard for treatment of GABHS pharyngitis is penicillin. Amoxicillin has often been used as a substitute for penicillin, although there are no microbiological advantages over penicillin therapy. Compliance has been better with bid/tds penicillin than with the traditional qds regimens. In a recent preliminary report, amoxicillin taken once daily has even been shown to be effective. Cephalosporins have also been used, with questionably improved failure rates compared with penicillin. Cepha losporins resist degradation by beta-lactamases and are very effective against co-pathogens.
To relieve symptoms Although antibiotic therapy has been shown to alleviate symptoms even in sore throat not caused by bacteria, the superiority of antibiotics over simple analgesics is marginal in reducing duration or severity. 21 Even in proven GABHS infection, the symptomatic improvement following penicillin, although superior to that following simple placebo in some studies, has been unimpressive in others, especially when compared with simple analge sics.22 Antibiotics should not be used to secure sympto matic relief in sore throat. [****] Even if the symptomatic benefit were more substantial, a single case of penicillin induced anaphylaxis would be a heavy price to pay.
EMERGENCY HOSPITAL ADMISSION
Admission to hospital will be required for few p atients with sore throat. The most common indications for admission are peritonsillar cellulitis, abscess or, more rarely, parapharyngeal abscess. In young adults, infectious mononucleosis with dysphagia is a common reason. The occasional patient with severe uncomplicated tonsillitis with dysphagia and dehydration may require admission. Sore throat associated with stridor or respiratory difficulty is the only absolute indication for admission to hospital.
To prevent cross infection The evidence in favour of the use of antibiotics to prevent cross infection in sore throat is mainly provided by army barracks outside the UK. No evidence shows that attempting to eradicate GABHS with routine antibiotic therapy for sore throat will produce any measurable health gain, and there will be some danger of encouraging the emergence of antibiotic-resistant strains of other organisms although GABHS remains sensitive to peni cillin despite its widespread use. An American study has recommended that when GABHS has been identified in children, a full 24 hours of antibiotic treatment should be given before return to school or day care. Antibiotics may prevent cross infection with GABHS in closed institutions ( such as barracks, boarding schools) but should not be used routinely to prevent cross infection in the general community. [***].
Com p l i cations
Following GABHS there are frequent complications, which include rheumatic fever (0.3 percent cases of untreated GABHS, three to five weeks after infection in the USA in endemic situations and 3 percent in epidemic circumstances) and p oststreptococcal glomerulonephritis ( 10- 1 5 percent of those infected with nephrotoxic as well as suppurative complications) . These arise from the spread of infection from pharyngeal mucosa via haema togenous, lymphatic or direct extension and include peritonsillar abscess, septicaemia, toxic shock otitis media/mastoiditis, descending necrotizing mediastinitis, Lemierre syndrome, septic thrombophlebitis of the internal j �gular vein and metastatic lesions (usually in the lungs and mostly caused by Fusobacterium
Acute and chronic p h a ryn g ea l infection I 1987
Chapter 1 52
necrophorum) orbital
m yosi tis, epiglottitis, rhinosinusitis
facts came to light during outbreaks of rheumatic fever
1 990.
and pneumonia. More recently, paediatric autoimmune
in 1985 and
neuropsychiatric disorder and acute disseminated ence
GABHS had been noted
phalomyelitis, which can affect children and adults, have
outbreaks. The outbreaks were observed in middle-class
been recognized as immune-mediated illnesses associated
areas in which compliance rates with medical therapy are
No previous significant increases in
in the communities prior to the
with GABHS infection. Similar to Sydenham's chorea, it
relatively high. Unlike most previous outbreaks, severe
usually presents as an abrupt onset obsessive-compulsive
pharyngitis was rarely noted and only
46 percent of
disorder including hand washing, preoccupation with
p atients reported having a recent sore throat. Only 24
germs and daytime urinary urgency. These symptoms
percent of the patients felt they had sore throats that were
on
resolve
the
treatm ent
of
the
sentinal
GABHS
pharyngitis, but recur with further episodes of infection
in
50
significant enough for them to seek medical help. Almost
20 percent of the cases were children, who received antibiotics for their pharyngitis (type of antibiotic, length
percent of cases.
Treatment failures are frequent and attributed mainly
of therapy and compliance issues were unclear). These
to poor compliance, antibiotic resistance, untreated close
findings suggest that outbreaks may, in fact, be more
contacts,
related to the rheumatogenic quality of the GABHS rather
carrier
states
and
antibiotic-related
or
co
pathogenic suppression of host immunity and necessary flora.
Patients
should
expect
improvement
in
than whether antibiotics were given.
the
symptoms of penicillin-sensitive streptococcal pharyngitis within 24 hours of initiation of treatment. The con tagious, and often the febrile, periods are also reduced to
KEY POINTS
one day. With erythromycin therapy, patients should
�----- ;' "
expect
improvement in
strep tococcal
resistance
72 to
hours.
The incidence of
erythromycin
•
consistently
exceeds 25 percent, therefore, patients on erythromycin therapy should be more closely monitored for treatment failure.
•
,
patient information leatlet may be belpful in pre v en t in g repeat consultation in straightforward acute sore throat consultations. Ra cteri a are not the most con1!J11on cause of acute �()re t h ro a t but GAI3HS �s still the most frequent bacterial pathogen. Despite some forms of acute pharyngitis being asociated with da.&s,icai presentations one cannot reliably disting--uish between viral and bac t eri al aetiolo g es on clinical grounds alone. In UK practice, there is in s u ffici ent evidence to s u pport the use of antibiotics in the management of ac u te sore throat both for symptom rt:' li ef and preve ntion of spread, reClllifnmt sore throat or to prevent rheumatic "fever, gl,omerulonephriti's or suppurative A
,
Prognosis
•
s
Streptococcal pharyngitis has a five- to seven-day course. Symptoms usuaJly resolve spontaneously without treat mentj however, rheumatic complications are still possible
i
•
although extremely rare in the UK. Suppurative compli cations, such as a PTA, may require surgical intervention. Mortality from pharyngitis is rare but may result from one of its complications or tonsillectomy.
�c�mplications.
The ca rrier state Patients e>..p - osed organism asymp tomat ically even after adequate antibiotic
therapy. Carriers are recognized as those who demon strate a positive culture but no rise in antistreptolysin 0 convalescent titre, and rates reported in the literature vary between
3
and 40 percent depending on the population
studied. Carriers are at little risk of transmitting the disease:
9
only
percent of those infected develop clinical disease,
40
percent risk of affecting family members and
i.e. only 3.5 percent produce disease within their families.
Specia l concerns
Best clinical practice I n vesti g ati ons are of l i mited val ue in the m anag e me n t of acute sore throat. More specifically, throat swabs do n ot give representative d at a about i n fectiou s agents deep in the tonsi l lar crypts and ra p i d a n t i g e n t esting rarely al ters p re scri b ing d ec is i on s ./ In streptococcal tonsi l l iti s the use of ant i bi otics is d isc ret ionary rather than proh ibi ted or mandatory. Th is is because the benefit in terms of symp t oms is only about 16 hou rs compared with placebo / In severe cases, where th e GP is concerned about t h e cli nical cond ition of the pat ient antibiotics should
./
.
.
While -prevention of rheumatic fever remains the primary reason for treating GABHS in the USA, several interesting
,
; .'
,
- �,
1988 I
./
./
./
./
./
PART 1 5
TH E UPPER D I GESTIVE TRACT
not be with held. Patient and doctor ed ucation about the lack of benefit of a ntibiotics i n the routine management of sore throat ca n have a significa n t i m pact on the a mount o f antibiotics prescribed. In cases of recu rrent sore throat associated with GAB HS (not necessa ri ly ca usal ) the l i mited evidence of benefit a vailable suggests that a ten -day cou rse of a ntibiotics may red uce the n u mber a n d freq uency of attacks. The i n ciden ce of rheu matic fever in the UK is extremely low and there is no su pport in the l iteratu re for the rou tine treatment of sore throat with penici l lin to prevent the development of rheu matic fever. Acute rheu matic fever remains a major problem i n tropical reg ions, resou rce-poor cou ntries a n d m i n ority i ndigenous com m u n ities, such as Austra l ian Abori g i n a l com m u n ities, a n d i n such a reas the a rg u men ts for treatment may be m u ch stronger. There is no evidence that the routine a d m i n istration of antibiotics to in divi d u a ls with sore throats wil l red uce the occu rrence of s u p p u rative com pl i cations. Antibiotics shou l d not be used to secu re sym ptomatic rel ief in sore t h roat.
TO NSI LLECTOMY Tons i l l ectomy rates
There are large international differences in tonsillectomy rates suggesting different cultural attitudes towards tonsillectomy and antibiotics. In many countries, parti cularly the Netherlands, paediatric but not adult rates fell significantly between 1 960 and 1 990. In fact, in the Netherlands, the sharp decline in paediatric rates was followed ten years later by an increase in adolescent tonsillectomy. Despite this, tonsillectomy was the most common NHS operation in Scottish children in 1 990 although with a two-fold variation in rates across health boards, suggesting significant variation in practice. In Scotland, between 1 990 and 1 996, the rate for tonsillec tomies in children declined from 602 per 1 00,000 to 5 1 1 per 100,000. In adults, tonsillectomy rate increased from 72 per 1 00,000 in 1 990 to 78 per 100,000 in 1 996. In Scotland, the length of inpatient stay after tonsillectomy has probably declined. Emergency readmissions within four weeks of discharge after tonsillectomy (and/or adenoidectomy in children) were 3 percent in Scottish patients, and varied from 0.5 to 3.4 percent across different trusts. The Scottish tonsillectomy audit highlighted differences in management of recurring sore throat by ear, nose and throat (ENT) surgeons and included variation in the rate of operation by area and differing management of children and adults.
Socioeconomic status impacts on tonsillectomy rates with immigrant populations being least likely to have access. Tonsillectomy rates have risen steadily in Australia over the last 20 years despite the introduction of guidelines which caused only a minor temporary decline.23 Evi d e nce fo r s u rgery i n recu rrent sore throat
The literature on surgery for sore throat is scanty, out of date and lacking in scientific validity. Most published studies refer to a paediatric population. The current, widely accepted criteria for surgery, which have been arrived at arbitrarily, are of the order of seven episodes of tonsillitis in the preceding year, five episodes in each of the preceding two years or three episodes in each of the preceding three years.2 4 They take no account of whether the condition is becoming worse or improving and make no distinction between children and adults, in whom the disease may behave differently. The small amount of information about adult sore throat and the effect of tonsillectomy is not scientifically robust by current standards but suggests that surgery is beneficial. 9 Recent studies,25 , 2 6, 27 evaluating less stringent criteria than previous ones, demonstrated that the relatively small benefits of adeno-tonsillectomy compared with controls probably were not justified because of the not insignifi cant risk of complications. A new, systematic review of paediatric randomized6 and nonrandomized trials 7 has shown that tonsillectomy in children reduced the number of episodes of sore throat by 1 .2 per year ( 95 percent CI - 1 .3 to - 1 . 1 ) . For sore throat -associated school absences the pooled risk difference was -2.8 days per person per year (95 percent CI -3.9 to - 1 .6) . This review also provides a discussion of the limitations of all available trials. 26 Referral fo r to nsi l l ectomy
Recurrent acute attacks of tonsillitis probably can be prevented by tonsillectomy, but tonsillectomy will not prevent recurrent sore throats due to other reasons. Hence, before considering tonsillectomy, the diagnosis of recurrent tonsillitis should be confirmed by· history and clinical examination and, if possible, differentiated from generalized pharyngitis. The natural history of tonsillitis is for the episodes to become less frequent with time, but there is insufficient epidemiological data for all age groups to allow predictions of this to be made in individual patients. Five RCTs of tonsillectomy versus nonsurgical manage ment in children have been reported.9 , 24, 25 , 26 , 27 , 2 8 Four were designed before 1 972 and none would satisfy current criteria fo� a well-designed, controlled and analysed study. In the most quoted reference, Paradise et al.'s 1 984 randomization was unbalanced in frequency of episodes
Ch apter 1 52 Acute a n d c h ronic pha ryngea l i nfection I 1989
and socioeconomic group.25 In this study, the number of episodes of sore throat after tonsillectomy was signifi candy fewer than in the control group, although when the number of days of illness with sore throat was taken into account, including those associated with surgery, benefit from tonsillectomy was less evident. No randomized controlled studies have been reported in adults. [****] Despite this lack of evidence, many noncontrolled studies suggest benefit in children who have had tonsillectomy, not only in the reduction of the number of sore throats but also in improvement in their general health. 29 , 3 0, 3 1 , 32 [ *** /**] The following SIGN guidelines are recommended as reasonable indications for consideration of tonsillectomy in both children and adults, based on the current level of knowledge, clinical observation in the field and the results of clinical audit. Patients should meet all of the following criteria: • •
• •
sore throats are due to tonsillitis; there are five or more episodes of sore throat per year; there are symptoms for at least a year; the episodes of sore throat are disabling and prevent normal functioning.
Consideration should also be given to whether the frequency of episodes is increasing or decreasing. [****/***/**] [Grade C] A recent postal survey showed that 84 percent of clinicians felt that they followed the guidelines but only 35 percent were able to recall accurately all four parts. Twenty-five percent of respondents worked in depart ments with ongoing implementation programmes but only 10 percent worked in departments where compliance was audited. 33 Otolaryngo l og i ca l assessment
Patients referred will rarely be seen by a specialist during an acute episode of sore throat, so the diagnosis of recurrent acute tonsillitis rests primarily with the referring doctor. Questioning of the patient by the specialist concerning the duration, severity and frequency of episodes as well as the degree of systemic upset, the presence of tender neck lymph nodes and the amount of time the patient has off school or work can usually confirm whether the above criteria are satisfied. Children with recurrent tonsillitis are significantly more likely to have large tonsils, with asymmetry, cervical adenopathy and tonsillar hyperaemia, than those who have not had tonsillitis.34 If the guidelines for tonsillectomy are met, management options should be discussed and the benefits of tonsillectomy weighed against the natural history of resolution and the temporary incapacity associated with tonsillectomy. Rulings in recent negligence cases reveal a shift in what the reasonable patient would expect in
deciding the risks doctors must disclose to patients when obtaining informed consent. A recent questionnaire study asked surgeons to tick which of ten complications they routinely told patients about and patients were asked how seriously they rated these complications. Most patients regarded potentially fatal bleeding, pneumonia and possible blood transfusion as very serious but only a minority of surgeons mentioned these.34 Consenting for taste disturbances is important in professional wine and food tasters. If the frequency of episodes is uncertain a period of watchful waiting of at least six months, during which the patient or parent can more objectively record the number, duration and severity of the episodes, may be suggested. Once a decision has been taken to carry out tonsillectomy it should be performed as soon as possible to maximize the period of benefit before natural resolution of symptoms may occur. There has been some discussion about open/direct access tonsillectomy, in which the GP makes a decision according to predefined locally set criteria, thereby avoiding an initial outpatient consultation. The literature suggests inappropriate refer ral rates of between 33 and 50 percent, suggesting either inappropriate practice or insufficient careful screening at preoperative assessment.3 5 , 3 6
I n d i cati ons for to nsillecto my
Indications for tonsillectomy include recurrent acute tonsillitis, as discussed above. A further indication is following resolution of a second PTA. The first PTA can be effectively managed by either needle aspiration,3? , 3 8 incision and drainage or quinsy tonsillectomy. [***] In young or poorly cooperative patients or if the quinsy has been inadequately drained tonsillectomy is curative and eliminates the chance of recurrence. The efficacy of tonsillectomy in preventing recurrent quinsies has only been addressed retrospec tively.39 , 40 [**] The recurrence rate of PTA after successful aspiration is 10-15 percent, suggesting that tonsillectomy is not required in most cases. Recurrence may be predicted on the basis of a history of two or more episodes of tonsillitis in the year preceding quinsy; 20-30 percent of patients have such a history. Tonsillectomy can be indicated for biopsy purposes in the following scenarios. •
•
Asymmetrical adult tonsil with normal mucosa in the absence of cervical adenopathy has an approximately 7 percent risk of malignancy,4 1 primarily B-cell lymphoma. This compares with 0.35 percent risk in all tonsils and no malignancy in tonsils where asymmetry was not noted. [***] Asymmetrical adult tonsil with mucosal abnormality and or cervical adenopathy has a very high risk of malignancy with asymmetry being the strongest
1990 I
•
•
PART 1 5
THE U PPER D I G ESTIVE TRACT
predictor. 42 Fine needle aspiration may be helpful in this context. 43 [**] As an oncological procedure for Ca tonsil. Radical tonsillectomy for Tl tonsil tumours or as p art of a composite resection for advanced tonsil cancer. For obstructive sleep apnoea (OSA) in children in conjunction with adenoidectomy is a well-recognized indication,44 but there are no randomized trials recruiting children with OSA for surgical treatment. 45, 46 [***]
Further indications for tonsillectomy are as follows. •
• •
•
•
In adults with gross tonsil hypertrophl 7 and OSA, or as part of uvulopalatopharyngoplasty (UPPP) or laser-assisted uvulopalatoplasty. [***] Severe haemorrhagic tonsillitis. [ *] Severe infectious mononucleosis with upper airway obstruction. [ **] Large symptomatic tonsoliths (tonsillar concretions ) . 48 As long-term management of IgA nephropathy. The long-term prognosis is no longer regarded as benign but with pulsed steroid therapy and tonsillectomy significant increases in clinical remission rates can be obtained (25 percent with tonsillectomy, 13 percent without) also with significant increases in renal survival.49, 50, 5 1, 52
N ew va r i a nt Creutzfe l d -J a kob d i sease a nd to n s i l l ecto my
New variant Creutzfeld-Jakob disease (vCJD) is an extremely rare disease with 89 confirmed cases in the UK since 1 996. It has a long incubation period of up to 40 years and is almost certain to be universally lethal. The majority opinion is that vCJD . is the human form of bovine spongiform encephalopathy (BSE) . This belief is based on the time connection between the BSE epidemic in cattle and the outbreak of vCJD in cattle. Also, the disease produced in animal models by injection of BSE and vCJD appears to be identical. vCJD prion is known to concentrate in lymphoid tissue and to be difficult to remove from surgical instruments. There are no known cases of transmission of vCJD via surgical instruments in humans but it has been demonstrated in animals, and classic Creutzfeld-Jakob disease has been transmitted in this way in humans. These facts made the introduction of disposable surgical instruments a logical step by the Department of Health on the advice of the Spongiform Encephalopathy Advisory Committee. 5 3 , 54 , 55 , 56 On this basis, in January 200 1, funding for the introduction of single-use surgical instruments for tonsillectomy as well as for improving decontamination of surgical instruments was announced. 57 " 5 8 59 D I' sposable mstruments were ' routinely available from June 200 1 , thus, no routine tonsillectomies were performed between January and June
of that year. Once the instruments were available, serious issues with quality arose. The Medical Devices Agency/ Medicines and Healthcare Products Regulatory Agency was alerted to the various problems and improvements were made. In October 200 1 , when the agency was notified about 18 cases of secondary haemorrhage a hazard notice was issued concerning the use of diathermy, but unfortunately problems continued. The Department of Health under took a telephone survey of 45 trusts. At least half reported problems with single-use instruments, some with severe consequences: three intensive therapy unit admissions and one death from secondary haemorrhage. On the basis of this increased risk to patients trusts in England and Northern Ireland were advised to buy high-quality reusable instruments and cease using single-use instru ments. During this period decontamination facilities had been significantly improved, and are due for significant further improvement and investment. The English and Northern Ireland National Prospective Tonsillectomy Audit (2004) of 33,92 1 patients treated with reusable instruments produced statistics of an overall return to theatre rate of 0.9 percent, with 0.7 percent primary and 0.2 percent secondary haemorrhages. 59 , 60 The only significant factor for an increased risk of haemorrhage was coblation tonsillectomy, which doubled the overall rate of return to theatre to 1 .8 percent ( 1 . 1 percent primary and 0.7 percent secondary) . There were too few patients treated with disposable instruments for the data to be meaningfully analysed. Interestingly, in Scotland and Wales, disposable instruments continued to be used as the raised level of secondary haemorrhage or serious compli cations were not experienced there. 6 1, 62, 63 [ ****] Follow ing a detailed analysis of single-use instruments available in the UK, highly specified sets of single-use instruments were introduced in February 2003, together with a single use instrument surveillance programme to monitor both postoperative complications and instrument behaviour. 64 The Welsh data have shown that there was a significant rise in serious postoperative primary haemorrhage, but not secondary haemorrhage, following the initial intro duction of single-use instruments that reverted to baseline with the introduction of specified single-use instruments in 2003. Diathermy does not appear to have affected the haemorrhage rates. The full Welsh audit data as well as the Scottish audit data are to be published and will, between them, provide ample data on single-use instruments. Whether this will lead to a reintroduction of single-use instruments in England and Northern Ireland in order to prevent transmission of vCJD prions is unclear. The presence of preclinical and subclinical prion infection in the UK is unknown but a recent screening of 2000 anonymous surgical tonsillectomy specimens with high sensitivity immunoblotting and immunohistochemistry detected no positive cases. 65 Prevalence screening on a national sc'ale may be indicated to establish the need for single-use instruments in tonsillectomy.
Ch apter 1 52 Acute and chronic p h a ryngea l infection I 1991
To n s i l l ecto my tech n i q ues
Tonsillectomy techniques are currently undergoing some thing of a revolution. Until about ten years ago dissection tonsillectomy (first described by Edwin Pynchon in 1 890) , with haemostasis performed with ties or diathermy was the standard but more recently there has been an explosion of different dissection instruments described in an effort to try and reduce postoperative pain and haemorrhage associated with this procedure (see the list below) . The principles of dissection tonsillectomy remain unchanged as outlined below. Current trials do not suggest that any one of these techniques is consistently clinically greatly superior to any other technique and so a large multicentre trial is probably needed. Cost effectiveness issues also need to be addressed before these newer techniques are widely adopted. Dissection techniques include: •
•
cold dissection techniques sharp/blunt ± snares and haemostasis with ties or diathermy mono or bipolar; diathermy or electrocautery dissection which uses an electrically heated instrument to cut or coagulate tissues; monopolar; 66 bipolar forceps tonsillectomy; 67 bipolar scissor tonsillectomy; 6 8 , 69 radio frequency/electrosurgery tonsillectomy in which the instrument itself does not become hot but rather produces a current flow that generates heat within the tissue; - somnoplasty tonsillectomy: bipolar thermal radio frequency ablation; - coblation (plasma-mediated ablation)tonsillectomy; - argon plasma coagulator tonsillectomy; harmonic scalpel (ultrasound) tonsillectomy; laser dissection tonsillectomy: CO 2 laser, potassium titanyl phosphate (KTP) and Nd-YAG laser tonsillectomy. _
_
_
•
• •
Nondissection techniques include: • •
guillotine tonsillectomy; intracapsular partial tonsillectomy.
PRINCIPLES OF DISSECTION TONSILLECTOMY
General anaesthesia is undertaken with maintenance of the airway using either uncuffed orotracheal or laryngeal mask in children. In adults, cuffed endotracheal tubes are preferable. Appropriate exposure of the tonsils through the open mouth is usually achieved with a Boyle Davis mouth gag. In all techniques apart from guillotine tonsillectomy, the tonsil is grasped and retracted forcefully towards the midline allowing identification of the intended plane of dissection, i.e. the soft areolar tissue between the capsule of the tonsil and the constrictor muscle of the pharynx.
The surgical plane is then entered with minimal loss of or trauma to the mucosal tissue of the anterior pillar of the fauces and uvula. In this process all instruments are directed at the tonsil rather than laterally into the tonsillar fossa to avoid trauma to the glossopharyngeal nerves and the carotid arteries. The various dissection techniques have been developed in an attempt to minimize tissue trauma and thereby postoperative pain and bleeding while remaining simple and of short duration. All the techniques have their advocates and detractors, and some comparisons between techniques have been made. All techniques have a learning curve; most studies comparing complications are too small, do not compare a range of techniques and thus reliable comparisons cannot be drawn. Electrocautery refers to using a heated instrument to cut or coagulate tissues. A significant reduction in intraoperative blood loss and operating time with bipolar diathermy compared with cold dissection was initially reported. Surgeons reluctant to use diathermy for tonsillectomy cite an increase in haemorrhage, pain and 2 slower healing as major deterrants 70 , 7 1, 7 while others regard these views as unfounded. 7 3 [ ****] In 1995, Tay74 conducted a prospective study on 104 patients comparing diathermy and cold dissection on different tonsils in the same patient. [ ****] No significant differences in pain or other complications were observed between the methods. The recent Cochrane review identified 22 studies comparing tonsillectomy by diathermy and dissection. 75 Only two studies met the inclusion criteria, one com paring mono polar and the other bipolar diathermy with cold dissection. These studies demonstrate reduced intraoperative bleeding but increased pain in the dia thermy group. They concluded that large well-designed randomized trials would be necessary to resolve this debate. [ ***] The most essential part of tonsillectomy is complete control of haemorrhage, which may be achieved initially by placing tonsil swabs in each fossa, and then traditionally, by ties or diathermy to any bleeding points. Diathermy is quicker but is possibly related to an increased risk of secondary haemorrhage. Electrocautery may be the method of choice in patients at high risk of bacteraemia. 76 At the end of the procedure blood clots need to be aspirated from the nasopharynx to avoid obstruction of the airway postextubation. In radiofrequency tonsillotomy, somnoplasty systems use radio frequency waves at 460 kHz and have a bipolar electrode. The electrode has a temperature sensor for adjustment of output power to allow accurate control of tissue temperature and total energy delivered. Two papers describing this technique have been published, but numbers are too sma11 to draw any conc 1uS l· Ons. 77 , 7 8 [ **] Two trials have been reported comparing radio frequency tonsillotomy with conventional techniques and suggest that this technique causes significantly less pain, probably because the mucosa is not breached. The
1992 I
PART 1 5
T H E U PPER D I G ESTIVE TRACT
numbers in both trials were too small to make meaningful comments on haemorrhage rates?9 , 80, 8 1 [ ****/**] Coblation tonsillectomy using radio frequency signals produces an electrodisassociation effect to generate a plasma of excited ions or an ionized field. The coblator handpiece is equipped with an electrode as well as an irrigation and suction channel. This can be used either to fragment and suction tissue from the field down to, but not through, the lateral portion of the capsule, a subtotal supracapsular tonsillectomy, or to perform a standard dissection-type tonsillectomy. Coblation is performed at a lower temperature than standard radio frequency proce dures and may cause less damage to adjacent tissue. Temple and Timms82, 8 3 reported reduced postoperative pain, more rapid healing and quicker resumption of normal activities than electrocautery in both paediatric and adult tonsillectomy. [ ****] Complication rates in a retrospective series of 528 patients are similar to conven tional techniques. 84 [***] Recent trials suggest a mixed picture with four RCTs being in favour of coblation and one suggesting that there is no benefit. 82, 8 3, 84 , 8 5, 86, 8 7, 88 [****/***] The English National Tonsillectomy Audit suggested that coblation is associated with a 3.4 times greater haemorrhage rate than cold steel dissection compared with bipolar diathermy which was 3 . 1 times greater than cold steel dissection. 60 Argon plasma coagulator tonsillectomy requires an argon plasma coagulation (APC) dissector, an argon gas source and a high frequency voltage generator. The APC dissector consists of a rigid tube with a ceramic tip through which argon flows to the tip, where an electrode serves as one pole frequency voltage source. The other pole is connected to the patient as a neutral electrode. Argon is ionized by the electrode tip and flows as a blue beam between the electrode and the tissues. This is an attractive technique because of its limited penetration ( 1 -2 mm of the beam) but good coagulative properties, thereby minimizing blood loss and postoperative pain. Technically, the procedure is akin to traditional cold dissection tonsillectomy. 89 Three prospective rando mized studies have been described. Bergler's study89 suggested reduced surgical time, less intraoperative blood loss and no increase in postoperative pain compared with cold dissection and bipolar diathermy haemostasis. Shah90 concluded that APC resulted in less thermal injury than monopolar cautery, more complica tions and longer operating times. Bowling's 2002 study9 1
suggested less postoperative haemorrhage with argon plasma coagulator tonsillectomy than with monopolar electrocautery. [****] The harmonic scalpel, based on US technology, has two mechanisms to cut and coagulate tissue. The first is a sharp blade vibrating at 55.5 kHz over a distance of 80 !lm. The other results from the rapid forward and backward motion of the cutting tip in contact with tissue, leading to fragmentation and separation of tissue planes. Coagulation occurs due to mechanical disruption of
hydrogen bonds and thus protein denaturation. The temperature rise caused by these frictional changes (50-1 00°C) is much lower than that of cutting and coagulation by electrocautery ( l 50-400°C). Other ad vantages are improved visibility due to reduced blood loss, charring, dessication and smoke as well as no risk of distant burns as no stray energy is present. Finally, it requires less force and tissue tension for incisions compared with traditional knife incisions. Five prospec tive studies comparing electrosurgery and the harmonic scalpel have been reported in the literature.92 , 93 , 94, 95, 96 [ ****] Three suggest that the harmonic scalpel may be associated with less postoperative pain than electrocau tery, although intraoperative blood loss and postoperative haemorhage rates were similar. Operating time did appear to be longer. One study showed no difference in pain scores while another showed only marginal early benefit and significant difficulty in achieving haemostasis. Both the last two studies comment on the high cost of the equipment.97 , 9 8 [ ****/**] Kothari et al.99 compared KTP laser tonsillectomy with standard dissection tonsillectomy in a randomized double-blind trial. [****] They found significantly less perioperative haemorrhage, more postoperative pain, more postoperative mood depression and a higher rate of reactionary and secondary haemorrhage, but the latter two were not significant. Caution should, therefore, be exercised in using this technique, particularly in day case surgery. [ ****] Guillotine tonsillectomy has a poor reputation but is a safe procedure when carefully performed and has been regaining popularity. l Oo It is most suitable for protuberant tonsils in the paediatric population. 1 0 1 A large dental prop may be more appropriate for guillotine tonsillect omy, as the lesser extent of mouth opening facilitates easier insertion of the whole tonsil into the guillotine, and thereby minimizes the risk of tonsil remnants and postoperative bleeding. The tonsil is pushed fully through the guillotine, which is then closed. Care has to be taken to ensure all tonsil tissue is through the guillotine and no anterior pillar mucosa is caught in the guillotine. If the tonsil cannot be completely fitted through the guillotine the procedure should be abandoned. Once the guillotine is closed it is left for a minute to compress vessels in the lower pole before cutting off the tonsil. The poor reputation relates mainly to excessive trauma to pillars, postoperative bleeding from an inadequately removed lower pole and persistent infection in tonsil remnants. These problems have not been resolved but have improved with the introduction of dissection tonsillect omy. The main advantages of guillotine tonsillectomy are significantly less pain and greater speed. 1 02 Guillotine tonsillectomy can be safely used by experienced surgeons as part of a range of techniques available but is probably not appropriate as a first-line technique for trainees. The practice of" guillotine tonsillectomy without any anaes thetic does seem unacceptable. 1 0 3 [ ****/**]
Chapter 1 52 Acute a n d ch ro n ic pha ryngea l infection I 1993
Intracapsular partial tonsillectomy, either as an out atient procedure as in laser-assisted serial tonsillectomy escribed in adults, 104 CO laser tonsillotomy in chil2 . · dren 1 05 or microdebrider partial tons illectomy, 106 IS b emg increasingly advocated for tonsillar hypertrophy as part of the management of OSA. The advantages appear to be reduction or near total ablation of tonsil tissue with significantly less pain and postoperative bleeding, although tonsil regrowth can occur. 1 06 Ko Ital· e t a I. be1 leve · that preservation of the tonsillar capsule prevents exposure of the pharyngeal muscles to the inflammatory effects of pharyngeal secretions, i.e. the capsule acts similarly to a biological dressing. Also, leaving the capsule means that the larger tonsil vessels are preserved and only the more distal small vessels exposed. The latter may well be less prone to haemorrhage.
�
Posto perative ca re
Discussion on whether tonsillectomy should be treated as a day case or requires an overnight stay has been ongoing in the literature since 1 992. 1 07 Enthusiasts for the day case cite the economic benefits, minimal morbidity, low reactionary haemorrhage rate after eight hours (0.49 percent) 1 07 and reasonable ability to control �ain and nausea as arguments in favour of day case tonsIllectomy in adults and children. However, day case discharge of adults is usually less reliable than of children because of greater problems with pain control. Detractors raise concerns about the high rate of medical and social contraindications as well as the lack of parental preference for this option, 108 variable reactionary haemorrhage rates and control of nausea, vomiting and pain. Successful day case surgery rates of up to 96 percent have been reported, 1 0 9 with adult rates closer to 50 percent being the norm.1 1 0 Shah et aI. l 1 1 emphasized the benefits of a dedicated home care team following day case tonsillect. 1 12 , 1 13 a er omy procedures. Drake-Lee and Harns, ft evaluating 500 children for day case tonsillectomy, produced a formula for day case targets in tonsillectomy, based on local criteria: proportions without medical or social problems; a proportion living within ten miles of the hospital; and a proportion without postoperative complications. After discharge from hospital 44 percent of patients or carers contacted health care professionals; pain was the leading indication for contact, and haemorrhage for visits in person. Telephone information was sufficient in 50 percent of patients. Telephone contact was followed by a visit in 89 percent of patients with haemorrhage and . 34 percent 0 f patIents WIt · . h pam. l l 4 The criteria for day case tonsillectomy are: •
• •
an available competent adult at home to manage potential problems; . access to a car to return the patient to hospItal; access to a telephone;
•
•
a home-to-hospital driving time of less than 20 minutes; no medical contraindications.
Monitoring for haemorrhage is the most important aspect of post-tonsillectomy care. This involves clinical observa tion of the patient for excessive swallowing, pallor, increases in pulse rate and monitoring blood volumes if coughing or vomiting up blood as well as trying to assess the bleeding point. It is good practice for all staff involved in the care of these patients to record estimated blood losses in theatre, in recovery and on the ward, accepting the limitations of such attempts. These then need to be assessed in the light of total expected patient blood volumes allowing 1 00 mLlkg for a child's blood volume. All cases of reactionary haemorrhage in children should be taken back to the theatre in order to obtain reliable control. In adults, with their greater blood volume, a short period of conservative treatment can be attempted prior to surgical reintervention.
POSTO PERATIVE PAI N/ANALGESIA REQU IREMENTS
Relatively little, quality information is available in the literature on post-tonsillectomy analgesia. Practice is, therefore, very individualized and may vary widely within departments. The audit of postoperative analgesia in . children following tonsillectomy by Homer et a 1. 1 1 5 IS instructive. Their initial audit showed significant levels of postoperative pain in 70 percent of children given a wi� e range of postoperative analgesia, as would be found m many departments. They then moved to a policy of oral paracetamol (20 mg/kg) and diclofenac ( 1 mg/kg) , except in asthmatics, two hours preoperatively as well as the uniform postoperative prescription of up to 100 mg/kg of paracetamol and 3 mg/kg of diclofenac in 24 hours with DF1 l 8 as rescue analgesia. Preprinted prescriptions, education of nursing staff in this standard policy and in using the pain scoring system were the conclusions of the audit, showing large reductions in pain scores at all time points despite not all doses of allowed analgesia being given. [**] A recent Cochrane review1 1 6 examining 13 trials concluded that NSAIDs did not significantly alter the number of peri operative bleeding events requiring surgical intervention. Seven further trials looking at bleeding that did not require surgical intervention came to the same conclusion. [ ****] A similar audit for adult tonsillectomy would be beneficial. One recent study in adults 1 l 7 suggested that NSAIDs, for example ketoprofen combined with �ll dosages of paracetamol and codeine as rescue analg�sla was sufficient for most adults at home followmg tonsillectomy. The median time for cessation of pai n . was 1 1 (3-24) days with median duration of an�lgesla taken of 12 ( 5-25 ) days. The median time for cessatlO � of pain on drinking was seven days ( 1 -1 8) and on eatmg
1994 I
PART 1 5
TH E U PPER D I G ESTIVE TRACT
solids 1 1 ( 1-20) days. Patients reported the first normal night of sleep at seven ( 0- 1 8) days and return to normal daily activities 12 ( 2-24) days. [**] In a double-blind randomized trial of cryotherapy against no treatment at the end of tonsillectomy, Robinson et al. l 1 8 demonstrated that cryotherapy patients recorded significantly less pain, less time off work and less analgesia use than control patients, with no added complications although the procedure added about ten minutes to each operation. [****]
late postoperative period following paediatric adenoton sillectomy. I 32 [ ****] TON S I L H I STOLOGY
Several studies support the view that in both adults and children only those patients with known risk factors should have their tonsils sent for histology. 1 33 [***] In children, reported figures for unexpected tonsillar malig nancy range from 0 to 0 . 1 8 percent.
ANTIEMETIC THERAPY POST-TONSI LLECTOMY
Three recent studies allude to the benefits of prophylactic single-dose antiemetic therapy using ondansetron or other selective 5HT type 3 receptor antagonists. 1 1 9, 1 20, 1 2 1 , 1 22 [ **** ] Concern has been expressed that use of antiemetics might mask clinical signs of bleeding. I 22
DIET POST-TONSI LLECTOMY
There is no evidence to suggest that particular post tonsillectomy diets have any impact on rate of recovery or complication rates. 1 23 , 1 24 [****]
ADJU NCTIVE THERAPY: LOCAL ANAESTHES I A, ANTI B I OTICS AND STEROIDS
Perioperative injection of local anaesthetic has been advocated for pain reduction, diminished perioperative bleeding and facilitation of dissection. A Cochrane review 1 25 indicated that studies were too small and did not show a significant effect size. A recent RCT using lignocaine and adrenaline-soaked swabs showed no benefit over saline-soaked swabs. 1 26 [****] Standard UK practice is not to give postoperative antibiotics following tonsillectomy. This view is sup ported by a prospective audit, 1 27 but a recent study 1 2 8 suggested a range of benefits including lower pain scores, less analgesia and shorter time to a normal diet. A new metaanalysis shows that postoperative oral antibiotics do not significantly reduce post-tonsillectomy pain but result in an earlier return to normal activity by about one day. 1 29 [****] A metaanalysis 1 30 of a single intraoperative dose of dexamethasone in paediatric tonsillectomy suggests a statistically significant reduction in post-tonsillectomy emesis (NNT 4. 1 7) during the first 24 hours and an increase in the number of patients advancing to soft or solid diet on postoperative day one (NNT 4.76 ) . This is extremely helpful as results from 3 1 randomized trials have been conflicting. These findings are supported by a Cochrane systematic review by the same authors. 1 3 1 [****] A recent RCT suggested that intravenous hydration for 24 hours postsurgery reduced postoperative pain in the
Co m p l i cati o n s
Table 1 52.1 summarizes post-tonsillectomy compli cations. Reactionary haemorrhage (bleeding peroperatively and within the first 24 hours) is the most feared complication post-tonsillectomy because of the risk of airway obstruc tion, shock and, ultimately, death if inappropriately treated or untreated. Fortunately, mortality post-tonsil lectomy has declined from approximately one in 3000 to one in 1 70,000 operations. Haemorrhage rates reported in the literature vary widely but most 'return to theatre' rates are less than 1 percent. They usually happen in the first eight hours after surgery and the majority within four hours. Various classification systems for the severity of 4 4 44 4 bleeding have been devised. 1 1 , 1 2 , 1 4 3 , 1 , 1 5 All are highly subjective and grade haemorrhage into minor and major, as well as subdividing the latter into those that do or do not require return to theatre and/or require transfusion. Despite the efforts of all surgeons low reactionary haemorrhage rates seem to be unavoidable. None of the techniques seem to be significantly more prone to reactionary haemorrhage than the others. However, for the newer techniques, large multicentre trials comparing them with each other and with more traditional methods are warranted to answer this question with greater confidence. Likewise, the incidence of haemorrhage is not related to grade and seniority of the surgeon. 1 46 Early concerns about the use of diclofenac increasing the rate of reactionary haemorrhage have not been borne out, 1 47 and many units now use it routinely. 1 1 6 The overall incidence of haemorrhage is not significantly different after cold steel dissection and diathermy but cold steel dissection is associated with a higher incidence of reactionary haemorrhage and dia thermy with a greater incidence of secondary haemor rhage, often greater than 500 mL. 1 48 Risk factors for a blood transfusion following tonsillectomy include end stage renal disease, hypertension, reduced haemoglobin and haematocrit. Patients with these risk factors require appropriate preoperative investigation, and secondary haemorrhage should be treated with an immediate return to theatre 'to avoid severe complications. 1 49 [***] Reac tionary haemorrhage occurs mainly in males, patients
Ch apter 1 52 Acute a n d ch ronic pharyngea l i nfection I 1 995
Table 1 52 . 1
Post-tons i l l ectomy com p l ications. I ntem'ledta te
hnmedia�e �' .
.
Reactiona ry haemorrhage Ai rway obstruction seconda ry to reactionary haemorrhage with blood entering a i rway, laryngospasm, d islodged teeth or forgotte n swabs Na usea and vom iting re lating to a naesthesia, opiate a na lgesia o r swa l l owed b l ood Excessive pa i n due to g reater than expected tissue tra u m a re lated to insertion of Boyle Davis mouth gag, uvu la or p i l l a r tra u ma d u ring dissection Ai rway fi res due to the use of d iathermy in the p resence of high oxygen concentrations a nd b u rning of swa bs
Su bcutaneous emphysem a 1 3 6, 1 3 7 Temporo m a n d i b u l a r joint d i slocation o r dysfu nction. I n a rece nt p rospective sing le- b l i nd tria l, 3 /27 patients experie nced sym ptom s a nd 1 1 /2 7 had red u ced i nterincisa l dista nce while there were no sym ptom s and no fi ndings i n t h e control g ro u p 1 3 9 De nta l i nj u ries
Postoperative fever Hypog lycae mia Hypovolaemia
Second a ry hae m orrh a ge Oedema of the uvu l a
Posto perative sca r ri n g Tonsi l rem na nts
Excessive pain often associated with ota l g ia
Pharyngea l ste nosis
I nfection i n tons i l l a r fossae p romoti ng secondary haemo rrhage
l\Ja sa l reg u rg itation /ve lopharyngea l i nsufficie ncy due to excess remova l of a nte rior p i l l a rs
Atl a ntoaxi a l s u b l uxation (Grisel's synd rome)
Taste d i stortion after tons i l l ectomy may be either perma nent, due to s u rg ica l i nsu lt to the l i ng u a l b ranch of the g l osso p h a ryngea l nerve o r te m po rary, d u e to p ressu re on the tong ue a nd zinc deficiency. Tem po rary cases re ported reso lved within six weeks 1 34, 1 3 5 G l ossopharyngea l ne rve pa ra lysis 1 38 [*]
Peritonsi l l a r abscess Pne u monia extremely ra re but a U RT i nfection at the time of su rg e ry is be l ieved to be a risk factor
Su bacute bacteria l endoca rd itis re lated to bacte raemia in patients with abnormal hea rt va lves Pu l monary embolus 1 40 Pu l monary oedema Su bcuta neous e m p hyse m a a nd pneumomed ia sti n u m 1 3 6, 1 37
Hyponatrae m i a
over 70) adults versus children) patients with a history of infectious mononucleosis and recurrent acute tonsilli 1 tis. 1 5 0, 5 1 [ *** ] Commonly held superstitions about post tonsillectomy haemorrhage) i.e. that they occur more frequently in redheads) in patterns of threes) on Friday 1 3 o r o n full moons) are not supported by the evidence base. 1 s2 [ *** ]
SECON DARY HAEMORRHAGE
A review on this subject suggests that it may be more common than is widely appreciated) occurring in about 9 percent of cases. Of these) 1 .4 percent were severe requiring a return to theatre. The incidence of secondary tonsillectomy haemorrhage increases with age) peaking between 30 and 34 years) with no statistically significant
difference between the sexes. The incidence of serious haemorrhage increases in older age groups but is not influenced by gender. Most (70 percent) present between days 4 and 7. A retrospective study of 1 5)2 1 8 showed a 0.4 percent secondary haemorrhage rate. 1 S3 POSTOPERATIVE FEVER
Postoperative fever is a common problem after tonsil lectomy; 4 percent of patients having a temperature higher than 37.5°C and 30 percent higher than 38°C in the first 24 hours post-tonsillectomy. l S4 However) there is no association between colony count) core cultures) blood cultures and fever) suggesting that fever is not caused by infection and therefore does not routinely require antibiotics.
1996 I
PART 1 5 TH E U PPER D I G ESTIVE
TRACT
To n s i l I ecto my o utco m es
adults it is more d i fficult t o achieve because o f difficulties i n postoperative analg esia management
Limited infonnation is available in this area. A recent 1 55 study suggested that after tonsillectomy, UPPP, septo
and patient perceptio n .
./ Careful postoperative monitoring for haemorrhage i s
plasty and turbinectomy patients are unlikely to perceive
mandatory with accurate fluid replace m e n t a n d early
a change in voice following their surgery. [H] Zielnik 156 Jukiewicz and Jurkiewicz. have demonstrated short
persiste nt bleed i n g .
term deficits in cellular and humoral immunity for up to
return to t h e atre being recomme nded in t he face of
./ Standardized postope rative analgesia regimens using
six months in children following adeno-tonsillectomy
1 00 mg/kg paracetamo l and 3 mg/kg d i clofenac i n 24
but have not sho wn that this is of clinical importance. 1 57 [** J Stewart has developed a comprehensive tonsil and
h o u rs for paediatric and, possibly. adu l t patien ts.
.!
adenoid health status instrument, which covers a wide range of indications but with only
single postoperative d ose of o ndansetron or si m ilar
vomit i n g .
1 5 items to complete.
The Scottish tonsillectomy audit outcome questionnaires
A
antie metic w i l l avoid most postoperative nausea and
if
A
single postoperative dose of dexa methasone i n
indicated a high satisfaction rate among patients of
chi l dren has b e e n shown to im prove short-term
97 percent at six months, 75 percent response rate at six months and 45 percent at one year. [ H ) The Glasgow
o utcome for a variety of factors.
Children's Benefit I nventory has been used to assess retrospectively the benefit of tonsillectomy. The results correlated well with parental satisfaction and estimates of technical success, such as residual sore throats . 1 58
P E R ITON S I LLAR ABCESS (QU I N Sy) Peritonsillar abscess is a collection of pus b etween the fibrous capsule of the tonsil, usually at the upper pole, and the superior constrictor muscles of the ph arynx.
, ' �.,;·���'RJ:s�ection tonsillectomy is the recommended ' ·':..?'· sf�dard technique, although guillotine
X
,
tons illectomy is
regaining
'. '
E p i de m i o l ogy
some popula rity
and new jntraca psular partial tonsillotomy
" :�'"
.
'
'
� " '�
C "
resolved and large
. :l::�l'7fiuired.
spective data on suppurative complications o f tonsillitis, such as quinsy, suggest that the incidence decreases modestly with increased antibiotic prescribing but pro bably not sufficiently to increase overall prescribing rates 1 59 in general practice. It usually arises as a complication of tonsillitis, but also de
.
,L,·.-
.>. ... .
,
in the absence of a history o f
age but the majority is in young adults between '
ty been filliY" :�' iif<, mtl.it1t�nti�':-
,.
novo
previous recurrent acute tonsillitis. I t may happen a t any
',
" , :, .c'." ver�us cold djssect iorr ����� n9� et
': :�\.
No current UK figures are available, altho u gh retro
techniques have been advocated. The principles of dissection tonsillectomy rema,in constant, but a range of new t oo]s has been used t hat i ncl u de rad iofrequeucy, harmonic scalpel, argon laser and coblater, w i t h reduced i n t raopera�ive blood loss and pO,S;Sibly less postoperative pain than
"!�,-' ;
20 and
3 9 years of age, which is surprising in view of the fact that
the incidence of tonsillitis peaks in childhood, suggesting 160 the aetiology must be more complex. Passy suggested that a PTA may also represent an abscess of Weber's glands, which are minor salivary glands located in the supratonsillar space. [** J
Best cl inical practice Bacte r i o l ogy ./ The most common i n dication for tonsillectomy is recurrent acute to nsil litis. The Scottish I ntercollegiate Guideline Network (S I G N ) recommendations for tonsi l lectomy are at least five episodes of tonsil l itis per year of at least o n e-year duration. These are arbitrary but a recent study suggests that less stringent criteria are not justified.
./ Paediatric d ay case to nsillectomy is safe i f sensibl e medical a n d soc i al criteria are ad h ered to, but i n
The bacteriology o f acute tonsillitis differs from that of PTA, and it may be that the complication only occurs in the presence of anaerobic organisms and the usual beta 61 haemolytic streptoco ccal infection. A recent s tudy1 noted an association between periodontal disease and PTA wh,ich may represent a source of anaerobic organ isms. Similarly, it may explain why quinsies can some times arise as a consequence of dental abscesses or third
Chapter 1 5 2 Acute a n d chro n i c pha ryngeal i n fect i on I
molar extractions . 1 62 Methicillin-resistant Staphylococcus aureus (MRSA) has been identified in a PTA.
•
1997
Needle aspiration o f pus is often curative and may also provide useful bacteriology in recurrent or nonresponsive quinsies and help clarify the difference between peritonsillar cellulitis and PTA.
Cl i n i ca l featu res
Bacteriological specimens do not need to be sent to the laboratory routinely after needle aspiration; this should be reserved for patients with a high likelihood
The main feature of the history is the progressive, usually
of infection by resistant organisms, such as diabetics,
unilateral, s ore throat over three to four days, odynopha
immunocompromised patients or patients with
gia, dysphagia for solids and eventually liquids, drooling of saliva,
trismus,
ipsilateral
otalgia
and
headache
associated with fever lethargy and ipsilateral lymphade
•
to
the
oropharyngeal
swelling
and,
mainly because of the lack o f predictive signs and the diversity of potential complications . 1 7 5
on
examination, limited mouth opening is virtually patho gno monic, 163 the tonsil is displaced medially by the
Routine s creening for infectious mononucleosis i n all patients presenting with PTA has been recommended,
nopathy. The patient often develops a plummy voice
secondary
recurrent PTAs ! 74 [ Gra de D ]
•
Transoral ultrasound is used in some countries 1 76 as an effective noninvasive method of differentiating pus
hyperaemic, b ulging mucosa of the anterior pillar over the
peritonsillar space and in addition the j ugulo digastric
fro m cellulitis (sensitivity
nodes are tender and enlarged. Bilateral quinsies have , been reported 1 64 1 6 5 and in association with infectious
percent) . [ Grade C] •
percent, specificity
62.3
Dental radiographs or an orthopantomogram may be helpful in the presence of coincidental dental disease
mononucleosis. 1 66 Peritonsillar abscess arising in patients
or uncertainty as to whether a dental abscess may be
with infectious mononucleosis is not linked to steroids prescribed to relieve upper airways obstruction in these 1 circumstances. 67
92.3
involved. •
Computed tomography ( CT ) has been used in the presence of suspected complications such as spread to the parapharynx, retropharynx and mediastinum.
D iffere nti a l d i a g n o s i s
[ Grade D] If descending necrotizing mediastinitis is suspected CT of the neck and chest is the investigation of choice, rather than chest radiograph,
Differential diagnosis can b e divided into infectious,
as it will pick up signs when the chest radiograph is
inflammatory, vascular and neoplastic. •
•
Infectious: peritonsillar cellulitis, parapharyngeal abscess, upper third molar abscess and coexistent infectious mononucleosis. 1 68 Inflammatory: Kawasaki disease presenting as PTA
still normal. 1 77 •
Magnetic resonance imaging (MRI ) angiography may be suitable for suspected vascular anomalies. [ Grade D ]
has been described . 1 69 Treatment is aspirin and intravenous gammaglobulin. •
• •
Vascular: post-traumatic internal carotid artery pseudoaneurysms can occasionally cause catastrophic 1 confusion , 70 Benign lesions: benign lymphoepithelial cyst. l 7 1 Neoplastic: large tonsil tumours with lateral extratonsillar spread, s uch as squamous cell carcinoma (SCC ) , l 72 tonsillar lymphoma and
•
•
rhabdomyosarcoma. 173 Peritonsillar space tumours: minor salivary gland tumours. Anterior pillar mucosal tumours: for example, Scc.
Usually, differential diagnosis based o n the clinical findings
is not a problem but, occasionally, needle aspiration of pus
from the peritonsillar space and or imaging techniques may be required to confirm the diagnosis. [ Grade D ]
Treat m e n t Admission t o hospital and treatment with intravenous antibiotics until acceptable swallowing is feasible sho uld be the baseline treatment offered to all patients. There is no evidence that admission to an ENT ward increases the 8 rate of secondary haemorrhage post-tonsillectomy. 1 7 Occasional reports
of successful
outpatient treatment
with either oral or intramuscular antib iotics have been reported but no data exist to compare this treatment with intravenous antibiotics in hosp ital. [Grade D ] Incision and drainage under sedation has been advocated in children, with subsequent home discharge, 1 79 but this
does not seem like safe p ractice despite a lack of described complications. Intravenous benzylpenicillin, which deals
with mos t relevant anaerobes as well as streptoco ccal infection, is the treatment of choice. In patients allergic to
I nvesti g ati o n
penicillin erythromycin should be used. [Grade D ] The use of steroids as an adjunctive treatment has been increasing, with one RCT repo rting a range of favo urable
Investigation i s not mandatory i n clear-cut cases, but may be helpful in less straightfo rward cases.
L l,
- _ .-
outcomes with steroids with no increase in complica tions. 1 80 [ Grade D]
A
single dose of intravenous steroid in
1998 I
PART 1 5 T H E UPPER D I G ESTIVE TRACT
addition to antibio tic therapy significantly reduces throat
resolution reoperation including contralateral thoracot
pain, time in hospital, fever and trismus. [ Grade A]
omy may be required.
The presence of an obvious p o inting abscess, clinical
Necrotizing fasciitis following PTAs has rarely been
antibio tics,
described. Treatments advocated include broad-spectrum
evidence of p us in the perito nsillar space on an imaging
antibiotics, abscess tonsillectomy and large-scale debride
modality would
ment of necrotic tissue. I 9 1
deterioration,
either
failure
to
respond
to
i.v.
all be reasonable indications for drainage
by needle
aspiration
or
using a
conventional
guarded quinsy knife. Needle aspiration is the most common treatment in the UK. I 8 1 It is relatively pain free, significantly contrib utes to pain relief compared with no 2 aspiration 18 and is not associated with any significant
complications, however, complete p us drainage may be
KEY PO I NTS •
less reliable than with a quinsy knife thus p otentially
predisposing to
greater
recurrence risks
and
delayed
complications. Metaanalysis of success rates for needle aspiration gives a rate of ranging between
10
94
and
•
percent with recurrence rates 15
percent.40
Quinsy knife
drainage is mainly used when needle aspiration has failed but is more painful than needle aspiration and has, historically, been asso ciated with some disastrous com
•
plications. Incision and drainage is less painful if carried o ut with proper infiltration of local anaesthetic at the site of
drainage
rather
than
Matsuda e t al. I 84 reviewed
local
anaesthetic
spray. 1 8 3
724 cases of quinsy i n Japan
•
and concluded that in view of the significant risk of mediastinitis
PTA!>
a re
decl i n e
becoming less common d espite the in ant ibiotic use for S O f e t h r oa t s in
generaf practice.
Usually, they follow on from acu[e tonsi Ui t is but see m to require a naerobic organ isms as well as beta-ha
( 1 .8 percent) incision and drainage was
preferable to needle aspiration. Abscess tonsillectomy is a technique with a poor reputation in the UK but is practised in Germany185. 1 86 with go o d results and minimal morbidity, in particular, no
increase
in
perioperative,
primary
or
secondary
Best cli n ical practice ./ Treatm ent i n vo lves hospita l a d miss i o n . i.v. a n t i b i otics and, poss i b l y, p rogressi ng to needle aspi ration,
haemorrhage with the additional advantage o f avoiding
i ncision a n d d ra i na g e or abscess ton s i l l ectomy,
recurrence and the need fo r elective delayed tonsillectomy admission. 1 87
More
recently,
secondary
figures after abscess tonsillectomy
'J
Med i asti nitis a nd necroti zing fasditis occasion a l ly
haemorrhage
a rise.
(22 percent with a
return to theatre rate of 1 1 percent) have been reported188 and these might be regarded as unacceptably high. In a paediatric pop ulation abscess
in which needle aspiration or
drainage requires general anaesthesia, abscess
tonsillectomy under
general anaesthesia may be
the
PARAPHARYN G EAL ABSCESS
treatment of choice. I 89 Elective tonsillectomy after recurrent quinsy is recom
The paraph aryngeal space lies on either side of the
mended as after tonsil-conserving treatments approxi
superior
mately
and oropharynx. It is b ounded laterally by the parotid
1 1 percent of cases recur by five years and 22 percent by 17-35 years. Abscess recurrence is rare after the
gland,
age o f 40 and therefore elective tonsillectomy is not
Medially
warranted.lBB
part
parotid it
of the fascia
pharynx, and
i.e.
medial
the
nasopharynx
pterygoid
is bounded by the superior
muscle.
constrictor
muscles, separating it from the pharynx. Superiorly it is limited by the skull base and inferiorly by the fascia surro unding the submandibular gland. Posteriorly the
Co m p l i cati o n s
space
communicates with
the retropharyngeal space.
The parapharyngeal space contains the carotid sheath Deep neck space infections and mediastinitis have been
with the internal carotid artery, internal j ugular vein,
described in 1 . 8 p ercent of cases. I B9 Mediastinitis is a
vagus nerve, styloid muscles, the last fo ur cranial nerves
condition with significant mortality
(23 percent ) l 90 even
and some lymph no des. Infection can spread to the
with aggressive management, i.e. combined neck and
parapharyngeal space from any of the other deep neck
m ediastinal drainage as well as appropriate antibiotic
therapy. If initial mediastinal drainage does not lead to
spaces, i. i. peritonsillar, retropharyngeal and submandi bular spaces.
Chapter 1 52 Acute and chronic pharyngea l infection I 1999
E p i dem i o l ogy
No figures exist for the incidence or prevalence of this condition. Parapharyngeal abscess can occur in any age group. The most common causes are tonsillitis, PTA or dental infection. Rarely, elective tonsillectomy, 192 excessive tonsillar manipulation by traditional Nigerian healers,193 mastoiditis, cholesteatoma associated with temporal bone fibrous dysplasia,194 pharyngeal foreign body, trauma from nasotracheal intubation/95 internal cysts and fistulae of branchial origin 196 or second pharyngeal pouches,197 can cause parapharyngeal abscess. Immunocompromise such as diabetes, non-Hodgkin's lymphoma ( NHL) 19 8 or chronic granulomatous dis ease, 1 99 HIV disease2 00 and aplastic anaemia2 01 may be predisposing factors. [**]
Bacteriol ogy
The bacteriology of deep neck space infections appears to changing with increasing numbers of cases being due to Gram-negative aerobic infections, which will not respond to first-line penicillin treatment and may be contributing to the significant mortality still associated with these · . 202 A recent survey of 1 8 5 cases from Taiwan con d1tlons. suggested that Klebsiella pneumoniae and Streptococcus viridans were the most common organisms, each accounting for 34 percent of cases.203 Pseudomonas aeruginosa in a patient with HIV disease, and in cat scratch disease204 and spinal tuberculosis (TB) 2 05 have been described. Invasive M-type 3 Streptococcus pyogenes infection causing necrotizing fasciitis in care home patients to spread to staff, which resulted in paraphar yngeal abscesses in two cases, has also been reported. 2 06 [**]
Cl i n ica l featu res
Clinical features are very similar to PTA except that the maximum swelling in the pharynx is more inferiorly placed and behind the tonsil with less oedema of the palate. In addition, there is the tender, firm but fluctuant swelling of the abscess to be felt in the neck rather than just lymphadenopathy. If a parapharyngeal abscess complicates a PTA then the clinical features can be indistinguishable. Occasionally, a parapharyngeal abscess can present as torticollis of the neck. 207 Diffe renti a l d i a g n o s i s
Differential diagnosis can be divided into infection, neoplastic and vascular lesions. •
i
L
Infection: PTA and spinal TB.
•
•
Neoplastic: primary tumours of the parapharyngeal space including deep lobe parotid tumours and local spread from tonsil tumours or lymphoma. Vascular lesions: including pseudoaneurysms of the common and internal carotid and lingual arteries. The latter is a rare complication post-tonsillectomy.
I nvesti gation
CT scanning of the neck and including the head if mastoiditis is suspected and the chest if mediastinitis is suspected should be carried out. However, CT scanning is not necessarily specific in differentiating abscess from cellulitis or inflammatory oedema and, therefore, a decision for surgical intervention should be based mainly on the clinical status of the patient. 20 8 [**] [Grade D ] Occasionally, plain soft tissue lateral films o f the neck or CT scanning may demonstrate a foreign body that has penetrated the pharynx. [Grade D ] Preoperative nasendoscopic assessment o f the upper aerodigestive tract can be helpful to assess the inferior extent of the 'pharyngeal airway bulge' in order to decide whether safe intubation is feasible or whether preopera tive tracheostomy under local anaesthetic is indicated. [ Grade D ] Treatm ent
Admission to hospital for i.v. antibiotics is the baseline treatment. Penicillin is the textbook recommendation, albeit without any current evidence base in the literature. Zahraa and Al-Boukai209 recommends cefuroxime in children, on the basis of experience with eight cases. Perhaps, in the light of the lack of evidence, aspiration of pus for microbiology at an early stage might facilitate appropriate treatment. Failure to respond to conservative treatment or clinical deterioration should prompt surgical abscess drainage. If necessary, a tracheostomy should be performed first, under local anaesthetic. The traditional site of drainage is through an incision on the side of the neck at the level of the hyoid bone. The para pharynx can then be reached by following the carotid sheath upwards. If the abscess appears to involve adjacent spaces, these should also be investigated clinically or radiologically. If the abscess emanates from the peritonsillar space an abscess tonsil lectomy should also be considered. Smaller parapharyngeal abscesses can be needle aspirated transorally, and I suspect regularly are, inad vertently, when more than 10 mL of pus is aspirated out of a presumed peritonsillar abscess. This reduces the length of stay in hospital and incidence of postoperative complications as well as shortening the anaesthetic time for the initial surgery.2 l0 Image guidance technolo gy may be helpful for drainage of parapharyngeal abs cesses
2000
I PART 1 5
THE U PPER D I GESTIVE TRACT
medial to the great vesse1s .2 1 i Needle aspiration through the tonsillar fossa post-tonsillectomy has also been described?1 2 Sichel
et
aI 208 .
reported
a
small
nonrandomized
1\
Best cl i n ical practice � CT is the i nvestigation of choice although pla i n fi lms a nd n asendoscopy may be he l pfu l. Asp i ration of pus
prospective study of nonsurgical management of isolated parapharyngeal space infections. All responded to i.v.
augmentin over a 9- to 14-day period.
may be helpfu l for microb i o l og ica l diagnosis. .; Base l i n e treatment is with i.v. cefu roxime i n hosp ital, progressi n g to extern a l surg ical d ra i nage th ro u g h the
Interestingly, those abscesses which threaten the airway
neck if th ere i s n o response or reso l ution w i thin 48
tend to be based more medial to the carotid sheath and can be successfully drained intraorally thus avoiding open
neck drainage.213 the
All
[ Grade D] .
above
treatment
recommendations
Major
complication
RETRO PHARYN G EAL ABSCESS rates
of 16
percent
have been
posterior pharyngeal walL
jugular vein thrombosis, carotid artery thrombosis, internal carotid artery pseudo aneurysm214 or blow
E p i d e m i o l o gy
aggressive treatment is then mandatory to avoid
Retropharyngeal abscesses (RPA) most commonly occur
artery aneurysm may be life saving.2 i6
between three and five years, due to a suppurating
necrotizing fasciitis. 2 1 7
adults and children it may occur very rarely secondary
out presenting with a Horner's syndrome. Early
fatality. 2is Endovascular stenting of internal carotid Acute pharyngeal perforation secondary to cervical
•
Mediastinitis requiring urgent drainage may occur
in children under six years of age, with a peak incidence retropharyngeal node following a URT infection. In
to foreign body penetration or due to spread from
even with early broad-spectrum antibiotic
cervical spine TB.221 The former is usually related to fish
Descending necrotizing fasciitis o f the neck and
the removal of a pharyngeal foreign body. They may
sternotomy and widespread debridement. The
these should all be carefully examined?22 A tuberculous
reconstruction? 19 Differential diagnosis from
of tuberculous cervical spondylitis, with an incidence of
bone penetration. Abscesses can develop before or after
treatment?1 8
•
mediastinum requiring drainage via a median debrided area may require subsequent
•
The retropharyngeal space lies immediately behind the
Carotid sheath involvement can result in internal
•
•
thrombosis, necrotizing fasditis a nd m ed iasti n i tis.
are
Co m p l i cat i o n s
reported.2i3
hou rs, or if th ere is evide nce of a i rway co mpromise.
./ Co mplications i nc l ude ca roti d s he ath vessel
dissecting thoracic aortic aneurysm is important.220
follow even apparently innocuous injury and, therefore,
retropharyngeal abcess is rare even in the presence
0.3-1 percent?22
Upper airways obstruction due to inferior abscess extension may require tracheostomy.
•
Symptomatic hyponatraemia due to a syndrome of
Bacte r i o l o g y
been described in izznfants with parapharyngeal
Only one study, from Taiwan, reports the bacteriology of
inappropriate antidiuretic hormone secretion has
abscesses presenting with fits and drowsiness.22o
votella
usuilly- d�e to.· . ' 'Pa'ra haIYng�aLab�cesses - tonsillitis, - pj:'A" or-: 9-�ntil Infecti-o: -. . Organisms. are changing with -increasing
p
•
deep neck space infections in children in which RPAs were
the most common groUp.223 The commonest pathogens
were S. viridans (41 percent) and S. aureus (26 percent) . K. pneumoniae, Escherichia coli, Enterobacter spp., Pre
K EY- PO�NTS
-
[**]
a;e�
� .
,
numbers - due to Gram-negative pathogens.
spp.,
described. [ ** 1
Salmonella spp.
and
MRSA
have been
Veillon ella spp. and Morganella have also been isolated.
Mixed infections were found in 46 percent of patients. It has been suggested that, at least in some paediatric patients, recent EBV infection may have an aetiological
Clinically' maximum intraoral-swelling - is
role in RPA formation?23
fluctuant abscess palpable- in -the 'neck.-
in adults, 'of which 1 2 percent were RPAs, showed that
behind the tonsil and - there may be, a -
A recent review of 2 1 0 deep neck space infections
S. viridans (39 percent) was the most common pathogen.
Ch apter 1 52
followed by Staphylococcus epidermis (22 percent) and then S. aureus (22 percent).224 The review also noted the aetiological role of dental infection (43 percent) and intravenous drug abuse ( 12 percent) . [H] Penicillin-resistant S . pneumoniae has been described as a causative organism in paediatric cases. 225 Blastomycosis as a cause of RPA has been described.226 Tuberculous abscesses are traditionally associated with cervical spine disease in adults, but have also been described in young children in the absence of neck disease. 227
Acute a n d chronic pharyngea l i nfection I 2001
tissue bulge in front of it as well as bone destruction. Patients need to be handled with great care because of the risk of precipitating neurological complications. Both CT and MRI can be used to delineate the abscess in greater detaiL [Grade D ] I n children, plain films and C T are the investigations of choice. 2 3 6 The accuracy of CT scanning in differentiating RPA from cellulitis was 74 percent with a false positive rate of 1 2 percent.237 , 2 3 8, 2 39 [Grade D ] Transoral needle biopsy may b e sufficient t o obtain diagnostic material for microbiological confirmation of TB.
Cl i n ica l featu res
In young children, suggestive features in the history include neck stiffness associated with fever, irritability, dysphagia, airways obstruction and, on examination, the posterior pharyngeal wall bulges forward although this clinical sign is easily missed. The diagnosis of RPA in infants and young children is easily overlooked and should be considered in the differential diagnosis of fever and irritability, in particular, when lumbar puncture results are normaL 228 A recent case of a neonate pre senting with stridor due to a RPA has been described229 as well as one happening in conjunction with a branchial cleft sinus.23o In adults, there may be few symptoms and little to find on examination. A history of previous TB contact, pharyngeal trauma by fish or chicken bone, dental problems and intravenous drug abuse must be specifically sought. Pain occurs at a relatively late stage and may be associated with fever. Neurological signs may develop due to cord compression. There may be bulging of the posterior pharyngeal wall on examination. There is usually nothing to feel in the neck unless the abscess is huge. [HI*] D ifferenti a l d i ag nosis
The following have been described as lesions in the retropharyngeal space: nasopharyngeal carcinoma,23 1 lipoma, malignant schwannoma, sarcoidosis, aberrant internal carotid artery, internal carotid artery pseudo aneurysm,232 Forestiers disease, Kawasaki disease and haematoma following whiplash injury. 233 Appropriate preoperative imaging with CT or MRI and transoral diagnostic biopsy is, therefore, recommended. 234 [H] From a symptom point of view, acute epiglottitis is the most important differential diagnosis in children.23 5 I nvesti gations
In adults, plain lateral films in flexion and extension show loss of normal curvature of the cervical spine with a soft
L-
Treatment
Surgical drainage is the norm in paediatric RPAs, probably because of the significant incidence of airway compromise at presentation (29 percent).23 7 In a retro spective series of 2 1 patients, 70 percent were drained transorally, 20 percent via an external cervical approach and 10 percent required a combined approach to provide adequate treatment. In a survey of the membership of the American Society of Pediatric Otolaryngologists 5 1 percent o f respondents indicated that 20-40 percent of RPA may resolve with antibiotics alone.23 6 [Grade D] Two recent reviews show that up to 75 percent of children with retropharyngeal abscesses respond to intravenous anti biotics. 240 Abscess recurrence may happen even after surgical drainage and should be considered in cases of clinical deterioration. Surgical drainage of adult post-traumatic abscesses may require endoscopy to remove the foreign body as well as drainage. Occasionally, the abscess does not develop until after removal of the foreign body. [Grade D ] Surgical drainage o f tuberculous RPA i s not usually necessary although, occasionally, neck exploration is required to obtain biopsy material in order to make a diagnosis. This can be carried out through a cervical incision with an approach in front of and medial to the carotid sheath. [Grade D] A series of ten patients showed an excellent outcome from early aggressive management with transoral decompression, occipitocervical fusion, as well as triple anti -TB therapy for 1 5 months. This allows for immediate neurological improvement, stability and early mobilization.222, 23 8 In patients with minor functional neurological deficits conservative neck stabilization is adopted. In patients with severe deficits, due to significant cervicomedullary compression caused by atlantoaxial dislocation or bone destruction, anterior decompression and posterior fusion is performed. Those patients with persistent reducible atlantoaxial dislocation undergo direct poster ior fusion. With this regimen a significant improvement is possible with judicious use of surgical options.222 [Grade C]
2002
I PART 1 5 THE U PPER D I G ESTIVE TRACT
Co m p l icati ons
./' Compl ications include mediastinitis, oto rrhoea, m e n i n g i tis spinal e p i d u ra l abscess, oste o mye l itis, ,
Complications, •
•
•
•
•
•
•
•
as
listed below are all level
3
Lemierre syn d rome, acute s u p p u rative thyroid itis a n d
evidence.
Mediastinitis is a well-described b ut rare complication of paediatric RPA. This condition, as well as the primary RPA, is usually managed surgically b ut successful conservative management of mediastinitis secondary to an RPA has been described.238 Otorrhoea from lateral extension of a parapharyngeal abscess has been described. 239 Spinal epidural abscesses have occasionally been described as a complication of RPAs in the absence of cervical TB and may be asso ciated with a poor prognosis. Lemierre sydrome, a severe systemic fusobacterial infection secondary usually to oropharyngeal infection b ut occasionally mastoiditis, resulting in internal jugular vein thromboplebitis, septicaemia with septic emboli spreading to metastatic sites. Osteomyelitis of the odontoid process associated with meningitis. Acute suppurative thyroiditis has been described following a p ost-traumatic RPA due to an ingested bone. Purulent meningitis has been described as a complication of adult RPA after treatment of odontogenic infection. 40 Twelfth nerve palsy. 2
twelfth n e rve pa lsy.
S PECI FI C VI RAL PHARYN G ITIS I nfect i o us m o n o n u c l eosis This is a common, acute, systemic viral infection presenting typically with sore throat and lymphadeno pathy, hence the name glandular fever due to the EBV, one of six human herpes viruses isolated from blood, lymph nodes and saliva.
EPI 0 EM I OLOGY
Infectio us mononucleosis is primarily a disease of young adults b ut can present in early childhood and older age groups. Transmission is via saliva, which has been demonstrated in volunteers, and it has thus been described as the kissing disease. Individuals with the antibody to the viral capsid antigen will not usually develop the disease. One case of recurrent infectious mononucleosis with persistent splenomegaly in the absence of immunodeficiency has been reported. The incubation period is normally five to seven weeks.
KEY PO I NTS CLIN ICA L FEATU RES •
RPAs
are usually due to supp u ra t ing
re:t ropharyngeal nodes in young children,
trauma rdated t o i nstru m en tation, fo reign bodies or, more ra rely, to TB of the cervical spine. • The most common orga nism is S. viridans alt hough Gram negatives are becom i ng i ncreasi ngly frequent. • Cl inic ally, the characterist ic forward bulging o f the posterior pharyngeal wan can be difficuh to recogn ize and in children . , ... . differential dia gnosis tfo m �piglott itis is a ·.�!;; P riority. ,;
--�.� :::� :-�,--;..::....�.
I'
.
Best clinical practice ;/
I nve stiga t i ons
Include p l a i n fi l ms in fl exion a nd
exte nsion and CT sca n n i n g .
,/ Treatme n t usu a l ly i nvolves transora l d ra i n ag e because of the risks of a i rway co m pro m i s e
.
There is a prodrome of four to five days with malaise, fatigue and headache. The most common symptom is tender cervical adenopathy, usually accompanied by sore throat. Pharyngeal signs range from acute follicular tonsillitis indistinguishable from follicular tonsillitis, to a grey membrane lining the oropharynx, petechiae on the soft palate and sometimes a PTA, which can be bilateral. Occasionally, all the lymphoid tissue of Waldeyer's ring may enlarge and become covered with a membraneous slough, with significant risk of respiratory obstruction. Airway obstruction in infectious mononucleosis may be aggravated by herpes infection. Rare, head and neck manifestations include periorbital oedema, especially of the lower lids, and cranial nerve mono- and polyneuro pathies of which facial nerve weakness is the most common. Six cases of isolated clinical hypoglossal nerve palsy due to infectious mononucleosis have been described. Isolated oculomotor nerve palsy with inflam mation of the nerve on MRI has been reported. A clinical presentation of infectio us mononucleosis with facial palsy and a parotid mass, both of which resolved sponta neously, hctve been recorded in a child. Combined tongue and vocal cord palsy have been reported. [*]
Cha p ter 1 5 2 Acute a n d c h ro n i c pharyngeal i nfection I
2003
SYST E M I C M A N I FESTATI O N S OF E PSTE I N-BARR VI R U S
mononu cleosis and in none with acute tonsillitis. The
I N FECTI O N
white cell count may be normal
The systemic manifestations of EBV infection are summar ized
in Table
1 52.2. The oncological risks following EBV
related infectious mononucleosis include the following. •
in the first week but is
usually raised in the second. The common serological tests depend on development o f heterophile antibodies, the most useful being agglutinins to sheep and horse red cells, and these antibodies are the basis of the Paul
Hodgkin's disease.
Bunnell and monospot tests. Both of these are screening
•
Genome-positive Burkitt's lymphoma.
tests. The monosp ot has a sensitivity of
•
Lymphoproliferative disorders in
specificity of
immunocompromised patients.
o ccur in healthy controls as well as in a variety of
•
EBV is a cofactor for the development of
conditions including mumps, systemic lupus erythema
nasopharyngeal carcinoma.
tosus, Mediterranean spotted fever and diabetes sarcoi
•
86 percent and a 99 percent. False positive monospots can
Recent developments in molecular and
dosis. These tests are usually positive in the first week of
immunological diagnostic approaches have suggested
the disease altho ugh approximately
that EBV has a causative role in chronic active EBV
develop a positive test and this figure may be higher in
10 percent never
infection syndrome, EBV-related haemophagocytic
children. Serological tests
lymphohistiocytosis, EBV genome-positive T-cell
typical and atypical severe forms of infecti o us mon o
lymphoma, natural kille r celi leukaemia/lymphoma,
nucleosis. The gold standard includes serologic evidence
Hodgkin's disease and gastric carcinoma .
of
EBV-specific
cannot distinguish between
antibodies,
the
most
useful
being
immunoglobulin ( Ig) M antibo dy to EBV viral capsid antigen D I AG N O S I S
The diagnosis is made from the clinical picture, together with the finding of mononucleosis on the peripheral bloo d film. The two clinical conditions with a similar picture
are
CMV
infection
and
toxoplasmosis.
during
acute primary EBV infection.
mononucleosis
can
be
aided
by
<
1 0 and an aspartate aminotransferase
>
1 50 are at
significant risk of complications and should be carefully monitored.
The
differential diagnosis of acute pharyngotonsillits from infectio us
found
Female patients without tonsillitis, and a white cell co unt
flexible
TREATM ENT
nasendoscopy. Lymphoid tissue is present in the naso
Treatment is symptomatic for mild-to - m o derate cases,
92 percent of patients with infectious
but reports are beginning to appear of severe cases being
pharynx
of
Ta b l e 1 52 .2
Th e syste m i c m a n i festations of EBV I n fection.
Com mon
Rare
Pyrexia usua l ly a cco m pa n ies the severe form of the d isease
G ast ro i ntesti n a l : a cute a p p e n d i cit is. m ese nte ri c ade n i tis.
G e n e ra l ized lym p h a d e n opathy
G e n i tourinary: gen ita l u l ceration. i nte rstitial n e ph ritis
S p lenomeg a ly occu rs i n 50% of pat i e nts with occasi o na l reports
NS: G u i l l a i n-Barre syn d rome, m ening oe nceph a l i tis, mye litis
pseud oa p pe nd Ici ti s
of ru ptu re fo l l ow i n g b l u n t soft tiss u e tra u m a or s p l e n i c infarcts H e patome g a ly a nd j a u nd ice occu r in 100/0 of pati ents a nd l iver fu nction tests are fre q u e n tly a b n orma l
Chro n ic fatig ue syn d rome fo l l owing i n fectious mononucleosis w ith a pre m o rb i d h istory of poor physical fu ncti o n i n g being the main pred i ct ive factor. The risk of ch ronic fat i g ue syndro m e postg l a n d u l a r feve r has b e e n estimated from 9 to
2 2010 six m o nths after g l a n d ular fever compared w i th 0-6010 fo l l o w i n g a n o rd i na ry U RT infectio n . EBV virus i nfection may have a ro l e I n i n itiating m U lt i p l e scl erosis Ascites
CVS : myocard it is. infective endoca rd i tis. pericard i tis
R u be l l iform skin rash sometimes occurs and a l m ost i nvari a bly if
RS : p n e u m on itis, b i l ate ra l e m pye m a and mediast i n i tis
a m p i c i l l i n is p rescribed H a e m : severe auto i m m u n e h a e m olytic a na e m i a , h a e m o ph a g ocytic syndrome apl astic a na e m ia and thro m b ocyto p e n i a a n d com mon varia b l e i m m u ne defici e ncy U ne xpected deaths poss i b ly re l a te d to u pper a i rway obstruction
ats, cardiovascu lar system ; NS. nervous system ; RS, respiratory system .
..
2004 I PART
15
TH E U PPER D I G ESTIVE TRACT
effectively treated with antiviral agents such as famciclo vir. This may be increasingly justified for some of the high-risk complications and prolonged fatigue syn dromes. Several antiviral drugs inhibit EBV cell replica tion in vitro but are of limited use in vivo. Novel anti-EBV compounds such as maribavir may be useful in the treatment of acute EBV infections. Ampicillin-based antibiotics should be avoided be cause of the certainty of producing a rubelliform rash. Acute upper airway obstruction secondary to infec tious mononucleosis is an indication for steroid treat ment. For those who fail to respond to intravenous steroids, acute tonsillectomy may be indicated. Patients who develop upper airway obstruction seem to be more prone to developing later recurrent tonsillitis and acute tonsillectomy has the incidental benefit of avoiding this complication. Rarely, tracheostomy may be required if tonsillectomy fails to relieve airway obstruction. [**] [ Grade D ] The role o f corticosteroids i n managing complications other than upper airway obstruction is less clearly defined but there may be a role in immune-mediated anaemia, thrombocytopenia and interstitial nephritis. Recent evidence suggests that infusions of leukocyte associated antigen-matched EBV cytotoxic T cells may form a navel strategy for both prophylaxis and treatment of EBV-induced lymphoproliferative disorders. In addi tion, a vaccine based on immunization with a structural antigen is under evaluation. EBV-related aplastic anaemia has been treated with syngeneic blood stem cell transplantation. New immunotherapeutic approaches based on cytotoxic T cells are being developed, depending on the degree of EBV antigen expression in infected cells. Hopefully, these approaches will provide the impetus for cytotoxic T-cell vaccine development. Contact sports should be avoided for four to six weeks even in the absence of splenic enlargement because of the risks of splenic rupture. [*] [ Grade D]
meningoencephalitis. Sixty-four percent had atypical lymphocytosis, 90 percent had biochemical evidence of hepatocellular injury and 1 7 percent had evidence of immunological abnormalities. Ragnaud reported mono nucleosis in 9 1 percent and that pharyngitis is much less common in adult CMV than with adult EBV mono nucleosis. In children, CMV pharyngitis is more common than in adults. [**] H e rpes s i m p l ex 1
Type 1 herpes simplex infection primarily involves the oral cavity and oropharynx and usually affects young children, being less frequently found in the late teens and early twenties. It causes severe vesicular and ulcerative stoma titis of the lips, tongue, gums, buccal mucosa and, occasionally, the oropharynx. The oropharyngeal involve ment may be an isolated pharyngitis without ulceration or vesicles. Children are systemically unwell with pyrexia, tachycardia and cervical adenopathy. Diagnosis is usually clinically obvious, although it may be confused with Stevens-Johnson syndrome. The condition is infective and may be transmitted to staff. Occasionally, severe ulcerative pharyngitis may be due to type 2 herpes simplex infection contracted by heterosexual oro genital contact. In the virology laboratory virus from an unruptured vesicle can be identified using fluorescent antibody or be seen as intranuclear inclusions on scrapings. Secondary herpetic infection takes place when the herpes virus resides within the posterior root ganglion. Intercurrent illness then results in the appearance of herpetic vesicles, usually in the lips or the angle of the mouth, as a typical cold sore. The treatment is usually supportive with appropriate analgesics and fluids. Acyclovir is active against herpes virus but does not eradicate it. It is effective only if started at the onset of infection. H erpes zoster
Cyto m eg a l ovi rus i nfecti o n
In a recent French study on nonimmunocompromised adults, those with CMV infection presented with fever ( 95 percent) , constitutional symptoms (80 percent), joint and muscle aches (41 percent) , shivering (32 percent) , abdominal pain (26 percent) , nonproductive cough (20 percent) , cutaneous eruption (20 percent) and diarrhoea ( 10 percent) . Examination found hepatomegaly (25 percent), splenomegaly (23 percent), adenopathy ( 1 9 percent), pharyngitis ( 9 percent), jaundice ( 3 percent) and signs of meningeal irritation ( 1 percent) . Fifteen percent had a gastrointestinal form of disease (hepatitis, jaundice, colitis, antral gastritis or cholecystitis) , 7 percent a haematological form and less than 2 percent each had pericarditis, pneumonitis, thrombocytopenic pur pura, polymyalgia rheumatica, cutaneous vasculitis and
Herpes zoster is the virus that causes chickenpox. Herpes zoster pharyngitis probably arises from the reactivation of virus particles in the cranial nerve nuclei after a previous attack of chickenpox, thus it is analogous to shingles or cold sores. It can, though, also appear during an epidemic of chickenpox. In the pharynx, herpes zoster can materialize in the distribution of the Vth, IXth and Xth cranial nerves. It often occurs with herpes zoster oticus (Ramsey Hunt syndrome) . The pharyngeal features may be transient and can easily be overlooked. They may give rise to pain on swallowing, vesicles and shallow ulcers, which heal rapidly, may be seen on the soft and hard palate, tonsil or posterior pharyngeal wall. Treqtment with antivirals should be started within 72 hours of onset of the lesions. Acyclovir has been the drug of choice in the past, but newer drugs such as valacyclovir
Ch apter 1 52 Ac ute a n d chro n i c pharyngea l infe ct i on
and famciclovir are equally effective and
have mo re
•
Screening tests inc l u d e th� monospot and Paul D unneU tests, but both have fabe pos i tives rates. EBV IgM to viral capsid a ntigens are t he gold standard t"()r accurate diagnosis.
•
Treat ment is symptoma t ic in straigh l forward
convenient dosing regimens and decreased incidence of post-herpetic neuralgia. A single dose of gabapentin reduces acute pain associated with herpes zoster infection.
Herpes zost er vaccination markedly reduces the incidence an d morbidity of this condition as well as the likelihood
-
cases
o f developing post-herpetic neuralgia.
I 2005
but antiviral agents may be just ified i n
presence of systemic complications. Acute upper ainvays obst ruction is managed with
the
H a n d , foot a n d m outh d isease
i .v. steroids and. rarely, tonsillectomy and
This i s usually caused by en terovirus
Ampicillin should be avoided invariably causes a rubelliform rash.
t rach eostomy.
7 1 or Coxsackie
as
it
vi ruses, b ut untypeable en teroviruses and mixed cultures may also be responsible. It is characterized by a vesicula r er uption in
the oral cavity and o ropharynx ca using
d ysphagia and dehydration, accompanied by vesicles on the hands and feet. It is nonnally accompanied by pyrexia malaise and vomiting. The illness is sh ort-lived and
VES I CU LAR A N D BU LLO U S ERU PTI O N S OF TH E PHARYNX
mainly affects young children but has been associated with mortality, for example in the
1 998 epidemic i n lead
Taiwan. Fulminant enteroviurus 7 1 infection may
to severe neurological complications, acute pulmonary embolus
and
cardiopulmonary decompensation.
Age
There are two types. • •
attendance.
as
have
larger
Hospital
families
admission,
and
careful
)
pemphigoid. These latter
kindergarten staging
Inflammatory: Steven-Johnson syn d ro me benign
mucous membrane pemph igus, pemphigus and
younger than three years has been associated with higher mortality
Viral: herpangina, herpes zoster, herpes simp lex.
conditions only rarely
involve the oropharynx wi tho ut the o ral cavity.
a nd
stage-based management reduces the fatality rate in those with cardiac complications. Initial investigations include stool cultures and a white blood cell co u nt. Currently, hand,
foot and mouth disease
is
not susceptible to
antiviral agents or vaccina tion and preve ntion of out
breaks in high-risk areas requires high -level su rveill a n ce and p ublic health interventions.
[**]
TO N S I L PLU G S A N D PSEU DOCYSTS Tonsil debris may accumulate in the tonsilla r crypts and, in particular, in the s upratonsillar cleft, and are referred to as tonsillar plugs. The patient may notice the accumula tio n, express it or seek surgical removal. The debris is of no significance except as
an
occasional possible cause of
halitosis or nasty taste in the mo uth a n d sho uld , on the
H e rpa n g i na
whole, be ignored. This is a self-limiting vesicular eruption that occurs in the oropharynx and a number of e nteroviruses
(30 and 7 1 )
and Coxsackievirus group A have been im pl icated. Its regular spread to the oropha rynx distingu ishes it from herpes simplex type 1 infection .
:K EY POI NTS
Accumulation of debris in a crypt may form a tonsillar pseudocyst resulting in a crea m-colou red epithelium covered lesion which likewise be
can
regress spontaneo usly and
ignored. Sometimes patients may become
extremely distressed by them, in which case tonsillectomy may be a reasonable o ption.
U N I LATERAL TO NSI LLAR E N LA RG E M E NT The concern about unilateral tonsillar enlargement is the
I nfectio u s mononucleos is •
•
Pharyngea l signs of EBV i n fection are d i ni(any i n d istu,lguishable from follicular t o nsillitis and even PTAs may occur as a complication. Ex"tensivc involvem�nt of Wa:l:deycr's ring may result in up p e r a irways obst ruction. Rare pr�.scntations i n cl u d e periorhirt a] oedema and diverse cranial Rolyncuropathics.
possibility of missing tonsillar mal ign ancy. The problem can be divided into •
the fo llowing categories.
Asymmetrical adult tonsil with normal mucosa in the absence of cervical adenopathy and approximately
7 percent risk of malignancy, prima rily B - cell 0.35 percent risk
lymphoma. This compares with
in
all tonsils and no mal ignancy in to nsils in which asymmetry was not noted. To nsillar asymetry on its own in the absence of other suspicious features does
2006 I
•
•
•
•
PART 1 5 TH E U PPER D I G ESTIVE TRACT
not indicate malignancy. Very rarely, isolated asymmetry of adult tonsils may be the only feature of sarcoidosis. Unilateral tonsillar enlargement in children in the absence of other suspicious clinical features, especially rapid tonsillar enlargement (within six weeks) , dysphagia o r night sweats, evidence o f immunocompromise, lymphadenopathy, hepatosplenomegaly, history of previous malignancy or persistent acute tonsillitis with failure to respond to medical treatment, does not appear to warrant tonsillectomy. Asymmetrical adult tonsil with mucosal abnormality and or cervical adenopathy has a very high risk of malignancy, mainly sec with asymmetry being the strongest predictor there. Fine needle aspiration may be helpful in this context. Rare tonsil tumours presenting with unilateral tonsillar enlargement including extramedullary plasmacytomas, Hodgkin's disease, leukaemia and metastatic deposits. Infective causes presenting as unilateral tonsillar enlargement including invasive candidiasis and actinomycosis of the tonsil.
When considering the problem of unilateral tonsillar enlargement the differential diagnosis may include PTA and any parapharyngeal space mass pushing the tonsil medially.
U LCERATION O F TH E TO N S I L
The differential diagnostic possibilities o f tonsil ulceration are interesting, but most can be excluded on history and so the main investigation is biopsy to determine the type of malignancy. The differential diagnostic possibilities are: •
•
• •
neoplastic: squamous carcinoma, minor salivary gland tumours, e.g. adenoid cystic, mucoepidermoid, lymphoma and, rarely, melanoma and myeloma; infection; acute: acute streptococcal tonsillitis, PTA, acute diptheria, EBV and CMV mononucleosis and Vincent's angina; chronic: syphilis, TB and acquired immune deficiency syndrome (AIDS) ; blood diseases: agranulocytosis, leukaemia; miscellaneous: aphthous ulceration, Beh'ret's syndrome, colloidal bismuth sub citrate intoxication presenting with acute renal failure, pemphigus vulgaris.
O E D E MA O F TH E UVU LA
Oedema of the uvula is unusual without an obvious precipitating cause. The patient complains of an onset
of a tickle or irritation in the throat together with a sensation of gagging. Examination shows oedema of the uvula. The causes may include: •
inhaled or ingested allergen, e.g. sesame seeds; irritation: maraijuana inhalation or intranasal cocaine consumption; • trauma: foreign bodies, surgery or endotracheal intubation, nasogastic tube placement, angina bullosa haemorrhagica; • infection: - acute: PTA, viral pharyngitis and candidiasis; - chronic: syphilis and TB; • tumours: see; • radiotherapy; • allergic angioneurotic diseases; . OSA; • severe pre-eclampsia; • blood diseases: agranulocytosis, acute leukaemia; • miscellaneous: aphthous ulceration and Beh'ret's syndrome. •
In the absence of an obvious cause, treatment mainly consists of antihistamines, steroids and antibiotics or specific treatment for hereditary angioneurotic oedema. The clinician must always bear in mind the potential seriousness of this condition as a cause of upper airway obstruction. Rarely, uvulectomy has been used to manage upper airway obstruction.
N O N S PECI FIC CH RO N I C PHARYN G ITI S
This is a common clinical diagnosis and relies on a history of long-standing throat discomfort of variable severity without any evidence of specific aetiological factors, with often little to find on clinical examination apart from prominent lymphoid tissue, especially lateral pharyngeal bands. Possible aetiological factors include: •
heavy smoking, including passive smoking; industrial/occupational irritants; • chronic sinusitis with post-nasal drip; • acid reflux; • poor dental hygiene; • psychological stress; • chlamydia pneumonia infection; • indoor secondary heating sources (which emit N0 2 and S0 ) . 2 Exclusion o f malignancy is the most important aspect of managing these patients. This requires a careful history, in particular, enquiring about localized pain to one side and earache, progressive dysphagia, or weight loss and careful p hysical examination of the whole upper aero digestive tract with a nasendoscope and otoscopy. Direct examination of the oral cavity and oropharynx, paying special attention to the tongue, floor of the mouth, •
Ch apter 1 52
bucco-alveolar sulcus region and manual palpation of the tongue including its base, is required. Finally, the neck must be carefully palpated to exclude lymph node metastases. Usually this is sufficient to exclude malig nancy in the absence of unexplained otalgia or progressive dysphagia but, occasionally, further investigations, mainly rigid panendoscopy under general anaesthetic to take biopsies, may be required. If physical examination bears out evidence of post nasal drip or significant acid reflux, both should be treated appropriately with intranasal steroids and proton pump inhibitors although there is little documentation to support this practice. One recent ReT from the USA suggested that proton pump inhibitors provided no benefit over lifestyle changes. Strong advice is given about cutting out smoking and alcohol if these are involved and an appropriate dental referral may need to be initiated. In those patients where stress is deemed to be a significant factor, neck and throat muscle relaxation therapies are deemed to be beneficiaL A large variety of nonspecific remedies has been used, such as gargles, antiseptic and analgesic throat spray, with no well-defined benefits. Surgery is of no demonstrable help in this situation and operations to remove excess extratonsillar lymphoid tissue are of no proven benefit.
SPECI FI C CH RO N I C PHARYN G ITIS
Acute a n d chronic pharyngea l i nfection I 2007
contagious. It is, therefore, very important to consider the possibility of primary syphilis in atypical oral or oropharyngeal ulceration. Secondary syphilis usually occurs several weeks (four to six) after the primary lesion and about 30 percent of patients at this stage will have a healing chancre. The features of the second stage are fever, headache, malaise, generalized lymphadenopathy, mucocutaneous rash and sore throat. The pharynx and soft palate display hyper aemia and inflammation and there may be lesions, which have been described as mucous patches or 'snail track' ulcers. The lesions are more commonly seen in the oral cavity than the oropharynx and are ulcerated lesions covered with a greyish white membrane, which when scraped off has a pink base with no bleeding. The secondary stage of the disease lasts a few weeks and, again, the lesions in the mouth and pharynx are infectious. About 30 percent of cases will go on to develop the tertiary stage. Tertiary syphilis develops 5-25 years after the initial infection and is characterized by lesions that may be widespread throughout the body or restricted to one or two organ systems. In the URT they are due to gumma. This is a granulomatous necrotic lesion that begins as a nodule and then breaks down to form an ulcer. It can arise in the hard palate, nasal septum, tonsil, posterior pharyngeal wall or larynx. The gumma, whether ulcerated or not, is typically painless. There is usually no lymphadenopathy unless the lesions are secondarily infected. When treated with penicillin the gumma will rapidly heaL
Syph i l i s DIAGNOSIS
This i s an infection by the spirochaete Treponema pallidum and, apart from the congenital form, is acquired by sexual intercourse. The disease progresses through primary, secondary and tertiary stages with the secondary stage being most likely to give rise to pharyngeal symptoms. The condition may present with almost any symptom in any organ system. The lesion of primary syphilis is at the site of initial inoculation and the organism can penetrate both normal and mucosal abrasions. After a decade of unprecedented decline in the 1 990s, the worldwide incidence of syphilis has been rising since 2000, mainly among HIV-positive men. This has been well-documented in the UK. Those patients immunocompromised by HIV h�ve a higher likelihood of developing neurosyphilis. In primary syphilis, the lesion is the chancre, which develops after an incubation period of 2 1 days. The most frequent extragenital sites for the chancre are lips, tongue, buccal mucosa and tonsiL The lesion begins as a papule that breaks down to form a painless ulcer with indurated margins. At the same time there may be non-tender uni or bilateral cervical lymphadenopathy. Secondary infec tion of the classically painless ulcer can result in pain. The ulcer usually persists for two to six weeks and then heals spontaneously, often despite inappropriate treatment. While the primary lesion is present the patient is highly
In the primary or secondary stage of the disease, spirochaetes can be identified by darkfield illumination microscopy in smears taken directly from the lesion. The spirochaetes can also be identified in biopsy specimens using silver stains or fluorescent-labelled antibody. Biopsy of a tertiary lesion provides a typical histopathological picture. Serological tests for syphilis fall into two main groups: those used to identify nonspecific antibodies to cardiolipin Venereal Disease Research Laboratory (VDRL) tests and those to detect specific treponemal antibodies ( T. pallidum immobilization (TPI) and fluorescent treponemal antibody (FTA) ) . The VDRL tests use a n antigen extracted from beef heart in a slide flocculation test. The VDRL reaction starts to become positive during the first or second week after the development of the chancre and 99 percent of patients with secondary syphilis have a positive reaction. A number of conditions give false positives for this test: • •
•
•
other treponemal infections: yaws, bejel or pinta; other nontreponemal infections: atypical pneumonia, malaria, smallpox and leprosy; immunological disorders: systemic lupus erythematosus, rheumatoid arthritis; old age (occasionally) .
_I
2008 I
PART 1 5 TH E LI PPER D I G ESTIVE TRACT
Synthetic VDRL reagents have been developed that will improve the sensitivity and stability of this test. Of the tests for specific antibody, TPI is the most specific but also the most expensive. It depends upon the ability of an antibody in the patient's serum to immobilize spirochaetes which are observed by darkfield illumination. The TPI test is 1 00 percent positive in patients with established secondary and tertiary syphilis and, if carried out correctly, is entirely specific. The FTA test involves the absorption from the patient's serum of cross-reacting antibodies using nonpathogenic treponemes and then the absorption of specific antibody by dried T. pallidum preparations. The absorbed antibody is identified by a fluorescein-labelled antihuman gamma globulin. The FTA test is positive in all patients with secondary and tertiary syphilis and the false positive rate is not as high as the VDRL reaction. Occasionally, patients with systemic lupus erythematosus and rheumatoid arthritis will have a positive result. Two rapid enzyme immune assay techniques, the Enzywell TP and the Syphilis ICE enzyme immunoassay (EIA) , have been developed. They have sensitivities and specificities greater than 99 percent and also diagnose previously treated syphilis in patients who are HIV positive. Both are significantly more sensitive than the FTA but not the TPI test. A new multiparametric assay for confirmation of the diagnosis of syphilis has been described. The availability of increasing numbers of EIA for detecting syphilis antibodies has led to a re-evaluation of the whole testing philosophy. Treponemal EIAs are an appropriate alternative to VDRL, rapid plasma reagin and treponemal haemagglutination (TPHA) tests for syphilis. If a treponemal EIA is used for screening an alternative treponemal test, such as TPHA, should be used to confirm the test. The FTA test is probably best left for specimens giving discrepant results.
TREATMENT
Penicillin is the treatment of choice, with 2.4 mega units i.m. in single or divided doses, being the standard for primary and secondary syphilis. In tertiary syphilis, 7.2 mega units in divided doses of 2.4 mega units at 7- to 14-day intervals is recommended. Azithromycin and ceftriaxone should gain more definitive roles in the future.24 1 Full details of treatment regimens can be obtained from the detailed guidelines on the management of early and late syphilis.
Tubercu l os i s
The pharynx i s not a common site for clinically manifest TB; however, it is the site of primary infection almost always in children and results in an asymptomatic
primary focus in the pharynx ( usually tonsil or adenoid) with cervical lymphadenopathy. Secondary TB affects the pharynx, but only in patients with massive positive and usually cavitating pulmonary TB. This is in contrast to laryngeal TB in which lesions do occur with low-grade or inactive pulmonary disease. The pharyngeal lesions are secondary to coughing up heavily infected sputum and consist of multiple, painful shallow ulcers in the pharynx or oral cavity. Occasionally, the pharynx is involved in patients with widespread military TB and here the lesions may be from blood-borne as well as sputum-borne dissemination of disease. Lupus vulgaris is a low-grade cutaneous form of TB and has been described in the nasal cavities and in the pharynx. Tuberculous otitis media is probably a blood-borne dissemination of the disease but, on occasion, can result from pharyngeal disease by spread from the Eustachian tube. The resurgence of TB has closely paralled the epidemic caused by HIV. In both the USA and Africa, the areas with the highest rates of HIV infection and high-risk groups, such as intravenous drug abusers, are those that have sustained the highest increase in TB. Poverty, over crowding and homelessness are the socioeconomic factors common to co-infection with both. HIV-infected in dividuals are at risk of reactivation of previous TB and to rapid progression of acquired infection. The presentation is often atypical and an increase in extrapulmonary TB has been demonstrated. The diagnosis is usually clear because of the associa tion with pulmonary disease, both clinically and radiologically, although pharyngeal SCC with pulmonary metastases is the obvious differential. Microscopic examination of stained smears for acid-fast bacilli is still one of the most useful tests for the initial diagnosis of TB. Although less sensitive and specific than cul ture the sensitivity can be greatly improved by using phenol auramine stain as compared with the older Ziehl Nielsen technique. Semi-automated and continuous monitoring systems developed specifically for the isola tion of mycobacteria include enzyme-linked immuno sorbent assay (ELISA) tests to detect antigens and polymerase chain reactions (PCR) to detect genetic elements. Pharyngeal TB requires no special treatment. It will, in principle, be treated at the same time as the pulmonary disease with triple therapy, usually isoniazid, rifampicin and pyrizinamide as first-line drugs. All cases should be treated in association with an interested specialist. Drug resistance (DR) worsens outcomes and may have significant cost implications. Multiple drug resistance (MDR) is found globally. Management relies upon treatment with at least three drugs to which the isolate is susceptible. Directly observed treatment strategy should be used in adults and children where there is a significant risk of ' noncompliance and is vital to cut down transmission of disease in the community. In TB cases
Ch a pter 1 52 Acute a n d chro n i c pha ryngeal i n fecti o n
I 2009
with MDR, stand ard regimens result in unacceptably high
In imm u n o co mpetent h umans, acquired toxoplasmo
(26. 1 p ercent ) . Fo r all o ther drug- resistant
sis usually gives rise to no symptoms. Some patients
failure rates fonn s
of TB,
rifampicin-based
sh ort-co u rse
ch emo
h ave a
sore throat with
malaise,
fever and
cervical
will present with
therapy p rovides satisfactory res ults. To prevent develop
adenopathy and. on occasion , a patient
ment of drug resistance, the proportio n of defa u l t ers must
cervical lymphadenopathy o nly. Th e fever and ma laise
be decreased, prevention and control st rategies end o rsed
may last fo r several weeks and many o rgan system s, such
by the Wo rld Health Organiza tio n
( WH O ) , a nd the
as lungs, skin, liver, spleen, myo cardium, pericardium,
Lung
liver, brain, eyes and skeletal muscles, may be involved .
Disease m ust be implemented nat ionwide. The errors
The d isease is usually self-limiting; rarely, symptoms
International
Union
Against
Tu bercu losis
DR
and
a re inappro p riate
persist for many years due to chronic active infection,
regimens, nonadherence to therapy by patients, the sale
bu t death is most unusual. The differential diagnosis
and availability o f over-the-co unter drugs, an interr u p
is u sua l ly from other glandular fever-type syndromes.
tion in the drug supply a n d t h e unavailability o f free
Eye disease presents as isolated retinocho ro iditis with
that lead to the development of
diagnosis
and
treatment.
organisms are spread in
As
a
result,
d rug-resista nt
the
community,
generating
little system ic or immunological response. Transplacental infection o ccurs in approximately 45 percent of women
secondary cases with primary DR, which i n t u r n can
wh o
spread and generate further cases. The uni nterrupted
effects range fro m subclinical infection to intrauterine
acq uire
toxoplasmosis
Damage
to
the
d uring
central
pregnan cy.
nervous
The
cycle of creation and circulation is responsible fo r the
d eath.
increases in DR. According to global data on anti-TB D R
retino choro iditis are the most common nonfatal affec
system
and
appearing i n the W H O mono graphs, DR i s so ubiqu itous
tio ns. Only
as to be enco untered in every co u ntry. Anti-TB DR
have cli nically apparent disease at birth but most
1 0-20 percent o f co ngenitally in fected infants will
among previously treated cases was fo und to be very h ig h
develop some sequelae in l ater life,
in some countries b u t remained relatively l o w i n others.
retino choroiditis.
most commonly
in a high propo rtio n o f patients
Toxoplasmosis in people with impaired immunity
prescribed pyrizinamide. Tuberculosis can be co ntro l led
has been docu men ted in association with cancer, organ
if appropriate policies are fo llowed, effective clin ical and
transplantat io n,
p ublic health management is ensured, and th ere a re
infecti o n . Pat ients with such conditions are more likely
Hepatotoxicity o ccu rred
connective tissue disorders
and
H IV
committed and coordinated efforts fro m within and
to experience reactivation of latent disease th an to acquire
outside the health sector. However, in the context o f an
new infections . Encephalitis and space-occupying l esions
epidemic o f AIDS, the incidence o f TB wil l inevitably rise. By
200 1 , less than 3 0 percent of global TB cases were
reported to have received effective diagnosis, t reatment
in
the brain may develop and, if untreated, rapidly
progress to d issem inated infection. A dye test fo r the serological diagnosis of toxoplas
and monitoring. Rapid expansion of effective TB contro l
m osis was d escribed in
services is urgently required to avert the continued high
fo rm. re ma ins the gold standard although fo r diagnostic
burden o f mo rbidity and mo rtality from TB and its e ffects
pu rposes it is restricted on grou nds of cos t to reference
o n the
HIV
pandemic.
1 948. This test, in modified
la bora to ries. Several t ests for specific antibody classes h a ve been developed and used for diagn ostic as well as epidemiological purposes. Lymph node biopsy, which
Toxo p l a s m osis
reveals follicular hyperplasia and typical epithelioid cells, is sometimes carried ou t to confirm the diagnosis. and
Treatment is usually unnecessary b ut in those in
Toxop lasma gondii
d ivid uals with severe systemic upset or im muno deficiency
that was first described in 1 908. The parasite has three
a co m bina tion of pyrimethamine a nd sulphadiazine is
Toxoplasmo sis
is
a
common
disease
mam mals caused by a protozoan called
of
birds
stages in its life cycle: tachyzoite, oocyst and tiss ue cyst.
ind icated, however, these are associated with significant
The i n fection can be transmitted to humans (zoonosis) by
side
the ingestion of cysts or food contamination with anim al
azithrimycin with simil ar effi cacy but fewer side effects
effe cts .
A
co mbinati o n
o f pyrimeth amine
and
faeces, the incorporation of tissue cysts or tachyzoites
has been used fo r sight- threatening o cular toxoplasmosis.
fro m transplanted organs or blood pro ducts fro m other
A twice weekly, 25 mg pyrimet hami ne/SaO mg sulphadox
h u m ans with acute or latent toxo plasmosis, and trans
in co mbination is used as effective p rophylaxis against encep hali t is
and
Pneum o cys tis
carinii
placental transmission from a mother who is acutely
toxo p lasmosis
infected . Abo ut 750 cases of toxoplasmosis occur annually
pneu monia in patients with advanced H IV infection. In
in the UK with a mean age of 30 years. The number
an e ffort to mini m ize side effects, considerable work is
of
ongo ing to develop new d rugs or drug combinations for
cases
rises
predom inating
evenly
from
adolescence
with
males
up to the age of 20 b ut after this age
-females p revail. The age distribution has risen over the
the
treatment
of
severe
sym p to m a tic
toxo plasmosis .
Early st udies s u ggest that macrolides and fluoroquino
1 9 80s. There is no lo nger a ny seasonal o r geographical
lones are possibly effective. A Co chrane review demon
distrib utio n .
strated a lack o f evid ence fo r routine treatment o f the
J
_ • .. . . . .
_._.
20 10 I
PART 1 5 TH E U PPER D I G ESTIVE TRACT
acute form of toxoplasma retinochoroiditis but weak evidence for treating chronic disease.
Lep rosy
Leprosy is a rare condition in the UK, with fewer than ten cases per year notified in the 1 990s. No definite cases of indigenously acquired leprosy have been reported since the disease became notifiable. Leprosy has been eradicated from northern Europe, but the disease is still endemic in Brazil, India, central Africa and parts of South East Asia. It is a curable, chronic infectious disease caused by the bacillus Mycobacterium leprae that mainly affects the skin and peripheral nerves but also the respiratory mucosa and eyes. Leprosy affects all ages and both sexes. It is still a stigmatizing disease and yet, despite its reputation, is not a highly infectious disease. Prolonged contact with an untreated person suffering from an infectious form and an inherent immunological susceptibility in the exposed person are normally required for transmission to take place. Leprosy usually begins as an anaesthetized area in a hypopigmented skin lesion that can arise anywhere within the body. Nerves and joints in proximity of such skin lesions become swollen and affected. The spectrum of disease that then develops depends upon the degree of cell-mediated immune response mounted by the host. If there is a vigorous host response tuberculoid leprosy, which is not infectious and clinically must contain less than five skin lesions, results. Borderline leprosy can progress to lepromatous leprosy with numerous skin lesions and which is infectious. Tuberculoid leprosy requires a short course of treatment (six months) and lepromatous leprosy requires treatment for up to two years. In the majority of patients the disease progresses without deformity or other serious effects. In a few p atients involved nerves become damaged, leading to loss of sensation and function with increased risk of trauma and infection, reduced circulation and muscle loss and, ultimately, limb deformity and disability. Early detection and correct treatment can avert the serious and irreversible effects of leprosy. Isolated leprosy of the pharynx does not occur. It spreads to the naso- and occasionally oropharynx from the nasal cavities. Lepro matous leprosy can affect the pharynx and gives rise to a combination of granulomatous lesions ulcerating and healing with fibrosis. The diagnosis is usually made by biopsy. Treatment is with chemotherapy, the single agent dapsone traditionally being used, but increasingly, alarming levels of resistance have developed. The Scientific Working Group on Chemotherapy of Leprosy controlled clinical trials of combined previously untreated lepromatous leprosy demonstrated that after treatment by one of several combined drug regimens, all of which included rifampicin, persisting M. leprae comprised only
a tiny proportion of the total population of organisms harboured by the average patient. Daily, as opposed to monthly, administration of rifampicin was not more therapeutically efficacious and carried greater risks of hepatotoxicity. During the trials it became apparent that persisting M. leprae does not pose as great a risk of relapse as was once believed. During multidrug therapy nerve function should be assessed regularly, and recent nerve function impairment, as well as drug reactions, should be treated with steroids. The expected recovery rate for nerve function impairment is 60 percent with steroid treatment. Bacillus Calmette Guerin (BCG) vaccination in childhood is helpful in p reventing the spread of leprosy. Chemoprophylaxis with dapsone and BCG provide protection for household contacts.
Scl e ro m a
This i s a chronic infective condition caused b y Klebsiella rhinoscleromatosis. The disease begins in the nose and only secondarily spreads to the pharynx where it produces granulomatous lesions and scarring.
Ca n d i d i asis Candida albicans is a fungus that is part of the flora of the oral cavity and oropharynx in 30 percent of normal individuals. In order for the organism to become pathogenic and symptomatic there must be some local or systemic change in the host. The p redisposing factors are listed in Table 1 52.3. Clinically, candidiasis may be asymptomatic or present with p ain and dysphagia. Examination reveals small white patches (pseudo membranous lesions) which when removed leave an erythematous ulcer or an erythematous lesion.
TREATM ENT
Candidiasis with local predisposing factors usually only responds well to local therapy, such as nyastatin drops or lozenges 100,000 units six hourly, and there is little risk of developing resistance. Candidiasis with systemic predisposing factors, in particular, with HIV infection, often requires systemic therapy although the increasing resistance of candida species to fluconazole is becoming a problem, especially in the HIV population. The evidence for p rophylactic use of fluconazole in the prevention of candida in HIV infection is good. Prophylaxis may also be warranted in patients who are expected to suffer prolonged neutro penia, fo; example those having bone marrow and solid organ transplants.
Chapter 1 52 Acute a n d c h ro n i c ph a ryng ea l i n fection I
Tab l e 1 52 . 3
Pred i sposi ng factors for ca n d i d i as i s
20 1 1
.
I. Loca l
: . 'S�S'temic disease and
or
immune comprdrtijS�§(:. "j'
� ' �(.
Loca l d i se a se : l i ch e n p l a n us, l e u kopla kia
Dia be tes m e l l itus
Syste m i c a n ti b i otics may change local o ra l flora suffi c i e ntly to
Lym p h o m a
"
.' - .
"
a l low overgrowth of ca ndida I m m u nosu pp ress i ve d ru g s
Radi othera py to the o ra l cavity a n d o ro p h a rynx
A I DS U su a l ly C. olbicons, bu t i nc re as i ng ly C. dubliniensis is be co m i n g t h e o p po rt u n isti c i nfective a g e nt
In patients with systemic risk factors o roph aryngeal
undetected. Although the number of births to HIV
candidiasis can spread to the oesophagus and, ultimately,
infected women has increased, the proportion of infants
in systemic candidiasis, which has a very poor prognosis with up to 60 percent mortality.
b o rn with HIV has d eclined significantly.
can result
In the
UK,
London, Brighton and Manchester are the
cities with the largest HIV-infected populations. Scotland differs from England and Wales in that
H IV a n d AI DS
cases ( rather than
3
28
p ercent of
percent) are related to intravenous
drug use.
2002
In
40 million people worldwide living whom 28.5 million were based in sub
there were
with HIV of
There were approxima tely diagno sed HIV infection in the
Saharan Africa. HIV is spreading in heavily populated
The diagnosis is o ften still mad e late i n the course o f the
areas such as India and China which until recently have
disease p ro gression.
had low levels of transmission. The HIV epidemic in the UK is similar to that in much of no rthern Europe
In the
UK
five health care workers have acquired HIV
through work-related incidents, one despite taking triple
while so uth-west Europe has experienced a much larger
drug post-exposure prophylaxis. A further
epidemic,
workers, some o riginally from the
especially
among
intraveno us
(IDUs) . A rapidly spreading epidemic,
drug
users
mainly
IDU
UK,
12
health care
who have worked
in high p revalence countries, were diagnosed in the
UK
associated, is taking place in Eastern Europe but does not
after acquiring HIV through needle-stick injury abroad.
UK.
Needle-stick injuries in health care workers tend to be
Paediatric HIV infection is also rising, with the maj o rity
much higher than passive surveillance records would
being infected vertically from mothers perinatally. In
suggest, ranging from
appear
to
have
impacted
significantly
on
the
15
developed co untries transmission rates vary fro m
20
to
1 000
health
care
14
to
839
workers
needle-stick inj uries p er
per
year.
Post-exposure
percent.
p rophylaxis
HIV continues to be associated with serious m orbidity,
following exposure to HIV to reduce the likelihood of
high costs of treatment and care, and significant mortality
seroconversion and is used in resp onse to o ccupational
even in low prevalence areas such as the
UK.
involves
the
use
of antiretroviral
drugs
New
exposure, particularly in health care workers travelling to
treatments, fo r example triple antiretroviral therapy, have
high-risk areas. It involves fo ur weeks o f antiretroviral
caused
therapy started as soon as p o ssible after exposure.
a
sustained
decline in HIV-associated
deaths
which with a rise in the nwnber of new diagnoses has
Antiretroviral resistance is becoming an issue and
resulted in a steep increase in patients requiring long
surveillance is complex. P rim ary and acquired antiretro
term treatment.
viral resistance rates reflect the relative usage of different
Men who have sex with other men remain the group in the
UK
antiretroviral drugs as well as the inherited genetic barrier
at highest risk of acquiring HIV, with evidence fo r
associated with individual drugs. HIV- l virus escapes
transmission continuing at a substantial rate. Seventy-one
relatively easily the selective pressure o f chronic drug
p ercent o f he te ro sexually a c qu ired H IV in fec ti on diag nosed in the UK in 200 1 was in people from Africa o r was
exposure, an d different classes and individual types of
associated with exposure there. Although the po tential
This
still exists for HIV transmissio n through injecting drugs,
to
there is no evidence for significant current HIV spread
long as possible. The recent development o f new drugs,
among
IDUs in
propo rti on
h· i .
1 3,000 p eople with un UK at the end of 200 1 .
the
UK.
of maternal
Despite the
HIV
infections
fact that the detected
in
antiretroviral drugs lead to resistance at different rates.
in
info rm atio n
needs
to
minimize resistance in particular,
boosted
be
taken
advantage
protease
inhibit o rs
pregnancy has increased (particularly in Londo n ) , pre
therapeutic doxorubicin
mother to
P-glycoprotein DR in AID S-related lymphoma.
in women whose HIV infection is
can
limit
the development of resistance. Modifications of chem o
ventable HIV infection is still being transmitted from child
of
individual patients for as
agents, in
such
as
liposomal
CHOP regimens, seem
encapsulated to
overcome
2012
1
• PART 1 5 TH E U P PER D I G ESTIVE TRACT
presentations, herpes simplex infections and oral
Pharyngeal and other head and neck manifestations of HIV infectio n are listed in
Table 1 52.4.
histoplasmosis; •
TU M O U RS OF TH E H EAD AND NE C K The
most
frequent
non-AIDS
defining
cancers
are
primary skin malignancies including melanoma, basal and SCCS. Risk factors included age greater than 40 years, longer duration of HN infection and opportunistic
infection.
antiretroviral therapy
The
use
of
a history of highly
active
is protective. Aerodigestive tract
(lung and head and neck) malignancies are becoming
AID S-defining dementia;
•
progressive multifocal leukoencephalopathy;
•
wasting.
The
type
of AID S - defining
illness
is
an
important
determinant of survival, for example encephalopathy and wasting are asso ciated with median survivals of less than three months, while others, for example extrapul monary TB and herpes simplex infection, are associated with median survival greater than two years .
increasingly common with continued improvements in HIV therapy. These neoplasms are associated with a younger age at diagnosis, cigarette smoking, advanced stage
at
presentation
and
more
aggressive
clinical
course. The reasons for this are not clear. Although these neoplasms are not AIDS defining, factors that may contribute to risk include HIV-related immuno suppression and co-infectio n with high-risk papilloma subtypes.
PRI MARY H IV I N FE CT I O N/A CUTE SERO C ONVERS I O N I LLN ESS Primary HIV can be asymptomatic or result in severe symptomatic illness. Common symptoms are pyrexia, pharyngitis, malaise, lethargy, maculopapular rash, mu cous membrane ulceration, cervical lymphadenopathy and headache. Non-head and neck manifestations of primary HIV infection might include gastrointestinal tract transit disturbances, weight loss, anorexia, abdom inal pain, myalgia arthralgia and neurological features.
AI DS DEFI N I NG H EAD A N D N ECK PRES ENTATI O N S AID S defining head and neck p resentations include:
The differential diagnosis is with glandular fever-type syndromes. A careful sexual history may provide a clue. It can be diagnosed by virology testing (HIV- l RNA level
5 0,000
•
Kaposi's sarcoma (KS ) ;
>
•
no n-Ho dgkin's lymphoma;
antibo dies (ELISA and confirmatory Western blot anti
•
opportunistic infections involving head and neck sites
body
including TB due to
complex
influenced by the severity of the symptoms in primary
in non-TB en demic areas a nd CMV, toxoplasmosis,
HIV infection , the duration of illness, the presence of
Mycobacterium avium
Cryptococcus neoformans with
Ta b l e 1 52 .4
;
neurological
copies/mL)
testing) .
in
the
Progression
absence to
of HIV-specific
late-stage
disease
is
neurological symptoms and that of oral candidiasis.
Pha ryngeal a nd other head a n d neck m a n ifesta tions of H IV i n fectio n .
Pha ryn gea l
Ot her head and neck
Acute seroconversion i l l n ess
O ra l cavity disease
O p po rtun istic infections, espec ially with
Sinonasal d isease. R h initis and rh inos i n u sitis a re extrem ely com mon. End osco pic s i n us s u rg ery can be helpfu l
candida O ra l hairy leu kop l a k i a
Cervical lympha denopathy m a i nly d u e to lym phoid hyperplasia b u t TB or fu ngal infection (cryptococcus or h i stoplasmosis) may be responsib l e. N eoplasms were least common a n d
i
Lym phoid tissue hyperp l asia, parti c u l a rly n the post-n asal s pa ce
i ncl uded N H L a n d SCC Sal ivary g l a nd disease : be n i g n Iym phoe p i th e l i a l cyst d i sease ; Iymphopro l i ferative swe l l i ngs may regress w i th a nti retroviral therapy, doxycyc l i n e sclerotherapy injection a n d low dose external beam rad i othera py
Neop lastic l esions
Paroti tis d u e to infecti o n of i n traparotid nodes with C MV a n d mycobacteria Diffuse CDS lym phocytosis syndro m e ; sa l iva ry stones N H L (natura l killer type) ; m a l i g n ant transform ation of ben i g n Iymphoepithelia l l esion i nto B cel l N H L; KS of i ntra pa rotid lym p h nodes Ea r d isease: Be l l 's pa lsy; sensori neu ra l heari ng possi bly related to a n tiretrov ira l thereapy ototoxici ty, and co nductive heari n g losses seconda ry to Eu stach ian tube obstru cti o n from l y m p h o i d hyperplasia o r chronic s u p p u rative otis media (CSO M) ; vesti b u l a r fa i l u re ; K S o f t h e external a u ditory meatus ; B-cell Iym poma o f the external a u d itory m eatu s ; CS O M with intracerebral com p l ications; re lapsing polychond riti s ; Pneumocystis carin ii i nfection causing a u ra l polyps
Chapter 1 52 Acute and chronic p h a ryngea l infection I 20 1 3
Currently, the experimental evidence is insufficient to recommend whether or not those diagnosed with primary HIV infection should routinely receive antiretroviral therapy although it is routinely given in the USA. Treatment of primary infection with highly active antiretroviral therapy does not prevent establishment of chronic infection. Very early therapy could, potentially, decrease the viral set point, prevent viral diversification, preserve immune function, improve clinical outcome and decrease secondary transmission. ORAL AND OROPHARYNGEAL LESIONS DUE TO OPPORTUNISTIC INFECTION
Oral candidiasis has been reported as the most prevalent oral lesion. Candida forms other than Candida albicans are more prevalent in HIV disease including Candida glabrata, Candida krusei and Candida dubliniensis. Fluconazole is the mainstay of therapy, although resis tance is developing. Penicillium marneffei, a newly described fungal infection, has been identified in South East Asia. Oral lesions common in the early years of the AIDS epidemic including KS, oral aphthous ulceration, AIDS-associated oral lymphoma and oral hairy leukopla kia ( OHL) all contain EBV DNA. Abundant viral replication only occurs in OHL and is due to a previously unknown mechanism involving concurrent expression of prolific, replicative and transforming proteins of the gamma herpes virus EBV. Kaposi's sarcoma has also been shown to contain a different herpes virus specific to this lesion which is now known as KS associated virus. Oral lesions, especially pseudomembranous and/or erythematous candidiasis and OHL, which are highly suggestive of HIV infection in individuals of unknown HIV status, and in those known to be HIV infected, indicate that the battle lines between HIV virion production and destruction of immunologically impor tant cells have been drawn. These observations have led to the almost universal inclusion of oral lesions in HIV staging. Recently, lower frequencies of oral disease due to highly active antiretroviral therapy (HAART) have been noted, except that oral warts may become more common as the viral load falls and the CD4 count rises. Human papilloma v;iruses (HPV) are associated with oral warts in HIV-positive individuals, a diagnosis that is increasing, but currently there is no evidence for an HPV-mediated increase in oral cancer. Types include verruca vulgaris, condyloma acuminatum and focal epithelial hyperplasia. In addition to HPV, herpes simplex virus infection is increasing in this group and may run an atypical course including presentation as an exudative erythema multi forme. In children with HIV infection, additional oral lesions include angular cheilitis, ulcerative gingivitis/ periodontitis and enamel hypoplasia, salivary gland disease, linear gingival erythema over retention and
delayed primary eruption o f teeth. OHL common in children than adults.
IS
much less
LYMPHOI D TISSUE HYPERPLASIA IN THE PHARYNX
Lymphoid tissue hyperplasia in the pharynx commonly involves all the tissues of Waldeyer's ring including adenoidal, palatine and lingual tonsils. Adenoidal hyper plasia and hypertrophy may cause Eustachian tube obstruction and otitis media with effusion. Biopsy of this tissue to exclude nasopharyngeal carcinoma and lympho ma is mandatory but radical adeno-tonsillectomy is to be avoided because of the bleeding risks. HIV viral RNA can be identified in this tissue but no other microorganisms. The complex immunological changes suggest that HIV may be disseminated through the upper aerodigestive tract via target cells. Subsequent presentation of viral antigens to the tonsillar and adenoidal lymphoid tissue results in simulated neoplastic proliferation of these structures, which are highly suspicious of HIV even in asymptomatic HIV-positive patients.
PHARYNGEAL NEOPLASMS
Pharyngeal neoplasms include KS, NHL and Scc. The outlook for patients with these malignancies has improved significantly with the use of HAART and more aggressive cytotoxic therapies. The relative risk of acquiring these conditions compared with non-HIV-infected individuals is for KS greater than 1 0,000, B-cell NHL greater than 1 00, NHL eight and multiple myeloma five. Children also have a high risk of leiomyosarcoma (RR 10,000). Kaposi's sarcoma appears to result from an uncontrolled expres sion of latency genes of human herpes virus-S. It is exquisitely sensitive to immune deficiency and its incidence has declined rapidly with the use of HAART while that of NHL has declined much less so. Patients with head and neck squamous carcinoma who are HIV positive in the absence of AIDS, presented at a younger age, more frequently experienced treatment-related complications and had a poorer outcome, suggesting that head and neck SCC may be an AIDS-defining diagnosis. Oral cavity and oropharyngeal tumours in HIV-positive patients respond to radiation therapy but there is a marked difference in the degree of acute reactions to treatment between patients with and without KS. Breakthroughs in technology have produced tests for HIV antibody that are highly accurate and easy to use and can give a preliminary result in 20 minutes or less. These will be used increasingly in a variety of health care settings, such as the management of medical emergencies, health care worker exposure, labour wards, military operations, disaster management and in the developing world. Work on HIV vaccine development is refocusing on passive vaccination with monoclonal neutralizing antibodies as these seem to provide impress ive protection in primates. =
201 2 I
PART 1 5 TH E UPPER D I G ESTIVE TRACT
p resentatio ns, herpes simplex infections and oral
Pharyngeal and o ther head and neck manifestations of HlV infection are listed in
Table
1 52.4. • •
TUMOU RS OF THE H EAD AND N ECK
The
most
frequent
non-AI D S
•
defining
cancers
are
primary skin malignancies inclu ding melanoma, basal
40 years, of HlV infection and a h istory of
and SCCs. Risk facto rs included age greater than longer duration opp o rtunistic
infection.
The
use
of
hi ghly
active
antiretroviral therapy is protective. Aerod igestive t ract (lung and head and neck) malignancies are becoming
histo plasmosis; Al DS- defining dementia; p ro gressive multi focal leukoencephalopathy; wastin g.
The type
o f AIDS- defining
illness
is
an
impo rtant
determinant of survival, for examp le encephalopathy and wasting are associated with median survivals of less than three months, while others, for example extrap ul monary
TB
and herp es simplex infection, are associated
with median survival greater than two years.
increasingly common with continued imp rovements in HN therapy. These neoplasms are associated with a younger age at di agnosis, cigarette smo king, advanced stage
at
presentation
and
more
aggressive
clinical
course. The reasons for this are not clear. Altho ugh these neo plasms are not AlDS de finin g,
fac tors that
may contribute to risk include HIV-related immuno suppression and co- infection with high-risk papillo ma subtypes.
PRI MARY HIV INFECTION/ACUTE SEROCONVERSION I LLNESS
Primary H IV can be asymptomatic or result in severe symp tomatic illness. Co mmon symptoms are pyrexia, pharyngitis, malaise, lethargy, maculopapular rash, mu co us membrane ulceration, cervical lymphadenopathy and headache. Non-head primary
and
neck manifestations of
HN infectio n might include gastr o intestinal
tract transit disturbances, weight loss, anorexia, ab dom inal pain, myalgia arthralgia and neurolo gical features.
AIDS D E F I NING H EAD AN D NEC K PRESENTATIONS
AIDS defining head and neck p resentations include: • • •
The differential diagnosis is with glandular fever-type syndromes. A careful sexual history may provide a clue. It can be diagnosed by virolo gy testing (HN- l RNA level
50,000 copies/mL)
absence
of HIV-specific
>
non- Ho dgkin's lympho ma;
antibo dies ( ELI SA and confirmatory Western blot anti
opportunistic infections involving head and neck sites
body
TB due to Mycobacterium avium complex in no n- TB endemic areas and CMV, toxoplasmosis, Cryptococcus neoformans with neurological
in flu enced by the severity of the symptoms in primary
including
Ta ble 1 52.4
testi ng) .
in
the
Kaposi's sarcoma (KS ) ;
P rogression
to
late-stage
disease
is
HN infection, the duration of illness, the presence of neurological symptoms a n d that o f oral candidiasis.
Pharyn g e a l and o t h e r head and n eck m a n i festa t i o ns of H IV i nfect i o n .
Pharyngeal
Oth e r head and neck
Acute s e roconve rs i o n i l l n ess
O ra l cavity d ise a se
O p po rt u n i stic i nfectio ns, especia l ly with
S i n o n asa l d isease. R h i n i t i s a n d rh inos i n u sitis a re extre m e ly com m o n . End oscopic s i n u s
candida Ora l h a i ry l e u k o p l a k i a
su rg e ry ca n be h e l pfu l Ce rvica l lym p h a d e n o p a th y m a i nly d u e to l y m p h o i d hyp e rp l a s i a b u t TB or fu n g a l i nfection (cryptococcus o r h istop lasm osis) may be responsi b l e. Ne o p lasms we re l east co m m o n a n d i nc l u d e d N H L a n d SCC
Lym p h o id tiss u e hyperplas i a , particu l a rly i n the post-nasal space
Sa l ivary g l a n d d i sease : be n i g n Iym p h oe pit h e l i a l cyst d i sea s e ; Iym p h o p ro l iferative s w e l l i n gs may reg ress w i t h a n tire t rovira l t h e rapy, d oxycycl i n e scl eroth e rapy i nj ection a n d l ow dose exte r n a l b e a m ra diothera py
N e o p las tic lesi o n s
Pa roti t i s d u e to i n fecti on of i n trapa rot i d n od es w i t h CMV a nd mycobacte ri a Diffuse C O B lym p h ocytosis syn d ro m e ; sa l iva ry stones NHL (na t u r a l k i l l e r type) ; m a l i g n a nt t ransfo r m a t i o n of b e n i g n Iym p h oe p i t h e l i a l l es i o n i nto B ce l l N H L ; KS of i nt ra p a ro t i d lymph n od es Ea r d i sease : B e l l's pa lsy ; se nsorineu ra l h ea ri n g possi b ly re lated to a nt i retrovi ra l th e re a py ototoxicity, a n d c o n d uctive hearing losses seco ndary to Eusta c h i a n t u b e o bst ructi o n from lym p h o i d hyp e r p l a s i a or ch ron ic su p p u rative o t i s m e d i a (CSOM) ; vesti bu l a r fa i l u re ; K S of t h e ext e r n a l a u d itory m eatus ; B -ce l l Iym po m a o f t h e exte rna l a u d i tory m ea t u s ; CSOM w i t h i nt race r e bra l complicq t i o ns; re l a ps i n g polyc h o n d ri t i s ; Pn e umocystis carinij i nfection c a u si n g a u ra l polyps
Ch apter 1 52 Acute a n d chro n ic pharyngeal i nfection I 20 1 3
Currently, the experimental evidence is insufficient to recommend whether or not those diagnosed with primary HIV infection should routinely receive antiretroviral therapy although it is routinely given in the USA. Treatment of primary infection with highly active antiretroviral therapy does not prevent establishment of chronic infection. Very early therapy could, potentially, decrease the viral set point, prevent viral diversification, preserve immune function, improve clinical outcome and decrease secondary transmission. ORAL AND OROPHARYNGEAL LESIONS DU E TO OPPORTUNISTIC I NFECTION
Oral candidiasis has been reported as the most prevalent oral lesion. Candida forms other than Candida albicans are more prevalent in HIV disease including Candida glabrata, Candida krusei and Candida dubliniensis. Fluconazole is the mainstay of therapy, although resis tance is developing. Penicillium marneffei, a newly described fungal infection, has been identified in South East Asia. Oral lesions common in the early years of the AIDS epidemic including KS, oral aphthous ulceration, AIDS-associated oral lymphoma and oral hairy leukopla kia ( OHL) all contain EBV DNA. Abundant viral replication only occurs in OHL and is due to a previously unknown mechanism involving concurrent expression of prolific, replicative and transforming proteins of the gamma herpes virus EBY. Kaposi's sarcoma has also been shown to contain a different herpes virus specific to this lesion which is now known as KS associated virus. Oral lesions, especially pseudomembranous and/or erythematous candidiasis and OHL, which are highly suggestive of HIV infection in individuals of unknown HIV status, and in those known to be HIV infected, indicate that the battle lines between HIV virion production and destruction of immunologically impor tant cells have been drawn. These observations have led to the almost universal inclusion of oral lesions in HIV staging. Recently, lower frequencies of oral disease due to highly active antiretroviral therapy (HAART) have been noted, except that oral warts may become more common as the viral load falls and the CD4 count rises. Human papilloma viruses (HPV) are associated with oral warts in HIV-positive individuals, a diagnosis that is increasing, but currently there is no evidence for an HPV-mediated increase in oral cancer. Types include verruca vulgaris, condyloma acuminatum and focal epithelial hyperplasia. In addition to HPV, herpes simplex virus infection is increasing in this group and may run an atypical course including presentation as an exudative erythema multi forme. In children with HN infection, additional oral lesions include angular cheilitis, ulcerative gingivitis/ periodontitis and enamel hypoplasia, salivary gland disease, linear gingival erythema over retention and
delayed primary eruption o f teeth. OHL common in children than adults.
IS
much less
LYMPHO I D TISSU E HYPERPLASIA IN THE PHARYNX
Lymphoid tissue hyperplasia in the pharynx commonly involves all the tissues of Waldeyer's ring including adenoidal, palatine and lingual tonsils. Adenoidal hyper plasia and hypertrophy may cause Eustachian tube obstruction and otitis media with effusion. Biopsy of this tissue to exclude nasopharyngeal carcinoma and lympho ma is mandatory but radical adeno-tonsillectomy is to be avoided because of the bleeding risks. HIV viral RNA can be identified in this tissue but no other microorganisms. The complex immunological changes suggest that HIV may be disseminated through the upper aerodigestive tract via target cells. Subsequent presentation of viral antigens to the tonsillar and adenoidal lymphoid tissue results in simulated neoplastic proliferation of these structures, which are highly suspicious of HIV even in asymptomatic HIV-positive patients.
PHARYNGEAL NEOPLASMS
Pharyngeal neoplasms include KS, NHL and Scc. The outlook for patients with these malignancies has improved significantly with the use of HAART and more aggressive cytotoxic therapies. The relative risk of acquiring these conditions compared with non-HIV-infected individuals is for KS greater than 10,000, B-cell NHL greater than 1 00, NHL eight and multiple myeloma five. Children also have a high risk of leiomyosarcoma (RR = 10,000). Kaposi's sarcoma appears to result from an uncontrolled expres sion of latency genes of human herpes virus-So It is exquisitely sensitive to immune deficiency and its incidence has declined rapidly with the use of HAART while that of NHL has declined much less so. Patients with head and neck squamous carcinoma who are HIV positive in the absence of AIDS, presented at a younger age, more frequently experienced treatment-related complications and had a poorer outcome, suggesting that head and neck SCC may be an AIDS-defining diagnosis. Oral cavity and oropharyngeal tumours in HN-positive patients respond to radiation therapy but there is a marked difference in the degree of acute reactions to treatment between patients with and without KS. Breakthroughs in technology have produced tests for HN antibody that are highly accurate and easy to use and can give a preliminary result in 20 minutes or less. These will be used increasingly in a variety of health care settings, such as the management of medical emergencies, health care worker exposure, labour wards, military operations, disaster management and in the developing world. Work on HN vaccine development is refocusing on passive vaccination with monoclonal neutralizing antibodies as these seem to provide impress ive protection in primates.
2016 I PART
)-
)-
>-
)-
>-
>-
15
THE U PPER D I G ESTIVE TRACT
adu lts a n d c h i l d ren to a ssess the efficacy, i n c l u d i ng dosage a n d d u ration , of antibiotic thera py with penici l l i n versus placebo. These trials would h ave to be ca rried out i n the pri m a ry ca re setting and the main outcomes would be d u ration a n d severity of sym ptoms, i n cl uding pain, fever, inabi l ity to eat and ca rry out usual a ctivities. Further tri a l s of a lternative anti biotics cou ld then va l idly be com pa red with the effectiveness of pen ici l l i n . A longitud i n a l cohort study is req u i red i n both a d u lts a n d c h i l d ren of the natu ra l h i story of recu rrent episodes of sore throat. The size of the cohorts shou ld be sufficient to a l low pre pa ration of a m u l tifactorial a n a lysis of those factors, wh ich m i g ht predict resolution / n o n resol ution. This is l i kely to i n cl u d e age, sex, n u m ber of s i b l i ng s/a d u lts in the home, deg ree of contact with peers (school, u n iversity, etc. ) , va rious i ndications of deprivation i n c l u d i n g socioeconomic g roup and exposure to ciga rette smoke. There is sti l l confl icting evidence on the role of perioperative loca l anaesth esia i njection and on postoperative a ntibiotics for ton si l l ectomy. Outcomes resea rch fo l l owing tonsi l l ectomy is a developing field. RCTs a re req u i red of tonsi l l ectomy versus nonsurg ica l m a nagement with d isease-specific o u tcom es, genera l h ealth outcomes a n d costings. Such tri a l s shou ld be suffi ciently powered to assess ben efit depen ding on frequency and severity of sym ptoms prior to operation. Stud ies re porting the prescri bing behaviour of G Ps for sore throat sym ptoms in rel ation to workload, time constrai nts and socioeconomic factors a re needed. La rge m u lticentre prospective tri a l s a re req u i red for different tonsi l lectomy techn iques and outcomes ; treatment mod a l ities for deep neck space infections; antivi ra l agents and stero ids in severe, atypica l g l a n d u l a r fever a n d defi n ing the risk of splenic ru ptu re with contact sport.
*
4.
*
5.
U ppa l K, Bais AS. Tons i l l a r m icroflora - su perfici a l su rface vs deep. Journal of Laryngology and Otology. 1 98 9 ; 1 03 :
6.
Schachtel BP, Fi l l i n g i m JM, Beiter OJ , La ne AC, Schwa rtz LA. Subjective and objective featu res of sore t h roat.
7.
D e l Mar C . Man aging sore throat: a l iterature review. I : Making the d i ag nosis. Medical Journal o f Australia. 1 99 2 ;
8.
Bu rke P, Bain J , Lowes A, Athersuch R . Rational decisions in managing sore throat: eva l u ation of a ra pid test. British
Brook I , Yocu m P, Shah K. Su rface vs core-tonsi l la r aerobic a n d anaerobic flo ra in recu rrent tonsi l l itis. Journal of the American Medical Association. 1 98 0 ; 2 4 4 : 1 696-8.
1 7 5-7.
Archives of Internal Medicine. 1 984; 1 44 : 49 7- 500.
1 5 6 : 5 7 2- 5 .
Medical Journal. 1 98 8 ; 2 9 6 : 1 646-9. 9.
La ing MR, McKerrow WS. Adu lt tonsi l l ectomy. Clinical Otolaryngology and Allied Sciences. 1 99 1 ; 1 6 : 2 1 -4.
1 0.
11.
Kiderman A, Ya phe J, Breg man J, Zemel T. Fu rst AL. Adj uva nt pred n isone therapy in p h a ryngitis: a ra ndomized controlled trial from genera l practice. British Journal of General Practice. 200 5 ; 5 5 : 2 1 8-21 . Toner JG, Stewart TJ, Ca m pbell J B , H u nter J. Tonsil flora in the very yo ung tonsi l l ectomy patient. Clinical Otolaryngology. 1 98 6 ; 1 1 : 1 7 1 -4.
1 2.
Little P, W i l l ia mson I , Warner G, Gould C, Gantley M, Kinn month AL. O pen ra ndom ised trial of prescribing strateg ies in manag ing sore th roat. British Medical Journal. 1 997 ; 3 1 4 : 7 2 2- 7 .
* 1 3.
Arro l l B. Antib iotics for u pper respiratory tra ct i nfections : a n overview o f Coch ra ne reviews. Respiratory Medicine. 200 5 ; 9 9 : 2 5 5-61 . This provides evidence tha t the use of
antibiotics in streptococcal sore throat is discretionary. 1 4.
Do l l m a n WB, Leblanc VT, Stevens L, O'Conor PJ, Turn idj e J D. A com m u n ity i ntervention to red u ce antibiotic u s e for u pper respi ratory tract infections in reg ional south Au stra l i a. Medical Journal of A ustralia. 200 5 ; 1 8 2 :
* 1 5.
Spurling GK, Del Mar CB, Doo l ey L, Foxlee R. Del ayed a ntibiotics for sym ptoms and com p l icati ons of respi ratory infections. Cochrane Database of Systema tic Revie ws. 2004; cited October 1 8 , 2004 ; 4: CD0044 1 7 . This shows
6 1 7 - 20.
tha t delayed an tibiotics do not significantly disadvan tage patients with sore throat. 1 6.
B l u mer J L, Goldfa rb J. Meta-ana lysis in the eva l uation of treatment for streptococca l pharyng itis: a review. Clinical
* 1 7.
Robertson KA, Vol m i n k JA, Mayosi BM. Antibiotics for the primary prevention of acute rheu m atic fever: a m eta ana lysis. BMC Cardiovascular Disorders. 200 5 ; 5 1 1 . A
REFE R E N CES *
1.
Therapeutics. 1 994; 1 6 : 604-20.
Scottish I nterco l leg iate Guideline N etwork. The management of sore throat and indications for tonsillectomy.
Ed i n b u rgh : S I G N ,
1 999. This gives a detailed
meta-analysis of RCTs on the use of an tibio tics for the
discussion of all the evidence relating to this topic. 2.
Ca plan C. Case against the use of throat cu lture in the ma nagement of streptococca l pharyng itis. Journal of
3.
Feery BJ, Forse l l P, G u la sekh a ra m M. Streptococca l sore throat in genera l practice - a contro l l ed study. Medical
primary prevention of acute rheumatic fever. 1 8.
Family Practice. 1 97 9 ; 8: 485-90.
Journal of Australia. 1 97 6 ; 1 : 989 -9 1 .
1 9.
McDonald M, Cu rrie BJ , Ca ra petis JR. Acute rh eumatic fever: a chink i n the cha in that l i n ks the heart to the throat? Lancet Infectious Diseases. 2004 ; 4 : 240-5. Taylor J L, Howie JG. Antibiotics, sore throats and acute ne phritis. Journal of the Royal College o f General Practitioners. 1 98 3 ; 3 3 : 7 83-6.
Chapter 1 52 Acute and ch ronic pharyngeal infection I 20 1 7
20.
21.
22.
23.
24.
*
25.
Del Mar CB, Glasziou PP, Spi n ks AB. Antibiotics for sore th roat. Cochrane Database of Systematic Reviews. 2004; cited 2004; 2. CD000023. Del M a r C . Managing sore t h roat: a l iteratu re review. I I . Do antibiotics confer benefit? Medical Journal of Australia. 1 992 ; 1 5 6 : 644-9. M idd leton DB, DiAm ico F, Merenste i n J H . Sta n d a rd ised sym ptomatic treatment versus pen i c i l l i n as i n itial thera py fo r stre ptococca l pharyng itis. Journal of Pediatrics. 1 988; 1 1 3 : 1 089-94. Rob MI, Westbrook JI, Taylor R, Rushworth R. I ncreased rates of ENT s u rgery a mong you ng ch i l d re n : h ave c l i n ica l g u ideli nes made a diffe re nce? Journal of Paediatrics and Child Health. 2004; 40 : 627-32. Pa rad i se J L, Bluesto ne CD, Bach m a n RZ, Co l born OK, Bern a rd BS, Taylor FH e t 01. Efficacy of tons i l l ectomy fo r recu rre nt t h roat i nfection in seve re ly affected ch i l d ren. Resu lts of pa ra l l e l random ized a n d n o n ra n dom ized c l i n ica l tria ls. New England Journal o f Medicine. 1 984; 3 1 0 : 674-83. Pa rad i se JL, B l u estone CD, Co l born OK, Bernard BS, Rockette H E, Ku rs- Lusky M. Ton s i l lectomy a n d adenotonsil lecto my for recu rrent t h roat infection i n moderately affected ch i l d ren. Paedia trics. 2002; 1 1 0 : 7-1 5. This paper evaluates less stringent indications for
34. 3 5.
3 6.
37.
38.
39.
*
40.
tonsillectomy than those discussed in 1984.
26.
27.
28.
29. 30.
31 .
32.
33.
va n Staa ij B K, van den Akke r EH, van der Heijden GJ , Sch i lder AG, Hoes AW. Adenotonsi l l ecto my for u pper respi ratory infections: evide nce based ? Archives of Disease in Childhood. 2005; 90: 1 9-25. van Staaij B K, va n den Akke r EH, Rovers MM, Hord ij k GJ , Hoes AW, Sh i l der AG. Effective ness of adenotons i l lectomy i n ch i l d ren with m i l d sym ptoms of t h roat i nfections or adenoto nsi l l a r hypertrophy: open ra ndom ized contro l l ed tria l. Clinical Otolaryngology and Allied Sciences. 2005; 3 0 : 60-3. McKee WJ. A contro l led study of the effects of tons i l lectomy and adenoidecto my in ch i l d ren. British Journal of Preventive and Social Medicine. 1 963 ; 1 7 : 49-69. Royd house N. A control led study of adenotons i l l ectomy. Archives of Otolaryngology. 1 970 ; 9 2 : 61 1 -6. Ca m i l le ri AE, MacKenzie K, Gateh ouse S. The effect of recu rre nt to nsi l l itis and tonsil lecto my on g rowth i n c h i l d hood. Clinical Otolaryngology. 1 995; 2 0 : 1 53-7. Ahlqvist-Rastad J, H u ltcra ntz E, Melander H , Sva n h o l m H. Body g rowth i n re l ation to tonsi l l a r e n l a rgement a n d tons i l lectomy. International Journal of Pediatric Otorhinolaryngology. 1 992 ; 2 4 : 55-61 . W i l l i a ms I I I EF, Woo P, M i l l er R, Kel l man R M . The effects of ade notons i l lecto my on g rowth in yo u ng ch i l d ren. Otolaryngology - Head and Neck Surgery. 1 991 ; 1 04 : 509- 1 6. Clement WA, Dem pste r J H . I m plementation by Scottish oto l a ryngol og ists of the Scottish I ntercol leg iate G u idel ines Network docu ment IVla nC1gement of Sore Th roats a n d I n d ications for Tonsi l l ecto my: fou r yea rs
41 .
42.
43.
44.
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n n '.lr\/rH1 P Ol I
i nfection I 2023
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153 Causes of dysphagia ELFY B CHEVRETION
Definition History and examination Special investigations Causes of dysphagia
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Summary Key points Best clinical practice References
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The data in this chapter are supported by a Medline search using the key word dysphagia and focussing on diagnosis and aetiology. The data for this chapter is based on expert opionion acquired in clinical practice.
DEFINITION Dysphagia is defined as having difficulty in swallowing which may affect any part of the swallowing pathway from the mouth to the stomach. An accurate diagnosis of the cause is based on a detailed history, clinical examination, which includes indirect laryngoscopy and/ or flexible nasolaryngoscopy, and special investigations. Approximately half of all patients with dysphagia are seen in ear, nose and throat (ENT) clinics. The otolaryngologist should know how to diagnose the cause of the condition and decide which patients to treat and which patients to refer either to a gastroenterologist, a neurologist or an oesophageal surgeon.
HISTORY AND EXAMINATION Patients complain that food or liquids are no longer being swallowed easily and that there is a sensation of food sticking. Patients will often try to localize the level of this sensation and the clinician must try to distinguish oropharyngeal from oesophageal dysphagia. In oropharyngeal dysphagia, there is difficulty in preparing and transporting the food bolus through the oral cavity, as well as initiating the swallow and this may be associated with
aspiration or nasopharyngeal regurgitation. In oesophageal dysphagia, patients complain of food sticking in their lower throat, neck, retrosternal region or epigastrium. The age of the patient should suggest the most likely cause. Children tend to swallow foreign bodies or have congenital problems. In middle-aged patients, a cancer or neurological disease should be excluded though more commonly they tend to suffer with reflux oesophagitis, hiatus hernia, anaemia, achalasia and the globus syndrome. In the elderly, cancer of the swallowing pathway is much more likely and must be excluded, but other common causes are stricture formation from longstanding reflux, pharyngeal pouch, motility disorders associated with ageing and neurological disorders. The history should include the onset, duration, progression and severity of the symptoms, as well as the types of food that give problems and any alleviating factors such as antacids. Eventually, with progressive symptoms, the patient may only be able to take sloppy foods and fluids with subsequent weight loss. The exception to this is achalasia where fluids are more difficult to swallow than solids. In addition, patients may complain of associated symptoms such as regurgitation, pain on swallowing (i.e. odynophagia), hoarseness, otalgia, coughing after eating or frequent chest infections. Regurgitation will be
2026 I PART 15 THE UPPER DIGESTIVE TRACT immediate with blockage of the swallowing pathway, such as in bolus obstruction or a tumour, as opposed to the later regurgitation of undigested food seen in a pharyngeal pouch. Odynophagia is present in patients with infection of the upper aero digestive tract, as well as oesophagitis and tumours. Hoarseness may be due to vocal cord palsy from infiltration of the recurrent laryngeal nerve or vocal cord fixation from infiltration of the larynx: itself by tumour. It may also be due to posterior laryngeal oedema secondary to reflux oesophagitis. An immobile vocal cord will also be associated with a bovine cough. Referred otalgia via the IX and X cranial nerves is usually a sinister symptom and a poor prognostic sign. Coughing after eating and recurrent chest infections suggest aspiration due to laryngeal incompetence andlor hypopharyngeal dysfunction, as develops with neurological diseases, and involvement of the recurrent laryngeal nerve by tumour causing anaesthesia of the larynx and pharynx. Some patients will only complain of a 'constant feeling of a lump in the throat' rather than food sticking, especially when swallowing saliva, the symptom not affecting mealtimes. This symptom, referred to as 'globus pharyngeus', is common in middle-aged women and although affecting the swallowing mechanism it is not true dysphagia. A comprehensive list of current medications and past medical history to include medical conditions and previous surgery needs to be obtained. The clinical examination should include a complete head and neck examination with careful inspection of the oral cavity, dentition and oropharynx and to include indirect laryngoscopy andlor nasolaryngoscopy to inspect the rest of the pharynx and larynx and to exclude pooling of saliva. Cranial nerve function is assessed to look for loss of tongue movement, wasting and fasciculation, loss of gag and cough reflexes, loss of pharyngeal and laryngeal sensation, the presence of hoarseness and loss of vocal cord mobility. The neck is examined for lymph nodes and other neck masses, thyroid enlargement, loss of laryngeal crepitus and the integrity of the laryngeal cartilages. General physical and neurology examinations should look for evidence of malnutrition, weight loss, chest disease, epigastric tenderness and abdominal swellings, loss of coordination, fasciculation and tremor.
SPECIAL INVESTIGATIONS The history and examination may not reveal the cause of dysphagia though it may suggest that the cause is either lower than the hypopharynx: or has a neurological or functional basis. In addition to blood tests, a variety of techniques are available to examine the swallowing pathway beyond the pharynx: visible at nasolaryngoscopy and to evaluate the mechanism of swallowing. The order in which these tests may be carried out will depend on the clinical findings.
Blood tests A full blood count and indices should be obtained in all patients to exclude anaemia as a cause or effect of the dysphagia. An erythrocyte sedimentation rate (ESR) or Creactive protein may be raised in malignancy or chronic inflammatory processes. Liver and renal function tests together with serum calcium levels should be acquired when nutrition is impaired or metastases are suspected. Thyroid function tests are indicated if dysphagia is caused by a goitre or thyroid malignancy. Creatine kinase levels may be elevated in myopathies.
Barium swallow All patients with dysphagia should have a barium swallow if the cause is not obvious after an ENT examination. The patient is given a cup of liquid barium to swallow and the bolus is followed fluoroscopically to the stomach. Documentation is on plane film only, dynamic features and anomalies being described in the report by the radiologist. Improved visualization of mucosal detail can be obtained by using effervescent granules of barium producing an air contrast study. Although a barium swallow is readily available, in practice the test focusses on the oesophagus and is poor for picking up pharyngeal disease, especially in the postcricoid area. Good views of the pharynx: and postcricoid space can be obtained if dedicated views are specifically requested. Barium swallow may confirm reflux, but it is not a very sensitive investigation as it fails to pick up 40 percent of cases. 1 It is useful for diagnosing a pharyngeal pouch, stricture, hiatus hernia or an obstructing oesophageal lesion. Figure 153.1 shows the barium swallow appearances of common causes of dysphagia. The use of barium is contraindicated when there is a risk of leakage into the mediastinum, such as in an oesophageal perforation, as it may cause an inflammatory response resulting in mediastinitis. In other situations it makes subsequent examination difficult. For example, a collection of barium outside the upper digestive tract may be retained for a long time making reexamination difficult and barium also obscures the endoscopist's view when searching for a foreign body. Barium is also contraindicated if aspiration is suspected as it is slow to clear from the lungs and the patient will need physiotherapy to clear it. A high osmolar, water-soluble, contrast medium should not be used if aspiration is a possibility as it can cause a chemical pneumonitis or pulmonary oedema. Instead, in patients with a suspected perforation andlor aspiration, a low molecular weight, nonionic, watersoluble, contrast medium should be used as this is less irritant and should cause minimal complications. Nevertheless, if an oesophageal perforation is suspected, but not shown by a water-soluble contrast examination,
Chapter 153 Causes of dysphagia
Barium swallow appearances of some common causes of dysphagia. (a) A large pharyngeal pouch with narrowing of the oesophageal lumen distal to the pouch; (b) pharyngeal carcinoma; (e) cricopharyngeal spasm; (d) an anterior postcricoid web on the lateral view of the barium swallow in a patient with Plummer-Vincent syndrome; (e) midoesophageal peptic stricture above a sliding hiatus hernia and evidence of reflux; (f) lower third ulcerating oesophageal carcinoma producing irregular constrictions of the lumen; (g) extrinsic compression of the oesophagus by mediastinal lymph nodes; (h) achalasia showing a dilated oesophagus with the smooth 'bird beak' tapering of the oesophagogastric junction; (i) candida of the oesophagus showing the typical 'shaggy' mucosa with multiple irregular filling defects involving most of the oesophagus. Figure 153.1
(i)
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2028 I PART 15 THE UPPER DIGESTIVE TRACT immediate reexamination with barium may demonstrate the abnormality.
Chest radiograph This should be carried out in all patients with true dysphagia. Signs of aspiration and chest infection, the presence of achalasia or the presence of a pulmonary neoplasm or metastases may be apparent.
Computed tomography Patients with malignant dysphagia should have a computed tomography (CT) examination of the neck, chest and abdomen to stage their disease, as should those with dysphagia due to extrinsic compression.
Magnetic resonance imaging of the head and neck Magnetic resonance imaging (MRI) is indicated when a neurological cause of dysphagia is suspected such as multiple sclerosis, cerebral tumours and intracranial extension of a nasopharyngeal carcinoma. It is particularly useful for lesions around the foramen magnum and the brainstem. It is also used to diagnose vascular anomalies.
Direct pharyngoscopy and rigid endoscopy under general anaesthetic This is performed to visualize and biopsy the pharynx and upper oesophagus in patients who complain of food sticking during swallowing, even if the barium swallow is normal, as this symptom may be an early sign of cancer in an area not easily visualized by barium examination. It is also carried out to obtain a biopsy and stage tumours of the pharynx and upper oesophagus that have been evident on clinical or radiological examination. It is the most reliable way of examining the postcricoid area.
Flexible upper gastrointestinal oesophagoscopy under intravenous sedation This is performed by either a gastroenterologist or by an oesophageal surgeon, to visualize, assess, stage and biopsy the oesophagus in patients with oesophagitis, Barrett's oesophagus and tumours. It is poor at detecting disease of the hypopharynx partly because gastroenterologists focus on the alimentary tract distal to cricopharyngeus, partly because this zone is passed through very rapidly, but perhaps more importantly because the flexible endoscopes cannot examine the piriform sinuses adequately.
Barium videofluoroscopy swallowing study Barium videofluoroscopy swallowing study (VFSS) is considered to be the gold standard for evaluating the swallowing mechanism? It is a comprehensive test for all phases of swallowing, but particularly useful for the oral and pharyngeal phases. Liquid, pureed and solid foods are used. The passage of these is observed in both the lateral and anteroposterior views and evaluated for transit time, pooling, aspiration, as well as the motor function and symmetry of the swallowing pathway. If aspiration is present, videofluoroscopy will identify the cause and manoeuvres can be designed and tested to reduce this, for example swallowing during breath holding, with or without a chin tuck, and with or without a head turn towards the affected side. This is particularly useful in patients with neurological disease, after surgery or radiotherapy.
Fibreoptic endoscopic evaluation of swallowing In a fibre optic endoscopic evaluation of swallowing (FEES) ,3, 4 a fibreoptic nasoendoscope is passed through the nose to observe the larynx and pharynx at rest and during the pharyngeal phase of swallowing. With it, pooling of saliva in the hypopharynx, reduced or absent endolaryngeal sensation and aspiration before and after swallowing can be detected. It is useful in neurological, frail and post-surgical patients and can be performed at the bedside. The test can be extended usefully by using coloured fluids, purees and solids. Unfortunately, all the phases of swallowing cannot be assessed directly and the cricopharyngeus and the oesophagus cannot be visualized.
Manometry This is employed to measure oesophageal pressures at rest and during swallowing to diagnose motility disorders. 5 A catheter with pressure transducers along its length is placed in the oesophagus and a multichannel system records the contraction amplitude, duration, coordination and velocity of each peristaltic wave. It is particularly helpful in patients with atypical chest pain and unexplained causes of dysphagia. Conditions with almost pathognomonic manometric findings include achalasia, diffuse oesophageal spasm, 'nutcracker oesophagus' and scleroderma. These conditions are discussed in Chapter 156, Oesophagal diseases.
Twenty-four hour ambulatory oesophageal pH monitoring This is' regarded as the most accurate method of diagnosing gastrooesophageal reflux. 5 It is especially
Chapter 153 Causes of dysphagia
useful when standard investigations such as flexible oesophagoscopy and barium swallow are normal in a patient with typical symptoms, or in patients with atypical symptoms such as chest pain, globus, hoarseness and recurrent chest infections. A pH sensor placed 5 cm above the manometrically defined lower oesophageal sphincter continually monitors the pH over the test period, while the patient records their symptoms, mealtimes, going to bed and getting up in a diary card or with an event marker on the pH recorder. Normal oesophageal pH varies between 5 and 7 and gastrooesophageal reflux is present when the pH is less than 4. The results are expressed as the percentage of time the pH is less than 4 over a 24-hour period - the DeMeester score. 6
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CAUSES OF DYSPHAGIA The classification of dysphagia maybe subdivided into the local and general causes of obstruction of any tube in the body with causes in the lumen, in the wall and external compression of the wall as first popularized by Ellis and Calne 7 in their Lecture Notes on General Surgery series. The author uses the equally popular 'surgical sieve' of congenital and acquired causes of dysphagia as summarized below. • Congenital: - choanal atresia; - cleft lip and palate; - laryngomalacia; - unilateral vocal cord paralysis; - laryngeal cleft; - tracheooesophageal fistula and oesophageal atresia; - vascular rings. • Acquired: - traumatic: • accidental and iatrogenic; • blunt trauma, penetrating injuries and compression effects; • direct injury and cranial nerve damage; • head injury. - infections: • acute pharyngitis, tonsillitis, quinsy; • glandular fever; • acute supraglottitis; • herpetic, fungal, cytomegalovirus mucosal lesions; • candidiasis; • tuberculosis; • submandibular, parapharyngeal and retropharyngeal abscesses. - inflammatory: • gastrooesophageal reflux disease ± stricture formation; • Patterson Brown-Kelly or Plummer-Vincent syndrome;
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• systemic autoimmune disorders: scleroderma and 'CREST' syndrome; systemic lupus erythematosus; dermatomyositis; mixed connective tissue disease; benign pemphigoid and epidermolysis bullosa; primary and secondary Sjogren's diseases; rheumatoid arthritis; Crohn's disease; sarcoid. oesophageal motility disorders: • achalasia; • diffuse oesophageal spasm; • 'nutcracker' oesophagus. neoplastic: • benign tumours of the oral cavity, pharynx and oesophagus; • malignant tumours of the oral cavity, pharynx and oesophagus; • nasopharyngeal carcinoma; • skull base tumours; • leukaemias and lymphomas; • enlarged mediastinal lymph nodes. neurological: • cerebrovascular accidents (stroke); • isolated recurrent laryngeal nerve palsy; • Parkinson's disease; • multiple sclerosis; • myasthenia gravis; II motor neurone disease . drug-induced: • drugs causing oesophagtis; • inhibitory drug side effects; • excitatory drug side effects; II drug complications. ageing: • presbydysphagia. miscellaneous: • foreign bodies in the pharynx and oesophagus; II caustic stricture; • pharyngeal pouch; • globus pharyngeus; • patients with tracheostomy; • thyroid disease.
Congenital Most congenital problems causing swallowing and feeding difficulties present in the paediatric age group, though some may present later in life. Choanal atresia, which is partial, can present at birth with feeding difficulties as the neonate is an obligate nasal breather and unable to suckle adequately, whereas complete choanal atresia presents with respiratory distress. The diagnosis is made by the lack of passage of air at the nostril, failure to pass a nasopharyngeal catheter and confirmed on axial CT after nasal decongestion.
2030 I PART 15 THE UPPER DIGESTIVE TRACT Cleft lip and/or palate are common congenital abnormalities associated with dysphagia depending on the severity of the abnormality. Sucking can be inefficient due to an inadequate lip seal and inability to seal off the nasopharynx and nasal cavity. The abnormality is picked up at the routine neonatal examination. Laryngomalacia is a congenital laryngeal abnormality and the most common cause of stridor in the first year of life that can be associated with dysphagia. Diagnosis is made by nasolaryngoscopy as an outpatient or direct laryngoscopy under general anaesthetic. Unilateral vocal cord paralysis may present with swallowing difficulties, as well as hoarseness and asp ira tion during feeding, rather than stridor as found in bilateral vocal cord paralysis. Diagnosis is made by endoscopic examination of the larynx. Laryngeal clefts are associated with dysphagia, but type I clefts involving the posterior larynx above the cricoid cartilage only need surgical correction if there is significant aspiration. Surgery is usually indicated in type II clefts extending to the lower border of the cricoid, type III clefts extending into the cervical trachea and type IV clefts involving the whole of the trachea. There is an association between laryngeal clefts and tracheoesophageal fistula. Diagnosis is made at endoscopy under a general anaesthetic. Tracheooesophageal fistula and oesophageal atresia present with both dysphagia and airway difficulties. There are many variations, but the most common is oesophageal atresia with a distal tracheooesophageal fistula. The diagnosis is made either at endoscopy, under a general anaesthetic, or by a contrast swallow. A nasogastric tube is passed into the oesophagus of the child lying prone and a nonionic contrast medium is injected down the tube as it is withdrawn. Vascular rings formed by anomalies of the great vessels may cause significant dysphagia depending on the abnormality, though they more commonly present with respiratory symptoms first. An anomalous subclavian artery (dysphagia lusoria) may present with dysphagia in adulthood. Other anomalies seen include a double aortic arch and an anomalous left pulmonary artery. Diagnosis can be made by endoscopy, barium swallow, CT or MRI
apparent until the patient resumes consciousness, starts feeding again and aspiration results.
Infections Infections are one of the most common causes of dysphagia and are obvious when they affect the oral cavity and oropharynx, but are more difficult to diagnose further down the tract. Acute onset of dysphagia during a coryzal-like illness suggests an infective cause for the dysphagia. Acute pharyngitis and tonsillitis are the most common cause presenting with fever, malaise and painful dysphagia, the degree depending on the severity of the inflammation. The initial viral infection usually predisposes to a secondary bacterial infection, most commonly a group A, beta-haemolytic streptococcus. Despite appropriate antibiotic therapy, tonsillitis can progress to a peritonsillar abscess ('quinsy') (Figure 153.2). Glandular fever caused by the Epstein-Barr virus can also cause pharyngitis with severe painful dysphagia and associated with marked cervical lymphadenopathy. Acute supraglottitis is now a rare cause of painful dysphagia in children, due to immunization with the Haemophilus inJluenzae type B vaccine. However, epiglottitis should be suspected in a child who becomes rapidly unwell with fever, stridor, painful dysphagia and drooling. The diagnosis is confirmed only after the airway has been secured by endotracheal intubation or tracheostomy. Supraglottitis in adults has a more protracted course,
Traumatic Trauma to the head and neck, chest or cervical spine may be accidental or iatrogenic and may involve blunt trauma, penetrating injuries or compression effects or a combination of these. Neck injuries may disrupt the swallowing mechanism directly or indirectly by affecting the cranial nerves IX to XII. Head injuries can produce a variety of neurological defects resulting in paresis, paralysis or loss of coordination of the swallowing mechanism which may not become
Figure 153'.2 Axial CT of the neck showing encroachment of the pharynx from a quinsy.
Chapter 153 Causes of dysphagia
stridor may not be present, and diagnosis can be confirmed by fibreoptic nasolaryngoscopy. Herpetic, fungal or cytomegalovirus mucosal infections can cause dysphagia and is usually seen in severely immunocompromised patients (e.g. leukaemia, lymphoma, acquired immunodeficiency syndrome (AIDS)), patients receiving chemotherapy or head and neck radiotherapy, and patients with diabetes. In addition, candidal infections are more common in patients on broad spectrum antibiotics or steroids. Oral candidiasis is diagnosed on clinical examination. However, candida affecting the hypopharynx and oesophagus may not be obvious to the clinician. Oesophagoscopy is the investigation of choice for diagnosis when a swab can be taken. The barium swallow demonstrates a characteristic 'shaggy' mucosal appearance that may make endoscopy unnecessary for some patients. Tuberculosis is a chronic infection that can cause dysphagia by either a mucosal lesion or compression of the oesophagus by enlarged lymph nodes. Diagnosis is by endoscopic biopsy of a lesion and axial CT of the chest delineates the extent of the disease. Abscesses of the head and neck spaces can result in significant painful dysphagia with drooling in patients who are already unwell with a high fever and torticollis of the affected area. The most common in adults are peritonsillar abscesses followed by submandibular and parapharyngeal abscesses (Figure 153.3). Retropharyngeal abscesses, which are rare in adults, are more common in children.
Inflammatory The inflammatory process causing dysphagia may be the result of mucosal damage from the reflux of peptic juice
Figure 153.3 Axial CT of the neck showing compression of the pharynx from a parapharyngeal abscess caused by penetration of a radioopaque ingested foreign body.
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through an incompetent cardiac sphincter into the oesophagus, as seen in reflux oesophagitis, or the result of a generalized inflammatory process, as seen in the systemic autoimmune disorders. Gastrooesophageal reflux disease (GORD) is one of the most common causes of dysphagia with most patients complaining of a tightness in the lower neck, constant throat clearing, retrosternal discomfort and hoarseness, and only complaining of gradually increasing dysphagia when the acid reflux is associated with stricture formation. Clinical examination may show erythema and oedema of the posterior larynx and lower pharynx, but usually a flexible oesophagoscopy is needed for diagnosis. The inflammatory changes seen in the oesophagus range from mild erythema, which is equivocal evidence of reflux, to erosions, confluent ulceration or stricture formation in more severe cases. A flexible oesophagoscopy should be performed in all suspected cases of GORD as there is an association between oesophagitis, Barrett's oesophagus and adenocarcinoma of the oesophagus. Twenty-fourhour ambulatory oesophageal pH monitoring is the most accurate way of confirming the diagnosis and is useful when standard investigations are normal. In Patterson Brown-Kelly or Plummer-Vincent syndrome, dysphagia mostly affects middle-aged or elderly women and is associated with atrophic gastritis and irondeficiency anaemia with its associated smooth tongue, angular stomatitis and koilonychia. The dysphagia is due to hyperkeratinization with web formation in the postcricoid region and can be seen on barium swallow, but may not always be found at rigid endoscopy. The dysphagia and the hyperkeratinization are treated with iron replacement, but the web may need dilatation. The condition is associated with the development of postcricoid carcinoma in a small percentage of patients. Systemic autoimmune disorders 8 are associated with dysphagia in a large proportion of cases, though the mechanism differs between disease groups. Diagnosis of this group of conditions is based on the clinical picture and auto-antibody profile, e.g. antinuclear factor and rheumatoid factor. Control of the disease with steroids and immunosuppressive drugs does not usually improve the dysphagia. Scleroderma and 'CREST' syndrome (calcinosis, Rayrraud's, oesophageal involvement, sclerodactyly, telangiectasis) are progressive disorders of connective tissue that may include atrophy and fibrosis of smooth muscle. They often affect the lower oesophagus resulting in poor peristalsis, severe gastrooesophageal reflux with stricture formation and Barrett's oesophagus. Systemic lupus erythematosus (SLE) is a progressive systemic inflammatory disease involving skin, joints and internal organs that can affect the oesophagus. The dysphagia tends to be mild. Dermatomyositis is a diffuse inflammatory condition affecting skin and skeletal muscle associated with malignancy in a high percentage of patients. Dysphagia
2032 I PART 15 THE UPPER DIGESTIVE TRACT may be secondary to hypopharyngeal and upper oesophageal involvement. Mixed connective tissue disease is an overlapping condition between SLE, polymyositis and scleroderma that often involves the oesophagus. Benign pemphigoid and epidermolysis bullosa are characterized by subepidermal and submucosal blisters respectively, leading to scarring and obstruction of the pharynx and oesophagus. There is often good response to steroids and dilatations. Primary and secondary Sjogren's diseases are associated with dysphagia as a result of xerostomia. Rheumatoid arthritis may involve the cricoarytenoid joint with resultant hoarseness and dysphagia. Crohn's disease is a nonspecific inflammatory disease of the alimentary tract from mouth to anus of unknown aetiology, characterized by discontinuous transmural ulceration. It may affect the oesophagus. Sarcoid is a granulomatous disease that may cause dysphagia by compression of the oesophagus by involved lymph nodes.
Oesophageal motility disorders These disorders can produce severe dysphagia in the absence of visible abnormalities, the diagnosis being made by manometry. 9 However, before the diagnosis of a dysmotility disorder is made, it is important to exclude a tumour or structural abnormality by endoscopy or radiology. Achalasia (cardiospasm) is due to failure of relaxation of the lower oesophageal sphincter with progressive dilation and hypertrophy of the oesophageal wall above. The cause is due to degeneration or absence of the ganglion cells of Auerbach's myenteric plexus in the oesophageal walL The condition is indistinguishable from Chagas disease, seen in patients from South America and which is due to infection by Trypanosoma cruzi and which destroys the ganglion cells. Patients complain of progressive dysphagia to fluids and then solids and eventually regurgitation of undigested food. Diagnosis is made on barium swallow showing initially a smooth 'bird's beak' tapering of the oesophagogastric junction which is later associated with a dilated oesophagus. Manometry is used to establish the diagnosis in early disease when the classic barium appearance has not yet developed and shows failure of relaxation of the lower oesophageal sphincter, absence of oesophageal peristalsis and a raised resting pressure in the oesophagus. Diffuse oesophageal spasm causes angina-like chest pain in the presence of normal coronary arteries and dysphagia. Manometry shows repetitive nonperistaltic, multipeaked contractions of high amplitude of the body of the oesophagus with intermittent normal peristalsis and incomplete lower oesophageal sphincter relaxation. Barium swallow shows a characteristic nonpropulsive peristaltic wave.
Nutcracker oesophagus also causes noncardiac chest pain associated with dysphagia. Manometry shows normal peristaltic waves of high amplitude in the distal oesophagus.
Neoplastic Both benign and malignant tumours may cause dysphagia by mechanical obstruction and also by neuromuscular InVaSIOn.
In the oral cavity, most tumours are malignant and of these 95 percent are squamous cell carcinomas. The patient may present with a lump in the mouth or with an ulcer that may result in odynophagia. Dysphagia is caused by tongue fixation. In the oropharynx, most malignant tumours are squamous cell in origin and usually ulcerative and a small percentage are lymphomas which present as smooth enlargements. The patient usually presents with a sore throat, referred otalgia or dysphagia and the tumour should be visible clinically. In the hypopharynx, rare benign tumours can be found such as leiomyomas, lipomas and fibrolipomas which cause dysphagia. The majority of tumours are squamous cell carcinomas, 60 percent occurring in the pyriform fossa. Large tumours are obvious from the symptomatology and should be seen on clinical examination. Small tumours and tumours of the postcricoid region or the cervical oesophagus can be more difficult to diagnose. The patient may only complain of a feeling of 'something in the throat', a crumb being stuck or have had any episode of food sticking. The ENT examination and barium swallow may be normal, but if the above symptoms are either constant or persistent, especially when associated with arytenoid oedema or pooling of saliva on examination, a direct pharyngoscopy and oesophagoscopy is mandatory. In the oesophagus, benign leimyomas can be found occasionally but the majority of tumours are squamous carcinomas. Adenocarcinomas may develop at the lower end either arising in gastric metaplasia as in Barrett's oesophagus or as a result of invasion of the oesophagus from a tumour developing at the cardiac end of the stomach. Dysphagia of short duration in an elderly male who smokes and drinks and which progresses from solids to liquids is classicaL Examination may show weight loss and anaemia, cervical lymphadenopathy and hoarseness with a bovine cough in advanced disease, but there may be little to find in early disease. The diagnosis is made on barium swallow. In all cases of pharyngeal and oesophageal malignancy, the diagnosis is confirmed by biopsy performed under general anaesthesia in order to assess and stage the tumour. Further assessment and staging of the primary growth, local spread and secondary deposits is made by CT scan ot the neck, chest and upper abdomen depending on the site of the primary.
Chapter 153 Causes of dysphagia
Nasopharyngeal carcinomas are known for their varied presentations and may present with cranial nerve palsies from skull base invasion resulting in speech and swallowing problems and hoarseness. Nasolaryngoscopy may reveal the tumour, but CT is mandatory to assess the skull base invasion. Skull base tumours, such as craniopharyngomas and chordomas, may cause dysphagia by compression of the parapharyngeal space or invasion of the cranial nerves. Leukaemias and lymphomas may cause dysphagia by oesophageal wall infiltration. Enlarged mediastinal lymph nodes due to lymphoma, or lymph node metastases, bronchial carcinoma or thyroid malignancy especially if retrosternal, can all cause dysphagia by external compression of the oesophagus. The level of the hold up can be seen on the barium swallow and the likely diagnosis made from a chest radiograph or CT scan of the chest.
Neurological Neurological causes of dysphagia 10 mostly affect the oropharyngeal phase of swallowing. Usually, the motor, sensory and coordinating centres for swallowing are affected directly by the disease and it is unlikely that the dysphagia would present as an isolated symptom without the other characteristic features of the neurological disease. In general, patients who present with an acute disorder causing dysphagia, such as a stroke, tend to improve with time, whereas patients with chronic neurological disorders will experience progressive swallowing difficulties. Diagnosis of the specific swallowing problem in these conditions is made by a careful head and neck examination, assessment by a speech and swallowing therapist and special studies including barium videofluoroscopy. Constant reevaluation is often needed. Cerebrovascular accident or stroke is probably the most common neurological disorder causing dysphagia by affecting the cortex or the corticobulbar tracts (pseudobulbar palsy) or by affecting the bulbar nerve nuclei (bulbar palsy). Recovery takes place within the first week in the majority of patients. Factors contributing to the dysphagia include delayed triggering of the swallowing reflex, cricopharyngeal dysfunction and reduced tongue control and pharyngeal contraction and cough. Loss of pharyngeal sensation associated with the dysphagia correlates well with aspiration, aspiration pneumonia being a major cause of death after a stroke. Isolated recurrent laryngeal nerve palsy can be associated with dysphagia and aspiration of liquids due to decreased pharyngeal gradient pressures and decreased glottic closure pressures, as well as inferior constrictor and cricopharyngeus muscle dysfunction. Combined superior
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and recurrent laryngeal nerve injury will have a greater impact due to the ipsilateral sensory deficit. Parkinson's disease is progressive and characterized by the triad of resting tremor, bradykinesia and rigidity, patients having difficulty in starting, performing and stopping a movement. The dysphagia is associated with changes in striated muscle under dopaminergic control and smooth muscle under autonomic control. The oral phase of the swallow is affected by rigidity of the tongue musculature and the pharyngeal phase by delayed contraction of the pharyngeal muscles. Findings on videofluoroscopy include impaired motility, hypopharyngeal stasis, aspiration and poor movement of the epiglottis. Multiple sclerosis is a demyelinating disease of the central nervous system. The patient may present with either relapses and remissions or a progressive syndrome. Swallowing problems tend to occur in end-stage disease in up to a third of the patients. Reduced pharyngeal peristalsis and delayed swallowing reflex are the most common features. However, the demyelinating lesions can occur in a single cranial nerve or cause a general dysfunction of all three phases of deglutition. Myasthenia gravis is characterized by fatiguable weakness of striated muscles due to impaired transmission across the neuromuscular junction. The diagnosis is a clinical one supported by the presence of acetylcholine receptor antibodies. Bulbar muscle weakness is the cause of the dysphagia manifested by slow and weak tongue movements, fatigue of swallowing and food residue in the oropharynx. There may be laryngeal penetration and aspiration. Motor neurone disease (amyotrophic lateral sclerosis) is a progressive disease of the corticobulbar and corticospinal tracts. Progressive swallowing difficulties affecting mainly the oral and oropharyngeal stage of swallowing together with dysarthria and anarthria, account for much of the misery of the disease.
Drug-induced Drugs can cause dysphagia directly by causing oesophagitis, or as part of their pharmacological action or normal side effects. 11 Swallowing tablets with insufficient water or just before going to bed can cause oesophagitis as oesophageal transit time is longer during sleep. The oesophagus at the level of the aortic arch is most commonly injured by both lack of neutralization of the saliva and contact by acidproducing drugs with a pH of less than 3, such as tetracyclines, doxycycline, vitamine C and ferrous sulphate. Broad-spectrum antibiotics and chemotherapeutic drugs may cause secondary viral ulceration or fungal infections. Stevens-Johnson syndrome is a more serious complication of antibiotic therapy with an acute erosive
1
2034 I PART 15 THE UPPER DIGESTIVE TRACT pharyngitis and oesophagitis causing dysphagia as well as delayed oesophageal strictures. Drug side effects may be inhibitory (e.g. anticholinergics, tricyclic antidepressants and calcium channel blockers) due to a decrease in oesophageal peristalsis and tone of the lower oesophageal sphinter. They may be excitatory (e.g. cholinergic agonists, cisapride and metaclopramide) and cause rapid oesophageal emptying and gastrooesophageal reflux. Dysphagia can be a complication of drugs such as antihypertensives, ACE-inhibitors, anticholinergics, antiemetics, antihistamines diuretics and opiates by causing xerostomia.
Ageing Presbydysphagia refers to swallowing difficulties due to ageing which affects all stages of swallowing. The oral phase is affected by loss of teeth and tongue connective tissue, reduced strength of mastication and weakness of the velopharyngeal reflexes. The pharyngeal phase is affected by decreased elevation of the larynx and prolongation of the pharyngeal transit time. In the oesophageal stage, there is prolongation of the upper oesophageal sphincter relaxation time and the oesophageal transit time. Despite these age-related changes and barium swallow abnormalities evident in one-third of otherwise healthy elderly individuals, few complain of dysphagia. However, as the swallowing mechanism is already compromised, severe swallowing difficulties may result from even minor insults, such as swallowing medications.
Miscellaneous causes of dysphagia FOREIGN BODIES IN THE PHARYNX
Small sharp foreign bodies, such as fish bones or spicules of meat bones, may lodge in the tonsil, base of tongue, vallecula or piriform fossa, the tonsil being the most common site. The patient will complain of a pricking sensation on swallowing and should be able to localize the site and side. Examination of the oral cavity, pharynx and larynx by inspection, palpation where appropriate and indirect laryngosopy and or nasolaryngoscopy will reveal most bones lodged in these areas. Examination of the neck should elicit tenderness at the site of impaction. A lateral soft tissue radiograph of the neck may help if the bone is ossified and radio-opaque, but not if it is purely cartilaginous. 12
FOREIGN BODIES IN THE OESOPHAGUS
A variety of foreign bodies impacting in the oesophagus are ingested by children and mentally deranged patients,
with the most common being coins. The size and shape of the foreign body will dictate where it lodges, but common sites are areas of constriction at the cricopharyngeus, at the level of the aortic arch and at the cardia. Bolus obstruction from large pieces of meat with or without a piece of bone, is often seen in elderly patients who cannot chew due to lack of teeth and patients with a benign or malignant oesophageal stricture. Patients present with painful dysphagia following recent ingestion of food or a foreign body. Adults tend to localize the level of the obstruction better than children or psychiatric patients. If obstruction is complete as in meat bolus obstruction, there will be drooling of saliva. Indirect laryngoscopy may confirm pooling of saliva. Neck examination may reveal subcutaneous emphysema if pharyngeal or oesophageal perforation has occurred. A lateral soft tissue radiograph of the neck and a chest radiograph may show a radioopaque foreign body, widening or the presence of an air bubble at the postcricoid space or subcutaneous emphysema. It may be necessary to perform a contrast swallow with a nonionic contrast, which has the added advantage of not interfering with subsequent oesophagoscopy as it is clear.
CAUSTIC STRICTURE
Acids or alkalis, such as caustic soda or ammonia ingested accidentally by children or by attempted suicide, cause burns first in the oral cavity and pharynx and then most commonly in the middle and lower oesophagus. Oedema of the laryngopharynx may produce respiratory difficulty. The burns may be superficial and heal completely or be full thickness and repair by fibrosis with stricture formation and dysphagia. In the acute phase, flexible oesophagoscopy is mandatory to assess the extent of the oesophageal damage prior to placing a feeding gastrostomy. Stricture formation is diagnosed at barium swallow and oesophagoscopy.
PHARYNGEAL POUCH
This is a mucosal dehiscence between the two parts of the inferior constrictor, the thyropharyngeus and the cricopharyngeus. The area is called Killian's dehiscence in the posterior pharynx and the pouch first develops in the midline, but as it enlarges it expands to one side, most frequently the left. Pharyngeal pouch is an example of a pulsion diverticulum, but its aetiology remains uncertain. Manometric studies suggest that it is associated with high intrapharyngeal pressures with a high resting tone in cricopharyngeus that is slow to relax. 13 Patients complain of a lump in the throat when the pouch is small, but as it enlarges there will be dysphagia as the pouch full of food compresses the oesophagus. Overflow of food into the pharynx will cause regurgitation of undigested food and overflow into the larynx will
Chapter 153 Causes of dysphagia
cause aspiration with bouts of coughing and eventually pneumonia. Diagnosis is confirmed by a barium swallow.
KEY POINTS ....•
GLOBUS PHARYNGEUS
Patients complain of a 'constant feeling of a lump in the throat' which is worse on swallowing saliva, but which does not interfere with the swallowing of either fluids or food. Although it affects the swallowing mechanism, this symptom being more common in women is not true dysphagia and rarely associated with serious disease. Although there may be a functional element to globus, it is associated with gastrooesophageal reflux with or without oesophagitis in a significant number of patients. I4 This group of patients have been found to have increased upper oesophageal sphincter pressures and it has been postulated that this is secondary to the gastrooesophageal reflux. Flexible nasolaryngoscopy is normal. If the symptom persists despite strong reassurance, some patients may be submitted to a barium swallow or rigid endoscopy to exclude other disease, notably tumours (see also Chapter 154, Globus pharyngeus) .
I 2035
Dysphagiaisclefineclasdi¥~ult;jl1
s~aU()-winga?d.llJ.~yaf~~ctapy Relrt .oftll~. ;MTallowing1?athwayf!offi thel1l0~thtothe stomach. . • Tneage of the patienfsuggeststhe1119st lil<ely cause of. dysp~agia;Inchik[renitis ofte~;due . ~o •.~?},1ge11.~t~,callsesora.S1Nall9wed ~orei~1}~b:64Y·l\I1iq
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etalgi~.i~:aJ?~ti~ll~.withpi~ghagiais ?~~ua~l¥~a;~il1is;t~r:syrnWto;~llaA~.a .pP?r ... ,. pro9Pc°stksigll"
.•. • . ;... / . .•. . •. . .•.•. .•.•••.•. . . .••.. / •.. •. .
:~)".1Ye~r~l()giF~. fa1f~es';OcfA~§J?~~~ian:8~tl~ . .
PATIENTS WITH A TRACHEOSTOMY
A tracheostomy tube with an inflated low-pressure cuff fashioned either percutaneously or by the open technique provides direct access to the airway, but can cause dysphagia by interfering with laryngeal elevation during swallowing and by direct pressure on the oesophagus if' the cuff is overinflated. IS
~.f~~stt~e··B~1Wfar:w~~,al)·p~q~ei;?fs~~llgM~g· .·.~.; . •.Inge~t,e<1;~orei~Il;~o~i~Mt7:l1d.t~lqdge".at··~i~es •. Qf,con~tri<.:tion~t . .tn.e.•. ~ti~~pha.f'Yflge~s,at • . tlle leveLof:.th:e.aorticarGhandatthecardia~ .
•. A. c()~tr~~t~~~11,QYV(f0r·Sl1$.f~cf~dpl!rf(}r(lti()li aA<:\/?r~a~Bi~atiql,1.s~p~clP~~ith.a.low . ' 11101ecul(lr;. . ~~ight)·.n9Pf()~ic,· ~'lter7sohlble contrast medium. Ba.rium .is contraindicated.
.·irrthesesitua~io¥~.~ .?esopb:a&eaL ~an.0Il1etrYcanbehelpfur in THYROID DISEASE
Thyroid goitre and benign and malignant thyroid neoplasms may cause dysphagia due to compression of the upper oesophagus. Extrinsic compression of the oesophagus is confirmed on barium swallow and axial CT scans of the neck and chest. The suspected thyroid disease is confirmed with the help of thyroid function and thyroid antibody blood tests, fine needle asp ira tion cytology, ultrasound and thyroid scanning of the thyroid.
pati~nts;\'Vghatyp~ca.;1c4estpa,ina:Il4
~p~xpl~inedgysp1iClgia. .'. '..
..•. . . •.'".
• T",eXlty-fouf11911rall1btilat99' qesoph~gefd pHm~l1itqri:t;lgistl1y.l):1ostaccllJ:a~ertl~thoq . ofdiagn.qsing.gastroeos?phage~l·.reflux~ . •
.J\.barh1l11videofluoroscopy s~all0'Yingstuay .is,the.·.g
SUMMARY Dysphagia is a common symptom which may affect any part of the swallowing mechanism from the mouth to the stomach. Approximately 50 percent of all cases are seen in ENT clinics and the ENT surgeon needs to: know how to diagnose the cause of the condition; distinguish oropharyngeal from oesophageal dysphagia; and decide who to treat and who to refer appropriately to the gastroenterologist, neurologist or oesophageal surgeon.
The ENT surgeon should distinguish between oropharyngeal and oesophageal dysphagia. ,/' All patients should have a barium swallow or upper GI endoscopy if the cause of dysphagia is not obvious after an ENT examination. An early sign of cancer in the post-cricoid area or cervical oesophagus is the persistent feeling of
2036 I
PART 15 THE UPPER DIGESTIVE TRACT
something stuck in the throat. A direct
7.
performed even if the barium and ENT examination is normal.
Ellis H, Caine R, Watson C. The oesophagus. In: Ellis H, Caine R, Watson C (eds). Lecture notes on general surgery.
pharyngoscopy and upper oesophagoscopy should be
*
Oxford: Blackwell Science Ltd., 1998: 151-7. 8.
Schechter GL. Systemic causes of dysphagia in adults.
Otolaryngologic Clinics of North America. 1998; 31 : 525-35. 9.
REFERENCES
Bancewicz J, Attwood SEA. Achalasia and motility disorders. In: Adam A, Mason RC, Owen WJ (eds). Practical
management of oesophageal disease. Oxford: Isis Medical 1.
Richter JE, Castell DO. Gastroesophageal reflux. Pathogenesis, diagnosis and therapy. Annals of Internal
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Medicine. 1982; 97: 93-103. 2.
11.
Stoschus B, Allescher HD. Drug-induced dysphagia.
12.
Ell SR, Sprigg A, Parker AJ. A multi-observer study
Dysphagia. 1993; 8: 154-9.
adult populations. Folia Phoniatrica et Logopedica. 1999; 51: 158-71. 3.
Langmore SE, Schatz K, Olson N. Endoscopic and
examining the radiographic visibility of fishbone foreign
videofluoroscopic evaluations of swallowing and
bodies. Journal of the Royal Society of Medicine. 1996;
aspiration. Annals of Otology, Rhinology and Laryngology. 1991; 100: 678-81. 4.
89: 31-4. 13.
Kidder TM, Langmore SE, Martin BJW. Indications and
A, Guidolin D et al. Functional and morphological study of the cricopharyngeal muscle in patients with Zenker's
dysphagia: Comparison with radiographic techniques.
diverticulum. British Journal of Surgery. 1996; 83:
Anggiansah A, Marshall REK. Use of the oesophageal
1263-7. 14.
Smit CF, van Leeuwen JA, Mathus-Vliegen LM, Devriese PP, Semin A, Tan J et al. Gastropharyngeal and
laboratory. In: Adam A, Mason RC, Owen WJ (eds).
6.
Zaninotto G, Costantini M, Boccu C, Anselmino M, Parenti
techniques of endoscopy in evaluation of cervical
Dysphagia. 1994 Fall; 9: 256-61. 5.
Dray TG, Hillel AD, Miller RM. Dysphagia caused by neurologic deficits. Otolaryngologic Clinics of North America. 1998; 31: 507-24.
O'Donoghue S, Bagnall A. Videofluoroscopic evaluation in the assessment of swallowing disorders in paediatric and
Media, 2000: 85-99.
Practical management of oesophageal disease. Oxford:
gastroesophageal reflux in globus and hoarseness.
Isis Medical Media, 2000: 35-52.
Archives of Otolaryngology - Head and Neck Surgery.
Richter JE, Bradley LA, De Meester TR, Wu WC. Normal 24-hr ambulatory esophageal pH values. Influence of
2000; 126: 827-30. 15.
Kronenberger MB, Meyers AD. Dysphagia following
study center, pH electrode, age and gender. Digestive
head and neck cancer surgery. Dysphagia. 1994; 9:
Diseases and Sciences. 1992; 37: 849-56.
236-44.
154 Globus pharyngeus PETROS D KARKOS AND JANET A WILSON
Definition Epidemiology Aetiology Diagnosis Management options and clinical recommendations Outcome: Follow-up and prognosis
2037 2037 2038 2039 2040 2040
Key points Best clinical practice Deficiencies in current knowledge and areas for future research References
2041 2041 2041 2041
The data in this chapter are supported by a Medline search using the key words globus pharyngeus, globus pharyngis, globus hystericus and focussing mainly on aetiology, diagnosis, management and outcome, as well as deficiencies in current knowledge and areas for future research.
DEFINITION Globus (globus pharyngis, globus pharyngeus) is a feeling of something stuck or a sensation of a lump or tightness in the throat. The term comes from the Latin globus, a ball. Hippocrates first mentioned the term in his treatises and regarded it as a disease of women being inextricably involved in the uterine axis from which all hysteria was believed to be derived at that time. 1 In 1794, the term 'globus' was defined in the Oxford University Dictionary as 'a choking sensation as of a lump in the throat to which hysterical persons are subject'. However, patients suffering from globus sensation have been found to have no higher scores for hysteria than healthy subjectsZ,3 and the term 'globus hystericus' has been abandoned. Today, patients are referred for investigations to otolaryngologists and gastroenterologists and rarely to psychiatrists or psychologists, even though globus has been identified as the fourth most discriminating symptom of somatization disorder, 4 after vomiting, aphonia and painful extremities. Globus is a well-defined, clinical symptom that is persistent, difficult to treat and has a tendency to recur. It
is often a nebulous clinical diagnosis to make because the symptoms are variable within and between subjects and objective clinical findings are by definition absent. Globus is considered functional when no organic explanation is detected. In the past 50 years the most popular organic explanations for the symptom are that globus can be an atypical manifestation of silent gastrooesophageal reflruC' 3, 5 or caused by oesophageal dysmotility.6,7[**I*]
EPIDEMIOLOGY Globus accounts for around 4 percent of otolaryngological referrals. 8 Up to 45 percent of the general population have mild, intermittent symptoms resembling globus at some time in their lives. 9 The peak incidence of the symptom is in middle age; the globus symptom is very uncommon in patients under the age of 20 and adolescents are much more likely to experience eating disorders than globus sensation. Older people can complain of globus sensation, but it is often difficult to differentiate this from age-related mucosal inflammation.
1
2038 I PART 15 THE UPPER DIGESTIVE TRACT
I
Since the time of ancient Greece, globus was considered a disease of women. The everyday experience of globus is reported more or less equally by both sexes 9 although from those seeking medical attention, three of four subjects are women. Deary et al., 10 in a survey of over 1150 middle-aged women shoppers, found that 6 percent described a persistent feeling of something caught in the throat in the previous three months. The same authors also showed that the most important predictor of hospital attendance was the severity of the globus sensation. [***1**]
AETIOLOGY A wide variety of explanations, physical and psychological, have been proposed over the last four decades. Some popular theories of the past include strap muscle spasm, hypertrophy of the lingual tonsils, sinusitis, anterior cervical osteophytes, overclosure of the bite, granular pharyngitis tonsillitis and thyroid nodules. One recent report of 88 patients linked globus with a wide variety of such lesions/ but the nonspecific nature of globus and the high incidence of these conditions in the general population makes a causative association hard to establish or refute. The most popular organic aetiological theory of recent years is that globus is an atypical manifestation of gastrooesophageal reflux or oesophageal dysmotility, and the association of globus with these disorders has been studied in detail over the past three decades. 11 In the general population, there is no symptomatic association of low-grade globus with reflux symptoms. 9 Several studies on this subject using ambulatory 24-hour pH monitoring, which is accepted as the most sensitive and specific test for gastrooesophageal reflux, give conflicting results and are hampered by the high prevalence of gastrooesophageal reflux in the middle-aged, western population. 11 Possible mechanisms for symptom production include contact of refluxed acid and pepsin with oesophageal and tracheal mucosa that activates vagal reflexes leading to reflux or spasm. 12 In addition, there may be direct inflammation of the upper oesophagus, with or without frank oesophagopharyngeal reflux. There may also be reflex cough and throat clearing in response to distal or proximal oesophageal acid exposure. This explains further the limitations of pH-metry in elucidating the role of acid in the generation of atypical symptoms. No one really knows whether the issue is one of excess acid, or excessive acid sensitivity - direct or reflex, or appearance of acid in an unusual location (oesophago-pharyngeal junction). Thus the issues of where to measure acid and what criteria of abnormality might be clinically significant in a patient with globus remain unresolved. A study of 142 patients with globus, using manometry, ambulatory pH monitoring, radiological examination
and distal oesophageal biopsy, demonstrated reflux in 23 percent of patients, implying that, while reflux may be responsible for globus in some patients, it is not the cause of the globus sensation in the majority of individuals with this symptom. 13 Other studies suggest that pathological reflux may be present in 30-40 percent of patients. 14, 15 While the precise figure will doubtless vary from sample to sample, depending on the clinical selection criteria for gastrointestinal investigation and the upper reference range used to define pathological reflux, it appears that at most reflux accounts for only a minority of the globus patients' symptoms - albeit, a substantial minority. Although earlier studies suggested abnormally elevated upper oesophageal sphincter pressures in some patients with globus, subsequent work with more appropriate manometric equipment did not confirm this result. 13 A more recent review of stationary manometry attempted to link the incidence of globus with a 'hypertensive' upper oesophageal sphincter. Only 3 percent (only one man) of 650 subjects with normal tonic upper oesophageal sphincter pressure had globus, but 28 percent of the 101 with elevated tonic pressures had globus. 16 In this latter globus group with elevated sphincter pressure, the numbers of men and women were almost equal. No relationship with reflux could be demonstrated, although only a minority had pH studies. The authors conclude that there may be two subgroups - women with heightened throat awareness, but normal sphincter pressure, and a second group with a greater prevalence of men and an abnormal high-pressure zone. The study was retrospective, however, and the symptom of 'globus' identified in this gastrointestinal investigation unit is likely to differ somewhat from that of patients presenting to otolaryngologists with a primary globus symptom. In 1983, Gray described inferior constrictor strain swallows caused by increased awareness of contact between the epiglottis and the lingual tonsils. This could provoke a vicious circle of dry saliva swallows with increased frequency of swallowing, reduction in interswallow interval, aerophagy and failure of upper oesophageal sphincter relaxation. 17 The tightly closed upper oesophageal sphincter is then postulated to be the origin of the sensation of a lump. This remains an intuitively appealing concept and one that can usefully be used as a model for the genesis of globus in patients in whom other explanations are lacking - but nonetheless, there is no investigative evidence to support its validity. Oesophageal dysmotility and its association with globus has been investigated for decades 6 ,7 and the results are again conflicting. Two of the largest recent studies however, seem to agree that minor, nonspecific oesophageal motility disturbances are common. is, 19 Knight et al. 19 found that 73 percent of 100 patients with laryngopharyngeal reflux symptoms undergoing manometry had motility problems, nonspecific in the majority, and not significantly related to coexistent reflux. The aetiological and practical significance of these findings, if
Chapter 154 Globus pharyngeus I
any, nonetheless remains unclear. Similarly, the report that demonstrated the rare condition of lower oesophageal sphincter achalasia in over 25 percent of globus patients is almost certain to have been dealing with a select group of patients. 7 The possibility of a psychogenic, nonorganic cause in the pathophysiology of globus has also been studied over the last 30 years. There is growing evidence that at least a substantial minority of women with globus is psychologically distressed, and this distress is often compounded by social stress factors. These patients can be depressed or anxious with or without associated panic attacks. 20 Many patients with functional somatic symptoms have an excess of previous medically unexplained symptoms. 21 They also tend to show underlying personality traits of neuroticism and to a lesser degree introversion, coupled with excessive somatic concern. IO External factors have also, however, been shown to be related to the onset of globus. Compared with control otolaryngology outpatients, globus patients show higher levels both of minor dayto-day irritations or 'hassles' and of major adverse life events (as assessed by the Bedford College Life Events and Difficulties Schedule).22,23 Of 50 patients with globus, 72 percent interviewed had a severe life event or major difficulty in the 12 months prior to presentation, compared with only 27 percent of controls. Globus patients have also been found to have fewer close, confiding relationships than control patients. 23 In many patients the aetiology appears multifactorial (Figure 154.1). [***/**/*]
DIAGNOSIS The diagnosis of globus sensation is rarely difficult to the experienced clinician. A combination of a detailed history, examination and minimal investigations together with a high index of suspicion is required. Full history should focus on the patient's symptom description. Globus may be described very variably - as a hair, a piece of skin, a blob of catarrh or a choking sensation, as well as the classic ball-like lump or a foreign body in the throat. True dysphagia and odynophagia are usually absent, as is weight loss. The sensation is typically maximal between meals and may well disappear with eating, leading the patient to eat more and gain weight. However, at least one in five patients will note persistence of the abnormal sensation during deglutition. 13 Globus is more troublesome at the end of the working day, probably because, like tinnitus, patients have more time to focus on their problems. Patients will often admit to repeated dry swallowing and throat clearing, if specifically asked. Symptoms of gastrooesophageal reflux should be sought, as frequent heartburn makes a reflux-related globus more likely (although the absence of reflux symptoms by no means· excludes a contribution from reflux to symptom generation). In one recent series of patients with laryngeal
2039
Major adverse life events
'Hassles' - - .
GORD
+/- oesophageal dysmotilty
Figure 154.1
Causes of globus sensation. GORD, gastro-
oesophageal reflux disease.
symptoms suspected of having reflux, globus (83 percent) was second only to throat clearing (88 percent) in frequency - while fewer than 40 percent of patients had symptomatic heartburn. 24 A part of the consultation that is frequently missed, often because of the clinician's reluctance to ask 'embarrassing' questions, is the psychological history. Major life events, history of panic attacks and anxiety are questions the clinician should be willing to address. 23 A symptom assessment scale to grade the severity of symptoms can be useful, particularly during patient follow Up.25 The major elements of the syndrome are the sensation of something stuck, a discomfort or irritation and a continual sense of wanting to swallow. 25 Elderly male smokers are not the typical globus patients and high index of suspicion is required to exclude sinister disease, such as pyriform fossa cancer. In a nonsmoking female patient, the only common head and neck squamous cancer is a post-cricoid lesion and this is usually found in elderly, iron-deficient patients and again is associated with true alteration in eating patterns. Examination should include complete otolaryngological assessment with emphasis on neck palpation and flexible laryngoscopy, which, if combined with video facilities for the patient to watch, can often reinforce reassurance that the laryngopharynx, while feeling abnormal to the patient, has no observable abnormality. Radiological swallow investigations, such as barium studies, are typically normal and add nothing to the
2040 I PART 15 THE UPPER DIGESTIVE TRACT diagnosis. Radiology is insensitive to much reflux and typically shows at most minor nonspecific pharyngeal abnormalities like cricopharyngeal indentations. I3 It is more valuable to reinforce the message that globus is essentially a sensory disturbance, like itching and tinnitus, than to expose the patient to unnecessary radiation exposure. Investigations, furthermore, may exacerbate the situation, as they tend to 'medicalize the patient's disease' and raise fresh anxieties. Even if negative, this may not, as the optimistic clinician hopes, reassure the patient, but rather make her or him feel that the doctor is looking for something that is eluding detection. The historical habit of using direct endoscopy under general anaesthesia to evaluate unselected globus patients 26 should now be abandoned. Flexible pharyngoscopy in the outpatient clinic is superior, cheaper and safer. The issue of possible reflux disease is better assessed by other means (therapeutic trial of antacids, flexible oesophagoscopy or pH-metry). Where the relevance of reflux remains in doubt, there may be benefit from the administration of pH-metry in conjunction with a modified symptom index. IS Only if there are atypical features in the history and clinical examination that raise the clinician's suspicion should any additional investigations to exclude sinister disease be embarked upon. In summary, the ever-increasing availability of fibreoptic flexible pharyngolaryngoscopy as an outpatient tool has aided reassurance and saved patients from unnecessary and expensive investigations. [**** /*** /**]
anything other than part of the natural history of the condition. Antidepressants have been used for the treatment of globus, but in small series. The early reaction to tricyclic drugs often includes a phase of heightened anxiety, causing many patients to discontinue therapy. In the small number of patients with low neuroticism scores and lower baseline levels of anxiety, however, there is some evidence that tricyclic antidepressants can actually be quite effective in resolving the symptom. There appears to be a learned response to stress causing increased tone in the muscles of the neck leading to a sense of a pressure at the front of the throat. Thus, relaxation training, acupuncture treatment and hypnotherapy have been used with some encouraging results. The vicious circle of dry swallowing and throat clearing should be explained. As with all vicious circles, it is a question of breaking it sufficiently for a new pattern of behaviour to be acquired. Once aware of this it can be controlled through a drink or yawn with the aim of eliminating it very quickly. 28 Waering et al. 28 believed that globus sensation might be associated with excessive laryngeal and pharyngeal tension. Strategies used in their study included careful assessment, especially of life stresses with additional symptoms of dysphonia and throat clearing, neck and shoulder exercises to reduce the laryngeal muscle tension and general relaxation techniques. Adequate rehydration and voice exercises and advice, together with avoidance of cigarette smoking and spirit intake can help particularly when globus is accompanied by dysphonia. [****/**]
MANAGEMENT OPTIONS AND CLINICAL RECOMMENDATIONS
OUTCOME: FOLLOW-UP AND PROGNOSIS
Reassurance is important and can, as stated above, be rendered more real for the patient if the otolaryngologist takes time to demonstrate the image of the relevant areas at flexible endoscopy on the video monitor. A strong history of gastrooesophageal reflux may respond to a powerful antacid, such as omeprazole as Shaw and Searl24 demonstrated in a study of 96 patients with laryngeal manifestations of reflux. However, it is difficult to predict success rates from antereflux therapy as at least 30 percent of globus patients suffer from reflux. 8 The small volume of level 1 evidence on empiric treatment of reflux has failed to demonstrate superiority of proton pump inhibitors over placebo, suggesting that laryngopharyngeal reflux may perhaps be a self-limiting 27 condition. If there is no symptomatic response to antacids, then either reflux is not relevant, or no longer relevant (even if acting as an initiator) or there is much slower response of cervical reflux symptoms to antacid than of dyspepsia, for unknown reasons. This last explanation is often cited by enthusiasts for the 'reflux hypothesis' of cervical symptom generation - but of course there is no evidence that such a slow 'response' is
Globus pharyngeus is an abnormally persistent symptom and is difficult to treat. Care must also be taken in outcome evaluation, to distinguish between improvements in the intensity of globus sensation and unchanged symptom levels, but with much lower levels of concern and 'throat awareness'. Much has been written about the aetiology of globus, but there are only few reports of the long-term follow up and prognosis of patients with globus sensation. Mair et al. S suggested that the sensation may persist at two years in 85 percent of women and 95 percent of men. Wilson et al.,29 in a follow-up study of 104 patients, concluded that, although there is a reduction in occult psychiatric morbidity in patients with the globus sensation over time, underlying personality traits remain stable and that there is a remarkable persistence of pharyngeal symptoms. Symptoms persist for at least two years in the majority of patients with more severe complaints and last as long as seven years in 45 percent of subjects. 3o The persistence of symptoms for years, even at a low level, should be explained to patients during consultation. It is perhaps more cost-effective to follow up and reassure patients in an outpatient setting rather than arrange for
Chapter 154 Globus pharyngeus
expensive and often negative investigations which, although reassuring for the clinician, often increase the patient's anxiety by creating the impression that something has been missed. A specialized 'globus clinic', if facilities permit, is often very helpful because it gives the opportunity for patients to meet with other 'sufferers' and realize that their symptoms are quite common! [**]
Deficiencies in current knowledge and areas for future research Precise role of gastrooesophageal reflux needs further research, in particular with reference to whether the patient is suffering from excess acid exposure or excess sensitivity. If excess acid, is it lower oesophageal acid exposure or pharyngooesophageal reflux? If excess sensitivity, is it of the lower oesophagus (with referred sensation) or of the pharyngooesophageal segment? There are no good randomized, controlled trials of antacid therapy. What is the role of inadequate social support/close confiding relationships in the aetiology? To what extent is globus part of a pattern of different, recurring functional somatic symptoms?
KEY POINTS • Globusis •. one ofmal1y()toiaryngological, .., functl()nalsomatic.·symptorns. • It occursinapersistenfform in upto6 percent of the fe111ale, western, rniddle-aged population at any onetime. • Thesyndiome is probablyheterogen~()lisa.nd mu.ltifactorial. .' It isassoci
REFERENCES 1. 2. 3. 4.
Identify any atypical features in the history - heavy smoking/drinking; true dysphagia rather than improved by the presence of a food bolus; progressive rather than fluctuating. Elicit likely relevance of clinical gastrooesophageal reflux. Careful clinical examination with flexible fibreoptic examination of the upper aerodigestive tract should be undertaken . ./ Reassure the patient and reserve further investigations for the 'atypical minority'. Over-investigation may reinforce anxieties. The more negative tests the doctor is seen to require, the more the patient fears they have some still undiscovered organic cause. Explain the uncertain pathophysiological mechanisms behind globus. Avoid dry swallows. Anticipate only a very slow resolution - but a fairly rapid reduction in throat awareness. Consider active psychological intervention in those with more obvious distress. This may be speech therapy, anxiety management groups or even psychotropic medication as local circumstances allow.
I 2041
5.
6.
7.
8. 9.
* 10.
Malcomson KG. Globus Hystericus Vel Pharyngis. Journal of Laryngology and Otology. 1968; 82: 219-30. Batch AJG. Globus pharyngeus (part 1). Journal of Laryngology and Otology. 1988; 102: 227-30. Batch AJG. Globus pharyngeus (part 2), Discussion. Journal of Laryngology and Otology. 1988; 102: 227-30. Othmer E, DeSouza CA. A screening test for somatisation disorder (hysteria). American Journal of Psychiatry. 1985; 142: 1146-9. Mair IWS, Schroder KE, Modalsli B, Maurer HJ. Aetiological aspects of the globus symptom. Journal of Laryngology and Otology. 1974; 88: 1033-40. Farkkila MA, Ertama L, Katila H, Kuusi K, Paavolainen M, Varis K. Globus pharyngis, commonly associated with esophageal motility disorders. American Journal of Gastroenterology. 1994; 89: 503-8. Moser G, Wenzel-Abatzi T-A, Stelzeneder M, Wenzel T, Weber U, Wiesnagrotzki S et 01. Globus sensation: Pharyngoesophageal function, psychometric and psychiatric findings and follow-up in 88 patients. Archives of Internal Medicine. 1998; 158: 1365-73. Moloy PJ, Charter R. The globus symptom. Archives of Otolaryngology. 1982; 108: 740-4. Thompson WG, Heaton KW. Heartburn and globus in healthy people. Canadian Medical Association Journal. 1982; 126: 46-8. Deary IJ, Wilson JA, Kelly SW. Globus pharyngis, personality, and psychological distress in the general population. Psychosomatics. 1995; 36: 570-7. Most recent epidemiological survey of population prevalence of globus.
"!
2042 I PART 15 THE UPPER DIGESTIVE TRACT 11.
12.
* 13.
14.
15.
16.
17.
18.
19.
Hill J, Stuart RC, Fung HK, Ng EKW, Cheung FM, Chung SCS et al. Gastroesophageal reflux, Motility disorders and psychological profiles in the etiology of globus pharyngis. Laryngoscope. 1997; 107: 1373-7. Tauber S, Gross M, Issing W. Association of laryngopharyngeal symptoms with gastroesophageal reflux disease. Laryngoscope. 2002; 112: 879-86. Wilson JA, Pryde A, Piris J, Allan P, Macintyre CCA, Maran AGD et al. Pharyngoesophageal dysmotility in globus sensation. Archives of Otolaryngology Head and Neck Surgery. 1989; 115: 1086-90. One of the largest studies to assess the true prevalence of pathological reflux (including on pH-metry) in unselected globus patients. Walther EK, Schmidt C. Globus pharyngis and gastroesophageal equivalents. Laryngo-Rhino-Otologie. 1997; 76: 225-8. Curran AJ, Barry MK, Callanan V, Gormley PK. A prospective study of acid reflux and globus pharyngeus using a modified symptom index. Clinical Otolaryngology. 1995; 20: 552-4. Corso MJ, Pursnani KG, Mohiuddin MA, Gideon RM, Castell JA, Katz PO et al. Globus sensation is associated with hypertensive upper esophageal sphincter, but not with gastroesophageal reflux. Digestive Diseases and Sciences. 1998; 43: 1513-7. Gray LP. The relationship of the inferior constrictor swallow and globus hystericus or the hypopharyngeal syndrome. Journal of Laryngology and Otology. 1983; 97: 607-18. Schima W, Pokieser P, Schober E, Denk DM, Moser G, Uranitch K et al. Globus sensation: Value of static radiography combined with videofluoroscopy of the pharynx and oesophagus. Clinical Radiology. 1996; 51: 177-85. Knight RE, Wells JR, Parrish RS. Esophageal dysmotility as an important co-factor in extraesophageal manifestations of gastroesophageal reflux. Laryngoscope. 2000; 110: 1462-6.
Brown SR, Schwartz JM, Summergrad P, Jenike MA. Globus hystericus responsive to antidepressants. American Journal of Psychiatry. 1986; 143: 917-8. 21. Deary IJ, Scott S, Wilson JA. Neuroticism,alexithymia and medically unexplained symptoms. Personality and Individual Differences. 1997; 22: 551-64. 22. Deary IJ, Smart A, Wilson JA. Depression and 'Hassles' in Globus Pharyngis. British Journal of Psychiatry. 1992; 161 : 115-7. 23. Harris MB, Deary IJ, Wilson JA. Life events and difficulties in relation to the onset of globus pharyngis. Journal of Psychosomatic Research. 1996; 40: 603-15. Many papers have looked at endogenous psychological risk factors for globus: This is one of only very few to address external pressures which precipitate symptom onset. 24. Shaw GY, Searl JP. Laryngeal manifestations of gastroesophageal reflux before and after treatment with omeprazole. Southern Medical Journal. 1997; 90: 1115-22. 25. Deary IJ, Wilson JA, Harris MB, MacDougall G. Globus pharyngis: Development of a symptom assessment scale. Journal of Psychosomatic Research. 1995; 39: 203-13. Describes development of the only scale for globus severity monitoring: Valuable for those researching globus. 26. Deary IJ, Wilson JA. Problems in treating globus pharyngis. Clinical Otolaryngology. 1994; 19: 55-60. 27. Karkos PD, Wilson JA. Empiric treatment of laryngopharyngeal reflux with proton pump inhibitors: a systematic review. Laryngoscope. 2006; 116: 144-8. 28. Wareing M, Elias A, Mitchell D. Management of globus sensation by the speech therapist. Logopedics, Phoniatrics, Vocology. 1997; 22: 39-42. 29. Wilson JA, Deary IJ, Maran AGD. The persistence of symptoms in patients with globus pharyngis. Clinical Otolaryngology. 1991; 16: 202-5. 30. Rowley H, O'Dwyer TP, Jones AS, Timon CI. The natural history of globus pharyngeus. Laryngoscope. 1995; 105: 1118-21. One of only two studies to look at long term persistence of globus.
20.
*
*
*
155 Pharyngeal pouch
GRANT BATES
Introduction Definition Incidence Diagnosis Key points Aetiol ogy Key points Patho logy Key points Management o ptions
The data in
•.
_
.
H istorical comment Operative details of the methods available for pharyngea l pouch surgery Best clinica l practice Outcomes Conclusions Key points Deficiencies in current knowledge and a reas for future resea rch References
�--
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·# f�'.
2043 2043 2043 2044 2045 2045 2047 2047 2048 2048
•
•
," ., . .... f"_..-' -. .,,,. ,
·Y-:-.:�.o,
this chapter are supported by a Medline search
...
•
0> '
•.
'
•
2048 2049 2055 2055 2059 2059 2059 2059
' . ... ",' • • I">
•
: .••.
using the key words pharyngeal pouch, hypopharyngeal
diverticulum and Zenker's diverticulum.
INTRODUCTION
DEFINITION
This chap ter deals with the management of pat ients who
A pharyngeal pouch is
have a pharyngeal pouch. The condition of pharyngeal
through a defect in the posterior pharyngeal wall. The
pouch is defined, together with the incidence, diagnos i s
terms Zenker's diverticulum and hypopharyngeal diverti
and
culum are also used.
a detailed
discussion
co ncerning aetiology.
The
pathology is discussed, particularly with reference to the risk of developing a carcinoma with in
a pouch. The
a
herniation of pharyngeal mucosa
The location of the herniation is the poster i or wall of the pha rynx through an area of natural
weakness be tween
treatment options, which include endoscopic surgery and
the two parts of the inferior constrictor muscle. This area
various types of external approach surgery, are discussed
was described by Killian in 1908 and is referred to
and a historical comment is included.
Killi a n's dehiscence. 1
as
Endoscopic surgery is emerging as the method of choice and therefore the operative techniques of endo
s urgery are discussed in detail. A review of the maj o rity of the published series involving ten or more patients since 1940 is g i ven , together with a summation of
INCIDENCE
the results for each technique (see below under Out
pouch in the general population because not
scopic
comes). The conclusions drawn are that endoscopic surgery involving either the CO2 laser or a stapling device is the method of choice and, ideally, one surgeon in each
large ce ntre should become a specialist in pouch surgery,
to quantify the incidence of pharyngea] all patients e present to a sp ec ialis t. The i ncidenc of presentat ion to an ear, nose and throat (ENT) speci alist was estimated as
It is difficult
0.47 cases per 100,000 per year by Juby in 1969.2 More
recently
(1999) the incidence
in
the Oxford region (UK)
_
l�
'�_
_ ____
2044
I PART 15 THE UPPER DIGESTIVE TRACT
was calculated as one case per 100,000 per year. It is likely
pharyngeal pouch the early symptoms are of solids
that more patients are being referred because of the less
sticking in the throat with the need to swallow several
invasive surgical techniques now used. Pharyngeal pouch is more common in men with a
times to clear the food. Frequently, the patient makes an attempt to chew every mouthful of food down to small
ratio of approximately 2:1. Patients are usually over the
fragments.
age of 50 years with the most common presentation being
impossible to enjoy a meal with friends, owing to the
As
the
condition
progresses
it
becomes
between the sixth and ninth decades. The condition of
excessive length of time taken to eat the meal and the fact
pharyngeal pouch affects Caucasians and is rare in Asian
that regurgitation sometimes occurs. Eventually, dyspha
and Afro-Caribbean races.
gia with semi-solid foods and then liquids develops. Occasionally, total dysphagia takes place and the patient is unable to swallow their own saliva. Severe weight loss and
DIAGNOSIS Patients present with symptoms of variable severity, not necessarily related to the size of the pouch. The majority of patients present with longstanding symptoms; indeed, it is the insidious onset and slow progression of the symptoms that cause most patients to present with a well developed
pouch and sometimes severe weight loss
(Figure 155.1). Dysphagia is the most common symptom and is present in virtually all patients. Dysphagia means that the patient must have either a mechanical blockage, neuro muscular incoordination or both. Dysphagia should be distinguished from the sensation of a lump in the throat that typifies the globus syndrome. In a patient with a
malnutrition accompanies this final state. Regurgitation of undigested food is present in 80 percent of patients with a pouch. Undigested food may regurgitate into the mouth during a meal, although more often it is after the meaL The regurgitation is more likely to happen when the patient is lying down and sleep may be disturbed by it. A few patients solve this problem by evacuating the pouch before going to bed by pressing on the side of their neck. Frequently, there is stasis of food in the pouch and this leads to a 'foul taste' and friends or relatives may complain about the patient's halitosis. Pulmonary complications frequently arise and result from aspiration of the pouch contents into the larynx. The aspiration may lead to chest infections, pneumonitis, lung abscess, bronchiectasis and lung collapse. Hoarseness occurs due to laryngitis caused either by aspiration or gastric reflux, which commonly coexist. The patient may complain of a lump in the neck that appears intermittently, and gurgling noises in the neck are sometimes noticed. The patient is often aware that food is sticking in the upper throat and frequently will point to the region just below the cricoid cartilage. Clinical examination may reveal a thin or malnour ished patient. The endoscopic view of the larynx and pharynx may be normal although sometimes 'pooling of saliva' can be seen. Occasionally, a soft compressible swelling may be found in the neck, usually on the left side in the anterior triangle. The differential diagnosis includes all motility disorders of the pharynx and oesophagus (globus, scleroderma, achalasia)
as
well
as
structural
oesophageal
disease
(neoplasm and strictures) and, finally, neuropathies and myopathies. Gastro-oesophageal reflux disease (GORD) is often present and virtually all motility disorders have been reported
in
association with GORD.
The
successful
treatment of GORD usually improves the symptomatol ogy of all motility disorders, and is certainly relevant in the treatment of patients with a pharyngeal pouch. The investigation needed to confirm the diagnosis is either a barium swallow or a contrast video swallow
(Figure 155.2). The latter provides considerably more information about the function of the pharyngeal muscles Fig u re 1 55.1
as well as the presence or absence of gastric reflux.3 It is Patients with a pharyngea I pouch are often
essential that the contrast study includes the lower
elderly and frail and may present with marked weight loss.
oesophagus and stomach because a lower oesophageal
Photograph used with kind permission of Albert Rolls OBE.
carcinoma can coexist with a pharyngeal pouch.
Chapter 155 Pharyngeal pouch I
2045
h
accepted. There is agreement abeut the site at whi c
a peuch ferms: the pesterier wall ef the mest caudal part ef the hypepharynx
between
thyrepharyngeus muscle and cricepharyngeus muscle.
the
eblique fibres ef
the
the herizontal fibres ef the
The area between these two.
muscles is triangular in shape and there are very few
muscle fibres in this part ef the pharyngeal wall
(Figures 155.4). This triangular area is called Killian's dehiscence after the man who. first described it in 1908. With the advent ef mere sephisticated and accurate 155.3 and
manemetric metheds fer measuring pharynge-eesepha geal sphincter functien, ene might have heped fer a cemmen
consensus
en aetielegy. On the contrary, even the
mest pepular theeries centinue to. be questiened.
[H/*)
The three main theeries that are currently proposed to. explain the fermatien ef a peuch are: first, that it eccurs mainly
because
ef
an
anatemical
weakness
in
the
pharyngeal wall; secend, spasm of the cricopharyngeus
muscle; third, various theeries that can be labell ed as
inceerdinatien of the pharyngeal muscles.
Killian's dehiscence: an area of anatomical weakness Van
Overbeek has propesed that anatemical dehiscence is
the majer cause ef pharyngeal peuches.4 He re as ens that in humans the larynx: is an impertant structure generally
Figure 155.2
Video swallow illustrating pharyngeal pouch and
cricopharyngeal bar.
l a rger
than in ether animals. In mest mammals the larynx skull base, but in human$ it has
is le ca ted just belew the
descended to.
the cervical
regien.
Censequently,
the
pharyngeal censtricter muscle fibres in humans (with the exceptien ef cricepharyngeus)
KEY POINTS,,;
Th�, ,co.nditioP" 0. C,curs ,almost excl,usivelY'in
• ,.
"
•
is attached to. the skull base. Hewever, the cricephar
yngeus muscle has herizental muscle fibres which arise
, Jnciclen�e., js o'ile
•
,·
Ca tl ca,s i ans ,
Dysphagia'"
.
.
"
.
-.,
.
regu,�gi.tatioil;l) hearsenes.
p:ulm6nary com�plications ,are the mciin. �y�p.toms:'.:· ,,',;; ," ::'0 ,', " . ,
I
", .. . ,: Differential. diagnesis:. glebus) �derederma, . . ac hal C;\si� , neeplasm, stricture,', neurepathies. .... , •
•
have assumed an
eblique ceurse because the raphe in the dersal midline
Iii
Common assetiatien with g as tre ·
-
oes ophage al .
frem either side ef the criceid cartilage and net the skull
base. Therefere, the 'descent ef the human larynx' gives rise to. Killian's dehiscence. (It sheuld be neted that pharyngeal peuches de eccur in other animals.) Van
Overbeek further prepeses that individual varia
tiens in anatomy are the cause of a pre di sposi tion fer hypepharyngeal diverticulum; for instance seme indivi duals with lenger necks might have a larger triangle of Killian.
Perrott
studied
the
pharyngeal
muscles
in
reflux.
cad avers and feund several different patterns ef fibre
swallow is best.
cricepharyngeus, and in each individual muscle.4•5 He
COntrast study re quired and dyna.mic:video·. .
arrangement
in the gap between thy rop haryngeus and
suggested that in seme ind i v iduals the arrangement ef the
cricepharyngeus muscle leaves denuded pertio n s, and
therefere these individuals were mere liable to. peuch
fermatien.
AETIOLOGY
Over the years, many theories concerning the aetiology of
pha ryngea l peuch have been advanced but no. ene theory
To acceunt fer the fact that pharyngeal peuches develop after 40
years ef
age, Van Overbeek suggests that
with ad vanc ing age there is less ef tissue elasticity and a
g
decrease in muscle tone. The large size ef the laryn e al
2046 I
PART 15 THE U P PER
DIG ESTIVE TRACT
�r---- Thyropharyngeus
----""'-::=+---- Killian's dehiscence
-+----- Cricopharyngeus
rare div e rt icula. In Van Overbeek's series of 545 patients with pharyngeal pouch, nine patients were from four families and three of the nine were brothers from the same family. All 545 patients were Caucasian.4 Van Overbeek states that his manometric studies showed that in normal people, as well as patients with a pouch, there is a high intraluminal pressure in the caudal hypopharynx that peaks during pharyngeal contraction. He proposes that in individuals with an anatomical predisposition (large or weak Killian's dehiscence) a mucosal prolapse takes place and over the years the intraluminal pressure produces a pulsion diverticulum that gradually increases in size. He found no significant differences in the maximal contraction pressure in the hypopharynx between patients with a pouch and normal individuals, and thus concludes that the problem is due to an anatomical weakness (Killian's dehiscence).
Spasm of the cricopharyngeus muscle Figure 155.3 Posterior view of pharynx to illustrate Killian's de hiscence. Redrawn f ro m the British Journal of Hospital Medicine with p e rm i ss i on from The Medicine Group (Journals) Ltd.
Hyoid External ----I'----'f+H+i11
b one
laryngeal nerve
Thyrophyaryngus Thyroid cartilage
....,..".....-----=-...,.- C ric o p h aryngeu s
�--Trachea Jr-��-R -=::�---- ecurrent laryngeal
The cricopharyngeus muscle normally is in a state of tonic contraction, but relaxes at the end of the second stage of swallowing when the sequential contraction of the pharyngeal constrictors occurs from above down wards. Various functional abnonnalities have been suggested to account for pouch formation. 6 8 Negus, Sutherland7 and Belsey favoured the theory that persistent tonic spasm of the cricopharyngeus muscle prevents the downward passage of the bolus and creates a high pressure above the cricopharyngeus that eventually ca uses herniation through Killian's dehiscence. Dohlman and Mattson9 stressed the importance of an intact prevertebral fascial layer that norm all y supports the posterior wall of the larynx. They reasoned that, with increasing age, the fascia ma y weaken, allowing the larynx to fall forwards and thus decrease the circumference of the cricopharyngeus muscle, which is normally stretched open during the act of swallowing. A functional obstruction would be produced and with elevation of intrapharyngeal pressure on swallowing, herniation of mucosa through the weakened posterior triangle, now unsupported by prevertebral fascia, would take place.
nerve
Figure 155.4
La t e ra l
view of pharynx and larynx showing pouch prot ruding between the thyroph aryngeus and cricopharyngeus muscles. Redra w n fro m the British Journal of Hospital Medicine with pe rm i ss ion from The M edicine Group (Journa ls ) Ltd.
skeleton may explain why pharyngeal pouches are more common in men. That an anatomical predisposition may play a prominent role in p ou ch formation is also supported by the familial incidence that happens with these relatively
Incoordination theories
Ardran, Kemp and Lund 10 used contrast cineradiography to examine 16 patients with pouches of differing sizes and 17 normal subjects. After the initial swallow, the main bolus descended into the phar ynx to be moved on by the pharyngeal stripping wave. In patients with pouches they found this to be defective in two ways: fi rst, the oropharyngeal contraction was weak, and second, the pharyngeal peristaltic wave was also weak together with early closure of the cricopharyngeus muscle. Conse quently, on their studies they proposed a mechanism of
Chapter 155 Pharyngeal pouch
pouch formation. The cricopharyngeus contracts prema turely
as
and
the
stripping
wave
descends
to
the
prematurely closed sphincter it pushes the posterior pharyngeal
which, in time, goes on to form a pouch.
al.ll came to similar conclusions by measuring
the intraluminal pressures in patients with pouches and comparing them with those of normal subjects. The resting tone of the cricopharyngeus was found to be
all subjects, but in patients with a pouch the
normal in
cricopharyngeus was found to contract a fraction of a second before pharyngeal contraction was complete so that p haryngeal oesophageal peristaltic sequence was not -
coo rdinated. Lichter12 also supported the incoordination theory. His
not all the abnormalities were noted in all patients on all swallows. This individual variability further complicates accurate pressure measurements.
wall down and forwards to meet the back of
the cricop haryn geal sphincter. A dimple is produced Ellis et
I 2047
manometric
sphincter relaxes
study for
showed
the
altho ugh
that
normal
amount
the
of time,
relaxation begins prematurely and therefore ends prema
p haryngeal pressures
turely. The effect is the same: high
conducive to herniation of mucosa through a muscle deficient area. Lichter also noted the phenomenon of repetitive pharyngeal swallow, thought to be
a
result of
obstruction to the swallow wave at the upper oesophageal
CONCLUSION
The true pathophysiology remains uncertain, altho u gh some mechanism incorporating incoordination between the des cending
peristaltic
wave and
cricopharyngeus
muscle is still most widely held as being responsible for creating an abnonnally high intraluminal pressure that subsequently leads to mucosal herniation thro u gh the weak area of Killian's dehiscence. Gastric reflux probably frequently contributes to the muscle incoordination. It is now agreed by the majority of surgeons that the cricopharyngeal muscle is involved pouch formation although
in
the aetiology of
its exact relationship may not
be understood and therefore a cricopharyngeal myotomy is recommended. With endoscopic techniques this is always carried out because the cricopharyngeus muscle lies within the bar that divides the pouch from the oesophagus . For operations involving pouch excision a separate myotomy is required.
sphincter, since it disappeared following sphincterotomy. 13 Hunt proposed that gastro-oesophageal reflux may lead to cricopharyngeal spasm or incoordination. The reported incidence of gastric reflux in patients wi th pharyngeal pouches ranges from 5 to 100 percent, with the incidence
in the normal population being put at 23
KEY POINTS •
percent. 14 The wide variation in these series could easily be explained by how persistently the symptom of reflux
al.ls studied 29
wa s sought and interpreted. Resouly et patients who underwent pouches
at
Queen
surgical correction
Alexandra
Hospital,
of pharyngeal Portsmouth,
•
•
Killliao's dehiscence is an area of potent i al weakness beh"een the thyropharyngeus and cricopluuyngcus muscle. Dysfunction of the cricopharyngeus muscle is involved in pouch formation. Gaslro-oesop'hageal reflux: may contribute.
UK.IS The patients were interviewed and barium swallow
studies performed from 3 to 48 months postoperatively. Of the pa tients sampled, 19 were found to have reflux and 20 dysmotility. Their findings suggest that many patients with a pouch may have a generalized oesophageal muscle dysfunction and not purely a localized incoordination of the cricopharyngeal muscle. Rarely, a pharyngeal pouch may form by traction as
opposed
pulsion.
to
The
adhesions
associated
with
su rgery to fuse the anterior cervical spine following trauma can (pu11' a pouch out
0f
the pharynx.
16,17
In summ ary, opinion concerning the pathophysiology of pharyngeal pouch is divergent. Part of the di sagree ment
may
techniques
.
be
ascribed
The
mechanical Furthermore,
high
stimulation the
to
differences
reactivity makes
anatomical
of the it
in
to
configuration
to
study. of
the
sphincter is such that normal pressure readings vary
with
the circumferential orientation of the pressure reading
catheter.
The histology of
an
excised pouch shows an epithelial
lining of stratified squamous ep ithelium and submucosa, often surrounded by fibrous tissue. Nearer the neck of the pouch, scanty muscle fibres are found in the wall.
[**/*]
Carcinoma occurring within a pouch
m easuring
sphincter
difficult
PATHOLOGY
IS
It should also be noted that although the investigators drew their conclusions from the pr edominant findings,
Carcinoma within a pouch was first described by Vinson in 1927; it
is a rare
problem with only 47 cases reported in 2o 19 Huang et al., in a series of 1249
the English literature.
patients, found four patients with a within the
p ouch,
malignancy arising
an incidence of 0.32 percent . In Van
Overbeek's series of 545 patients only two (0.4 percent) had a carcinoma.4 However, Bradley et
aI.,
in a retro
spective review, found that out of 50 pharyngeal pouch
2048 I
PART 15 THE UPPER DIGESTIVE TRACT
excisions, two had carcinoma in situ and two had invasive
MANAGEMENT OPT I O N S
carcmoma. Carcinoma usually seems to occur in individuals who
The management options for patients with a pharyngeal
.
21
have had a very longstanding pouch, with the average duration of symptoms in Huang et al.'s four patients being greater than seven years. The main predisposing factor is thought to be chronic irritation and inflamma tion of the pouch lining caused by food retention. It has been stated that barium studies show a constant filling defect as opposed to the filling defect due to food debris,
which
may
move
or
alter
between
films.
Symptoms indicating a carcinoma are rapidly increasing dysphagia, pain and or blood in the regurgitated food. Nodes or a mass in the neck may be found. Patients with a pouch do not normally complain of pain or bleeding and the
dysphagia
endoscopy
usually
progresses
is required
slowly.
An
urgent
in any individual with these
suspicious symptoms, whether or not they have had a pouch treated before. The endoscopic management of a pharyngeal pouch should include a close inspection of the pouch lining with a
biopsy
of
any
areas
that
look
suspicious.
Close
inspection with a Hopkins rod is recommended and it may be necessary to wash the food debris out of the pouch with saline in order to obtain a reliable view of the pouch mucosa.
at
a meeting
in
Dohlman's
first
1951,
questioned
the
procedure;
to
which
Professor
relieves the retention in the sac, contributes to a more normal appearance and function
in the mucous mem
brane,
and consequently diminishes the danger of , cancer. 22 However, carcinoma certainly can arise in the
approach
surgery.
essential to consider the overall health of the patient carefully as well as assessing how much effect the pouch is having on the individual's quality of life. A small pouch may cause minimal symptoms, in which case the patient may or may not present to their general practitioner. In tum, the general practitioner may well only refer the patient to a specialist when their symptoms are causing major problems. Certainly, when pouch excision was in vogue there was sometimes a reluctance to refer patients because of the daunting operation they faced. From the specialist's perspective most patients who present
will have symptoms that are interfering with their
enjoyment of life. Careful consideration of the patient's general health and their specific symptoms then needs to be undertaken. When weighing up the decision as to whether to operate or not it is important to consider that the symptoms associated with a pharyngeal pouch usually increase with time whereas the elderly patient's overall health tends to decline. In Zenker's original review, 13 of 22 patients died because of the complications associated
in some of the published series are a reflection of this
frailty. Therefore, the ideal surgical method is one that req uires a short anaesthetic and the minimum surgical intervention. The modern endoscopic techniques em ploying either stapling or laser fulfil these criteria. Pouch operations include: •
- laser;
pharyngeal bar and after pouch excision (at the junction of pouch and oesophagus). In all reported cases there has been a delay of several years before the carcinoma often
the
patient
has
had
persistent
symptoms and multiple procedures.23
endoscopic: - diathermy;
pouch wall following endoscopic division of the crico
and
external
The majority of patients undergoing pharyngeal pouch
Dohlman replied: 'I suppose the operation, as soon as it
occurred
and
surgery are elderly and frail. The mortality rates observed
possibility of a carcinoma arising in the pouch wall following
surgery
Particularly for patients with a pharyngeal pouch, it is
with living with a pouch.
Carcinoma arising after pouch surgery Lodge,
pouch can be divided into three groups: conservative, endoscopic
- stapling device; •
cricopharyngeal myotomy alone;
•
excision ± cricopharyngeal myotomy;
•
inversion + cricopharyngeal myotomy.
HISTO R I CAL CO M M ENT Ludlow of Bristol was the first, in 1769, to identify a patient with a pharyngeal pouch.24 In 1878 the clinical •
Carc in o ma developing in
a
percent).
pouch
is
rare
(0.4
features were reported by Zenker,25 who described a hypopharyngeal diverticulum as a pulsion diverticulum
•
At operation it is
•
Carcinoma can rarely occur after pouch
of a pharyngeal pouch, performed the year before in 1885.
surgery.
It was an incidental finding while operating on an army
lining
•
of
essential
to
examine the
the pouch.
ltapid dysphagia) pain
or
blood-stained
secretions equals potential carcinoma.
above the oesophageal inlet.25 In 1886, Wheele?6 reported the first successful excision
officer who had acquired a lateral pharyngocoele from overexercisirrg his voice on the parade ground. This patient recovered completely and his swallowing returned
155 Pharyngeal pouch I
many of the early attempts at to normal. eXCISIOn were unsuccessful being complicated by sepsis and, in particular, mediastinitis. Other methods were therefore advocated inversion of the sac and diverticulopexy, in which the fundus of the sac is secured high up in the neck. All of pharyngeal surgery had mortality rates until the advent of anltIDilOtllCS; Stetten, in 1910, reported a 17 percent mortality rate for pouch excision.27 Even when antibiotics were available, pouch continued to carry external excision of a significant morbidity and mortality. A high fistula rate meant that in most series of pouch excision the average of hospital was in excess of 12 days.28 The use of an autosuture device to excise the pouch, while at the same time sealing the wound edges, improved the results for pouch excision considerably.29,30 Inversion of a pharyngeal pouch was first described by Girard in 1 895.31 This technique was developed to avoid the risk of opening the sac, associated as it was with the serious problems of sepsis and fistula formation. Stell and when it is compared repopularized this rate excision there is a lower with and the has a shorter hospital The principle of endoscopic treatment, in which the bar is divided to create a common so that the bolus must pass into the oesophagus, was first described by Mosher in 19 1 7.34 The common wall between the oesophageal lumen and the was divided with punch forceps. Mosher noted that 'a small cresenteric rim was to be left at the bottom of the pouch to wall off the mediastinum' and that 'should symptoms return it should be an easy matter to cut the common wall still more'. Six patients were treated successfully until Mosher discontinued the procedure when his seventh ae'veH)DE�a mediastinitis and died. The concept of creating a common cavity endoscopically was restored to favour by Dohlman and Mattson.9 Dohlman introduced for the common wall prior to it. He pointed out that division of the bar or septum, within which lay the muscle simultaneously produced a cricopharyngeal myot omy. Dohlman carried out 100 diathermy divisions in 39 and a recurrence rate of 7 pal:1erlts, with no percent. It should be noted that many of his operations Other individuals could not involved at least two procedure achieve his results and this dlathe�rmlY did not gain universal ac<:eptarlCe because many after the patients complained of opera,UOln and required revision pnKeaUlres. Most r"'"t"A"... ",.�"tnr'" reviews showed that the results for excision and endoscopic cricopharyngeal bar division were similar, with both groups having significant and a high recurrence rate. However, one individual figures did stand out; Van Overbeek's series of all treated endoscopically, is still the The first 328 patients were treated by Dohlman's technique using diathermy and, subsequently, 216
2049
patients were treated with a microscope coupled with a carbon dioxide laser to divide the bar. Van all other published series at the success rate time and had the lowest complication rate. Despite Van Overbeek's success with endoscopy in the r'lje(nt�namalS, surgeons in the UK continued with pouch in more or less excision and surgeons, numbers.36 A survey, in 1996, of cardiothoracic surgeons and ENT surgeons showed that with surgeons of 25 surgeons pharyngeal pouches and most of the operated solely through an external approach. Of the 405 half performed external excison ENT surgeons and half used an endoscopic technique. More than 75 performed three or percent of all the surgeons per year. 36 less In the 1990s, developments in laparoscopic surgery stapling devices that allowed division and sealing of tissue simultaneously. Collard was the first surgeon to use a to divide the common wall between the pouch and the oesophagus while at the same time the walls of the pouch and the Inc:1eTJerlae:ntJly in 1993, Martin-Hirsch and describing a similar Newbegin published a case endoscopic using a gun.38 Several centres then developed and refined the so that by the time of the 19 96 survey 28 per cent of ENT surgeons were using a device if used an endoscopic technique. In the following year, the National Confidential Enquiry into Perioperative Deaths (NCE POD) in the UK recommended that en
In order to obtain informed consent, a thorough discussion with the IS required. The author
2050
• PART
15 THE UPPER DIGESTIVE TRACT
explains the procedure with diagrams and gives the patient a DVD,
Technique: endoscopic
which illustrates the technique and
discusses the complications. It is prudent to mention
Under general anaesthesia with endotracheal intubation, a
the following points.
Weerda distending diverticuloscope
•
The possibility of not being able to complete the operation safely. During the preoperative assessment it should be possible to identify the patients in whom access may be difficult. The biggest problem encountered is prominent teeth (usually with expensive crown work) and this may be combined with retrognathia
(Figure 155.5).
These patients
should be told that it may not be possible to staple the pouch safely and an alternative strategy should be discussed prior to surgery. •
Patients should be told that there is a risk of damaging their teeth.
•
There is a risk of perforating the pouch during attempted endoscopic stapling. Should this happen a small tear can be sutured endoscopically or managed conservatively, but if it is a large perforation it would be prudent to open the neck, find the perforation and excise the pouch. It follows that any surgeon undertaking pouch surgery should be competent in
scopy
155.6).
(UK)
(Karl
Storz Endo
Ltd., Slough, UK) is introduced
(Figure
If present, the upper teeth are protected with a
gum guard or wet swab; the latter allows a little more room for the scope. The opening to the oesophagus is identified and the upper blade of the diverticuloscope is carefully inserted into the oesophagus, simultaneously the lower blade enters the neck of the pouch. The blades of the diverticuloscope can be adjusted in two directions, and the necessary adjustments are made until a good view of the cricopharyngeal bar is obtained
(Figure 155.7). The
scope is then suspended with a laryngoscope holder
(Figures 155.8
from the
and
pouch
155.9).
using
a
Food debris is gently cleared rubber-tipped
sucker
and
adherent debris can be washed out with saline from a SO mL syringe. A Hopkins telescope is used to inspect the
lining of the pouch. Any abnormality of the mucosa should be biopsied although it is rare to have to do this. At times, the lining of the pouch will be inflamed and under these conditions it is important to take extra care,
head and neck surgery and the patient should be warned preoperatively that external surgery is a possibility. •
The very small pouch represents a challenge: too small to staple, too small to excise and possibly too hazardous to laser; the patient should be informed preoperatively of the options of living with the symptoms or having a cricopharyngeal myotomy via an external approach.
•
When quoting figures as part of the informed consent, the optimum arrangement is to quote personal figures if this is possible, but if it is not, a conservative interpretation of the outcomes given at the end of this chapter could be used. Figure 155.6 Weerda distending diverticu loscope (Karl Storz Endoscopy (U K) Ltd., Slou gh, UK) .
Figure 155.5 This expensive crown work belonged to a top flight ba rrister and made access for endoscopic pouch surgery difficult but not im possible.
Figure 155.1 A good view of the oesophagus. cricopharyngeal bar a nd pouch can be obtained through the Weerda scope.
Pharyngeal pouch I 2051
Chapter 155
S
n
Figure 155.8
Suspension a pparatus is connected to the Weerda scope and under direct view the surgeon can insert the stapl ing g u n once the pouch lining has been inspected.
Figure 155.9
The Hopkins telescope is used to inspect the mucosa of the pouch lining carefully and a l so is useful in checking the position of the jaws of the stapling gun.
with gentle suction in order to prevent any bleeding. The
staples is rotated so that the staples are in the upper jaw,
presence of blood impedes the view of the operator.
which will be inserted into the oesophagus, with the
Once a satisfactory view of the cricopharyngeal bar is ® obtained an Endopath EZ35B linear cu tting stapling
(lower jaw) going into the pouch staples
gun or similar device is removed from the packet and
introduced through the Weerda diverticuloscope until
checked. At this stage, the end of the gun carrying the
the cricopharyngeal bar lies between the two jaws of the
is introduced.
should
be
available.
anvil (Figure 155.10). Spare
The
gun
is
carefully
2052
I PART 15
THE UPPER DIGESTIVE TRACT
Figu re 1 55.10 Close up view of the jaws of the stapl i ng gu n. The staples are held in the upper jaw which is inserted into the oesophagus a nd the a nvil (lower jaw) goes into the pouch.
gun. The jaws are closed and locked in place. Visual
inspection
and
gentle
traction
ensure
that
there
is
adequate tissue between the jaws. The gun is fired and this divides the septu m and simultaneously seals each of
Figure 155.11 Cricopharyngea l bar has been cut by the stapling device and then the edges sealed with a triple row of staples.
the cut edges with a triple staggered row of staples
(Figures 155. 1 1 and 155.12). The release button is then
pressed to free the jaws and the gun is gently removed, m aking
sure that the jaws are not snagged on any tissue.
Tips and tricks for pouch stapling MAXIMIZING THE VIEW It is most important to try and obtain the best view
possible prior to placing the jaws of the stapling gun over the cricopharyngeal bar. In edentulous pa ti ents with a wide
mouth the Weerda
scope affords an
excellent
stereoscopic view and should be used whenever possible.
If
a
good view can be obtained the operation is usually
straightforward. However, difficult access) and a little trauma and possibly bleeding can convert the situation into one where the surgeon will really struggle.
A few
simple precautions can ensure the best view possible. •
Use a small endotracheal tube, with minimal cuff
A close-up view of the divided cricopharyngea l bar. Note there a re often a few loose staples that are of no concern.
arthritic neck needs care bu t does not often prevent access. If it is not possible to obtain a view with the Weerda scope the Negus pharyngoscope can be used
i nfl at ion.
155.13).
•
Ensure that the patient is totally paralyzed.
•
Use the Weerda scope
•
Figure 155.12
possible to obtain an adequate view in order to complete
if it will fit.
Use a wet swab to protect the teeth
(Figure
In the author's experience it has always been
if the access is
limited.
the operation, but the Negus scope has been required
in
approximately 20 percent of patients. The view afforded by the Negus scope is inferior to the wide view obtained
•
Be prepared to alter the degree of neck extension.
•
with the Weerda scope. The stapling gun does fit down
Use a sucker with a rubber tip; this limits mucosal
the Negus scope; however, the l ast movement involv ing
damage and bleeding. •
placement of the jaws over the cricopharyngeal bar is
Wash out any debris with
•
Use the Hopkins rod.
•
Be extremely gentle with the tissues.
50 mL of saline.
completed 'blind', even if the Hopkins telescope is used simultaneously. Once in place and with the jaws locked, gentle traction on the stapling gun confirms to the operator that there is tissue be tw een the jaws, and the g u n can be safely fired.
DIFFICULT ACCESS In about 20 percent of p atients access will be difficult
owing to a combination of prominent teeth and retro gnathia.
The
intubation
anaesthetist
will
usually
confirm
that
has been difficult (grade'3 or 4). A stiff or
NO APPARENT OESOPHAGEAL OPENING
The oesophageal opening is obviously present, but at times
it can be hard to find. The reason is that as a pouch
pter 155
when
there
in
I-" ...... ,LH�'JH'-.U-
In most
If the gun the
155.13
The
lever
AND SUBSEQUENT
used when access
or
device will fit
1nclrh,·",rl'",nflu
device is removed.
when the
down this scope.
release
free the mechanism.
PREVENTING A MANAGEMENT
is difficult and both the
2053
the operator is too much with one series at least two sets of
V\;;�,ILU';o..u.y
pouch I
and
is
overambitious
pl"I�Nn,np::\1
stalOllr:lg device may fail and if this nalDDI;:ns defect in the tissues of the bar appears. that the
circumstances it is
of the tissues
not sealed the suture via the
several such as the 'Bercr needle holder
holders are
once
"",.lu
is identified it may be pm;SlOle
If a small
and
.... r,\ ....
these
na:)o�:astI1C tube should then be inserted and
the oe�)O]:)nage:al lumen must lie anterior and behind the
of mediastinitis
for
slit
to open the
oe�;ODnallUS if
necessary. Insertion wound drain If the
DIVISION OF THE SEPTUM
a
recommended. is traumatic it
na:)O�:aSl:nc tube. In most had a
bar should be
,_>7,,,,,,,,'_£"\11"1
SIa1;mIlg
"'YI""\{'"'",rI"l'I"'"
wise to inser t a
series one or more small
....
,.,t''' ..... r€'
in the
man who underwent an uneventwith a
initial recovery and after 48 hours he revealed a
device to cut co:m!=)letelY because the anvil this is most unusual and the mechan-
to saw the end of the anvil and or
surface. It
of the
remain unclear.
THE LARG E POUCH "'"...,:...,., """"",. the septum that most of his patIents underwent two
c)<;"�/'U'j.L'"
the easier it is to deal with SIalJllr.lg
�",""U,U.L'-l,"",""
With a
pouch there is
bar and as many sets of
operanons.
takes to divide the bar are used.
A
that extends into the mediastinum is not a contra indication
JAMMING Failure of the too much tissue is
although there are more
gun
rare but the
can
if
between them. This occurs
is to
pOllCnes should be dealt
2054 I
PART 15
THE U PPER DI G ESTIVE TRACT
TH E SMALL POUCH
A patient with a small pouch presents the biggest challenge whether an endoscopic or external approach is used. Unfortunately, small pouches can be symptomatic and some patients who simply have a prominent cricopharyngeal bar and not even a true pouch sometimes also have significant dysphagia. If there is a sufficient cricopharyngeal bar to fill half the jaws of the gun then stapling is likely to work, but a bar smaller than this makes stapling impossible. Advocates of CO2 laser division claim that the laser is able to deal with smaller pouches than the stapling device. While this may be true the margin for error is small. The other options are to let the patient tolerate their symptoms until a more substantial pouch develops or to perform an external cricopharyngeal myotomy.
PREVI OUS PO UCH S U RG ERY
If the patient has had a previous pouch eXCISIOn or inversion and then develops a recurrence it might be assumed that endoscopic stapling would be difficult; this is not the case. Occasionally, scarring twists the pouch to one side or the other but usually the appearances are the same as a pouch presenting for the first time. Following diathermy, laser or stapling division recurrent surgery is usually straightforward.
REC U R R E N C E
A significant recurrence rate occurs with all endoscopic procedures but given the minimal discomfort of the first procedure, most patients are usually willing to undergo a repeat stapling, which is not difficult. The same cannot be said for revision external surgery which is difficult and associated with an increased complication rate. If a patient has recurrent symptoms after an endoscopic procedure, contrast studies are rarely helpful.43, 44, 45 The contrast coats the pouch wall before passing into the oesophagus and the radiologist invariably reports that there is a recurrent pouch. It is only necessary to consider the patient's symptoms when assessing the need for revision surgery.
Postoperative care The patient should not eat or drink for the first few hours after the operation, giving the surgeon time to check the patient's general well-being and, in particular, confirm the absence of neck or back pain, tachycardia and surgical emphysema. A nasogastic tube is not routinely required but should be inserted · if there is significant mucosal damage. Antibiotics are not routinely required and should be reserved for complications. Asensible approach
is to allow the patient to drink water initially and then proceed to a soft diet on the evening of surgery if all is well. The majority of patients can be discharged on the first postoperative day, and can eat normally. Most patients having been denied a good swallow for months need little encouragement. It seems logical to treat patients with symptomatic gastric reflux with protein pump inhibitors although as yet there is no evidence to suggest that this practice reduces the risk of recurrence.
D IVI S I O N OF TH E CRICOPHARYI\l G EA L BAR U S I N G A CO2 LASER
The Weerda scope is used and the cricopharyngeal bar identified in exactly the same way as for pouch stapling. Swabs soaked in saline are placed around the mouth. An operating microscope with a 400-mm objective lens and attached laser is used. The cricopharyngeal bar is then divided using a continuous cutting CO 2 laser beam at 1 5-20 W power. A nasogastric tube is not essential and the patient is monitored postoperatively in the same manner as for stapling. Division of the septum using a laser requires experience because it is often difficult to judge the exact amount of septum that can be safely divided without causing a perforation. Inadequate division, on the other hand, results in recurrence of symptoms requiring revision surgery. A potential advantage of the laser over the stapling technique is when access is difficult, necessitating the use of a small scope; a better view is obtained because there is no stapling device in the way. The laser can also be used on a cricopharyngeal bar that is simply too small for the jaws of the stapler; however, division of such a small bar does carry with it an increased risk of perforation.
The cricopharyngeal myotomy: sol e procedure The approach through the neck tissues is the same as for pouch excision. The assistant passes an oesophagoscope down to just beyond the level of the cricopharyngeus and then withdraws it slightly and rotates the scope so that the light shines through and highlights the muscle fibres, which are divided with a knife. These fibres often do not look substantial and it is important to divide along a length of at least 3 cm. An alternative method is to use the microscope to identify the fibres although it is still helpful to have a solid object, such as a large nasogastric tube, within the lumen.
Pouch excision The operati"on is performed under general anaesthesia with the patient intubated. A pharyngoscope is passed
Chapter 1 55
and the openings to the pouch and the oesophagus are identified. A nasogastric tube is passed down the oesophagus. A large bougie can also be passed down the oesophagus alongside the nasogastric tube. Food debris is gently removed from the pouch with a rubber-tipped sucker. The lining of the pouch is carefully inspected with a Hopkins telescope in order to exclude a carcinoma. The pouch is then packed with ribbon gauze soaked in either proflavin or bismuth iodoform paraffin paste, and the proximal end of the strip of gauze brought out through the mouth. The patient is then finally positioned with a sandbag under the shoulders and the head extended and rotated away from the side of the incision. Either a horizontal incision (level with the upper border of the cricoid) , or a vertical incision ( along the anterior border of the left sternomastoid muscle) is made. The deep cervical fascia is incised along the anterior border of the sternomastoid muscle, which is retracted laterally. The anterior belly of the omohyoid muscle is divided. The sternohyoid and sternothyroid are retracted towards the midline. The middle thyroid veins are then ligated and divided and this allows the ipsilateral lobe of the thyroid gland to be turned forwards. The contents of the carotid sheath are retracted laterally while the pharynx and larynx are gently rotated to the right. It is good practice to identify the left recurrent laryngeal nerve. It is in close proximity to the inferior thyroid artery which may have to be ligated and divided. The recurrent laryngeal nerve enters the larynx just inferior to the cricothyroid joint. The dissection is then carried posteriorly along the anterior aspect of the prevertebral fascia so that the tracheoesophageal groove is identified. The pouch will lie immediately above this and can usually be palpated because of the packing within it. It should also be possible to feel the boogie within the oesophagus. The bougie within the oesophagus provides 'a base' on which dissection of the pouch can be carried out and it also helps prevent the excessive excision of oesophageal walL Sharp dissection of the connective tissue surrounding the pouch is necessary before forceps (Babcock) can be used to grasp the fundus of the pouch. The anaesthetist is then asked to remove the gauze packing. The pouch is carefully dissected free of the oesophagus and the neck of the pouch is carefully cleaned of muscle fibres at its junction with the pharynx. The pouch should be completely mobilized so that it can be held at right angles to the long axis of the oesophagus, with its neck dissected down to the point where the mucosal sac protrudes through the muscular defect of the pharynx. Care must be taken not to pull normal mucosa out through the deficiency. A cricopharyngeal myotomy is completed (see above under The cricopharyngeal myotomy: sole procedure) , and then a large swab should be placed under the pouch to collect any spillage. The neck of the sac is clamped, the pouch excised and the wound edges sealed, preferably using an autosuture stapling gun .
., ( .�
Pharyngea l pouch I 2055
Pouch inversion The pouch is identified endoscopically and packed. The approach is the same as that used for excision. Once the cricopharyngeal myotomy has been completed, a non absorbable purse string suture is passed extramucosally around the neck of the pouch. The pouch is then inverted into the oesophageal lumen and its neck closed with the purse string suture. Recurrence following pouch excision or inversion is common and occurs in more than 10 percent of patients. Contrast studies may be useful in patients who have recurrent symptoms following pouch excision, although a postoperative contrast study by Zeitoun et al. 46 showed a multitude of abnormalities even among those patients who were asymptomatic. Their conclusion was that excision of a pharyngeal pouch does not appear to restore a normal swallow.
Best cl i n ica l practice -/
Strive to obta i n a good view. Treat tissues with g reat respect. ./ A biopsy for abnorma l mucosa . .! If th ere is sign ifica nt tra u m a insert nasogastric tu be. ./ For a sma l l perforation use an endoscopic sutu re. if For a l a rge perforation open the neck and repair. ./ Postoperative contrast stud ies a re u n h e l pfu l . .!
OUTCO M ES The result of the majority of published series involving ten or more patients is shown in Table 155.1. In some of the series detailed data were collected at the time of surgery but in many of the publications the collection of data was retrospective and is therefore incomplete. [ **/* ] A clear trend does emerge from the data. First, pouch excision with or without a cricopharyngeal myotomy is an operation that is usually 90 percent successful, has a recurrence rate of greater than 10 percent and is associated with major complications in at least 20 percent of patients. Lengthy anaesthesia is required and the duration of stay in hospital is usually greater than 12 days. Endoscopic procedures are now just as efficient as pouch excision and are associated with a lower complica tion rate. A few indications for pouch excision remain, including the patient in whom either the pouch or oesophagus is perforated during an attempted endoscopic procedure or the patient in whom a carcinoma is suspected. Some surgeons also advocate pouch excision 2 for young patients and for those with large pouches. 4 The results are better for pouch excision if a stapling
Table 155.1 No.
Resu lts of a l l the major published series for pouch su rgery i nvo lving more than te n patients from 1 940 to 2003.
Author/Ref
Do h l m a n 9
Date of
No.
surgery
patients
1 940- 1 960
1 00
Exclusions
No. a ba n d one d
No. surgeons
Technique
Do h l m a n 's diathermy:
Success
90%
+
Recurrence
Compli cations
7%
No major
1 8/ 1 1 0 (1 60f0)
Fistula:
Length of
Follow-:,up (lTlohths:
service (d ays)
mean, ra ng e)
Not g iven
Not g iven
staged for large pouches Agg e rho l m , I I I u m47
1 989-2001
Excision (without
110
1 00/1 1 0 (9 1 0f0)
Parker, Hawthorne23
1 962- 1 971
24
Several
0
Dolma n's d iath ermy Excision - myotomy
1 6/24 (660f0) 3/7 (430f0) 6/9 (660f0)
70f0 4/7 (57%) 3/9 (33%)
Excision
42/48 (880f0)
6/4
Dohl mans
49/58 (840f0)
1 5/58 (26%)
1 3/ 1 9 (680f0) 7/9 (770f0) 1 4/ 1 5 (930f0)
4/ 1 9 (2 1 0f0) 1 /9 ( 1 1 0f0) 1 / 1 5 (70f0)
1 8/ 1 8 (1 00%) 9 1 .5%
80f0
90.60f0
1 6/2 1 6 (7.40f0)
Various
83.3% 70.60f0
1 / 1 8 (5.50f0) 3/1 9 (1 7.60f0)
?1 ?1
Dohlman's diathermy
6/ 1 3 (460f0)
?1
Excision
2 6/36 (725)
2/36 (5.50f0)
Excision
22/23 (960f0)
1 /23 (40f0)
ESS
1 5/20 (75%) 7/9 (780f0) 3/5 (600f0) 3/3 (1 000f0)
2/20 ( 1 0f0) 1 /9 ( 1 1 0f0)
Excision - myotomy
4
Todd28
1 950-1 972
9 48
18
58
6
Freeland, Bates32
1 975-1 985
Morton, Bartlei3
1 982-1 989
19 9 15
Van Overbeek4
1 964- 1 982
18 328
0
5 3
Excision ± myotomy
Inversion ± myotomy
Excision
Inversion D o h l m a n s : staged for
Nil
l a rge pouch
1 98 1 - 1 992 8
Van Eeden, Lloyd, Tranter44
9
Mora n , W ilson, AI
1 967- 1 984
Muhanna1 4
18 19 73 13 36
10
M i rza, Dutt, M i n has,
1 989-1 999
CO
216
2
laser: staged for l a rge pouch
ESS
14
23
4
Dohlmans Inversion
2 (2%); RLNP: 10 (90f0); other: 13 (1 20f0); death : 1 (0.90f0); tota l : (30%) Neck pa i n : 1 RLN P: 1 ; p n e u monia : 2 RLN P: 2; haematoma: ??? fistu l a : 2 R LN P : 9 (1 9%) ; fistu l a : 9 (1 90f0); med iasti nitis: 2 (40f0) ; pneumonia : 5 (1 00f0) ; stenosis: 3 (5%); tota l : (90f0) Fistu l a : 2; haemorrhag e : 1 ; stenosis: 2; tota l : (9%) RLNP: 7 (370f0): fist u l a : 3 (1 6%) RLNP: 1 (70f0); fistu l a : 2 (1 3%) ; wound i n fecti o n : 3 (200f0) 1 death (6%) Perforati o n : 7 (3.30f0); haemorrha g e : 4 ( 1 0f0) ; oes/trach fistu l a : 1 (0.30f0); stenosis: 8 (20f0); med iasti nitis: 3 (1 .420f0); death : 1 (0.30f0) Perforation : 12 (5.50f0) ; haem orrha g e : 1 (0.40f0)
1 (7.50f0); perforation: 5 (380f0) RLNP: 2 (5.50f0) ; fistu l a : 4 ( 1 1 0f0) ; stenosis: 2 (5.50f0) Perforation: 3 (1 30f0) ; RLNP: 1 (40f0); w o u n d infection: 1 (40f0) Perforation: 3 (1 50f0) Perforation: 1 ( 1 1 0f0)
5-6; 2-8 9
�18
4 16 9 (5-61 )
40
3 ( 1 - 1 0)
40
2.26 4
Average
RLNP:
Irving42
20 9 3 3
7 (6%);
med iosti n i tis:
myotomy)
Nil R N LP:
2 (660f0)
8.5 (4- 1 6)
3 (1 -6) 5.8 (3-8) 5 (4-6) 6.7 (3- 1 0)
Average
10 43
Cricopharyngeal myotomy alone
11
Mackal8
1 957- 1 994
Dohlmans
42
3/42 (7%)
11
+
(5- 1 1 0)
1 ; lung 1 ; perforatio n : 1 ; tota l : 1 4% Fistu l a : 6; RLN P: 2 ; e m physe m a : 2 ; stricture: 1 ; g l ottic oedema: 1 ; tota l : 27%
16
+
(5-365)
4.5
Not given
3 (4%) ; 2 (3%); pneu mothorax: 1 ( 1 %) Perforatio n : 2 (1 3%) ; b l e ed i n g : 1 (6.6%)
Not given
Ave rage
+
48- 1 32
Bleed i n g :
3 (2- 1 4)
37 (3-96)
Not g ive n
Not give n
1 (0-4)
9.3 (1 .5-25)
3.1 7 (2- 1 1 )
Results o f surgery
1
developed carci n o m a ; med iasti n itis:
Not g iven
2;
stenosis: abscess:
13
30
Dilatation
20
Mostly
High
i n effective
12
Benja m i n ,
1 987-1 992
34
0
1 989-2001
69
Pouch
Laser
30/32 (93.8%)
1 /32 (3. 1 %)
Perforatio n :
Laser
58/67 (86%)
6/69 (8.70/0)
Perforation:
2
G a l l a g e r49
13
Kresper, Kacker,
74 14
Bradw e l l , Bieger,
<2
cm a n d
Remacle50
cm
1 085-1 993
15
Laser
1 1 /1 5 (73%)
2/ 1 5 (1 3%)
1 989- 1 999
61
Laser
53/61 (87%)
6/61 ( 1 0%)
Strachan,
4.8 (1 - 1 2 1 )
bleed i n g :
4.5
(2- 1 1 )
H o m e r51
15
Nyrop, Sve ndstrup,
Laser
66/70 (94%)
3/70 (4%)
1 (2%); 3 (5%); i n fl a m mation : 2 (3%) Mediasti n itis: 1 ( 1 %)
ESS
66/68 (97%)
6/68 (8.8%)
Perforation;
1;
ESS
1 3/1 5 (86%)
2/ 1 5 (1 3%)
Perforati o n :
1 (3%)
perforatio n :
Jorg e nsen52
16
Lippert, B e n e d i kt,
1 984- 1 996
70
1 99 5- 1 999
74
1 996-2000
32
H e i nrich, Werner53
17
Cook, H u a n g ,
6
denta l :
5
Richstmeier, Scher40
18
Jara m i l lo, McLay43
1
5
+
1
supervised
repoerted on
registrar
15
patients to having at least
19
Bates, Steve n to n 54
20
Collard , Qtte,
1 994-2004
230
0
0
1
+ su pervised
ESS
1 97/230 (86%)
41 /230 (1 8%)
Denta l :
ESS
5/6 (83%)
1 /6 (1 6.6)
Nil
ESS
32/37 (86%)
4 (9%)
Perforatio n :
8 (3010) ; 1 (0.4%)
registrar
1 992
6
1 992-1 999
37
0
0
perforatio n :
2.1 (1 -6)
60 (3- 1 38) 2- 1 6
Keste ns37
21 22
N ew b i g i n , Sood41 Counter, H i lton,
1 993-1 997
28
1 994-1 998 1 997-2000 ?-2000
25 30 23
1 997- 1 998 1 992-1 996
23 102
death :
1;
d e n ta l :
3;
<2
2-43 ( 1 9)
1
ESS
1 6/9 (84%)
6/1 9 (22%)
Perfo rati o n :
3 ( 1 1 %)
4.1 ( 1 -3 1 )
5 9 (55-73)
ESS
20/25 (80%) 96% 1 4/1 6 (87%)
9/25 (36%) 1 /30 (4%) 2/ 1 6 (1 3%)
Perforation:
2 (8%)
3.4
24-60 1 3.2
22/23 (96%) 96/98 (98%)
1 /23 (4%) 4/ 102 (4%)
1 (4%) 1 (1 %)
4
Baldwin55
23 24 25
Raut, Pri m rose56 Stoeckli, Sc h m i d 57 Thaler, Weber,
0
ESS
0
ESS
Nil Nil
Gold berg, Weinstei n 58
26 27
Luscher, Johansen59 Narne, Cutrone,
0
0 4
Chelia60
1 -1 1 ,
comparative studies;
1 2- 1 6,
laser studies;
1 7-27, ESS
(stapl ing) studies.
24/ 1 2
fol low-up
Lim ited
ESS
Lim ited
ESS
Perforatio n : Perforati o n :
1 2 (4-22) 1 6 (1 -45)
2058 I
PART
1 5 THE U PPER DIG ESTIVE TRACT A note of caution should be added, in that the length of follow-up in the reported series is very variable and it is possible that the recurrence rate for both laser and stapling will rise as more long-term follow-up results are reported. However, a big advantage of the endoscopic technique is that when a recurrence occurs, revision is straightforward. The criticism that a carcinoma may be missed at the time of endoscopic resection is not borne out by the results. There are no reports of this happening in the literature. Bradley's report of a carcinoma in situ being found within the wall of a resected pouch of two patients is of concern, and the advice to inspect the mucosa of the pouch thoroughly with a Hopkin's rod at the time of the operation seems entirely appropriate. The reported cases of a carcinoma developing some time after endoscopic resection and, indeed, after pouch excision, underline the fact that if a patient presents with increasing dysphagia, pain or blood stained regurgitated fluid, then early investigation is required whether they have had pouch surgery or not. The NCEPOD inquiry noted that pharyngeal pouch surgery is an uncommon procedure associated with a significant mortality of 1-2 percent. In the year of the study ( 1 9951 1 996), there were seven deaths following open surgery and one after endoscopic stapling.39 The one death that followed endoscopic stapling has been published but the other seven have not. The 1 996 survey of pouch surgery in the UK showed that 75 percent of surgeons were doing less than three operations a year. NCEPOD recommended that because the majority of patients undergoing pharyngeal pouch surgery are elderly and represent a high risk, specialist head and neck surgeons should perform the surgery and, ideally, there
device is used to excise the pouch and seal the edges of the 2 , 0 pharynx. 9 3 Pouch inversion also appears to reduce the complication rate but the number of patients reported in 2 the literature is smalL 3 , 33 Endoscopic procedures involving division of the cricopharyngeal bar can be seen to produce good results, in p articular, when the larger series under the care of one surgeon are considered. Dohlman's figures for the period 1 940-1 960 remain most impressive, with 39 patients being treated with diathermy, a 90 percent success rate and no major complications.9 The majority of Dohlman's patients did, however, require two-staged operations. Similarly, Van Overbeek's diathermy series of 328 patients recorded a success rate of 9 1 .5 percent, a revision rate of 8 percent and a relatively small number of major complica tions.4 Table 1 55.2 shows that when multiple surgeons, each doing a small number of operations, attempt Dohlman's diathermy technique, the success rate drops to 70 percent with a revision rate of 19 percent, and the complication rate rises. With the advent of the Weerda telescope and the CO 2 laser, Van Overbeek changed to laser division in 1 98 1 and his next 2 1 6 consecutive patients showed the same success rate and recurrence rate as diathermy, but there was a reduction in the number of complications. When the results of several large studies using the laser technique are summated, it can be seen that the technique has a success rate of 90 percent and a recurrence rate of 7 percent. The complication rate is low but higher than for endoscopic stapling. The results for endoscopic stapling are impressive with a success rate of 90 percent, a revision rate of 12 percent and a very low complication rate.
Ta ble
1 55.2
No. patients
Sum mati on of resu lts for the different techniq ues. M ethod
Success
Revision rate
Com p l ications
Length of stay
278
Excision
255 (9 1 0/0)
40 (1 4.3)
587
ESS
530 (90%)
63 ( 1 2.6%)
463
Laser
41 7 (90.6%)
34 (7.3%)
1 00 328
Doh l ma n by Doh l m a n Doh l m a n by Van Overbeek
90% + 91 . 5%
7% 8%
Doh l ma n by m u ltiple su rg eons
56/79 (70%)
1 5/79 ( 1 9%)
79
LI\J P: 35 ( 1 2%) ; fistu l a : 33 ( 1 1 .8%) ; mediastin itis: 4 ( 1 .4%) ; stenosis: 5 (1 .8%) ; pneu mon i a : 8 (2.9%) ; death ; 1 (0.3 5%) ; other: 22 (7.9%) Perforation : 1 4 (2.8%) ; denta l : 1 5 (2.8%) ; death ; 1 (0.2%) Perforation : 1 7 (3.6%) ; bleed in g : 4 (0.9%) ; mediasti n itis : 4 (0.86%) ; other: 6 ( 1 .29%) No major Perforatio n : 7 (3 .3%) ; med iastin itis: 3 ( 1 .42%) ; stenosis : 8 (2%) ; death : 1 (0.5%) ; haemorrhage: 2 (0.52%) ; fistu la : 1 (0.3%) LI\J P: 1 ( 1 .26%) ; perforation : 6 (7.6%) ; med iasti n itis: 3 (3.79%) ; other; 3 (3.79%)
12
2 4
+
C h a pter
should be one, or at most two, surgeons within an ENT department who are trained and competent in this type of surgery: The summated results from the main published series support this recommendation. NCEPOD further recommended that pouch stapling should be the procedure of choice; the summated results indicate that both stapling and laser division of the cricopharyngeal bar should be the operations of choice at the present time. CONCLU S I O N S The short-term results with endoscopic procedures are superior to external operations. Endoscopic stapling or laser division are quick and bloodless, are associated with minimal discomfort and avoid the need for a nasogastric tube. Endoscopic techniques permit an early oral intake and early hospital discharge, thus reducing the morbidity and costs traditionally associated with pharyngeal pouch surgery. The long-term outcome of endoscopic techni ques has often been questioned and now that long-term series have been published there does appear to be a recurrence rate of at least 10 percent. This is no higher than the average for pouch excision, and revision surgery via the endoscope is relatively easy and successful. [** /* 1 Endoscopic stapling is a relatively new technique so the recurrence rate may well increase with time. The results for stapling and laser division are similar. Stapling has the theoretical advantage of reducing the risk of perforation and mediastinitis, whereas the laser permits a better view when there is limited access. Cricopharyngeal myotomy as a sole procedure has a role in the treatment of the very small pouch, but there are now few indications for pouch excision. The experience of the surgeon appears to be of the utmost importance. At times, pouch surgery can be difficult and the complications life-threatening. Surgeons who have developed an interest in pouch surgery sufficient to publish large series have the best results.
KEY POINTS · •
• •
• • '. '
•
• •
Pharyngeal,rouch occllrs in ' elderly, sowetimes frail; , patients. Inddence is qne per 100,000 per year. Diagnosis is made with barium or. video swallow. Surgery improves quality of life. Endoscopic resectiQn with .a , stapling devi.ce orTaser· is ,the treatrnent ' of choice. Recllrrel1ce is , easily treated with endoscopic techniques. Carcinoma. is rare but vigilance is required. Surgeons with a special inierest in pouch surgery shollld treat all . patients.
1 55 Pharyngea l pouch I 2059
Deficiencies in cu rrent know l e d g e a n d a reas fo r fu tu re resea rch ,.. The very sma l l pouch is difficult to treat endoscopica l ly. Changes in the desig n of the stapling device might help resolve this problem, na mely a device that cuts and sta ples a long the whole length of the jaws. Access is d ifficult in 20 percent of patients. Improvements in endoscopes and viewing te l escopes may red uce the degree of d ifficulty. At the present time, surgery usi ng a flexi ble endoscope is associated with a high com p l ication rate, but a method may be devised to d istend the tissu es in a similar ma n ner to laproscopic su rgery. )- The recu rrence rate for a l l types of pouch su rg ery is high and may be re l ated to persistent gastric reflux. Agg ressive treatment of the gastro-oesophagea l refl ux may be appropriate but the evidence is lacking. fo:- Fol lowing all types of pouch surg ery, patients a re rarely com pletely asym ptomatic and it wou l d be usefu l to have a method for treati ng these residual sym ptoms, which a re probably due to a n u nderlyi ng neuromuscular incoord i n ation. J'. The single report of a delayed perforation fo l lowing stapling is worrying and the mechan ism as yet is u nclear. N ewbegin (perso n a l com m u n ication) has suggested that m u lti ple stapling at one session may lead to delayed ischaemia and, if this is tru e, then it may be a ppropriate to red uce the n u m ber of sta p l i ngs and repeat the proced u re if the patient remains sym ptomatic. Doh l m a n and Va n Overbeek d id exactly this for patients with larg e pouches. i> The best operative methods at the present time a re endoscopic sta p l i n g and l aser d ivision and a long term prospective ra ndom ized trial comparing these two techniques may be justified. , I n the U K, virtu a l ly all pharyngea l pouch su rgery is now performed by ENT surgeons. Subspeci a l ization is slowly happe n i ng and is to be encou raged so that with i n each major centre only ENT surgeons with a specia l interest in pouch surgery sho u l d manage pouch patients.
REFERENCES 1.
Ki l l ian Von G. Ueber den m u n d der speiserohre. Zeit fur Ohremheilkunde. 1 908 ; 5 5 : 1 -41 . 2. J u by H B. The treatment of pharyngea l pouch. Journal of Laryngology and Otology. 1 969 ; 83 : 1 067-71 .
2060 I 3.
*
4.
5.
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7. 8. 9.
1 0.
11.
1 2.
1 3. 1 4.
1 5.
1 6.
1 7.
1 8.
1 9.
20.
21 .
PART
1 5 THE U PPER DIG ESTIVE TRACT
Richardson B E, Bastia n RW. Videoendoscopic swa l l ow i ng study for diag nosis of Zen ker's d iverticu li. Laryngoscope. 1 998; 1 08 : 721 -4. Va n Overbeek JJ M. Meditation on the pathogenesis of hypopharyngeal (Ze n ker's) d iverticu l u m and a report of en doscopic treatment in 545 patients. Annals of Otology, Rhinology, and Laryngology. 1 994; 1 03 : 1 78-84. Perrott JW. Anatomical aspects of hypophargynea l d iverticu la. Australian and New Zealand Journal of Surgery. 1 962 ; 3 1 : 307- 1 7. Neg us VE. Pha ryngea l d ive rticula. Observations on the evol ution and treatment. British Journal of Surgery. 1 9 50 ; 3 8 : 1 29-46. Sutherland H D. Cricopharyngeal achal asia. Journal o f Thoracic a n d Cardiovascular Surgery. 1 9 62 ; 43 : 1 1 4-26. Belsey R. Fu nctional d isease of the esophag us. Journal of Thoracic and Cardiovascular Surgery. 1 996; 52 : 1 64-8. Doh l m a n G, Mattsson O. The endoscopic operation for hypopharyngeal d iverticu la. Archives of Otolaryngology. 1 960 ; 7 1 : 744-52. Ard ra n G M , Kem p FH, Lund WD. The aetiology of the posterior pharyngea l d iverticu l u m . A cinerad iographic study. Journal of Laryngology and Otology. 1 964; 7 8 : 339-49. El l is G H , Sch legel .IF, Lynch VP, Pa i n SW. Cricopharyngeal myotomy for pharyngo-oesophageal d iverticu l u m. Ann als of Surgery. 1 9 69 ; 1 70: 340-9. Lichter L. M otor d isorder in pharyngo-oesophagal pouch. Journal of Thoracic and Cardiovascular Surgery. 1 978; 7 6 : 272-5. H u nt PS, Con ne l l AM, Smittey TB. The cricopharyngeal sph incter in gastric reflux. G u t. 1 9 70 ; 1 1 : 303-6. Mora n AG O, Wi lson JA, AI M u ha n n a AH. Pharyngeal d iverticu la. Clinical Otolaryngology and Allied Sciences. 1 986; 1 1 : 2 1 9-25. Resou ly A. Braat J, Jackson A, Eva ns H. Pharyn gea l pouch : l i n k w ith refl ux and oesophageal dysmoti lity. Clinical Otolaryngology and Allied Sciences. 1 994; 1 9 : 241 -2. Sood S, Henein RR, J i rg is B. Pharyngeal pouch fol l owing anterior cervical fusion : a case re port. Journal o f Laryngology a n d Otology. 1 999; 1 1 2 : 1 085-9. Salem MA, Cable HR. Acq u i red pharyngea l d iverticu lum fol lowi ng anterior cervical fusion operation. British Journal of Clinical Practice. 1 994; 48 : 1 09- 1 2. Winnans CS. The pharyngo-oesophagea l closu re mecha n ism : a manometric study. Gastroenterology. 1 972; 6 3 : 768-77. Siddiq MA, Sood S. Cu rrent management i n pharyngea l pouch su rgery by U K Otorh inolaryngolog ists. Annals of the Royal College of Surgeons of England. 2004; 86: 247-52. H u a n g B, U n n i K, Payne WA. Long-term su rviva l fo l lowing d iverticu lectomy for ca ncer i n pharyngo-oesophageal (Ze n ker's) d iverticu lum. Annals o f Thoracic Surgery. 1 984; 3 8 : 207 - 1 0. B ra d l ey PJ, Cockaar A, Quraishi MS. Pharyngeal pouch ca rci nom a : rea l or imagin ary? Annals of Otology, Rhinology, and Laryngology. 1 999 ; 1 08 : 1 027-32.
22.
23.
24.
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*
28. 29.
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31 . 32.
33. 34.
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*
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38.
*
39.
Lodge WOo I n : Proceedings of the 4th I nternational Conference of Otolaryngology 1 949. London: British Medica l Association, 1 9 51 ; 2: 71 5-7. Pa rker AJ, H awthorne M R. Endoscop ic d iverticulotomy versus external d iverticul ectomy in the treatment of pha ryngea l pouch. Journal of the Royal College of Surgeons of Edin burgh. 1 988; 3 3 : 61 -4. Ludlow A. A case of obstructed deg l utition, from a preternatura l d i l atation of, and bag formed in the pha rynx. Medical Observations and In quiries. 1 7 69 ; 3 : 85- 1 01 . Zen ker FA, Va n Zienssen H. Cyclopedia of the practice o f medicine. Ba ltimore : Wood W, 1 878. Wheeler WL. Pha ryngocele and d i lation of phary nx, with existi ng diverticu l u m at lower portion of pha rynx lyi ng posterior to the oesophagus, cure by pharyngotomy, bei ng the first case of the kind recorded. Dublin Journal of Medical Science. 1 886; 82 : 349-56. Stetten D. The rad ica l extirpation of pharyngo oesop hageal pressu re d iverticu la. Annals of Surgery. 1 9 1 0 ; 51 : 300- 1 9 . Todd G B . T h e treatment of pharyngea l pouch. Journal o f Laryngology and Otology. 1 974; 8 8 : 307-1 5. Pagliero KM. Use of autosutu re d u ring oesophagea l and pharyngea l d ive rticu lotomy. Clinical Otolaryngology and Allied Sciences. 1 985; 1 0: 263-4. Westmore GA. Sta ple g u n in the su rgery of hypopharyngeal d iverticu la. Journal of Laryngology and Otology. 1 999 ; 1 04: 553-6. G i ra rd C. Du tra itement des d iverticu les de l'oesophClge. Assoc. Franc d e Chir Proc 'verb. 1 896; 1 0 : 39 2-407. Free l a n d AP, Bates GJ. The treatment of a pharyngeal pouch: i nversion or excision? Annals of the Royal College of Surgeons of England. 1 987; 69 : 57-8. Morton RP, Bartley J R F. I nversion of Zen ker's d ive rticu l u m : t h e preferred option. Head and Neck. 1 99 3 ; 1 5 : 253-6. Mosher H P. Webs and pouches of the oesophag us, thei r diagnosis and treatment. Surgery, Gynecology and Obstetrics. 1 9 1 7 ; 2 5 : 1 7 5-87. Hollinger PH. Experience w ith the Doh lman technique. Annals of Otology, Rhinology, and Laryngology. 1 961 ; 70: 1 1 1 7-23. Bates GJ, Koay CB, Sharp H R. Cu rrent practice in pharyngea l pouch su rgery i n Eng land a nd Wales. Ann als o f the Royal College of Surgeons of England. 1 99 7 ; 7 9 : 1 90-4. Col l a rd J M , Otte JB, Kestens PJ. Endoscopic stapling technique of oesophagodiverticul otomy for Zen ker's d iverticu l um. Annals of Thoracic Surgery. 1 99 3 ; 56: 573 -6. M a rtin-H irsch DP, l'Jewbegin CJ. Autosutu re G IA G u n : a new a pplication in the treatment of hypopharyngea l d iverticu la. Journal of Laryngology and Otology. 1 99 3 ; 1 07 : 7 23-5. Resou ly A. Pharyngea l pouch su rgery. Compi led by G ray AJG, Hoile RW, I n g ra m GS, Sherry KM. The report o f the national con fidential enquiry into peri-operative dea ths. 1 995-6. London CEPOD, 1 966; 32.
Cha pter
40. Cook RD, H u ang PC, Richstmeier WJ , Scher RL. Endoscopic sta ple/assisted esophagod iverticu lotomy: an excel lent treatment of choice for Zen ker's d iverticu l u m . Laryngoscope. 2000 ; 1 1 0 : 2020-5. 41 . Sood 5, Newbeg in C.J R. Endoscopic sta p l i n g of pharyngea l pouches in patients from the Yorkshire region. Journal of Otolaryngology and Otology. 2000 ; 1 1 4: 853-7. 42. M i rza 5, Dutt SN, M i nhas 55, Irving RM. A retrospective review of pharyngeal pouch su rgery in 56 patients. Annals of the Royal College of Surgeons of England. 2002 ; 84: 247-5 1 . 43. Jara m i l lo MJ, McLay KA, McAteer D. The l ong -te rm clin ico-radiologica l assessment of endoscopic sta p l i n g of pharyngeal pouch : a series of cases. Journal of Laryngology and Otology. 2001 ; 1 1 5 : 462-6. 44. Va n Eeden 5, Lloyd RV, Tra nter RM. Com pa rison of the endosco pic sta p l i n g tech nique with more esta bl ished proced u res for pharyn gea l pouches: resu lts and patient satisfaction su rvey. Journal of Laryngology and Otology. 1 999 ; 1 1 3 : 237-40. 45. Ong CC, Elton PG, M itch e l l D. Pha ryngeal pouch endoscopic sta p l i n g : a re post-operative ba ri u m swa l low rad iog raphs of any va lue? Journal of Laryngology and Otology. 1 999; 1 1 3 : 233-6. 46. Zeitou n H, Widdoswson D, Hammand Z, Osborne J. A video-fl uoroscopic study of patients treated by d iverticu lectomy and cricopharyngea l myotomy. Clinical Otolaryngology and Allied Sciences. 1 994; 1 9 : 301 -5. 47. Aggerholm K, I l i u m P. Su rgica l treatment of Zen ker's d iverticu l u m . Journal of Laryngology and Otology. 1 990; 1 04: 3 1 2-4. 48. Mackay IS. The treatment of pharyngeal pouch. Journal of Laryngology and Otology. 1 976; 90: 1 83-90. 49. Benja min B, G a l lag her R. M icro-endoscopic laser d iverticu lotomy for hypopharyngeal d iverticu l u m. Annals of Otology, Rhinology, and Laryngology. 1 993 ; 1 02 : 675-9. 50. Krespi y. Kacker A, Remade M . Endoscopic treatment of Zen ker's d iverticu l u m using CO2 l aser. Otolaryngology and Head and Neck Surgery. 2002 ; 1 2 7 : 309- 1 4. 5 1 . Bradwell RA, Bieger AK, Strachan DR, Homer JJ. Endoscopic l aser myotomy i n the treatment of pharyngea l
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53.
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1 55 Pha ryngea l pouch I 2061
d iverticula. Journal of Laryngology and Otology. 1 99 7 ; 1 1 3 : 223-6. Nyrop M , Svendstru p F, Jorgensen KE. Endoscopic CO2 laser th era py of Zen ker's d ive rticu l u m : experience from 61 patients. Acta Oto-Iaryngologica. Supplementum. 2000 ; 543 : 232-4. Lippert BM, Bened i kt J F, Hein rich H R, Werner JA. Man agement of Zen ker's d iverticu l u m and post l a ryngectomy pseudo-d iverticu l u m with the CO2 laser. Otolaryngology and Head and Neck Surgery. 1 999 ; 1 2 1 : 809- 1 4. Bates G, Steventon l'l. Outcomes from pharyngeal pouch sta p l i n g on 230 consecutive patients. Presented at the 5th European Con g ress of Oto-Rhino-La ryngology H ead and Neck Surgery. (EU, F.O.5) Rhodes September 1 1 - 1 6th, 2004. Cou nter PR, H i lton M L, Baldwin D. Long-term fo l low-u p with endoscopic sta p l e d iverticu lotomy. Annals of the Royal College of Surgeons of England. 2002 ; 84: 89-92. Raut W, Pri m rose WJ. Long-term resu lts of endoscopic sta p l i n g d iverticu lotomy for pharyngea l pouches. Otolaryngology and Head and Neck Surgery. 2002 ; 1 2 7 : 225-9. Stoeckl i SJ , Sch mid S. Endoscopic sta pler-assisted d iverticu loesophagostiomy for Zen ker's d iverticu I u m : the patient's satisfaction and subjective rel ief of sym ptoms. Surgery. 2002 ; 1 3 1 : 1 58-62. Th a l er ER, Weber RS, Gold berg AN, Wei nstein GS. Feasi bil ity and outcome of endoscopic sta pl e-assisted esophagodiverticu lostomy for Zenker's d iverticu l u m. Laryngoscope. 2001 ; 1 1 1 : 1 506-8. Luscher MS, Joha nsen LV. Zen ker's d iverticu l u m treated by the endoscopic stapling tech n iq u e. Acta Oto laryngologica. Supplementum. 2000 ; 543 : 235-8. Narne 5, Cutron e C, Bonavina L, Ch ella B, Peracchia A. En doscopic d iverticu lotomy for the treatment of Zenker's d iverticu l u m : resu lts in 1 02 patients with sta ple-assisted endosco py. Annals o f Otology, Rhinology, and Laryngology. 1 999; 1 0 8 : 8 1 0-5.
156 Oesophagal diseases ROBERT C MASON
Introduction Gastro-oesophageal reflux Key points Barrett's oesophagus Motility disorders Key points
2062 2062 2065 2065 2066 2066
Oesophageal carcinoma Key points Oesophagea I perforation and tracheo-oesophagea I fistu la Key points Miscellaneous conditions References
2067 2070 2070 2071 2072 2072
The evidence for this chapter is based on a Medline search using the key words oesophageal cancer, gastro-oesophageal reflux, oesophageal motility and oesophageal perforation; and Adam A, Mason RC, Owen WJ (eds). Practical management of oesophageal diseases. Oxford: Isis Medical Media, 2000; and Paterson-Brown S, Garden JO. Companion to specialist surgical practice: upper gastrointestinal surgery, 3rd edn. Philadelphia: W.B. Saunders Co. Ltd., 2006.
INTRODUCTION The oesophagus is a short muscular tube lined with squamous epithelium, the function of which is to transmit nutrition in three seconds from the pharynx to the stomach. It is strange that such an insignificant organ is the source of much morbidity and mortality. In this short chapter not all diseases can be discussed so focus will be on four conditions which account for over 95 percent of oesophageal disorders - gastro-oesophageal reflux (GOR), motility disorders of the oesophagus, oesophageal carcinoma and oesophageal perforation/ tracheo-oesophageal fistula.
GASTRO-OESOPHAGEAL REFLUX Gastro-oesophageal reflux is a common condition. Up to 5-10 percent of the population have daily reflux symptoms, and 40 percent symptoms on a monthly basis. Medical opinion is sought by 25 percent and less than 5
percent are referred for surgery. Of those suffering from reflux, 70 percent will be symptomatic on a daily basis ten years after their symptoms began. Complications are rare, with strictures occurring in 2 percent and Barrett's oesophagus in less than 1 percent. Gastro-oesophageal reflux results from failure of the lower oesophageal sphincter. This is not a true sphincter but is made up of several components, the most important of which is a length of intraabdominal oesophagus and the angle between the oesophagus and fundus of the stomach. Measured manometrically it is 2-5 cm in length and has an intraluminal pressure of 15-25 mm of mercury. Although frequently associated with a sliding type of hiatal hernia, both can exist separately. Gastro-oesophageal reflux is not associated with rolling hiatal hernia, in which the gastro-oesophageal junction lies in a normal position, and the fundus herniates either via the true hiatus or para hiatal defects into the chest. This type of hernia is associated with gastric volvulus and can present with chest pain, or as an air fluid level seen behind the heart on chest radiograph.
Chapter 156 Oesophagal diseases I
Presentation and management The commonest symptom, by far, is heartburn, usually exacerbated by stooping or consuming a heavy meaL Less common symptoms include atypical chest pain, dysphagia and globus due to reflex oesophageal or cricopharyngeal spasm, nocturnal asthma and hoarseness of the voice due to acid overflow into the larynx, and tooth decay. Patients with a suspected diagnosis of myocardial infarction will be found to have an oesophageal cause for their pain in 25 percent of cases. 1 Most patients with intermittent symptoms will selfmedicate with over the counter antacids or H2 receptor antagonists. Patients with more persistent symptoms will present to their general practitioner. In the absence of alarm symptoms of dysphagia and weight loss and a long history it is safe to give a short course of a proton pump inhibitor such as lansoprazole 30 mg per day. If there is doubt, however, alarm symptoms or the patient is over 40 years and has developed the symptoms de novo or failed to respond to the above, the patient must undergo endoscopy. Whereas this will not exclude minor reflux in an undamaged oesophagus, it will demonstrate oesophagitis and the complications of reflux stricture, Barrett's oesophagus and cancer. It is crucial to biopsy any abnormality. Barium swallow/meal will demonstrate a hiatal hernia and show reflux but cannot detect oesophagitis or Barrett's oesophagus. Having excluded serious disease, the patient should be treated medically with high-dose proton pump inhibitors
Figure 156.1
2063
up to 30 mg bd lansoprazole or lansoprazole 30 mg mane and ranitidine 300 mg nocte. If the patient has significant oesophagitis or stricture/ulceration on initial endoscopy it is wise to re-endoscope after six weeks of treatment to ensure healing. Severe oesophagitis can be confused with malignancy, even on biopsy, and it is recommended that rebiopsy on treatment is undertaken to be sure of the diagnosis. In the absence of dysplasia or malignancy it is safe to adjust the dosage on symptomatic response. There is no evidence to suggest that long-term treatment with proton pump inhibitors is hazardous to the patient. Further investigation is reserved for those who fail medical treatment, require full-dose therapy to control symptoms or are being considered for surgery. Such investigations centre on assessment of 24-hour oesophageal pH, oesophageal manometry and the Bilitec probe for 'bile reflux'. It is important that these tests be performed with patients off treatment for five days to avoid a false negative result. 2 , 3 The role of manometry in GOR disease is to exclude other motility disorders and to determine accurately the position of the lower oesophageal sphincter. The presence of low amplitude peristalsis in the presence of reflux is of no significance for therapy. With the probe positioned 5 cm above the detectable lower oesophageal sphincter, 24-hour pH measurement is taken (Figure 156.1). This measures the intraluminal pH over 24 hours, and with the use of diary cards and marking the recording, symptoms can be accurately associated with the pH. Although an
Combined pH and bilirubin monitoring in a patient with supine acid and bile reflux.
2064 I
PART 15 THE UPPER DIGESTIVE TRACT
intraluminal pH of < 4 for more than 4.5 percent of a 24hour period is considered abnormal, the association of symptoms with periods of acid exposure is of most importance - the De Meester score. A high score invariably is associated with significant acid reflux. If there is no association then serious doubt should exist as to the diagnosis. There is a small group of patients with 24-hour pH measurements in the normal range, i.e. < 4.5 percent who have an association between any acid and pain and a positive Bernstein test. These patients have the so-called irritable oesophagus and present a therapeutic challenge. Patients who have previously undergone gastric resection may have alkaline reflux of duodenal contents - bile reflux. This will produce a negative 24-hour pH measurement but is positive for bile using the Bilitec probe which detects bile pigment. How such patients, who are rare, should be managed is unclear but revisional surgery with conversion to a 60-cm Roux-en-Y loop may be necessary if medical therapy with alginates and proton pump inhibitors fails.
The role of surgery
demonstrating better results with either technique providing a short 1-2-cm loose wrap is achieved; nor has division of the short gastric vessels been proven to be of benefit. What is crucial to the outcome is that the operation is carried out for the correct reasons and by an experienced surgeon. It is accepted that repair of the crura is important as is fixation of the wrap to the gastro-oesophageal junction and or crura to prevent slippage. Dysphagia is reduced by performing the wrap and crural repair with a 48F or larger bougie in the oesophagus. Complications of this surgery include oesophageal perforation, dysphagia, gas bloat and chest pain. Dysphagia may be the result of a slipped wrap, which is an early complication of the laparoscopic approach and a late complication of open surgery. If there is any complication in the immediate postoperative period, a contrast swallow is mandatory as early recognition of a slipped wrap or perforation and reoperation can save the patient. Late failure should be investigated by barium swallow, endoscopy and repeat 24-hour pH and manometry.
Complications of gastro-oesophageal reflux
Debate exists as to the role of surgery in the uncomplicated patient. Some clinicians advocate surgery for any patient who requires regular therapy for symptom control. They argue that this avoids long-term drug ingestion and over time is cheaper to the health economy. In the best hands, however, a successful result will only be achieved with surgery - Visic 1 - in 85-90 percent of cases. This means that 10-15 percent will undergo a procedure with a mortality of 0.1 percent and morbidity of 5-10 percent (dysphagia, gas bloat) and be worse off. These are frequently young, previously fit patients. A conservative approach is recommended. Good indications for surgery are volume reflux, failure to respond to medical treatment with positive pH and manometry and proven oesophagitis. Reasonable indications are breakthrough symptoms on reducing medication, and unusual presentations of reflux with positive studies. Dubious indications include the irritable oesophagus and symptoms with negative studies. Surgery has no role in patients with aerophagia, functional gut disorders or those with major anxiety disorders. If a patient is asymptomatic on a low dose of proton pump inhibitor they are wise to stay on it!
Severe long-standing reflux can result in oesophageal ulceration and stricture formation. Such ulcers may bleed and perforate and be difficult to differentiate from cancer. Multiple biopsies and aggressive medical therapy followed by rebiopsy are mandatory. If the ulcer fails to heal, computed tomography (CT) scanning and endoluminal ultrasound may reveal the true diagnosis. Benign strictures should be treated with full-dose medical treatment, gentle balloon dilatation and biopsy after dilatation to exclude cancer (Figure 156.2).
Which operation? Although many procedures are described, the operation that has stood the test of time is a floppy 360 Nissen fundoplication. 4 This can be performed by both an open 5 or laparoscopic approach. There is no evidence 0
Figure 156.2 Balloon dilatation of a benign stricture using a through channel endoscopic balloon.
Chapter 156 Oesophagal diseases
Stricture and ulceration are good indications for elective antireflux surgery when malignancy has been excluded.
KEY POINTS • Heartburn isa common symptom, found in almost half of the population. • Young patients canbesafe1ytreated eipecta.ntly.with H2Ranta.gonistsorproton pump inhibitors. • Patients over 40~ years-old and those with recurrent symptoms should have· endoscopy. before .~tartingtreatment···toexdudeBarrett)s ()esophagus. .• Surgery forGO ~is only indicated ina minority?f p~tients~thJailed'l11eclical treatmeJ:lt and withpositiye 24-hourpHand symptom index. . • The operation •. of choice is probably a laparoscopic 360. floppy Nissen, ·flindOplication. . 0
BARRETT'S OESOPHAGUS Barrett's oesophagus is defined as the presence of more than 3 cm of columnar lined oesophagus (Figure 156.3). It is now recognized that short segment Barrett's can exist with less than 1 cm of columnar lined oesophagus or merely tongues of columnar lined epithelium. It has been calculated that the incidence of Barrett's in the normal population is 0.5-2 percent. Of these, 1 percent will develop high-grade dysplasia and 0.3 percent invasive cancer (Figure 156.4).6 This emphasizes the importance of detailed histological examination of this abnormal epithelium.
The risk of malignant change is minimal if the epithelium is fully differentiated cardiac-type epithelium. The risk increases if there is intestinal metaplasia and is significant in the presence of dysplasia. Such changes are patchy and multiple biopsies - four quadrant, every centimetre are recommended. The malignant risk overall is low with one cancer per 100 years follow-up. With high-grade dysplasia, however, the chance of an early carcinoma being found in the specimen is up to 50 percent. 7 How should Barrett's be managed, bearing in mind that most are asymptomatic? Patients with a fully differentiated epithelium need follow-up every three years, those with mild dysplasia every six months and those with severe dysplasia, confirmed by two independent pathologists, should be considered for more radical therapy. There is broad acceptance that all cases of non dysplastic Barrett's oesophagus should be treated with proton pump inhibitors. Debate exists as to whether they should have antireflux surgery and whether the Barrett's segment should be destroyed with argon beam electrocoagulation. This is subject to ongoing clinical trials as it is unclear whether the changes of Barrett's oesophagus are reversible. Mild dysplasia should be treated by full-dose medical treatment with proton pump inhibitors and follow-up, as described, with multiple biopsies. If this reverts to fully differentiated epithelium the periods between repeat endoscopy can be prolonged.
Normal oesophagus
Months
Oesophagitis
MonthsNears
Years
Dysplasia (high grade) Years
Adenocarcinoma
Figure 156.3
Endoscopic appearance of Barrett's oesophagus.
I 2065
Figure 156.4
Progress of Barrett's oesophagus.
2066 I PART 15 THE UPPER DIGESTIVE TRACT Owing to the significant association with adenocarcinoma, high-grade dysplasia demands aggressive treatment as the disease is potentially curable. In fit patients, total oesophageal resection should be undertaken. In the unfit, destruction with argon beam or photodynamic therapy are options.
laparoscopic approach should be reserved for the few balloon failures. Failure of surgical myotomy is usually the result of an inadequate myotomy and there is no evidence that combining myotomy with an antireflux wrap improves results. Failed myotomy can be treated by balloon dilatation.
MOTILITY DISORDERS
Diffuse oesophageal spasm and nutcracker oesophagus
These conditions, which include achalasia, scleroderma, diffuse oesophageal spasm, nutcracker oesophagus and visceral myopathy, present a diagnostic challenge as they are frequently associated with significant symptoms of pain and dysphagia but with an apparently normal oesophagus on barium studies and endoscopy. Some motility disorders, achalasia, can be treated with a high degree of success but others will respond less well to treatment. It is also important to recognize those conditions such as visceral myopathy, which may represent a generalized gut failure, from others, and pseudo achalasia, which may be masking malignancy. They have a short history and weight loss. As previously mentioned, up to 30 percent of patients with a diagnosis of myocardial infarction, admitted as an emergency, will be found to have an oesophageal cause for their pain, and motility disorders account for over 50 percent of these patients. The diagnosis is made with oesophageal manometry after exclusion of more serious conditions by endoscopy and barium studies.
Achalasia This condition is characterized by failure of relaxation of the lower oesophageal sphincter during swallowing due to degeneration of the myenteric plexus. Individuals present with long-standing dysphagia and regurgitation. The diagnosis must be excluded in patients with 'resistant reflux'. Endoscopy and barium studies may be normal although in long-standing disease the oesophagus will dilate with a smooth tapering stricture at the distal oesophagus. The diagnosis is made with oesophageal manometry demonstrating synchronous contractions in the oesophageal body and failure to relax in the sphincter. Care must be taken in interpreting the results of 24-hour pH measurement as fermentation of food in the oesophagus can lead to a false positive pH measurement. Treatment is based on sequential dilatation of the lower oesophageal sphincter with intraluminal balloons of 30, 35 and 40 mm under fluoroscopic control obliterating the waist. This balloon myotomy is safe, effective in over three-quarters of cases and can be repeated. 8 Surgical myotomy by either an open or
These conditions are characterized by severe chest pain and dysphagia. They primarily involve the lower twothirds of the oesophagus, can be associated with muscle hypertrophy and with contraction pressures in the region of 400-mm mercury pressure. The presence of sequential peristaltic contraction waves associated with occasional multipeaked high-amplitude, long-duration contractions confirms the diagnosis (Figure 156.5). As the symptoms are intermittent, ambulatory manometry may be required to confirm the diagnosis. 9 It is important that symptoms are associated with the manometric abnormality. The results of treament are generally disappointing although calcium channel blockers may provide some relief. Balloon dilatation of the lower one-third of the oesophagus can be of benefit in cases of significant dysphagia and pain but there is now no role for long oesophageal myotomy.
Scleroderma There is an association between scleroderma and other connective tissue disorders and dysphagia and reflux. The mural fibrosis of the lower two-thirds of the oesophagus produces low-amplitude contractions and little in the way of lower oesophageal sphincter activity. This is associated with free reflux. Treatment is maximal medical therapy. If surgery is required, usually for nocturnal volume reflux, then a 270 wrap is preferable to prevent dysphagia. 0
Chapter 156 Oesophagal diseases
Figure 156.5
I 2067
Manometric picture of diffuse oesophageal spasm showing multipeaked high-pressure waves.
OESOPHAGEAL CARCINOMA Oesophageal cancer is increasing in incidence faster than any other malignancy in the developed world, with a ten.:. fold increase in the last 20 years. 10 This increase is not in cases of squamous cancer, which have remained stable, but in the incidence of adenocarcinoma - Barrett's cancer. This type of carcinoma has been classified by Siewert and Stein,11 based on the site of the main focus of the tumour: type 1, lower one-third oesophagus; type 2, at the oesophagogastric junction; and type 3, in the gastric cardia within 5 cm of the oesophagogastric junction. This carcinoma appears to be related to the damaging effects of GOR at the gastro-oesophageal junction. Such reflux may be the result of eradication of Helicobacter pylori, the disappearance of which has led to a reduction in distal gastric cancer and an increase in proximal disease. In spite of increased awareness and access to endoscopy (Figure 156.6), more than 50 percent of patients are unsuitable for curative treatment at presentation due to inadequate fitness or advanced disease. 12 Although there is an increasingly important role for radical chemoradiotherapy as primary treatment for squamous cancer, surgical resection is the only proven curative therapy available for adenocarcinoma. In deciding on whether surgery should be considered, three questions need to be addressed.
Figure 156.6
Endoscopic picture of oesophageal carcinoma.
1. Will the patient survive the operation - comorbid features cardiorespiratory and hepatic status? 13 2. If the patient survives the operation is there a good chance of at least 18 months of survival? Quality of life measures show that patients who do not survive this long have poor quality of life. 14 3. Can complete resection be achieved? If macroscopic disease clearance is not achieved, the
2068 I
PART 15 THE UPPER DIGESTIVE TRACT
patient's survival is severely compromised. There is no role for palliative resection. IS If the answers to these questions are positive and surgery is undertaken in a good centre with high throughput + 25 resections per year, an in-hospital mortality of < 5 percent and 5-year survival of 25-30 percent can be achieved. 16 This emphasizes the correct assessment of the physical state of the patient and accurate staging. The presence of co-morbid disease, especially cardiorespiratory and liver disease, substantially increases the operative risk. The presence of weight loss of > 10 percent of the premorbid weight and near total dysphagia are harbingers of advanced disease and poor survivaL The ability to stage the disease more accurately has improved with the advent of spiral CT scanning (Figure 156.7) and endoluminal ultrasound (Figure 156.8). The
latter can be combined with fine needle aspiration biopsy of suspected glands. Together, they can now deliver an accuracy for T stage and N stage in excess of 80 percent, long-term survival being dependent on micro metastatic disease. 17 Which operation should be performed? A summary of approaches with pros and cons for each is shown in Table 156.1. There is no evidence from either trials or meta-analysis to demonstrate superiority for one approach; nor does avoiding thoracotomy using a transhiatal approach reduce complications (Table 156.2). The best approach is that which gives the best exposure to the most difficult part of the operation. The most frequently used organ for replacement of the oesophagus is the stomach with the left colon reserved for cases where the stomach is not available. There is no evidence to demonstrate whether anastomoses are best placed in the chest or neck, or whether a pyloroplasty is routinely required to prevent gastric stasis. 26 Controversy exists as to the extent of lymphadenectomy that should be undertaken. It has been proposed that extensive three-field lymphadenectomy improves survivaL There is no evidence from randomized trials to support this, and there is an increase in complications
Loss of layer pattern. Tumour extends to M. propria, but not through Nodes suggestive of - - - - involvement
Figure 156.7
A T3 N1 junctional adenocarcinoma. There is
Rounded, sharp edged, non-hyper echoic centre, size approximately 1 cm
transmural thickening on the CT scan with involved left gastric
Figure 156.8
nodes.
positive oesophageal carcinoma.
An endoluminal ultrasound image of a node-
Cons Transhiatal
18
Avoids thoracotomy
Not a cancer op
19
Reduced morbidity
Only junctional Ca
Anastomosis in neck
Leak, stricture and recurrent laryngeal nerve
Exposure
Thoracotomy
palsy Lewis-Tanner
20 21
Three stage
Lower thoracoabdominal Minimally invasive
22
23 24
Lymphadenectomy
Poor hiatal exp
Stapled anastomosis
Two stage
Total oesophageal resection
Thoracotomy
Lymphadenectomy
Increased morbidity
Anastomosis in neck
Three stage
Good hiatal exposure
Lower one-third only
One incision
Costal margin
Reduced morbidity
Time Not a cancer op
Chapter 156 Oesophagal diseases
with the radical approach. The main benefit is probably that of improved staging, which may result in stage migration. 27 There is increasing evidence that multimodal therapy may improve survival of patients undergoing resection (Table 156.3). Adjuvant radiotherapy has not been shown to benefit patients but neoadjuvant chemoradiotherapy and chemotherapy alone have been demonstrated in randomized trials to improve survival over surgery alone at two and three years. 29 , 31, 32 No study follows up patients beyond this so any benefit with regards to cure is not evident and doubt has been expressed that such treatment only benefits patients when the control group does badly - adjuvant therapy improves bad surgery.
Palliation of malignant dysphagia In spite of better staging, surveillance for Barrett's and improved surgery, the majority of patients will be Table 156.2
I 2069
unsuitable for radical treatment due to advanced stage of disease or poor fitness. These patients require palliation of their symptoms, in particular dysphagia, with due regard to their overall quality of life. This can be achieved by either intubation of the malignant stricture with a plastic tube or self-expanding metal stent (Figure 156.9), or destruction of the tumour by laser, injection of alcohol, use of argon beam electrocoagulation of thermal ablation. 33 There are many series of individual techniques that have a high success rate and few prospective randomized controlled trials comparing treatments. Those that exist have fewer than 100 patients randomized. They are shown in Tables 156.4 and 156.5. The conclusion is that the best palliation is achieved by self-expanding metal stents of the covered Nitinol variety, especially when the tumour is mural or extramuraL For polypoid intraluminal disease, the best palliation is achieved with laser or argon beam. In patients, who are fit, with advanced disease, the addition of chemoradiotherapy may benefit in improving relief of dysphagia and possibly prolonging survival.
Metanalysis of transhiatal versus Lewis-Tanner oesophageal resection.
Respiratory
24
25
Cardiovascular
12.4
10.5
Chylothorax
3.4
2.1
Anastomosis leak
16
10
Anastomosis stricture
28
16
Recurrent laryngeal nerve palsy
11.2
4.8
6.3
9.5
Thirty-day mortality Five-year survival Total number of cases
24
26
2675
2808
Sixty-two papers 1986-1996. Reprinted with permission from Ref. 25.
Table 156.3
Multimodal therapy. 0
ObserVation Preoperative radiotherapy
Does not improve survival in patients
1147
28
undergoing resection Preoperative chemoradiotherapy:
Improves three-year survival over
With 5FU, cisplatin and 40 Gy
from 6 to 32%
113
29
With 5FU, cisplatin, vinblastin and 45 Gy
from 15 to 32%
100
American Society of Clinical
Preoperative chemotherapy with 5FU and
Has no survival benefit at 2 years, 35
440
30
802
31
603
American Society of Clinical
surgery alone:
Oncologists 1997 cisplatin compared with surgery alone
versus 37% Has a survival benefit at two years, 25 versus 35%
Postoperative chemoradiotherapy with 5FU, leucovorin and 45 Gy
Improves survival from 41 to 52%
Oncologists 2000
2070 I PART 15 THE UPPER DIGESTIVE TRACT
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OESOPHAGEAL PERFORATION AND TRACHEOOESOPHAGEAL FISTULA
Figure 156.9 A self-expanding metallic stent placed through a lower one-third oesophageal carcinoma. Contrast shows good flow.
Table 156.4
Spontaneous perforation of the oesophagus - Boerhaave's syndrome - usually follows a bout of vomiting after a heavy meal. The sudden onset of chest pain and dyspnoea should alert one to the diagnosis. It is rare for the perforation to be contained by the mediastinum and clinical signs of subcutaneous emphysema and a hydropneumothorax may be present. Following resuscitation, which may include placement of an intrapleural drain, an oesophagogram should be performed. This should show the leak but if it does not, a CT scan with barium should be performed. The site of perforation is the lower end of the oesophagus rupturing to the left pleural cavity in most cases. Higher perforations tend to rupture to the right side. The management depends on the time between perforation and diagnosis, whether the leak is contained by the mediastinum and whether other disease is present.
Randomized trials of palliation: part 1.
Laser versus plastic tubes Laser versus ethanol injection Laser versus brachytherapy Laser alone versus laser plus radiotherapy or brachytherapy Laser alone versus laser plus ECF chemotherapy
Observation
References
No difference in relief of dysphagia or morbidity No difference in relief of dysphagia or frequency of treatment No difference in relief of dysphagia The addition of radiotherapy or brachytherapy reduces frequency of intervention; no survival benefit ECF reduces need for laser and po~sibly prolongs survival
34 35 36 37,38
39
Chapter 156
Table 156.5
Randomized trials of palliation: part 2.
Obs~~ati~r{O
technique
Stent versus Stent versus Stent versus Stent versus Stent versus
Oesophagal diseases I 2071
plastic tubes laser laser plus radiotherapy thermal ablation surgical bypass
Both relieve dysphagia, stents more than tube; less morbidity with stents Stents greater than laser at relieving dysphagia More restenosis morbidity/mortality with laser plus radiotherapy Thermal ablation greater survival; stents, pain More relief of dysphagia with stents; mortality with surgery 26%
In patients presenting within 24 hours in whom the rupture extends into the pleural cavity, the treatment is surgical with thorough pleural toilet and closure of the defect with interrupted sutures, possibly over a T tube and placement of two large chest drains. At the same time it is advisable to place a gastrostomy tube for gastric decompression and a feeding jejunostomy. If any doubt exists at surgery as to the length of the tear, endoscopy should be undertaken on surgery as the mucosal defect may be longer than the muscle defect. In stable patients with rupture contained by the mediastinum, conservative treatment as outlined later can be instituted. In delayed diagnoses or patients with associated disease, the best plan is to insert chest drains and transfer to a specialist centre as such patients may require complex resection and delayed reconstruction. 47 The other major cause of perforation is iatrogenic following instrumentation of the oesophagus (Figure 156.10). Management depends on the site of perforation, whether it is contained by the mediastinum, whether contamination has occurred after rupture and whether associated disease is present. High perforations are usually associated with perforation of an unexpected pharyngeal pouch at endoscopy. Presentation is by neck pain and the presence of subcutaneous emphysema. These should all be managed conservatively with nil by mouth, intravenous antibiotics and placement of a nasogastric tube under imaging for feeding. If sepsis ensues this should be simply drained and management of the pharyngeal pouch left until later. The common cause of perforation in the mid/lower oesophagus follows dilatation of a stricture, either benign or malignant. If the perforation is contained by the mediastinum on contrast swallow and contamination has not occurred, it is best treated conservatively. The opportunity should be taken to screen a nasogastric tube into the stomach for initial gastric decompression and, later, feeding. The patient must be strictly nil by mouth and given intravenous antibiotics and acid suppression. If the perforation involves a pleural cavity a chest drain should be placed. Surgery is only indicated in unstable patients with sepsis and hydropneumothorax. In patients with known malignancy and perforation it is wise to insert a covered self-expanding metal stent to seal the perforation if this can be placed within 12-24 hours before contamination of the mediastinum occurs. It is now accepted that perforated oesophageal cancer behaves as T4
40,41,42 43 44
45 46
Endoscopic view of an instrumental perforation of the oesophagus. The true lumen is to the right and mediastinum to the left.
Figure 156.10
disease and there is no role for urgent resection. Stents must not be placed in cases of benign perforation as they inhibit healing and lead to persistent sepsis necessitating surgical removal if the patient survives. 48 , 49 Such management is based on personal experience and published series. There are no randomized trials comparing conservative and surgical treatment. Tracheo-oesophageal fistula is associated with other disease in all but a few rare traumatic cases. The cause is usually advanced malignancy of the oesophagus or trachea, or is secondary to radiotherapy. This condition in the past was invariably fatal, but the advent of covered stents placed in either the oesophagus, trachea or, in rare cases, both simultaneously can correct the problem. 50 Owing to the advanced stage of the underlying malignancy, life expectancy is usually measured in weeks or at most months. There is no role for surgery in this condition.
2072 I PART 15 THE
UPPER DIGESTIVE TRACT
• Perforations involving the pleural cavity and unstable patients should be managed by formal repair if spontaneous or by stentingif cancer is present.
* 10.
Pera M, Cameron AJ, Trastek VF, Carpenter HA, Zinsmeister AR. Increasing incidence of adenocarcinoma of the esophagus and esophagogastric junction.
* 11.
Gastroenterology. 1993; 104: 510-3. Siewert JR, Stein HJ. Classification of adenocarcinoma of the oesophagogastric junction. British Journal of Surgery.
MISCELLANEOUS CONDITIONS The presence of candida oesophagitis should raise the possibility of an immunocompromised patient. Diverticulae in the body of the oesophagus are frequently asymptomatic and found when performing endoscopy for other reasons. They may be traction type secondary to mediastinal lymphadenopathy or pulsion type secondary to a motility disorder. They rarely require treatment but if large and causing dysphagia, resection and correction of the underlying cause may be required.
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Alderson 0, Courtney SP, Kennedy RH. Radical transhiatal
randomised controlled trial. Surgery. 1987; 102: 19-24. 27.
Dresner SM, Griffin SM. Pattern of recurrence following
Diffuse oesophageal spasm: diagnosis by ambulatory 24
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Chapter 156 Oesophagal diseases
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Arnott SJ, Duncan W, Gignoux M, Girling OJ, Hansen HS, Launois B et al. Preoperative radiotherapy in esophageal carcinoma: a meta-analysis using individual patient data (Oesphageal Collaborative Cancer Group). International Journal of Radiolog~ Oncolog~ Biolog~ Physics. 1998; 41: 579-83. Walsh TN, Noonan N, Hollywood 0, Kelly A, Keeling N, Hennessey TP. A comparison of multimodal therapy and surgery for esophageal adenocarcinoma. New England Journal of Medicine. 1996; 335: 462-7. Kelsen DP, Ginsberg R, Pajak TF, Sheahan DG, Gunderson L, Mortimer J et al. Chemotherapy followed by surgery compared with surgery alone for localized esophageal cancer. New England Journal of Medicine. 1998; 339: 1979-84. Cunningham 0, Allum WH, Stenning SP, Thompson IN, Van de Velde CJ, Nicolson M et al. MAGIC Trial Participants. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. New England Journal of Medicine. 2006; 355: 11-20. MacDonald JS, Smalley SR, Beneditti J, Hundahl SA, Estes NC, Stemmermann GN. Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. New England Journal of Medicine. 2001; 345: 725-30. Tan BS, Mason RC, Adam A. Minimally invasive therapy for advanced oesophageal malignancy. Clinical Radiology. 1996; 51: 828-36. Alderson 0, Wright PD. Laser recanalization versus endoscopic intubation in the palliation of malignant dysphagia. British Journal of Surgery. 1990; 77: 1151-3. Carazzone A, Bonavina L, Segalin A, Ceriani C, Peracchia A. Endoscopic palliation of oesophageal cancer: results of a prospective comparison of Nd:YAG laser and ethanol injection. European Journal of Surgery. 1999; 165: 351-6. Low DE, Paglerio KM. Prospective randomized clinical trial comparing brachytherapy and laser photoablation for palliation of esophageal cancer. Journal of Thoracic and Cardiovascular Surgery. 1992; 104: 173-8. Sargeant IR, Tobias JS, Blackman G, Thorpe S, Glover JR, Bown SG. Radiotherapy enhances laser palliation of malignant dysphagia: a randomised study. Gut. 1997; 40: 362-9. Spencer GM, Thorpe SM, Blackman GM, Solano J, Tobias JS, Lovat LB et al. Laser augmented by brachytherapy versus laser alone in the palliation of adenocarcinoma of the oesophagus and cardia: a randomised study. Gut. 2002; 50: 224-7. Highley MS, Parnis FX, Trotter GA, Houston SJ, Penson RT, Harper PG et al. Combination chemotherapy with
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157 Neurological disease of the pharynx ROBERT J SANDERSONt, PAUL TIERNEY AND RICHARD ADAMSON
Introduction Anatomy Physiology Presentation Investigation and assessment of neurological dysphagia Old age Myogenic disorders Movement disorders Demyelinating disorders Systemic infections
2074 2074 2075 2076 2076 2076 2076 2078 2078 2078
Motor neuron disease Peripheral nerve lesions Neurodevelopmental disorders Glossopharyngeal neuralgia Management of neurogenic problems Key points Best clinical practice Deficiencies in current knowledge and areas for future research References
2079 2080 2080 2081 2081 2082 2082 2082 2082
The data in this chapter are supported by a Medline search using the key words pharynx, pharyngeal disease, nervous system disease and neurological disorders. Subsequent searches related to each disease process concentrated on diagnosis, management and outcome. Background reading and references are from the Otolaryngological Clinics of North America textbooks. Most of the evidence is levels 3 and 4.
INTRODUCTION The intimate relationship between the lower cranial nerves means that many combinations of nerve lesions can present with similar symptoms involving loss of pharyngeal function. Any problems with swallowing, speaking or breathing may indicate neurological disease with pharyngeal manifestations. A neurological cause is more likely if there is no anatomical deformity, although asymmetry may result from a unilateral loss of function.
ANATOMY The nerve supply to the pharynx is complex and there is a close relationship between the glossopharyngeal (IX) and vagus (X) nerves as both nerves share nuclei in the
medulla. When considering neurological problems in this area, the two nerves should be considered together (Figure 157.1). The afferent components include fibres for the special visceral sense of taste, together with general sensory fibres for pain, temperature and touch. The cell bodies of the gustatory fibres are in the inferior ganglia of IX and X. Taste fibres run from the posterior third of tongue via IX and vagal fibres supple some taste areas on the epiglottis. The taste buds on the epiglottis rarely persist into adult life. 1 Central projections from the ganglion cells run to the gustatory nucleus via the tractus solitarius. IX also includes fibres for pain, temperature and touch for the posterior tongue, upper pharynx, Eustachian tube and middle ear. The vagus carries similar fibres from the lower pharynx, larynx and apper oesophagus. These areas are endodermal in origin and sensory fibres could be considered visceral by
Chapter 157 Neurological disease of the pharynx
I 2075
Nucleus of tractus solitarius Dorsal
Spinal trigeminal nucleus
Tractus
Spinal trigeminal tract
Inferior salivary nucleus ~
Gustatory--l-+-~---- Motor---l-L---ll-----&~J
______ Preganglionic
~----+-+-I--
parasympathetic motor Nucleus ambiguus Inferior olivary nucleus
Glossopharyngeal
Vagal
Figure 157.1
Arrangement of glossopharyngeal and
vagal nuclei.
ongm, but the sensations are somatic in nature. It is thought that fibres ascend in the sphinothalamic tract and end in the spinal trigeminal nucleus. Such afferent fibres are important in the gag reflex. 2 The afferent components involve motor fibres to striated muscle in the pharynx originating from the nucleus ambiguus. These neurons supply the muscles of the soft palate, pharynx and larynx apart from the tensor veli palatini, which is supplied by the trigeminal nerve. The nucleus ambiguus has connections with the nucleus of the spinal tract of the trigeminal nerve and from the nucleus of the tractus solitarus. This establishes a mechanism for the reflexes of coughing, gagging and vomiting. 3 , 4 Glossopharyngeal and vagal fibres leave the skull via the jugular foramen and the inferior ganglion of the vagus is crossed by the cranial root of the accessory nerve. The pharyngeal plexus is found on the posterolateral wall of the pharynx overlying the middle constrictor. It is formed by the union of pharyngeal branches from the glossopharyngeal and vagus nerves and the cervical sympathetic. The glossopharyngeal component is purely afferent at this level and the pharyngeal fibres of the vagus carry some motor fibres from the cranial part of the accessory nerve, in addition to some sensory fibres. It is important to note that the corticobulbar supply to the cranial nuclei supplying the pharyngeal plexus is both crossed and uncrossed. Muscles supplied by the pharyngeal plexus are therefore not paralysed as a result of a unilateral lesion of the upper motor neuron type. 2
PHYSIOLOGY Neurological disorders of the pharynx usually present as dysphagia or problems with swallowing. Indeed, over 75 percent of oropharyngeal dysphagia has an underlying neurological cause. 5 An understanding of the physiology of swallowing is vital in the assessment of such patients.
The act of swallowing can be divided into three stages: oral, pharyngeal and oesophageal. The oral phase is under voluntary control whereas the pharyngeal and oesophageal are involuntary. Neurological disorders affecting the pharynx impair swallowing by altering motor and/or sensory function in the oral and pharyngeal phases.
1. The oral phase is the only voluntary stage in the swallowing process, and consists of masticating the food and preparing it into a bolus for passage into the oropharynx and the pharyngeal stage of the swallow. The main muscles of mastication are the masseter, temporalis and the pterygoids which are supplied by the mandibular branch of the Vth nerve. The tongue is obviously important in this phase and is supplied by the XIIth nerve. The VIIth nerve also plays a role by supplying buccinator and the orbicularis oris. 2. The pharyngeal phase is involuntary and is a highly complex mechanism that passes food through the oropharynx, through the cricopharyngeus and into the upper oesophagus. During this stage the laryngeal sphincter must close to prevent aspiration of food. The nasopharynx is also closed off from the oropharynx by contraction of the muscles of the soft palate and the posterior pharyngeal wall. This prevents nasal regurgitation of food. The pharyngeal phase relies on the coordination of many muscle groups including the muscles of the soft palate supplied by the Vth, IXth and Xth nerves and the supra- and infrahyoid muscle groups supplied by the Vth, VIIth, IXth and XIIth nerves. The pharyngeal muscles are also important, being supplied by the IXth and Xth nerves, as is the cricopharyngeus supplied by the Xth and sympathetic nerves.
2076 I PART 15 THE UPPER DIGESTIVE TRACT 3. The oesophageal phase is again involuntary, and propels the food bolus down the oesophagus. This phase is mediated by the Xth and sympathetic nerves. As can be seen, the whole swallowing mechanism is highly complex and involves many peripheral nerves acting in both a motor and sensory function, with the whole mechanism being coordinated in the brainstem and also being influenced by higher centres in the brain.
PRESENTATION Neurological disease of the pharynx often presents to the ear, nose and throat (ENT) clinic as a patient with a preexisting diagnosis undergoing multidisciplinary assessment for management of their dysphagia and/or aspiration. Many neurological disorders can, however, present primarily with dysphagia and therefore may be seen initially by the ENT clinician. It is important to differentiate neurological dysphagia from other causes of dysphagia, especially structural. Although this may require further investigation, such as imaging or endoscopy, the history and clinical examination will usually be highly predictive of the underlying disorder. It must be borne in mind that a patient's dysphagia can sometimes have both a structural and neurological element. History must, of course, include a general medical history, with a more focussed history including details of chronology, effects of food consistency, exacerbating or ameliorating factors, prior diagnoses and treatments, and the patient's perception of severity. Symptoms associated with neurological dysphagia include: • • • • •
drooling; nasal regurgitation; coughing/choking; throat clearing; wet voice.
Examination must include assessment of the oral cavity, pharynx and larynx as well as a full neurological examination including cranial nerves, to elucidate other signs of neurological diseases, such as muscle wasting and fasciculation. Particularly important is examination of the glossopharyngeal (sensory) and vagus (motor) nerve in the gag reflex.
INVESTIGATION AND ASSESSMENT OF NEUROLOGICAL DYSPHAGIA Once a structural abnormality has been ruled out and an underlying neurological condition is suspected, the mainstay of investigation is video fluoroscopy. This investigation will accurately demonstrate the physiology of the swallow and can often confirm an underlying
neurological problem. It is rarely disease specific however, and the assessment of a neurologist is often crucial in accurately diagnosing the underlying disease. Videofluoroscopy is important in the rehabilitation of swallowing, allowing the swallowing therapist to evaluate different safe swallow techniques. Videofluoroscopic findings in neurogenic pharyngeal dysphagia include: • • • • •
nasal regurgitation; decreased pharyngeal contraction; retention of contrast in vallecula/pyriform sinuses; aspiration; abnormal opening of the pharyngo-oesophageal segment.
The video examination identifies aspiration of contents into the respiratory tract and is very useful to see whether a patient can swallow safely without the risk of aspiration. In the acutely unwell patient with dysphagia, for example following a cerebrovascular accident, a functional endoscopic evaluation of swallowing (FEES) assessment can be performed at the bedside and provides a rapid and reliable assessment of the ability of the patient to swallow safely.6 This examination is performed by observing the patient's pharynx and larynx with the flexible nasopharyngoscope during and following swallowing boluses of varying consistency and volume. The boluses are dyed with blue food colouring to improve the contrast between the bolus and the mucosa. The causes of loss of pharyngeal function are listed in Table 157.1. The other neurological condition that may present to the otolaryngologist is glossopharyngeal neuralgia. In this case it is pain rather than loss of function with attendant dysarthria, dysphagia or dysphonia that is the primary presenting feature.
OLD AGE With advancing age there is uncoupling of the oral and pharyngeal stages of swallowing with a significantly longer oral stage and almost complete passage of the bolus into the vallecula prior to laryngeal elevation and initiation of the pharyngeal swallow. Furthermore, the bolus volume distending the pharynx required to stimulate the pharyngeal swallow is three to five times that in younger people. This leads to less efficient pharyngeal clearing and a higher likelihood of aspiration. Although this deterioration in the swallowing mechanism is often asymptomatic, in the absence of other demonstrable disease these findings and associated symptoms could be attributed to an age-related process.
MYOGENIC DISORDERS Myotonia is' characterized by continued muscle contraction after cessation of voluntary effort. Myotonic dystrophy is
Chapter 157 Neurological disease of the pharynx I 2077 Table 157.1
Neurological causes of pharyngeal dysfunction.
Myogenic }1.cqyitedcentral syndromes
disOrders
infections
dise.clse.
nerve lesions
Myopathies
Stroke
Parkinson's
Poliomyelitis
Motor neurone disease
Diabetes
Myotonias
Pseudobulbar palsy
Diptheria
Leukaemia
Dystrophies
Vasculitis
Dystonias/ dyskinesia Huntington's
Rabies
Skull base lesions
Myasthenia gravis
Neurodevelopmental disorders Syringomyelia/ syringobulbia Klippel-Feil Arnold-Chiari syndrome Cerebral palsy
an autosomal dominant condition characterized by progressive bilateral facial weakness, temporal balding, cataracts and a progressive weakness of peripheral musculature, including the palate. This can lead to dysphagia and dysphonia. Videofluoroscopy may reveal rigid paralysis leading to nasal regurgitation and tracheal aspiration. Successive swallows show both improvement and decreased duration of pharyngeal contraction. Myopathies tend to present with weakness in the absence of sensory symptoms. They are often congenitaL The pathophysiology of disease is varied, ranging from chronic acute inflammation and necrosis (polymyositis) to an immunopathy (myasthenia gravis).
muscle strength. The acetylcholine receptor antibody test is now more widely used but false negatives can occur? [***] When first described, the condition was termed 'gravis' because it was fatal in many cases. Cholinesterase inhibitors, thymectomy, corticosteroids and immunosuppressive drugs have been used in many centres with success. 8 Although there are no controlled trials that support the use of one regimen over another, if a thymoma is present then tumour removal is an additional benefit of surgery.9 [**]
Myasthenia gravis
A cerebrovascular event is probably the most common neurological disorder of the pharynx. It is estimated that after a stroke, up to 50 percent of patients suffer at least temporarily with dysphagia and aspiration. Stroke syndromes can lead to upper or lower motor neuron effects. The stroke effects are commonly due to infarction or haemorrhage; however, a vasculitis may also interrupt vascular supply in association with connective tissue disorders. Pseudobulbar palsy is due to the interruption of cortical influences on the lower bulbar musculature. Bilateral cortical bulbar interruption leads to dysarthria, dysphagia, drooling, impaired gag reflex and aspiration. There may be inappropriate behaviour indicating loss of higher function. Strokes affecting the brainstem have a more direct effect on pharyngeal function. Involvement of the medulla, vagal nuclei or lower cranial nerves can lead to severe swallowing problems and altered speech. 10 Wallenberg's syndrome is a classic brainstem vascular syndrome secondary to occlusion of the posterior inferior cerebellar or vertebral artery. Patients present with vertigo, severe nausea, hoarseness and ataxia. Examination reveals a number of ipsilateral signs: absent corneal reflex, Horner's syndrome, facial anaesthesia and paralysis of the palate. There is contralateral diminution of pain and temperature sensation. Palatal and laryngeal
Myasthenia gravis is a disorder of neuromuscular transmission at skeletal muscle. The disease is usually an acquired autoimmune disorder caused by the presence of immunoglobulin G autoantibodies against acetylcholine receptors at the neuromuscular junction, associated with reduction in the number of these receptors. There is also a more rare hereditary form with genetic abnormalities of the neuromuscular junction. The disease is more common in women, the peak incidence being in the twenties and thirties, and in men the fifties and sixties. Myasthenia gravis should be considered when otherwise healthy patients present with laryngeal weakness, varying dysphonia and dysphagia. Videofluoroscopy shows decreased pharyngeal mobility, laryngeal penetration and some silent aspiration. 7 Often, the findings at video fluoroscopy significantly outweigh the patient's symptoms. Poor prognosis correlates to the severity of pharyngeal dysfunction. Nasal regurgitation due to palatal weakness is also a typical presentation in younger patients and may be associated with ocular muscle fatigue. The demonstration of weakness of muscle groups by continued use and recovery after a short rest is diagnostic. Pharmacological testing is possible by intravenous injection of edroponium (tensilon) to improve
Stroke
1--
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DEMYELINATING DISORDERS
weakness reflects involvement of the nucleus ambiguus; typically it has a good prognosis. Rarely, dysphagia may be the only symptom of a brainstem stroke. It is important to diagnose a stroke rapidly as there are now interventions that can treat the acute stroke depending upon its aetiology. It is also important in the prophylactic treatment of further strokes. A stroke can usually be diagnosed on clinical grounds but a computed tomography scan will help to differentiate embolic and haemorrhagic stroke, and this is important in treatment. A magnetic resonance (MR) scan is especially useful in identifying brainstem strokes. If a patient is demonstrated to be aspirating early, percutaneous endoscopic gastronomy (PEG) placement, as opposed to nasogastric tube, significantly lowers the incidence of aspiration pneumonia.l1 Surprisingly, tracheostomy increases the risk of aspiration and is an inappropriate measure if employed purely to protect the airway.12 [***] Palatal myoclonus reflects damage to the dentate nucleus of the cerebellum, red nucleus of the basal ganglion, inferior olive and the central tegmental tract, due to involvement of the basilar artery. All patients presenting with myoclonus should be investigated with magnetic resonance imaging. Division of the tensor tympani muscle has been advocated but relief may be obtained by injection of botulinum toxin. 12 [**/*]
Multiple sclerosis is the most common disease caused by an inflammatory demyelinating process in the central nervous system. It is characterized by multifocal areas of demyelination with relative preservation ofaxons, loss of oligodendrocytes and astroglial scarring. Autoimmune and infective aetiologies have been postulated. Clinical diagnosis is a combination of clinical and MR scan findings, although strict clinical criteria for research purposes have been developed. Multiple sclerosis can cause dysphagia if the corticobulbar tracts or brainstem are involved. Dysphagia is usually an end-stage symptom with 10-33 percent of patients affected,15 although earlier in the disease patients may have occasional choking episodes on food or fluids, especially when tired. Video fluoroscopy commonly demonstrates reduced pharyngeal peristalsis and delayed swallowing reflex and, again, can help in identifying successful strategies to improve the swallow. PEG feeding may become necessary as the condition progresses. Treatment includes corticosteroids and in some cases interferon- ~lb may be useful. 16 Various other medications have been reported for relief of specific symptoms. There is no known cure.
MOVEMENT DISORDERS
Guillain-Barre syndrome
Parkinson1s disease
Guillain-Barre syndrome is characterized by endoneural perivascular mononuclear cell infiltration together with multifocal demyelination of peripheral and cranial nerves. In two-thirds of patients there is a preceding event one to four weeks prior to the onset of neurological symptoms. This is most commonly an upper respiratory or gastrointestinal infection, surgery or immunization. It causes subacute weakness and sensory loss involving the oral cavity, pharynx and larynx as well as the limbs. Most patients recover but need supportive care, sometimes involving ventilation.
Parkinson's disease is a relatively common disorder with a cumulative lifetime risk of one in 40. It is a slowly progressive disease caused by degenerative changes in the zona compacta of the substantia nigra. There is macroscopic pallor of this area of the brainstem with depigmentation and loss of neurons. Depletion of doperminergic neurons of the substantia nigra leads to reduced striatal dopamine, the major biochemical abnormality in Parkinson's disease. It is characterized by a combination of tremor at rest, bradykinesia, rigidity and loss of postural reflexes. It is caused by a neuronal loss, with Lewy bodies, in the substantia nigra. Swallowing problems are due to delay in initiation of swallow, irregular movement of the epiglottis and stasis in the pyriform fossae. The dysphagia may be partially due to autonomic dysfunction and, in cases of multiple system atrophy, patients can present with rapid weight 10ss.13 Levodopa, a dopamine precursor, is often given early in the disease as 'it relieves symptoms. However, this treatment is associated with complications, such as involuntary movements and neurotoxicity. Dopamine agonists (ropinirole) have also been used as an alternative treatment option. 14 [***]
Multiple sclerosis
SYSTEMIC INFECTIONS Poliomyelitis Poliomyelitis is caused by an RNA enterovirus of high infectivity that leads to destruction of neurons in the anterior horn cells of the spinal cord. However, the cerebellar vermis and the brainstem nuclei, including the nucleus ambiguous, V, VII, XII and vestibular nuclei, may be affected. The generalized nature of the infection means that the mu'Sculature of the orofacial and pharyngeal regions may be affected. Acute infection is now rare. In
Chapter 157 Neurological disease of the pharynx
England and Wales, there were only 21 cases of paralytic poliomyelitis between 1985 and 1991. 17 Bulbar poliomyelitis is present in 20 percent of cases as acute infection with a high associated mortality. However, the disease remains a problem for those infected previously as there is evidence that problems with dysphagia and sleep apnoea can surface many years after infection. The onset of symptoms may be insidious and may only become apparent when muscular weakness affecting respiratory function occurs. Objective testing of asymptomatic patients with a previous history of poliomyelitis reveals delayed pharyngeal transit time and impaired tongue base and pharyngeal wall movements in many cases. Muscle biopsies reveal muscular atrophy with lymphocytic infiltration of muscle fibres with denervation of single fibres due to deterioration of distal nerve synapses. IS The development of symptoms related to pharyngeal function following a previous history of poliomyelitis should lead one to suspect post-polio syndrome. Management is directed at excluding other possible causes and rehabilitation in a multidisciplinary setting with a speech and language therapist. [***/**]
Diphtheria Corynebacterium diphtheriae rarely causes problems in the developed world following widespread active immunization. The bacterium produces a potent toxin and pharyngeal infection is also associated with the formation of a grey pseudomembrane causing airway obstruction. Treatment is with antitoxin which should be administered intravenously immediately. A penicillin should also be given to treat the bacterial infection. The toxin produces neurological manifestations, such as palatal and pharyngeal weakness, which persist after treatment as fixed toxin is not neutralized by the antitoxin. Transmission is normally by airborne droplet infection and exposed individuals should be treated with penicillin or erythromycin and given a booster dose of toxoid. [Grade B]
I 2079
Treatment of the acute phase is aimed at symptom control and adequate analgesia should be administered. The administration of famciclovir (500 mg three times daily) or oral acyclovir (800 mg five times daily) decreases the formation of new lesions and reduces acute pain. 19 Post-herpetic neuralgia rarely occurs under the age of 50 years, but is a problem in the elderly. Controlled trials of oral antiviral drugs with or without steroids have not shown a significant reduction in the incidence of postherpetic neuralgia. 2o Persistent neuralgia is both debilitating and distressing and as yet there is no universally accepted treatment despite many trials of therapy. Tricyclic antidepressants, carbamazepine and phenytoin have been used with varying success. The development of regimens for the prevention of treatment of post-herpetic neuralgia remains an important goal for researchers in this field. 2l [****]
Rabies Rabies is a zoonosis, endemic in many countries although eradicated in the UK since 1903. The virus is highly neurotrophic and replicates in the central nervous system following exposure. It then spreads centrifugally along efferent nerves. The most common presentation is a combination of inspiratory muscle and laryngopharyngeal spasm associated with terror and hydrophobia. Cranial nerve palsies may occur with prominent fasciculation. Patients are unable to swallow their own saliva and without supportive treatment 30 percent die during a hydrophobic spasm within the first few days. Once rabies encephalomyelitis is established, it is invariably fatal. Preexposure vaccination is highly effective in prevention. However, if exposure occurs without vaccination then correct cleaning of the wound and optimum postexposure vaccination with vaccine and immunoglobulin can reduce the risk of rabies developing to near zero. 22 , 23 [****/***]
Botulism Herpes zoster Varicella zoster is an exclusively human herpesvirus that causes chickenpox, becomes latent in cranial nerve and dorsal root ganglia and once reactivated can produce shingles (zoster) and post-herpetic neuralgia. Zoster is ten times more frequent after the age of 60, but can occur at any age. It is characterized by radicular pain and a vesicular rash. In the pharynx, the vesicles may be found over the palate, pharynx and laryngeal inlet on one side only. Palsies of the lower cranial nerves can occur, but often develop some weeks after the acute phase. It is thought that infarction of the blood supply to the nerves takes place.
Botulism, caused by the potent toxin of Clostridium botulinum, causes a dramatic weakness of the lower cranial nerves and skeletal muscles after ingestion of the poison. The patient often presents as a bulbar palsy with dysphagia, diplopia and ptosis. It is treated by the administration of an antitoxin.
MOTOR NEURON DISEASE Motor neuron disease refers to a group of degenerative motor system disorders with overlapping clinical features and unknown aetiology. Amyotrophic lateral sclerosis (ALS), progressive bulbar palsy (PBP) and primary lateral
2080 I
PART 15 THE UPPER DIGESTIVE TRACT
sclerosis (PLS) have all been described in the literature under the common title of motor neuron disease. The most common disorder is ALS with an incidence of 1.2-2.2 per 100,000 per year. Approximately 10 percent of cases are familial with an autosomal dominant pattern of inheritance and onset is normally in the sixth decade of life. The disease process can present with combinations of upper and lower motor neuron signs and bulbar involvement. The sensory and autonomic systems are usually spared. Focal weakness is an early presentation and, when associated with regional fasciculations and upper motor neuron signs, is strongly suggestive of ALS. Around 25 percent of patients have involvement of the bulbar region at onset and may be misdiagnosed as having had a stroke. Diagnosis is based on clinical findings and requires both upper motor neuron (UMN) and lower motor neuron (LMN) signs to be present in the bulbar region and in two spinal regions. Electromyography and nerve conduction studies can contribute in the diagnostic work up. Magnetic resonance imaging of the brain and spinal cord may be required to exclude other disorders. The disease is normally relentless in its progress and the average survival time is three years. 24 Treatment involves supportive care and symptom control. Treatment of bulbar dysfunction invoives improving speech, maintaining communication and avoiding aspiration, while maintaining nutrition and managing secretions. Use of a percutaneous gastrostomy should be considered at a relatively early stage before aspiration occurs. Sialorrhoea may be reduced by amitriptyline at night (25 mg), which can also help pseudobulbar emotional lability. A multidisciplinary approach will involve speech therapists, physiotherapists and palliative care teams. Pharmacological treatment is now available in the form of riluzole which inhibits release of glutamate and has been shown to prolong tracheostomy-free survival. 25 This intervention has been approved in the UK by the National Institute of Clinical Excellence and there are ongoing trials to determine the optimum dosage regimen. [****]
primary temporal bone tumours, metastases, jugular bulb thrombosis, glomus tumours and skull base necrosis secondary to malignant otitis externa can all cause combinations of peripheral nerve deficits. The various causes and epohymous names are shown in Table 157.2. Cranial nerve neuropathies secondary to lymphoma, leukaemia and carcinoma may be due to infiltration directly with or without involvement of neural foramina. Amyloidosis may directly infiltrate nerves causing autonomic neuropathy or specific cranial nerve deficits. Diabetic neuropathies usually affect oculomotor nerves, although the lower cranial nerves may be involved.
NEURODEVELOPMENTAL DISORDERS A number of neurodevelopmental disorders can affect pharyngeal function. Syringomyelia is caused by a progressive enlargement of a cystic cavity involving the medulla or upper spinal cord. When the medulla is involved, it is normally known as syringobulbia. The Arnold-Chiari malformation may be associated with herniation of the brainstem through the foramen magnum. Compression of the brainstem can cause respiratory distress, dysphagia and apnoea. Treatment involves shunting the associated hydrocephalus and decompressing the brainstem. Dandy-Walker syndrome results from prenatal obstruction to the outflow of cerebrospinal fluid (CSF) through the fourth ventricle with formation of a cyst in the posterior fossa?6 Once more, compression can lead to neurological compromise. Klippel-Feil syndrome is synonymous with fusion of cervical vertebrae during development. There may be compression of the brainstem associated with shortening of the neck. Cerebral palsy is a blanket term to describe a collection of motor deficits present at birth. Pharyngeal problems relate to abnormalities in neuromuscular coordination and paresis or paralysis of pharyngeal musculature. Supportive measures involve a multidisciplinary approach with close attention to nutritional needs while preventing aspiration.
PERIPHERAL NERVE LESIONS The lower cranial nerves may be affected by local disease involving the brainstem, skull base, neck or thorax. The nerves IX to XII are most commonly involved together in disease affecting the skull base. Nasopharyngeal carcinoma, Table 157.2
Syndrome Vernet's Collett-Sicard Villaret's Jackson's
Iatrogenic dysphagia Iatrogenic dysphagia can have numerous causes and is often related to medication. Neuroleptics are well known
Eponymous cranial nerve palsies and causes.
Cranial nerves IX, X, XI IX, X, XI, XII IX, X, XI, XII, Horner's X, XII, corticospinal tract
Jugular foramen (tumours, aneurysms) Posterior laterocondylar space (parotid tumours, chemodectomas, metastases) Posterior retroparotid space (pa~otid tumours, chemodectomas, lymphadenopathy) Chordomas, metastases, schwannomas
Chapter 157 Neurological disease of the pharynx
for causing extrapyramidal side effects, and other commonly used drugs, such as prochloperazine and metoclopramide, can cause similar effects. These include tardive dyskinesia and lingual or laryngeal dystonia. Medications that cause central nervous system depression, such as benzodiazepines, can also cause or make pre-existing dysphagia worse by suppressing brainstem function. Surgery can also cause problems with swallowing. This includes surgery to the neck, for example, anterior cervical spinal surgery and carotid endarterectomy, that interferes with the function of the pharyngeal plexus and recurrent laryngeal nerve. Posterior cranial fossa surgery can affect the lower cranial nerves and thyroidectomy as well as potentially affecting the function of the recurrent laryngeal nerves and also the superior laryngeal nerve.
GLOSSOPHARYNGEAL NEURALGIA Glossopharyngeal neuralgia is similar to the more common trigeminal neuralgia but is localized to the distribution of the IXth cranial nerve. Although it was originally described by Galen, the first reports in the literature date from 1910. 27 ,28 The annual incidence is 0.8 per 100,000 population and there are cases of coexistent trigeminal neuralgia. 29 , 30 Presentation is with a stabbing pain related to the area of the tonsil and tongue base. The neurological examination is normal and the pharynx and larynx are free of disease. During the intervening periods the patient is symptom free. The average recurrence rate for a second episode is only 3.6 percent per year and twothirds of patients will only have a single documented episode. 30 Some patients will present with associated syncope due to vagal nerve stimulation during an attack. 31 [**1*] Treatment is initially directed at control of symptoms. In all cases it is advisable to exclude possible skull base lesions by appropriate examination and imaging prior to embarking on treatment. In some cases, a long styloid process will be the cause of symptoms. This syndrome is known eponymously as Eagle's syndrome and resection of the process via the tonsillar fossa normally relieves symptoms. In cases without skull base disease, direct application of cocaine over the site of discomfort can provide relief. Carbamazepine has been used for both trigeminal and glossopharyngeal neuralgia for many years. 32 Some of the success ascribed to medical treatment may be explained by the high natural resolution rate of the condition, but it is worth trying in the first instance. In cases that fail to resolve with medical treatment then referral to a neurosurgical colleague may be considered. Jannetta has described glossopharyngeal and trigeminal neuralgia as a vascular compression syndrome and has advocated intracranial microvascular decompression. 33 ,34 [**/*]
I 2081
MANAGEMENT OF NEUROGENIC PROBLEMS The management of neurological disorders requires a precise diagnosis and, where possible, treatment of the underlying condition. For patients who have a chronic untreatable disease, treatment should be focussed on avoiding aspiration when feeding and thereby repeated chest infections and pneumonia. It may be possible early in the course of a chronic disease, with the help of a swallowing therapist, to develop strategies that still allow an oral intake, without aspiration. This may include modifying the diet, by appropriate alterations in taste, temperature and texture. Generally, solid foods are easier to swallow than liquids or pureed food. Thermal stimulation of the anterior fascial arch has been shown to be beneficial in some patients. As many patients with neurological dysphagia retain their intellectual capabilities, they can sometimes be taught to hold a full breath consciously before swallowing and produce a cough following the swallow to try and prevent aspiration. The patient should always be fed sitting upright, with head slightly forward and the neck flexed, as these positions afford greater airway protection. It has been shown that head rotation during swallowing in patients with unilateral pharyngeal weakness facilitates bolus propulsion by the pharyngeal muscles on the stronger side and increases relaxation of the cricopharyngeus muscle. While a true supraglottic swallow may not be possible in most patients with dysphagia, it may be helpful in some patients. The Mendelsohn's manoeuvre, which prolongs laryngeal rise by prolonging contraction of the tongue, may also help opening of the pharyngo-oesophageal segment. Many patients, however, are unable to tolerate an oral diet and need feeding with a tube. If this is going to be long term then thought should be given to a gastrostomy tube rather than a nasogastric tube, as most patients find a gastrostomy easier to use, more comfortable and discreet. The patient can usually be fed overnight allowing freedom throughout the day. A gastrostomy tube can also usually be inserted percutaneously and does not require a general anaesthetic. Surgical procedures may have a role in treating neurogenic dysphagia and include cricopharyngeal myotomy when radiographic studies fail to show relaxation of the cricopharyngeus. The potential benefit of the surgical myotomy can be assessed preoperatively with a 'medical myotomy' using botulinum toxin. Vocal cord medialization is also of value when there is an associated vocal cord paralysis that does not allow closure of the airway when swallowing. Despite tube feeding, and the possible use of surgical procedures to improve swallowing, many patients are still at risk from aspiration (see Chapter 159, Management and treatment of intractable aspiration). A tracheostomy allows frequent suction of the respiratory tract but even when cuffed does not totally prevent aspiration, also there are problems with a long-term cuff, and a tracheotomy itself fixes the larynx and impairs swallowing. There is a
2082 I PART 15 THE
UPPER DIGESTIVE TRACT
case, in rare situations, of performing a laryngeal diversion operation to prevent aspiration if there is any prospect of long-term recovery. If there is no hope of long-term recovery, a laryngectomy can be considered to prevent aspiration. These procedures must be individually discussed with patients and their families, and will obviously depend on the underlying disease and its prognosis. Both of these procedures will cause the loss of speech (often this has already been affected by the underlying disease), and other ways of communication need to be considered. Finally, the psychological consequences of dysphagia and its cause need to be addressed with a low threshold for treatment of depression and anxiety.
lacking controls and based on small selected series.
35
Our ability to influence the progression of many neurological diseases is handicapped by delayed diagnosis. Future research effort should focus on: objective diagnostic tests for motor neurone disease at an early stage; nerve growth factors in peripheral nerve disorders; neurosurgical treatments for Parkinson's disease. there is a need for large, randomized, controlled trials assessing interventions to establish evidence for best practice.
REFERENCES 1.
..• i:~~~~rdf()gif~1~~()ndit~()rl~ca~dcQct*t:;~ot·75····· ....
;}\g~fceE!~£:or,~)p~aryn~eal~yspJ,1."gia.
.. ·1cc~r~~e~~agB-bsis'permits<;lirect~dlIledical ·(}~isR~g!calt~~~apy. ·•·• · · ••••·.·.IIi~.r()~r~~~~'1~dis~asej . Sllppprtive.t~r~ c·: inv91yesac l11ulticifscipH:n.ary approach..
Cagan RH (ed.). Neural mechanisms in taste. Boca Ratan, FL: CRC Press, 1989.
2.
Kiernan JA (ed.). Barr's: The human nervous system: An
anatomical viewpoint, 7th edn. Philadelphia: LippincottRaven, 1998. 3.
Car A, Jean A, Roman C. Deglutition: Physiologic and neurophysiologic aspects. Revue de Laryngologie Otologie. 1998; 119: 219-25.
4.
Nakazawa K, Umezaki T, Zheng Y, Miller AD. Behaviour of bulbar respiratory neurons during frictive swallowing and vomiting. Otolaryngology - Head and Neck Surgery. 1999; 120: 412-8.
5. Recurrent attacks of pharyngeal discomfort require imaging of the skull base.
diagnosis and treatment. Primary Care. 1996; 23: 417 -32. 6.
Early administration of antiviral therapy reduces acute
Rhinology, and Laryngology. 1997; 106: 705-9. 7.
Hopkins LC. Clinical features of myasthenia gravis.
8.
Sanders DB, Scoppetta C. The treatment of myasthenia
essential.
if An early neurological opinion is essential in cases of
Neurologic Clinics of North America. 1994; 12: 243-61.
diagnostic uncertainty as objective tests are often not
gravis. Neurologic Clinics of North America. 1994; 12:
available.
if Neurological disease is common in patients
Kaye G, Zorowitz R, Baredes S. Role of flexible laryngoscopy in evaluating aspiration. Annals of Otology,
pain in herpetiform infections.
if Urgent post-exposure vaccination in rabies is
Trate D, Parkman H, Fisher R. Dysphagia: Evaluation,
343-59. 9.
Werneck LC, Cunha FM, Scola RH. Myasthenia gravis: A
presenting with dysphagia. It is important that there
retrospective study comparing thymectomy to
is both a high clinical index of suspicion and an
conservative treatment. Acta Neurologica Scandinavica.
adequate clinical examination to identify these diseases.
2000; 101: 41-6. 10.
if Management of dysphagia is best achieved by a
Norton B, Homer-Ward M, Donnelly M, Long R, Holmes G. A randomised prospective comparison of percutaneous
multidisciplinary team skilled in managing such
endoscopic gastrostomy and nasogastric tube feeding
problems over a prolonged period.
after acute dysphagic stroke. British Medical Journal. 1996; 312: 13-6. 11.
Betts RH. Post-tracheostomy aspiration. New England
Journal of Medicine. 1965; 273: 155.
Deficiencies in current knowledge and areas for future research There is a significant lack of objective diagnostic
12.
Varney SM, Demetroulakos JL, Fletcher MH, McQueen WJ, Hamilton MK. Palatal myoclonus. Treatment with
Clostridium botulinum toxin injection. Otolaryngology Head and Neck Surgery. 1996; 114: 317-20. 13.
Quinn N. Parkinsonism - Recognition and differential
tests in this field and the literature on the management
diagnosis. British Medical Journal. 1995; 310:
of neurogenic dysphagia is largely anecdotal,
447-52.
Chapter 157 Neurological disease of the pharynx I 2083
14.
* 15. 16.
17.
18.
19.
20.
21.
22.
23. 24. 25.
Marsh L, Dawson TM. Treatment of early Parkinson's disease. British Medical Journal. 2000; 321: 1-2. Dray T, Hillel A, Miller R. Dysphagia caused by neurological deficits. Otolaryngologic Clinics of North America. 1998; 31: 507-24. European Study Group on Interferon Beta-l b in Secondary Progressive MS. Placebo-controlled multicenter randomised trial of interferon beta-l b in treatment of secondary progressive multiple sclerosis. Lancet. 1998; 352: 1491-7. Joyce R, Wood 0, Begg N. Paralytic poliomyelitis in England and Wales 1995-1991. British Medical Journal. 1992; 305: 79-82. Sonies Be. Dysphagia and post-polio syndrome: Past, present and future. Seminars in Neurology. 1996; 16: 365-70. Wood MJ, Johnson RW, McKendrick MW, Taylor J, Mandai BK, Crooks J. A randomized trial of acyclovir for 7 days or 21 days with and without prednisolone for treatment of acute herpes zoster. New England Journal of Medicine. 1994; 330: 896-900. Kost RG, Straus SE. Postherpetic neuralgia - pathogenesis, treatment, and prevention. New England Journal of Medicine. 1996; 335: 32-42. Gilden DH, Kleinschmidt-DeMasters BK, LaGaurdia JL, Mahalingam R, Cohrs RJ. Neurologic complications of the reactivation of varicella-zoster virus. New England Journal of Medicine. 2000; 342: 635-45. Warrell MJ, Nicholson KG, Warrell DA, Suntharasamai P, Chanthavanich P, Viravan C et al. Economical mUltiple-site intradermal immunisation with human diploid-cell-strain vaccine is effective for post exposure rabies prophylaxis. Lancet. 1985; 1: 1059-62. World Health Organisation. World survey of rabies, No. 32 for year 1996. www.who.int/emc-documents/rabies. Ross MA. Acquired motor neurone disorders. Neurologic Clinics. 1997; 15: 481-500. Riluzole for motor neurone disease - full guidance. www.nice.org.uk.
26.
27. 28.
29.
30.
31.
32.
33.
34.
* 35.
Pollack IF, Pang 0, Kocoshis S, Putnam P. Neurogenic dysphagia resulting from Chiari malformations. Neurosurgery. 1992; 30: 709-9. Peet MM. Glossopharyngeal neuralgia. Annals of Surgery. 1935; 101: 256-68. Weisenberg TH. Cerebello-pontine tumor diagnosed for six years as a tic doloureux: The symptoms of the irritation of the ninth and twelfth cranial nerves. Journal of the American Medical Association. 1910; 54: 1600-4. Katusic S, Williams DB, Beard CM, Bergstalh E, Kurland LT. Incidence and clinical features of glossopharyngeal neuralgia, Rochester, Minnesota, 1945-1984. Neuroepidemiology. 1991; 10: 266-75. Kobata H, Kondo A, Iwasaki K, Nishioka T. Combined hyperactive dysfunction syndrome of the cranial nerves: Trigeminal neuralgia, hemifacial spasm and glossopharyngeal neuralgia: ll-year experience and review. Neurosurgery. 1998; 43: 1351-62. Barbash GI, Keren G, Korczyn AD, Sharpless NS, Chayen M, Copperman Y et al. Mechanisms of syncope in glossopharyngeal neuralgia. Electroencephalography and Clinical Neurophysiology. 1986; 63: 231-5. Ekbrom KA, Westerberg CE. Carbamazepine in glossopharyngeal neuralgia. Archives of Neurology. 1966; 14: 595-6. Jannetta PJ. Observations on the etiology of trigeminal neuralgia, hemifacial spasm, acoustic nerve dysfunction and glossopharyngeal neuralgia: Definitive microsurgical treatment and results in 117 patients. Neurochirurgia. 1977; 20: 145-54. Resnick OK, Jannetta PJ, Bissonnette 0, Jho HD, Lanzino G. Microvascular decompression for glossopharyngeal neuralgia. Neurosurgery. 1995; 36: 64-9. Hughes T, Wiles e. Neurogenic dysphagia: the role of the neurologist. Journal of Neurology, Neurosurgery, and Psychiatry. 1998; 64: 569-72.
158 Dysphagia: management and intervention
ALISON PERRY
2091
Introduction
2084
Best clinical practice
Management of dysphagia
2086
Tr e a tm e nt
Deficiencies in current knowledge and areas for future
2086
Conclusion
2091
Key points
2091
2091
research
2092
References
The data in this chapter are supported by a search of the following databases: Medline, PubMed, Database of Abstracts of Reviews of Effectiveness
ClNAHL, ClinPSYC, (DARE), Evidence Based Medicine Reviews (EBM Reviews), the
Cochrane database of systematic reviews and the Cochrane Controlled Trials Register. Refereed articles were retrieved using the key words dysphagia, swallowing, swallowing disorders, and the search focussed on diagnosis and management.
INTRODUCTION
The prevalence data are difficult to ascertain as there is a variety of terms used to define dysphagia; different methods are used to collect data across different studies
Convention
and, for some syndromes, the prevalence of dysphagia is
'Speech therapy' and 'speech therapists' have been used as the generic term in this chapter for swallowing interven tion by clinicians who therapists
(SLTs)
in
Australia and in the
are
the
termed speech UK,
speech
and language
pathologists in
USA and logopedists across much
of Europe.
unknown.2 T here is a wide variety of assessing and reporting methods
used.
For
example,
when
examining
the
intervention for dysphagia after acute stroke, a recent Cochrane review found that five different studies invol ving 'dysphagic patients' gave five different definitions.3
[****]
Incidence. prevalence of dysphagia Information on the incidence and prevalence of dysphagia is
scarce.
Using
calculations
investigators in the
based
on
ECRI
data,
Scope and increase of dysphagia practice by speech and language therapists: evidence for efficacy
USA have estimat'ed that approxi
mately 300,000 to 600,000 people each year are affected by
There is evidence of a growing research base to dysphagia
approximately 51,000 of these arose from disorders other
of practice,' as witnessed by the fact that, for example,
than stroke.l
there were 400 dysphagia-related scientific and research
dysphagia
resulting from neurological disorders and
intervention and a move towards evidence-based models
Chapter 158 Dysphagia: management and intervention I
papers published in 1997, compared with 175 in 1980.4 However, 'more' is not necessarily 'better'. In 1999, alarmed by increasing costs for dysphagia assessment and treatment, the Health Care Finance Administration in the USA commissioned a report from the Agency for Health Care Policy and Research (AHCPR). This report is useful to consider in some detail as it illustrates how an evaluation of the evidence can importantly inform the need for clinical development and change. 1 The AHCPR undertook a large-scale systematic review for an evidence-based assessment of methods used for diagnosing and treating dysphagia in elderly individuals with neurological disease, and specifically those methods employed by speech therapists. In order to examine the evidence for dysphagia intervention, four questions were tackled. 1. How does the diagnosis of dysphagia or aspiration affect treatment courses and patient outcomes? 2. What are the indications for diagnosing patients using a bedside swallowing examination (BSE), modified barium swallow (NIBS) (or videofluoroscopic swallowing study), fibreoptic endoscopy (FEES) and/or any other instrumental exams? 3. Is one diagnostic technology more effective than another? 4. When is noninvasive therapy appropriate, and when should feeding tubes be used in certain patient populations. Four thousand, six hundred and forty-six items were retrieved in the form of journal articles, book chapters, manuscripts, monographs, web pages and personal communications. Largely, only US literature was used, so as not to influence information by using potentially different healthcare systems and practices. In this systematic review, the overall conclusion in terms of design was that the subject sizes in the studies were almost universally too low, with resulting low statistical power and hence unreliable results. The evidence regarding the first question above suggested that a significant reduction in the occurrence of pneumonia was observed when a systematic pro gramme of diagnosis and treatment of dysphagia in an acute stroke management plan was implemented. These data were from historically controlled studies so, although the level of evidence was not the highest, the effects observed were substantial so 'the results must be taken as , evidence of efficacy of these programs .l [***] Regarding the second question, the report concluded 'the risk for developing aspiration pneumonia cannot be accurately predicted from any single clinical sign or symptom'. A further conclusion was that 'there is a clear cut need to optimize a brief initial exam that employs several key symptoms to accurately detect patients with
2085
possibly unsafe swallows and who therefore need more intensive testing'. Research did not demonstrate any significant advantage of one test over another; no one test could be used as a 'gold standard', as none was 100 percent accurate. The third question could not be answered because the results of the studies of diagnostic test performance that addressed this question were contaminated by the fact that treatment necessarily followed diagnosis of a swallowing disorder. Thus, it was impossible to determine the purely diagnostic abilities of each test employed. Two cost-effectiveness models were constructed to examine this further, and the results indicated that the use of a full BSE in dysphagia programmes reduced costs. Evidence on the fourth question consisted of limited data from a single randomized control trial (RCT), indicating that a soft mechanical diet including thickened liquids results in a lower morbidity than did a pureed diet. [****] The authors pointed out that, although numerous other studies have been conducted on the treatment of dysphagia, their designs make it impossible to assess the efficacy of individual treatments. The review concluded: 'a well designed trial that compares dysphagia programs using different diagnostic modalities is needed'.l [****]
Defining terms
Dysphagia is the term used to describe difficulty with eating and swallowing, arising from the Greek 'dys' (with difficulty) and 'phagia' (to eat) and has many definitions. Most frequently, the definition used is 'difficulty in , moving food from mouth to the stomach .5 In reality, speech therapists are involved in managing oropharyngeal dysphagia as, once the problem is at, or below, the level of the lower pharynx (i.e. where swallowing/peristalsis becomes involuntary), then little can be gained from behavioural intervention and oesophageal level dysphagia is usually managed surgically/medically. Aspiration (the entry of food or liquid into the airway below the level of the true vocal folds) and penetration (entry of food or liquid into the larynx to the level of, but not below, the true vocal folds) may, or may not, be symptoms of dysphagia. The association between demonstration of occasional or chronic aspiration and development of aspiration pneumonia is, as yet, unknown. Often, we make the assumption that detection of aspiration will have a direct link to the development of pneumonia but this may not be the case as, although the quantity and frequency of aspiration may be important, there may be other factors that play an even more important role. One study has found that dependency on others for feeding was a dominant risk factor for developing aspiration pneumo nia, rather than dysphagia alone. 6 [***]
2086
I PART 15 THE UPPER DIGESTIVE TRACT
MANAGEMENT OF DYSPHAGIA
TREATMENT
Approaches to an oropharyngeal swallowing problem may be medical, surgical, prosthetic, behavioural or a combination of these. Regardless of the approach taken, the swallowing therapist is usually involved with reducing morbidity (dysphagia) and preventing mortality, rather than 'curing' or reversing the condition. 'Management' refers to all the nondirect interventional aspects of dysphagia therapy in which speech therapists engage, and includes: education (of staff, families, patients); collaboration (with staff, families); changes to the eating environment; and teaching behaviours to caregivers to increase the safety of the patient with dysphagia if/when eating. Timing of swallowing rehabilitation is important. For people undergoing treatment for head and neck (H&N) cancer, for example, a decision may need to be made early in planning treatment for temporary or permanent nutritional support where the treatment is likely to be protracted, as patient comfort and motivation - as well as hydration and nutrition - are important considerations. 7
The literature regarding child and adult interventions in dysphagia are quite different, with most literature from intervention with children being largely around cleft palate babies and children with cerebral palsy. In adults, the literature on intervention is richer, with populations studied ranging from those with neurological aetiologies such as motor neurone disease (MND), Parkinson's disease (PD) or stroke, to people with H&N cancer. The treatment offered by speech therapists for people with dysphagia may be divided into compensatory strategies (which are not aimed at changing swallowing physiology) and rehabilitative therapy (which is aimed at changing swallowing physiology).8 The former includes: postural changes; changes of volume/speed of food delivery; dietary changes; changing oral awareness and/or using prostheses. The latter will include use of range of motion (ROM) (oral) exercises, resistance exercises and gaining voluntary control over swallowing by using different manoeuvres.
The rehabilitation phase of dysphagia intervention is usually begun once the medical and surgical treatment is finished and the patient is healed enough to try to swallow. For surgically treated patients with head and neck cancer, this may be seven to ten days post-surgery if there are no complications. If radiotherapy is pursued, then assessment and treatment begins if/when swallowing problems are reported. For stroke patients, once they are alert and orientated, then assessment and therapy will begin. With babies who have neurological problems such as cerebral palsy, or who have structural abnormalities such as a cleft palate, speech therapists are often involved in managing and treating the emerging swallowing problems in the neonate. Usually, if patients are in hospital, then speech therapy is daily for inpatients, with ongoing outpatient (usually weekly) appointments after discharge. Goals are often long term, aimed at optimizing swallowing function. However, the swallowing therapist will often have seen the patient throughout the course of the planned interven tions in order to monitor changes in swallowing function and to provide a source of care, support and information for patient and family. Psychological distress, particularly anxiety, is a com mon sequela of dysphagia; fear of their disease and of swallowing may be common presentations in patients with H&N cancer. Patients undergoing chemotherapy and radiotherapy typically experience loss of appetite and may be anorexic as a result.7 Oral pain from mucositis, difficulty with initiation of swallowing, as well as altered oropharyngeal sensation and biomechanics secondary to cancer and its treatment, all need careful assessment and management in patients with head and neck cancer.
Compensatory strategies
Compensatory stategies are defined as 'those which redirect and/or improve the flow of food and eliminate the patient's symptoms, such as aspiration, but do not necessarily change the status of the patients' swallow'.8
POSTURAL TECHNIQUES These are changes in head and neck posture that change the pharyngeal dimension and redirect food in systematic ways. Such changes may be effective in reducing or eliminating aspiration in 75-80 percent of patients5,9 including infants, children and some patients with cognitive impairment. [***] However, due to physical constraints or cognitive deficits, some people will not benefit from such intervention. Postural changes that have been shown to be effective in clinical research studies include the following. •
•
•
Head back (utilizes gravity to clear oral cavity). This is used to improve inefficient oral transit of the bolus. Chin down (widens valleculae to prevent the bolus from entering the airway; reduces risk of aspiration). This is used if the triggering of the swallow reflex is delayed; also it is used to clear residue from the valleculae, if there is evidence of reduced posterior movement of the tongue base.9,Io Head rotation towards the damaged side (directs the bolus down the stronger side). This is used with patients where a unilateral vocal fold palsy or a hemi laryngectomy results in aspiration during the 11 swallow.
Chapter 158 Dysphagia: management and intervention I
•
•
•
Lying down on one side (eliminates the effect of gravity on the pharyngeal residue). This is used with patients where there is demonstrated reduced pharyngeal contraction, where residue is seen 12, 13 throughout the pharynx. Head tilt towards the stronger side (eliminates the damaged side of the pharynx from the direction of bolus transit). This is used in cases of unilateral oral and pharyngeal palsy on the same side (illustrated by residue on the same side of the mouth and pharynx).4, 8, 9 Head rotated (pulls the cricoid cartilage away from the posterior pharyngeal wall, reducing pressure on the cricopharyngeal sphincter). This posture is used where cricopharyngeal dysfunction is demonstrated (by visible residue in the pyriform sinuses).s
Postural techniques may be effective in eliminating aspiration across a variety of ages and conditions. Children and adults who have undergone H&N cancer resections, or who have dysphagia arising from neuro genic conditions, may benefit from the above, either tried alone or in combined postures (e.g. chin down and head tilt to damaged side). These manoeuvres have good evidence-based research to support their use, albeit sometimes in a single population studied, or with a small number of subjects. [***] In general, the evaluation of postural changes takes place under the conditions of a videofluoroscopic swallowing study (VFSS), which allows an assessment of the changes in swallow status and reduction/elimination of aspiration when the therapeutic technique is used.
CHANGES
11\1
VOLUME/SPEED OF FOOD PRESENTATION
The regulation of the amount of food taken per bolus, and the speed at which the food is given, may improve dysphagia in some patients. A particular volume of food may elicit a faster pharyngeal swallow and this needs to be regulated.14 [***] Where a patient has a delay in triggering the pharyngeal stage swallow, or has weak pharyngeal musculature such that the bolus takes time to clear, each swallow may take two or three attempts per bolus to clear. If eating too quickly, food can rapidly build up in the pharynx and aspiration may ensue.
TECHNIQUES TO IMPROVE ORAL SENSORY AWARENESS These techniques are usually used with people who present with a delayed onset of the swallow (either at the oral or the pharyngeal stage). They may include: increasing downward pressure of the spoon against the tongue when food is presented; presenting a sour bolus (lemon flavoured barium); presenting a cold bolus; presenting a bolus needing chewing; presenting a larger
...
2087
volume of bolus; allowing self-feeding from hand to mouth.8 Techniques that enhance sensory input, by changing taste, temperature and volume of the bolus presented, may assist patients who have a swallow apraxia; whereas, generally, giving verbal instructions may not necessarily assist these people. There is evidence that these techniques may also result in reducing the delay to triggering the pharyngeal stage of the swallow in some patients. IS [***]
TECHNIQUES TO IMPROVE SPEED OF TRIGGERING THE PHARYNGEAL SWALLOW The application of thermal/tactile stimulation to enhance sensory input and thereby trigger a more efficient/ speedier triggering of the pharyngeal swallow, has been 1 ,1 well developed and described. s, 8, 6 7 Thermo-tactile stimulation involves using a paediatric laryngeal mirror (size 00) that has been held in crushed ice to chill it. The mirror is then firmly rubbed along the anterior faucial arches, four or five times, before presenting the bolus to be swallowed. The technique 'heightens oral awareness and provides an alerting stimulus to the cortex and brain stem such that, when the patient initiates the oral stage of the swallow, the pharyngeal swallow will trigger more , rapidly .8 This technique facilitates faster triggering of the pharyngeal stage of the swallow and reduces the delay for up to several swallows later, before the reapplication of the icing is necessary. [***/**] An exaggerated suck-swallow action, with the use of vertical tongue-jaw movements with the lips closed, also facilitates triggering of the swallow. This technique also allows saliva to be taken to the back of the mouth, which may help some oral cancer patients who have limited saliva control.8
DIETARY CHANGES Generally, elimination of certain food consistencies may be necessary, but perhaps should be considered as the last compensatory strategy.s Patients who present with a delay in triggering the pharyngeal swallow and/or reduced airway closure are those most at risk from aspiration of thin fluids and these patients may not demonstrate improvement when using compensatory strategies such as postural changes or oral sensory procedures. There are occasions, such as when aspiration is demonstrably constant on a VFSS, where textures (such as thin fluid) are to be avoided, but such elimination is hard for the person with dysphagia, who is often extremely thirsty. This often results in noncompliance with advice and/or difficulty in adhering to therapy. It is desirable to involve the dietetics and speech pathology team members in the early stages when
2088
I PART 15 THE UPPER DIGESTIVE TRACT
planning treatment for people undergoing head and neck cancer, as nutritional problems occur in 30-90 percent of hospitalized cancer patients18 and several studies have demonstrated that malnourished patients endure longer hospital stays.19 An individual swallowing programme and active monitoring of nutritional intake may reduce hospital stay and improve the outcome of care. For example, in people undergoing radiotherapy as part of oral or pharyngeal cancer treatment, mucositis and oral dryness may result in food of high viscosity ('wet' or 'slidy' food), such as tinned peaches or banana mashed with a thin cream, being easier to swallow than dry, hard food, such as dry biscuits or crusty bread. Food preferences, religious and cultural sensitivities need to be acknowledged, as this is likely to improve compliance with therapy recommendations.
PROSTHETICS Intraoral prostheses can prove invaluable compensatory aids when improving swallowing in patients who have undergone surgical resections - including patients with H&N cancer. Typically, prostheses are used when patients are left with part, or all, of the soft palate ablated and a defect left in the reconstructed area. An acrylic or plastic palatal obturator can then be manufactured by the maxillofacial prosthodontist to address the defect. A palatal lift (which lifts the soft palate into a closed position) can be used for patients with velar incompe tence due to paralysis (as, for example, sometimes arises with people who have MND). This lift may improve hypernasality in speech as well as reducing nasal reflux during swallowing. Prostheses may also be necessary for patients who have significant (> 50 percent) tongue resected and/or the remaining tongue is severely reduced in movement. A palate-lowering, reshaping or augmentation device for these patients may mean that the remaining tongue can achieve tongue-palate contact during swallowing for better oral bolus transit, and a normal diet can be resumed. The majority of patients with oral and oropharyngeal deficits who are using intraoral prostheses usually experience either mixed results or have unchanged oral function.2o,21 [**]
Rehabilitative therapy
Rehabilitative therapy is designed to change swallowing physiology and may be divided into indirect and direct intervention. Indirect therapy is used with patients who are deemed unsafe on oral intake and involves no food or liquid being used; rather, exercises (ROM, resistance exercises, chewing
and swallow manoeuvres without food) are used and the patient only swallows their own saliva. Direct therapy involves the patient being taught to gain control over the bolus, using small amounts of food or liquid, using specified swallowing sequences. This is only used when patients can successfully swallow small amounts with no aspiration. Generally, the best results are obtained when the patient is able to follow directions, practise techniques with the clinician and then gain independence by practising when the clinician is not present.
ROM, RESISTANCE EXERCISES AND BOLUS CONTROL ROM (oral) exercises are used to improve the extent and motion of the lips, jaw, larynx and vocal folds (adduction exercises). Usually, the patient will use a mirror for visual feedback and will be encouraged to extend the target structure (e.g. lips) in a desired direction (e.g. spread) until maximum stretch is felt. The structure is held in extension for a second, and then relaxed.8, 22 Resistance exercises are designed to improve strength in specified articulators (e.g. tongue, lips, jaw) and involve the patient pushing the target structure (e.g. tongue) against a resistance (e.g. spatula or wooden tongue depressor held against the lips) and holding the posture of pushed tongue against the spatula for a second or so. Biofeedback devices such as the Iowa Oral Perfor mance Instrument (lOPI) have been used to give visual feedback from the pressure recording, thereby indicating changes in tongue strength. This device consists of a bulb placed in the mouth behind the front teeth (rather like a large lollipop on a stick) and this bulb, containing pressure transducers, is then connected to a computerized feedback display. The flange on the bulb is held by the patient on the tongue, behind the front teeth and the patient pushes hard against the bulb until the tongue pressure is sufficient to result in a green light being illuminated on the computerized display. This light then has to be held green, by tongue endurance, for a specified time (say five seconds). The settings may be changed as the resistance improves and muscular strength is regained. A Therabite system may be used to improve jaw opening where trismus is evident. The system applies an opening pressure to the upper and lower dental arches. The appliance is inserted into the mouth and, by what is essentially a system of ratchets, the jaw is mobilized and the dental arches pushed apart?3 Again, as with other ROM and resistance exercises, the posture is held for approximately five seconds, and then released. With all ROM and resistance exercises, there is a high level of muscle activity and therefore fatigue, and patients sometimes need to be cautioned to practice little and often throtIgh the day, rather than for extended periods at a time.
Chapter 158 Dysphagia: management and intervention I
The Kay Swallowing Workstation contains a number of biofeedback applications, such phy
(for
recording
laryngeal
as
SWALLOWING MANOEUVRES: TAKING VOLUNTARY
surface electromyogra
elevation),
tongue
CONTROL OVER PHYSIOLOGY
and
Five swallowing manoeuvres, all designed to change
pharyngeal transducers (for pressure recordings) and
swallowing physiology, have been researched and devel
videofluoroscopy. These may be used, in isolation or combination,
2089
oped to date. Good evidence exists as to their efficacy in
for feedback when teaching swallowing
reducing and/or eliminating aspiration when used with
manoeuvres.
different levels of swallowing dysfunction and/or different
Bolus control and chewing exercises can be used to
populations. [*** /**]
improve fine motor control of the tongue. Usually, a wad of gauze tied to a piece of string (which is held for control) is used for chewing practice, at least initially. This
1. The supraglottic swallow.
may be temperature-changed if desired - e.g. by soaking
2. The super-supraglottic swallow.
the wad in ice chips and then wringing out.
Table 158.1
indicates the most commonly used indirect
3. The Mendelsohn manoeuvre. 4. The effortful swallow.
therapy
5. The S haker manoeuvre.
techniques and their effect on swallowing physiology.
Table 158.1
...
'
Rehabilitative therapy: indirect procedures commonly used for dysphagia management.
Procedur� used ROM - lip exercises
Technique
..
'
..
_ ..
:';;
.:'·{-,:;.) -s-.
1. Tightly stretch and purse lips in contrasting feel and /00/
�' ·�: ·�:�! 16:� j1:�! �� � �.! ri i 6.g f , ',--
.
�.
.
�
1mprove labiaI closure
positions 2. Press lips tightly together
3. Open wide and then close tightly, contrasting /a/ and /m/ ROM - tongue exercises
1. Tongue ti p elevation; tongue base retraction
Improve tongue flexibility and ROM
2. Tongue protrusion/retraction 3. Lateralization movements - to left and then the right sides of the mouth ROM - jaw exercises
1. Unassisted jaw opening and closing 2. Mechanically assist jaw opening with stacked tongue
Improve mobility of jaw; Prevent/ eliminate trismus/ hypomobility
depressors along opening
3. Therabite jaw movement rehabilitation system Resistance lips
1. Hold a tongue depressor between lips (central position) while
Improve lip strength and ROM
clinician 'tugs' to remove 2. Hold tongue depressor tightly on right side of lips; then left Resistance tongue
1. Provide resistance to tongue depressor or spoon held on blade
Improve tongue strength and ROM
of tongue 2. Provide resistance similarly with tongue pushed out against the spatula, to each side against the spatula, and then down to lower lip/chin
3. Use IOPI (pressure transducer) for visual feedback of tongue pressure generated Bolus control exercises
Provide progressively smaller objects, controlled by clinician
Improve lingual control/direction of bolus
holding, to manipulate in mouth. As control improves, patient progresses to holding liquid or paste bolus in a cohesive manner Bolus propulsion exercises Chewing exercises Tongue base exercise
Patient pushes on a liquid-soaked gauze, held by its end so cannot be swallowed
Gain control over anterior-posterior movement of the bolus
Patient chews on wad of dampened gauze, gum or food
Improve control and ROM for chewing
1. Patient pulls tongue back and holds for a second
Improve tongue base ROM
2. Pretends to yawn; gargle 3. EffortfuI swallow manoeuvre Suck-swallow exercise
Use of vertical tongue-jaw suck-swallow actions, with lips closed
1mproves saliva control; assists triggering of pharyngeal stage of swallow
This table is adapted from research papers and chapters in the dysphagia field, and largely summarizes the work of Logemann5 and Sullivan?
2090
I PART 15 THE UPPER DIGESTIVE TRACT
The supraglottic swallow is designed to teach voluntary
closure of the vocal folds before, during and after the , 24 swallow,s. 8
patient will approximate, 'swallow your saliva a few times and feel your neck movements as you swallow. Feel the
the following, 'inhale and hold your breath (to adduct
lift as you swallow (patient if necessary). Now, this time, when you swallow and feel the voice box lift, do not let it
Cough immediately after the swallow, before breathing in'.
seconds'.
Instructions to the patient involve an approximation of
vocal folds); swallow firmly while holding your breath.
The clinical reality is that this is a difficult task as almost
everyone inhales immediately after the swallow, before the
Adam's apple, or voice box, feels lightly with fingers
drop back down. Hold it up with your muscles for several The
Shaker
manoeuvre,
which
is
a
head-raising
exercise designed to strengthen laryngeal movements
cough, thereby drawing any aspirate which may be left on
during swallowing,
may need to be practised with dry/saliva swallows before
The instructions to patients approximates, 'lie down on
occurs.
without raising your shoulders. Hold that posture for a
entrance to the laryngeal vestibule before, during and
repeated three times, and then 30 repetitive short head
top of the vocal folds into the subglottis. This technique
any attempt at introducing small bolus consistencies
The super-supraglottic swallow is designed to close the
after the swallow. Instructions to the patient would
has been
used
in older normal
individuals to strengthen hyoid and laryngeal movements. the floor or bed.
Try and lift your head to see your toes,
minute and then relax for a minute'. This exercise is
'breathe in, hold your
raisings are done, and the whole exercise is carried out three times a day,8, 30. 31
clear any leftover food'. The effort of bearing down usually
improvements in anterior laryngeal movement, upper
involve
approximation of,
an
breath and bear down hard. After the swallow, cough to
closes the false cords, tilting the arytenoids posteriorly to
meet the base of the epiglottis, thereby closing the airway entrance as tightly as possible.23,24 The effortful swallow is designed to raise the posterior
motion of the tongue base during the pharyngeal phase of
Results of this regime with older people demonstrated
oesophageal
sphincter opening and reduced 1 pharyngeal intrabolus pressure.B, 3 [***)
Table
158.2
summarizes
these
hypo
manoeuvres,
the
physiological effect and the rationale behind their use.
All of the swallowing manoeuvres shown in Table 158.2
swallowing and thus improve bolus clearance from the 8, 24, 25. 26 valleculae.s, Instructions to the patient approx-
manipulate voluntarily the oropharyngeal swallow as it
throat muscles'. The technique may be useful where a
techniques will begin as part of the VFSS, and this is
pharyngeal fibrosis and the patient has reduced phar
for assessing change. Postural variations are the easiest to
valleculae
swallowing
undertake and demand both good concentration and an
is designed to increase
appropriate swallowing manoeuvre may be introduced
imates, 'as you swallow, squeeze hard with
all of your
post-radiotherapy and/or surgical treatment results in
yngeal
sensation,
with
seen
on
a
post-swallow
pooling
video fluoroscopic
in
the
assessment. An effortful swallow may better clear that 25. 27 [**)
bolus?4.
The Mendelsohn manoeuvre
the duration of laryngeal elevation during swallowing, thereby
increasing
cricopharyngeal
duration and extent of opening.27, 28,29 Instructions to
the
the
occurs. Wherever possible,
introduction of treatment
useful both to the patient for feedback and to the clinician
utilize, whereas swallowing manoeuvres can be tiring to ability to increase muscular effort.
For patients who are deemed unsafe on oral intake, the
and practised with saliva swallows until the patient can
demonstrate (usually confirmed on VFSS) that they are safe to take small amounts orally without aspiration.
Changing swallowing physiology: manoeuvre; purpose; rationale.
Table 158.2
t\tI,anoeOvre
the
require an ability to follow instructions in order to
'
.
Purp,0se, - - -
�
..
-
-
,
�
....
�
' .
: .
.
,
-
\.
�'-
R�_tioijale ,
_ :. - '10.. ••
',"1,
.1.
•
�l
' "
t o
Supraglottic swallow
To improve reduced or late vocal fold closure
Voluntary breath holding adducts vocal folds
Super-supraglottic
To reduce closure of laryngeal vestibule/airway
Effortful breath holding tilts arytenoids forwards. clOSing
swallow
entrance
Effortful swallow
To improve posterior movement of tongue
Mendelsohn manoeuvre
This improves range (height) of laryngeal
airway entrance before, during and after swallowing Effort increases posterior tongue base movement
base; to increase oropharyngeal pressure movement Improves opening time of cricopharyngeus Shaker manoeuvre
To increase hyoid motion, and thereby increase
Laryngeal movement upwards and forwards opens the upper oesophageal sphincter, prolongs elevation of the hyoid/larynx movement and sphincter opening time Hyoid motion is responsible for biomechanical upward/
time of opening of the upper oesophageal
forward movement of larynx and this, in turn, is
sphincter
responsible for cricopharyngeal opening
7 5 This table is adapted from papers and chapters in the dysphagia field but l a rg ely summarizes the work of Logemann and Sullivan.
Chapter 158 Dysphagia: management and intervention I
CONCLUSION There is a s t rong evidence base for dysphagia assess ment ,
management and treatment, and mos t of this work has
been
spearheaded
Northwestern
Professor
by
University
in
Jeri
Chicago
Logemann
who
2091
".. There is a, sound evidence b ase . for therapeutic efficacy in these'patientsbut outcome measures need better definition. and agreement.
at
must
be
acknowledged as havi n g led the way over the last 25 years t ow ards a s ci entific, detailed
dy sphag ia.
However,
we
must
also
reco
un derst anding of
gnize
that
dysphagia
Best clinical practice 1----
--------���-- I
therapy as a specialism evolved from a clinical need,
.I If dysphagia is suspected, an urgent referral to a
benchmark for disorder. This is unlike many other aspects
./ In severe cases, where audible aspiration is heard,
without data from normal
swallowing to provide a
of speech pathology practice (e.g. child l ang uage devel
opment, voice disorders) where normative milestones are usually well re sea r ched and p ublished.
Al though many of the papers p u b lished in the field of dysphagia have been remarkable in their detail and exam i nation of d i sorder, without good data published for n ormal swallowing we have a problem when assessing
speech and language therapist is warranted, nonoral feeding may be necessary (via nasogastric tube or, if long term, then via percutaneous endoscopic gastrostomy
(PEG).
,/ A videoflouoroscopic swallowing study remains the optimal way to detect the presence of silent aspira tion.
what is ' normal ' from 'abnormal' in swallowing phy siol ogy, and what constitutes a 'safe' swallow.
Effi cac y data regarding measurement of the aspects of swallow i ng targeted in t herapy, such as increasing airway cl osu re , extent of lar ynge al elevation etc., may be
Deficiencies in current knowledge and areas for future research
are these being translated into changes in sw allo wi ng
). There is a notable lack of description and
reassuring for the therapist to collect, but we might ask:
status for the pa tien t and,
so eagerly recorded?
if not, then why are they beillg
Despite the fact that speech therapy services in acute
hospitals have, across the USA, UK, Europe and Australia,
been overwhelmed by in creasing numbers of referrals for pa t ients needing swallowing therapy, data regarding the
functional outcomes of s u ch a therapeutic explosion have been slow to follo w .
measurement of normal swallowing in the literature, which may be due to the fact that the most objective form of swallowing assessment involves using radiation (videofluoroscopy), albeit in quite small doses (approximately 0.5 mSvj ; and this has been difficult to justify in order to study swallowing in normal populations. Hence, the data on swallowing have been largely derived from populations who demonstrate dysphagia. More recently, studies have attempted to address this lack, and now questions are being raised as to the advisability of assessing anatomical structures by a clinical oromotor and/or
KEY POINTS" •
•
speech examination and extrapolating from this to predict how those same structures perform in 31 32 swallowing. ,
Dysp hagia is a costly, prevalent and debilitating disorder. Speech therapists have an inrpor'tanfJ�:art;J9 ' .. p"ta y, iil managing�, p-atielit.s'1�thj dy�pha,gia��I '- ..
involv� 'manageme,nt ,'and/or, treatment: ite,atme�t may; in�Glve' ," : '-'ei'ther: c�mp,ens�:t�ry t echili-qu,es. (no,t ;�Jm�d� " , a� ' c'9.,an �g 's' wall!QwingphY$'iolog-y) .o.t',-··:�,;; --.�,'
).- There is a need for: normative data on swallowing function(s);
.
,. Swallowing theI�py,may
"reh�?ilitat,iye ,th�apy,
���q'/����apgil?g :>"
the";latter m.a{lJe·,air�·ct.o{' �, " indirect : " , ,,, . ,\ - :" :>< ',:,. :: "�- ,�I. " - . , , '\:.,' O nly patjentS.who·,have·no <eVidenc�'Qr:--·,.� ',aspiration shouid be. tominenced on oral feeding and direct ,therapy; 'ot,hers'·should:. remain nil by'mouth while illciire ct : ' ' physiology);,
techniques 'a.r;e 'pursued.
.<.
.'
.
'
an examination of which clinical information is of value when assessing potential risk of aspiration; agreement regarding assessment and measurement of dysphagia, uS'mg VFSS;
;,�:\
-c
"
,;
r
assessing what are the changes in swallow measures that will result in a changed consistency diet for the patient?
,
evidence on outcomes of therapy, i.e. are we addressing 'real' or 'surrogate' outcomes? Does the change in measured data such as laryngeal elevation, for example, change the swallowing outcome for the patient?
2092 I
PART 15 THE UPPER DIGESTIVE TRACT
REFERENCES
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*
2.
AHCPR pub. no 99-E023, Diagnosis and treatment of
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Lazarus CL. The effects of bolus volume, viscosity, and
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Reilly S. Dysphagia. In: Reilly S, Oates J, Douglas J (eds). Evidence based practice for speech pathologists.
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London: Whurr, 2004. For an overview of EBP in
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Bath PMW, Bath FJ, Smithard DG. Interventions for
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Martin-Harris B. The evolution of the evaluation 18.
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Lundt OS, Casiano RR. Rehabilitation of speech and
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*
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Shaker R, Kern M, Bardan E, Taylor A, Stewart ET, Hoffman
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159 Management and treatment of intractable aspiration
ELFY B CH EVRETION
2103
Definition
2094
Summary
2103 2103
Pathophysiology
2094
Key points
Causes of aspiration
2095
Best clinical practice
Symptoms and signs
2095
Deficiencies in current knowledge and areas for future
Special investigations
2096
Conservative management of chronic aspiration
2096
Acknowledgements
2103
Surgical management of chronic aspiration
2097
References
2103
2103
research
The data in this chapter are supported by a Medline search using the key word aspiration and limiting the search to human and the English language.
DEFINITION
in
drug,
alcohol,
metabolic,
epileptic
and
general
anaesthetic related depressed states of consciousness. Aspiration is defined as laryngeal penetration of secretions,
Intractable,
such as saliva, ingested solids and liquids, or refluxed or
episodes of aspiration. It is most commonly seen in
or chronic,
aspiration refers to repeated
regurgitated gastric contents below the level of the true
neurological disorders and requires careful assessment
vocal cords.1 It happens as a result of impairment of the
and management to prevent life-threatening pulmonary
protective function of the larynx that leads to contamina
complications.
tion of the respiratory tract and can cause a variety of pulmonary complications that may be life-threatening. Oropharyngeal aspiration takes place in 45 percent of
PATHOPHYSIOLOGY
normal subjects during sleep.2 This would suggest that mere penetration of the upper airway is insufficient to
Aspiration of fluid with a pH < 2.5 produces an intense
produce disease and that other factors contribute to this
inflammatory reaction. Cytokines, such as interleukin 8
process. Reflex clearance mechanisms and host defence
and tumour necrosis factor alpha, are released, accom
competence are critical. In animal studies, the pH of the
panied by an influx of neutrophils.
aspirate,
increased
its
quantity
and
the
degree
of
bacterial
alveolar
capillary
This results in
membrane
permeability,
contamination determine whether pulmonary disease will
leakage of fluid and, ultimately, to damage to epithelial
develop and also its severity.
and alveola[ lining cells. The consequence of this is an
Aspiration may be an isolated event due to temporary
impairment C?f the airway protective mechanism as found
increase in total lung water. dependent
In more
on the pH and the
severe
cases,
volume of aspirate,
Chapter 159 Management and treatment of intractable aspiration I
widespread pulmonary oedema can develop into life
•
threatening acute respiratory distress syndrome.3, 4
Mechanical: nasogastric tube;
Minor repeated aspiration of smaller quantities of
- endotracheal tube;
acidic fluid usually takes place at night and affects the
- tracheostomy tube;
most dependent areas of lung, often segments of the
Miscellaneous:
upper lobes. It can produce damage from immediate particulate mechanical obstruction or by infection leading to pneumonia. Solid material that is retained in the lungs may produce problems months or even years later through provocation of a foreign body reaction and granulation tissue which produces local obstruction of the airway and distal infection. Over time, severe pulmonary fibrosis may develop.
2095
•
- severe debilitation. Impairment of the laryngeal protective mechanism in the above conditions is due to loss of motor activity and sensation of the larynx whether this is as a direct result of disease of the central nervous system, larynx, pharynx and oesophagus or due to altered consciousness. In the clinical setting the laryngeal incompetence is often associated with hypopharyngeal dysfunction. Neurological disorders are the most common cause of chronic aspiration with cerebro
CAUSES OF ASPIRATION
vascular accidents being top of the list, especially those involving the brainstem with bilateral cranial nerve palsies.
The causes of chronic aspiration are as follows. •
Neurological: central: •
cerebrovascular accident (stroke);
•
multiple sclerosis;
•
motor neurone disease;
•
Parkinson's disease;
•
progressive supranuclear palsy;
•
multiple cranial neuropathies;
•
head injury;
swallowing mechanism and the clearance reflex mechan ism in this population. It is also seen in the paediatric population where it is usually related to severe neurolo gical dysfunction.
SYMPTOMS AND SIGNS
•
anoxic brain injury;
Comprehensive evaluation of a patient with chronic
•
intracranial infection;
aspiration requires a careful history, clinical examination
•
intracranial tumours;
and special investigations to establish both the diagnosis
•
drug intoxication;
and the underlying cause of the aspiration.
peripheral nerve disorders:
Patients may complain of coughing or choking during
•
Guillain-Barre syndrome;
swallowing, suggestive of aspiration. In patients who
•
poliomyelitis;
aspirate
•
chronic inflammatory demyelinating
penetration and the presenting symptoms may be those
polyneuropathy;
of contamination of the respiratory tract. Patients may
neuromuscular junction:
silently
there
is
no
cough
after
laryngeal
complain of recurrent chest infections with fever and a
•
myasthenia gravis;
productive cough or the symptoms of any one of a variety
•
Lambert-Eaton myasthenic
of pulmonary complications, some of which may be life
syndrome;
threatening. These include laryngobronchospasm, airways
•
botulism;
muscle disorders:
•
Aspiration is most likely to occur in the elderly, presumably due to age-related changes in both the
•
muscular dystrophy;
•
polymyositis;
obstruction, tracheobronchitis, pneumonia, pulmonary abscess, sepsis and death. Patients may also complain of associated symptoms from. the underlying cause of the aspiration such as
•
dermatomyositis;
dysphagia, regurgitation, dysphonia, weakness, numb
•
inclusion body myositis;
ness, loss of coordination and tremor.
Gastrointesinal disease: - gastro-oesophageal reflux;
Often, the cause of the aspiration is obvious from the history. Specific enquiry should be made into any previous
- oesophageal dysmotility;
history of neurological, gastrointestinal, laryngeal and sys
- achalasia;
temic disorders in addition to a history of trauma, previous
- pharyngeal pouch;
surgery and a comprehensive list of current medications.
- pharyngeal stricture;
The clinical examination should include a complete
- cricopharyngeal spasm;
head and neck examination with careful assessment of
- pharyngeal and oesophageal
cranial
tumours;
nerve
function
to
look
for
loss
of
tongue
movement, wasting and fasciculation, loss of gag and
- postsurgical dysfunction;
cough reflex, loss of pharyngeal and laryngeal sensation,
- postradiotherapy dysfunction;
the presence of hoarseness and loss of vocal cord mobility.
! .
2096 I
PART 15 THE LIPPER DIGESTIVE TRACT
The larynx and hypopharynx are visualized by indirect
saline to clear the airways of secretions. It enables staging
laryngoscopy and/or nasolaryngoscopy to exclude pool
and biopsy of upper aerodigestive tract tumours and
ing of saliva or witness the passage of saliva into the
endoscopic stapling of pharyngeal pouches.
glottis
and
the
upper
trachea.
A
general
physical
examination should evaluate the severity of any pulmon ary
complication
as
well
as
look
for
evidence
of
Barium videofluoroscopy swallowing study
neurological disease or other possible underlying cause This is the gold standard for evaluating the swallowing
for the aspiration.
mechanism.5 It is a comprehensive test for all phases of swallowing,
but
is
particularly
useful
for
the
oral
SPECIAL INVESTIGATIONS
and pharyngeal phases and for identifying aspiration.
The cause of chronic aspiration in the majority of patients
used. The passage of the bolus is observed in both the
will be due to an existing neurological disorder. A number
lateral and anteroposterior views and evaluated for transit
of special investigations are available both to diagnose and
time, pooling and aspiration, as well as the motor
evaluate the severity of the aspiration. The order in which
function of the swallowing pathway. If aspiration is
the following tests may be carried out will depend on the
present, videofluoroscopy will identify the cause and
Barium in liquid or mixed with pureed and solid foods is
manoeuvres can be designed and tested to reduce this, for
clinical findings.
example swallowing during breath
holding,
with or
without a chin tuck and with or without a head turn
Chest radiograph
towards the affected side. This is particularly useful in patients
There is no typical radiographic pattern of aspiration and
with
neurological
disease,
after
surgery
or
radiotherapy.
any distribution of pulmonary infiltrates seen with the right clinical setting should suggest aspiration. Diffuse bilateral lung infiltrates may be seen in massive aspiration
Fibreoptic endoscopic evaluation of swallowing
or infiltrates may be seen in dependent lung segments, such as the posterior segments of the upper lobes and
A fibreoptic nasoendoscope is passed through the nose to
superior segments of the lower lobes in patients lying in
observe the larynx and pharynx at rest and during the pharyngeal phase of swallowing.6 With it, pooling of
the supine position.
saliva in the hypopharynx, reduced or absent endolar yngeal sensation and aspiration before and after swallow
Contrast swallow
ing can be detected. It is useful in neurological, frail and postsurgical patients and can be performed at the bedside.
A barium swallow should be avoided when aspiration is
The test can be extended usefully by using coloured fluids,
suspected as barium is slow to clear from the lungs and
purees
the patient will require physiotherapy after the procedure.
swallowing cannot be assessed directly and the cricophar
It is useful to diagnose a pharyngeal pouch, stricture,
yngeus and the oesophagus cannot be visualized.
and solids.
Unfortunately,
all
the phases
of
hiatus hernia or an obstruction of the oesophagus, in which case the presenting symptoms should be dysphagia, odynophagia or regurgitation. A high osmolar, water-soluble contrast medium is
CONSERVATIVE MANAGEMENT OF CHRONIC ASPIRATION
contraindicated if aspiration is suspected as it can cause a chemical pneumonitis or pulmonary oedema. Instead, in
The initial management of a patient who has chronic
patients
aspiration should include aggressive treatment of any
weight,
with
suspected
aspiration
a
low
molecular is
infective pulmonary complications with antibiotics, chest
preferable as this is less irritating to the lungs and should
physiotherapy and prevention of further aspiration by
cause minimal complications.
conservative means. In patients with mild or reversible
nonionic,
water-soluble
contrast
medium
aspiration, the adoption of specific swallowing man oeuvres to achieve a safe swallow, such as the supraglottic
Direct rigid endoscopy of the upper aerodigestive tract under general anaesthetic
language therapist, may be all that is necessary. In severe
This is performed when it is necessary to visualize the
patient is kept nil by mouth, with frequent suctioning
swallow sequence under the direction of a swallowing and cases more aggressive management is required.
The
larynx, pharynx, oesophagus, trachea or large bronchi. It
of saliva from the oral cavity and pharynx, the head of the
enables the removal of large particles of aspirated food
bed is elevated in patients with reflux, and nutrition
from the airways as well as bronchial lavage with normal
maintained by an alternative route.
Chapter 159 Management and treatment of intractable aspiration
continue, surgery may be indicated to prevent further
The enteral feeding techniques available are: •
nasogastric feeding tube;
•
pharyngostomy;
•
gastrostomy;
•
jejunostomy.
I 2097
soiling of the respiratory tract. The goals of surgical treatment should be cessation of aspiration and restora tion of swallowing and speech using the simplest and most
effective
procedure.
The
procedure
reliable with a low complication rate,
Only the last two have been shown to be associated with
should
be
be reversible
should the underlying cause of the aspiration improve,
decreased aspiration in neurological patients. Percuta
and with the option of performing the procedure under
neous endoscopic gastrostomy is both a safe and an
local anaesthetic available in debilitated patients. Deci
effective means of feeding directly into the stomach. In
sions about surgical treatment of chronic aspiration
patients who continue to experience reflux and aspiration
should
a percutaneous endoscopic jejunostomy placed directly
condition
into
improvement.
the
jejunum
aspiration.
Open
further
decreases
the
chances
of
gastrostomies or jejunostomies are
take into
account
including
all
aspects of a patient's
prognosis
and
potential
for
Some conditions require a specific operation aimed at
required in patients who have had previous extensive
a correctable cause of the aspiration.
abdominal surgery as the percutaneous route is not
persistent isolated unilateral vocal cord paralysis which can be treated by vocal cord medialization techniques;
feasible in such patients. Nasogastric
tubes
Examples are:
are
easily
placed,
but
poorly
pharyngeal pouch which can be treated by endoscopic
tolerated long term by patients as they can be uncomfor
stapling or
table and are unsightly. They may decrease but not
cricopharyngeal spasm which can be treated by crico
removal
by an
external
neck
approach;
eliminate aspiration and some studies suggest that they
pharyngeal myotomy; hiatus hernia which can be treated
may actually predispose to aspiration? Total parenteral
medically or by Heller's operation; laryngeal, pharyngeal
nutrition is the intravenous route of providing nutrition
or oesophageal tumours.
and may be necessary if gut absorption is poor. However,
Patients with significant aspiration causing repeated
in certain cases it may not provide sufficient nutrition and
life-threatening pulmonary complications may require
can be associated with complications such as liver failure.
dissociation of the upper air and food passages by either
A tracheostomy with an inflated low-pressure cuff,
closing, diverting or removing the larynx. There have
Table 159.1,
fashioned either percutaneously or by the open technique,
been many procedures described, as listed in
provides
efficient
but few allow both phonation and swallowing as well as
pulmonary suction and reduces the work of respiration
being reliable and potentially reversible. The advantages
by decreasing the upper airways dead space. Although a
and disadvantages of the most commonly used techniques
tracheostomy may decrease aspiration it may not prevent
are discussed below.
direct
access
to
the
airway
for
it and it is not effective in patients with severe aspiration. It may, in fact, predispose to aspiration by interfering with elevation and anterior movement of the larynx
Vocal cord medialization techniques
during the pharyngeal stage of swallowing, and it prevents the generation of an effective cough. Cuff deHation can
Vocal cord medialization techniques are used in patients
result in penetration from secretions that have pooled
who aspirate as a result of an isolated unilateral vocal
above the cuff while overinflation of the cuff can impair
cord palsy. Aspiration is most likely to happen in a high
swallowing by pressure on the oesophagus. Long-term use
vagal lesion or when both the superior and recurrent
of a cuffed tracheostomy tube may cause tracheomalacia.
laryngeal nerves are injured as in these situations the
Aspiration with the tracheostomy tube in place can be
hemilarynx will lose all sensation as well as vocal cord
confirmed by the Evans blue dye test, which involves
mobility. With an immobile vocal cord the larynx cannot
recovering the dye in the tracheostomy aspirate after
function as a sphincter or generate an effective cough
placing it on the patient's tongue. A tracheostomy should
when aspiration occurs. Vocal cord medialization by the
only be used as a short-term measure in the management
type I Isshiki thyroplasty with or without arytenoid
of aspiration to provide access for pulmonary suction. To
adduction or injection of the vocal fold with Teflon,
minimize the incidence of tracheal mucosal injury and
Gelfoam, collagen or silicone may result in an improved
tracheomalacia
a
low-pressure
cuff
that
is
denated
periodically is used.
cough and voice and reduce or eliminate aspiration. These techniques will not restore laryngeal protective function in severe cases of laryngeal incompetence and there have been no successful reports of using these
SURGICAL MANAGEMENT OF CHRONIC ASPIRATION
techniques bilaterally. 8 The type I Isshiki thyroplasty uses an external neck approach to place a synthetic implant in the paraglottic
In patients where conservative management has failed to
space to displace the paralysed vocal cord towards the
prevent
midline. The procedure can be performed under local
aspiration,
and
pulmonary
complications
2098 I PART
15 THE UPPER DIGESTIVE TRACT
Table 159.1
Surgical options for prevention of intractable aspiration.
Tracheostomy
Procedure
Phonati.on
[**1
Potentially
Author/Reference
reversible
Injection of vocal cords Teflon
No
Yes
No
Lewis et 01.8
Gelfoam paste
No
Yes
Yes
Schramm et oJ.
Collagen
No
Ye s
Yes
Hoffman et OJ.
Silicon
No
Yes
No
Iwatake et
Isshiki type
9
lO
af.11
I thy ro p lasty
af.'2
± Arytenoid adduction
No
Yes
Yes
Pou et
Cricopharyngeal myotomy
No
Yes
No
McKenna et
Narrow field laryngectomy
Stoma
No
No
Canon, McLean 14
Solid endolaryngea I stent
Yes
No
Yes
Weisberger et
Vented endolaryngeal stents
Yes
Yes
Yes
Eliachar et
Epiglottic flap closure of larynx
Yes
No
Yes
Habal, Murra/7
Strome, Fri ed 1
af.13
af.'5 af.16
Modifications of epiglottic flap closure B
Striation of cartilage
Yes
No
Yes
Posterior flap open
Yes
Yes
Yes
Brookes,
Laryngeal suspension
Yes
No
Yes
Warwick-Brown et
False cord closure
Yes
No
Yes
Cummings et 01.21
Vertical laryngoplasty
Yes
Yes
Yes
Blitzer22
McKelvie19 al?O
al?3
Subperichondria I cricoidectomy
Yes
No
No
Eisele et
Partial submucosal cricoidectomy
Yes
Yes
No
Krepsi
Glottic closure
Yes
No
Yes
Montgomery25
Trachea-oesophageal diversion
Stoma
No
Yes
Lindeman26
Laryngotracheal separation
Stoma
No
Yes
Lindeman et 01.27
anaesthetic
for
fine
tuning
intraoperatively
reversible as the implant can be removed
function
returns.
In
some
patients
is
aspiration. Medical treatment of laryngopharyngeal reflux
may
spasm. Cricopharyngeal dilatation is only short lived.
and
if vocal cord
aspiration
et 01.24
with
a
proton pump inhibitor is helpful
in some cases of
continue owing to the technique failing to close a
Localized injection of botulinum toxin into the crico
posterior glottic chink. Arytenoid adduction may be
pharyngeus at endoscopy8 or percutaneously,29 has been
used, in addition, to complete the closure but this part of
the operation is not reversible.
12
used
to
relieve
the
spasm
of
the
cricopharyngeus
temporarily and assess the need for cricopharyngeal
Injection of the vocal fold with Gelfoam paste9 or
myotomy. If swallowing improves, a myotomy may be
collagenlO can be given to patients in whom spontaneous
helpful. In debilitated patients botulinum toxin injections
recovery of the vocal fold is possible as these substances
can be performed every four to six months.
are resorbed over a period of six to ten weeks. [n patients
A cricopharyngeal myotomy is approached through
where permanent vocal cord paralysis is expected, Teflon,
a skin crease incision at the level of the cricoid cartilage.
a nonabsorbable material can be injected
The transverse fibres of cricopharyngeus are found by
with extreme
care to avoid overcorrection and airway obstruction as
retracting sternomastoid and the carotid sheath laterally
Teflon cannot be easily removed. Complications with
and the
Teflon include extrusion and foreign body reaction. In
are divided, taking care not to damage the recurrent
recent years Teflon has been superseded by silicon.ll
laryngopharynx
medially.
The muscle fibres
laryngeal nerve or the mucosa of the cervical oeso phagus.13 Cricopharyngeal myotomy may not be of benefit on its
Cricopharyngeal myotomy
own but may be in combination
with other procedures
such as surgery for a pharyngeal pouch. Neurological Cricopharyngeal muscle dysfunction or spasm seen on
barium videofluoroscopy may cause a variety of symp toms ranging from a 'globus' sensation to dysphagia
with
pooling of saliva in the hypopharynx, dysphonia or
patients with conditions such as motor neurone disease, brainstem stroke or myopathies who have difficulty in all
three stages of swallowing may derive only limited or no
benefit from cricopharyngeal myotomy.
2099
Chapter 159 Management and treatment of intractable aspiration I
Epiglottic flap closure of the larynx (epiglottopexy)
Narrow field laryngectomy Total laryngectomy allows the patient to breath through a
stoma and is the most definitive method of separating the
This technique uses the epiglottis as a £lap to close the
upper air and food passages. It is reliable but irreversible.
laryngeal inlet. W hen first described,t7 this technique
It was the treatment of choice in the middle of the last 1 century. A narrow field laryn gectomy 4 (Figure 159.1) is
incision
less extensive than a total laryngectomy for the treatment
of laryngeal cancer as it preserves the hyoid bone, the
strap
muscles
and
as much
pharyngeal
mucosa
as
involved approaching the larynx through an infrahyoid and
aryepiglottic
denuding folds
and
the
edges
arytenoids
of
and
the
epiglottis,
suturing the
epiglottis down to the aryepiglottic folds and arytenoids
(Figure 159.4).
A tracheosto my
is required. Modifications
possible. It can be performed under local anaesthetic in
of this procedure include: wedge exci s i on or striations of
severely
the epiglottic cartilage to decrease its tensile strength and
ill patients. Communication can be re-established
by tracheosophageal puncture and insertion of a voice prosthesis such as a Provox or Blom-Singer valve if coordination will allow it; if not, an artificial larynx can
decrease the incidence of posterior dehiscence of the 18 flap; leaving the posterior flap open to allow phona tion; 19 suspension of the larynx to the mandible to increase protection of the airway;20 closure of the larynx
be used.
at
the
level
of the
false
cords to
improve airway
protection? 1
Prevention of intractable aspiration by epiglottopexy is
Endolaryngeal stents
effective
in about
50
percent of patients,31
but the
proced ure can be revised in failures. Epiglottopexy has Aspiration can be prevented by solid silicone endolar yngeal
stents15
placed
anaesthetic and secured or
vented
endoscopical ly under general with neck sutures (Figure 159.2)
end01 aryngea I
tracheostomy
stents
(Figiue 159.3).
16
inserted
through
the
advantage
that
it
allows
swallowing in patients who have
both an
phonation
and
open posterior flap
and that it is potentially reversible endoscopically.
a
The success of the proced ur e
is dependent on the stent being the correct size for the patient to avoid leakage around tracheostomy is required
it or e xt r u sion. A in both types of stent but the
Vertical laryngoplasty
technique is reversible as the stent can be removed. Vented
stents allow phonation. Oral intake is not tolerated
This technique involves fashioning a tracheostomy and then incising the laryngeal mucosa around the edge of the
in all
epi glottis along the aryepiglottic folds, the arytenoids and
patients in which case other means of feeding are required.
the interarytenoid area. The epiglottis and supraglottic
Stents tend to be used in the short term because of patient
discomfort. Weisberger/o in 1991, reported a reduction
in
aspiration
with res olu ti on of pulmonary complications in 24 of 25 patients fitted wi th solid endolaryngeal stents. In three patients the stents had to be replaced with larger ones and this was successful in two patients However, .
,
larynx can then be tubed by vertical suturing in two layers.
This
allows
(Figure 159.5). et
al. in
both
phonation
and
swallowing
The technique was fust reported by Biller
1983 to control aspiration in patients who had
undergone total glossectomy.32 It was subsequently used by Blitzer
in
1987 in patients
with chronic aspiration but
only eight patients achieved adequate swallowing without
he failed to give much information on patient outcome?2
laryngectomy.
patients over an eight-year period although they preferred
aspiration after stent removal and six patients required a
In 1996) Harcourt and Brooks33 reported on nine
Figure 159.1
Narrow field laryngectomy:
(a)
outline of resection which leaves the hyoid in place; (b) pharyngeal mucosal closure; (c) reinforcement of closure with strap muscles.
2100 I
PART 15 THE UPPER DIGESTIVE TRACT
Figure 159.2
Solid endolaryngeal stent, shaded black.
Figure 159.4
Epiglottic flap closure.
to phonate, and in two of these patients the tracheostomy was reversed.
In one patient aspiration was reduced
enough to change from a cuffed tracheostomy tube to a silver tube to allow phonation but gastrostomy feeding continued. Two patients died in the late postoperative period.
Subperichondrial cricoidectomy Sub perichondrial removal of the cricoid cartilage was first developed in narrow
field
1987
by Cummings
laryngectomy
reported by Eisele et
and
as
an alternative to
the
technique
was
al. in 1995?3 They used this
technique successfully without complications in four patients
(Figure 159.6). It separates the upper air and
food passages permanently and reliably when recovery is not
expected
and
can
anaesthetic in severely
be
performed
under
local
ill patients. A tracheostomy is
fashioned and the cricoid cartilage is exposed and incised vertically. The cricoid is removed after both the inner and outer perichondrium is elevated circumferentially
to
allow removal of the cartilage. The inner perichondrium Figure 159.3
Vented endolaryngeal stent.
and
subglottic
mucosa
are
transected
horizontally,
inverted and closed horizon tally, followed by closure of to call the technique epiglottic plication and included a
the
cricopharyngeal myotomy as part of the procedure to
formation is decreased by rotating the sternohyoid muscle
prevent pooling of secretions.
Five patients achieved
control of aspiration, resumed an- oral diet and were able
outer
perichondrium.
The
incidence
of
fistula
into the sp'ace produced after separating it from the hyoid bone.
Chapter
Figure
159.5
159 Management and treatment of intractable aspiration I
Vertical laryngoplasty: (a) outline of mucosal incisions; (b) elevation of mucosal flaps;
(e)
mucosal closure;
(d)
2101
closure
of outer layer of mucosa.
o (e) Figure
159.6
trachea;
Cd)
Subperichondrial cricoidectomy:
(a)
vertical incision of the cricoid; (b) submucosal dissection;
(c)
closure of distal
interposition of sternohyoid flap seals and closes the larynx.
Figure
159.7
Glottic closure:
(a)
laryngofissure
exposure of the endolarynx; (b) approximation and closure of the true and false vocal cords.
Partial submucosal cricoidectomy
Glottic closure
This technique controls chronic aspiration in patients who have undergone extensive pharyngeal or b ase of tongue resections as it enlarges the pharyngeal inlet and narrows the laryngeal inlet.24 A tracheostomy is fash ioned, the cricoid cartilage exposed, the posterior perichondrium elevated and the posterior half of the cricoid removed submucosally without breach of the subglottic mucosa. A cricopharyngeal myotomy IS performed to enlarge the pharyngeal inlet further.
This procedure, which closes the larynx at the level of both the true and false cords, successfully eliminated aspiration in 12 patients when first reported by Montgomery in 1975 (Figure 159.7).25 Although poten tially reversible, no patients in his series were well enough to attempt this. After fashioning a tracheostomy, a midline thyrotomy exposes the true cords, ventricles, false cords and posterior commissure, all of which are denuded of mucosa. Both the true cords and the false
2102
I PART 15 THE UPPER DIGESTIVE TRACT
cords are sutured together. Sasaki modified the technique by
swinging
a
sternohyoid
muscle
flap
to give
an
additional layer of closure. This was later reported as successful in 15 patients.34, 35 Although this technique has a high success rate, allows swallowing and is potentially reversible,
there is complete
reversal may be difficult and
loss of phonation and
it is hard to believe that
glottic stenosis would not ensue.
Tracheo-oesophageal diversion and laryngotracheal separation These two procedures, which were devised by Lindeman in 1975 and 197626,27 for the prevention of aspiration, are
effective, dependable and technically relatively uncompli cated. Both have a low complication rate and can be performed under local anaesthetic in debilitated patients. These techniques are acceptable to patients as the larynx is preserved with an intact neural input and, therefore, the possibility of subsequent reversal exists. They have even been employed in paediatric patients. Postoperatively, most patients will tolerate a normal diet depending on their neurological function. The main drawback of the procedure is loss of
speech,
although most patients
Figure 159.8
Tracheo-oesophageal diversion.
Figure 159.9
Laryngotracheal separation.
manage with an electronic larynx. The tracheo-oesophageal diversion procedure
159.8)
(Figure
is recommended for patients who do not have an
existing tracheostomy as a tracheo-oesophageal anasto mosis can be fashioned. This allows direct drainage of secretions penetrating the larynx into the oesophagus. The trachea is divided between the fourth and fifth tracheal rings and the proximal trachea anastomosed end to side to an opening in the oesophagus. The distal trachea is brought out as an end stoma onto the skin of the neck. In patients who already have a high tracheostomy the technically easier laryngotracheal separation procedure
(Figure 159.9) oesophagus
is
is used as anastomosis of the trachea and not
possible.
The
trachea
is
divided
between the second and third tracheal rings. The proximal trachea is formed into a blind-ending pouch and the closure reinforced with rotated sternothyroid muscle. The distal segment is brought out as an end stoma onto the skin of the neck. Concerns about accumulation of saliva and food residue in the blind-ending pouch have not been warranted
as barium studies
have
shown
emptying of the pouch when the patient is supine. In 1984, Krespi et
al.36 described a modification of the
tracheo-oesophageal diversion technique to allow the creation of a tracheo-oesophageal anastomosis in patients with
a
pre-existing
tracheostomy.
His
modification
eliminates pooling of secretions in the blind-ending
pouch. This involves creation of an anterior tracheal
mucosal flap following partial resection of the cricoid with
the
first
and
created by suturing the tracheal flap to an opening in the oesophagus. Since
Lindetman's
original
reports
on
these
two
rings
procedure� to control aspiration, several others have also
anteriorly. A tracheo-oesophageal anastomosis is then
used the procedure successfully.37, 38, 39 Reversal of both
cartilage
second
tracheal
Chapter 159 Management and treatment of intractable aspiration I
procedures
with
re-establishment
of
swallowing
2103
.I Surgical treatment should aim to stop aspiration and
and
speech has been reported in pa tien ts showing evidence
restore swallowing and speech using the simplest and
of neurological improvement) normal laryngeal function
most effective procedure. [Grade
endoscopically and absence of aspiration on video barium
DJ
.I Patients with significant aspiration causing repeated life-threatening pulmonary complications may require
studies.
dissociation of the upper air and food passages by either closing. diverting or removing the larynx.
SUMMARY
(Grade DJ
.I Treatment options depend on the expectation of
Intractable aspiration is a serious condition which if left
recovery of neurolog'lcal function. [Grade
DJ
untreated or inadequately treated leads to recurrent chest infections,
septicaemia
evaluation
of
the
and
problem
death. and
a
full
of
any
Following treatment
correctable causes) a number of treatment options
is Deficiencies in current knowledge and areas for future research
available depending on whether recovery of neurological function is anticipated. When there recovery
the
preferred
treatments
is no chance of are
narrow
field
laryngectomy and subperichondrial cricoidectomy. When recovery
is
possible)
laryngotracheal
diversion
� The evaluation of the treatment modalities for
and
chronic aspiration are level 3 evidence on small patient numbers. There is a need for better levels of
separation are preferred.
evidence with randomized controlled trials.
KEY POINTS •
•
is the laryngeaJ penetration of secretions or gastric contents below the level of the vocal cords. Neurological disorders are the most common cause of chron.ic aspiration wi,th cerebrovascular accidents being top of the Aspiration
list. •
•
Often t.he cause of aspiration is obvious from the history. There is no typical radiographic pattern of
ACKNOWLEDGEMENTS The author would like to thank Nick Moffatt for the illustrations included in this chapter.
REFERENCES *
1.
•
D
W. Chronic aspiration. In: Cummings CW (ed.).
Otolaryngology - head and neck surgery. St. Louis.
aspiration. •
Eisele
swallow for suspected aspiration should be with a low molecul'ar weight,
Missouri: Mosby Year Book Inc, 1993: 2061-70.
Contrast
2.
Huxley El. Viroslav J, Gray WR, Pierce AK. Pharyngeal
nonionic, water-soluble contrast medium to
aspiration in normal adults and patients with depressed
minimize pwmonary complications. If aspira�ed, a high osmolar water-soluble contrast medium can �a1i1SC chemical pneulDonitis or pulmonary oedema.
consciousness. American Journal of Medicine. 1978; 64: 564-8.
,
3.
Goldman G. Welboum R, Kobzik L, Valeri CR, Shepro D, Hechtman HB. Tumor necrosis factor-alpha mediates acid aspiration-induced systemic organ injury. Annals of Surgery. 1990; 212: 513-20.
*
4.
Modelska K, Pittet JF, Folkesson HG, Broaddus VC, Mattay MA Acid-induced lung injury. American Journal of
Respir a to ry and Critical Core Medicine. 1999; 1 60: .I The initial management of a patient with chronic
1450-6 . 5.
aspiration should include aggressive treatment of
the assessment of swallowing disorders in paediatric and
any infective pulmonary complications and
adult populations. Folia Phoniatrica et Logopedica. 1999;
prevention of further aspiration by conservative means. (Grade DJ
.I Where conselVative management has failed to prevent aspiration and pulmonary complications continue, surgery may be indicated. [Grade D]
O'Donoghue S, Bagnall A. Videofluoroscopic evaluation in
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Kidder TM, langmore SE, Martin BJ. Indications and techniques of endoscopy in evaluation of celVical dysphagia: comparison with radiographic techniques. Dysphagia. 1994; 9: 256-61.
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7.
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laryngectomy for intractable aspiration. Laryngoscope.
Alessi OM, Berci G. Aspiration and nasogastric intubation. Otolaryngology and Head and Neck Surgery. 1986; 94: 486-9.
8.
Lewis WS, Wikholm RP, Passy V. Bilateral vocal cord Teflon
aspiration by subtotal and submucosal cricoid resection. Annals of Otology, Rhinology, and Laryngology. 1985; 94:
pneumonia. Archives of Otolaryngology - Head and Neck
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of Otolaryngology - Head and Neck Surgery. 1975; 101:
for vocal cord paralysis: temporary rehabilitation of glottic
679-82. 26.
Laryngeal collagen injection as an adjunct to
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with the tracheoesophageal anastomosis for intractable
Iwatake H, lida J, Minami S, Sugano S, Hoshikawa T,
aspiration. Annals of Otology, Rhinoiogy, and Laryngology.
for unilateral vocal cord paralysis. Acta Otolaryngologica
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Supplementum. 1996; 522: 133-7.
Treatment of dysfunction of the cricopharyngeal muscle with botulinum toxin A: Introduction of a new, non-
framework surgery for the management of aspiration in
invasive method. Annals of Otology, Rhinology, and
1998; 19: 1-7.
Laryngology. 1994; 103: 31-5. 29.
McKenna JA, Dedo HH. Cricopharyngeal myotomy:
disorders. Otolaryngologic Clinics of North America. 1998;
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Eliachar I, Roberts JK, Hayes JD, Tucker HM. A vented
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endangering chronic aspiration pneumonia. Use of an
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Surgical closure of the larynx for intractable aspiration. Archives of Otolaryngology - Head and Neck Surgery.
Brooks GB, McKelvie P. Epiglottopexy: a new surgical
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Warwick-Brown NP, Richards AE, Cheeseman AD.
Laryngoscope. 1984; 94: 1298-301. 37.
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Eisele OW, Yarington Jr. CT, Lindeman RC, Larrabee Jr. WF.
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separation procedures for treatment of intractable
Blitzer A. Evaluation and management of chronic
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Baron BC, Dedo HH. Separation of the larynx and trachea for intractable aspiration. Laryngoscope. 1980; 90:
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Cummings CWo Epiglottic sewdown (epiglottopexy) procedure. In: Cummings CW, Sessions DG, Weymuller EA
Krespi YP, Quatela VC, Sisson GA, Som ML. Modified tracheoeosophageal diversion for chronic aspiration.
Epiglottopexy: a modification using additional hyoid suspension. Journal of Laryngology and Otology. 1986; 21.
Kirchner JC, Sasaki CT. Surgery for aspiration.
technique to prevent intractable aspiration. Annals 293-6. 20.
Sasaki CT, Milmoe G, Yanagisawa E, Berry K, Kirchner JA.
Strome M, Fried MP. Rehabilitative surgery for aspiration. Archives of Otolaryngology. 1983; 109: 809-11.
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Harcourt JP, Brooks GB. Epiglottic plication for intractable aspiration. Clinical Otolaryngology and Allied Sciences.
Habal MB, Murray JE. Surgical treatment of lifeepiglottic flap to the arytenoids. Plastic and
Biller HF, Lawson W, Baek S M. Total glossectomy: a technique of reconstruction eliminating laryngectomy.
laryngeal stent with phonatory and pressure relief capability. Laryngoscope. 1987; 97: 1264-9.
Laurian N, Shvili Y, Zohar Y. Epiglotto-aryepiglottopexy: a surgical procedure for severe aspiration. Laryngoscope.
Weisberger EC, Huebsch SA. Endoscopic treatment of aspiration using a laryngeal stent. Otolaryngology and Head and Neck Surgery. 1982; 90: 215-22.
Weisberger EC. Treatment of intractable aspiration using a laryngeal stent or obturator. Annals of Otology, Rhinology,
Cannon CR, McLean WC. Laryngectomy for chronic aspiration. American Journal of Otolaryngology. 1982; 39:
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Wisdom G, Blitzer A. Surgical therapy for swallowing
indications and technique. Annals of Otology, Rhinology, and Laryngology. 1992; 101: 216-21. 14.
Schneider I, Thumfart WF, Pototschnig C, Eckel HE.
Pou A M, Carrau RL, Eibling DE, Murry T. Laryngeal high vagal lesions. American Journal of Otolaryngology.
13.
Lindeman RC, Yarington CT, Sutton D. Clinical experience
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Takeyama I. Transcutaneous intracordal silicon injection
12.
Lindeman RC. Diverting the paralysed larynx: a reversible procedure for intractable aspiration. Laryngoscope. 1975;
Hoffman H, McCabe 0, McCulloch T, Jin S M, Karnell M, medialization laryngoplasty. Laryngoscope. 2002; 112:
11.
Montgomery WW. Surgery to prevent aspiration. Archives
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Krespi YP, Pelzer HJ, Sisson GA. Management of chronic
injection. An ineffective treatment for recurrent aspiration Surgery. 1991; 117: 427-9. 9.
1995; 105: 322-5. 24.
39.
EibliQg DE, Snyderman CH, Eibling C. Laryngotracheal
Eisele OW, Seely DR, Flint PW, Cummings Cw.
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Subperichondrial cricoidectomy: an alternative to
review of 34 patients. Laryngoscope. 1995; 105: 83-5.
PART
16
THE UPPER AIRWAY EDITED BY JOHN HIBBERT
160 Anatomy of the nasopharynx Alexander C Vlantis and C Andrew van Hasselt
2107
161 Benign conditions of the nasopharynx Victor J Abdullah and C Andrew van Hasselt
2116
162 Anatomy of the larynx and tracheobronchial tree
2130
Nigel Beasley
163 Assessment and examination of the upper respiratory tract
2145
Jean-Pierre Jeannon and Marcelle Macnamara
164 Physiology of the larynx
2155
Lesley Mathieson and Paul Carding
165 Voice and speech production
2164
Paul Carding and Lesley Mathieson
166 Objective evaluation of the voice
2170
Julian McGlashan and Adrian Fourcin
167 Disorders of the voice
2192
Julian McGlashan
168 The professional voice
2211
Meredydd Harries
169 Speech therapy in ENT practice: scope, science and evidence for intervention
2216
Alison Perry
170 Phonosurgery
2234
Meredydd Harries
171 Acute infections of the larynx Andrew C Swift
2248
172 Chronic laryngitis
2258
Kenneth MacKenzie
173 Laryngeal trauma and stenosis
2271
Lisa Pitkin
174 Upper airway obstruction
2286
Paul Pracy
175 Tracheostomy Paul Pracy
2292
2305
176 Physiology of sleep and sleep disorders John Fleetham
2313
177 Obstructive sleep apnoea: medical management Dev Banerjee
178 The surgical management of snoring Marcelle Macnamara
2325
160 Anatomy of the nasopharynx ALEXANDER C VLANTIS AND C ANDREW VAN HASSELT
General description of the nasopharynx Layers of the nasopharyngeal wall Fascial relations of the nasopharynx Bones of the nasopharynx Muscles of the nasopharynx
2107 2108 2108 2110
Blood vessels of the nasopharynx Lymphatics of the nasopharynx Nerves of the nasopharynx References
2113 2113 2114 2114
2111
The data in this chapter are supported by an Index Medicus/MedlineTM search using the key words anatomy, nasopharynx, post-nasal space, structure and focusing on anatomy and histology; blood supply and surgery were also used.
GENERAL DESCRIPTION OF THE NASOPHARYNX
160.1). Posterior to the tubal elevation is the lateral
The nasopharynx (post-nasal space) is the part of the pharynx posterior to the nasal cavities and above the level of the junction of the hard and soft palate. The nasopharynx has a roof, floor and walls on its posterior and lateral sides. The roof and posterior wall merge smoothly and are formed by the mucoperiosteum which lies on the body of the sphenoid, the basisphenoid and the basiocciput. Inferior to the pharyngeal tubercle, mucosa covers the pharyngobasilar fascia which lies anterior to the basiocciput, arch of the atlas and body of the axis. 1 The floor of the nasopharynx is formed anteriorly by the superior surface of the soft palate which is continuous with the floor of the nasal cavities. Posteriorly, the floor is deficient where the nasopharynx communicates inferiorly with the oropharynx through the pharyngeal isthmus. The main feature of the lateral wall is the tubal elevation (torus tubarius, Eustachian cushion) - an inverted T -shaped mucosa-covered prominence created by the pharyngeal projection of the auditory tube
pharyngeal recess (fossa of Rosenmiiller) which is formed by the projection of the tubal cartilage into the pharynx. 2 The lateral wall begins at the choana (posterior nasal aperture), and is formed by mucosa overlying the medial pterygoid plate, the tensor and levator palati muscles, the tubal elevation and the superior constrictor muscle. The pharyngeal opening of the auditory tube (pharyngotympanic tube ostium, Eustachian tube opening or orifice) is approximately 1 cm behind the posterior end of the inferior turbinate. The salpingopharyngeal mucosal fold extends inferiorly from the posterior part of the tubal elevation and is raised by the salpingopharyngeus muscle. The salpingopalatine mucosal fold extends anteriorly from the anterior part of the tubal elevation to the superior surface of the palate. The levator palati muscle raises a bulge in the floor of the pharyngeal opening of the auditory tube. The nasopharynx communicates anteriorly with the nasal cavities through the choanae, inferiorly with the oropharynx through the pharyngeal isthmus and laterally with the middle ears through the auditory tubes.
(Eustachian tube,
pharyngotympanic tube)
(Figure
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PART 16 THE UPPER AIRWAY
may be present submucosally throughout the nasopharynx also contribute to Waldeyer's ring. The submucosa is a strong fibrous layer that lies between the mucosa and muscular layer of the pharynx, and forms the epimysial covering of the constrictor muscles on their internal surface. The submucosa continues superiorly as the aponeurosis of the superior constrictor muscle, the pharyngobasilar fascia, and attaches the pharynx to the skull base. The muscular layer consists of an outer circular muscle layer that is made up of the superior, middle and inferior constrictors, and an inner longitudinal muscle layer that is formed by the stylopharyngeus, salpingopharyngeus and palatopharyngeus muscles. The adventitia is the buccopharyngeal fascia which is a loose connective tissue layer that covers the external surface of the muscles as their external epimysium and blends with the surrounding fascia.
Figure 160.1
View of the lateral nasopharyngeal wall. A,
FASCIAL RELATIONS OF THE NASOPHARYNX
inferior turbinate; B, choana; C, nasopharyngeal tonsil; D, salpingopalatine fold; E, tubal elevation; F, auditory tube opening; G, tubal tonsil; H, pharyngeal recess; I, soft palate; J, palatoglossal fold; K, palatine tonsil; L, lingual tonsil; M, palatopharyngeal fold; N, salpingopharyngeal fold.
LAYERS OF THE NASOPHARYNGEAL WALL The wall of the nasopharynx consists of four layers. The mucosa of the nasopharyngeal is continuous with that lining the nasal cavities, the auditory tubes and the oropharynx. The junction between the ectoderm-derived nasal cavity mucosa and the endoderm-derived nasopharyngeal mucosa varies in its position posterior to the choanae. There are three types of epithelium in the nasopharynx: columnar, pseudo stratified, ciliated 'respiratory-type' epithelium with goblet cells and seromucinous glands is found in the region of the choanae, on the roof and upper portion of the posterior wall; nonkeratinizing, stratified squamous epithelium is found on the lower half of the lateral and posterior walls and is continuous with that in the oropharynx;3 an intermediate epithelium of columnar cells with short microvilli instead of cilia lies between these two zones. A vascular connective tissue layer, the lamina propria, lies immediately beneath the epithelium and contains mucosa-associated lymphoid tissue and serous and mucous glands. Lymphoid nodules - the nasopharyngeal tonsil or adenoids - aggregate on the posterior wall of the nasopharynx. Together with the palatine tonsil and lingual tonsil, they constitute the major part ofWaldeyer's ring or nasal-associated lymphoid tissue and belong to the mucosa-associated lymphoid tissue system. 4 Lymphoid tissue found on the rim of the tubal elevation, the tubal tonsil (Gerlach's tonsil) and lymphoid nodules that
Fascial layers divide the neck into fascial spaces, each of which contains distinct anatomical structures and provides potential pathways for the spread of tumours and infection. The use of cross-sectional imaging of the neck has led to insights into head and neck anatomy and pathology. Interpretation of these images can precisely locate a lesion, evaluate tumours and assess the extent of infiltration or infections.
Cervical fascial layers The fascial layers of the neck, which facilitate movement between neck structures, are divided into the superficial cervical fascia and the deep cervical fascia. The superficial cervical fascia is a thin layer of subcutaneous connective tissue that lies between the dermis and the deep cervical fascia and envelops the platysma and muscles of facial expression. The deep cervical fascia consists of the superficial, middle and deep layers. The superficial layer of deep cervical fascia (investing layer) envelops the sternocleidomastoid and trapezius muscles and the parotid and submandibular glands. It contributes to the formation of the carotid sheath. The middle layer of deep cervical fascia (visceral layer) is a thin layer of loose areolar fascia that splits to enclose the pharynx, oesophagus, larynx, trachea and thyroid gland. It extends from the skull base to the upper mediastinum and contributes to the formation of the carotid sheath. A portion of the middle layer of deep cervical fascia that is related to and encloses the pharynx, called the buccopharYugeal fascia, covers the external surface of the buccinator and superior constrictor muscles. Both these
Chapter 160 Anatomy of the nasopharynx
muscles arise from the pterygomandibular raphe and allow the pharynx to move freely, relative to neighbouring structures such as the carotid sheath and vertebrae. Below the level of the pharynx it is called the visceral fascia. The deep layer of the deep cervical fascia (prevertebral fascia) comprises of two layers. The prevertebral layer extends from the base of skull to the coccyx and surrounds the vertebrae and spinal muscles. The alar layer, an anterior subdivision of the prevertebral fascia, stretches between the transverse processes of the vertebrae and extends from the skull base to the level of T2 where it fuses with the posterior aspect of the visceral fascia. The deep layer blends with and contributes to the formation of the carotid sheath (Figure 160.2).5
Cervical fascial spaces The deep fascial spaces are divided into midline spaces and paired lateral spaces. The midline spaces consist of the pharyngeal mucosal, retropharyngeal and prevertebral spaces, and paired lateral spaces of the parapharyngeal, carotid, masticator and parotid spaces (Figure 160.3). The pharyngeal mucosal space (visceral space) encloses the pharynx and is composed of mucosa, submucosa and pharyngeal constrictors. The buccopharyngeal fascia surrounds most of the space laterally and posteriorly. Superiorly, where the muscle is deficient - the sinus of Morgagni - the buccopharyngeal fascia fuses with the
Sagittal view of the fascial layers and spaces posterior to the nasopharynx. A, buccopharyngeal fascia; B, anterior compartment of retropharyngeal space; C, alar layer of prevertebral fascia; D, posterior compartment of retropharyngeal space; E, prevertebral fascia; F, prevertebral space. Figure 160.2
I 2109
pharyngobasilar fascia to form one layer attaching the pharynx to the skull base. 6 The retropharyngeal space lies between the buccopharyngeal (visceral) fascia anteriorly and the prevertebral fascia posteriorly. It lies below the skull base, behind the pharyngeal mucosal space, medial to the carotid spaces and anterior to the prevertebral space. Anterior to the cervical vertebrae the prevertebral fascia splits into two layers. The anterior subdivision, the alar fascia, divides the retropharyngeal space into anterior and posterior compartments. 7 The anterior compartment - the space bordered anteriorly by the buccopharyngeal fascia (middle layer of deep cervical fascia, visceral layer) and posteriorly by the alar fascia (the anterior layer of the deep layer of deep cervical fascia) - is the true retropharyngeal space, since it exists between two different layers of deep cervical fascia (an interfascial space). The retropharyngeal space extends from the skull base to the level of T2, where the alar fascia fuses anteriorly with the visceral fascia; this space allows movement of the pharynx and larynx during swallowing. The posterior compartment of the retropharyngeal space is bordered anteriorly by the alar layer of fascia and posteriorly by the prevertebral layer of fascia; it is, therefore, a space lying within a fascial layer (an intrafascial space). The posterior compartment extends from the skull base to the diaphragm. These spaces provide pathways for the spread of infection from the neck into the chest. A
Figure 160.3 Axial view of the nasopharynx showing fascial spaces. A, pharyngeal mucosal space; B, parapharyngeal space (prestyloid parapharyngeal space); C, masticator space; D, anterior compartment of retropharyngeal space; E, posterior compartment of retropharyngeal space; F, prevertebral space; G, carotid space (poststyloid parapharyngeal space); H, parotid
space.
2110 I PART 16 THE UPPER AIRWAY median raphe divides the retropharyngeal space into two halves. The prevertebral space lies posterior to the prevertebral fascia and extends from the skull base to the coccyx. The parapharyngeal space is the fibrofatty space that lies lateral to the nasopharynx. 8 This space, shaped similarly to an inverted pyramid, extends from a small area on the temporal bone near the foramen lace rum to the greater cornu of the hyoid bone. 9 The medial border of the parapharyngeal space is formed by the buccopharyngeal fascia on the external surface of the superior constrictor, and at a slightly lower level by the fascia on the lateral surface of the tensor and levator palati muscles. lO The medial pterygoid muscle, the ramus of the mandible and the deep lobe of the parotid form the lateral border of the parapharyngeal spac~. The carotid sheath forms its posterior border. The anterior portion of the parapharyngeal space lies between the levator and tensor palati medially and the medial pterygoid laterally. A layer of fascia that extends from the medial pterygoid plate and tensor palati to the spine of the sphenoid and the styloid process loosely divides the parapharyngeal space anterolaterally (prestyloid parapharyngeal space) from the carotid space posteromedially (poststyloid parapharyngeal space).ll The parapharyngeal space is important because of its central location and its relationship to other spaces in the neck: the pharyngeal mucosal space is medial; the masticator space, anterolateral; the parotid space, lateral; the carotid space, posterior; and the retropharygeal space, posteromediaL 12 The carotid space (carotid sheath, poststyloid parapharyngeal space) is an enclosed fascial space that extends from the jugular foramen to the aortic arch. l3 Its medial relation is the lateral. aspect of the lateral pharyngeal recess, and is separated from the lumen of the nasopharynx by the superior constrictor muscle and pharyngobasilar fascia. It lies lateral to the prevertebral space and the retropharyngeal space, posterior to the parapharyngeal space, and posteromedial to the fascia that joins the styloid process and muscles to the tensor palati and medial pterygoid plate. 14 Fascia from all three layers of the deep cervical fascia condense to form the carotid sheath. The masticator space is bound on all sides by the superficial layer of the deep cervical fascia. It contains the muscles of mastication - the medial and lateral pterygoids, the masseter and the temporalis. It also contains the ramus of the mandible and the mandibular division of the trigeminal nerve. The superomedial portion of the masticator space adjacent to the skull base is in the infratemporal fossa. l3 The parotid space lies lateral to the parapharyngeal space, anterior to the carotid space and posterior to the masticator space. It is bound on all sides by the superficial layer of deep cervical fascia. The masticator and parotid spaces occupy the infratemporal fossa (Table 160.1).
Table 160.1
Contents of the cervical fascial spaces.
Fascial space Parapharyngeal Pharyngeal mucosal Masticator Parotid Carotid
Retropharyngeal Prevertebral
. Contents Fat, arteries, veins, trigeminal nerve, salivary gland rests, lymph nodes Mucosa, lymphoid tissue, muscles of the pharynx, minor salivary glands Mandible, muscles, trigeminal nerve Parotid gland, facial nerve, lymph nodes, arteries, veins Carotid artery, internal jugular vein, cranial nerves IX-XII, lymph nodes, sympathetic fibres 15 Fat, lymph nodes Vertebrae and prevertebral muscles
BONES OF THE NASOPHARYNX In the midline, the nasopharynx is bounded by the palatine, vomer, sphenoid and occipital bones and by the atlas. Laterally are the pterygoid processes, sphenoid, temporal and occipital bones. The choanae are formed by the vomer medially, the body of the sphenoid superiorly, the medial pterygoid plate laterally and the horizontal plate of the palatine bone inferiorly. The petrous portion of the temporal bone lies between the greater wing of the sphenoid and the basilar part of the occipital bone. The levator palati and the cartilaginous portion of the auditory tube attach themselves to the petrous apex. Posterior to their attachment is the carotid canal and the jugular fossa. 16 The basiocciput, the basilar part of the occipital bone, with the pharyngeal tubercle on its inferior surface, is the quadrilateral portion of the occipital bone anterior to the foramen magnum. The longus capitis inserts on either side of the midline of the basiocciput; posterolateral to the insertion lies the rectus capitis. The hypoglossal canal, with the hypoglossal nerve and the meningeal branch of the ascending pharyngeal artery, is at the anterior base of each occipital condyle. 17 The sphenoid bone lies anterior to the occipital and temporal bones, and has a body, two greater wings, two lesser wings and two pterygoid processes. In the midline, the anterior surface of the body articulates with the perpendicular plate of the ethmoid, and the rostrum of the inferior surface of the body articulates with the alae of the vomer. The posterior portion of the body - the basisphenoid - articulates with the basilar part of the occipital bone, the basiocciput, and together form the clivus. 1 The lateral surface of the greater wing contributes to the infratemporal fossa and gives rise to the attachmen't of the superior head of the lateral pterygoid muscle.
Chapter 160 Anatomy of the nasopharynx
The pterygoid process of the sphenoid is a perpendicular process that arises from the junction of the body and greater wing. Each process has a medial and lateral plate that are fused anteriorly, creating the pterygoid fossa. The fossa contains the medial pterygoid and tensor palati muscles. Cranial to the pterygoid fossa lies the scaphoid fossa which gives rise to the tensor palati. The anterior surface of the pterygoid process forms the posterior wall of the pterygopalatine fossa. 18 The lateral surface of the lateral pterygoid plate forms the medial wall of the infratemporal fossa and gives rise to the inferior head of the lateral pterygoid muscle; the medial surface gives rise to the medial pterygoid muscle. 18 At the base of the lateral pterygoid plate are the foramen ovale (mandibular nerve, accessory meningeal artery) and the foramen spino sum (middle meningeal vessels). The medial pterygoid plate articulates with the vertical part of the palatine bone anteriorly and has the pterygoid hamulus at the lower end, around which the tendon of tensor palati hooks. At the base of the medial pterygoid plate lies the foramen lacerum, bounded by the sphenoid, petrous portion of the temporal bone and basilar portion of the occipital bone. The internal carotid artery runs across the cranial aspect of the foramen; lateral to the foramen lies a groove for the auditory tube. The vertical part of the palatine bone lies between the maxilla and the pterygoid process and forms the posterior part of the lateral wall of the nasal cavity. It has a medial nasal surface, which articulates with the inferior and middle turbinates, and a lateral maxillary surface that faces the pterygopalatine fossa. The posterior free margin of its horizontal part is attached to the palatine aponeurosis of the tensor palati muscle. Between the lateral pterygoid plate and the maxilla lies the pterygomaxillary fissure that leads to the pterygopa1atine fossa. This small fat-filled triangular space, which lies between the pterygoid process posterolaterally, the maxilla anterolaterally and palatine bone medially, contains the maxillary nerve, sphenopalatine (pterygopalatine) ganglion and the terminal branches of the maxillary artery.19 The pterygopalatine fossa communicates with the choana, the scaphoid fossa, the nasal cavity, the hard palate, the middle cranial fossa and the orbit. The atlas lacks a body; two lateral masses are connected to each other by anterior and posterior arches. The anterior margin of the foramen magnum is connected to the upper border of the anterior arch of the atlas by the anterior atlanto-occipital ligament. Posterior to the anterior arch lies the odontoid process of the axis. 1 The dens or odontoid, a superior projection of the body of the axis, articulates with the anterior arch of the atlas. The anterior arch of the atlas is connected to the body of the axis by the anterior atlantoaxial ligament. The ligament is thickened medially as the superior continuation of the anterior longitudinal ligament of the spine. 1
I 2111
MUSCLES OF THE NASOPHARYNX Pharyngeal muscles The superior constrictor is a quadrilateral muscle that arises from the lower part of the posterior margin of the medial pterygoid plate, the hamulus, the pterygomandibular raphe or ligament, the posterior end of the mylohyoid line of the mandible and the side of the tongue. The fibres of the muscle pass backwards and insert into the median pharyngeal raphe, which, in turn, is anchored to the pharyngeal tubercle or spine on the basilar part of the occipital bone by an aponeurosis. The fibres of the superior constrictor do not reach the skull base but are attached to it by an aponeurosis. The superior constrictor is a sphincter that prevents reflux into the nasopharynx, and has a peristaltic function during swallowing. The pharyngobasilar fascia, which lies in the gap between the superior constrictor and the skull base, the sinus of Morgagni, fuses with the buccopharyngeal fascia to form a single layer of fascia. The auditory tube passes through this gap. The pharyngobasilar fascia is attached to the pharyngeal tubercle, the basiocciput, the petrous temporal bone medial to the carotid canal and to the posterior border of the medial pterygoid plate (Figure 160.4). The palatopharyngeal (velopharyngeal) sphincter is a band of mainly superior constrictor muscle fibres, with some palatopharyngeus fibres, that arises from the upper
Figure 160.4
Attachment of pharyngobasilar fascia to the
skull base. A, maxilla; B, sphenoid bone; C, palatine bone; D, vomer; E, temporal bone; F, occipital bone.
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PART 16 THE UPPER AIRWAY
surface of the palatine aponeurosis, passes lateral to the levator palati and blends posteriorly with fibres from the opposite side. The band ridges the pharyngeal wall as Passavant's ridge, which can be seen when the soft palate is elevated. The salpingopharyngeus arises from the posterior region of the pharyngeal projection of the auditory tube and passes inferiorly to blend with the palatopharyngeus and inferior constrictor. It elevates the upper lateral wall of the pharynx.20
Prevertebral muscles The longus capitis arises from the transverse processes of the cervical vertebrae and inserts into the inferior surface of the basilar part of the occipital bone. It separates the nasopharynx from the lower clivus and vertebrae. 21 Figure 160.5
Palatal muscles
Axial view of pharyngobasilar fascia at two
levels: left side, upper nasopharynx; right side, lower nasopharynx. A, masseter; B, temporalis; C, lateral pterygoid; D, tensor palati; E, auditory tube; F, medial pterygoid; G, levator
The levator palati muscle is situated lateral to the choana, and arises within the pharynx from the inferior surface of the petrous part of the temporal bone and by a few fibres from the medial lamina of the auditory tube cartilage. It is medial to the pharyngobasilar fascia. It passes above the upper concave margin of the superior constrictor and then below the floor of the pharyngeal opening of the auditory tube and is inserted into the palatine aponeurosis. It opens the pharyngeal orifice of the auditory tube and elevates the soft palate during swallowing. 22 The tensor palati muscle is situated lateral to the auditory tube and the levator palati. It arises from the scaphoid fossa at the base of the medial pterygoid plate, the lateral lamina of the auditory tube cartilage and the spine of the sphenoid. It is lateral to the pharyngobasilar fascia (Figure 160.5). It descends vertically between the medial pterygoid plate and the medial pterygoid muscle and ends as a tendon that hooks around the pterygoid hamulus. The tendon turns medially and inserts into the palatine aponeurosis. 23 It actively opens the auditory tube and tenses the soft palate during swallowing. The uvular muscles, intrinsic muscles of the soft palate, arise from the posterior nasal spine of the palatine bones and the palatine aponeurosis, and insert into the uvula. They stiffen the soft palate. The palatoglossus arises from the soft palate aponeurosis and passes in front of the palatine tonsil to insert into the lateral side of the tongue. It acts as a constrictor of the fauces. The palatopharyngeus arises from the soft palate aponeurosis and the posterior border of hard palate and passes behind the palatine tonsil to blend with the stylopharyngeus and pharyngeal constrictors. It elevates the pharynx during swallowing (Figure 160.6).
palati; H, pharyngobasilar fascia; I, longus capitis.
Figure 160.6
Muscles of the lateral nasopharyngeal wall. A,
palatine bone; B, medial pterygoid plate; C, tensor palati muscle; D, auditory tube; E, sinus of Morgagni; F, uvula muscle; G, levator palati muscle; H, superior constrictor muscle; I, longus capitis; J, palatoglossus muscle; K, middle constrictor muscle; L, palatopharyngeus muscle; M, salpingopharyngeus muscle.
Masticator muscles The lateral pterygoid muscle arises as two heads, one from the greater wing of the sphenoid and the other from the
Chapter 160 Anatomy of the nasopharynx
I 2113
lateral surface of the lateral pterygoid plate. The fibres pass horizontally backwards and insert into the neck of the mandibular condyle. It opens the mouth and protrudes the mandible. The medial pterygoid muscle arises in the pterygoid fossa from the medial surface of the lateral pterygoid plate and maxillary tuberosity. The fibres pass inferiorly backwards and insert into the medial surface of the ramus and the angle of the mandible. 23 It closes the mouth.
The pterygoid part gives rise to pterygoid branches which supply the pterygoid muscles and tensor palati. The pterygopalatine part gives off four branches in the pterygopalatine fossa: the descending palatine artery that gives rise to the greater and lesser palatine branches which supply the palate; the artery of the pterygoid canal that supplies the upper pharynx and auditory tube; the pharyngeal artery that supplies the upper pharynx and auditory tube; and the sphenopalatine artery that supplies the posterior portion of the nasal cavity.27
The auditory tube
Veins
The auditory tube runs anteriorly and inferiorly from its bony part in the petrous portion of the temporal bone to the nasopharynx. The longer cartilaginous part is medial to the foramen ovale and spinosum (which lie in line with the lateral pterygoid plate), lateral to the foramen lacerum and, more posteriorly, lateral to the carotid canal. The tensor palati separates the auditory tube from the mandibular nerve. The auditory tube opens near the root of the medial pterygoid plate anterior to the foramen ovale. 24
A submucosal plexus of veins communicates with an external pharyngeal plexus of veins. Veins corresponding to all branches of the maxillary artery then drain into the pterygoid plexus, which has deep and superficial components that communicate with each other. The pterygoid plexus receives tributaries from foramina of the skull base, the masseter and pterygoid muscles, the pterygopalatine fossa and the cavernous sinus. The main drainage of the pterygoid plexus is into the internal jugular vein via the maxillary, retromandibular and common facial veins. 24
BLOOD VESSELS OF THE NASOPHARYNX Arteries
LYMPHATICS OF THE NASOPHARYNX
The ascending palatine artery, a branch of the facial artery, ascends towards the skull base on the external surface of the pharynx and then winds medially over the upper border of the superior constrictor muscle. It supplies the levator palati, the soft palate, the superior constrictor and the auditory tube, and anastomoses with other arteries supplying the nasopharynx. The ascending pharyngeal artery, a branch of the external carotid artery, ascends vertically between the carotid sheath and the pharynx to the skull base. It gives off a number of perforators to the superior constrictor muscle, supplying the lateral and posterior pharyngeal wall above the level of the palate. 25 The ascending cervical artery arises from the thyrocervical trunk or from the inferior thyroid artery. It winds upwards behind the carotid sheath and anastomoses with the ascending pharyngeal artery. The maxillary artery is the larger terminal branch of the external carotid artery. It travels through the substance of the parotid gland, passes between the ramus of the mandible and the sphenomandibular ligament, passes either deep or superficial to the lateral pterygoid muscle and enters the pterygopalatine fossa. 26 The maxillary artery is divided into three parts: mandibular, pterygoid and pterygopalatine. The mandibular part gives rise to the middle meningeal branch which passes through the foramen spinosum to supply the dura.
The retropharyngeal space contains two groups of lymph nodes: medial retropharyngeal lymph nodes, which are often absent in adults, and larger, more constant, lateral retropharyngeal lymph nodes,zs The lateral group is known as the nodes of Rouviere. 29 The first echelon nodes that usually drain the nasopharynx are the retropharyngeal nodes. 30 Lymph from the lateral wall of the nasopharynx drains either to the lateral retropharyngeal nodes or directly to upper jugular (level lIb) lymph nodes. 31 Lymph from the roof and posterior wall of the nasopharynx usually drains to lateral retropharyngeallymph nodes, but may occasionally drain directly to upper jugular (level lIb) lymph nodes. The lymphatic drainage of the nasopharynx is often bilateral, draining to both sides of the neck. 32 Lateral retropharyngeal lymph nodes usually drain into upper jugular (especially level lIb) and posterior triangle (especially level Va) lymph nodes, but may occasionally drain directly into mid-jugular lymph nodes (level IlI),zs The retropharyngeal nodes also drain lymph from the posterior nasal cavity, the posterior oropharyngeal wall, the soft palate, the pharyngeal tonsil, the auditory tube and middle ear. All lymph from the head and neck eventually drains into the upper, middle and lower jugular groups of deep cervical lymph nodes. Efferent vessels from these lymph nodes drain into a (lymphatic) jugular trunk, which on
2114 I PART 16 THE
UPPER AIRWAY
the right joins the junction of the subclavian and internal jugular veins, and on the left joins the thoracic duct. 2s
* 10.
Teresi LM, Lufkin RB, Vinuela F, Dietrich RB, Wilson GH, Bentson JR et al. MR imaging of the nasopharynx and floor of the middle cranial fossa. Part I. Normal anatomy.
Radiology. 1987; 164: 811-6.
NERVES OF THE NASOPHARYNX
11.
Harnsberger HR, Osborn AG. Differential diagnosis of head and neck lesions based on their space of origin. 1. The
The motor, sensory and autonomic nerve supply of the pharynx is from the pharyngeal plexus, which is formed from branches of the glossopharyngeal and vagus nerves and the sympathetic chain. The pharyngeal plexus lies medial to the buccopharyngeal fascia on the external surface of the constrictor muscles. The pharyngeal plexus supplies motor innervation to all muscles of the pharynx, apart from the stylopharyngeus, which is supplied by the muscular branch of the glossopharyngeal nerve, and to all muscles of the soft palate except the tensor palati. 33 The mandibular branch of the trigeminal nerve supplies the tensor palati and lateral and medial pterygoids. The anterior rami of CI-C3 supplies motor innervation to the longus capitis. Sensory innervation is from the nasopharyngeal branches of the pharyngeal plexus, pharyngeal branches of the maxillary nerve and pharyngeal branches of the glossopharyngeal nerve.
suprahyoid part of the neck. American Journal of
Roentgenology. 1991; 157: 147-54. 12.
Chong VF, Mukherji SK, Goh CH. The suprahyoid neck: normal and pathological anatomy. Journal of Laryngology
and Otology. 1999; 113: 501-8. 13.
Mukherji SK, Castillo M. A simplified approach to the spaces of the suprahyoid neck. Radiologic Clinics of North
* 14.
America. 1998; 36: 761-80. Silver AJ, Mawad ME, Hilal SK, Sane P, Ganti SR. Computed tomography of the carotid space and related cervical spaces. Part I: Anatomy. Radiology. 1984; 150: 723-8.
15.
Olsen KD. Tumors and surgery of the parapharyngeal
* 16.
Standring S (ed.). Gray's anatomy, 39th edn. London:
17.
Standring S (ed.). Gray's anatomy, 39th edn. London:
18.
Standring S (ed.). Gray's anatomy, 39th edn. London:
space. Laryngoscope. 1994; 104: 1-28. Churchill Livingstone, 2005: 470. Churchill Livingstone, 2005: 464-5. Churchill Livingstone, 2005: 467.
19.
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Couldwell WT, Sabit I, Weiss MH, Giannotta SL, Rice D. Transmaxillary approach to the anterior cavernous sinus: a microanatomic study. Neurosurgery. 1997; 40:
1.
clivus and nasopharynx. Otolaryngologic Clinics of North
*
20.
Standring S (ed.). Gray's anatomy, 39th edn. London:
21.
Hitotsumatsu T, Rhoton Jr. AL. Unilateral upper and
America. 2001; 34: 1105-21. 2.
3.
Mancuso AA, Bohman L, Hanafee W, Maxwell D.
4.
Churchill Livingstone, 2005: 629.
Computed tomography of the nasopharynx: normal and
lower subtotal maxillectomy approaches to the cranial
variants of normal. Radiology. 1980; 137: 113-21.
base: microsurgical anatomy. Neurosurgery. 2000; 46: 1416-52.
Ali MY. Histology of the human nasopharyngeal mucosa.
Journal of Anatomy. 1965; 99: 657-72.
*
1307-11.
Enepekides DJ, Donald PJ. Transoral approaches to the
22.
Gibb A (eds). Nasopharyngeal carcinoma, 2nd edn. Hong
Hellings P, Jorissen M, Ceuppens JL. The Waldeyer's ring.
Acta Oto-rhino-Iaryngologica Belgica. 2000; 54: 237-41. 5.
Lindner HH. The anatomy of the fasciae of the face and
Kong: The Chinese University Press, 1999: 18. 23.
Goldenberg RA. Surgeon's view of the skull base from the
24.
Vrionis FD, Cano WG, Heilman CB. Microsurgical anatomy
lateral approach. Laryngoscope. 1984; 94: 1-21.
neck with particular reference to the spread and treatment of intraoral infections (Ludwig's) that have
6.
*
7.
progressed into adjacent fascial spaces. Annals of Surgery.
of the infratemporal fossa as viewed laterally and
1986; 204: 705-14.
superiorly. Neurosurgery. 1996; 39: 777-86.
Gibb A. Anatomy and development. In: van Hasselt CA,
25.
of the velopharyngeal blood supply: a fresh cadaveric
Kong: The Chinese University Press, 1999: 21.
study. Plastic and Reconstructive Surgery. 1998; 102: 655-67.
Grodinsky M, Holyoke EA. The fascia and fascial spaces of 26.
Stepnick DW, Maniglia AJ, Bold EL, Maniglia N.
of Anatomy. 1938; 63: 367 -407.
Intraoral-extramaxillary sinus approach for ligation of the
Guinto G, Abello J, Molina A, Gallegos F, Oviedo A, Nettel B
maxillary artery: an anatomic study with clinical
et al. Zygomatic-transmandibular approach for giant tumors of the infratemporal fossa and parapharyngeal
correlates. Laryngoscope. 1990; 100: 1166-70. 27.
space. Neurosurgery. 1999; 45: 1385-98. 9.
Huang MHS, Lee ST, Rajendran K. Clinical implications
Gibb A (eds). Nasopharyngeal carcinoma, 2nd edn. Hong
the head and neck and adjacent regions. American Journal 8.
Gibb A. Anatomy and development. In: van Hasselt CA,
Carrau RL, Myers EN, Johnson JT. Management of tumors
Standring S (ed.). Gray's anatomy, 39th edn. London: Churchill Livingstone, 2005: 579.
28.
Gibb A. Anatomy and development. In: van Hasselt CA,
A (eds).
arising in the parapharyngeal space. Laryngoscope. 1990;
Gibb
100: 583-9.
Hong Kong: The Chinese University Press, 1999: 25-6.
Nasopharyngeal carcinoma, 2nd edn.
Chapter 160 Anatomy of the nasopharynx
* 29.
Rouviere H. Lymphatic systems of the head and neck. Tobias MJ (trans). Ann Arbor, Michigan: Edwards Brothers. 1938. 30. Ferlito A, Shaha AR, Rinaldo A. Retropharyngeal lymph node metastasis from cancer of the head and neck. Acta Oto-Iaryngologica. 2002; 122: 556-60. 31. Chong VF, Fan YF, Khoo JB. Retropharyngeal lymphadenopathy in nasopharyngeal carcinoma. European Journal of Radiology. 1995; 21: 100-5.
I 2115
King AD, Ahuja AT, Leung SF, Lam WM, Teo P, Chan YL et al. Neck node metastases from nasopharyngeal carcinoma: MR imaging of patterns of disease. Head and Neck. 2000; 22: 275-81. 33. Bejjani GK, Sullivan B, Salas-Lopez E, Abello J, Wright DC, Jurjus A et al. Surgical anatomy of the infratemporal fossa: the styloid diaphragm revisited. Neurosurgery. 1998; 43: 842-53.
32.
161 Benign conditions of the nasopharynx
VICTOR J ABDULLAH AND C ANDREW VAN HASSELT
2116
I ntroduction
2116
Congenital conditions Acquired conditions Benign neoplastic lesions
Deficiencies in current knowledge and areas for future
2122
References
2124
Other benign neoplasms of the nasopharynx
2125
Best clinical practice
2121
2122
Acquired cystic conditions
2124
Key points
2125
research
2125
The data in this chapter are supported by a Medline search using the key words benign nasopharyngeal lesions.
subdivided into transethmoidal, sphenoethmoidal, sphe
INTRODUCTION As an integral part of the upper respiratory tract posterior to
the
nasal
cavity,
the
nasopharynx
contains
the
no-orbital and transsphenoidal. 2 The transsphenoidal type is the least frequently encountered, with an estimated
incidence of one in 700,000 live births.3
Eustachian tube openings and is related to the skull base.
Transsphenoidal meningoencephalocoeles are further
Congenital benign cranial lesions may arise from defective
divided into intrasphenoidal, if they are confined to the
fusion of the skull base. Other congenital conditions
sphenoid, and true transsphenoidal, if they traverse the
include a 'deficit in the form of the nasopharynx, which
floor of the sinus.4 These herniations may well affect
may hinder airflow, or tortuous anomalous courses of
important structures such as the pituitary gland, the optic
vessels. Acquired conditions may be of an infective nature,
nerves and even the third ventricle in their course through
involving
lymphoid
the skull base.5, 6 In the paediatric patient, they may
tissues, or be of a benign cystic or neoplastic nature
present as part of a spectrum of midline fusion defects,
the nasopharyngeal mucosa and
arising from the tissues within the area.
upper airway obstruction or recurrent bouts of meningi tis. Most of these signs and symptoms are obvious within
the first year
CONGENITAL CONDITI ONS
of life.
Transsphenoidal meningoencephalo Jabre et al. described one case
coeles are rare in adults.
and their review of the world literature revealed 14
documented adult cases.7 Those happening within the
Transsphenoidal meningoencephalocoeles
sphenoid sinus presented with cerebrospinal fluid (CSF)
Nasal meningoencephalocoeles are rare, with an estimated
transsphenoidal
to arise from defective fusion of the ossification centres
cases with 'endocrine dysfunction that included hypo
at the skull base
gonadism,
rhinorrhoea incidence of one in 35,000 live births.l They are believed
(Figure 161.1)? These lesions are
or
visual
impairment
whereas
the
encephalocoeles presented with
true visual
impairment and no CSF leak. In both groups there were hypothyroidism,
hyperprolactinaemia
and
Chapter 161
Benign conditions ot
Trabecular
Membranous
Cartilaginous
neurocranium
neurocranium
viscerocranium
Trabeculae
Ala orbitalis
"I
•
Mem�
2119
�
viscerocraniur. ..... �
Trabeculae
cranii
Nasal capsule
fused
Ala temporalis
Hypophyseal
�$opharynx I
�
cartilages
Hypophyseal cartilage
Otic capsule
Internal auditory meatus
Parachordal
Occipital
cartilage
cartilage
Occipital sclerotomes
Former site
Notochord
of notochord
(b)
(0)
Frontal bone Lessor
Ethmoid
and Parietal bone
Petrous part of temporal bone
Body of sphenoid
Nasal
Occipital
bone
bone Incus
Petrous part of temporal
Squama
bone
temporalis
Maxilla
Stapes
Mandible Occipital
Malleus
bone
Foramen
T hyroid
Hyoid
cartilage
magnum
(e)
(dl
Figure'61.1
Stages in the development of the skull.
(a)
Six weeks, showing the various cartilages that will fuse to form the
chondrocranium. (b) Seven weeks, after fusion of some of the paired cartilages. (c) Twelve weeks. showing the cartilaginous base of the skull or chondrocranium formed by the fusion of various cartilages.
(d)
Twenty weeks, indicating the derivation of the bones of the
foetal skull. (a-c) Are viewed from above; (d) is a lateral view. Redrawn from Before We Are Born: Basic Embryology and Birth Defects, 2nd Edition; Moore, KL; page
diabetes
insipidus.
219; © 1983.
w i th permission from El sevi er.
Surgical treatment) which may be
probably because of their thicker lining} are best left alone if
transcranial} transpalatal or a combination of both, is
no
often a difficult undertaking, as would be expected. In
meningoencephalocoeles
major
problem
arises.
children, other associated craniofacial defects may require
much distortion of the surrounding anatomy.
are
The
true
transsphenoidal
invariably associated with
correction} and injuries involving normal structures are not uncommon because of the distorted anatomy. There is little phalocoeles. The intrasphenoidal cases with CSF rhinor
Rathke's pouch remnant and pharyngeal hypophysis
rhoea which require repair seem to be best treated using a 7 transsphenoidal approach. The true transsphenoidal cases,
The
which do not seem to be associated with CSF leakage,
an ectodermal upgrowth from the stomodeum and as a
experience of the rare adult nasopharyngeal meningoence
pituitary gland
develops
from two sources,
as
·�
uPPER AIRWAY
therefore, to have adenohypophysial tissue with functional potential in the nasopharynx. This was first des
down growth from the neuroectoderm of the diencepha lon
(Figure 161.2). The ectodermal upgrowth in the form
of a
pouch,
known
as
Rathke's
pouch,
forms
12
cribed by Erdheim and Stumme in 1909.
the
Many studies
pituitary)
have since confirmed the presence of such extrasellar
pars tuberalis. The neuroectoderm forms the pars nervosa
133 cases, reported a length, width and depth of 9.6, 1.5
adenohypophysis
(glandular portion of the
pituitary tissue.13,
comprising the pars anterior, the pars intermedia and the
and 1
(Figure 161.2). Rathke's pouch passes upwards through
degree of obliteration.8,9, 10,11
McGrath, in 1971, having studied
respectively,9 situated
in the mucoperiosteum
of the roof of the nasopharynx. In
the future body of the sphenoid via the craniopharyngeal duct to the sella turcica which may undergo
mm,
14, 15
of 50 neonatal cadavers
a varying
a
histological study
in India,16 the incidence was
reported to be 16 percent. Different tumours of tills
It is not uncommon,
•
Rathke's pouch of stomodeum
(upgrowth trom roof of primitive mouth)
Infundibulum of diencephalon (downgrowth from floor of forebrain)
� �
FbOCOfdiOO
Ji
d
:::
Diencephalon ______���......c:;
... ---�-------. ....Ir-T-
Rathke's pouch
�.
Rathke's pouch
'\
Stomodeum (primitive mouth
'\.......�----i�+- Notochord
cavity)
Oral ectoderm
(bJ
lc)
Former site of oropharyngeal
(a)
membrane
Optic---/- chiasma Pars intermedia
Infundibular
Pars tuberalis
Anterior lobe
stem
Pars distalis (anterior lobe)
Pars intermedia
�h
J (� ��
()-- Regressing stalk ke'SPouch
FOrmerSite ot
stalk of Rathke's
l
pouch
(d) Figure 161.2
(e)
�
Pars nervosa (posterior lobe) Pharyngeal
Colloid
containing
root
vesicles
In1racraniaJ. intraosseus and pharyngeal accessory anterior lobe tissue
(fJ
The development of the pituitary gland (hypophysis). (a) Sagittal section of the cranial end of an embryo during
development stage 1 1 (a bout 24 days), showing Rathke's pouch as an upg row t h from the stomodeum and the neurohypophysi al bud from the forebrain. (b-d) Successive stages of the developing pituitary gland . By eight weeks, Rathke's p ouch loses its connection with the oral cavity and is i n close contact with the infundibulum, the primord i um of the stalk and the posterior lobe of the pituitary
(neurohypophysis). •
(e,f)
pituitary (adenohypophysis). Redrawn from © 19 83, wi th permission from Elsevier:
Before We Are Born: Basic Embryology and
Birth
Defects,
2nd Ed i tion; Moore, Kl.; page 248;
Chapter 161 Benign conditions of the nasopharynx I
pharyngeal hypophysial tissue have also been ' , , 8 ' ' 0 I 1 1 dl 17 M d 1 me cysts may a so anse from reporte . Rathke's pouch.19 It is interesting that tissue of this nature is not commonly found in routine adenoidectomy speci mens. Richards and Evans17 proposed that a routine adenoidectomy would not encompass the pharyngeal hypophysis but that a radical adenoidectomy might well do so. [**] Congenital glioma Nasopharyngeal glioma is a rarity and represents the collection of heterotropic neural tissue within the naso pharynx. This is a developmental deficit in the embryo resulting in the separation of neural tissue from the brain. If a connecting tract is present, it is, strictly speaking, an encephalocoele. True developmental sequestration of neural tissue in an abnormal site, nonetheless, remains a possibility.20 An isolated report of a case of nasophar yngeal glioma with an initial persistent tract at birth that sealed after three months casts new light on its development.21 A nasopharyngeal glioma might well have been an encephalocoele of which the connecting tract had sealed with time. Branchial cysts of the nasopharynx
2119
3.
teratomas are benign neoplasms. However, malignant teratocarcinomas, which are invasive and invariably lead to the patient's demise, can occur in the nasopharynx; 4. epignathi are highly differentiated trigeminal tumours. A hairy polyp probably arises from either the segregation of epithelial and mesodermal elements during the fusion of the lateral palatine processes31 or from the incomplete reabsorption of the buccal nasopharyngeal membrane.32 It is usually detected early in life because of difficulties in breathing and swallowing.33, 34 Half of the cases are detected within the first year of life.35 A hairy polyp can present later in life and there are reports of its discovery in older patients,28,36 which serves to highlight its benign nature. These polyps are usually situated in the lateral nasopharynx or on the nasopharyngeal surface of the soft palate. They may be pedunculated and can grow to up to 6 cm m d'lameter.29 Macroscopically, they are grey or white with a hairy surface resembling skin. Microscopi cally, the polyp is covered by skin with hair follicles and deeper tissues comprising adipose tissue, muscle, cartilage and even bone.37 Excision of the lesion is invariably curative. .
Congenital deficit in nasopharyngeal form
Nasopharyngeal branchial cysts arise in the lateral wall of the nasopharynx. Some are situated between the upper pole of the tonsil and the Eustachian orifice,22 and others can extend all the way to the skull base.23 Shaheen24 reported two cases in which the cysts were situated at a higher level, stretching from the nasopharyngeal vault to behind the Eustachian orifice. The cyst contains lymphoid tissue in its wall and has a lining of columnar or squamous epithelium. Michaels25 believes that, although this is often designated a 'branchial cleft' cyst, it is more likely to have arisen from the first branchial pouch. Branchial cysts of the nasopharynx may be excised using the transpalatal route24,26 or endonasally with the help of an endoscope.27
A congenitally narrowed nasopharynx in association with craniofacial anomalies is regularly encountered by the otolaryngologist. Upper airway obstruction may present in infancy, as infants are obligate nasal breathers. In less obvious cases, the condition is manifested by sleep disordered breathing as the narrowed nasopharynx is further compromised by the growth of adenoid tissue. Congenital syndromes in which this problem is com monly encountered include Down's syndrome, Crouzon's syndrome ( craniofacial dysostosis), Apert syndrome (acrocephalosyndactyly) and cases of the more common Treacher Collins syndrome.
Hairy polyp or nasopharyngeal dermoid or teratoid
DOWN SYNDROME
The so-called hairy polyp of the nasopharynx is a well-recognized clinical condition which represents a dermOl'd28 or a teratOl'd29 tumour of the nasopharynx. A dermoid tumour is composed of ectodermal and mesodermal elements but, as a rule, lacks endodermal structures. A teratoid tumour possesses tissues from all three germinal layers but the tissue elements may be' poorly differentiated. In 1888, Arnold30 classified these ontogenetic tumours into four groups. 1. dermoid tumours; 2. teratoid tumours;
Down syndrome is genetically defined by a nondisjunc tion mutation that results in trisomy 21. The incidence is one in 700, which is more common than all other chromosomal anomalies. Its phenotypical features are well described.38,39, 40,41 A study conducted on 75 Down individuals using lateral cephalometric evaluation re vealed significant deficiencies in the midface, mandible and endocranium when compared with age-matched normal controls.42 The midface hypoplasia contributes to the smaller volume of both the nasopharynx and the oropharynx.43 The prevalence of sleep-disordered breathing/obstructive sleep apnoea in Down syndrome
I PART 16 THE UPPER AIRWAY
2120
subjects ranges between 54 and 100 percent as compared with
[***]
2 percent in normal children.44
Tortuous vessels in the nasopharynx The normal internal carotid artery runs in a straight course to the skull base. The pharynx lies anteromedial
CROUZON SYNDROME
and is normally at least 1.5 cm away with fatty areolar
Crouzon syndrome is an autosomal dominant craniosy nostosis. The
syndrome is
characterized by midface
hypoplasia with relative mandibular prognathism with an anterior bite and class III occlusion. The orbits are shallow and eyes may appear proptosed. Frontal bossing is a marked feature. Premature craniosynostosis may require cranioplasty procedures to make space for the brain.
Airway
obstruction
because
of
the
narrowed
nasopharynx in the newborn period and severe obstruc tive sleep apnoea may necessitate a tracheostomy.
tening occurs when the foetal heart and great vessels descend into the mediastinum. Failure of or incomplete uncoiling can result in the vessel assuming a wide loop in the coronal, saggital or, rarely, transverse plane of the neck
(Figures
161.3
and
161.4).
Such an anomaly
is rare but well recognized.47, 48, 49. 50 This emphasizes the importance of palpating for pulsating vessels while undertaking an adenoidectomy. A medialized internal velocardiofacial syndrome.Sl•52 In this syndrome, where
Apert syndrome is a rare autosomal dominant cranio Similar
arch and dorsal aortic root, is normally coiled. Straigh
carotid artery is a well-described entity associated with
APERT SYNDROME
synostosis.
tissue and pharyngeal veins in between.46 In the embryo, the internal carotid artery, derived from the third aortic
to
Crouzon's
syndrome,
midface
hypoplasia is prominent with relative class III occlusion.
pharyngoplasty may be undertaken for velopharyngeal insufficiency, this internal carotid anomaly is particularly relevant.
The most characteristic features are: 'tower skull', which is a high, prominent, steep forehead (acrocephalic) and syndactyly. The nasopharyngeal and oropharyngeal air ways are narrowed. A tracheostomy is often necessary.
TREACHER COLLINS SYNDROME
Treacher Collins syndrome, which was assigned the term mandibulofacial dysostosis by Franceschetti and Klein,4s is the most common of the genetic syndromes. It is an autosomal dominant condition. Typical features include downsloping palpebral fissures, coloboma of the outer one-third of
the lower eyelid, with ciliary agenesis.
Hypoplasia of the zygoma and short mandibular rami contribute to the typical appearance of a small face. There
Internal carotid artery
may be atresia of the external auditory canals and ossicular deformities. One-third of patients may have a cleft palate. Upper airway obstruction is usually due to the
Unshaded
hypoplastic mandible but may be associated with a
area
narrowed nasopharynx. A tracheostomy is often needed. The management of the multiple abnormalities arising
overlies tonsil
from the syndrome always calls for a multidisciplinary approach. The otolaryngologist plays an important role both otologically and in establishing a safe airway, which may be in the form of a nasopharyngeal tube, laser inferior turbinectomy, adenotonsillectomy and, often, a tracheostomy. The use of continuous positive airway pressure, which is a difficult undertaking for a child and their family, has provided encouraging preliminary results in well-supported centres. A safe airway facilitates corrective procedures by neurosurgeons and maxillofacial surgeons. With the introduction of distraction osteogene sis, the corrective craniofacial procedures can now be
Figure 161.3
performed much earlier, optimally at two years of age,
sagittal plane of the neck. Redrawn from Ref. 46, by permission
and be minimally invasive.
from Cambridge University Press.
Internal carotid with aberrant loop lying in the
Ch apter 161 Benign cond itions of the nasopharynx I
2121
sleep-disordered breathing. It is generally accepted that this is caused by antigen-stimulated increased lymphocyte
B activity. It remains unclear whether this increased B-cell activity is due to a higher number of surface pathogens or
to an altered cell response to normal pathogens.56 After �'T---Internal carotid artery
five years of age, adenoid size remains constant while the nasopharynx increases in size. 57 The decrease in adenoid size with age and their functional alterations remain poorly understood.58 The
blood
ascending
supply
pharyngeal
to
the
adenoids
artery,
the
is
from the
ascending
palatine
artery, the pharyngeal branch of the maxillary artery, the artery of the pterygoid canal and branches from the tonsillar branch of the facial artery. Venous drainage passes to the pharyngeal and pterygoid plexuses which
flow into the internal jugular and facial veins. The nerve
supply is from the pharyngeal plexus and lymphatic drainage passes to the retropharyngeal and pharyngo maxillary lymph nodes. 59 The human nasopharynx is a natural reservoir for bacterial
species
nontypeable
such
as
Haemophilus
Streptococcus
pneumoniae,
and
injluenzae
Moraxella
(Branhamella) catarrhalis, which all adhere to epithelial cens. The microflora of early Figure 161.4
Internal carotid with aberrant loop lying in the
coronal plane of the neck. Redrawn from Ref. 46, by permission from Cambri dge Un iversity Press.
the nasopharynx is established in childhood.60, 61, 62 The presence of bacterial
and viral strains in the nasopharynx, similar to those in the middle
ear
cavity in episodes of acute otitis media,
is well established.63,64 The role of the adenoids in
middle ear effusion and recurrent acute otitis media
are dealt with
in Chapter 72, Otitis media with effusion.
In populations where nasopharyngeal carcinoma (NPC)
is endemic, infectious mononucleosis involving the
ACQUIRED CONDITIONS
adenoids can present similarly to NPC with lymphadeno
pathy,
Adenoids
particularly
in
patients
who
have undergone
to nsillectomy. A less common but relevant infective condition of the
Adenoids in the nasopharynx develop from the fusion of two lateral primodia during early foetal life and form the
parts
central part of Waldeyees ring. They are covered by
nasopharyngeal TB occasionally mimics the condition.
pseudostratified ciliated columnar epithelium. From the surface, deep crypts penetrate into the adenoid tissue. These crypts are covered by a particular reticular crypt epithelium
specialized
for
the
uptake
of
antigens.
Antigens are processed and presented to Band T cells within the adenoids, in which B cells predominate,
comprising 60 percent of adenoid lymphocytes, with
T cells comprising the remaining 40 percent.53 Immuno
East Asia where
Arnold et a1.65 found granulomas in
NPC
is prevalent,
19 of 1124 patients
suspected of NPC. Of the 19 cases, three additionally had NPC.
Nasopharyngeal TB
can
also
occur
following
radiation therapy for NPC.66 In a large series of 843 TB
cases reviewed by Rohwedder in 1974, respiratory
tract
involvement,
with
16 had upper
pharyngeal
and
nasopharyngeal involvement present in five cases only.67 Primary
nasopharyngeal
TB,
without
puJmonary
or
systemic involvement, is rare.68 The commonest pre
which feed out through lymph and blood to the upper
sentation of nasopharyngeal TB is with cervical adenitis
mucosa,
include
IgG,
19A,
IgM
and
although in animal models adenoidal B cells mitted to producing IgA.54 Adenoids
are
not
radiologically
visible
are
on
IgD,53
(70 percent).69 The diagnosis is usually based on
a
com
fine needle aspirate of the cervical lymph node and/or a
plain
common presentation is nasal discharge or obstruc 7), 12,73,74 tion?O, Computed tomogTaphy (CT) and
radiographs in infants under one month of age, becoming radiologically demonstrable in all infants at six months.55
From 'the age of two to five years hypertrophy and
hyperplasia of the adenoids occur and may result in
t.
of South
globulins (Ig) produced by the B cells of the adenoids, airway
,
nasopharynx is nasopharyngeal tuberculosis (TB). In
biopsy
of
a
nasopharyngeal
magnetic resonance imaging
lesion.
The
next
most
(MRI) are usually unhelpful
in the diagnosis of nasopharyngeal TB which is best established using tissue samples.
[**]
2122
I PART 16 TH E UPPER AIRWAY
Rhinoscleroma, still fairly common in Central and South America, Egypt and some parts of Africa, the Middle East, India, Indonesia and the Philippines,7s can extend into the nasopharynx and eventually to the oropharynx, and rarely to the trachea and bronchi.76 The disease is characterized by deforming 'scleromatous' nodules which are a consequence of inflammatory fibrosis. Mucosal atrophy with crusting, granulation nodule formation and stenosis are well-recognized stages of the disease?6 Klebsiella rhinoscleromatis has always been identified as a possible causal organism but deficient cell-mediated immunity against the organism may also be a relevant factor.77 [***]
ACQUIRED CYSTIC CONDITIONS Cyst of bursa pharyngeal embryonalis (Thornwaldt1s cyst) The bursa pharyngeal embryonalis, also called Thornwaldt's bursa, is formed by the traction of the notochord on the retropharyngeal wall at the site of their contact. It lies in the midline and at the junction between the nasophar yngeal vault and the posterior pharyngeal wall. The bursa extends backwards and upwards above the uppermost fibres of the superior constrictor muscle. This bursa may be a seat of inflammation and cyst formation.78 The well known Thornwaldt's cyst is formed as a result of the obstruction of the bursa orifice and is not the same as cysts of Rathke's pouch which lies inferior to the sella turcica and ventral to the site of the bursa. Thornwaldt's cysts are usually asymptomatic but larger 1-2 cm cysts may be symptomatic. The symptoms may include halitosis, nasal discharge, nasal obstruction, epistaxis, prevertebral spasm and obstruction of the Eustachian tube.79 The appearance is usually one of a smooth mucosal mass with a central dimple.8 0 Excision or marsupialization may be necessary for symptomatic cysts.
Retention cysts Cysts of the midline and lateral nasopharynx are not uncommon. These cysts arise as a result of the obstruc tion of the duct of a seromucinous gland.31 The lining of these cysts may be either squamous or columnar epithelium or both.81
BENIGN NEOPLASTIC LESIONS Juvenile angiofibroma is a fibrous and vascular tumour that commonly involves the nasopharynx. Radiological evidence, drawn from over 20 years, reveals the probable origin of this tumour to be the recess behind the
see chapter on juv. angiofibroma.
pterygopalatine ganglion at the exit aperture of the pterygoid canal.82 Juvenile angiofibroma was known to Hippocrates.83 The first authentic case was treated surgically by Liston84 in 1841, and the histopathology of this resected tumour was verified to be angiofibroma in 1987 by Myhre and Michaels.8s The term 'nasopharyn geal fibroma' was introduced by Chauveau86 in 1906, and Freidberg87 suggested the name 'angiofLbroma' in 1940. [**] The incidence of juvenile angiofibroma is less than 0.5 percent of head and neck tumours and occurs exclusively in males.88 In Harma's series of 52 cases,89 the average age of patients at symptom onset was 15.3 years (age range 10-25 years). The role of pubertal hormones is controversial. Some authors support the theory that angiofibroma is an androgen-dependent tumour by establishing the presence of dihydrotestosterone receptors in the tumour tissue.9 0 , 91 Others favour the theory that juvenile angiofibroma is an oestradiol or oestrogen progesterone-dependent tumour.92,93 It is perhaps more relevant that Dillard et al. established the presence of activated transforming growth factor �1 in the fibroblasts and endothelial cells of juvenile angiofibroma in 100 percent of their 19 study cases.94 Further studies are needed to clarify the role of this factor. [**] Macroscopically, the tumour has a lobular surface and is grey or pinkish grey. Microscopically, juvenile angio fibroma is unencapsulated and has a characteristic structure of blood vessels set in a stroma of fibroblasts and collagen. Deeper blood vessels are thick walled whereas superficial vessels are thin walled with few or no muscle fibres. The overlying epithelium is either respira tory or stratified squamous in type.9S Clinically, most patients have minor symptoms of painless, unilateral nasal obstruction and epistaxis. Juvenile angiofibroma can, nonetheless, cause life-threa tening haemorrhage. Neel et al.96 provided a detailed account of the possible local extension of juvenile angiofibroma based on the pattern observed in their more advanced cases. The sites of involvement were summarized and modified by Michaels97 as follows: •
• •
•
• • •
fills nasopharynx and posterior nasal cavity; may enter mouth from behind; fills sphenoid sinus and erodes sella turcica; erodes medial wall of the antrum, which it then enters; spreads behind maxillary antrum, erodes pterygomaxillary fossa and enters cranial fossa; enters infratemporal fossa and also passes behind the zygoma, bulging in the supratemporal fossa; enters inferior orbital fissure and orbit.
If the orbit is involved, the patient may have proptosis and facial swelling. Intracranial invasion appears in 10-20 percent of all patients, being more frequent in younger adolescents.' 98 occur.99
Table 161.1 til.
.
' ..
Synopsis of classification systems for ang iofibroma. . 1
• .'
Joh,ns et at,1'9SQ
,I'r
:1" )
.�
I. Disease confined to the nasopharynx and nasal
Chandler- et af.,
1984
I. Tumour confined to
Fisch.
1983
I. Tumour limited to the
nasopha rynx
cavity
Andrew et al.•
1989
I. Tumour limited to the
,/.... ....
1996
Ra�owski
IA. Tumour limited to posterior
IA. Limited to nose and/or
,
'/.:"';",
nasopharynx and nasal
nasopharynx and nasal
nares and/or
cavity with no bone
cavity. Bone destruction
nasopharyngeal vault. No
negligible or limited to the
paranasal sinus extension
destruction
et al••
�$io'n(etal.,.t981
: : .�. - i.' ;- .-
. ..
nasopharyngeal vault
sphenopalatine foramen II. Disease involving
II. Tumour extending into nasal
II. Tumour invading the
II. Tumour invading the
lB. Same as IA but with
nasopharynx or nasal
cavity and/or sphenoid
pterygomaxillary fossa, the
pterygomaxillary fossa or
extension into one or more
cavity with extension to
sinus
maxillary, ethmoid and
the maxillary, ethmoid or
paranasal sinuses
the pterygomaxillary fossa
sphenoid sinuses with
sphenoid sinus with bone
and/or maxillary sinus
bone destruction
destruction
III. Involvement of more than
III. Tumour extending into one
III. Tumour invading the
lila. Tumour invading the
IIA. Minimal lateral extension
the anatomic sites listed in
or more of the following:
infratemporal fossa, orbit
infratemporal fossa or
through the
II. but without intracranial
antrum, ethmoid sinus,
and parasellar region
orbital region without
sphenopalatine foramen.
involvement
pterygomaxillary fossa,
remaining lateral to the
intracranial involvement
into and including a
infratemporal fossa, orbit
cavernous sinus
lB. Extension into one or more sinuses
IIA. Minimal extension into pterygomaxillary fossa
minimal part of the
and/or cheek
medial-most part of the pterygomaxillary fossa
IV. Intracranial extension
IV. Tumour extending into
IV. Tumour with massive
cranial cavity
liB. Full occupation of
Ilib. Tumour invading the
liB. Full occupation of the
invasion of the cavernous
infratemporal fossa or
pterygomaxillary fossa,
sinus, the optic chiasmal
orbital region with
displacing the posterior
with or without erosion of
region or pituitary fossa
intracranial extradural
wall of the maxillary
orbital bone
(parasellar) involvement
antrum forwards. Lateral
pterygomaxillary fossa
and/or anterior displacement of branches of the maxillary artery. Superior extension may occur, eroding the orbital bones IVa. Intracranial intradural
IIC. Extension through the
IIC. Infratemporal fossa with
tumour without infiltration
pterygomaxillary fossa into
or without cheek or
of the cavernous sinus,
the cheek and temporal
posterior to pterygoid
pituitary fossa or optic
fossa
plates
chasm IVb. Intracranial intradural tumour with infiltration of
III. Intracranial extension
IliA. Erosion of skull base minimal intracranial
the cavernous sinsus, pituitary fossa or optic chasm IIIB. Erosion of skull base extensive intracranial with or without cavernous sinus Reproduced with permission from Ref. 101, http://www.informaword.com
2124
I PART 16 TH E U P PER AIRWAY
The diagnosis is made clinically and radiologically.
Biopsy of a suspected juvenile angiofibroma is unneces
3,6 percent
in
a series in which primary radiotherapy
was used.110 Chemotherapy has also been carried out recurrent
tumours
with
encouraging
results.ll1
sary. CT diagnosis is based on two constant f eatures
for
1. mass in the nose and pterygopalatine fossa;
tumours have been observed both clinically and radio. 88,112,113,114,115,116 . logl'cally. The lflVO Iu t'Ion process lS
which are:
2. erosion of bone behind the sphenopalatine
Spontaneous
regression
usually very slow.
foramen at the root of the pterygoid plate and
of
recurrences
and
residual
[*""]
clinical findings.
With the expansion of the tumour, anterior bowing of the posterior antral wall may be seen on plain radiographs
and CT. This is the 'antral sign' described by Holman and
Miller in 1965.100 Growth of the tumour posteriorly
causes erosion of the sphenoid process of the palatine
OTHER BENIGN NEOPLASMS OF THE NASOPHARYNX Other benign neoplasms are rare. Schwannomas may . 1 7 In the nasop harynx. 1 They tend to be slow growing
. anse
bone, the pterygoid canal and the base of the pterygoid
but can spread locally by bony erosion. There is
at the base of the pterygoid process and the dipole of the
glioma but the ceil of origin remains uncertain.llS Minor
invasion carries a high incidence of recurrence unless
tumours are regular lesions in the nasopharynx. These
process. In cases with deep extension, the cancellous bone
greater wing of the sphenoid are involved. This kind of appropriate radical surgery is performed. Intracranial
extension is usually via the greater wing of the sphenoid
an
isolated report of nasopharyngeal gangliocytic paragan
salivary gland tumours119 can occur but none of these
rare benign tumours often come as diagnostic surprises during the biopsy of a nasopharyngeal mass.
or the superior orbital fissure as the tumour extends 8 through the orbit outside the rectus muscle cone. 2 MRI characteristically displays the 'bag of worms' appearance and may be employed to aid diagnosis or to show the
soft tissue extent of the tumour. Various classification systems
based
on
radiological
proposed (Table 161.1).101
findings
have
been
Juvenile angiofibroma should be surgically removed
and the preferred technique is using a midfacial degloving approach to avoid facial scaning,102, !O3, 104 or endoscopically combined with embolization.
lOS
Whichever tech
nique is employed, meticulous attention should be paid to
drilling out the base of the pterygoid, the pterygoid canal
and
the basisphenoid to minimize the chances of recurrence.106 In the past, a lateral rhinotomy approach L 7, 1 8 was most popular. 0 0 In rare cases a craniofacial
approach may be needed for intracranial tumours.
Recurrence of juvenile angiofibroma after surgical 88, 82 and can be removal is common (36-39 percent)
predicted
by
CT
features
such
as
invasion
of
the
\
'
' ,�'
.v ,
'
-
'
.
�S - ��i.-�; �;co nge;d.���C�.b �;9..i��9 �h
' m�y �e ' d��:t ? : ; , .';.:.... defecttve ,ruslOn of-the ,skull base ;";','i. (�fanss, �noidaf,'�e�ingocoeles:' Rathke's �
j?9��� �e�;�cp\'
gli��a,.
,,:< <_�_ cysts of the nasopharYnx <;1nd
,-
-
p,\�thi a. L" '
hairy: polypI
."
, nasophary:ngeal d�rmoid) or abn'o'trhalities in": :,-' ' , Jopn of the nasopharynx (tio�zori, A pert 'v L,,, -
�; '�.,
"
+-: .. '- ,--arid -Treacher Collins syndromes}:,:- ,:
:'; ;.'�'�, me,ningoen��i?h�ocoelcs - -- �.may ,present with c1inical.fe�tUre� suggestive _ of ompr:essio n of pituitary gi'and, :�p-tic tract -:,
i _�
c
..
>
•
..�
cancellous bone at the base of the pterygoid and deep
�� third ventricle" and in chil dfe:n , - as pan - qf �he spectrum of midline fu sio n_ defects, upper airw.ay
obstruction.or recuoept to CSp, rhinnordlea� SUrgi� _
meningitis due
correction in children is
usually p:artof ci-
�omJ,Jle", s�a�iofacial procedure With:;,: -significant' as,sociated
invasion of the greater wing of the sphenoid. Howard 1 et al. 06 reported encouraging results in reducing
- ��-and ,
recurrence by meticulously drilling ou t the pterygoid
base, the pterygoid canal and the basisphenoid. Recur
,
,', KEY.:-POI ", ; ,: ,: " , NTS
. indic'a:tibns -for intervention. "
' _� -
" : _ i; _
'
rate and preoperative embolization.109 Embolization is
�0Iogical de�elopment, R�thk�;s pouch p�sesupw�rds -through _�he '_fuhir e ,
into the deep cancellous spaces of the sphenoid which
craniop���'yngeal :du.ct
rence is also recognized in tumours with a rapid growth believed to be associated with shrinkage of the tumour
revascularizes and grows postoperatively. However, it may still be prudent, and will probably remain the preference of surgeons undertaking endoscopic resection, to embo lize the tumour prior to surgery.
Radiation therapy should be reserved for multiple
tumour recurrences as head and neck-induced malig
nancy is a real risk and has been reported at a rate of
. '.
DU1;ip'g:"emb
body of-ihe, ,$phenoid via the
'
-
--
_ wh-ich may ,u11clergo var yi ng -deg.iee�- ' of- obliteration. Therefore, it- is not , tinCOtnrTI _n to find - remnants of anterior pituitary, -tissu� , with runctional potentiai in ,the_ - nas-opharynx. __
Endocrine anterior pituit�ry tiss_ue may
give arid:eysts, Routine would n�t enco'mpass such
rise to functional turon,ti'rs adenoidectomy
9
,
�
-
,
.
, -
_
Cha pter 1 6 1
,�: ,tiSSl1C l)ut r�di� adeJ).oidectom}' might well " , do' s'o. " ' .. • Congen ital gl iomalencep h alocoele is a ( ' : .': :::' ' developm�ntal defLCil resulting in t he separation of neural t iss u e from the brai n . Branchial cy s ts of t h e nasopharynx are • loca t ed on t.he lateral wall and contai n lym phoid t issue and ilife likely to have arisen from t h e first branchi'al pOlich. • Hai ry polyps or nasopharyngeal d e rm oids . '" . a rises fro m either the segre g atIo n of epithcli
" " ", : i ' ,'
c .,'
.
..
.
_
.
•
•
_
.-�,
.
'
'" 1, , '- 6b.ser¥ed ·'-o:yt i� · v¢ry slow:' ' ,: �', ::! � )'.,"t , � ' ;�����. ��-:.« � , ? <'\ .
,
IILI
_ ,
,
_
'
.
'�,,,
i
\
I
'
Best cl i n ical practice ./ S u r g i cal intervention for m i ningomylocoeles, preferably endoscopic skuJl base proced u res, is Pru d ent planning or a review of d e c i sion on surgery is
adenotonsille.c tomy or t racheosto my.
call ed for i f a h i gh morbid i ty proced u re is
comtem p l ate d in a sm all child.
./ Tortu o us internal carotid arteries must be recognized when conte m plat ing su rgical proced u res on the nasopharynx.
./' CT sca n fea tu res of juvenile angiofi bro m a are diag nost i c. An a p p ro p r i ate a p p roach, open, endoscopic or combined, should be selected based on the
.
ind ivi d u al tumour. The most i m portant ste p in su rgery
of the nasop h arynx are: ·. � . ." i n fective ( adcn o it b due to S. p"eW1l01l;ae, H. . � .
is the d rilling of the pterygoid base, the pterygoid canal an d the basisphenoid to avo i d recu rren ce .
: catarrhalis) ; int"cct toUS , . �: ' . mononucleosis i n populations where N PC is ' co m m o n ; n asop har yn geal TJ3 c a n mimic:;� " :. ' ' .: Nl.
'
.
NPC; rh,i nosclero m a tos i s ;, cY$t ic cond i t ioii� ' :
' neopJa�tic
angio,fibroma �d: ,·.-· , ., r· : .: '� " , . ' .. . .
.
Juvenile angio fibroma is a raT§\ .cp!):qil,i.p.Q.i,n. : ' young males aged 1 0-25. It us�i-ity:;:p:res�nts·,· wi t.h m i n o r s y mpJQms, 6'£ uni1a�r af:has:a).--: ' / · .
o bsitru c ti o n , although occasionally J�eie' may" be li-fe-threatenirig :'h aemo rrhage'; :AU' areas. '
..
may' be in�olved. ' Biopsy of suspected juvenile" angiofib:roma is unnecess�ry. CT ,di�gnosis is.. based on two co n sta n t featutes:· . a mass in 'the .
. "
Defi ci e n ci es i n cu rrent know ledge a n d a reas for futu re resea rch )- Molecular and i mm unolog i cal research wiJl add more information abou t the lymphoid tissu e i n the nasopharynx,
>- I m ag e - g u i d e d su rgery a nd three-d i m ens ional planning a n d robotic surg ery would m a ke the area accessible
s(] 'rrounclin g ' the ' nasopharynx
nose and pterygopalatine
.
, '. : , '- f residu-aJ�'an.cl: reeurt'"ent .tumours has�'bee�: . :,
>.
.
•
embolization.
ind i ca ted in CSF leakage or a i rway obstruct ion.
Acq u i red cond i t io n s
schwa n n o m as) .
with
:���{;�j':��thei r�sk \�f i n duced maligJ1�ncy., and , ' , ��jf�:',}�h,�'mQth:etapy- .may have ' a place in !1lan�ging <,--,- ':_:'.:r.:t�eurt�U4�, S pont.a neous i'¢gr�ssio�n of ,
.
l es ions ( benign j uvenile
a
is co m mo n ana-: can be predicted by CT fe'atures. Radiation·: therapy. should be -" , :�::,�:�, reserv�4 ·fo r multiple' recu;rteri��s because -of
The ma nag,ement of �he multiple .- ' abno rmalities present alw'ays calls for a mu l t i d i sciplinary team. The ,otola ryngo lugist 's ro l e i nvolves management of ot it is med ia with effusion due to Eus t ac h ia n t ube dysfunct jon, laser i n ferior t u rbi nectom y to improve th e airway, c. ,' , -
cyst, retention 'cyst ) ;
and is useful to · show the soft extent o f t umO U f. Su rgical . ren'l.ova� is mid fa.cia"' deglovmg a'pproach . o r
" Reciurence
syndrome or Trcacher Coll i n
(Thornwald fs
t issue
'-', �, " �·�e,n90s<:o.pically co mbi ned
syndrome.
i" j1uel1zae,
MRl
,�b�ra:CteristicallY' ,displays the bag of worms
)�,,:,, -�'ppear@<;e.
Do wn's syndrome, erouzon's syndrome,
A pert
�' . I(id'iCat SUFg�ty ',is pt:rformed.
h:���, via
,<
.' ,
r
.
B e n i g n con d i tions of the nasopharynx I 2 1 25
and accessibility safer possibly_ ). Genetic st udies would u n cover the unknown in nasopharyngea I an gi ofibroma.
fossa; · er.osion of'
bone ' behind the sphenopalatine foramen-at
the root of the pterygoid plate. Radiqlogkal
erosion of the sphenoid p r o ce ss of the
.
palatine bone> pterygoid canal and the' 'base
of t h e pterygoid p rocess carries a hi gher
.
incidence of re c ur re n ce unless ..appropriate
�--
.
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I PART 1 6 THE U PPER AIRWAY
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!
'-
162 Anatomy of the larynx and tracheobronchial tree NIGEL BEASLEY
Introduction Embryology Anatomy of the larynx
2130 2130 2131
INTRODUCTION The human larynx protects the lower respiratory tract, provides a controlled airway, allows phonation and the generation of a high intrathoracic pressure for coughing and lifting. The evolution of the larynx provides an insight into its functional priorities. In its most primitive form, it can be found as a muscular sphincter around the entrance to the respiratory tract in the bichir lungfish preventing the entry of water in the aquatic environment. The African lungfish has both a sphincter and dilator, allowing both active opening and closing of the airway. The Mexican salamander possesses lateral cartilages which aid in opening the respiratory tract. The ability of the larynx to allow speech is only found in humans and represents a more specialized function of the larynx.
EMBRYOLOGY Embryology of the larynx During the fourth week of embryonic development, the tracheobronchial diverticulum appears in the ventral wall of the primitive pharynx just below the hypobranchial eminence (Figure 162.1). The edges of this groove form the oesophagotracheal septum which fuses caudally, leaving a slit-like aperture cranially into the pharynx (Figure 162.2). The resulting tube is lined with endoderm from which the epithelial lining of the entire respiratory tract develops. The cranial end of the tube forms the larynx and trachea and the caudal end the bronchi and lungs.
Anatomy of the trachea and bronchi Key points Further reading
2140 2144 2144
These tubes of endoderm grow into the mesenchyme from which the connective tissue, cartilage, nonstriated muscle and vasculature of the bronchi and lungs develop. Arytenoid swellings appear on both sides of the tracheobronchial diverticulum and, as they enlarge, the epithelial walls of the groove adhere to each other, and the aperture of the larynx is occluded until the third month, when the lumen is restored. The arytenoid swellings grow upwards and deepen to produce the aryepiglottic folds. The hypobranchial eminence becomes the epiglottis. The glottis forms just above the level of the primitive aperture. The thyroid cartilage develops from the ventral ends of the cartilages of the fourth pharyngeal arch and appears as two lateral plates each with two chondrification centres. The cricoid cartilage and the cartilages of the trachea develop from the sixth arch during the sixth week with the trachea increasing rapidly in length from the fifth week onwards. The mesoderm of each pharyngeal arch differentiates into the cartilage, muscle and vascular structures of that arch. Each arch receives an afferent and efferent nerve supply for the skin, muscles and endodermal lining of that arch, which in the case of the fourth and sixth arches are the superior and recurrent laryngeal branches of the vagus which supply the larynx. The primitive recurrent laryngeal nerve enters the sixth visceral arch on each side below the sixth aortic arch artery. On the left side, the arch artery retains its position as the ductus arteriosus so the nerve is found below the ligamentum arteriosum after birth. On the right side, the dorsal part of the sixth arch artery and the whole of the fifth arch artery disappear leaving the nerve below the fourth arch artery which becomes tlie subclavian artery (Figure 162.3). Occasionally, the proximal portion of the fourth arch artery also
Chapter 162 Anatomy of the larynx and tracheobronchial tree
7
8
9
I 2131
Right vagus nerve Left vagus nerve External carotid artery
10 1b
n+---11
12
Internal carotid artery
-r~-r~~-----14
Right recurrent laryngeal nerve
.~-->.----===--
2
3 4
15
5 ----~Id___'b-+·I
16
Left recurrent laryngeal nerve
17
Ligamentum arteriosum
6 -----I---------f-
Right subclavian artery Figure 162.1
Arches and elevations in the floor of the
foregut. 1a, First arch, maxillary process; 1b first arch, mandibular process; 2, second pharyngeal arch; 3, third pharyngeal arch; 4, fourth pharyngeal arch; 5, tracheobronchial diverticulum; 6, oesophagus; 7, endodermal lining; 8,
Aorta Figure 162.3
The relationship between development of the
branchial arches and recurrent laryngeal nerves. The numbers indicate the number of the branchial arch.
tuberculum impar; 9, first pharyngeal pouch; 10, maxillary nerve; 11, mandibular nerve; cartilage and artery; 13, second pharyngeal cleft; 14, hypobranchial eminence; 15, ectodermal
Embryology of the tracheobronchial tree
covering; 16, mesenchyme in fourth arch; 17, superior laryngeal nerve.
3
5
(0)
(b)
The right and left lung buds appear before the tracheobronchial diverticulum is converted into a tube. They grow out into the pleural cavities below the common cardinal veins and divide into lobules, three appearing on the right and two on the left. It is uncertain whether the lung budding pattern determines the septal pattern of the lungs or whether the development of connective tissue septa controls the final form of the lungs. Each primary bronchus continues to divide until by birth some 18-23 generation of divisions have appeared. The bronchial tree is fully developed by the 16th week. During the course of development the lungs migrate downwards so that by birth the bifurcation of the trachea is opposite T4.
-1-------6
ANATOMY OF THE LARYNX Figure 162.2
Development of the tracheobronchial
diverticulum and oesophagus. (a) Laryngotracheal groove appears in the ventral aspect of the foregut. (b) The edges of the groove close in to form the oesophagotracheal septum. 1, foregut; 2, laryngotracheal groove; 3, oesophagotracheal septum; 4, trachea; 5, lung bud; 6, stomach.
disappears leaving nothing in contact with the right recurrent laryngeal nerve, which instead of being pulled down into its usual position passes directly from the main vagal trunk to enter the larynx.
.
(-
General description The larynx extends from the laryngeal inlet to the inferior border of the cricoid cartilage (Figure 162.4). It lies opposite the third to sixth cervical vertebrae, being a little higher in women than in men. The infantile larynx is proportionally smaller than that of the adult compared to body size and is more funnel shaped. Its narrowest part is at the junction of the subglottic larynx with the trachea and even slight swelling in this area may result in marked
2132 I PART
16 THE UPPER AIRWAY
airway obstruction. The laryngeal cartilages are much softer in the infant than the adult and collapse more easily on forced inspiration. The larynx starts high up under the tongue in early life and with age assumes an increasingly lower position in the neck. As the larynx grows, there is little difference in its size between boys and girls until after puberty when the anterior-posterior (AP) diameter of the larynx almost doubles in men to reach a final AP diameter of about 36 mm in men and 26 mm III women. The larynx is divided anatomically into the supraglottis, glottis and subglottis by the false and true cords (Figure 162.4). The supraglottis consists of superiorly the epiglottis and aryepiglottic folds as they sweep down to the arytenoids. Its lower border is the ventricular bands (false cords) which form the upper border of the glottis. The glottis includes the vocal cords and anterior commissure and posterior commissure. The definition of the junction between the glottis and the subglottis has been debated in the literature at some length and is either defined as at the level of the vocal folds or 5-10 mm below. The sub glottis becomes the trachea at the lower border of the cricoid. The framework of the larynx consists of the hyoid bone and a number of cartilages connected by ligaments, membranes and intrinsic and extrinsic muscles to give it stability. It is lined with a mucous membrane that is continuous above with the pharynx and below with that of the trachea. The spaces around the larynx are filled with adipose tissue and loose connective tissue and are key to understanding the spread of tumours within the larynx.
Hyoepiglottic ligament
The framework of the larynx HYOID BONE
The hyoid is aU-shaped bone which provides the upper attachment for many of the extrinsic muscles of the larynx and suspends the larynx in the neck (Figure 162.5). It consists of a body anteriorly from which the greater cornua project backwards on each side. The lesser cornua are two small conical eminences which are attached to the upper part of the body of the hyoid by a fibrous band and sometimes to the greater cornua by way of a synovial joint.
THYROID CARTILAGE
The thyroid cartilage is composed of two lamina which are fused in the midline anteriorly giving rise to the laryngeal prominence (Figure 162.5). The angle of fusion is about 90° in men and 120° in women. The posterior border of each lamina is prolonged above a1?-d below to form the superior and inferior cornua. The superior cornu is long and narrow and curves upwards, backwards and medially ending in a conical extremity to which the lateral thyroid ligament is attached. The inferior cornu is shorter and thicker and curves downwards and medially. On the medial surface of its lower end is a small oval facet joint for articulation with the cricoid cartilage. On the external surface of each lamina, an oblique line curves downwards and forwards from the superior thyroid tubercle, situated just in front of the root of the superior horn, to the inferior thyroid tubercle on the lower border of the lamina. This line marks the attachment of the thyrohyoid, sternothyroid and inferior constrictor muscles. On the inner aspect of the thyroid
Quadrilateral membrane (upper part fibroelastic membrane)
Body of hyoid bone
Epiglottis Thyrohyoid membrane
Muscular process of arytenoid
Cricoid lamina Cricoid arch
Vocal process of arytenoid Vestibular fold and ligament Thyroepiglottic ligament Laryngeal ventricle Vocal fold and ligament Cricothyroid ligament Cricovocal ligament (lower part fibroelastic membrane)
Figure 162.4 laterally.
Greater horn of hyoid bone
Thyrohyoid membrane Cartilago triticea
Lesser horn of hyoid bone
Lateral thyrohyoid ligament
Median thyrohyoid ligament
Superior cornu of thyroid cartilage
Cricoidthyroid ligament
Thyroid lamina Thyroid notch
Cricoid arch
Oblique line
Cricoid cartilage
Inferior cornu of thyroid cartilage
Cricotracheal ligament
Cricothyroid membrane
Sagittal section across the larynx looking
Figure 162.5
The framework of the larynx.
J
Chapter 162 Anatomy of the larynx and tracheobronchial tree
cartilage just below the thyroid notch in the midline is attached the thyroepiglottic ligament and below this and on each side of the midline, the vestibular and vocal ligaments and thyroarytenoid, thyroepiglottic and vocalis muscles are attached. The fusion of the anterior ends of the two vocal ligaments produces the anterior commissure tendon. The remaining parts of the inner aspect of the thyroid lamina are smooth and are mainly covered by loosely attached mucous membrane. The superior border of each lamina gives attachment to the thyrohyoid ligament and the inferior border, on the medial portion of its inner aspect, the cricothyroid ligament. CRICOID CARTILAGE
The cricoid cartilage is the only complete cartilaginous ring in the airway (Figure 162.6). It forms the inferior part of the anterior and lateral walls and most of the posterior wall of the larynx. It has a deep broad lamina posteriorly and a narrow arch anteriorly with a facet for articulation with the inferior cornu of the thyroid cartilage near the junction of the arch and lamina. Rotation of the cricoid cartilage on the thyroid cartilage can take place about an axis passing transversely through both joints. The lamina has sloping shoulders on which the articular facets for the arytenoids are found. A vertical ridge in the midline of the lamina gives attachment to the longitudinal muscle of the oesophagus and produces a shallow concavity on each side for the origin of the posterior cricoarytenoid muscle. The entire inner surface of the cricoid cartilage is lined with mucous membrane. THE ARYTENOID CARTILAGES
The arytenoid cartilages are irregular, three-sided pyramids with a forward projection, the vocal process, attached to the vocal folds and a lateral projection, the muscular process, to which are attached the posterior cricoarytenoid and lateral cricothyroid muscles (Figure 162.6). Between these two processes, the anterolateral surface is irregular and divided into two fossa by a crest
Corniculate cartilage
I 2133
running from the apex. The upper triangular fossa gives attachment to the vestibular ligament and the lower to the vocalis and lateral cricoarytenoid muscles. The apex is curved backwards and medially and is flattened for articulation with the corniculate cartilage. The medial surfaces are covered with mucous membrane and form the lateral boundary of the posterior glottis. The posterior surface is covered by the transverse arytenoid muscle. The base is concave and presents a smooth surface for articulation with the sloping shoulders of the upper border of the cricoid lamina. This is a synovial joint with lax capsular ligaments allowing both rotatory movements and medial and lateral gliding movements. The posterior cricoarytenoid ligament prevents forward movement of the arytenoid cartilage. CORNICULATE AND CUNEIFORM CARTILAGES
The corniculate cartilages are two small conical nodules of elastic fibrocartilage which articulate through a synovial joint with the apices of the arytenoid cartilages. They are situated in the posterior part of the aryepiglottic fold. The cuneiform cartilages are two small elongated flakes of fibroelastic cartilage, one in each margin of the aryepiglottic fold. EPIGLOTTIS
The epiglottis is a thin, leaf-like sheet of elastic fibrocartilage which projects upwards behind the tongue and the body of the hyoid bone. It is attached inferiorly to the thyroid cartilage, just below the thyroid notch in the midline, by the thyroepiglottic ligament and also to the hyoid bone anteriorly by the hyoepiglottic ligament. The space between these ligaments forms the preepiglottic space. From the sides of the epiglottis, the aryepiglottic folds pass down to the apex of the arytenoids. The posterior surface of the cartilage is indented by numerous small pits into which mucus glands project. The anterior surface of the epiglottis is covered with mucous membrane superiorly and forms the posterior wall of the vallecula. The mucous membrane overlying the epiglottis is reflected on to the base of the tongue, forming the glossoepiglottic fold in the midline and laterally the lateral glossoepiglottic folds.
Ligaments and membranes of the larynx Muscular procej-s of arytenoid cartilage Vocal process
Cricoid cartilage Figure 162.6
The cricoid and arytenoids.
EXTRINSIC LIGAMENTS
The extrinsic ligaments of the larynx connect the laryngeal cartilages to the hyoid above and trachea below (Figure 162.5). Superiorly, the thyrohyoid membrane stretches between the upper border of the thyroid cartilage and the posterior surface of the body and greater cornua of the hyoid. The membrane is composed
2134 I PART
16 THE UPPER AIRWAY
of fibroelastic tissue, reinforced by fibrous tissue in the midline as the median thyrohyoid ligament and posteriorly as the lateral thyrohyoid ligament. The latter connects the tip of the superior cornua of the thyroid cartilage to the posterior ends of the greater cornua of the hyoid. The ligaments often contain a small nodule of cartilage, the cartilago triticea. The membrane is pierced by the internal branch of the superior laryngeal nerve and by the superior laryngeal vessels. The cricotracheal ligament unites the lower border of the cricoid with the first tracheal ring.
INTRINSIC LIGAMENTS
The intrinsic ligaments of the larynx connect the laryngeal cartilages together, strengthen the capsule of the intercartilaginous joints and form a broad sheet of fibroelastic tissue, the fibroelastic membrane, which lies beneath the mucous membrane of the larynx forming an internal framework (Figures 162.4 and 162.7). The fibroelastic membrane is divided into an upper and lower part by the laryngeal ventricle. The upper quadrilateral membrane extends between the lateral border of the epiglottis and the arytenoid cartilages. The upper margin forms the framework of the aryepiglottic fold and the lower margin is thickened to form the vestibular ligament underlying the vestibular fold (false cord). The lower part is thicker containing many elastic fibres. It is commonly called the cricovocal ligament, cricothyroid ligament or conus elasticus. It is attached below to the upper border of the cricoid cartilage and above it is stretched between the inner surface of the midpoint of the laryngeal prominence of the thyroid cartilage anteriorly and the vocal process of the arytenoid behind. The free upper border of this membrane constitutes the vocal ligament the framework of the vocal fold (true cord). Anteriorly, there is a thickening of the membrane, the cricothyroid ligament, which connects the cricoid and the thyroid cartilages in the midline.
Hyoid bone
Thyoid cartilage
Muscles of the la rynx The extrinsic muscles of the larynx attach the larynx to neighbouring structures and maintain the position of the larynx in the neck (Table 162.1). The infrahyoid muscles oppose the elevators of the larynx by 'paying out rope' during contraction of the suprahyoid elevators. Descent of the larynx is due to elastic recoil on the trachea. The intrinsic muscles are all paired and move the cartilages in the larynx and regulate the mechanical properties of the larynx (Table 162.2 and Figures 162.8, 162.9, 162.10, 162.11 and 162.12). They control the position and shape of the vocal folds and control the elasticity and viscosity of each layer.
The glottis The glottis lies between the false and true vocal cords which cover the vestibular and vocal ligaments, respectively (Figures 162.4 and 162.7). Laterally, a horizontal slit opens into an elongated recess, the laryngeal ventricle. From the anterior part of the ventricle, the saccule of the larynx ascends between the vestibular ligament and the inner surface of the thyroid cartilage as high in some people as the upper border of the thyroid cartilage. It occasionally protrudes through the thyrohyoid membrane. Fibrous tissue surrounds the saccule. The vestibular folds are two thick folds of mucous membrane each enclosing a narrow band of fibrous tissue, the vestibular ligament, which is the lower border of the upper quadrilateral membrane. It is fixed in front at the angle of the thyroid cartilage just below the attachment of the epiglottic cartilages and behind the anterolateral surface of the arytenoid cartilage just above the vocal process (Figure 162.8). The vocal folds extend from the middle of the angle of the thyroid cartilage to the vocal process of the arytenoid cartilages and underlying them is the upper border of the conus elasticus. Each fold is a layered structure consisting
Quadrangular membrane Thyroepiglottic m.
False vocal fold True vocal cord
Conus elasticus Lat. cricoarytenoid m. Inf. pharyngeal constrictor m.
:nrv\th"r"irl
m. , Figure 162.7
Coronal section through the
larynx looking anteriorly.
Chapter 162 Anatomy of the larynx and tracheobronchial tree
I 2135
Infrahyoid group Thyrohyoid
Oblique line of thyroid lamina
Inferior border of the
Elevates the larynx on a
greater cornu of the
fixed hyoid or depresses
hyoid
the hyoid on a fixed
Hypoglossal (C1 root)
larynx Sternothyroid
Posterior surface of manubrium and
Oblique line of the
Depresses the larynx
Ansa cervicalis (C2, 3 roots)
Depresses the larynx by
Ansa cervicalis (C1, 2, 3
thyroid lamina
edge of the first costal cartilage Sternohyoid
Clavicle and posterior surface of the
Lower edge of the body
lowering the hyoid
of the hyoid
roots)
manubrium
Suprahyoid group Mylohyoid
Mylohyoid line on inner aspect of the
Midline raphe and body of the hyoid
Raises and pulls the hyoid anteriorly
Genial tubercle on mandible
Stylohyoid
Back of the styloid process (splits
(inferior alveolar branch of V3)
mandible Geniohyoid
Nerve to mylohyoid
Upper border of the body of the hyoid
Raises and pulls the hyoid
Hypoglossal (C1 root)
forwards
Base of greater cornu of
Retractor and elevator of
Facial nerve
the hyoid for
the hyoid
swallowing
around the digastric tendon) Digastric
Digastric notch on the
Anterior belly pulls the
Lower border of the
medial surface of
mandible (fibrous
the mastoid
sling holds the
process
tendon to the lesser
hyoid anteriorly and up Posterior belly pulls the hyoid posteriorly and up
Posterior belly - facial nerve Anterior belly - nerve to mylohyoid
cornu of the hyoid) Stylopharyngeus
Medial aspect of the styloid process
Posterior border of the
Elevates the larynx
Glossopharyngeal nerve
Helps tilts the larynx
Accessory nerve
lamina of the thyroid cartilage (side wall of the pharynx)
Palatopharyngeus
Palatine aponeurosis
Posterior border of
and posterior
thyroid alar and
margin of hard
cornua
forwards
(pharyngeal plexus)
palate Salpingopharyngeus
Eustachian tube
Posterior border of the
Elevates the larynx
Pharyngeal plexus
thyroid cartilage (side wall of the pharynx)
of a superficial layer of nonkeratinizing, stratified squamous epithelium, beneath which is the lamina propria. This has three distinct layers. The superficial layer (Reinke's space) contains a fibrous substance with similar characteristics to gelatin. The intermediate layer contains elastic fibres and the deep layer collagen fibres. The intermediate and deep layers make up the vocal ligament. The vocalis muscle, which forms the main body of the vocal fold, lies lateral and deep. The layered structure of the vocal fold is not uniform in its entire length. At the anterior end of the vocal fold there is a mass of collagen fibres which are connected to the inner perichondrium of the thyroid cartilage and to
.
",
the deep layer of the lamina propria posteriorly. Adjacent to this mass of collagen fibres just posteriorly, there is another mass of elastic fibres continuous with the intermediate layer of the lamina propria called the anterior macula flava. A similar structure is seen at the posterior end of the membranous part of the vocal fold. These structures appear to serve as cushions to protect the ends of the vocal folds from mechanical damage caused by vocal fold vibration. The anterior three-fifths of the vocal cord is between the vocal folds and is called the intermembranous part of the cord. The remaining two-fifths posteriorly are between the vocal processes of the arytenoid and are
Table 162.2
Intrinsic muscles. Origin
Insertion
Function
Effect
Lower and medial surface of the back of the cricoid lamina
It fans out to be inserted into the back of the muscular process of the arytenoid
Abducts and elevates the tip of the vocal process The vocal fold becomes elongated and thin. The free edge of the vocal fold is rounded and passively stiffened
Lateral cricoarytenoid
Superior border of lateral part of the arch of the cricoid
Muscular process of arytenoid
Transverse arytenoids - unpaired
Posterior surface of the muscular process and outer edge of the arytenoid Posterior aspect of the muscular process (superficial to the transverse arytenoid)
Crosses over and attaches to the same point on the other arytenoid
Opens the glottis. Upper horizontal fibres rotate the arytenoids and move the muscular processes towards each other separating the vocal processes and abducting the cords. Lateral vertical fibres draw the arytenoids down the sloping shoulders of the cricoid separating the arytenoids Adducts and lowers the tip of the vocal process by rotating the arytenoids medially Adducts the vocal fold and controls the position of the vocal fold
Name
Open and close the glottis Posterior cricoarytenoid
Oblique arytenoids - paired
Control the tension of the vocal folds Thyroarytenoid (vocalis) A broad sheet of muscle which lies lateral to and above the free edge of the cricovocal ligament. The lower part of the muscle is thicker and forms a distinct bundle called the vocalis muscle. Cricothyroid This is the only intrinsic muscle that lies outside the cartilaginous framework of the larynx
Alter the shape of laryngeal inlet Aryepiglotticus A continuation of the oblique arytenoid Thyroepiglotticus A continuation of the thyroarytenoid
Apex of the other arytenoid
Back of the thyroid prominence and cricothyroid ligament
Vocal process of arytenoid and anterolateral surface of the body of the arytenoid
Lateral surface of the anterior arch of the cricoid. Fibres fan out and pass backwards in two groups
Lower oblique fibres pass backwards and laterally to the anterior border of the inferior cornu of the thyroid cartilage. Anterior straight fibres ascend to the posterior part of the lower border of the thyroid lamina
Posterior aspect of the muscular process of the arytenoid
Fibres pass around the apex of the opposite arytenoid and insert into the aryepiglottic fold Fibres pass upwards into the aryepiglottic fold
Back of the thyroid prominence and cricothyroid ligament
Vocal fold adducted, lowered, elongated and thinned. The edge of the vocal fold becomes sharp and is passively stiffened No significant effect on the mechanical properties of the vocal fold
Lowers, shortens and thickens the vocal folds causing the edge of the fold to be rounded. The body of the fold is actively stiffened but the transition layers are passively slackened. Many fibres are prolonged into the aryepiglottic fold some continuing to the margin of the epiglottis as the thyroepiglottic muscle which tends to widen the inlet of the larynx pulling the aryepiglottic folds slightly apart Rotates the cricoid cartilage about the horizontal axis passing through the cricothyroid joint. It lengthens the vocal folds by increasing the distance between the angle of the thyroid cartilage and arytenoids. On contraction, the vocal folds are brought into a line between the anterior commissure and the posterior cricoarytenoid ligament, the level of the vocal folds is lowered and the entire fold elongated and thinned. The edge of the vocal fold becomes sharp and all the layers are stiffened Weak sphincter of the laryngeal inlet Widens the inlet of the larynx pulling the aryepiglottic folds slightly apart
All the intrinsic muscles of the larynx are supplied by the recurrent laryngeal nerve except the cricothyroid, which is supplied by the external branch of the superior laryngeal nerve. The unpaired transverse arytenoid and paired oblique arytenoid make up the interarytenoid muscle.
~~
~A
Chapter 162 Anatomy of the larynx and tracheobronchial tree
Cricoid cartilage Posterior
I 2137
Arytenoid cartilage JMuscular process ~ocal process
-------7J3~~~~"::=::::~~
cricoarytenoid muscle Lateral cricoarytenoid muscle Transverse and oblique arytenoid muscles Cricothyroid muscles Thyroarytenoid muscle
Thyroid cartlilage
Vocal ligament
Figure 162.8
\--\--t~~~--------
Dissected view of the larynx from above.
Superior laryngeal nerve Foramen for superior laryngeal vessels and internal branch of superior laryngeal nerve
Internal branch External branch Superior laryngeal artery
Oblique and transverse arytenoid muscles
\",'~It----~+-----Inferior
pharyngeal constrictor muscle
~~~~=-j---==-
Posterior cricoarytenoid muscle
Thyroid branches
~~~~~----- Cricothyroid muscle
Vertical partL Cricothyroid Oblique pa~
muscle
Cricopharyngeus muscle (part of inferior pharyngeal constrictor) Recurrent laryngeal nerve Inferior thyroid artery
Figure 162.9
Figure 162.10
Lateral view of the larynx with extrinsic
muscle removed.
Lateral view of the larynx (complete).
called the intercartilaginous portion. The height of the vocal folds diminishes towards the anterior commissure mainly because the inferior edge of the vocal fold slopes upwards. At the anterior commissure the lower edges of the vocal folds form the apex of the triangular fixed part of the epiglottis, so tumour involving the anterior commissure usually involves the subglottis.
Mucous membranes of the larynx The mucous membrane lining of the larynx is closely attached over the posterior surface of the epiglottis, the
corniculate and cuneiform cartilages and over the vocal ligament. Elsewhere, it is loosely attached and prone to oedema. Most of the larynx is lined by pseudo stratified ciliated columnar 'respiratory' -type epithelium. The upper half of the posterior surface of the epiglottis, the upper part of the aryepiglottic fold, the posterior glottis and the vocal folds are covered with nonkeratinizing stratified squamous epithelium. Mucous glands are freely distributed throughout the mucous membranes and are particularly numerous on the posterior surface of the epiglottis where they form indentations into the cartilage and in the margins of the lower part of the aryepiglottic folds and in the saccules. The vocal folds do not possess any glands
2138 I
PART 16 THE UPPER AIRWAY
Aryepiglottic muscle
--+-1-------- Epiglottis
Oblique and transverse arytenoid muscles
Thyroepiglottic muscle Thyroarytenoid muscle
Posterior cricoarytenoid muscle Lateral cricoarytenoid muscle Figure 162.11
Cricothyroid muscle (cut away)
Latera I view of the larynx with the
ipsilateral thyroid cartilage and cricothyroid muscle removed.
Epiglottis Aryepiglottic fold Cuneiform tubercle Corniculate tubercle
L_-+.I------- Aryepiglottic muscle -y----+-+----Oblique arytenoid muscle Transverse arytenoid muscle ""?';;-------Posterior cricoarytenoid muscle Cricoid cartilage
Figure 162.12
and the mucous membrane is lubricated by mucus from the glands within the saccules. The squamous epithelium of the vocal folds is therefore prone to desiccation if these glands cease to function, for example after radiation.
Spaces within the larynx PREEPIGLOlTlC SPACE
The preepiglottic space is a wedge-shaped space with the point of the wedge inferiorly (Figure 162.4). It is bounded anteriorly by the thyrohyoid ligament and hyoid
Posterior view of the larynx.
bone and posteriorly by the epiglottis. Superiorly, the hyoepiglottic ligament connects the epiglottis to the hyoid bone. Tumour may spread into this area through small perforations in the epiglottis or directly through, the hyoepiglottic ligament. The preepiglottic space IS continuous laterally with the paraglottic space. PARAGLOlTlC SPACE
The paraglottic space is bounded laterally by the thyroid cartilage, medially by the conus elasticus and quadrangular membrane and posteriorly by the piriform fossa mucosa. It' encompasses the laryngeal ventricles and saccules (Figures 162.8 and 162.13).
Chapter 162 Anatomy of the larynx and tracheobronchial tree
I 2139
~----------------17
16
2
Figure 162.13
Axial section at C5 showing the
relationship of the larynx to the surrounding
3
15
structures. 1, Sternohyoid; 2, omohyoid; 3,
4
14
sternocleidomastoid; 6, external laryngeal nerve; 7,
5
13
space; 9, hypopharynx; 10, pyriform fossa; 11,
thyrohyoid; 4, thyroid cartilage; 5, inferior constrictor muscle; 8, retropharyngeal cervical sympathetic ganglion; 12, vagus nerve; 13, internal jugular vein; 14, internal carotid artery; 15, superior thyroid artery and vein; 16, arytenoid
6
7
8
9
10
11
12
Nerve supply of the larynx The motor and sensory nerves of the larynx are derived from the vagus by way of its superior and recurrent laryngeal nerves (Figure 162.9). The superior laryngeal nerve arises from the inferior ganglion of the vagus and receives a branch from the superior cervical sympathetic ganglion. It descends lateral to the pharynx behind the internal carotid artery and at the level of the greater horn of the hyoid divides into a small external branch and a larger internal branch. The external branch provides motor supply to the cricothyroid muscle, while the internal branch pierces the thyrohyoid membrane above the entrance of the superior laryngeal artery and divides into two main sensory and secretomotor branches. The upper branch supplies the mucous membrane of the lower part of the pharynx, epiglottis, vallecula, vestibule of the larynx and the lower branch descends in the medial wall of the piriform fossa beneath the mucous membrane and supplies the aryepiglottic fold and the mucous membrane of the larynx down to the level of the vocal folds. In its course beneath the mucous membrane of the medial wall of the piriform fossa it is accessible for injection of local anaesthesia providing excellent anaesthesia for most of the piriform fossa. The internal branch of the superior laryngeal nerve also carries afferent fibres from neuromuscular spindles and other stretch receptors in the larynx. The superior laryngeal nerve ends by piercing the inferior constrictor of the pharynx and unites with an ascending branch of the recurrent laryngeal nerve. This branch is called Galen's anastomosis and is purely sensory. The right recurrent laryngeal nerve leaves the vagus as it crosses the right subclavian artery and loops under the artery ascending in the tracheoesophageal groove to reach the larynx. On the left, the nerve originates from the vagus as it crosses the aortic arch. It then passes under the arch and the ligamentum arteriosum to reach the tracheoesophageal groove. In the neck, both nerves follow
cartilage; 17, vocal fold.
the same course and pass upwards accompanied by the laryngeal branch of the inferior thyroid artery. They pass deep to the lower border of the inferior constrictor muscle and enter the larynx behind the cricothyroid joint. The recurrent laryngeal nerve then divides into motor and sensory branches. The motor branch has fibres derived from the cranial root of the accessory nerve which supply all the intrinsic muscles of the larynx, except the cricothyroid. The sensory branch supplies the laryngeal mucosa below the level of the vocal folds and also carries afferent fibres from stretch receptors in the larynx. The relationship between the recurrent laryngeal nerve and the inferior thyroid artery is variable. The nerve may cross in front of, or behind the artery or may pass between the terminal branches of the artery. On the right there is an equal chance of the nerve being in any of three locations in relation to the artery, on the left it is more likely to lie posterior to the artery.
Laryngeal vasculature ARTERIAL
The arterial supply of the larynx is derived from laryngeal branches of the superior and inferior thyroid arteries and the cricothyroid branch of the superior thyroid artery (Figure 162.9). The superior laryngeal artery arises from the superior thyroid artery and passes deep to the thyrohyoid muscle. Together with the internal branch of the superior laryngeal nerve, it pierces the thyrohyoid membrane to supply the larynx. The inferior laryngeal artery arises from the inferior thyroid artery at the level of the lower border of the thyroid gland and ascends on the trachea with the recurrent laryngeal nerve. It enters the larynx beneath the lower border of the inferior constrictor to supply the larynx. The cricothyroid artery is a branch of the superior thyroid artery and passes across the upper part of the cricothyroid ligament to supply the larynx.
2140 I PART 16 THE UPPER AIRWAY
ANATOMY OF THE TRACHEA AND BRONCHI
VENOUS
The veins leaving the larynx accompany the arteries. The superior laryngeal veins enter the internal jugular vein by way of the superior thyroid or facial vein. The inferior laryngeal veins drain into the inferior thyroid veins which connect with the brachiocephalic vein. Some veins drain into the middle thyroid vein and then into the internal jugular vein.
LYMPHATIC DRAINAGE
The lymphatic drainage of the larynx is separated into upper and lower drainage groups by the vocal folds. The larynx above the vocal folds is drained by vessels that accompany the superior laryngeal vein and pierce the thyrohyoid membrane emptying into the upper deep cervical lymph nodes. The larynx below the vocal folds drains to the lower deep cervical chain often through prelaryngeal and pretracheal nodes. The vocal folds themselves are firmly bound down to the underlying vocal ligament and there are no lymphatics present in this plane.
General description THE TRACHEA
The trachea is a cartilaginous and membranous tube about 11 cm in length which extends from the lower border of the cricoid cartilage to the carina, where the trachea bifurcates into the left and right main bronchi (Figure 162.14). The bifurcation is at the level of T5 posteriorly and the manubrio sternal angle anteriorly. The trachea moves upwards during swallowing and down and forwards during inspiration. The trachea lies in the midline in the neck and deviates slightly to the right in the chest to reach the bifurcation. The trachea is D-shaped in cross-section with incomplete cartilaginous rings anteriorly and laterally and a straight mucous membrane posteriorly. The transverse diameter is greater then the antero-posterior diameter in adults. In children, the trachea is smaller and more mobile than in the adult and the bifurcation IS higher until the age of 10-12 years.
Right middle lobe bronchus
Left upper lobe bronchus
Figure 162.14
The tracheobronchial tree and
views seen on endoscopy. Right lung, upper lobe bronchus: " apical; 2, posterior; 3, anterior, middle lobe bronchus; 4, lateral; 5, medial, lower lobe bronchus; 6, apical; 7, medial basal (cardiac); 8, anterior basal; 9, lateral basal; , 0, posterior basal. Left lung, upper lobe bronchus: " apical; 2, posterior; 3, anterior; 4, superior lingula; 5, inferior lingula, lower lobe bronchus; 6, apical; 7, anterior hasal; 8, medial basal; 9, lateral basal; '0, posterior basal.
Chapter 162 Anatomy of the larynx and tracheobronchial tree
RIGHT MAIN BRONCHUS AND BRANCHES
At the tracheal bifurcation the right and left main bronchi are separated by a narrow ridge, the carina. The right main bronchus is about 5 cm long and extends to its division into the right middle and lower lobe bronchus. It is wider, shorter and more vertical than the left main bronchus making an angle with the carina of about 25-30° (Figure 162.14). It is therefore more likely that food, fluid and foreign bodies aspirated into the airway will enter this side. The right main bronchus has a posterior membranous wall and a series of cartilaginous rings which are similar in structure to those of the trachea. The diameter is about 17mm (±4mm) in men and 15mm (±4mm) in women. The right pulmonary artery is at first below and in front of the right main bronchus. The azygos vein arches over the right main bronchus. The right upper lobe bronchus arises from the right lateral aspect of the right main bronchus about 12-20 mm from the carina. It runs superolaterally to enter the hilum of the lung. It is about 1 cm in length and divides into three segmental bronchi which supply the apical, posterior and anterior segments of the upper lobe. The most notable variation is an apical segmental bronchus arising directly from the right lateral aspect of the trachea just above the carina. The right middle lobe bronchus arises about 2.5 cm beyond the origin of the right upper lobe bronchus from the anterior aspect of the right main bronchus. It is directed forwards, downwards and laterally, and after a short distance divides into the lateral and medial segmental bronchii. The right lower lobe bronchus divides into an apical segmental bronchus, a subapical segmental bronchus, a medial basal segmental bronchus and anterior basal segmental bronchii, which then divide into lateral and posterior basal segmental bronchii.
LEFT MAIN BRONCHUS AND BRANCHES
The left main bronchus is about 5.5 cm long and extends from the carina to its division into the upper and lower lobe bronchi (Figure 162.14). It is about 2-3 mm narrower than the right main bronchus and more horizontal, making an angle with the trachea of about 45°. It extends laterally beneath the aortic arch and crosses anterior to the oesophagus, thoracic duct and descending aorta. The left pulmonary artery lies first anterior then superior to it. At the level of T6, it enters the hilum and divides into an upper and lower lobe bronchus. The left upper lobe bronchus arises from the anterolateral aspect of the left main bronchus about 5.5 cm from the carina. It curves laterally for a short distance, then divides into the apicoposterior and anterior segmental bronchi, which enter the apical segment of the left lung. The apicoposterior bronchus further divides into the apical and posterior segmental bronchi. The caudal division of the upper lobe bronchus is the lin gular bronchus which divides into the superior lingular and
I 2141
inferior lin gular segmental bronchi. The left lower lobe bronchus is smaller than the right. Its first branch is the apical segmental bronchus which arises posteriorly about 1 cm below the origin of the lower lobe bronchus. The inferior lobe bronchus continues for another 1-2 cm, then divides into the anteromedial and posterolateral stem. The former divides into the medial basal segmental and lateral basal segmental bronchi and the latter into the anterior basal and posterior basal bronchi. The lung is divided functionally into a series of bronchopulmonary segments, each with its own bronchus and its own blood supply from the pulmonary artery. Each segment is surrounded by connective tissue continuous with that of the visceral pleura and forms a separate respiratory unit of the lung.
Structure of the trachea and bronchi The trachea and extrapulmonary bronchi consist of a framework of incomplete rings of hyaline cartilage united by fibrous tissue and nonstriated muscle. They are lined by mucous membrane. THE CARTILAGES
The tracheal cartilages are incomplete rings which stiffen the wall of the trachea both anteriorly and laterally. Behind where the rings are deficient, the tube is flat and is completed by fibrous and elastic tissue and nonstriated muscle. The cartilages are about 4 mm high and 1 mm thick. Two or more of the cartilages often unite partially or completely and are sometimes bifurcated at their extremity. They are highly elastic, but may become calcified with age. In the extrapulmonary bronchi, the cartilages are shorter, narrower and rather less regular, but similarly arranged. The first tracheal cartilage is broader than the rest and is sometimes joined with the cricoid cartilage to which it is connected by the cricotracheal ligament. The last tracheal ring is thick and broad in the middle and its lower border is prolonged into a triangular process which curves downwards and backwards between the two bronchi forming a bridge which underlies the carina.
THE FIBROUS MEMBRANE
Each of the cartilages is enclosed in perichondrium. This is continuous with a sheet of dense, irregular connective tissue forming a fibrous membrane between adjacent rings of cartilage and at the posterior aspects of the trachea and extrapulmonary bronchi where the cartilage is incomplete. The fibrous layer of the perichondrium and the fibrous membrane are composed mainly of collagen intermingled with some elastic fibres. The fibres cross each other diagonally allowing a change in diameter of the
l 2142 I PART 16 THE UPPER AIRWAY enclosed airway and the elastic component provides the property of elastic recoil when the membrane is stretched. Nonstriated muscle fibres are present within the fibrous membrane at the back of the trachea. Most of these fibres are transverse and are inserted into the perichondrium of the posterior extremities of the cartilage. They constitute the trachealis muscle. Contraction of these fibres reduces the cross-section of the trachea and bronchi. A few longitudinal muscle fibres lie external to the transverse fibres. The relative thickness of the muscle increases as the branching bronchi become narrower. The outer fibrous and muscular layers of the trachea and bronchi are continuous with the fascial planes of the surrounding muscle and the oesophagus and also with the loose areolar tissue of the mediastinum.
sympathetic fibres are post-ganglionic branches of the second to fifth thoracic ganglion with an occasional contribution from the stellate ganglion. The parasympathetic fibres to the trachea and bronchi are carried in the vagus nerve. The vagal efferents from the bronchial mucosa are bronchoconstrictor to the bronchial muscles and secretomotor and vasodilator to the bronchial mucous glands. The vagal afferents (from the inferior ganglion) are involved in the cough reflex. Efferent sympathetic fibres are dilators to the bronchi and the pulmonary arterioles.
Vasculature of the tracheobronchial tree BLOOD SUPPLY
THE MUCOUS MEMBRANE
The lining of the trachea and bronchi is a pseudostratified, ciliated, columnar epithelium with numerous goblet cells resting on a broad basement membrane. The cilia beat the overlying layer of mucus upwards to the larynx and pharynx, where it is swallowed. Deep to the epithelium and the basement membrane is the lamina propria, rich in longitudinal elastic fibres. Next is the submucosa of loose irregular connective tissue in which are situated larger blood vessels, nerve trunks and most of the tubular glands and lymphoid patches. Deep to the submucosa is the perichondrium and fibrous layer.
SMALLER BRONCHI
With increased branching of the segmental bronchi the epithelial lining becomes thinner and eventually single layered. There are fewer goblet cells on a narrower basement membrane. The cartilage plates also gradually become smaller and fewer in number and are not found in the wall of smaller bronchi. Circular muscle fibres almost completely surround the tube inside the cartilages, replacing the fibroelastic tissue layer found in the trachea. The muscles contain numerous elastic fibres and are arranged in an interlacing network, partly circular and partly diagonal, so that their contraction constricts and shortens the bronchus.
Nerve supply of the tracheobronchial tree The muscle fibres of the trachea including the trachealis are innervated by the recurrent laryngeal nerves which also carry sensory fibres from the mucous membrane. Sympathetic nerve fibres in the trachea are derived mainly from the middle cervical ganglion and have connections with the recurrent laryngeal nerves. The lungs are supplied by the anterior and posterior pulmonary plexuses situated at the hilum of each lung. The efferent
The trachea is supplied by the superior and inferior thyroid arteries. The thoracic part of the trachea and the bronchi to the respiratory bronchioles are supplied by the bronchial arteries. There are three bronchial arteries: two for the left lung and one for the right. The left bronchial arteries usually arise from the anterior aspect of the descending thoracic aorta. The right is more variable and may arise from the aorta, the first intercostal artery, the third intercostal artery, the internal mammary or the right subclavian artery. The arteries lie against the posterior walls of the bronchi. The tracheal veins drain upwards to the thyroid venous plexus. The bronchial veins form two distinct systems. The deep bronchial veins commence as a network in the intrapulmonary bronchioles and communicate freely with the pulmonary veins. They eventually join to form a single trunk which terminates in a main pulmonary vein or in the left atrium. The superficial bronchial veins drain the extrapulmonary bronchi, the visceral pleura and the hilar lymph nodes. They terminate in the azygos vein on the right side and in the left superior intercostal vein or the accessory hemiazygos vein on the left.
LYMPHATIC DRAINAGE
Lymphatics in the tracheobronchial tree arise in a plexus beneath the mucous membrane and penetrate the muscular coat to form a plexus in the outer fibrous membrane. Within this layer, pulmonary-associated lymph nodes are found. Lymphatics from the smaller bronchi drain into pulmonary nodes found around the airway. These then join lymphatics from the large bronchi to drain into bronchopulmonary nodes found beneath the points of division of the intrapulmonary airways. Inferior tracheobronchial nodes are found beneath the divisions of larger bronchi and the subcarinal group are found beneath the bifurcation of the trachea. Lymphatics from the' trachea drain into the pretracheal and paratracheal groups of lymph nodes.
Chapter 162 Anatomy of the larynx and tracheobronchial tree I
All of these lymphatics drain on to either the right or left paratracheal nodes by way of the right and left superior tracheobronchial nodes. The right superior tracheobronchial nodes drain the whole of the right lung and also communicate with the left upper lobe. The left superior tracheobronchial nodes drain the greater part of the left lung. The subcarinal nodes are important as they drain from both lungs and in turn drain to both right and left paratracheal nodes. Lymphatics from the right and left paratracheal nodes unite with vessels from the internal thoracic and brachiocephalic lymph nodes to form the right and left bronchomediastinal trunks which drain into the right lymphatic duct and left thoracic ducts or independently into the junction of the internal jugular vein and subclavian veins.
2143
The isthmus of the thyroid gland usually lies over the second to the fourth tracheal rings. Anterior relations of the trachea lower in the neck and superior mediastinum include the inferior thyroid veins, the thyroid ima artery (when present) and the thymus gland. The latter is small and insignificant in the adult, but quite large and fleshy in infants. Lower in the mediastinum, the left brachiocephalic vein, the arch of the aorta, the brachiocephalic and left common carotid arteries, the deep part of the cardiac plexus and a variable number of pretracheal and paratracheal lymph nodes lie anterior to the trachea (Figure 162.16). In infants, the brachiocephalic artery lies at a higher level and crosses the trachea just as it descends behind the suprasternal notch. The left brachiocephalic vein may project upwards into the neck to form an anterior relation of the cervical trachea and is a potential surgical hazard during tracheostomy. The right and left lobes of the thyroid gland which descend to the level of the fifth and sixth tracheal cartilages lie on either side of the trachea, as does the carotid sheath enclosing the common carotid artery, the internal jugular vein and the vagus nerve. The oesophagus
Relations of the tracheobronchial tree
TRACHEA Anteriorly, the trachea is covered by skin, superficial and deep fascia and by the sternohyoid and sternothyroid muscles in the lower part of the neck (Figure 162.15).
'<----12
2
Figure 162.15
3
Axial section at C7 showing the
relationship of the upper trachea to surrounding structures. 1, Sternohyoid muscle; 2, sternothyroid
4
muscle; 3, sternocleidomastoid muscle; 4, thyroid gland; 5, left vagus nerve; 6, cervical sympathetic ganglion; 7, left recurrent laryngeal nerve; 8, oesophagus; 9, inferior thyroid artery; 10, common carotid artery; 11, internal
5
6
7
8
9
10
11
jugular vein; 12, trachea.
2
3
~-'----~~Br- 7 8 9
4
5
10 11
Figure 162.16
12
relationship of the thoracic trachea to surrounding structures. 1, Second costal cartilage;
Axial section at T4 showing the
2, aortic arch; 3, left vagus nerve; 4, left recurrent laryngeal nerve; 5, thoracic duct; 6, 6
fourth thoracic vertebra; 7, superior vena cava; 8, right phrenic nerve; 9, tracheal bifurcation; 10, azygos vein; 11, right vagus nerve; 12, oesophagus.
2144 I PART
16 THE UPPER AIRWAY
lies behind the trachea and in the groove between them is the recurrent laryngeal nerve.
HILUM OF THE LUNG
The hilum of the lung transmits the following structures within a sheath of pleura: the pulmonary artery, two pulmonary veins, the bronchus, the bronchial vessels the lymphatics, the lymph nodes and the nerves (Figure 162.17). The bronchi are situated posterior to the pulmonary vessels and the pulmonary arteries lie above the veins. The bronchial vessels hug the posterior surface of the bronchi. All of these structures lie between the anterior and posterior pulmonary plexuses. The right side differs from the left in one respect in that there is an additional upper lobe bronchus which lies above but still posterior to the pulmonary vessels.
Impression of oesophagus
Cardiac impression Pulmonary veins
Bronchus Pulmonary artery
Anterior to the hilum of the lung on the left is the phrenic nerve and on the right the superior vena cava and the phrenic nerve. Posteriorly on the left side are the descending aorta and the vagus nerve and on the right is the vagus nerve. Superiorly, on the left is the aortic arch and on the right is the azygos vein. Inferiorly, the pulmonary ligaments are merely a sleeve of slack pleura allowing the necessary freedom for the structures of the hilum of the lung.
KEY POINTS • Slight swelling in the subglottic laryrix cart caUse severe airway obstruction in infants. • The preepiglottk and paraglottic spaces are connected· and allow the spread of tumours within the .larynx. • the. post~rior cricoarytenoid. is the only abductor of the vocal cords. • All . thelntrisicmuscles ofthe larynx, ·except the cricothyroid,are supplied by the recurrent laryngeal nerve. • Tl1erig~rmainbronchusiswider,. shorter ap.dmore vertical than theleftmaking it 11l0restlsceptible to aspiration;
Pulmonary ligament
FURTHER READING Middle lobe
Armstrong WB, Netterville JL. Anatomy of the larynx, trachea, and bronchi. Otolaryngologic Clinics of North America. 1995; 28: 685-99.
(a)
Negus V. The comparative anatomy and physiology of the larynx. London: Heineman, 1949. Impression of oesophagus
Meller SM. Functional anatomy of the larynx. Otolaryngologic
------7'~
Clinics of North America. 1984; 17: 3-12.
Impression of aortic arch Pulmonary artery
* Sadler T. Langman's medical embryology, 8th edn. Philadelphia: Lippincott Williams, 2000. Sasaki CT, Isaacson G. Functional anatomy of the larynx.
~ir-t-------'<---
Left bronchus
Otolaryngologic Clinics of North America. 1988; 21: 595-612.
a-I'--------t-=-
Pulmonary veins Cardiac impression Pulmonary ligament
(b) Figure 162.17
Structures in the hilum of the lung: (a) right
hilum; (b) left hilum.
Sinnatamby C. Last's anatomy, 10th edn. London: Churchill Livingstone, 1999.
* Williams P. Gray's anatomy, 38th edn. London: Churchill Livi ngstone, 1995.
163 Assessment and examination of the upper respiratory tract JEAN-PIERRE JEANNON AND MARCELLE MACNAMARA
Introduction
2145
Rigid laryngoscopy
Assessment in the clinic
2145
New techniques in laryngeal endoscopy
2150
Key points
2146
Conclusions
2152
Technique for flexible laryngoscopy
2146
Best clinical practice
2152
Operative laryngoscopy
2148
References
2152
Key points
2149
2149
The data in this chapt er are supported by Medline, PubMed, hand searches and the Cochrane review database.
INTRODUCTION
It is not routine practice in the otolaryngology clinic to undress a patient in order to examine the respiratory
The purpose of the chapter is to review the techniques
system, however, this should be done if the clinical history
available for accurate and safe examination and assess
suggests chest disease, such as suspected metastasis or
ment of the upper respiratory tract. The otolaryngologist
severe chronic obstructive airways disease (COAD) limit
must have a systematic method to process symptoms and
ing fitness for surgery, that might impact decision making
signs in order to achieve the correct diagnosis.
for the ENT condition. Clinical signs and symptoms of upper respiratory impairment in clude :
ASSESSMENT IN THE CLINIC Evaluation of the patient begins as soon as he/she enters into the clinic room. Preliminary assessment of t heir respiratory status can be made during history taking. The pat ient with respiratory distress may be unable to speak a few words before needing to rest, whereas a healthy
• dyspnoea; • t achyp onea ; • stridor; • dysphonia; •
cyanosis ;
•
use of accessory muscles of respira tion.
individual will converse without difficulty. The quality of
The examiner should be aware of general systemic signs
Persistent or progressive dysphonia may suggest
as
the voice can also be subjectively monitored at this time.
an
of disease that are relevant to the respiratory tract, such cigarette
stammg
j aundice
organic lesion in the larynx compared to intermittent
anaemia
dysphonia that may suggest a functional disorder.
important.
and
to spider
the
hands,
naevi,
clubbing,
which may
be
2146
I PART 16 THE UPPER AIRWAY
Nasal airway
The upper airway begins with the nasal cavity and therefore the nasal airway should always be assessed. A1though it is covered in later chapters, a summary is provided here. Nasal airflow and patency should be subjectively assessed through each of the nares using palmar surface of the thumb or a shiny lax: tongue depressor. Anterior rhinoscopy should be supplemented with endoscopic examination of the nose in order to inspect the posterior nasal cavity.
; _t(� I'QINt�'; ";
, "
;" ';"
.
: . \ .- }f: :: ;::; :
,,
";.
- '� ;';£;�1��;�¥1!1��lfE��:���I;� �� "
:- . ,":",¢9mp�cations. �s116uld ,rp.,�p."thgt: .It '�:lliViv.e{a�� . . . - �pat�. 'cit the range of ot91MYhgdlogy skills. ' .' - '-'j , \ r�"', ',ElexiHfe·. enqoscQPY -is· righ �V:iepllJdng; th;e • ' , �,'� ''-'-ab�>¥e a�' ��e�.�rSt cho1�{-ot t001"(or' .;, : ' ,' ' : ..>.\-.::,: " ::': .. ex�m�l1a�i(j"n: of the :u'p�;e r -aerodigestive-(t a�(:'-' . ',:-" w'ith ext�nded uses including milk nasendoscopy, videoe.ndoscop}' including
Laryngoscopy
Indirect laryngoscopy examination with a mirror, a technique with an illustrious historyl is still used as a method of visualizing the larynx. As a technique, it has some limitations including perceptual errors/ difficulties in user reliably recording side of lesion, learning curve in acquiring and maintaining ski1l3 and a significant failure rate which, prior to the era of readily available flexible endoscopy, often mandated direct endoscopy under general anaesthesia. (*1 Significant advantages include widespread availability in all ENT departments, low cost to buy and maintain and a learning curve that is not insurmountable. Regular practice on all suitable patients in the early years (an anatomic model to facilitate this process has been described3) and continued later use can often be the saving grace. [*] A small amount of literature exists on minor laryngeal procedures that can be carried out with indirect techniques apparently successfully,4, 5, 6 including obtaining photographic images as the sole operator. [**I*} It is a procedure free of complications except for gagging and failure to visualize the lesion as illustrated,7, 8 unfortunately occurring more frequently than with flexible or direct laryngoscopy. (**] Failure of indirect laryngoscopy suggests that microlaryngoscopy may be difficult.9 [**) Magnifying laryngeal and nasopharyngeal mirrors have been described. 10 [*} Endoscopic assessment, either with a rigid or flexible laryngoscope, has supplanted mirrors due to better optical resolution and higher sensitivity.il, 12 [***/**} Endoscopes in the ENT clinic should now be considered the standard of care. The rigid Hopkins rod system uses 70 or 90° angled lenses and allows an excellent view of the larynx through a transoral approach. This is the favoured technique for laryngologists in the 'voice clinic'. This is because the wider rigid rod lens produces a much higher optical resolution for more detailed assessment of phonation.13 [***] Laryngoscopy can be supplemented with stroboscopy, laryngography or digital acoustic voice analysis (see Chapter 166, Objective evaluation of the voice),
hypopharynx and
cervical oesophagus, biopsy,,,
' J.'(,�; ," i'�.1pd foreign body removal] with ,the ':':'�:'�"'�yaiJabihit)' of increasingly fine bore biopsy ,\�· j-!. thannels) as well as paediatric and, iJl ,:>�'i:-'i':,'�p;articular, n e on ata l assessment. ,:�::,:��.':�:pespite eight randomized studies on top ical<'�!: "., ,�S.,,/�:paesthesia for flexible en dosc opy, the " ·7;·�video.c:e for choice of agent and the extent 0f ; .:--: ';·· ��. i�:; f..' l:::,!h:��e.�t:a.re not clearcut. ;�-: ·�:&;. at�Te' :cp-nsent Q�11 ..•, Th;�r,e�)is"up significant l�t�r . , 1"�"":" J��,}l�S ahd; in' particular, : c'o�p.ii<;a:tldps wbJ9h/1. :;=:,. e c :"" , s "�dwi�; . i':'� ��hlde :�is omfort of varii&l '�,: 6c�\t sio�rllij..epista).is with dilfi�tift ifishdo'n,'T{' i "::��'; e'x2es'�i:V;�' gagging, coughing and transient laryngospasm, poss�ble gluteraldehyde allergy and infection due to .laryngoscope 'cQntamjnati0n. '., , '�:\.':" :pote:ntial area� ,'df c-pncern"possibly.·a:.v6�(lt;d:·" '. '-hy' widespre'ad'1:l,s:e�of . ." " . sheaths. " �' . ,
:'(;)":'," :
�i :Z��� �;h �2
� :��
',- �"
"
�
'.
'
TECHNIQUE FOR FLEXIBLE LARYNGOSCOPY
The endoscope is passed through the anterior nares, along the floor of the nose under the inferior turbinate. Passage between the middle and inferior turbinate or through the opposite nostril may be necessary if the airway is narrowed. Once the endoscope is in the postnasal space, the patient is asked to inspire through the nose, this opens the postnasal sphincter allowing passage of the endoscope into the oropharynx (Figure 163.1). A step- wise assessment 0 f the larynx is made: the vallecula is inspected (by tongue protrusion), the supraglottic larynx, followed by the glottic larynx. Attention should be taken to record accurately the correct side of any lesion identified as errors are common. 14
[**]
Chapter 163 Assessment and examination of the upper respiratory tract I
2147
during difficult insertion, excessive gagging in the absence of local anaesthesia, coughin�, transient laryngospasm
and possible gluteraldehyde allergy and infection due to laryngoscope contamination. Paediatric, including neo natal, flexible awake nasendoscopy are now accepted
procedures but, particularly in the latter group, are more frequently associated with more frequent episodes of
significant oxygen desaturation, laryngospasm, broncho spasm and coughing?8
[***]
Psychogenic pain and other
symptoms may be experienced by some patients which may last for prolonged periods. The increased prevalence of MRSA, hepatitis Band C and HIV has resulted in more rigorous infection control systems to be implemented for all invasive procedures. Sterilization practices vary considerably throughout the country?9 Figure 163.1
Flexible laryngoscopy in the clinic.
milk nasendoscopy for swallowing evaluation,I5 videoen doscopy of the hypopharynx and cervical oesophagus
16
including biopsy and foreign body removal through a biopsy channel, flexible endoscopic evaluation of swallow ing
with sensory testing, paediatric adenoid assessment17
[***1**1 *)
Topical nasal administration of local anaesthetic is often used prior to flexible laryngoscopy in the clinic in order to decongest the nose and facilitate examination.19 percent) or as paste
(4
use disposible sheath systems and some still only wipe cols for high risk patients demonstrated a parallel lack of uniformity. A similar divergence in practice has been recorded in South
well
as contamination
[****)
•
[***]
derivatives
cophenylcaine or amethocaine being used?O authors have
such as
[***]
The risk of transmitting infection between scope and
vCJD transmission is probably extremely low provided scrupulous attention is placed to the detail of decontamination. •
The risk of transferring infection from the user to the scope is minimized by removal of all jewellery, including wristwatches, proper hand decontamination
questioned the
and the wearing of disposable gloves. •
four are double blind randomized trials, 22. 23, 25, 26, 27 but all
Should an outbreak of infection occur, a logbook should be available which records patient details,
have some methodological flaws. [***] Two of the double blind studies23,25 unfortunately draw inappropriate
responsible for sterilization, and the method of
conclusions from their data. A further well-designed,
sterilization. Details of the instrument used,
time and date of use, name of
all options may be warranted. Current e v idence suggests
that the benefits of local anaesthesia cannot be large in
lI ser
and person
including serial numbers, should be recorded in the
sufficiently powered, double blind study incorporating
patient's notes. •
Appropriate training programmes for all involved staff and an up-to-date list of authorized personnel
these circumstances.
and what each individual authorization covers should
The new consent policy adopted recently in the UK has been designed to reduce patient-doctor complaints and
be available in each department. Policies need to
medicolegal
cover these issues when the scopes are used
claims.
It
has
been
suggested
that
all
fonn to be completed. Thus far, it is not routine clinical
•
disinfection of the endoscopes is required.
flexible laryngoscopy in the clinic. Currently, there is no No significant discussion of complications of flexible
Even if the disposable sheath is the preferred mode of ensuring clean nasendoscopy, daily high-level
practice to obtain written consent before performing literature on this subject.
in a
variety of settings outside ENT departments.
interventions, including laryngoscopy, require a consent
hs '.-
[*]
but for gastroscopes is 1 in 1.8 million. The risk of
Some
necessity of using any anaesthetic for this procedure?1, 22 [***] Eight randomized studies20, 21, 22, 23, 24,25, 26, 27 have been published, of which
Nat i onal guidelines for the
patient has not been quantified for nasendoscopes,
the delivery system for
newer
[*J
The main points to come out of these guidelines
are summarized below.32
percent). However, concerns
from
have resulted in
Africa.3o
cleaning of nasendoscopes have now been produced.31
regarding the possible cardiotoxicity and drug misuse, as cocaine,
(67 percent) use a chemical
endoscopes betw'een patients with alcohol wipes. Proto
Cocaine was traditionally used in the past either as aerosol
(10
Most hospitals
delivery and duration of soak vary widely. A few hospitals
Newer extended uses of flexible nasendoscopy in elude
and neonatal upper airway assessment 18
[*]
soak system) but the type of disinfectant, method of
•
Used scopes from locations distant to the site of decontamination should be transported to the place
nasendoscopy exists in the literature but these include
of decontamination in a labelled disposable bag in its
discomfort of variable degree and occasional epistaxis
case if possible.
2148 •
•
•
I PART 16 THE UPPER AIRWAY
Decontamination involves both cleaning and high level disinfection. Methods chosen need to be approved by manufacturers to uphold service contracts and warranties. Inspections of scopes should be visual and by formal leak testing. Cleaning may be manual or mechanical but must remove all visible debris. It is no longer possible to use gluteraldehyde for chemical high-level disinfection owing to unacceptable risks to staff. Suitable liquids include electrolyzed saline (sterilox); chlorine dioxide (tristel); peracetic acid (steris, nu-cidex, perasafe, gigasept). Disinfectant impregnated wipes are not suitable as the sole mode of disinfection. There is no ideal agent but the above are currently considered acceptable.
Some departments still use gluteraldehyde baths, which produce the highest level of disinfection,31 and/or mechanized cleaning systems between each fibreoptic examination, the time taken for each of these can be between 10 and 20 minutes.33 [****1*] Gluter
aldehydebased high-level disinfection (Cidexplus percent
=
gluteraldehyde)
poses
significant
3.2
safety
issues for staff and patients, as well as institutional cost concerns,34 because of the need for staff time and training, fume cupboards for extraction of vapours, slow
turnover
of
endoscopes
and
therefore
large
numbers of expensive endoscopes required for a high turnover
service
such
as
ENT.
[*]
Staff
health
concerns relate to occupational asthma,35 sneezing
(38
percent), headache (32 percent), watering eyes
(8.3
percent), skin rash and chronic cough
[**/*]
(25
percent).36
Most of these problems pertain to staff handling
endoscopes after disinfection but, if endoscopes are not
dry
on
delivery
to
medical
staff,
transmitted to doctors and patients.
may
be
A recent best
nursing best practice forum34 made sensible recom mendations, including an overall decrease aldehyde-based high-level disinfection.
[*]
in
gluter
Mechanical
cleaning processes for nasendoscopes are less impor tant than for gastrointestinal endoscopy as the level of contamination is much lower. Many different types of machines exist but there is no real evidence base for
do not require a special machine for application and removal which, if previously improperly used, regularly damaged the endoscope covering at the tips which was costly or impossible to repair.39 [****/*] There was no significant difference between sheathed and unsheathed endoscopes from the user and patient perspective, as well as in image quality.40 [****] This may well provide a much more cost-effective, user friendly and safe solution than gluteraldehyde disinfection. Flexible endoscopes are expensive and relatively fragile instruments. They require careful handling, maintenance and cleaning; a designated health practitioner should be responsible for their care. Storage of endoscopes is best achieved with the scopes hung vertically in storage cupboards. This prevents repeated twisting and bending of the scope, which will result in breaking of the optical fibres thus reducing the lifetime of the scope. Considerations of consent, accurate documentation of findings and sterilization are important as they all have time and resource implications in the clinic.
OPERATIVE LARYNGOSCOPY Anaesthetic considerations for laryngoscopy in the operating theatre
Accurate assessment of the larynx under general anaesthetic requires a systematic approach with coopera tion of both the otolaryngologist and anaesthetist work ing in the shared airway. It is therefore important to develop a good working relationship with one's anaes thetic colleague and have a system that both are happy to work with. Laryngoscopy, when applied to appropriate patients, can be performed safely as a day case procedure.41 [**] There are several methods of performing laryngos copsy under general anaesthesia and there is a balance between maintaining a secure airway and obtaining a clear unobstructed view of the larynx. A systematic review of each technique will be discussed, the clinician must decide upon a technique that is most satisfactory for him or herself.
their necessity or efficacy in otolaryngology practice. More research is needed in this area. Out of hours cleaning and disinfection of nasendoscopes by junior medical staff is a real problem, mainly due to lack of knowledge and access to the appropriate facilities usually based in outpatient departments.26,37 Most
[***] ENT departments are implementing a flag
system to record details of each laryngoscopy episode.
Disposable sheaths have been introduced in order to reduce the necessity of formal sterilization between examinations. These have been shown to be effective in acting as a barrier to infection, even by viral particles,38 and they have now been improved in design so that they
MICROLARYNGOSCOPY TUBE
The microlaryngoscopy tube is a small diameter cuffed endotracheal tube (ET), which is placed in the posterior glottis. The diameter ranges from 16 to 22 French gauge. This type of tube has been shown to be safe for operative laryngeal microsurgery.42 [**] If transoral laser micro surgery is planned, specifically designed noncombustible nonreflective laser tubes are used. These have indicator dyes incorporated into the cuff to identify whether the cuff is damaged, in order to reduce the risk of an airway fire hazard.43, 44, 45 [**]
--
Chapter 163 Assessment and examination of t h e upper respiratory tract I
., V isualization of difficult areas can be
TOTAL INTRAVENOUS TUBELESS ANAESTHESIA
This
tec hnique
continuous
involves
anaesthesia
intravenous
infusion
maintained
of
2149
propofol
improveq
by
with
topical lignocaine and the patient br eath ing sponta
n eously. It has been described for both diagnosti c and
•
with spe cialist rigid scopes and/or
'the use of angled Hopkins rods.
__N.�w techniques include contact endoscopy
, . arid lar yngeal
ultr a sound .
therapeutic laryngoscopy, including laser microsurgery.
It is not recommended for high risk patien ts (ASA III or or
IV)
pat ients
with
an
obstructed
airway.
Total
intravenous tubeless anaesthesia should only be under taken by those who have expertise in this te chn ique.46 • 47,48
[***1**]
RIGID LARYNGOSCOPY
i
The pat e nt is prepare d and anaesthetized as standard for
the operating theatre. The p o s ition is supine, with head extension and neck flexed in order to open the lar �geal
inlet. Eye cover, dental pr otect ion and septic dr aping are
HIGH FREQUENCY JET-VENTILATION
-
High pressure j et
(Venturi)
ventilation of anaesthetic
gases without an ET tube can be ad mi nistere d v ia the
supraglott is, glott is, subglottis or via the transtracheal!
cricothyroidotomy route . This technique has been widely
49 surgery, in clu din g laser, the
used for endolaryngeal advantage
being
the
is
airway
free
of
combustible
material, thus providing a clear view of the larynx and 4
dee p anaesthesia is obtained to allow for microsurge r y.
[***]
8
L ar ge multicentre studies of 643 pat ients based in
France and 872 patients in the USA have shown low
complication rates using this technique. Problems such as pneumothorax were encountered in 1 percent , hypoven
tilation in 2 percent and surgical em physem a in 8 percent of cases. 50. 51
[***]
i
The Ventur tec hnique has also been
[**)
described in p aediatric p ractice.52
Relative contra
indications to using this technique would
or obstructed
airway,
difficult
access
(micrognathia/overhanging teeth) or
be the unstable to
the larynx
respirator y [**]
(with emphysematous bullae ) .52.53
failure
applied.
The widest scope to maximize vision
orally in
is passed per
the midline and the tongue is negotiated in order
to visualize the epi glottis . Care must be taken to prevent
dental trauma and trauma to the lips. The endoscope is
used to elevate the epiglottis in order to visualize the
larynx. Different scopes can be utilized to inspe ct the subsites of the endolar ynx, such as the anterior commis
sure scope which is designed to maximize the view of the an terior glott i s
(Figure
163.2).
Suspensi on of the
lar yngo sc ope allows the surgeon to have both hands free to operate.
Rigid laryng osc opy offers improved visualization of
i
the larynx through better illumination , h gher magnifica
ti on an d wi de r an d deeper fields of vision. By inc orpor
atin g the microscope and combination of 0, 30 and 70°
angle d endoscopes , a full perspec tive of the endolarynx
can be apprec iated .
The angled en doscopes allow better perspectives of the
ventricle, free edge and under surface of the v ocal co r d .
It is important to define and reco rd accurately the
findings of the laryngoscopy. The site, extent, dimensions,
shape, colour and surface characteristics of the lesion should be defined. Vocal cord
")K:E'i �: 'POINts ; , ':\ ' �.,� '�:}_� ��. - :,.. � �'->-.....:{�� - �;:,. � .� ,'-::�>': �r�;'.. ",.�;"" �,.::..j;- . «"� ,�1 �, 'IT'-' : � . ·· " . ,,·.. .-· '.·�'�.:..b ' -,: ' ::>.c' ';--? .." - ,,:� .".,,�!',;; : "'. ..., :.,. .. - ; ; , � _7 :� , .," ,' ,�, , ". ', . ;' > �' �Clos� £oQperation with � ' rie,',Sr an�e�:tlletic _ .-" r :;t� coIiI��e!s in deciding w'heili�!", "to'opt'Jor�_ -
�,
0 � ••
•
.... . ,� . . \
. •.
._
-, ;--i·�;\. usi�g-a:�icrolaryngosco '<\-�l�ttaven�-�s'tube'less
\'
•.
'
diagrams s hould be en courage d (Figure
.
p-y tube,,b-t0tal';"'-
anaest1:Iesia 'or high
, '. c:o::�ireqU'en�y:.jet 'V�il�i�J�� 6ri
v
mobility and airway
patency should be re co r de d. The use of printe d operative
�
163.3).
Photo doc umentation is bec omin g an impor tant part
,
�
of otolaryng olo gy practice.
It
improves case review
between clinicians and is increasingly forming p art of
, <" "'tW6 bein g co n'friindicate d "in the o bsttuc ted " : "air!'Vay� -.. - , ' . . • . The corre-ct 'patrent positi on for rigid "
.
,
" "
'
� , -
,
"
"
'
'
:·';Ia.�Yngosco'py
: , , inc ( n'eck ifexed- to' open 'the laryngeal inlet. ' . A �de ch o ice ' o ., ' . a��ila ble ) usually the widest scope to maximize vision should be' chosen with
suspension allowing '.
free.
the surgeon both hands
Accurate recording on preprinted diagrams
and/or photo documentation is ideal.
Figure 163.2
A selection of rigid endoscopes for laryngoscopy.
2150
• PART 16 THE UPPER AIRWAY
L
R
Figure 163.3 R
N
T
routine practice in the current medicolegal climate. High
resolution digital imaging is now available to facilitate still, video and hard copy documentation.
iodine.
A
in vivo and in situ. The
modified
Hopkins
rod
laryngoscope is applied against the mucosa of the larynx.
At
magnifications
of
x60
and
x 150,
cytological
characteristics of the cells , nuclei and cytoplasm can be
appreciated. 54
[**]
Premalignant conditions,
research
tool
to
as
a substitute for histology, but a
allow
better
understanding
technique in the larynx involves applying the ultrasound
probe against the external surface of the larynx during
microlaryngoscopy. This holds potential in providing
information regarding invasion of deeper compartments of the larynx, such as paraglottic and pre-epiglottic
spaces.S7
[**]
The
usefulness
of
laryngology is still being evaluated.58
this
technique
in
[**}
such as
dysplasia, could therefore potentially be detected earlier. It is not designed
but does show promise for a wider application in the
Ultrasound scanning is a well-established method of
process involves staining the epithelium with methylene Lugors
The use of contact
imaging in the head and neck. A new application of this
This new technique allows for microscopic assessment of
or
[***/**J
endoscopy in the larynx is confined to clinical research
Laryngeal ultrasonography
Contact endoscopy and microlaryngoscopy
blue
and formal histology.55,56
future.
NEW TECHNIQUES IN LARYNGEAL ENDOSCOPY
the epithelial cells of the larynx
Printed operative diagrams used to
record fi ndings.
L
M
of
the
cytological changes which occur in the laryngeal epithe
lium in the transition from normal to disease. Preliminary
studies have shown good correlation between its findings
Assessment of the obstructed or difficult airway Those patients that present for endoscopic assessment
with upper airway obstruction pose a complex problem
Chapter 163 Assessment and examination of the upper respiratory tract I
for the otolaryngologist and anaesthetist. This short section will discuss the assessment of these patients and provide a management algorithm.
PREOPERATIVE ASSESSMENT
Preoperative assessment must be carried out in order that both surgeon and anaesthetist are prewarned of potential problems beforehand. Mild to moderate chronic airway obstruction may exist undetected by the patient . These patients may have compensated for this compared to the patient that presents with acute severe airway dysfunc tion. Questioning regarding presence or absence of stridor at rest or on exertion, lying flat, or when bending down, decreased exercise tolerance and nocturnal dyspnoea when lying supine are all indicative of a problem. An assessment of the patients' respiratory reserve is essential. Those patients with respiratory failure will tend to desaturate rapidly if there is prolonged or difficult intubation. Medical conditions, such as rheumatoid arthritis, obstructive sleep apnoea, acromegaly and mucopolysacharidosis, have an association with difficult airway management, and likewise craniofacial syndromes, particularly Treacher Collins and Pierre Robin syndrome. Features suggesting a difficult airway on general examina tion are given in Table 39.2 in Chapter 39, Recognition and management of the difficult airway. Specific features include short neck, receding jaw, maximal mouth open ing/gape less than three fingerbreadths, inability of lower jaw to protrude beyond upper jaw (jaw slide), short thyromental distance less than three fingerbreadths indicating high larynx, Malampiti score which classifies visibility of oropharyngeal structures and limited atlan toaxial movement. The anaesthetist usually carefully assesses these specific features, but some appreciation of the potential problems by the surgeon is important. Prediction of potential airway difficulty is a complex business but can be rewarding when severe or obvious problems are identified. When there are no obvious problems, evaluation is imperfect and safe airway management depends on the adoption of a strategy that is able to respond to unexpected difficulty with intuba tion or oxygenation. Specific investigations other than careful flexible nasendoscopy are rarely safe in acute airways obstruction but plain radiographs, CT/MRI and flow loops may well be indicated in chronic stable obstruction, particularly in suspected subglottic lesions. All patients undergoing panendoscopy for stridor should be counselled and consented regarding the possibility of a tracheostomy being performed.
OPERATIVE MANAGEMENT
Securing a safe airway is the primary aim of the procedure, followed by an accurate assessment of the
2151
cause, level and degree of airway obstruction, a biopsy may also be necessary. It should be remembered that tumours of the supraglottic larynx and tongue base are a particular problem. A moderate chronic airway obstruction may develop into complete obstruction with respiratory arrest when the patient lies supine with muscle relaxant administered. Tumours may be haemorrhagic and friable and this may make the intubation difficult. The difficult intubation equipment should be ready for these patients which includes a selection of laryngoscopes, intubating bougies/guidewires, endotracheal tubes and fibreoptic intubation equipment. The team should decide upon the following options for airway management: • •
•
•
awake fibreoptic intubation; induction anaesthesia and endotracheal intubation with/without guide wires or bougies; induction anaesthesia and jet ventilation (endolaryngeal or percutaneous); local anaesthetic tracheostomy.
The chosen airway strategy must have a plan A and plan B, both for intubation, ventilation and extubation (see section on strategy and alternative techniques in Chapter 39, Recognition and management of the difficult airway). The patient is asked to breathe 100 percent 02. Looking at the bag will indicate the degree of airflow. Anaesthesia may be induced in the operating theatre, alternatively the surgeon should be in the anaesthetic room with the rigid laryngoscope ready and tracheostomy set available for a surgical airway to be secured if necessary.
Failed intubation
If the anaesthetist is unable to identify the glottis and intubate, the patient should be maintained with the facemask and reoxygenated. The ENT surgeon should then attempt endotracheal intubation. The rigid broncho scope is often quoted as a useful method of finding the glottis in difficult airway patients. The author's preference is to use the anterior commisure scope to visualize the glottis. A rigid bougie can be passed through the scope into the trachea and a small ET tube passed over it. In certain difficult cases with the airway obstructed by tumour, a retrograde intubation approach can be adopted. The rigid laryngoscope scope can be passed . into the hypopharynx and then slowly withdrawn WIth . · 59,60 [*J the tip angled antenorIy to see the gIottiS. Tracheostomy under local anaesthetic is not an �asy procedure in a patient with an acute airway obstructIOn. Consent for emergency tracheostomy should always be taken when planning any surgical procedure that may
2152
I PART 16 THE UPPER AIRWAY
but the principles of use remain essentially
have an associated significant risk of airway obstruction.
handling
T he principles of emergency tracheostomy include:
unchanged.
allow
New
palpation of the trachea. In t he
conscious patient, constant reassurance is mandatory as the patien t may be struggling and unable to lie still for a long period of time.
Pressure on the larynx '
(20 mL of
1 percent
photo
documentation
will
techniques
include
contact
endoscopy
and
laryngeal ultrasound. The management of the obstructed airway will always
but has been hugely facilitated by the much wider availability
remain amongs t otolaryngology s greatest challenges
of awake fibreoptic intubation skills in most anaesthetic departments .
lignocaine) should be injected if t ime or pa t ient condition permits and is strongly advocated
quality
'
during dissection may worsen the pa t ient s sense of obstruction. Local anaesthesia
High
increasingly become the norm.
• Positioning t he patien t supine with sufficient neck extension to
,
.
• T he opera tion is more difficult in small children and fat necked adults because of difficulty in tracheal
Best clinical practice
palpation. • A vertical midline incision is made from the inferior aspect of the thyroid cartilage to the suprasternal notch and continued through the infrahyoid muscles and thyroid is thmus irrespective of bleeding although ,
an experienced assistant providing suction and
Examination of the upper airway should include:
.! flexible nasolaryngoscopy; ./ microlaryngoscopy; .I Hopkins rod telescopes: ./ photo documentation.
retraction is most helpful.
• After carefully palpating for the cricoid cartilage in
ord er to avoid cutti ng it, a vertical incision is made
in the trachea from the second to fourth ring, the knife rotated through 90° and an appropriate t u be rapidly inserted
•
.
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Ku PK, Tong MC, Kwa n A, va n Hasselt CA. Modified
and Laryngology. 1 99 5 ; 1 04 : 3 3 3. 55.
tubeless a nesthesia during e ndoscopy for assessment of 2003 ; 8 2 : 1 2 1 -5.
Otology. 2000 ; 1 1 4 : 43 7 -40. 56.
Aun CS, Houghton IT, So H Y, Van Hasselt CA, Oh TE.
Paludetti G. Preliminary experiences with contact endoscopy of the larynx. European Archives of Oto-rhino-
Willia m s SR, va n Hasselt CA, Aun CS, Tong MC, Carruth JA.
laryngology. 2000 ; 2 5 7 : 68-71 . 57.
l a ser surgery of the larynx. American Journal of Otolaryngology. 1 993 ; 1 4 : 2 7 1 -4.
1 9 99 ; 256: 3 1 6-22. 58.
I hra G , Hieber C, Scha bernig C, Kraincuk P, Adel S, Ploch I
1 7 67-70. 59.
Soffer m a n RA, Johnson OL, Spencer RF. Lost airway during a nesthesia i nduction : alternatives for m a na gement.
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Laryngoscope. 1 997 ; 1 07 : 1 47 6-82.
9 40-2.
Bourgain .I L, Oesruennes E, Fisch ler M, Ravussin P.
Ta mura E, Kitahara S, Kohno N. Clinica l assessment of intralaryngeal ultrasonography. Laryngoscope. 2001 ; 1 1 1 :
W, Aloy A. Supra l aryngeal tube less com bined highfrequency jet ventilation for laser surgery of the larynx
Arens C, G l a nz H. Endoscopic high-frequency ultrasound of the larynx. European Archives of Oto-rhino-Iaryngology.
Tubeless a nesthetic technique for optimal carbon dioxide
50.
Carriero E, Ga l li J, Fa d d a G, Oi Girola mo S, Ottaviani F,
Tubeless a naesthesia for microlaryngeal surgery. Anaesth esia In tensive Care. 1 99 0 ; 1 8 : 497 -503 .
49.
Wardrop PJ, Sim S, McLaren K. Contact endoscopy of the larynx: a qua ntitative study. Journal of Laryngology and
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Andrea 1Vl, Oias 0, Sa ntos A. Contact endoscopy during
endotracheal tube i n laser laryngea l surgery: experiences tubes. Laryngoscope. 1 99 0 ; 1 00 : 1 283-7.
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Ohara SS, Butler PJ. High freq uency jet ventilation for microlaryngeal laser surgery. An i m proved technique.
surgery of the larynx. Laryngoscope. 1 9 7 6 ; 8 6 :
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Ihra G , Hieber C, Adel S, Kasha nipour A, Aloy A. Tubeless com bined high-frequency jet ventilation for
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164 Physiology of the larynx LESLEY MATHIESON AND PAUL CARDING
Introd uction Laryngeal innervation Functions of the larynx Key points
2155 2155 2159 2162
Deficiencies in current knowledge and areas for future research References
2162 2162
The information in this chapter can be explored more extensively by undertaking a Medline search, using the key words laryngeal innervation, neuroanatomy of phonation, laryngeal mechanoreceptors, phonatory biomechanics, vocal fold vibration, vocal registers.
INTRODUCTION
LARYNGEAL INNERVATION
This chapter is concerned with the functions of the larynx, with particular emphasis on its role as the source of the voice. The motor and sensory laryngeal nerve supply is described and the neuroanatomy of phonation is discussed in greater detail. A concise section on the role of the larynx in swallowing, coughing and effort closure is followed by a more extensive description of the biomechanics of phonation. It should be noted that it is essential to be familiar with the considerable potential range of laryngeal adjustments which can occur in normal phonation, in order to avoid drawing inappropriate conclusions during laryngoscopic examination. The larynx has a number of functions, the most important of which is to protect the airway by means of its capacity for sphincteric action during swallowing and by its sensitivity. It also acts as a valve which can control air pressure and airflow, and as a vibrator for generating sound; both functions are of fundamental importance during breathing, weight bearing and phonation. This chapter is concerned with the neurology and biomechanics of the laryngeal functions and lays the foundations for Chapter 165, Voice and speech production.
The vagus nerve (cranial nerve X) provides all the innervation to the intrinsic laryngeal muscles and the sensory structures of the larynx. It also supplies the pharynx, palate, trachea, bronchi, lungs, heart, external ear and parts of the gastrointestinal tract. Some of the fibres of the vagus originate in the medulla in the nucleus ambiguus, whereas others originate at a higher level. Fibres from the upper section of the nucleus ambiguus join the glossopharyngeal nerve (cranial nerve IX) and those from the inferior portion join the accessory nerve (cranial nerve XI). The nerve fibres originating in the cranial nerve nuclei form the lower motor neurone pathway. The right and left vagus nerves, which they form, provide ipsilateral innervation to the larynx. The neural 'commands' that travel down to the cranial nerve nuclei are largely responsible for what is ultimately transmitted to the laryngeal muscles via the lower motor neurone pathways. These commands are fashioned by complex interaction of, and constant remodelling by, many cortical, basal ganglia and brainstem influences. Cranial nerves IX, X and XI are so intimately connected in the medulla that all the muscles supplied
2156 I
PART 16 THE UPPER AIRWAY
by them are frequently involved either equally or progressively in medullary lesions. For this reason, Walshe 1 grouped them together in pathological conditions affecting the nucleus ambiguus in what he termed the 'glossopharyngeal-accessorius complex'. Nuclear lesions of the vagus may be associated, therefore, with paralysis of the palate, tongue and larynx. The vagus forms a flat cord from its many united filaments and leaves the skull through the jugular foramen, passing vertically down the neck within the carotid sheath. It branches to form the superior laryngeal nerve (SLN), the recurrent laryngeal nerve (RLN) and the pharyngeal nerve. • The superior laryngeal nerve branches off from the vagus at the ganglion nodosum (inferior ganglion), below the level of the jugular foramen and subdivides into the internal and external superior laryngeal nerves. The internal branch of the superior laryngeal nerve consists of both sensory and parasympathetic secretomotor fibres which supply glands within the tissue above the level of the vocal folds. This branch, in turn, divides into three branches supplying the vallecula, the epiglottis and the pyriform sinus (or pyriform fossa). The density of nerve endings providing sensory innervation appears to be greatest at the laryngeal inlet as part of the protective mechanism for the respiratory system. The laryngeal surface of the epiglottis has the greatest sensory innervation, whereas the vocal folds have a lower density of sensory fibres. 2 The anterior portion of the vocal folds also have a lower density of touch receptors than the posterior half. The external branch of the superior laryngeal nerve provides the motor supply to the cricothyroid muscle. • The left and right recurrent laryngeal nerves provide the motor supply to all the intrinsic laryngeal muscles except the cricothyroid muscle which, as noted above, is innervated by the external branch of the SLN. The recurrent laryngeal nerves contain both adductor and abductor fibres? They differ significantly with regard to their origin and pathway. The right RLN arises from the main trunk of the vagus in front of the subclavian artery and the left RLN arises from the vagus at the arch of the aorta around which it winds before ascending to the larynx. Because of its extensive course, the left recurrent nerve is more liable to injury than the right and is especially vulnerable to pressure from aortic aneurysm and intrathoracic masses. It is also easily injured during thyroidectomy and thoracic surgery. The left vocal fold, therefore, is affected much more frequently than the right by laryngeal paralysis. The recurrent laryngeal nerves on both sides ascend in the groove between the trachea and oesophagus for a variable distance in different individuals. Then they divide into anterior and posterior branches before entering
the larynx behind the cricothyroid articulation. The RLN provides the sensory supply to the glottis and subglottis (see Figures 164.1 and 164.2) . • The pharyngeal nerve descends between the internal and external carotid arteries to supply the middle pharyngeal constrictor muscle. Its fibres subsequently join with the glossopharyngeal and external laryngeal nerves, together with branches from the sympathetic trunk, to form the pharyngeal plexus. The pharynx and all the muscles of the soft palate, except the tensor palati, are supplied by fibres from the pharyngeal plexus. Cranial nerves V (trigeminal), VII (facial), XII (hypoglossal) and cervical spinal nerves CI-C3 provide the motor supply for the extrinsic laryngeal muscles (see Figure 164.3).
Laryngeal mechanoreceptors Free fibrils and terminal filaments enclosed in capsules constitute the receptor end organs (the mechanoreceptors) embedded in the laryngeal tissues at sites sensitive to muscle stretch and airflow pressures. Some are involved in protecting the airway while others contribute to the control of phonation. 4 Reflex closure of the larynx is triggered by tactile receptors in the glottic and supraglottic mucosa, which evoke reflex contraction of the laryngeal muscles. Similar receptors in the subglottic mucosa elicit laryngeal closure and cough. 5 Wyke6 ,7 postulated that mechanoreceptors are found in three sites: 1. The mucosal lining of the larynx (subglottic
mucosal mechanoreceptors): The corpuscular
Superior laryngeal nerve
----t-
V'»..~'i.l8-:f7+l'f;;:----=~W--'~r---
External branch
Internal branch
------1~~ \
Inferior --------1~" constrictor muscle
Ansa galeni Recurrent laryngeal nerve
Figure 164:1
Distribution of the vagus nerve to the larynx
(lateral view). Redrawn with permission from Ref. 3.
Chapter 164 Physiology of the larynx
I 2157
Right superior laryngeal nerve
Epiglottis Common carotid artery
Common carotid artery
Vagus nerve Vagus nerve Recurrent laryngeal nerve
Recurrent laryngeal nerve
Arch of Aorta Recurrent laryngeal nerve
Recurrent laryngeal nerve
Oesophagus
Figure 164.2
Middle pharyngeal constrictor muscle (subsequently pharyngeal nerve filaments combine with branches from sympathetic trunk and glossopharyngeal and external laryngeal nerves to form pharyngeal plexus)
Posterior view of the larynx showing
the distribution of the left and right laryngeal nerves.
Vagus nerve
Redrawn with permission from Ref. 3.
External branch
Internal branch
Motor supply to cricothyroid muscles
1. Sensation to: - supraglottic tract - valleculae - epiglottis - pyriform sinuses 2. Secretomotor fibres to: - supraglottic glands
Motor supply to all intrinsic laryngeal muscles (except cricothyroid)
Pharyngeal plexus
Pharynx and soft .palate
Figure 164.3
Diagrammatic representation of the laryngeal nerve supply. Note that the vagus supplies the gastrointestinal tract,
external ear, heart, lungs, bronchi, trachea, pharynx, palate, and larynx. Redrawn with permission from Ref. 3.
2158 I PART 16 THE UPPER AIRWAY nerve endings in the subglottic mucous membrane covering the surface of the vocal folds are particularly numerous and sensitive to the stimuli of muscle stretch, air pressure level, liquid and touch. 4 They discharge impulses into the afferent fibres of the vagus. 2. The capsules of the articulatory joints (articular mechanoreceptors): The existence and function of this group remain controversiaL 3. The extrinsic and laryngeal muscles (myotatic mechanoreceptors): The tone of the laryngeal muscles depends on the myotatic reflex, which is a function of the muscle spindles. The laryngeal muscles contain a large number of muscle spindles.
The neuroanatomy of phonation Phonation is dependent upon the integrated functioning of many elements of the central nervous system (eNS) and peripheral nervous system (PNS). Although the motor and sensory tracts serving the larynx are relatively well understood, the way in which phonation is initiated and controlled continues to be the subject of neurological research. In addition to the cortical loci associated with voluntary phonation, there is evidence of subcortical representation which is responsible for reflex laryngeal function and involuntary phonation. 8 There is some evidence that the periaqueductal grey matter (PAG) , a region of the midbrain, is a crucial site for mammalian voice production. 9 Not only is it involved in the production of emotional or involuntary sounds, but it also appears to generate specific respiratory and laryngeal motor patterns fundamental to human speech and singing. Davis et al. conclude that the patterned muscle activity corresponding to the major categories of voiced and voiceless sound production are represented in the PAG. Its role might also include integration of cortical and subcortical aspects of language with basic respiratory and laryngeal motor patterns by which speech is produced. 10, 11, 12, 13 The linguistic demands of intonation, phonemic differentiations and emotional nuances in quality would appear to be regulated by such an independent subcortical reflex neural system. The motor activity for vocalization appears to be integrated through a projection from the PAG to a column of neurones, known as the nucleus retroambigualis (NRA). This nucleus appears to playa significant role in generating respiratory pressure and laryngeal adduction, which occurs in both vocalization and vegetative manoeuvres, such as coughing. Larson 11 has suggested that the cortical mechanisms involved in vocalization and speech may have a role in modulating the subcortical systems which are involved in involuntary, or vegetative, phonation such as crying. It is
possible that these are the mechanisms for coordinating timing, pitch and intensity fluctuations with the segmental and suprasegmental aspects of speech and language. There is also evidence arising from clinical cases that the frontal lobes and other cerebral structures are important in the integrated neurological systems required for phonation. The neural pathways for voluntary vocalization arise in the precentral gyrus of the motor cortex in both cerebral hemispheres, and fibres descend as part of the corticobulbar tract, which is part of the pyramidal system or 'direct activation' tract. On reaching the medulla, some fibres of the corticobulbar tracts take a direct pathway, remaining on the same side of the body throughout their route. These fibres synapse with the ipsilateral tenth cranial nerve (vagus) nucleus and subsequently with lower motor neurones without interruption. Other fibres decussate and change sides at the bulbar level to synapse with the contralateral vagal nucleus. The vagal nuclei in the nucleus ambiguus within the reticular formation of the medulla lie in a group of cells also containing the ninth and eleventh cranial nerve elements. They are influenced by both the pyramidal and extrapyramidal systems (see below). Motor and sensory tracts from both cerebral hemispheres, the basal ganglia and the cerebellum extending to the cranial nerve nuclei in the brain stem are known as upper motor and sensory tracts. The indirect neurones of the pyramidal tract have multiple offshoots and synapses with the basal ganglia and reticular formation in the brainstem. They appear to contribute to temporospatial orientation while the direct system is related to discrete movement. The upper motor neurones do not govern isolated muscles, but groups of muscles. The frontobulbar portions of the pyramidal tracts connect with cranial nerves IX to XII (as well as I to VIII), thus controlling articulation, phonation and respiration. The extrapyramidal system refers to tracts other than the pyramidal tracts and includes the basal ganglia in the cerebral hemispheres, the substantia nigra and subthalamic nucleus in the upper brainstem, the cerebellum and the thalamus among other structures. The basal ganglia consist of the corpus striatum and its associated nuclei, the caudate and lenticular nuclei. The latter is divided into the putamen and the globus pallidus. The cerebellum has an integrating and controlling role over movements which arise in other parts of the motor system. It regulates the force, speed, range, timing and direction of movements throughout the body so that excesses are inhibited. The extrapyramidal system influences the pyramidal tract, the function of which is to regulate the muscle tone required for posture and for changing position. It is also involved in the automatic component of skilled voluntary movement. The specific function of each of these elements of the extrapyramidal system with respect to phonation is unknown, but phonation
Chapter 164 Physiology of the larynx
may be influenced adversely by neurological conditions involving these structures. 13 The extrinsic and intrinsic muscles of the larynx are under voluntary cortical controL They are responsible for the prephonatory tuning which precedes phonation and is followed by the phasic, tonic and volitional contractions and also maintenance of length, tension, bulk and position of the vocal folds. 14 The phonatory modulations which take place in speech, however, happen with a precision and speed which suggests a finely coordinated system of reflex controls over the laryngeal muscles themselves, and over the abdominal and intercostal muscles that maintain subglottic air pressure at appropriate levels. 5 It seems that such fine tuning cannot be cortically regulated. 15 Stimulation of all categories of laryngeal mechanoreceptors initiates activity in the larynx which presumably ensures that the vocal folds are stabilized and return to their preset pattern following displacement by the expiratory air stream. This process, by monitoring the tonicity and position of the vocal folds, enables necessary adjustments to be made instantaneously and accurately. Although it would seem inevitable that there must ultimately be integration of this servosystem with other control systems during phonation, Wyke 15 and Kirchner5 stated that this process is independent of auditory feedback.
FUNCTIONS OF THE LARYNX Swallowing (deglutition) During swallowing, the primary function of the larynx is to prevent food and liquid entering the airway. This is achieved by means of the sphincteric action of the aryepiglottic folds and the true and false vocal folds which occurs simultaneously with elevation of the larynx. The process of swallowing can be divided into the oral stage and the pharyngeal stage. The oral stage is under voluntary control and consists of the oral preparatory stage and the oral transport stage. 16 The food bolus is manipulated by the tongue and broken down by the teeth before being propelled towards the oropharynx. The pharyngeal stage of swallowing is a reflex activity which is initiated as the bolus reaches the back of the tongue. During this phase, the glottis is closed by adduction of the arytenoids and contraction of the lateral cricoarytenoid muscles, false vocal folds and true vocal folds. Vocal fold adduction during swallowing is thought to average approximately 2.3 seconds. 16 The airway is also protected by the epiglottis which covers the laryngeal entrance and directs the bolus in two parts into the valleculae and the pyriform sinuses. The two columns of the divided bolus meet at the upper border of the cricopharyngeus muscle which relaxes to allow the bolus to enter the oesophagus. Rapid laryngeal elevation occurs during the pharyngeal
I 2159
phase of the swallow and appears to be essential for normal swallowing. This manoeuvre produces a drop in pressure and transient negative pressure in the cricopharyngeal sphincter as the bolus passes from the pharynx into the oesophagus. It has been established that if laryngeal elevation is impaired, the pressure drop during deglutition is slower and the fleeting negative pressure does not occur,17 so contributing to swallowing problems.
Coughing Coughing is the process by which material is expelled from the airway. It is preceded by rapid inspiration, followed by forceful closure of both the vocal and vestibular folds. Air pressure is then built up below the adducted folds as the diaphragm ascends spasmodically until the folds separate explosively and mucus or foreign material is expelled.
Effort closure Laryngeal structure has evolved in order to contain intrathoracic pressure, so as to provide a stable fulcrum for the upper limbs. Expiratory effort against a closed glottis is known as the Valsalva manoeuvre. 18 During any form of exertion involving use of the arms, the vocal folds are firmly adducted preventing expulsion of air and collapse of the chest walls, thus providing a fixed origin for the arm and shoulder muscles. This fact is clinically important in that those who have undergone laryngectomy or who have paralysis of one or both vocal folds, for example, may have difficulty with weightbearing activities because of their inability to close the glottis effectively. Clinical experience also sugggests that trauma to the vocal fold mucosa can occur or be aggravated by forceful, prolonged vocal fold adduction during some types of physical training, such as working with weights. Effort closure of the larynx also occurs during childbirth and defaecation as the abdominal contents are compressed by the abdominal muscles in order to achieve expulsion.
The biomechanics of phonation When the larynx is at rest and respiration is quiet, the vocal folds abduct on inspiration and slightly adduct on expiration. They move up and down slightly in sympathy with the outflow and inflow of respiratory air, while the larynx descends on inspiration and ascends on expiration. 19 The folds are drawn wide apart to a position of full abduction in forceful inspiration.
2160 I PART 16 THE UPPER AIRWAY
",~
~ ~
,~
n
INITIATION OF VOICE
Immediately before phonation, the vocal folds rapidly abduct to allow the intake of air. Wyke 1S has termed this the 'prephonatory inspiratory phase'. Subsequently, the vocal folds are adducted by the contraction of the lateral cricoarytenoid muscles. The vocal note is generated by pulmonic air (air from the lungs) as it is exhaled between the adducted vocal folds. The vocal folds working together, therefore, constitute a vibrator which is activated by the excitor, the exhaled air. The production of the vocal note at this point is the result of the repeated vibratory movement of the vocal folds, known as vocal fold oscillation. The mobility and deformability of the vocal folds determines the ease with which vocal fold vibration can be initiated. 20 Subglottic air pressure increases below the adducted vocal folds until it reaches a level which overcomes their resistance and blows them apart, thus setting in motion the vibratory cycles which result in phonation. The vocal folds, in common with all vibrators, have a degree of inertia which has to be overcome in order for phonation to occur. The amount of air pressure required to begin voicing is known as the 'phonation threshold pressure,.21 The size and tension of the vocal folds in combination with the viscoelastic properties of the vocal fold cover will affect the phonation threshold pressure?2
THE VIBRATORY CYCLE
Each vibratory cycle of the vocal folds consists of three phases: adduction, aerodynamic separation and recoil (Figure 164.4). As the increased subglottic air pressure overcomes the resistance of the adducted vocal folds at the onset of phonation, the vocal folds peel apart from their inferior border. When they finally separate at their superior margin, a puff of air is released. The resulting negative pressure in the glottis, caused by the Bernoulli effect, results in the vocal folds closing rapidly as they are sucked together, the inferior vocal fold margins closing first. (The Bernouilli effect is a drop in pressure dependent on particle velocity. In relation to the vocal tract, Maran 23 describes it as follows, 'When air passes from one large space to another (e.g. from lung to pharynx), through a constriction (the glottis), the velocity will be greatest and the pressure least at the site of the constriction.' As a result of the drop in pressure at the glottis, the vocal fold mucosa is drawn into space between the vocal folds.) Contact between the vocal folds increases until the subglottic air pressure is high enough to blow the vocal folds apart again, and the cycle recommences. Each cycle of adduction, separation and recoil is the manifestation of a mucosal wave travelling from the inferior to the superior surface of each vocal fold. The process by which this undulating wave of movement of the mucous membrane occurs is dependent on what is known as the cover/body theory.
(1 )
(2)
(3)
(4)
r~
(6)
(7)
(8)
'~(9)
(5)~ Figure 164.4 Vocal fold vibratory cycle. Redrawn with permission from Ref. 3.
That is, the vocalis muscle provides the firm body of the vocal fold over which the mucous membrane cover of the vocal fold is blown by the expiratory air stream. These undulations of the thin cover of the vocal folds and any abnormalities of the mucosal wave can only be observed using laryngostroboscopy or high speed photo graphy. 22 The periods of vocal fold contact and lack of contact in one vibratory cycle can be divided broadly into closed and open phases, respectively, with associated closing and opening phases?4 The closing phase of the vocal folds is more rapid than the opening phase. The phases of the vibratory cycle can be classified, therefore, into four stages as shown in Table 164.1. The vocal folds have to be structurally and functionally symmetrical, at the same level and close rapidly in order that a clear vocal note can be initiated and maintained?S Insufficient approximation of the vocal folds (glottal insufficiency) results in air wastage and production of breathy voice. When the vocal folds fail to approximate completely along their membranous portion, with a slightly increased aperture in the cartilaginous section, turbulent air escapes and is audible in the voice. In production of notes of middle pitch, the interarytenoid muscles adduct the cartilaginous portion of both vocai folds and hold them together while the anterior portion of each fold is gently adducted but
Chapter 164 Physiology of the larynx Table 164.1 The periods of vocal fold contact and lack of contact in one vibratory cycle. Phase Closing Closed Opening
Open
Description The vocal folds begin to close rapidly from their lower margin The medial edges of the vocal folds are in full contact The vocal folds begin to separate from their lower margin and gradually peel apart. The superior margin remains in contact until the end of this phase The vocal folds are separated, the longest part of a normal vibratory cycle
I 2161
and chest, but these terms are regarded as unsatisfactory by voice scientists, many of whom refer to three main vocal registers: falsetto, modal and vocal fry. These classifications, however, do not relate directly to each other. Baken and o rliko fP 1 note that the problems of definition and terminology have been clarified by Hollien's32 suggestion that registers should be defined in terms of laryngeal behaviour, rather than in acoustic terms, as registers are governed by the degree of contraction of the vocalis muscle. As a result, the terms loft, modal and pulse registers can be used with less confusion. They describe the vibratory pattern of the vocal folds and the acoustic parameters being produced.
VOCAL REGISTERS: CHARACTERISTICS OF VOCAL FOLD ADDUCTION AND VIBRATION
• Loft register (or falsetto) covers the highest frequencies of the voice. The vocal folds are lengthened, extremely tense and thinned so that there is minimal vibration. The knife-thin free edges are almost adducted and subglottic air pressure is high. During the production of these high frequencies, the larynx is raised by the suprahyoid muscles and the pharynx is shortened. • Modal register encompasses the range of frequencies usually employed in speech and singing. The membranous portions of the vocal folds are adducted and make complete closure in the closed phase of each vibratory cycle. In cross-section, the vocal folds are triangular in shape. In low notes the intrinsic muscles relax, the folds increase in bulk, and their opposing surfaces deepen from 3 to 5 mm. They vibrate slowly along their whole length, the lower surfaces of their 'lips' making contact and separating as the upper surfaces approximate in a rolling motion or figure of eight. In lowest notes, the infrahyoid muscles pull the larynx down. • Pulse register (or glottal fry, vocal fry or creaky voice) occurs during the lowest vocal frequencies and is a feature of normal speech. This terminology reflects the pulsatile nature of the laryngeal sound generated. There is a long closed phased in each vibratory cycle.
Significant variations in vocal fold vibratory characteristics and adduction can also be observed according to the vocal register which is being used. The subject of vocal registers is confusing and controversial. This is partly because the definition of what constitutes a register has been unclear, but also because a number of terms are used to describe each register. Traditionally, registers have been regarded as the perceptually distinct regions of vocal quality over certain ranges of pitch and loudness,22 but listener identification of the change from one register to another is not reliable. 30 The terms used vary according to whether they are being employed by singers or speech· scientists, but even then their use is not uniform. Singers tend to classify the registers as head, middle
The terminology and underlying modes of vocal fold behaviour during the production of each register are outlined in Table 164.2. Appreciation of the normal patterns of vocal fold movement and the way in which laryngeal adjustments affect the sound of the voice is essential to evaluating laryngeal findings in cases of disordered voice. Considerable variations of structure and function can be found even in the normal larynx and there are probably even more permutations of laryngeal behaviour. A comprehensive range of vocal tasks throughout the patient's pitch range during laryngoscopic examination is essential, therefore, if inappropriate conclusions regarding laryngeal disease are to be avoided.
Reproduced with permission from Ref. 3.
free to vibrate in the expiratory airflow. Although full vocal fold adduction during phonation has traditionally been regarded as the norm, clinical observation and various studies have refuted this view by showing that normal phonation can occur when there is incomplete glottal closure. 26 , 27 This pattern of vocal fold adduction is more common in women than in men. In all speakers, incomplete glottal closure can be considered normal in high frequency modal voice (see below) and in falsetto, when hourglass or spindle glottal configurations can occur in normal subjects. 28 It also appears that different types of glottal configurations are associated with different age groups. Incomplete closure of the posterior part of the vocal folds (posterior glottal chink) is a common finding in young and middleaged women, but elderly women are more likely to exhibit anterior chinks. 26 ,29 It is essential, therefore, that clinicians dealing with vocal problems recognize that incomplete vocal fold closure may be a normal glottal configuration during phonation in certain subjects and at certain frequencies.
2162 I
PART 16 THE UPPER AIRWAY
Table 164.2
Vocal registers.
~RegJsterima{in~lude
·.·EHui\falentterms
Loft register Highest vocal frequencies
Falsetto
Thin, tense, lengthened.
275-1100
Minimal vibration
Modal register Range of fundamental frequencies most
Chest, head, middle, heavy voice
Complete adduction
100-300
Vocal fry, glottal fry, creaky voice
Long closed phase
20-60
commonly used in speaking and singing
Pulse register Lowest range of vocal frequencies: laryngeal output is perceived as pulsatile The terminology related to vocal registers is not consistent. Various overlapping terms are used which have theoretical bases (see under Vocal registers: Characteristics of vocal fold adduction and vibration). Reproduced with permission from Ref. 3.
REFERENCES Edinburgh: Churchil Livingstone, 1952: 46-52 .
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Sasaki CT, Weaver EM. Physiology of the larynx. American Journal of Medicine. 1997; 103: 95-175. This reference provides detailed and fundamental information about the physiology and biomechanics of the larynx, which is essential for a comprehensive understanding of the processes involved in phonation at both a gross and microscopic level. 3. Mathieson L. Greene and Mathieson's the voice and its disorders, 6th edn. London: Whurr, 2001. 2.
4.
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Diseases of the nervous system, 7th edn.
1. Walshe FMR.
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Phonosurgery - assessment and surgical management of voice disorders. New York:
In: Ford CN, Bless DM (eds).
...
Raven Press, 1991: 43-76. 5.
•• It is. essential to>oe·awareof the eitensiye.~t#llg~ . •·Qf.riOTl11aI p~tterns···bf
yogal. fdidJ:l)oyernent inonkr to c
Kirchner JA. Factors influencing glottal aperture. In: Bless DM, Abbs JH (eds).
Vocal fold physiology. San Diego:
College Hill Press, 1983: 77-81. 6.
.···l11~ev~lid·jlldgements()111aryngo- . .•. ~<:()pice)(!l1l1illation);in.c:ase~. ofdJsordered
Garrett JD, Larson CR. Neurology of the laryngeal system.
Wyke B. Recent advances in the neurology of phonation
British Journal of Disorders of Communication. 1967; 2: 2-14. 7. Wyke B (ed.). Ventilatory and phonatory control systems. and reflex mechanisms in the larynx.
Oxford: Oxford University Press, 1972. 8.
Aronson AE.
Clinical voice disorders, 3rd edn. New York:
Thieme, 1990. 9.
Deficiencies in current knowledge and areas for future research
Davis PJ, Zhang SP, Winkworth A, Bandler R. Neural control of vocalization: Respiratory and emotional influences.
10.
Journal of Voice. 1996; 10: 23-38.
Davis P, Zhang SP, Bandler R. Pulmonary and upper
The following areas require further study:
airway afferent influences on the motor pattern of
)- sensorimotor control of phonatory behaviour;
vocalization evoked by excitation of the midbrain
)- the neural processes involved in acoustic self-
periaqueductal gray of the cat.
monitoring of phonation; )- the integrative control by the central nervous system
Brain Research. 1993; 607:
61-80. 11.
Larson CR. The midbrain periaqueductal gray: A
of laryngeal function for speech, respiration and
brainstem structure involved in vocalization.
swallowing.
Joutnal of Speech and Hearing Research. 1988; 28: 241-9.
r
Chapter 164 Physiology of the larynx
12. Zhang SP, Bandler R, Davis P. Brain stem integration of vocalization: Role of the nucleus retroambigualis. Journal of Neurophysiology. 1995; 74: 2500-12. Zhang SP, Davis PJ, Bandler R, Carrive EP. Brain stem 13. integration of vocalization: Role of the midbrain periaqueductal gray. Journal of Neurophysiology. 1994; 72: 1337-56. Bowden REM. Innervation of intrinsic laryngeal muscles. 14. In: Wyke B (ed.). Ventilatory and phonatory control systems. Oxford University Press, 1972: 370-82. 15. Wyke B. Neuromuscular control systems in voice production. In: Bless DM, Abbs JH (eds). Vocal fold physiology. San Diego: College Hill Press, 1983: 71-6. 16. Perlman A. Normal swallowing physiology and evaluation.
comprehensive understanding of the processes involved in phonation at both a gross and microscopic level.
23.
* 24.
detailed and fundamental information about the essential for a comprehensive understanding of the processes involved in phonation at both a gross and microscopic level.
* 25.
biomechanics of the larynx, which is essential for a comprehensive understanding of the processes involved in
17.
phonation at both a gross and microscopic level.
26.
27.
reference provides detailed and fundamental information about the physiology and biomechanics of the larynx, which is essential for a comprehensive understanding of
28.
the processes involved in phonation at both a gross and microscopic level.
20. 21.
* 22.
Titze IR. Mechanical stress in phonation. Journal of Voice. 1994; 8: 99-105. Farley GR, Barlow SM. Neurophysiology, biomechanics, and modeling of normal voice production. Current Opinion in Otolaryngology and Head and Neck Surgery. 1994; 2: 233-9. Titze IR. Principles of voice production. New Jersey: Prentice Hall, 1994. This reference provides detailed and fundamental information about the physiology and biomechanics of the larynx, which is essential for a
Woo P, Colton R, Casper J, Brewer D. Diagnostic value of stroboscopic examination in hoarse patients. Journal of Voice. 1991; 5: 231-8. This reference provides detailed and fundamental information about the physiology and
Current Opinion in Otolaryngology and Head and Neck
*
Maran AGD. Logan Turner's diseases of the nose, throat and ear, 10th edn. Sevenoaks, Kent: John Wright, 1988. Hirano M, Bless DM. Videostroboscopic examination of the larynx. London: Whurr, 1993. This reference provides physiology and biomechanics of the larynx, which is
Surgery. 1994; 2: 226-32.
Mendelsohn MS, McConnel FMS. Function in the pharyngoesophageal segment. Laryngoscope. 1987; 97: 483. 18. Sionim NB, Hamilton LH. Respiratory physiology. St Louis: CV Mosby, 1976. Tucker H. The larynx. New York: Thieme, 1993. This 19.
I 2163
29.
30.
31. 32.
Biever DM, Bless DM. Vibratory characteristics of the vocal folds in young adult and geriatric women. Journal of Voice. 1989; 3: 120-31. Gelfer MP, Bultemeyer DK. Evaluation of vocal fold vibratory patterns in normal voices. Journal of Voice. 1990; 4: 335-45. Murry T, Xu JJ, Woodson GE. Glottal configuration associated with fundamental frequency and vocal register. Journal of Voice. 1998; 12: 44-9. Sodersten M, Hertegard S, Hammarberg B. Glottal closure, transglottal airflow and voice quality in healthy middleaged women. Journal of Voice. 1995; 9: 182-97. McGlone RE, Brown WS. Identification of the 'shift' between vocal registers. Journal of the Acoustical Society of America. 1969; 46: 1033-6. Baken RJ, Orlikoff RF. Clinical measurement of speech and voice. San Diego: Singular, 2000. Hollien H. On vocal registers. Journal of Phonetics. 1974; 2: 125-43.
165 Voice and speech production
PAUL CARDING AND LESLEY MATHIESON
Introduction
2164
Paralinguistic fe a tures of voice and speech
2167
Characteristics of the sound source/glottal signal
2165
Key points
2168
Deficiencies in current knowledge and areas for future
Modifying the glottal signal
2165
Vocal resonance
2166
Fundamentals of speech/articulation
2166
2169
research References
2169
The information in this chapter can be explored more extensively by undertaking a Medline search using the key words speech, voice, articulation, larynx, phonatory biomechanics, vocal fold vibration, vocal registers, intonation, phonetics and paralinguistic features.
INTRODUCTION
behaviours
represents
arguably
the
most
advanced
sensorimotor system to be found in the human body,l This chapter outlines how humans produce speech and
Speech and voice require precise coordination of reflexive
voice. The characteristics of the glottal source (vocal fold
and learned behaviours
vibration) are described. How the sound is modified
movements
within the oral tract is then addressed in detail. This is
flexibility of the vocal tract and the anatomical variations
executed
resulting
with
in intricate
accuracy and
muscle
speed.
The
followed by a brief explanation of the
fundamental
betWeen people allows for an enormous range of normal
principles
Finally,
voice and speech qualities and an inevitable overlap
of
speech
and
articulation.
the
importance of the paralinguistic features of voice and
between 'normal' and 'abnormal' parameters. This has
speech are illustrated.
implications for how we assess and measure components
The vibration of the vocal folds (phonation) consti tutes the raw glottal sound source. However, the voice we hear
is far
more complex
than the acoustic signal
generated by the vibrating larynx.
This fundamental
of
speech
and
voice
for
diagnostic
and
outcome
evaluation purposes.2 The main features of human voice and speech production are described in more detail below.
vibratory sound is modified and resonated by the rest of
The specific characteristics of an individual's speech
the vocal tract to produce a recognizable voice quality.
and voice are the product of the organic and phonetic
Hence analysis of voice quality (perceptual or instru
features of the speaker.3 Organic factors are derived from
mental) must recognize the role of the whole vocal tract
the
ln the production of the sound that finally radiates from
apparatus; the dimensions and geometry of the nasal
the mouth. Furthermore, the articulatory structures of the
and oral structures,
vocal tract (lips, tongue and soft palate) shape the sound source in an infinite nwnber of combinations to mq,ke speech. This coordination of phonatory and articulatory
nature
of
the
speaker's
individual
anatomical
pharynx, larynx and respiratory
system. Phonetic features refer to the speaker's habitual muscular aajustments of the speaking apparatus in terms of long-term
muscle
'settings'
(for
example,
larynx
---,
Chapter 165 Voice and speech production I
2165
posItion or tongue body position). The specific anato
features. Frequency increases with a lengthening of the
individual and produces a voice and speech quality which
the vocalis muscles.6 The perceptual correlate of fre
muscular habitual settings are learnt (often unconscious)
two is a complex one. The frequency, intensity and
and personal needs.
ways to lead to a given pitch perception.s Considerable
mical configuration of the vocal tract is unique to each distinguishes one speaker from another. The phonetic behaviours which fulfil the speaker's social, geographical
vocal folds and the subsequent thinning and stiffening of quency is pitch, although the relationship between the
spectral properties of a sound interact in very complex normative data of habitual speaking pitch or speaking fundamental frequency exist,S although there is a huge
CHARACTERISTICS OF THE SOUND SOURCEI GLOTTAL SIGNAL
range of what is considered 'normal' depending on the age, sex, emotional state, communicative intent, mood and personality of the speaker. Similarly, there are data on
The quality of the sound source is wholly dependent upon
vocal pitch range both in terms of maximum range and
More specifically, it is dependent upon the nature of vocal
are three pitch registers: loft (or falsetto) register, modal
the vibratory characteristics of the laryngeal structures.4
habitual speaking range. It is generally accepted that there
fold adduction during phonation and the regularity of the
(or middle) register and pulse (or chest) register. These
mucosal waves of the lamina propria (see Chapter 164,
registers basically distinguish between different vibratory
adduction of the vocal folds during phonation will result
contraction of the vocalis muscles.? Short-term (cycle to
in audible air leakage and a 'breathy' voice quality.
cycle) variance in the frequency of vocal fold vibration is
Physiology of the
larynx).
For
example,
incomplete
patterns of the vocal folds determined by the degree of
Whisper occurs when there is insufficient vocal fold
called 'jitter' or pitch perturbation. In a speaker who is
adduction to achieve vibration, but sufficient adduction
trying to maintain a stable pitch, a measurement of jitter
to produce audible turbulent air. An irregular mucosal
may indicate instability in the phonatory mechanism and
waveform vibration will result in an aperiodic sound that
may be a further useful index of dysphonia.2
will be perceived as 'hoarse'. A pressed or strained voice quality occurs when the vocal folds are strongly adducted
Vocal loudness is the perceptual correlate of amplitude -
the size of the oscillation of the vocal folds. The
(often with supraglottic muscular involvement) and there
amplitude of these vibrations is largely determined by the
is raised subglottal air pressure. In a hypothetically
force of the transglottal airflow. Increasing both the air
perfectly functioning larynx, adduction of the vocal folds would be complete during the closed phase of phonation and the vibration of the mucosal waveform would produce a perfectly periodic sound signal (a sine wave).
flow through the larynx and vocal fold resistance (and subsequent subglottal pressure) will result in an increase in vocal loudness. Like vocal frequency, there are data on normal vocal intensity (habitual and range) in a variety of
The sound that would be produced would solely contain a
settings.4 Short-term variance in the intensity of the vocal
fundamental frequency and its harmonics. However, all
signal is called 'shimmer' or amplitude perturbation. An
human
inability to maintain stable amplitude when intended may
voices
are
a
combination
of
periodic
and
aperiodic sound. Aperiodic sound or 'noise' is a sound that is not a harmonic of the glottal signal. The main
indicate
important
characteristics
of
the
dysphonic
speaker.2
sources of 'noise' in the larynx are air escape and irregular
vibration.2 The more severe the noise component of the
sound (in relation to the periodic component), the more
MODIFYING THE GLOTTAL SIGNAL
hoarse the voice will sound.2 It is possible to measure the degree of 'hoarseness' in a voice by calculating the ratio of
modified by the rest of the vocal tract to produce the
usually termed a harmonics-to-noise ratio (HNR).s It is
voice quality that radiates from the speaker's mouth to
important to note that the acoustic HNR measurement
the listener's ear. In a normal voice, the glottal signal is
provides some indication of the degree of hoarseness, but
HNR
essentially periodic and composed of a fundamental
no information as to the source of the noise component.4
frequency and its harmonics. This complex acoustic signal
HNR measurement has become a popular measure of
is then filtered by the supralaryngeal tract with some
dysphonic severity and of change in voice quality during
treatment.2
The frequency of the glottal signal is a result of the
anatomical structures resonating different harmonics of the source signal more than others. Changes in the shape of the whole vocal tract (and the dimensions of the oral,
number of vibratory cycles per second (measured in
nasal, pharyngeal and laryngeal cavities relative to each
hertz). The rate of vibration of the vocal folds is a
other) can be achieved in numerous ways. For example,
function of the vocal fold length, elasticity, tension and mass, and their subsequent resistance to subglottal air pressure.4 The maintenance of a steady vocal frequency requires control of all of these interacting physiological
h
The sound source produced by the vibrating vocal folds is
periodic sound compared to aperiodic sound. This is
protruding the lips, retracting the tongue base, lowering
the larynx or lowering the soft palate will all dramatically alter
the
sound
of
the
resultant
voice
even
when
performed in isolation. The fact that the voice is more
2166
I PART 16 THE UPPER AIRWAY
than its vibratory source is a fundamental principle of auditory evaluation of voice quality.8 It is important to
complication of the uvulopalatopharyngoplasty (UPP)
surgical procedure is the resultant hypernasal speech.
note that some voice quality rating scales concentrate on laryngeal vibratory features only (i.e. the GRBAS scale), whilst others take into account distinguishing perceptual
FUNDAMENTALS OF SPEECH/ARTICULATION
features of the whole vocal tract (e.g. the Vocal Profile Analysis Scheme). The modification of the sound source
Orchestrated movements of the organs of articulation
by the supraglottic vocal tract also represents the main
change the vocal sound into recognizable speech. This
problem
in
the
instrumental measurement
of
voice
quality. For this reason most methods of acoustic analysis prefer to analyse a 'steady-state' prolonged vowels where the speaker is attempting to maintain steady pitch and intensity and where the variance in supralaryngeal tract configurations are kept to a minimum.
process is often called the 'source-filter' model of voice production. 10
These
articulatory
movements
can
be
classified as vowels or consonants (although the actual distinction between the two is theoretically complex). In
simple terms, vowels are sounds in which there is no
obstruction to the flow of air as it passes from the larynx to the lips. Consonants require a more definite obstruc
tion by one or more of the articulators in the oral tract.
VOCAL RESONANCE
This distinction becomes less useful for sounds such as 'w'
As explained above, the supralaryngeal tract acts as a
articulated like vowels. For this reason, these sounds are
resonating chamber
commonly called 'semi-vowels'.ll
or 'y'
generated by
for
the
complex acoustic signal
the vibrating vocal folds. The
specific
which we call consonants but are, in reality,
W, Y
All vowel sounds are continuants, i.e. they have length
geometry.and dimensions of an individual speaker' s vocal
of varying periods of time. For practical purposes, it is
tract will determine the 'timbre' or resonating properties of
sufficient to differentiate between short vowels (i.e. pit)
the voice. Skilled speakers and singers learn to manipulate
and long vowels (i.e. part). In a diphthong, two vowel
these oral, nasal and pharyngeal structures to maximize
sounds are combined (i.e. fire). Vowel articulations are
their resonant properties. This is not an easy thing to do
made by varying the resonating shape of the oral and
since vocal resonance will of course continually change as
pharyngeal cavities.
we speak (i.e. change vocal pitch or intensity, articulate
Changing the shape of the vocal tract subsequently
different sounds). Oral resonance is affected by the degree
changes its resonating behaviour; different shapes re
of jaw movement, mouth opening, tongue body raising
sponding to
and pharyngeal constriction. Nasal resonance is affected by
structure of the glottal sound source. The resonance
different components
of
the
harmonic
excessive or too limited action of the velopharyngeal
peaks of the vocal tract are called 'formants'. These
sphincter
formant structures vary for each vowel and are easily
during
speech
(or
some
degree
of
nasal
obstruction). For a majority of speech, the velopharyngeal
identifiable on a sound spectrograph.5 It is possible to
sphincter is closed. The diaphragm of the velum reflects a
distinguish between vowels by changing
majority of the sound into the oral cavity. However, some sound will naturally resonate through into the nasal cavity. The final result is a sound with an appropriate oral/nasal balance. Appropriate oraVnasal resonance is not only necessary for normal sounding speech and voice, but is important to facilitate good voice projection (by enhancing the fundamental frequency and its harmonics).
Velopharyngeal incompetence or significant lowering of the soft palate will result in a hypernasal speech quality. In extreme cases, audible nasal air escape can be heard during speech. There is evidence to suggest that listeners tend to associate negative personal attributes to indivi duals with hypernasal speech.9 Structural abnormalities,
such as a cleft palate or submucosal cleft, will often result in
marked hypernasality. Conversely, an inability to
produce appropriate nasal resonance (especially for the sounds n, m and ng) .will result in hyponasal speech quality. This is, of course, most likely to occur in space occupying conditions of the nasopharynx. Removal of the
space-occupying lesion or tissue may result in hypernas
ality, although this is likely to be temporary in most cases. A
significant
but
poorly
investigated
possible
(1) the height of (2) the part of the tongue which is raised (front, centre, back) and (3) the the tongue raising in the mouth,
position of the lips (spread or rounded). For example, the
vowel /i :/ as in 'see' is made with the front of the tongue raised and with lips spread. In contrast, the vowel /u:/ as in 'sue'
is made with posterior· tongue raising and
rounded lips. Diphthongs (i.e. 'beer', 'air' ) start with one oral tract articulatory shaping and glide to another. Speech consonants are defined by their much clearer articulation (and often obstruction of the airflow) within the oral tract. A distinction can be made between consonants using three main elements:
1. the place of articulation (i.e. lips, alveolar); 2. the manner of articulation (i.e. plosive, fricative); 3. the sttte of the larynx (voiced or voiceless). All of these elements require further explanation. Consonants are clearly articulated at different places within
the
articulation
oral
tract.
between
Bilabial the
consonants
upper
and
refer
lower
to lips
(p,b,m.w). Labiodental consonants require top teeth and lower lip articulation (f,v). Dental articulation refers to
Chapter 165 Voice and speech production
tongue
tip
and
top
teeth
occlusion
(th).
Alveolar
consonants are made by the tongue tip touching the ridge behind the teeth (t,d,n,s,z,r,ch.dj). Articulation of the middle tongue with the hard palate produces 'y'. Velar consonants
require posterior tongue and soft palate
articulation (k,g,ng) (see of standard consonants).
Table 165.1 for a complete list
The manner of consonant articulation refers to how
the airflow is obstructed in the oral tract. Traditionally,
these are split into five categories: plosives, fricatives, affricates, nasals and approximants. English plosive
consonants
Ip,b,t,d,k,g/.
These
has
plosives
six
have
different places of articulation (see earlier in this section and
Table 165.1). In all cases, one articulator is moved
against another in order to interrupt completely the air flow through the vocal tract. The air is temporarily compressed behind the point of articulation and then released with an audible noise called 'plosion'. In contrast,
fricatives are continuant consonants (they can continue for a long time). The main characteristic of fricatives is the air turbulent sound that is made by. air hissing
I 2167
for all other standard consonants and vowels. Inadequate velopharyngeal competence will result in inappropriate 'nasalization'
of
non-nasal
consonants
and
vowels.
Permanent obstruction in the nasopharynx and lower nasal passages will result in 'denasalization'
of nasal
consonants. Approximant consonants occur when the articulators are not sufficiently close to produce 'com
plete' consonants, such as plosives, fricatives or nasals.
Again, the place of articulation can vary (see
Table 165.1).
These consonants are articulated similarly to vowels and
are therefore often called semi-vowels. English examples
of approximants include w and y. The lateral approximant
'I' varies slightly since the passage of air escapes along the
sides of the tongue.
Finally, consonants can either be 'voiced' or 'voiceless'.
A number of consonants can be 'paired', where the only difference between them is whether their articulation is accompanied by voicing or not (i.e. p and b, t and d, k and g, s and z). The place and manner for both members of each pair is the same. The only difference is that the first in each pair is 'voiceless' - there is no vibration of
through the close (but not complete) approximation of
the vocal folds for the split second that these consonants
two articulators. Like plosives, fricatives have different
are being articulated. The voiceless consonant 'h' does
places of articulation (see
not have a voiced twin in standard English. This means
Table 165.1). Examples of
English fricatives include f, z, and s. Affricates
combination of plosion and fricative articulation. A common example is the affricate consonant heard at the beginning and end of the word 'church'. It begins with the plosive t and then the tongue moves to the position for
that in connected speech, vocalization is not continuous.
Phonation is switched on and off (for milliseconds of
time) to signal voiceless consonants. This extremely
subtle phonatory timing is crucial for intelligible speech and is a characteristic problem of some dysphonic voices.
the fricative sh. The plosive is followed immediately by
In
the fricative noise, but is heard as one consonant sound.
bold type ..
Table 165.1, the voiced consonants are signalled by
There are only two affricate sounds in English ch and dj (as in the beginning and ending sounds in 'church' and 'judge' ) and both are articulated with the tongue tip and alveolar components. The basic characteristic of the nasal consonants (m, n, ng) is that air escapes through the nose. The air is prevented from passing through the mouth by
PARALINGUISTIC FEATURES OF VOICE AND SPEECH
obstructive lip or tongue articulation and the soft palate is
Speech and voice are more than simply the products of
lowered to allow nasal air escape. The soft palate is raised
muscular movements. For example, they represent . an
Table 165.1
Standard English consonants.
:
Plosive
BjJabial
\-.'
Labiodental.
Alveolar
Palatal
td
p b
fv
Fricative
Dental
Velar , ;
6:1 oftal
kg
s z sh jzC ch djd
Affricate Nasal
m
n
Approximant
w
I r
Bold signifies voiced: aAs in 'th ink'. bAs in
'th at'.
cAs in. 'mea sure' dAs in '1 aw' eAs in 'si ng'.
nge y
H
2168
I PART 16 THE UPPER AIRWAY
immensely powerful (and efficient) means of conveying
understanding of the components of phonatory beha
mood, personality and intent. Our speech and voice also
viour (e.g. laryngeal muscle tone, pulmonary airflow,
provide messages about our education, social status,
subglottal pressure, supralaryngeal tension) provides a
emotional state and personality. All of these things are
physiological explanation for these paralinguistic features
interpreted from the way the speaker uses features such
of voice.
as speech rhythm, speech rate, vocal intonation, vocal
The emotional content of a verbal message is also likely
tone or quality and voice loudness. 'Everything is said in
to be reflected in changes in vocal tone or quality.18 These
a certain way, in a certain tone of voice and at certain
result from changes in laryngeal and supralaryngeal
10udness,.4 However, it is rare for a speaker to be using
tension, which in turn affect vocal features. For example,
these features consciously
a
actor). The features
unconscious
may
be
(unless the speaker is an use
more
of these
revealing
paralinguistic
than
the
speaker
anticipated and more enlightening than the language
breathy
vocal
quality
may
indicate
anxiety19
or
vulnerabilitf O and may be interpreted as revealing lower
social class, especially when associated with harshness.21 Conversely, vocal creak (low pitched, irregular vocal fold
content of what is being spoken. It is partly for these
vibrations) may indicate a relaxed state and has been
reasons that voice or speech impairment may result in
shown, at least in one study, to correlate with higher
severe
levels
distress.12,
of
personal
handicap,
disability
and
Speech rhythm is learnt as an integral part of early childhood
social status.21 Vocal loudness appears to be different between the sexes even when the context and linguistic
13
speech,
voice,
language
and
commu
content are similar: men talk more loudly than women.21 Not surprisingly, we commonly associate vocal loudness
nication development. Early babbling is a 'working vocal
with
guidance system in which the ear monitors vocal tract
inappropriate loudness may indicate insensitivity and
confidence
and
an
extrovert
personality,
but
activity and informs speech-motor control systems about
poor pragmatic skills.22 Clearly, the interpretation of a
targets and adjustments needed for mimicry of ambient
speaker' s vocal quality and volume are, like all other
speech'.14 Speech rhythm is language- and even accent
paralinguistic features, subjective and may subsequently
specific. Speech rhythm (and stress) is one of the most
result in misunderstandings.
difficult linguistic features for foreign speakers to master
Almost all paralinguistic aspects of speech and voice
and will distinguish them from truly bilingual speakers
are intuitively known but not consciously learnt (or
who were exposed to several speech rhythm patterns from
manipulated). They contribute as much to our indivi
birth. To complicate the matter further, regional accents
dual speech and voice characteristics as our specific
often
For
anatomical configurations and habitual vocal settings.
example, it may be possible to identify locals from
These paralinguistic features of speech and voice remain
demand
different
speech
rhythms
again.
Newcastle simply by how they stress the syllables in the
a crucial aspect of speech and voice production and help
word 'Newcastle'. Locals will stress the second syllable
to explain why many people with a speech and voice
(New
castle), whereas most other speakers will naturally
stress the first syllable (Newcastle). Finally, loss of rhythm
disorder report severe personal, social and economic consequences.
and incorrect stress may render speech almost unin telligible even when articulation and voice production are normaL 4 Speech rate is often interpreted as an indicator of anxiety (if it is too fast) or low intellect (if it is too slow).15 Our speech rate is also likely to reflect our state of arousal (excited, drowsy, stressed, etc.) and is clearly linked to other physiological variables such as pulse and
KEY POINTS •
respiratory rate.
vocal folds, combined with the resonation
Vocal intonation refers to the use of varying vocal
pitch to indicate various grammatical, psychosocial and semantic
features.
We
use
intonation
to
the sound throughout the vocal tract. •
indicate
to
indicate
certainty
in
a
statement)
and
to
of the laryngeal structures. •
by the listener. Similarly, the pitch range used by a
siveness.16 Habitually low pitch may indicate depression
and
high
pitch
may
suggest
anxiety. 17
A
clear
Orchestrated movements. of the organs of articulation modify the vocal sound into
speaker may reflect emotional status. A wide frequency range which may be interpreted as sadness or impas
The quality of the glottal sound is wholly dependent upon the vibratory characteristics
Patterns of intonation are often used unconsciously by
range indicates arousal in contrast to a narrow ('flatter' )
The specific characteristics of an individual' s organic and phonetic features of the speaker.
•
manipulate conversation (e.g. to encourage a response). the speaker and are, of course, open to misinterpretation
of
speech and voice are the product of the
communicative intent (e.g. to characterize a question or
The voice is the product of the vibrating
recognizable speech. •
Paralinguistic features of voice and speech include speech rhythm, stress, accent and vocal intonation.
Chapter 165 Voice and speech production I
9.
Deficiencies in current knowledge and areas for future research
Monographs. 1968; 35: 429-34. 10.
Fry DB. The physics of speech. Cambridge: Cambridge
11.
Roach P. English phonetics and phonology, 3rd
University Press, 1979.
differences on non-organic voice pathology.
)- Closer mapping of acoustic and ph ysiological
edn. Cambridge: Cambridge University Press, 1999. 12.
measurement to the auditory features of speech and
41: S101-66. 13.
scale for supraglottic features of voice quality needs
27: 179-82. 14.
features of speech and voice in psychiatric and
Locke JL. Wh y do infants begin to talk? Language is an unintended consequence. Journal of Child Language.
psych ological differential diagnosis requires further study.
Wilson JA, Deary IJ, Millar A, MacKenzie K. The quality of life impact of dysphonia. Clinical Otolaryngology. 2002;
to be developed.
» Th e application of the analysis of paralinguistic
Ramig LO, Verdolini K. Treatment efficacy: voice disorders. Journal of Speech, Language and Hearing Research. 1998;
voice is required.
". A reliable and practical auditory perceptual rating
Addington DW. Th e relationship of selected vocal characteristics to personality perception. Speech
»- Studies are needed on the cultural differences in speech and voice and the importance of these
2169
1996; 23: 251-68. 15.
Ryan EB, Giles H, Sebastian RJ. An integrative perspective for th e study of attitudes towards language variation. In: Ryan EB, Giles H (eds). The social psychology of language, attitudes towards language variation, Vol. 1. London: Edward Arnold, 1982.
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16.
Scherer K. Expression of emotion in voice and music. Journal of Voice. 1995; 9: 235-48.
1.
Fawcus R. Chapter 1, The human voice. In: Freeman M,
17.
London: Whurr Publishers, 2000.
Moses PJ. The voice of neurosis. New York: Grune and Stratton, 1954.
Fawcus M (eds). Voice disorders and their management. 18.
White A, Deary IJ, Wilson JA. Psychiatric disturbance
*
2.
Carding PN. Measuring the effectiveness of voice therapy.
and personality traits in dysphonic patients. European
London: Whurr, 2000.
Journal of Disorders of Communication. 1997; 32:
*
3.
Laver J. The phonetic description of voice quality. Cambridge: Cambridge University Press, 1980.
307-14. 19.
Gudykunst WB. Intergroup communication. In: Giles H
*
4.
Mathieson L. Greene and Mothieson's the voice and its
(ed.). The social psychology of language and
disorders, 6th edn. London: Wh urr, 2001.
communication studies. London: Edward Arnold,
*
5.
Baken RJ, Orlikoff RE. Clinical measurement of speech and voice, 2nd edn. San Diego: Singular, 2000.
6.
Harris
T,
Harris S, Rubin JS, and Howard DM (eds). The
voice clinic handbook. London: Wh urr, 2000.
*
7.
Freeman lVi, Fawcus M. Voice disorders and their Management. London: Whurr, 2000.
21.
Scherer K, Giles H. Social markers in speech. Cambriqge: Cambridge University Press, 1979.
Hollien H. On vocal registers. Journal of Phonetics. 1974;
2: 125-43. 8.
1986. 20.
22.
Street RL, Hopper R. A model of speech style evaluation.
Carding PN, Carlson E, Epstein R, Mathieson L, Shewell C.
In: Ryan EB, Giles H (eds). The social psychology of
Formal evaluation of voice quality in the UK. Logopedics,
language, attitudes towards language variation, Vol. 1.
Phoniatrics, Vocology. 2001; 25: 133-8.
London: Edward Arnold, 1982.
166 Objective evaluation of the voice
JULIAN McGLASHAN AND ADRIAN FOURCIN
Best clinical practice
General considerations on objective methods of
2170
evaluation Specific objective methods of evaluation
2174
Key points
2185
2185
Deficiencies in current knowledge and areas for future
2185
research
2185
References
Medline and Embase searches were performed using the key words from the chapter subheadings and with reference to
Clinical measurement of speech and voice.1
Many of the methods of assessment have not been validated thoroughly
except for the self-rated patient questionnaires Voiss and VBI
[***].
quality of life measures, for example Voiss and VBI, but Grades
[**1*]
Clinical recommendations are, at best, Grade B for
C and D for the other measures with no single measure
that can be classed as the absolute gold standard.
GENERAL CONSIDERATIONS ON OBJECTIVE METHODS OF EVALUATION
both to the act of voice production and also to the
Introduction
ance in the normal ratio of periodic sound and noise
mechanisms of voice production . Pathological phonation is associated with an imbal components of the acoustic signal resulting
The aim of this chapter is to provide a theoretical basis for the selection of voice measurements, discuss some of the practical issues involved in making the measurements and to give a description of the utility of some of the more clinically relevant measures.
in poor voice
quality. Voiced sounds can contain either high levels of aperiodic sound waves (often perceived as a rough voice) or additive noise (often perceived as a breathy voice), or both, making interpretation of speech by the listener more difficult. Adequate communication also depends on there being enough energy in the signal, i.e. it must be loud enough to overcome the threshold of hearing of the listener. The other main features of acoustic signals are
Phonation. voice and voice quality
the fundamental frequency determined by the sound source (usually the vocal folds) and harmonic compo
The term
A more
precise definition of 'voice' is the acoustic
their
dependence
outputs from the vocal tract that are characterized by on
vocal
fold
vibratory
inputs. 2
Impaired and absent voice production are referred to as dysphonia and aphonia, respectively.3
nents (determined by the nature of vocal fold vibration and vocal tract resonance). The fundamental frequency of the acoustic signal is perceived as the pitch of the voice. Voice, therefore, provides the framework on which spoken language is constructed.
By means of voice/
phonation quality, pitch range and the systematic use of
Chapter 166 Objective eva l u ation of the voice I 2171
pitch patterning (intonation) a wide range of information about the speaker's gender, age, personality, emotional status and physical health is conveyed. Every human voice is unique because of anatomical, physiological, psycholo gical, cultural, sociolinguistic and behavioural factors. Our voices change throughout our lifetime, but there are also minor, and sometimes major, fluctuations through out a day. As a consequence, defining a normal voice and parameters for measurement for an individual or population is a difficult task. There is a large variability in what is perceived as normal and there is also a continuum between 'normal' and 'abnormal/pathological' voice.
The purpose of an d proble m s with voi ce m easurem e nt
•
•
•
•
Objective measures used in the evaluation of voice have three potential uses: 1. to help characterize the voice and voice problem, thereby providing supportive evidence for a differential diagnosis (e.g. reduced contact quotient in cases of vocal fold paresis or palsy) and pointers for treatment; 2. to provide a measure of severity of the disorder (e.g. self-administered questionnaires) and degree of variance from established normal values (e.g. measures of perceptual evaluation of voice, mean speaking fundamental frequency); 3. as an outcome measure to help assess responsiveness to treatment (e.g. measures of perceptual evaluation of voice and self administered questionnaires).
Visual assessment of the larynx (including, on occasions, diagnostic microlaryngoscopy) remains mandatory for confirmation of diagnosis in all cases. Previous high hopes that acoustic and other measures would provide a noninvasive means of diagnosing voice conditions have not been realized to date due to poor specificity and sensitivity. Attempts have been made to set standards for measurement and assessment.4, 5, 6 These have largely been developed from expert consensus opinion and as a whole are not widely used in routine clinical practice.
•
•
•
•
Perceptual evaluation of the voice: using rating scales to grade the presence and severity of defined qualities of the voice that we can hear, e.g. hoarseness, roughness, breathiness. Acoustic analysis: extracting and objectively evaluating various factors related to the acoustic waveform recorded using a microphone placed near the mouth (e.g. fundamental frequency, intensity, perturbation measures). Electrolaryngographyl electroglottography: indirect measures of vocal fold vibration (e.g. fundamental frequency, degree of contact, perturbation measures) determined by measuring changes in high frequency electrical conductance between two electrodes placed on the skin over the thyroid cartilage. V isual assessment: inspection of the structure and dynamic function of the larynx and rest of the vocal tract together with the vibratory patterns of the vocal folds during phonation (e.g. using endoscopic laryngoscopy including stroboscopy, videokymography and high-speed digital cinematography). Aerodynamic measures: indirect measures of the forces that initiate and maintain vocal fold vibration (e.g. subglottal pressure and airt1ow). Quality of life measures: using self-administered, validated disease-specific or generic questionnaires to assess the patient's perception of the impact of the voice condition on their quality of life, in terms of physical complaints and restriction in participation in daily activities (e.g. Voice Handicap Index, Voiss). [***] Voice accumulator and tests of vocal loading: these are means of sampling the voice or aspects of vocal function either over a prolonged period of time or before and after a specified vocal stress test. Combined measures: attempting to provide a multidimensional measure of voice function (e.g. Dysphonia Symptom Index, Hoarseness diagram, self organizing maps for voice disorder classification).
Types of voi ce m ateri al
Sustained vowels have traditionally been used as voice test material in clinical practice for the following reasons. •
Overvi ew of m ethods of objecti ve eval u ation of voice u sed i n cl i n i cal pract i ce
•
There are many hundreds of measurements of voice that have been developed over the years and the relevance of many of these to the patients' complaints is often not clear. However, the more commonly used measures in clinical practice can be broadly categorized into the following groups.
•
•
They are the simplest separable components of speech. Loudness, pitch, intonation and timbre can, to a degree, be separated and controlled for far more readily than for other speech sound classes. They predominantly reflect vocal fold vibratory activity. If analysis of phonatory onset and offset is excluded, the stable midportion of the utterance is thought to represent the intrinsic quality of a voice which is independent of language.7, 8
2172 I •
PART 16 THE LIPPER AIRWAY
The measurement is quick and easy to perform.
More recent attention has been paid to the use of fluent speech as the test material. This is largely because: •
•
•
•
fluent speech is more directly relevant to the patient's day-to-day experience; it is more related to ordinary voice production and also to a listener's impression of the speaker's phonatory ability, than sustained vowels; there is a continuing need to search for more clinically relevant measures of voice production; it is recognized that the analysis of a short segment of the most stable part of a sustained vowel does not take into account the acoustic cues associated with vowel onset and offset, pitch, loudness and intonation control that take place during speech production.
Fluent speech is not much more time-consuming to acquire (a minimum of 40 seconds is required) and analysis can be performed automatically by many soft ware packages. Both types of material provide comple mentary information about the voice. In singers, however, it may be of value to perform specific singing tasks particularly in an attempt to highlight problem areas with their voice. Useful tests include observation of the acousticlelectrolaryngograph output of pitch glides and by performing a phonetogram (see below under Phoneto gramslvoice range profiles) to assess the extremes of the dynamic range of the voice in terms of loudness and pitch.6
SUSTA I N E D VOWELS
Although the vowel systems of the world's languages cover a very large range of sound types, three oral (without nasalization) vowels are almost universally present: 9 1. a close ('high' ) front articulation Iii (as in English beet); 2. a back ('high') lui (as in English boot); and 3. an articulatory open vowel IAI (as in English card). They give a good basis for the representation of vowel timbre variation and oral articulatory contrasts and they appear very early in speech development. They are staple ingredients of many of the reported clinical studies of pathological voice production. 1 Measurements are usually made on a 1000-ms midsection of the sustained vowel, usually Iii or IAI, produced at a comfortable pitch and loudness.10 Effort levels and day-to-day variability may influence the results and must be taken into consideration when comparing inter- and intrasub ject results. l l Figure 166.1a illustrates a contrast between what can be elicited from a normal voice and one with impairment.
The use of vowel material also provides a link to the voice production elicited in laryngostroboscopy using a rigid endoscope. Here, the laryngologist is obliged to ask for a front, relatively close, setting of the tongue (e.g. 11/, lei or 131 (see Figure 166.2)), so as to get as clear a view as possible of the whole of the vocal folds. In addition, in phonetogram analysis (see below under Phonetogramsl voice range profiles) sustained vowel sounds are used to produce a series of pitches across the individual's natural range each at minimum and maximum loud ness.1S, 16,17,18,19
SPEECH
Speech samples include utterances such as consonant vowel sequences or fluent speech: Consonant-vowel sequences
These are used in two situations: 1. for the investigation of rapid voice 'switching' in diadochokinetic sound sequences. The rate (mean number of utterances per second) vf repetition of utterances, such as alternate voiceless consonants with a vowel, e.g. IpV/, ItV/, IkVI ('pu-tu-ku' ) or IpV/, It3/, Ik31 ('pu-terr-kerr' ) can be measured and an assessment made of the accuracy of articulation and rate variability during the task.2 0 2. in the determination of laryngeal airway resistance.2 1 Here the sound sequence is a succession of only IpVI - the bilabial closure providing a time interval during which intraoral pressure equals that at the glottis. Fluent speech samples are intended to provide a much closer approximation to ordinary discourse. Two types of material are typically used: 1. Read text. Read text has the advantage that the same sets of speech sounds are elicited for each recording and essentially the same duration of speaking time is obtained. In this way, subjective assessments can be randomized and measurements are based on directly comparable data allowing cross-clinical comparisons to be made. The disadvantage is that some patients are not able to read aloud or experience anxiety which can affect their voice quality. Three common texts are used in the UK: The north wind and the sun,22 The rainbow passage23, 24 and Arthur the rat.2S The speaking time depends on the reader and this is a basic failing of text dependent elicitation since voice quality and intonation range are a function of ease of production. A rough rule, however, is that a 40second sa'Inple is needed for perceptual evaluation in order to begin to obtain a useful representation
Chapter 166 Objective evaluation of the voice I 2173 Speaker A: Normal Time Hz
Speaker B: Nodules Patrern
120 60 4D9S
0.80'
I��tt
240
PI
0.54
0.66
...
•
Sp
Sp
Lx
(a)
.,.-...o.IL..._________________ ..__
20
�------�@�
10
10
5
5
;€ e....
;€ o
>
:=: :.0
co ..Q
20
g
2
� ..Q
e
2
e
0...
0...
0.5
0.5
0.2 100
200
100
500
Fx(Hz}
200 Fx
(Hz)
500
®
®
500
500
N � N X LL
N � 200
N X LL
III.
100
200
100
(e) 100
500
200 Fx1
(Hz)
100
200 Fx1
500
(Hz)
Sustained vowels and con nected speech for two women. (a) Speech and electrolaryngograph waveforms (pi, pitch and loud n ess; Sp, acoustic; Lx, contact) showing smooth onset of a sustai ned vowel [A] for a n ormal voice and irregular onset and offset for a patient with nodules. (b) Analyses of two-mi n ute speech samples for the two voice types: total (DFx 1 , every vocal fold cycle, in red) and 'pitch-pairs' (O Fx2, in black). (e) Cross plots (CFx) of the whole speech sam ples com paring one vibratory cycle to the consecutive cycle. Percentage irregularity scores for the normal subje ct and the patient with n odules are 3.4 and 14.7 percent. respecti vely. Figure 166.1
2174 I
PART 16 THE UPPER AI RWAY
Notional position of tongue in oral cav ity
BACK
CENTRAL
FRONT
HIGH Figure 166.2
�nglish vowels with
Some British
key words. This stylized articulatory-auditory map shows the relationships among the steady vowels Notional
of standard British English. The lips are spread for
position
the front vowels and rounded for the back (with
of tongue
the exception of 'bard'). Key words are given in
and jaw
ordinary spelling on the left in bold and on the right in a phonetic transcription that makes use of the international SAMPA symbols, which require only the use of a standard keyboard.12. 13.
14
The map is a Iso used for
diphthongs, gliding vowels as in 'bait. bite. bowed beard .. . •. using arrows to show the starting point and direction of tongue and jaw movement
Table 166.1
Example of normative data based on a total of 43 female and 14 male Portuguese subjects with no self-reported voice
problems (including smokers).
Wo m en '
Men .;-...
ryiean Mean SFF
�. '
.
,
,.
(Hz)
Reading'
Conversation
Reading
Conversation
109.6
109.2
190.3
186.6
Dynamic frequency range DFx 1 90% (octaves)
1.18 ± 0.49
0.75±0.18
1. 12 ±0.48
0.86±0.22
Ofo Irregularity score (CFx)
12. 5± 7.3
23.5± 15.6
Mean contact quotient (Ox)Ofo
45.9
46.3
44.1
43.8
5.9
7.5
6.1
7.3
Standard deviation of contact quotient (Qx)Ofo
12.3± 7.4
7.6±5.2
Reused with permission from Ref. 26.
of the main voice characteristics, while a longer text, e.g.
SPECIFIC OBJECTIVE METHODS OF EVALUATION
measures.
Perceptual evaluation of voice
Arthur the rat (120 seconds) is ideally required for electrolaryngography (ELG) 2. Spontaneous discourse. Spontaneous discourse has the advantage of greater relevance to the daily
use that a patient makes of voice. It has the disadvantages, however, that it may provide
variable material for assessment and a degree of spontaneity of speech that some people find
Table 166.1). The mean speaking fundamental
frequency is slightly higher for read texts.27 It should be noted that for both types of spoken material the extent to which it is representative of the use of voice and in the important than the duration of the sample.
voice
strained, etc.
Read text and spontaneous discourse are not identical
number of incorporated 'intonation groups'
loudness, pitch, intonation and timbre (tone quality)?8 In English, there are many hundreds of descriptors of 'normal'
difficult.
(see
Ordinarily, overall voice quality is regarded as being determined primarily by four basic perceptual factors:
is more
quality,
29,30,31
e.g.
clear,
bright,
dark,
dull,
There is an almost equal richness of
expression for the labelling of pathological voice qualities, e.g. harsh, gravelly, whispery, etc.32 Attempts have been made using factor analysis to reduce these large lists of overlapping
features
to
small
sets
of
nonredundant
scales.30, 32, 33, 34 Most authors, however, agree that the most significant contributions to hoarseness are rough 6, 37 ness and breathiness.24, 35, 3
Chapter 166 Perceptual evaluation of the voice refers to the process
website, although there were no papers published on its
of assessing and grading the severity of these distinctive
qualities in
a speaker's voice
by
use at the time of writing. The
'expert/trained'
an
VPA is recognized as
being a valid and detailed descriptor of voice quality from a phonetic perspective, but is generally thought to
listener.38 It remains one of the most important, widely
be too complex and is not a valid tool for assessing
used, reliable and valid methods of voice evaluation in the clinical field.
2175
Objective evaluation of the voice I
This is not only because the listener>s ear
outcome. 52
Inter- and intrajudge reliabilit y of the perceptual rating
may be the only tool available in a clinical setting as it
requires no expensive equipment, but it is in keeping with
of voice quality depends on the following.
auditory perceptions?9 Perceptual voice characteristics
•
the patient's complaints which are mainly based on their
The training and experience of the assessor. In a study
have been shown to have a quantifiable basis that can
by Yamaguchi et
laryngoscopic
the GRB part of the scale indicating that it can be
correlate
with
other
forms
observations
of
and
assessment, acoustic
namely
analysis.
used confidently by professionals of different
Roughness, for example, correlates not only with jitter
linguistic/cultural backgrounds with appropriate 42 training. , 54, 55 This conclusion confirms the previous
and shimmer but also the presence of spectral sub
harmonics. 39
Numerous
schemes
have
been
developed
finding of Anders et
(Table
166.2) which require the expert listener to rate the voice
•
characteristics using either categorical or visual analogue
scales. Worldwide, the GRBAS scheme
•
(Table 166.3) is
probably the most widely used. Each dimension is rated on a four-point scale, where
ality, 1::: mild,
0 ::: no perceived abnorm 3::: severe abnormality.
2::: moderate and
• •
CDS.43,44 The CAPE V is a new measure
by techniques such as analysis by synthesis or
or human voice).59
The quality being judged. The
GRBAS scheme has been found, for example, to
for percept�al evaluation,
Sch�me
Abbreviation
Grade (of hoarseness), rough, breathy, aesthenic, strained
GRBAS
Grade (of hoarse ness), rough, b reathy. aesthen i c, strained, i nstab i l i ty
GRBASI
Rau higke it (rou ghness). Behauchtheit (breathinessl. Hei serke itsgrad (hoarseness) meth od
RBH
Consensus aud i tory perce ptual eva l u at i on of voice
CAPE V
Buffalo III
4Q 41,42 43,44
45 4S
47
Vo icing evaluation scheme VPA
Voca l profi le analysis
:Factor
R�ferences
32
Hammarberg eval uation scheme
48,49,50
The psychoacousti c and physiological fi n d i ngs associated with each of the five dime n s ions of the GRBAS scheme.39.
Tabl e 166.3 ,.
'
· ' ,PsY ho �c ustIciphys r�� i.c 1 .
�
in
part be due to the difficulties with definition of the
such as pitch and loudness. Details are given on the
�
58
The validity of perceptual analysis can be improved
and strain.42,60 For aesthenia (weakness), this may
visual analogue scale and also encompasses other factors
Su mmary of the most co�r:r:on schemes desc!ib�
The assessors' auditory references. 56, 57,
be most reliable for grade and less so for aesthenia
which replaces the four-point scale with a lOO-mm line
Table 166.2
aL for Finnish, German and
American listeners' perception of hoarseness.55
comparison of similarity to external stimuli (synthetic
The REB scheme is the German equivalent and comes with training
al. 53 there were minimal differences
in ratings between American and Japanese listeners for
�
i�
� correfate�':>' r• . _ �" '• •••_ ...... �••
-
o
C
•_ . , .
' �,,'- �,_-; ".', . . ...
. �;"-_:
'-: ,
,_�-:��•.•,.
•
•
:'�
, j �,..... � 1"
,,,,,.' :-";.
__�'
"
f· ..
Grade (G)
Overal l rating of seve r i ty of abnorm a l ity of voice
Roughness (R)
I rreg u la r pertu rbation of pitch a n d ampli t u d e, noise in l ow freq u e ncy region and the p rese n ce of spectral
Breathi ness (B)
Noise be low the m i d freq u enci es, i n comp l ete clos u re of vocal fo l ds resu l ting in high expiratory flow rate
S1
" , ' , " ,',.",
' .
> i
'
su bharmon ics Aesthe nia (Al Stra i n
(5)
Less harmon i c conte n t in the high freq u e n cy reg ion, i rreg u l a ri ty of pitch and amp l i tude, a fading amp l i tude contour Reflects higher pitch, noise in the higher frequ e n cies, i ncreased amp l i tud e of the hi gher harmon ics an d i ncreased p i tch and a mpi itu d e pertu rbation
2176 I PART 16 TH E U PPER AI RWAY
• •
•
term53 and the fact that it relies on the listener hearing a fall in the amplitude contour of the voice.61 The type and length of voice samples being judged.62 Perceptual evaluation can be made on a sustained vowel, a short phrase, spontaneous speech or a read passage. Evaluation on running speech rather than a sustained vowel is usually recommended as it is more complex and more likely to reveal abnormalities of the voice,54 , 63 although this has been challenged.64 Whether categorical or continuous rating scales are used?9, 38, 52, 54 , 65
For GRBAS there appears to be a trade off between better interjudge reliability with the original four-point scale and finer judgements of voice quality with a visual analogue scale.66 As is often the case with rating scales, the extreme ends of the spectrum (normal and severe) are rated more reliably than the intermediate points.35 Reliability may also be improved if reference dysphonic voices are provided58,67 or by allowing the listener to vary acoustic parameters of a synthetic voice token to create an auditory match of the voice.30 , 68
closure results in a voice that is perceived as 'bright' and can be seen to have a slowly reducing spectral slope. Conversely, incomplete or slow vocal fold closure results in less energy in the 'acoustic spectrum', fewer higher harmonics with inadequate energy radiating from the lips and consequently a steeper spectral slope. The voice may be perceived as breathy or in more extreme cases making the sound pattern unrecognizable or inaudible.69 An excellent summary of various measures used in acoustic analysis that have been developed between 1902 and 1990 can be found in Buder.70
M I CROPHON ES
For accurate measurements of these acoustic measures across the range of vocal frequencies and intensities, a good quality condenser or electret omnidirectional pressure sensitive microphone is required?1 The sound pressure wave radiating from the mouth is converted by the microphone into an electrical signal such that the induced voltage change is proportional to the pressure level. Ideally, it should have a minimum sensitivity of 60 dB and reasonably flat frequency response (i.e. equally sensitive to all audio frequencies) across the range of human hearing (20-20,000 Hz).1, 6 The recording system should be calibrated and the microphone-to mouth distance kept constant. The microphone may be head- or boom-mounted.71 The head-mounted micro phone is usually positioned 8 cm from the corner of the mouth offset by 45° to avoid overstimulation from the breath stream particularly from plosive sounds.72 A boom-mounted microphone is usually held 30 cm from the mouth.73 The amplified electrical signal is then most commonly recorded directly to hard disc or DAT tape and a variety of software programmes is available for display of the waveform and statistical analysis. Analogue tapes are generally not of adequate quality and minidiscs compress the acoustic signal. They may be adequate for clinical recordings of the voice, but are not generally recommended for detailed acoustic analysis. -
Acousti c an d e l ectrol aryngograph meas u res ACOU STI C M EASU RES
Acoustic measures of the voice quantify the physical characteristics of the sound pressure waveform radiating from the lips. The waveform representing the periodic pulse of air pressure produced by the opening and closing (vibration) of the vocal folds can be analysed in terms of an 'acoustic spectrum' consisting of a series of sine waves. According to Fourier's theorem, these sine waves (harmonics) have whole number related frequencies of which the lowest (first harmonic) is known as the fundamental frequency (Fo) and multiples thereof the second, third, fourth, etc., harmonic (e.g. if Fo 120 Hz, second harmonic 240 Hz, third harmonic 360 Hz, etc). Fo in cycles per second of hertz is calculated from the period or time taken to complete one vibratory cycle: =
=
=
Fundamental frequency 1
Time to complete one vibratory cycle· Depending on the nature of the sound, for a given Fo the strength or amplitude of the harmonics changes as the frequency increases and the rate of change is known as the spectral slope (usually measured in dB/octave) (Figure 166.3a,d). Vocal fold closure occurs much faster than vocal fold opening and it is this abrupt closure that largely determines ( 1 ) the amount of energy in the acoustic spectrum, (2) the overall number of harmonics produced and (3) the energy in the high frequencies. This abrupt
ELECTROLARYNGOG RAPH
The electrolaryngograph consists of two electrodes placed on the skin on either side of the thyroid cartilage. A high frequency current (3111Hz) is applied between the two electrodes held at a constant voltage and the changes in electrical conductance with vocal fold vibration are recorded. Experimental data have shown that the change from maximal to minimal conductance reflects the change in contact area between the mucosa of the two vocal folds during a vibratory cycle (Figure 166.3)?4 This signal is unaffected by resonances of the vocal tract and so provides an' accurate method of determining the funda mental frequency of the voice. If the soft tissues of the
Chapter Modal voice [i)
-0
voice I 2177
Breathy voice [i]
80
70
70
60
60
50
50 co
1 66 O bj ect iv e evaluation of the
40
40
(J) "0
30
30 20
20
10
10
0
0
(a)
(d) 2
3
2
4
3
4
KHz
KHz
Maximum separation
Maximum separation
(f)
(c)
Time (ms)
Figure
166.3
(a,d) Average spectra for sustained [i] in modal and breathy voice q u alities; (b,e) stroboscopic views of closure and open
p h ases; (e,f) e l e ctrol aryng og rap h vocal fol d contact waveforms.
neck are thick or there is poor contact of the electrodes on the skin of the neck, it is not always possible to detect a waveform.
SOUND INTENSITY AND SOUND PRESSURE LEVEL
The amplitude of the signal relates to its sound pressure or strength. As a listener, we perceive this as loudness. In practice, sound intensity is measured in terms of the logarithmic ratio of the absolute sound pressure to a reference sound pressure level (SPL) expressed in decibels. This means that doubling the sound pressure raises the SPL by 6 dB (for a more in-depth discussion, see Baken and Orlikoffs and Speaks76). Speech intensity levels for sustained vowels are quite different from connected speech due to the physiological and linguistic pauses in the latter causing marked fluctuations in pressure. Comparison of results published
in the literature is extremely difficult due to the lack of standardization of the measuring techniques.75 The mean SPL for a read text passage of connected speech produced at a comfortable phonation level by healthy subjects is approximately 70 dB measured at 30 cm from the mouth. However, the intersubject variability is approximately 20 dB for men and slightly less for women and the intrasubject variability for repeated measurements is approximately 3 dB.77
FUNDAMENTAL FREQUENCY AND Fo RANGE
Fundamental frequency (Fo) measures can be made on short segments (1-2 seconds) of a sustained vowel made at a 'comfortable pitch and loudness' or a 1-2-minute sample of speech when it is known as the speaking fundamental frequency (SFF). Mean frequency (Hz) and perturbation measures (see below under Measurements of
2178
I
PART 16
THE
U PPER AIRWAY
perturbation) can be determined from the sustained vowel.
(Figure 166.4) can be
Frequency histograms
plotted
from
a
speech
passage
giving
a
graphical
It is important to document whether the Fa was measured from the acoustic or electrolaryngographic signal and how it was calculated, as there are many algorithms
voice. In the Speech Studio programme (Laryngograph
algorithms can lead to errors in calculation resultin g,
Ltd, London,
UK), for example, frequency measurements
are displayed on a logarithmic scale which is divided into 120.25
tone
'bins'
between 27.5
and 440 Hz.
These
that
can
be
used
to
extract
it. I
representation of the dynamic frequency range of the
Some
for example, in spuriously recording subharmonics or complete drop-outs. The reliability of the automatic Fa
calculation
worsens
with
increasing
severity
of the
with all methods, although the electrolaryngo
frequency 'bins' correspond well to perceived pitch and
dysphonia
tend to bias the higher frequencies. In addition, a second
graph generally provides the most robust method for the
frequency histogram (DFx2) can be overlaid on the graph.
speaking voice/B. 79 as it uses a signal derived directly
This counts the 'pitch-pairs', i.e. when two consecutive
from the sound source. This output signal is relatively
periods differ by no more than 10 percent and represents
simple in appearance compared to the more complex
the minimum number of consecutive vibratory cycles that
waveform of the acoustic signal, allowing clear detenni
can potentially be perceived as periodic.
Poor voice
nation of periodicity. Time-domain peak-picking algo
with poor correspondence (Figure 166.1b).
rithms derived from the speech pressure waveform always
quality is in general associated
between the DFxl and DFx2 histograms
Various characteristics can be measured such
as
the
mean, mode and median SFF and the 80 and 90 percent
give an Fa estimation even when the voice quality is poor or when the electrolaryngograph neck electrodes cannot be used.79,
A lower than average mean SFF is found
ranges. Examples of normative values for vocally 'normal' healthy individuals,
including
smokers,
are given
in
Table 166.1.
80
in conditions
that increase the mass per unit length of the vocal fold mucosa,
such
as
Reinke's
oedemaB1, 82
and
(o} Broadband spectrum
/ (c\
Figure 166.4
Sin ger's formant.
(a)
The way that the singer has gradually increased the acoustic pressure by the control of his vocal
fold vibration is shown; (b) Spectrogram analysis of the evolution of formant grouping as timbre is en hanced and reduced Spectrum analysis
(LPC
analysis for the sound
and FFT) made at the beginning of the sound
[A]
[A]
)
(0-4 kHz); (c)
(as in card with n ormal formant placements; (d) The spectral
in the inteNal with 'singer's formant' adjustment.
Chapter 166 Objective evaluation of the voice I 2179
hypothyroidism.83,84 A higher than average SFF is seen in puberphonia,85 ,86 scarring of the vocal folds, laryngeal cancer63 and in some cases of compensated recurrent laryngeal nerve palsy. A restricted frequency range is found in both organic conditions of the vocal folds, neurological conditions, such as Parkinson's disease,87,88 and psychological con ditions, e.g. depression and to a lesser extent schizo phrenia.89,90 Some patients also find empirically that by restricting their frequency range they can maintain a reasonably stable vocal fold vibratory pattern and voice quality. An extended range with good correspondence between DFx1 and DFx2 indicates an exaggerated use of the dynamic range of the voice. In contrast, a large range with poor correspondence suggests poor control over vocal fold vibration and is associated with perceptually severe dysphonia.
1 been used in both adults and children.98,99, 00 It is usually produced by recording the patients' ability to produce sustained vowels (usually ten continuous, periodic cycles 11 of an fa!) 0 across their frequency range at the quietest and loudest note they can produce.99 Experience in performing the procedure to a given protocol is extremely 18 19 102 The leatures . . C 0 f mterest are the overall Important. " shape, loudness and frequency ranges and phonatory area.19,103 It is of value in determining and documenting areas of difficulty of the singing voice104 and for demonstrating improvement in the dynamic range of the voice following treatment of voice disorders.105,106 It is not widely used in the UK as it is quite time-consuming to perform, but it is commonly performed in many other European phoniatric departments.
CO NTACT QUOTI E N T M EASU REM E N T M EASU R E M ENTS OF PERTU RBATION
Sustained vowels: jitter and shimmer
It is normally possible for an individual to produce a vowel for several seconds with little variation (perturbation) in the frequency (jitter) or intensity (shimmer). Pathological voice samples have been shown to have higher levels of jitter and shimmer than normal,91,92,93,94,95 although for jitter these have not been universal findings.96,97 Al though widely used as 'objective' measures of voice, there are limitations to their utility. For a detailed discussion on jitter and shimmer measurements, see Baken and o rlikoff. 27,75 Connected speech: percentage irregularity score
Plotting frequencies of successive vocal fold vibrations against each other during running speech (approximately 120 seconds) should result in a well-defined single diagonal distribution for normal voice (speaker A, Figure 166.1c). In pathological voice, the ability to control cycle to-cycle variation in frequency is impaired resulting in deviation from the diagonal line (speaker B, Figure 166.1c). This deviation can be quantified by measuring the number of data points straying ± 3 percent away from the diagonal and expressing this as a percentage of the total number of data points registered. It can be seen that the CFx percentage irregularity score values for normal individuals in Table 166.1 (which include smokers) are greater for men and for conversational voice. For the two examples in Figure 166.1c, the irregularity scores are 3.4 percent (normal) and 14.7 percent (pathological).
PHON ETO G RAMSNO I C E RAN G E PROFI LES
A phonetogram is a visual display of the dynamic range of the voice in terms of frequency and vocal intensity and has
As well as frequency measurements, it is also possible to derive information about the degree of contact between the vocal folds during the vibratory cycle from the electrolaryngograph waveform. This can be expressed as a percentage of the cycle: Percentage contact quotient Qx Lx
closure width 70% down from positive peak Time to complete one vibratory cycle
There appears to be a positive correlation between contact 1 quotient and vocal intensity for sustained vowels.107, 08 The contact quotient also increases with the level of vocal training, 10 9,110 but also in pathological conditions when the mass of the vocal folds is increased, such as Reinke's oedema and muscle tension dysphonia where the voice is pressed. Reduced contact quotients are usually found in cases of vocal fold palsy and paresis and in some cases of muscle tension dysphonia associated with weak and breathy voices. The standard deviation of the contact quotient is generally increased in dysphonic patients,26 reflecting the increased difficulty in controlling the degree of contact in speech tasks.
SPECTROG RAM
A spectrogram is the three-dimensional display of time (x axis), frequency (logarithmic display on y axis) and amplitude (spectral energy represented by increasingly dark shades of grey) of a recorded sound signal (Figure 166.4b). In normal voice production when a sustained vowel sound is produced over a few seconds the vibratory conditions and vocal tract remain stable. This leads to a relatively stable harmonic structure which can be seen as a series of dark bands on the spectrogram. A fundamental law of digital signal processing (Nyquist sampling theorem) is that it is not possible to capture frequencies that are greater than one half of the samp1·mg rate.1
2180
I
PART 16 TH E U PPER AI RWAY
Frequency and time resolution are therefore inversely related. This means that the higher the frequency sampling rates (narrow-band spectrogram) the more individual frequencies are seen. Conversely at lower frequency sampling rates (broad-band spectrogram), the harmonic structure is seen less clearly as individual frequency bands merge forming broad bands. These harmonic groupings are known as 'formants' (Figure 166.4). The most dense and central parts of these broad bands, i.e. those with the greatest energy or amplitude, represent the resonant frequencies of the vocal tract. They vary in position depending on the constrictions in the vocal tract which in turn are determined by the relative position and shaping of the tongue and lips.69 Often the energy pattern of the higher frequencies cannot be seen in a standard spectrogram. If however it is important to visualize the energy pattern in this region, it is possible to enhance it using computer software available in most spectrogram analysis packages, a process known as 'pre-emphasis'.
LO NG-TERM AVERAGE SPECTRU M
W hilst the spectrogram shows how the frequency-energy distribution in a sound changes with time, the long-term average spectrum removes the time axis and shows how the energy (relative amplitude level in dB) is, on average, distributed across frequency. Some workers consider long-term average spectrum (LTAS) as a potentially good index of voice quality.1 LTAS is, however, an analysis of the whole speech signal and not only combines informa tion about the average distribution of formant resonances but also of the average spectrum of voice excitation.111
LI N EA R P R E D I CTIVE CO D I N G AN D FAST FOU R I ER TRANSFORM
Linear predictive coding (LPC) and fast Fourier trans form (FFT) are mathematical ways of providing a spectral 2 representation of the formants of the speech signaL 11 Essentially they are ways of picking out and displaying the formant peaks (Figure 166.4d). Although it is probably more reliable overall to pick out the formant frequencies by hand, these automated techniques provide a quick, useful alternative. They are not always reliable, particu larly if the signal changes abruptly, the Fo is too high (above 350 Hz) and if there are significant anti resonances, i.e. when there is significant nasalization of the speech sound.1
TH E S I N G E R'S FO RMANT
Western classical singers are able to adjust their vocal tract in such a way that the acoustic result is the clustering of the third, fourth and fifth formants around the 3 kHz region to produce a sound that has great carrying power
and allows the voice to be heard above the sound of an orchestra.113,114 Its production is also thought to require the vocal folds to close rapidly.
M EASU R E M ENTS OF 'NOISE' RATIOS
Rather like speech itself, voice can be considered to have two components: ( 1 ) a well-defined periodic signal that has a clear harmonic spectrum and (2) an additional , source of random 'spectral noise .11s,116 Noise in this context results from the operation of two distinct mechanisms, which can operate singly or together. The first is aperiodic vibration of the vocal folds or some other structure within the vocal tract, e.g. the false cords, and the second is turbulent airflow, e.g. air leakage through an incompletely closed glottis. Spectral noise increases with the openness of the vowel, i.e. it is greater for vowels such as I{I (as in bad) and least for lui and Iii (as in boot and beet, respectively).117 This holds true for both normal and rough voices. Increasing vocal effort and moving from falsetto through modal to creaky (pulse) voice also increases the spectral noise. In general, there is a reasonable correlation (0.74-0.92) between spectral noise and the perceived roughness of a voweL 118 The most common measures used in clinical practice to assess the relative contribution of the periodic signal and noise in the acoustic output are the harmonics-to-noise ratio, the normalized noise energy and the signal-to-noise ratio. Unfortunately these measures do not distinguish between pathological changes as a result of turbulent noise and 2 irregular glottal excitation. 119,1 0 Harmonics-to-noise ratio
The harmonics-to-noise ratio (HNR) (measured in dB) is the mean intensity of an average waveform (noise-free) divided by the mean intensity of the isolated noise component for the series of waveforms in the utterance.69, 12 1 The greater the noise, the lower the HNR (see Table 166.4). Conceptual HNR dB _ -
10
x
Iog 10
Energy contained in the harmonics alone . the nOIse aIone Energy 111 .
Table 166.4 Some exa m p l es of H N R va l ues for M (as in bud) vowel in norm a l , dysphonic a n d treated patien ts. There was n o statistica l differe nce between men a n d women.
Norm a l Preop dysphonics Postop
n
Mean (dB) SO
Range (dB)
42 20
1 1 .9 1 .6
2.32
7.0- 1 7.0 1 5.2-9.6
20
1 1 .3
3.1 3
5.9- 1 7.6
Reused with permission from Ref. 1 21 .
Chapter 166 Objective eva l uation of the voice I 2 1 8 1
The correlation between the HNR and perceptual evaluation has varied considerably between studies. Yumoto et al.1 22 found a correlation between hoarseness and HNR of 0.809, but Wolfe et al.12 3 noted a 0.32 correlation with a seven-point severity of dysphonia score. De Krom 124 found that the HNR ratio was an excellent predictor of breathiness and Wolfe et al. 1 2 5 found that HNR was the most useful measure out of 25 for the prediction of perceptual severity of hoarseness, breathi ness and roughness for a dysphonic population. HNR, however, requires an appreciable time for its calculation for an utterance of several seconds duration and tends to overestimate the noise energy in the presence of jitter and shimmer.12o -
N ormalized noise energy
The normalized noise energy (NNE)126 assesses the relative level of vocal noise to that of harmonics, but bases the analysis on a relatively small number of vocal periods (as opposed to individual cycles as in the HNR) and is therefore much faster to calculate. This has an added advantage that it avoids the effects of drift in fundamental frequency or intensity during the utterance which can be a problem in the calculation of the noise component of the HNR. Like other acoustic measures, the degree of effort used in producing the voice sample, day-to-day variabilityl l and algorithms for calculating the noise energy in the signal can all influence results69 so care must be taken when comparing studies. The NNE has been shown to correlate with perceived breathiness in dysphonic children. 1 2 7 A few studies have been published where it has been used as an outcome measure and to distinguish pathological from normal voices, but its clinical usefulness is still unclear. 126, 1 2 8, 12 9, 130 Signal-to-noise ratio
An alternative approach that avoids the need for harmonic analysis yet effectively achieves the same end result is to calculate the 'signal to noise ratio': 13 1 SIN dB =
20
x loglo
Average amplitude of mean vocal fold cycle . , Average of dIfference between mean and raw cycles
The underlying concept here is that since noise is random its average is zero and the average amplitude will be an essentially noise- free estimate. Subtraction from the raw signal then leaves the noise alone. The process depends, however, on the assumption that the voice signal is truly periodic. In practice, it is difficult perceptually to distinguish between the sensations associated with: ( 1 ) frequency irregularity from cycle to cycle of vocal fold vibration, (2) amplitude irregularity from cycle to cycle and ( 3 ) the presence of random noise in the voice.
G lottal-to-noise excitation
Glottal-to-noise excitation (GNE) quantifies the amount of additive noise (turbulence) in a voice sample and, unlike the HNR and NNE, has been shown to be independent of noise from irregular vocal fold vibration, i.e. from frequency and amplitude perturbations.12o Although it shows great promise as a measure of breathiness/ 1 9,1 32 it is not in widespread clinical use at present.
Visual assess m ent
Visual inspection of the larynx is mandatory for diagnosis or exclusion of laryngeal disease. This can usually be performed in the clinic, but occasionally a diagnostic microlaryngoscopy needs to be performed either when the patient cannot tolerate an examination in the clinic or when the diagnosis is still uncertain, e.g. the aetiology of chronic laryngitis. For more detailed descriptions of laryngostroboscopy and other imaging techniques, see Refs1 33, 1 34, l 35 , l 36 , l 37, 1 38, 139.
Aerodyn am i c m easures
Clinically, there are three main factors that can be measured which are of interest in voice production: air volume, airflow and air pressure.1 40
A I R VOLU M E
The air volume used during phonation is a percentage of the total respiratory volume. In normal conversational speech, the speaker pauses for breath when the lung volume reaches the resting expiratory reserve volume and inhales to a lung volume typically above the tidal volume level.1 41 Air volumes during phonation can be measured either by using a traditional spirometer or by mathema tically integrating the oral airflow signal from a pneumo tachograph.1 40 As a mouthpiece or face mask has to be used, phonation is limited to sustained vowels. Body plethysmography should be used and remains the gold standard if measurements of air volume changes during speech or singing are required. Alternative approaches are to use magnetometers and inductance plethysmographs placed over the chest and abdominal walls, although the . accuracy 0 f th ese techmques · has been questlOne d.20 1 42 '
AI R FLOW
The mean airflow rate (MFR) is usually measured using a pneumotachograph or hotwire anemometer placed in a mouthpiece or face mask. 1 43 It is calculated by dividing the volume of air displaced during phonation on a sustained open vowel such as [ { ] (as in bad) by the duration of that phonation.40 The vocal velocity index
2182 I PART 16 T H E U PPER A I RWAY
(VVI) was designed to provide a degree of flow comparison normalization between differently sized speakers.144 It is calculated by dividing the MFR by the speaker's vital capacity. Normal values for a range of British speakers have been reported.145 Laryngeal dis orders are often associated with excessive air escape and consequently increased MFR and VVI.1 4 3 Conversely, where glottal contact is excessive in conditions such as spasmodic dysphonia these values are reduced.14 3,144 ,146 Both the MFR and VVI have been used as objective outcome measures following treatment. The maximum phonation time (MPT) is a simple clinical test of glottal competence.40 It is measured by asking the subject to inhale as deeply as possible and then sustain a steady [ { ] vowel ( as in bad) for as long as possible. The longest of three repeated measurements is selected. Values under ten seconds are regarded as pathologica1.40 The measurement is of limited clinical value as it is not reliable14 7 and does not distinguish between inefficient glottal valving from reduced poor respiratory reserve and poor driving pressure of vocal fold vibration.14 3 The slz ratio is a variation of the NIPT whereby the maximum sustained time for a speaker to make both an lsi and /zl sound are recorded.14 8,149 A normal speaker can usually maintain the sound for approximately the same amount of time giving a ratio of approximately one. As the /zl sound is dependent on vocal fold vibration, abnormalities which interfere with this vibration150 or affect glottic closure would be expected to reduce the Izi value but not have any significant effect on the lsi time thus increasing the ratio. Although this simple test is used quite widely, in practice some of the original precepts have been challenged as it depends on eliciting a maximum performance in a speaker. Subsequent studies have shown that there is a wide range in normal values and its sensitivity and utility are therefore questionable.14 3 The phonation quotient151 is defined as the vital capacity divided by the MPT. The idea is that there is some correction for the size of the speaker's movable air supply on maximal vowel duration. Although it correlates with the NIFR, it is less sensitive and is of dubious clinical value.14 3 The airflow during each glottal cycle (glottal volume velocity waveform) can be estimated by a technique known as inverse filtering. This is derived from the oral airflow signal measured using a special pneumotacho graph placed in a circumferentially vented face mask. Inverse filtering aims at processing the airflow signal to eliminate the effects of the vocal tract resonances. From this residual measures such as peak flow (Llsec), AC flow (Llsec), minimum flow (Llsec) and maximum flow declination rate (Llsec/sec) can be derived. It is mainly used as a research tool. Orallnasal airflow ratios can be measured and calculated and are of most utility in relation to the assessment of velopharyngeal function and, for particular
classes of speakers (see Baken and Orlikoff152 for a useful overview) .
AI R PRESS U R E
The vocal folds will only vibrate when the air pressure in the subglottis overcomes the tissue resistance of the vocal folds. The phonation threshold pressure is the minimum subglottal pressure required to induce oscillation.1 53, 154 Low frequency phonation threshold pressure has been measured at 0.3-0.4 KPa and generally increases with the frequency of vibration, increased tissue viscosity (stiffness) and increased glotticlfalse cord constric tion.153,155 ,156 ,157 Normal values (using direct methods of measurement) during habitual phonation range from 5 to 10 cm H 0.40 There is a positive correlation with 2 intensity.1 58 Sustained oscillation requires precise control of not only the subglottic pressure, but also the airflow and laryngeal impedance.1 59 ,160 Subglottic pressure is potentially an extremely im portant clinical value to measure as failure to generate an adequate, stable level can result in abnormal speech intensity levels or sudden shifts in the fundamental frequency.161 An inadequate subglottic pressure can result from chest disease ( lung parenchyma or thoracic wall), laryngeal disease or neuromuscular conditions that affect the laryngeal resistance, e.g. vocal fold palsy.158 Excessive subglottal pressures are seen in hyperfunctional voice conditions when the voice is pressed or there is spasmodic dysphonia.16 2, 16 3 Unfortunately, subglottic pressure during phonation is not easy to measure. The most accurate method of measuring subglottic pressure is to place a pressure sensing device in the subglottis. This can be achieved by performing a percutaneous cricothyroid or tracheal puncture with a large bore hypodermic needle and attaching it to a pressure transducer.16 3 Alternatively, a very small pressure transducer can be inserted via the nose and positioned directly in the subglottis.40 ,158 Both these direct methods are mainly used in research studies as they are invasive. Subglottic pressure may also be estimated indirectly by using a body plethysmograph or a pressure transducer placed in the oesophagus.140 , 1 58 An alternative, more practical clinical method is to measure oral pressure during the production of a sound sequence such as Ipi-pi pi-pi-pil at a constant rate, pitch and loudness.21 During the production of Ipl, vocal folds are abducted and the peak intraoral pressure is essentially equal to that throughout the airway, including the subglottis. An estimate of the average subglottal pressure during vowel production can be obtained by measuring pressure at the midpoint of a line connecting two successive pressure peakS . 140 ' 164 rrh'IS meth0 d I' S sImpIe to use and proVI' des a reasonable e�timate of subglottic pressure,156, 165, 166 but care must be used in interpretation and extrapolation of .
Chapter the
from
results
this
very specific sp eec h
task i n to
connected speech . 1 63, 1 64
1 6 6 O bjective eva l uation of the vo ice I
2 1 83
fol lowing t reatment for u nilateral vocal fold paralysis, vocal cyst/polyp, muscl e tension dysphonia 1 S 1 and also in . 1 82. 1 83 . an d a fter specifi c VOIce spasmo d l· C dysp homa 1 84, 1 85 t herapy p rogrammes.
Qu al ity-of-life m easu res It could be argued that o nce the patient has been assured that they do not have a seriou s underlying cause fo r their
voice problem, the need for treatment is determined by their
degree of impairment, disability a nd/or hancli 6 , 68, 1 69, 1 70, 1 7 1, 1 2, 1 73 V i a r ous disease-specific patient 7 cap . 1 7 1 self-report questionnaires h ave been developed 1 74 (Table
1 66 . 5) to assess the impact of the voice compla in t
in te nn s
Voiss
rigorous
of physical complaint and res triction in participation in . . . 3 J 75, 76, 177, 1 78 h ) T e daily activIties an d response to treatment. ' questionnaire
developmen t, bu t
has
undergone
the
most
is not yet widely usedY18 The Voice
Handicap Index (VHI) has been translated into several 7 languages) 9, 180 and is currently the most widely used
measu re. It consists of 30 items which assess the impact of
the voice disorder on physical, functional and emotional aspects o f the patient's quality of life . ) 72 The patients rate their perception of their voice problem from 0 :::: never to 4 :::: always,
giving
a
possible
total score
of
120
Table 1 66.6. O t her stu dies have shown higher mea n scores fo r pa tients with vocal cord palsy (total score :::: 75), b u t otherwise similar values fo r mu scle tension dysphonia cysts/pOlypS . l S I
improve ment
Table 1 66.5
The
VBI
( > 50 percent)
showed
in
s igni ficant sco res
Some of the m o re co m m o n ly used p a t i e n t se l f
t
Pa i e nt self- report
que:stionn�i�e :: ' ,
"
"
;
" _" .
Pa tient q u est i o n n a i re of voca l perfo r m a n ce (VPQ)
.
'.
two quite distinct
methods in use for this type of d ata collection . One is
based on the use of running analysis, the other on raw data acqu isition.
ANALYS I S ACCU M U LATI O N
I n order to avoid th e need for very large storage capa city, one class o f data accum ulator has been designed so that it . . I 6 . . fonnatlOn S or resp on ds to an d on1y stores mtensity In both intensity and fundamental frequency. This confers the
dual
advantages
o f privacy
to
the wearer
efficiency in post- acquisition processing . 1S7
and
Portable
DAT recorders h ave been used for shorter
intervals of raw data collection, but with the obj ective of
providing for much more in tensive post-acquisition 8 analysis. 1 s In this way results are now beginnirtg to be
reported that give sampled measures over the work ing day that cover intensity, timing, fundamental fre
quency and also spectral balance. Modern digital proces
s i ng a nd miniat urization are now advancing to the point where very comprehensive data accumulation will provide
Re,fereoCes 1 75
1 72
Vo ice h a n d i ca p i n d e x (VH I )
for not only greater analytic depth , but also fo r warning
bio feedback to the wearer in the working environment . 1 87
Com b i n e d m easu re m e nts
1 71
Vo ice-relate d q ua l i ty of l i fe (V- ROOl)
1 74
Voice activity a n d pa rt icipation (VAAP)
1 68
Voice sy m p tom scale (Vo i ss)
1 73
Vo ice h a n d icap i nd ex- 1 0 (VH 1 - 1 0)
1 66. 6
a
mean
total
re port q u est i o n n a i res.
Table
speaker's working day. There are
SI G NAL ACCU M U LATI O N
Typical values for the VHI to tal and subs cores a re s een
and
Voice accu mu lation is a generic tenn that is used to
d escribe the collection of voice data during an individual
(see
Table 166.5). in
Voice accu m u lators
There is an intrinsic attra ction in combining multifactor meas ures of voice function to help discriminate between
normal and pathological voices. 1 2o Several schemes have
been developed including the Dysphonia Symptom Index,
M e a n (SO) p re trea t m e n t VH I scores for c o h o rts of w o m e n patie nts p res e n ti n g w i th voca l fo l d n od u les, u n i l atera l vocal fo l d
pa l sy a n d pri ma ry m u scle te n s i o n dys p h o n ia (MTO) c.om pa red t o contro l s (' N o vo ice p rob le m').
Group (n) Mea n a g e ± S O F u n ct i on a l Physica l E m0ti o n a l Tota l score
Co ntrol
(29J
37.2 ± 1 3 .8 1 .96 (7. 52) 3 .53 (4.03) 1 .1 0 (1 .90) 6. 60 (7.52)
U n publ ished w o rk by Stavrou laki and McGl ashan .
(2 1 )
Nod u l es (3 8)
Pa l sy
30.8 ± 1 2.2 1 2. 3 1 (7.25) 1 9.72 (6.70) 1 0.86 (7.02) 42 .55 ( 1 9.06)
57.7 ± 1 7.0 1 2. 68 (8.85) 1 6.62 (7.21 ) 9.05 (7.57] 38.85 (2 1 .65)
MTD
(36)
43.4 ± 1 2.2 " .73 (8. 03) 1 8.70 (8.5 1 ) 1 1 . 1 7 (8.93) 41 .60 (23.02)
2184 I PART 16 TH E U PPER AIRWAY
Hoarseness diagram and the use of self-organizing maps, although the utility of each has yet to be established for routine clinical practice.
DYSPH O N IA SYMPTOM I N DEX
The Dysphonia Symptom Index (DS!) is a single quantitative measure that has been derived by multi variate analysis from 387 dysphonic subjects. It is calculated by summing four weighted aerodynamic and acoustic factors as follows: x
0. 1 3
+
Maximum phonation time (s)
+
Highest frequency (FO) achievable (Hz)
-
Lowest intensity (dB)
- Jitter (%) + =
x
x
x
0.0053
HOARSEN ESS DIAG RAM
The Hoarseness diagram has been proposed as a means of classifying voices acoustically by their degree of breathiness or 'noise features' (as determined by the GNE (see under Measurements of 'noise' ratios)) and roughness or 'aperiodicity features' (as determined by the combination of weighted values of jitter, shimmer and the mean period correlation). These four measures were extracted from 22 well-known acoustic measures of voice quality based on sustained vowels and determined by correlation analysis, mutual information analysis and principal component analysis. For a more detailed discussion see Refs 36, 1 1 9.
0.26 USE OF S ELF-ORGAN IZI N G MAPS FO R VO ICE DISORDER
1.18
CLASSI FICATI O N
1 2.6 (correction factor)
DSI score
A perceptually normal voice gives a maximum value of + 5 , while lesser values (to a maximum of -5) represent worsening degrees of dysphonia. The inverse DSI score has also been shown to correlate well with the VHI total score.1 89 It is not entirely clear why these specific measures should characterize dysphonia particularly, as different vocal disorders may predominantly affect one factor more than another and there are fundamental sex differences between some of the normal measurements.
Using six multidimensional measures (Table 166.7) taken from the Kay Elemetrics Multidimensional Voice Program (MDVP) and cepstral analysis programmes, it has been possible to distinguish normal female voices from those with dysphonia, pre- and post-treatment functional dysphonia voices based on analysis of one second of a sustained /a/ voweL1 90 These have been determined by using self-organizing maps and correlat ing them with perceptual voice quality ratings. Although currently based on relatively small databases, some conclusions can be drawn from the data (see Table 166.8) .
Table 166.7 Six m u ltidimensional measures taken from the Kay Elemetrics M DVP a nd cepstra l ana lysis prog ra m mes used in determ i n i ng norm a l from patho logical voices. Abbreviation
Details
Amplitude pertu rbation quotient
APQ
%
Deg ree of voice breaks
DVB
Rah monic a m p l itude
RAM
Soft phonation i ndex Sta ndard deviation of the fu nda menta l freq ue ncy Va riation of a m plitude
SPI STD
Measure
a
VAM
of varia b i l ity of pea k-to-pea k a m p l itude with in the ana lysed voice sa mple at a smooth ing factor of 1 1 periodsa % ratio of tota l d u ration where fu ndamenta l freq uency ca n not be tracked to the ti me of the co m plete voice sa m p l ea Ampl itude of the first dominant peak in the ce pstra l ana lysis, w h i ch corresponds to the harmonic pea k of the spectru m of the signal b Ave rage ratio of the lowe r-frequency to h igher-frequency harmonic energya Sta ndard deviation of a l l extracted period-to-period fu nda menta l frequency va lues within the 1 -second sa m plea % coefficient of va riation of the pea k-to-peak a m p l itude for vo ice sa m p l es
From the Voice d isorders d ata base, Kay Elemetrics Corporation, 1 994.
b From CSL, Kay Elemetrics Corporation,
Table 166.8
1 994.
Exa mples of a bnorm a l patte rns of the M DVP measurements in different voice disorders.
Voice condition l'J on patho logica l Spasmodic dysphonia Pretreatment m uscle te nsion dysphon ia (fu nctional dysph o n ia ) Reused with permission from Ref. 1 90.
Low val ues/variabil ity
H igh
APQ, VAM ( a n d most other measures) RAM RAM
RAM APQ, VAM, DVB, STD SPI, APQ, VAM
va lues
Chapter 16 6 Objective eva l u ation of th e vo ice
q u al ity co nti n u es to i m p rove. Althou g h cu rrently
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>- Give n the co m p l e x ity of voice , the h u g e ra nge of norm a l i ty a nd ' n ormal' i nter- a n d i n tras u bject va ria b i l i ty, it is u n l ikely that a n y s i n g l e ac oustic, ae rodyna m i c or other mea s u re will be sensitive a n d s pec ific e n o u g h to chara cterize a g i v e n type of vo ice
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a n d cost w i l l a lso play a n i m portant pa rt i n dete rm i n i n g wh ich tests a re a ccepta b l e i n cl i n i ca l practice. ). Th e patie nt's perception of th e i r i m pa i rment,
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./ La ryn g ostro boscopic exa m i n ation of the voca l fo l d s
once s e rious l a ryngeal d isease has been excl u d e d .
rema i ns the gold sta n d a rd exa m i nation for c l i nical assess m e nt of the larynx. a lthou g h i n terpretation of the i m ag es is l a rgely s u bjective with poor i nter- a n d i n tra rater r e i iabil ity,
./ Pe rceptu a l a na lysis of the voice has good re l i a b i l ity particu l a rly for gra d e of h o a rseness, rou g h ness a n d bre ath i ness fol lowing s u i ta b l e t ra i n i ng .
if S e l f-assess m e nt q u estio n n a i res a re perh a ps o f m ost cli nical va l ue as a n o u tcom e measure a nd a re s i m p l e t o admin ister. [Grade B J
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167 Disorders of the voice
JULIAN McGLASHAN
Introduction
2192
Best clinical p rac tice
Patient assessment
2192
Deficiencies in current knowledge and areas for future
Tre atm ent ove rv i e w
2194
Specific voice disorders
2196
Key points
2205
2205
2206
research
References
2206
The data in this chapter are s upported by Medline, Embase and the Cochrane Library searches. Unfortunately, there are very few good qual ity, randomized, controlled studies to support the views in this chapter and most of the evidence is level 2-4.
Objective evaluation of the voice). Although we normally
Dysarthria: Difficulty in articulating words, caused by impairment of the muscles used in speech. Dysarthrophonia: Dysphonia in conjunction with dysarthria, for example after a cerebrovascular accident,
associate a disordered voice as one that is hoarse, this is
head injury or part of a degenerative neurological
INTRODUCTION A normal voice is difficult to define (see Chapter 166,
not always the case. It may only cause problems when
condition, such as motor neurone disease.
certain demands are placed upon it. A disordered voice
Dysphasia: Impairment of the comprehension of
can be defined as one that has one or more of the
spoken or written language (sensory dysphasia) or
following characteristics:
impairment of the expression by speech or writing
stable in a wide range of
•
it is not audible, clear or
•
it is not appropriate for the gender and age of the
acoustic settings; speaker; •
(expressive dysp hasia), especially
when associa ted with
brain injury. Hoarseness: A perceived rough, harsh or breathy quality
to the voice.
it is not capable of fulfilling its linguistic and paralinguistic functions;
PATIENT ASSESSMENT
•
it fatigues easily;
•
it is associated with discomfort and pain on
Ideally, the patient should be assessed in a voice clinic
phonation.
where a voice therapist and a laryngologist are present. The
initial assessment of the patient is
Key defin itions are as follows.
laryngologist's role in the
Dysphoni a: Any impairment of the voice or difficulty
serious underlying causes, determine the impact of the
speaking.
condi tion on the
to formulate a diagnosis or differential diagnosis, exclude
quality of life and provide information
Chapter 167 Disorders of the voice
about treatment options and prognosis. A voice therapist can also contribute significantly to this process and the process of assessment, including laryngeal examination, is often shared in a multiprofessional voice clinic or undertaken in speech therapist-led parallel voice clinics. Speech therapists have particular expertise in assessing voice production, breathing patterns, posture, the presence of disorders of articulation, fluency and communication and psychologically related issues. Voice disorders are often multifactorial in aetiology and to complicate matters patients may develop compensatory vocal behaviours in order to be able to communicate effectively. This may mask the true underlying or primary disorder, for example muscle tension imbalance secondary to extraoesophageal (laryngopharyngeal) reflux. There are four main causes of voice disorders: 1. inflammatory; 2. structural or neoplastic; 3. neuromuscular;
I 2193
• an increased effort and/or reduced stamina of the voice or one that tires with use; • difficulties or restrictions in the use of their voice at different times of the day or related to specific daily, social or work-related tasks; • a reduced ability to communicate effectively; • difficulty in singing; • throat-related symptoms (soreness, discomfort, aching, dryness, mucus), particularly related to voice use; • the consequent emotional, psychological effects caused by the above. Many of the patient self-report questionnaires that have been developed to measure the impact of the voice problem on the quality of life are concerned with these areas of voice complaint (see Chapter 166, Objective evaluation of the voice).
General examination
4. muscle tension imbalance. More often than not patients will have more than one condition contributing to their voice disorder. For example, a patient with vocal fold nodules may well have a degree of muscle tension imbalance and extraoesophageal reflux.
General examination should include that of the oral cavity, oropharynx, nasal cavity, lower cranial nerves, neck for lymphadenopathy, masses and signs of increased muscle tension, external laryngeal skeleton and position, posture, breathing pattern and general affect. 3, 6
VI DEOLARYNGOSTROBOSCOPY
History A detailed history is required and good examples of checklists can be found in Matheison, l Colton and Casper2 and Harris et al. 3 In assessing singers and other professional voice users, an understanding of their occupational and voice requirements is essentiaL 4, 5 In summary, it is important to determine: the nature and chronology of the voice problem; exacerbating and relieving factors; lifestyle, dietary and hydration issues; contributing medical conditions or the effects of their treatment; • the patient's voice use and requirements; • the impact on their quality of life, social and psychological well-being; • their expectations for outcome of the consultation and treatment.
• • • •
The patients' complaints are most frequently related to: • changes in voice quality (hoarseness, roughness and breathiness) ; • a pitch that is increased or decreased which is not appropriate for their age and sex; • an inability to control their voice as required (pitch breaks, voice cutting out); • an inability to raise the voice or make the voice heard in a noisy environment (reduced loudness);
Visual inspection of the larynx is mandatory for diagnosis or exclusion of laryngeal disease. This is usually performed in the clinic, but occasionally a diagnostic microlaryngoscopy needs to be performed when this cannot be tolerated or when the diagnosis is still uncertain, for example, in some cases of chronic laryngitis. The simplest method of examining the larynx and vocal folds is with a mirror? Although excellent views can be obtained by an experienced examiner, the images are relatively small, of brief duration and frequently the anterior glottic region is not well visualized. In addition, the mucosal wave cannot be seen due to the relative speed of vibration of the vocal folds (usually over 100 cycles per second) compared with the ability of the retina to process individual images (five images per second).s Superior views of the larynx can generally be obtained using flexible fibreoptic and videoscopic endoscopes inserted through the nose or rigid endoscopes inserted through the mouth. Using stroboscopy gives additional information about the vibratory pattern of the vocal fold mucosaS, 9 and improves the accuracy of diagnosis. It has led to changes in diagnosis in approximately 30 percent of cases when compared to examination with continuous light alone. lO , 11, 12 Several rating forms for assessing the laryngostroboscopic images have been described, but none have been shown to have good inter- or intrarater reliability.3, s, l3, 14 Although they are not used regularly in clinical practice, they are useful in ensuring that a
2194 I PART 16 THE Table 167.1
UPPER AIRWAY
Key features in the interpretation of laryngostrob�scopic images. '.
,
, (
Glottal closure pattern
taryrig6strobBs<:opic evaluation Anterior or posterior gap Hourglass or spindle shaped Irregular or regular Closed phase
absent/reduced/normal/
Symmetry
of amplitude
Periodicity (regularity)
regular/variable/irregu lar
Degree of change
absent/decreased/
prolonged Mucosal wave (right/left) in
of phase
response to changes in pitch and loudness
increased Description of lesion
Colour Shape Multiple/single Surface
Vocal fold opening/closing pattern (right/left)
Range full/reduced Normal/lag Presence of spasm/tremor
Supraglottic appearance
False cords medial constriction: right/I eft/both Anteroposterior constriction (arytenoid-epiglottic approximation) Prominence/lesion(s)
Symmetry of arytenoids (vocal
SaggitaI/coronaI/axia I planes
processes and apices/ corniculate cartilages)
systematic evaluation of the images is performed. The
clinical psychologist, specialist singing teacher
important features are listed in Table 167.1.
(familiar with voice problems in singers), neurologist, respiratory physician, gastroenterologist or upper gastrointestinal surgeon.
Further assessment If the diagnosis is not clear from the initial assessment,
TREATMENT OVERVIEW
the patient may undergo one of the following options. •
Further in-depth assessment by a voice therapist: - to ascertain more background information including exploration of contributing psychological issues; - to undertake a probe or trial therapy to deconstrict the larynx and assess response to a treatment regime;
•
A trial of vocal hygiene/lifestyle advice or medical
treatment. • •
Laryngeal electromyography. Objective voice measurements (see Chapter 166,
Ideally, the patient should be assessed in a multipro fessional
voice
clinic
by
a
laryngologist
and
voice
therapist and an agreed treatment plan formed. Not all
patients
treatment
presenting
and
some
with
may
be
a
voice happy
disorder being
want
given
a
diagnosis, an explanation of their voice problem and be reassured there is no serious underling condition pre sent. If treatment is required, it will usually consist of one or more of the following options depending on the patient's
symptoms,
vocal
requirements
and
findings:
Objective evaluation of the voice).
•
vocal hygiene, lifestyle and dietary advice;
•
Twenty-four hour pH monitoring ± impedance
•
voice (speech) therapy;
testing or oesophagoscopy.
•
specialist therapy, for example singing therapy,
•
A diagnostic microlaryngoscopy.
•
Referral to another voice disorders team or
•
medical tre�tment;
professional for a second opinion, for example a
•
phonosurgery.
osteopathy;
clinical
Chapter 167 Disorders of the voice
Vocal hygiene, lifestyle and dietary advice It is likely that most patients with a voice disorder will benefit from advice on these issues. Depending on the relevance to the patient this may consist of a discussion or video presentation either in individual or group sessions. Additional material is usually given in patient information leaflets. The areas covered may include:
• an explanation of how the voice works; • the links between lifestyle, phonatory and nonphonatory vocal activities and stress on voice disorders; • the potentially traumatic effects to the vocal folds of 'vocally abusive behaviours', such as talking or singing too loudly, talking too fast, shouting, throat clearing and harsh coughing; • communicating effectively without raising or straining the voice, for example using a whistle in the school playground or using amplification devices where practical and conserving the voice where possible or in extreme situations discussing the possibility of changing jobs; • the importance of adequate hydration for vocal fold function, i.e. by drinking water, use of steam inhalations and avoiding excessive amounts of drinks containing caffeine, i.e. coffee, tea and colas; • smoking cessation, reducing alcohol and social drug consumption (particularly spirits, cannabis and cocaine) and avoiding exposure to fumes, dust and dry air; • diet and reflux reduction, for example avoiding eating late at night, large or fatty meals. More details are available in Chapter 168, The professional voice and Chapter 169, Speech therapy in ENT practice: Scope, science and evidence for intervention.
Voice therapy This is the mainstay of treatment for muscle tension dysphonia (MTD) and may be delivered as an individual course of therapy, usually for no longer than eight sessions, or in groups. Examples of the latter include groups for voice care, professional voice users and for presbylaryngis. The aims of voice therapy sessions are: • to help the patient find a better voice quality which is stable, reliable and less effortful to produce; • to make better use of vocal resonance and tonal quality; • to increase the flexibility of the voice by improving the pitch range and loudness without undue effort; • to increase the stamina of the voice.
I 2195
Various techniques are used including one or more of the following: • vocal exercises with the aim of tar getting and strengthening specific muscle groups and improving glottal closure and efficiency; • increasing awareness of and reducing excessive tension in the muscles around the larynx, neck and shoulders; • advice on posture and improving breathing during speech; • laryngeal massage; • general relaxation exercises and stress management; • psychological counselling; • remedial singing lessons. Some techniques may need additional specialist input from clinical psychologists, singing teachers and osteopaths, for example. Ideally, these individuals should be part of the extended voice disorders team (see Chapter 168, The professional voice and Chapter 169, Speech therapy in ENT practice: scope, science and evidence for intervention for more details).
Medical treatment This mainly includes treatment for acid reflux and upper respiratory tract infections and allergies. It may also include recommendations to change medication for other medical conditions, for example asthma inhalers, diuretics and other antihypertensive medication. An excellent website which lists medications that can potentially cause an effect on the voice can be found at www.ncvs.org/ncvsl info/vocollrx.html. Botulinum toxin injections into the laryngeal muscles may be used in cases of spasmodic dysphonia and arytenoid granuloma (see Chapter 172, Chronic laryngitis and Chapter 157, Neurological disease of the pharynx for more details).
Phonosurgery, including medialization procedures Phonosurgery refers to any surgery designed primarily for the maintenance, restoration or enhancement of the voice. IS It encompasses the following. • Microlaryngoscopic surgery: The vocal folds or occasionally false cords are inspected and lesions removed using a microscope and endoscope. The aim is usually to remove pathological tissue and attempt to restore the normal surface contour and layered structure of the vocal fold. • Laryngeal injection techniques: Various synthetic, biological and autologous materials are usually injected laterally into the muscle of deep layers with a view to augmenting the vocal fold.
2196 I PART 16 THE LIPPER AIRWAY
•
Laryngeal framework surgery: Transcutaneous
be multifactorial, may require empirical treatment or a
surgery performed on the cartilaginous skeleton of
biopsy and microbiological culture, for example in the
the larynx, for example, laryngoplasty (thyroplasty),
case of tuberculosis, or may resolve spontaneously without
arytenoid adduction and cricothyroid approximation
a cause being identified. Patients often complain of:
with a view to improving glottic closure and body
•
•
cover differential tone.16
•
hoarseness;
Nerve-muscle pedicle graft techniques:
•
huskiness;
Nerve-muscle pedicle graft techniques are used for
•
reduced pitch;
bulking out or restoring tone to the vocal fold.
•
loss of part of the range of the voice;
Reinnervation and electrode pacing techniques:
•
pitch instability;
Reinnervation and electrode pacing techniques are
•
an increased effort to speak;
used for restoring tone to the vocal fold or
•
vocal fatigue and pain or discomfort on speaking;
stimulating contraction of specific muscles.
•
More information can be obtained from Chapter 170, Phonosurgery, Chapter 157, Neurological disorders of the pharynx and Chapter 173, Laryngeal trauma and stenosis.
throat symptoms, such as globus sensation and irritation, dryness, throat clearing or chronic cough.
Laryngitis is simply a
descriptive term indicating a
variable degree of erythema, oedema, epithelial change which may include ulceration, leukoplakia and stiffness of the mucosa of the vocal fold. There is often an increased amount of thickish mucus present, which may be white,
SPECIFIC VOICE DISORDERS
grey, yellow or green in colour. There may be associated
The most common voice disorders seen in secondary
and interarytenoid regions of the larynx and the pharynx.
inflammation of the rest of the subglottic, supraglottic practice in a voice clinic are: •
muscle tension dysphonia;
•
laryngitis/muscle tension dysphonia secondary to poor vocal hygiene, dietary and lifestyle issues;
•
extraoesophageal reflux (laryngopharyngeal reflux);
•
vocal fold nodules;
•
vocal. fold polyps;
•
vocal fold cysts;
•
vocal fold palsy and paresis;
•
arytenoid granulomas.
Less frequently seen conditions include: •
sulci and mucosal bridges;
•
spasmodic dysphonia;
•
papillomatosis;
•
microvascular lesions;
•
laryngeal trauma, including post -surgical causes;
•
other neuromuscular causes;
•
hyperkeratosis, dysplasia and carcinoma;
•
endocrine causes;
•
amyloid;
•
other laryngeal tumours.
In severe cases there may be associated shortness of breath and stridor. The voice is usually hoarse (rough, strained, breathy or whispery), which may be due to impaired vocal fold vibration due to stiffness from the inflammatory process and/or secondary to muscle tension imbalance. This can result in the vocal folds being held splinted apart, extra effort being required to induce vocal fold vibration causing perilaryngeal pain or discomfort. Accurate diagnosis may require a diagnostic micro laryngoscopy with biopsy. Treatment consists of reduced voice use and abuse, voice rest, vocal hygiene, lifestyle and dietary advice, appropriate medical or surgical treatment (see Chapter 171, Acute infections of the larynx; Chapter 172,
Chronic laryngitis; Chapter 90, Paediatric voice
disorders; Chapter 91, Juvenile-onset recurrent respira tory papillomatosis; and Chapter 100, Gastro-oesopha geal reflux and aspiration, for more details).
SPECIFIC INFLAMMATORY CONDITIONS
Arytenoid granuloma Arytenoid granulomas are benign inflammatory lesions that arise from the medial surface of the arytenoid cartilages and in particular the vocal processes. Other
Inflammatory disorders OVERVIEW OF INFLAMMATORY DISORDERS OF THE LARYNX
terms for them include: •
contact ulcer or granuloma;
•
vocal process granuloma;
Int1ammation of the larynx can be broadly classified into
•
intubation granuloma;
infective and noninfective causes. Sometimes the aetiolo
•
contact pachydermia;
gical factors are easily identified in the history, for
•
peptic granuloma.
example, hoarseness associated with an upper respiratory
These consist of a proliferation of granulation tissue
tract infection. In many other cases the cause may be less clear, for example in cases of extraoesophageal reflux, may
with epithelial hyperplasia. They result from injury to the thin mucoperichondrium over the vocal processes from
Chapter 167 Disorders of the voice
mechanical trauma, either following intubation or repeated high velocity impact of the vocal processes against each other from throat clearing, coughing or talking in a habitually low pitched, creaky, hyperfunc. 1 manner. 17, 18 Men tend to develop granulomas tiona secondary to hyperfunction, while women develop them more commonly as a result of intubation. In addition, extraoesophageal reflux is recognized as an important aetiological factor either contributing to the symptoms leading to the mechanical trauma or preventing healing of the damaged mucosa. 19 , 20 Patients present with a change in the voice and/or vocal fatigue, a constant tickling sensation, discomfort or pain localized to the posterosuperior aspect of the larynx which is worse on phonation, coughing and throat clearing and it can radiate to the ear. In addition, there may be symptoms associated with extraoesophageal reflux, including choking episodes and, in severe cases, stridor. These symptoms may come on insidiously, after intubation, an infection or a period of stress. They may be unilateral or bilateral and range from a nodular, diffuse thickening over the vocal process to large pedunculated, exophytic masses obscuring the posterior glottis (Figure 167.1). The main treatment principles include reducing the effects of laryngeal irritants, i.e. stopping smoking, improving vocal hygiene, treating any respiratory tract infections, allergies and extraoesophageal reflux. 21 Voice therapy, in terms of raising awareness of and reducing hyperfunctional and vocally abusive behaviour and psychological counselling where necessary, is also of use. 22,23 Surgery d oes not usua11y cure arytenOl'd granulomas when used in isolation, as there is a high rate of recurrence. It is useful in confirming the diagnosis histologically, excluding a carcinoma and in debulking large lesions. 24 Laser vapourization after biopsy reduces the amount of bleeding but it is important to avoid thermal damage to the underlying cartilage. 19 There is no good evidence in support of the use of antibiotics or
Figure 167.1
Arytenoid granuloma.
I 2197
steroids in general. Botulinum toxin injections into the thyroaryte~oid .muscle can be useful as an adjunct
treatment III resIstant cases as it helps reduce the impact of vocal processes against each other allowing the epithelium to heal. 25
Structural or neoplastic lesions OVERVIEW OF STRUCTURAL OR NEOPLASTIC LESIONS
Structural abnormalities can result from neoplasms which may be benign or malignant, or trauma to the laryngeal skeleton or soft tissues. Tumours of the larynx are dealt with in Chapter 194, Tumours of the larynx, and laryngeal skeletal trauma in Chapter 173, Laryngeal trauma and stenosis. This chapter will be confined to discussing the more common benign lesions resulting in referral to secondary care clinics and which involve the superficial layers of the vocal folds. When a patient is observed to have a nodular swelling, i.e. a localized swelling on the membranous portion of one or both the vocal folds, it is important to consider the differential diagnosis in Table 167.2. Accurate diagnosis can be challenging and depends on a detailed history, the use of stroboscopy and to some · . 26 27 Even t h en, a working extent 0 bJectIve measures.' diagnosis should be made and a decision needs to be made as to whether to try an empirical trial of therapy or proceed to a diagnostic microlaryngoscopy. A conservative approach is to reserve a 'microlaryngoscopy and proceed' for 'failed therapy' cases after appropriate informed consent.
SPECIFIC STRUCTURAL OR NODULAR LESIONS
Vocal fold polyps
A true vocal polyp is a benign swelling of greater than 3 mm that arises from the free edge of the vocal fold (Figure 167.2).28 It is usually solitary, but can occasionally affect both vocal cords. It is claimed that polyps are the most common structural abnormality that cause hoarseness and they affect men more than women. 29 They are most frequently seen in smokers and between the ages of 30 and 50 years. 29 ,30 In many cases the exact cause of polyp formation is not known, but most authors agree that phonotrauma is an important aetiological factor. 31 Some are heralded by a sudden onset of hoarseness or loss of voice after yelling or shouting, particularly if the vocal folds are inflamed from acute infective laryngitis or extraoesophageal reflux. There appears to be disruption to the vascular basement membrane, capillary proliferation, thrombosis, minute haemorrhage and fibrin exudation. 32 , 33, 34, 35 Although some polyps have a haemorrhagic appearance, others are more gelatinous and grey. Whether these gelatinous
2198
I PART 16 THE UPPER AIRWAY
Table 167.2
The differential diagnosis of a nodular lesion. Haemorrhagic lesions
Yellowish lesions
True vocal nodules
Haemorrhagic polyp
Rheumatoid nodule
'Physiological nodules'
Ectasia
Epidermoid cyst
Prenodular swellings
Papilloma
Grey, white or translucent lesions
Pseudocyst
Carcinoma
Polyp
Arytenoid granuloma
Mucus retention cyst ± cont act lesion
Epidermoid cyst ± con t act lesion
Localized oedema of the vocal fold from: Reinke's oedema
Lower lip of
a
sulcus
Associated with a vascular abnormality, for example ectasia
Polyps can shrink spontaneously or even be coughed up. Voice therapy may provide the patient with coping strategies, preventative advice and may help ease symp toms, but is unlikely to result in resolution of the polyp.31 Any concomitant inflammatory conditions should be treated.
Most polyps need removal under a general
anaesthetic
and
a
variety
of
techniques
to
achieve
this have been described (see Chapter 170, Phonosur 0, 1 gery).34, 4 4 , 42 The aim is to restore the smooth edge of the vocal cord allowing them to close fully and vibrate normally.
Vocal fold nodules Vocal nodules are bilateral, small swellings (less than 3 mm in diameter) that develop on the free edge of the Figure 167.2
vocal fold at approximately the midmembranous portion
Vocal fold polyp.
(Figure 167.3).
In some cases, particularly in singers, they
may be smaller, more pointed and white in colour polyps have a different pathogenesis is not known. In
reflecting a more superficial response to trauma.43, 44
addition,
They may be associated with microwebs at the anterior
the
distinction
between
nodules,
polypoid
nodules, polyps and localized Reinke's oedema can be
commissure in up to 23 percent of cases.43,
difficult both clinically and histologically and to some
variable
extent is academic as a decision to treat will be made on the patient's symptoms and on clinical grounds.28, 36
thickening of the epithelium with a variable degree ,of
Occasionally, a sulcus, mucosal bridge or intracordal
size
and
are characterized
45
They are of
histologically
by
underlying inflammation. 46 The exact incidence and prevalence of nodules in the
cyst is found immediately opposite on the other vocal
general
fold.37,38 It is hypothesized that in these cases the
population studies nodules have been shown to be the
resulting disordered vibration and stiffness of the vocal
cause of persistent hoarseness in just under 25 percent
fold makes it more likely to damage the other vocal cord causing localized trauma and polyp formation. Alteration in voice quality and voice complaints
is
not
known,
but
in
various
in
children47 and in 6 percent of adults with voice problems. Higher percentages are found in teachers and singers with
will
depend on the effect of the mass of the polyp (and any other associated lesion) on vocal fold vibration, its effect
on vocal fold closure and the secondary compensatory changes, i.e. increased muscle tension.34 The patient may
complain that the voice is hoarse, has lowered in pitch,
cuts out in speech, that they have lost part of the range of the voice and that it is a strain to speak. 39 Very rarely, large polyps can cause difficulty in breathing and episodes
of choking.
population
voice problems.48,49 In children, they are more common
in boys than in girls, while in adults they are very much more commonly found in women particularly under the age of 30.46,50 The aetiology of vocal nodules is not known, but , traditionally they are thought to be due to (voice abuse sl rather than overuse.52 Voice abuse is characterized by forced voice production due to strain in the neck and shoulder region producing a harsh quality to the voice. 53, 54 It may be precipitated by talking for prolonged periods
Chapter 167 Disorders of the voice I
Figure 167.3
Figure 167.4
Vocal fold nodules.
in a loud voice (often above background noise), repeated shouting andlor singing above one's natural range and occasionally repeated coughing and throat clearing. The vocal folds are thought to impact on each other in such a way that the repeated trauma of the midmembranous portions
leads
to
localized
swelling
and
epithelial
thickening.55 Shearing forces may be important and a whiplash hypothesis has also been proposed.56 Psycho logical factors, nasal, throat and chest infections, allergies and extraoesophageal reflux are increasingly being recog
nized as playing an important part in the aetiology of vocal nodules.57, 58, 59 Nodules disappear spontaneously in b oys with the relatively large growth of the larynx in puberty.
60
The voice quality is often husky and breathy worsening
with perilaryngeal
discomfort or throat soreness on phonation. The voice
may become a little deeper in pitch and associated with voice breaks particularly at the higher end of the range of the voice.
The vocal
folds are usually hourglass in
appearance with often only the nodules making contact at the midmembranous zone. There is no good evidence on which to base the treatment of vocal fold nodules.61 Nodules may develop after the individual has been projecting and using their voice more than usual and often settle spontaneously once the demand on the voice returns to 'normal'. be
left
alone.
Aggravating
factors,
such
as
inadequate vocal fold lubrication, allergies, infections
and extraoesophageal reflux, should be treated to reduce their irritant effects. Tn the UK, the mainstay of treatment for persistent vocal noduJes is voice therapy (Chapter 169,
Speech therapy in
ENT practice: scope, science and
evidence for intervention) with the aim of modification of lifestyle and vocal behaviour, providing information and guidance
on
voice
care,
producing
the
voice
the nodules persist. Some argue that complete and rapid return of voice function is only possible if the nodules are excised. Others would reserve surgery for those who fail voice therapy and remain symptomatic.61 Most would agree that a significant number of nodules recur
is
perfonned
without
voice
therapy
either
if surgery pre-
or
postoperatively. 51 If surgery is performed, the aim must be precise excision of the nodule alone with no exposure
or damage to the underlying ligament.4o, 42, 62, 63, 64 Pseudocysts
The exact definition of a pseudocyst varies between authors. Some define it
as
a lesion that differs from cysts
serous fluid, having an appearance similar to that of a blister.42 Others have defined it as localized Reinke's oedema which may indicate the presence of underlying paresis.65 The exact aetiology is not known, but is probably phonotrauma. Reinke's oedema
Reinke's oedema is a term used to describe the vocal folds when they become chronically and irreversibly swollen
(Figure 167.4). Other terms for the condition include: •
more
effectively with less strain and coping strategies. Not infrequently the voice and voice function improves, but
polypoid vocal cord, polypoid degeneration or polypoid hypertrophy; cordal polyposis or polypoid
If
nodules are not causing significant voice problems they should
Grade 4 Reinke's oedema.
and polyps in that it has no cyst wall and is filled with
In girls, they may persist into early adulthood. with voice use and often associated
2199
corditis; •
chronic oedema of vocal folds;
•
pseudomyxoma or pseudomyxomatous laryngitis;
•
smoker's larynx.
It
occurs
almost
exclusively
in
moderate
to
heavy
smokers, although the exact role of smoking in inducing
these changes is not kn0W11.66,67 Some studies have also suggested that voice strain and extraoesophageal reflux may also play a part in its development, although the Importance ·
0f
these other >: lactors
IS •
1
not c ear.
6 . 68, 69 6
Hypothyroidism may be found as a concomitant feature an aetiological
in some cases, but is not thought to be
2200 I
PART 16 THE LIPPER AIRWAY
factor.7o The epithelium shows nonspecific changes and 1 the basement membrane layer is usually thickened.33, 7 ,72
and the presence of leukoplakia. In most cases con servative measures, such as reassurance, an explanation of
In Reinke's space, there are lakes of oedema, extravas
their
ated erythrocytes and thickening of the walls of the
smoking cessation, should be tried initially. Hypothyroid
subepithelial vessels.69,73,74, 75 The true prevalence of Reinke's oedema is unknown. It
condition
and
vocal
hygiene
advice
including
ism, upper airway infections and allergies and extra oesophageal reflux should be treated to reduce the throat
is probably one of the most common conditions to affect
symptoms associated with these conditions. The role of
the vocal folds in smokers and it is very likely that many
voice therapy is controversial but may be indicated if
people with this condition do not seek medical attention.
vocal
A metanalysis of 1538 cases showed that men are affected
dysphonia are prominent in a well-motivated patient. It
more or less equally to women,76 although the pitch
certainly has a role in restoring voice function after
lowering effects on the voice are more conspicuous in
surgical treatment.
women. Patients most commonly seek a medical opinion between the ages of 40 and 60 years of age.66 Patients with even quite severe Reinke's oedema may have no complaints about their voice or problems with voice use. The most common symptoms are:77,78 •
deepening of the pitch of the voice with women often
•
gruffness of the voice;
•
effortful speaking;
•
an inability to raise the pitch of the voice;
•
choking episodes;
•
other symptoms associated with extraoesophageal reflux.
issues
and
excessive
muscle
tension
Surgical treatment should be considered when: •
leukoplakia is present and a histological diagnosis is
•
gross Reinke's oedema is present causing choking
•
pitch elevation of the voice is the main requirement
required; episodes or airway compromise;
being mistaken for a man, particularly on the telephone;
hygiene
of treatment. Other symptoms may not necessarily be helped by surgery
and
there
is
the
potential
for
making
patients worse by causing scarring or an irregular edge to the vocal fold. Patients must be aware that after surgery: •
friends and relatives may not recognize them by their voice;
The diffuse lesions of the membranous part of the vocal fold are bilateral in 62-85 percent of cases, although they
•
the singing voice may be permanently altered;
may be asymmetrical. 66,69 Typically the vocal folds are
•
speaking may be more effortful for up to one year (or occasionally permanently), particularly if excessive
grey or yellowish in colour with prominent superficial
mucosa is removed due to stiffness from scarring and
vessels. Alternatively the oedematous folds may appear
anterior web formation;
diffusely red when coexistent extraoesophageal reflux should be suspected. Leukoplakia is uncommon, but may
•
be due to hyperplasia, dysplasia or very rarely carcinoma in situ. In severe cases the vocal folds look like bags of
•
The principles of surgery for Reinke's oedema include:
deep inspiration79 and is frequently underestimated if an assessment is only made on phonation as the oedematous
•
reducing the bulk of the mucosa (mass per unit
•
obtaining a straight mucosal edge, i.e. avoiding
length) of the vocal fold;
tissue bunches up on the superior surface and into the ventricle. A severity grading system has been proposed by Savic80
leaving small deposits of the myxoematous material
(Table 167.3). There may be a variable degree of
behind;
associated increased muscle tension present. The decision to treat a patient with Reinke's oedema depends on their symptoms, the severity of the oedema Table 167.3
8o 81 Grading of Reinke's oedema. ,
•
avoiding damage to and exposure of the underlying ligament, thereby reducing the chances of scarring and web formation.
'Reduction glottoplasties' can be performed with phono surgical instruments or one of the new generation of
Grade
microspot lasers.42, 63,77,84 The myxoematous material Marginal edge oedema
2
the Reinke's oedema is likely to return within two years if the patient continues to smoke.82,83
fluid that flop up and down through the glottis with respiration. The severity of the swelling is best judged on
the voice seldom returns to 'normal', but is generally of better quality;77,78
Obvious sessile swelling, thrown over vocalis muscle during phonation
3
Large bag-like swelling, filled with fluid
4
Partially obstructing lesion, medial borders in contact a long most of length
from the superficial lamina propria layer is aspirated, removed with forceps or vaporized and the epithelial edges apposed following excision of redundant mucosa as necessary.63,67 Good results from unilateral treatment have been reported with patients often electing not to have further' surgery on the second side.85 Postoperative voice therapy may be required.
Chapter 167 Disorders of the voice I
2201
Endocrine causes Hyperthyroidism has been associated with anxiety,
increased
and tremor affecting the voice,86
hoarseness
The vocal folds have been reported as looking (hypervas cularized and hyperkinetic'.
Hypothyroidism is associated
with: • h oarseness ; •
deepening of the pitch of the voice;
•
voice fatigue and weakness;
•
dryness of the throat;
•
slow and hesitant speech.
Small prevalence studies have not shown an increase in prevalence of biochemical hypothyroidism in patient's with Reinke s oedema 87
but one uncontrolled study that subclinical hypothyroidism may be more prevalent 88 Al th ough the vocal folds are often described '
,
suggested
Figure 167.5
Mucus retention cyst.
Figure 167.6
Epidermoid cyst.
.
as being oedematous in hypothyroidism, there is little histological evidence to support m yxoedematous
infiltra
tion of the vocal folds or muscles. Abnormalities of endocrine function, in particular related to the thyroid and sex hormones, can have varied effects on the voice and voice function Most have not .
in great detail and are beyond the scope of this chapter Of note are the effects of androgen s and
been studied .
androgenic drugs, such as Danazol, wh ich cause irrever sible enlargement of the female larynx with the con 89 90 effects of deepening of pitch. , The
sequent
fundamental frequency of the voice is lowered and the high tones lost at the menopause 90 For reviews on the .
endocrinological effects on the voice) see Refs90,91. Cysts, sulci, mucosal bridges and vergeture Cysts are found less frequently than polyps and nodules and sulci and mucosal bridges even less so. There are two primary types of cyst: a mucus retention cyst and an epidermoid cyst. Both cause the voice to be constantly
Ventricular cysts need to be differentiated from other
hoarse which may worsen with use with varying degrees
tumours (see Chapter 194, Tumou rs of the larynx), but
of roughness and breathine ss
depending on the inter
ference with vocal fold vibration and closure. Part of the vocal singing range may be affected with pi t ch breaks or cutting out altogether.
(Figure 167.5) is thought to arise from a blocked minor salivary gland, possibly secondary to phono trauma or inflammation. It is lined by A mucus retention cyst
cuboidal
or
low
columnar
epithelium
and
can
be 2 associated with oedema and fibrosis in Reinke)s space 3 .
It is usually unilateral and is found on
the free edge of the
vocal fold or can arise in the ventricular fold (false cord)
(Figure 167.5). In the vocal fold they should be suspected in cases of asymmetrical nodular swellings ( cyst plus
contact nodule) and can be difficult to distinguish from 92 polyps on laryngoscopy. Stroboscopy can help in the
can affect the voice by prolapsing on to the vocal fold
in te rfer in g
with
vibration
Epidermoid mous
and
are
trauma or some defect in epithelialization du ring devel 93 ( congenital or dysembryoplastic theory).32,
op ment
They are thought to arise as a result of voice abuse and misuse 94 Large cysts cause a yellowish/white bulge within ,
the vocal fold, but smaller deeper cysts may only be the
presence
the
mucosal
performing a cordotorny.92
by
and
retention cyst, microinclusion of epithelium from surface
by
and
keratin
how these cysts develop, but various theories have been
in
microlaryngosc�py
with
proposed including a metaplasia in a longstanding mucus
reduction
on
filled
exudate in the surrounding Reinke's space. It is unclear
suspected
,
made
secondary
cholesterol debris.32 There is often an inflammatory
differential diagnosis but frequently a definitive diagnosis be
causing
cysts (Figure 167.6) are lined by squa
epithelium
can
onJy
and
hyperfunction,
of localized wave
on
absence
or
stroboscopy
or
abnormal blood vessels over the cyst or the appearance
2202
I PART 16 THE UPPER AIRWAY
of unilateral or bilateral chronic laryngitis.92 The diagnosis may
only
be
confirmed at 32 38 these cases. '
cordotomy .In
microlaryngoscopy
and
mild. Many will require surgery but this must be done
The term <sulcus' has been used to describe different
entities in the literature. The following entities can be
A sulcus vocalis is best used to describe a local-
Phonosurgery).
(Figure 167.7). Bouchayer
et aI?8 describe them as
seem logical that trauma to the neck of a cyst would lead to it widening and discharging its contents. A mucosal bridge
(Figure 167.8) may also be found
in the presence of sulci and epidermoid cysts. This rare finding is thought to arise by the rupture through of the deep aspects of two sulci or cysts to form a tubed pedicle of mucosa. •
possible.42 It is important to avoid leaving part of the wall localized scarring and poor voice results (see Chapter 170,
ized invagination of the mucosa of varying depth
•
precisely preserving the overlying mucosa as much as behind which will result in a recurrence or causing
distinguished: •
Patients with vocal fold cysts should be given a trial of voice therapy, particularly when symptoms are relatively
A sulcus vergeture
(Figure 167.9) is a unilateral or
32,95,96
This
is
more
so
for
mucus
retention cysts as dissection of the thin wall is more difficult. Postoperative voice therapy helps patients to restore vocal function and improvement may continue for up to nine months. There may occasionally be problems with glottal closure following excision of large cysts and fat or collagen medialization may be of benefit. Ventri cular fold cysts should be removed to confirm the diagnosis. There is the potential that they can cause airway obstruction if large or they become infected. Complete sharp dissection of the cyst with microlaryngo scopy instruments or vvith the laser is the treatment of choice.
more commonly bilateral linear adherence of the epithelium to the underlying ligament or muscle along the membranous portion of the vocal fold. Reinke's space exists superolaterally and inferomedially to the vergeture. They are thought to result from a congenital failure of development of Reinke's space
as
they are commonly apparent at
puberty and can be farniliaL38 Patients
with
sulcus
voca lis
and
mucosal
bridges
present with variable degrees of dysphonia and roughness and breathiness, depending on the number of lesions, position and depth of the sulcus, the effect on glottal closure
and
degree
of
associated
inflammation
and
muscle tension dysphonia. Patients with sulcus verge ture
often
have
a
high
pitched
monotone,
(aesthenic), breathy and strained voice which
is
an
weak effort
to produce.
Figure 167.7
Sulcus vocalis. With thanks to Romain Perouse.
Figure 167.8
Mucosal bridge. With thanks to Romain Perouse.
Figure 167.9
Sulcus vergeture.
Chapter 167
The treatment of both types of sulci is difficult and the results variable. If surgical treatment is required for sulcus vocalis, then careful dissection of the pocket off the ligament is required. The difficulty is
in defining the plane
between the base of the sulcus and the ligament and avoiding excessive resection of the mucosa and damage to the ligament.62, 97 Sulcus vergeture may be best treated by bilateral medialization procedures rather then attempted
resection of the vergeture, which is technically extremely difficult. 98
Disorders of the voice
I
2203
the condition.103 A palsy or paresis should be considered in any case where the complaint is of effortful phonation,
throat discomfort or vocal fatigue with use or where the . VOIce . ( cracks'. 104 PerceptuaIIy, t he vOice may sound
breathy, unstable or higher in pitch. An obvious laryngeal
paresis will show asymmetry of movement on abduction
and adduction, i.e. it 'lags behind' the normal side. This
asymmetry may only be apparent on prolonged observa
tion using a fibreoptic endoscope and asking the patient to phonate and then sniff repeated Iy. More subtle signs
are an asymmetry of phase and amplitude of the mucosal
Microvascular lesions
wave and apparent bowing on the affected side on
Microvascular lesions (varices or capillary ectasias) are
stroboscopy.
An effect on the voice may be the first sign of a more
collections of abnormally large and weakened vessels that are most commonly found
(83 percent) on the superior
general
neuromuscular disorder,
such as
Parkinson's
or medial aspect of the midmembranous portion of the
disease, motor neurone disease, multiple sclerosis and
vocal folds
myasthenia gravis.
(Figure 167.10).99 They are most frequently
lOS
Neuromuscular disorders should
seen in professional vocalists (including singers) and are
always be considered in patients where the vocal folds
thought to arise secondary to repetitive trauma, hormo
look normal but the pattern does not fit with a muscle
nal variations or repeated inflammation.lOo, 101 They may
tension dysphonia, fails to respond to treatment or the
be occasionally incidental findings, but can result in vocal
dysphonia worsens.
fold haemorrhage,101 scarring and polyp formation. The lesions can interfere with the vibratory pattern of the
Spasmodic
dysphonia
is
an
uncommon
and
fre
quently overlooked condition. Classically it is classified
vocal folds, causing a lack of clarity of the voice, vocal
as adductor, abductor, mixed and tremor and respira
fatiguelO2 or sudden dysphonia associated with haemor
tory forms, although further subtypes have been de 106 1 scribed. , 07 The adductor form is characterized by a
rhage.101
Voice
and
singing
therapy,
treatment
of
associated inflammation and occasional precise vaporiza
strained/strangled quality to the voice which cuts out at
tion or point diathermy of the feeding vessel(s) may be 1 1 required. 0
the onset of phonation, while the rarer abductor
type
(approximately 15 percent) is characterized by breathy breaks following consonant sounds.107, 108,109 Some
patients present with a whispery (compensated voice) that is easier for them to use in conversation. Others have
Neuromuscular causes Neuromuscular causes are considered
a
in detail in Chapter
157, NeUJological disease of the pharynx. Apart from a
vocal fold palsy, they are relatively uncommon. The prevalence of vocal fold paresis in dysphonic patients is unknown, but appears to be higher than previously thought
if monopolar needle electrodes are used to detect
mixed
form
that
becomes
more
obvious
during
treatment, as the UJltreated form often worsens or is complicated by tremor. The spasmodic laryngeal activity can be seen by careful observation with a fibreoptic endoscope during speech. The mainstay of sympto matic treatment remains botulinum toxin injection into specific intralaryngeal muscles, although the results are not always predictable and poorer for those with the 11 , Ill, 112, 113 abductor form and those with tremor.107, 0
Improvements in outcome
in the future may come with
better targeting of the involved muscles.
I 14
Muscle tension dysphonia or 'functional dysphonia' OVERVIEW OF MUSCLE TENSION DYSPHONIA
Muscle tension imbalance causing MTD is one of the biggest causes or contributors to voice disorders. Although it is often a 'diagnosis of exclusion', i.e. the 'the vocal folds look and move normally', it is often
present with inflammatory, structural and neurological laryngeal muscles try to overcome a
conditions as Figure 167.10
-\
Microvascular lesions (arrow).
deficiency
in
the
voice�producing
mechanism,
for
2204 I
PART 16 THE UPPER AIRWAY
of
•
poor vocal hygiene;
nonnal vocal fold vibration or nasal blockage affecting
•
talking in poor acoustic environments or above
example,
poor
respiratory
function,
impairment
resonance. In addition, MTD can lead to trauma and
background noise for prolonged periods at work or socially;
structural changes in the vocal fold mucosa, for example, some cases of nodules. It is for the laryngologist and voice
•
therapist to agree a treatment plan with the patient in these more complex cases. Muscle tension dysphonia is therefore a group of conditions characterized by an imbalance of the synergist and antagonist muscles affecting the vocal fold position and tensioning relative to one another and also the position of the larynx relative to the rest of the vocal tract
exposure to excessive environmental dust, smoke or fumes.
The degree of dysphonia is variable ranging from an
intermittent problem related to a particular voice task, for example teaching, to severe and constant hoarseness. Other symptoms include: •
pitch of the voice may be too high or too low and reduced in range;
(Figure 167.11). Usually one or more sets of muscles is
a sensation of tightness, constriction or lump in the
hyperfunctional giving recognizable patterns of clinical us, 116, U7, 8 11 It is
•
now thought that previously described hypofunctional
•
effortful voice production;
states are either 'end stages' of hyperfunctional laryngeal .. 7 116 . 11 actIvIty1 ' or represent an underIymg paresIs. 9 The
•
discomfort on speaking or singing;
•
vocal fatigue.
presentation and laryngeal appearance.
.
hypotheses are: •
The variability in the voice quality may be apparent
that chronic imbalance of muscle pull, for example, of the cricothyroid muscle can lead to irreversible
joint damage and ligament stretching giving a flaccid •
throat;
during the consultation or with probe voice therapy. The
laryngeal patterns on laryngoscopy have been classified into six main groups,121 although some of these
bowed appearance to the vocal folds;
features may also be seen in the normal population.122
that a viral neuropathic paresis has developed causing
Palpable increased tension and often tenderness in the
hypotrophy of the thyroarytenoid muscle and
suprahyoid, thyrohyoid and cricothyroid muscles may
consequent poor glottal contact and secondary
also be found, although these findings are not always consistent.116, 121, 123
compensatory hyperfunction.120 The evidence to support this comes from electromyographic
studies.104 True
hypofunctional
neurological
•
vocal hygiene, dietary and lifestyle advice;23
in myasthenia gravis, Parkinson's and
•
motor neurone disease, but are relatively uncommon. There are multiple primary aetiologies of MTD4,23
•
voice therapy targeted at specific muscle 16 24. 125 groups;6, 1 , 1 ' "6 27 I aryngea I mantpu I atlOn; 1 - 1
including:
•
behavioural therapy;128
conditions such as
•
cases
do
exist
in
Treatment, if required, consists of identifying pre
cipitating causes and treating as appropriate, such as:
stress, anxiety and depression;
•
conversion disorders;
•
postural and breathing problems;
•
.
.
medical treatment, for example of extra oesophageal reflux.
SPECIFIC MUSCLE TENSION DYSPHONIAS
Puberphonia 'adolescent transitional voice diso r der or 'mutational falsetto' '
Normally at puberty the voice drops by an octave in boys, but only three to four semitones in girls.129 In boys, the transition takes from 18 months to three years and is usually completed by the age of 14. This voice change in puberty is accompanied by pitch instability and register breaks. The voice appears to be too high in pitch for the individual's age and sex and is often described as 'never broken'. The voice
is
often
momentarily deeper
on
nonphonatory tasks, such as laughing or coughing and this is a key indicator of the condition. Even if it is recognized that the individual has 'two voices', i.e. higher and lower pitched, the latter is not perceived, as their Fig u re 167.11
Muscle te nsi on dysphonia. This is just one of
the many patterns of muscle tension seen.
voi.:e is abn�rmal so consequently not used. T he voice can tire and be effortful to produce on shouting or when
2205
Chapter 167 Disorders of the voice I
p roje cted . Occasionally some patients experience pain
and discomfort
in t he supralaryngeal regi on due to the 3O There is often some elevated p osition of the larynx.I associated ps ychologica l d istress as the boys are often
ridiculed and taunted because of their abnormal voice
and inferred effemina cy.
129
1 8 is stiffened, bowed, atrophic-looking vocal folds. 3 O t he r factors that will affect voice quality are laryngeal position, vocal tract atrophic changes and loss of lung capacity.
Patients may just require an explanation of their voice p roblem and be happy with the exclusion of malignancy. If
treatment is indicated, then vocal care and voice therapy
p u bertal c h anges , the total
with the aim of building up the laryngeal m usculature and
length of a boy's vocal cords grow by as much as 60 percent reaching between 17 and 23 mm in th e bass voice
improving vocal control is most usually offered Injection . medialization procedures using fat or bilateral (modified)
with a relative increase in the ratio of the membranous
thyroplasties have been used
and cart ilaginous parts of the vocal cord. The thyroid
although the results with fat are less p redictable .
As part of the normal
1
with good effect , 39.
virtually doubles in size and the dimensions of all other aspects of the laryngeal anatomy increase proportionally. The ep i glottis changes fr om an omega cartilage
shape to a more flattened shape. It also increases in size and elevates . The mucosal lining of the vocal cord becomes stronger and thicker. The cric othyroid muscle inc reases in bulk and strength to enable the thyroid cartilage to tilt forward for
head or falsetto voi ce.
""KEY POINTS I
,�
\Vhcn assessing •
In p u berp ho nia, the larynx t e nds to be held high in the 1 8 neck, thereby shor tening the vocal tract. 2 The cricoid
usually tilted backwards and the vocal folds lax and limited in their ability to a dj ust to demands in change in tension and vibrational frequency. car tilage is
mucosal waves.
The
cricothyroid
•
16
•
and who are not concerned by their voice generally have a 0f
ch· Olce
.
IS
vO.ice t herapy,
116 , 128 , 131
although occasionally botulinum toxin injections into the cricothyroid muscles have been shown to be effective in resistan t cases. 132 Laryngeal framework surgery is
•
contraindicated. Pres byl a ryn 9 is . , 133 134, 135 . charactenstlCS. In has certam ' males, the mean fundamental frequency tends to rise after 1 the age of 50 36 and the voice is o ften perceived as high
. . The agemg VOICe
pitched, thin and reedy in old age. In women, the mean fundamental frequency tends to decrease with age . Voice
predominant
eA-traoesoph-agea'l reflux may
voice, those that attend at the be hes t of family and friends
The treatment
the
condition(s)
com p la ints? Por example, the treatment
It is important to excl ude org an ic conditions, such as
poor prognosi s regarding resolution.
\%ich is/are
causing the symptoms rel a t e d w the voice
harmonics- to -noise ratios within normal limits and a 131 reduced contact quotient on electrolaryngography.
Although most who present are keen to improve their
- muscle tension imbalance (dysphonia). Is there any suspicion of a malignant or premalignant condition being present?
•
mental within the normal fe male ra nge, intensity and
endocrinological abnonnalities, vergeture and scarrin g.I
ant: or more of the followiJlg four present? - infbmmator>" causes; - structural or neoplastic causes; \Vhi,ch
- neuromuscular causes;
remains excessively
contracted. Acoustic analysis shows a spe aking funda
patient, it is important to
conditions fS
rem ain too
The vocal folds are stre tched and trun with minimal
a
co nsid e r :
•
be
more
of effect.ive
in relieving the patient's �yrnptoms in Reinke's oedema than surgical debu�kjng. Vvhich is or was �he primary cond itio n and which are secolldary o r compensatory? The symptoms and signs of.a sec ond a r y muscle: tension dysphonia may mask the presence of an underlying paresis for example. \Vil1 treating the (easily treatable factors' im prove the patient symptoms enough to either reverse structural laryng.eal changes or i mprove the laryngeal biomechanics sufficiently for adequate funet ionaI voice production, i.e. the voice may flot be perfect , but they can live \\,'ith it? Could the po�entia1 complications of an intervention, particularly surgical treatment, create more prol)lerllS th.an they help? .
-"-".- -
change may be related to the general fitness, voice use and previous training of the
individual.137 The changes are
related to ossification of the laryngeal skeleton, arthritic changes in the cricothyroid and cr icoaryten o id joints, reduced muscle volume with a preferential loss of type I (slow contracti ng) muscle fibres, an increase in density of
collagen deposition and decreased hyaluronic acid in the
lamina p rop r ia, associated with a reduction in fibroblasts
and atrophic changes in t he ep itheli al layer. The net effect
I,'
Best clinical practice .I B est clinical practice is achieved by accurate clinical diagnosis with good quality imaging techniques and having a patient-focused approach, taking into consideration their vocal requirements and concerns.
140
2206 I
PART 16 THE UPPER AIRWAY
./ A multiprofessional team approach allows cost
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168 The professional vOice MEREDYDD HARRIES
Classification Physiology of voice Surgery on the vocal tract Acute illness Key points
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Best clinical practice Deficiencies in current knowledge and areas for future research References
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The data in this chapter are supported by a Medline search using the key words voice, professional and singer.
CLASSIFICATION The professional VOIce can be divided into three categories: 1. The singing performing voice. 2. The speaking performing voice. 3. Voice demanding professions. Professional voice users as a group have their own special needs, the foremost being that their voices are crucial to their careers. Whereas the voice demanding professions, such as teachers, telephonists, telesales, lawyers, etc., need a normal voice to function, the performing voice needs to be at an optimum. This chapter concentrates on the performing voice but the same standard of professional service is demanded for all; a teacher is equally as important as a top professional singer in a West End musical.
opening of the lips and the nasal vestibules. Certain frequencies are amplified and these peaks of frequency are called the formants of voice. The cluster of the third, fourth and fifth formants are known as the singer's formant and are related to the architecture of the vocal tract. 2 It is the pattern of these frequencies that gives the voice its characteristic quality. The fourth and fifth formants are related to the ratio of the volume of the supraglottis (vocal folds to aryepiglottic folds) compared to the vocal tract. 3 This may explain the belief that certain people are born with the potential for a great voice but to achieve this great voice also requires a great deal of work in learning how to use this instrument correctly. Performing artists have certain characteristics of which the laryngologist needs to be aware in the management of their voice disorders.
Personality
PHYSIOLOGY OF VOICE The signal emerging from the vocal folds is a simple harmonic wave. 1 This signal is altered as it passes through the vocal tract (the resonator) from the vocal folds to the
Performers are often flamboyant high achievers and everything in life is a drama. Indeed, a performer's life often moves from crisis to crisis. Although this personality has perhaps been integral in achieving the performer's status, it can also lead to the belief that an upper
2212 I PART 16 THE UPPER AIRWAY respiratory tract infection can be a catastrophic incident. Performers also have to take on the personality and character of their performing role which involves not only voice abuse, such as screaming and shouting, but also altering the configuration of their vocal tract for different accents and to disguise their age and personality. Prolonged supralaryngeal constriction to give certain emotions such as anger or sadness can, in the long term, lead to secondary structural abnormalities of the larynx. 4
Demands The phrase 'a starving actor' is, unfortunately, still applicable and performers are in an extremely competitive market. An inexperienced performer may take on roles outside their range and indeed may be under considerable pressure to do this. The hours of rehearsal are frequently demanding, often with eight performances a week. Some roles are beyond the capacity of one performer although, thankfully, musical/theatre directors are now acknowledging this and are beginning to appoint two performers for one extremely challenging role. Even the more established performer may also require a great deal of courage to be in conflict with the director as his or her reputation may be adversely affected. Performers are now requested to be more versatile and not only singers but also actors and, specifically, dancers. The constricting costumes and physical activity can affect their classical breathing technique. Singers are also asked to sing in different styles, for example, in opera the larynx needs to be lower or vertical and the main emphasis is on vowels. Musical theatre, however, is almost the antithesis of opera singing in that the position of the larynx is higher, there is little vibrato and the consonants are given greater emphasis ('belt' -type style). The more versatile the performer the more employable he or she is.
to the side of the mouth. Amplification with microphones has now become such an accepted part of the performer's life that top performers will often bring their own sound mechanics to improve this. During a performance, being able to hear the voice is desirable for control of pitch and loudness. Auditory feedback is frequently carried out with an earpiece or from side speakers but in some performances this is impossible, making it difficult for the performer to judge what the audience can hear. The Lombard effect is the tendency to increase vocal intensity in response to increased background noise. Singers performing in large halls or outdoor concerts with no auditory feedback tend to over-sing and strain their voices, especially early in their careers. 5
Lifestyle/travel The normal humidity in a plane is 5 percent but at the end of a transatlantic flight can be up to 28 percent. 6 This comes from incidental loss from the body and stresses the importance of hydration for top professionals during international travel. The ambient noise on an aeroplane can be greater than 60 dB and again it is advisable for professional voice users to use their voice minimally during flight. Cross-infection is also common during air travel but can occur at any time. Jet lag is equally important and indeed, in a recent survey, general fatigue was one of the main complaints from performing voice users. 7 Changing time zones can affect normal practice hours which is relevant as auditions are frequently carried out in the mornings, completely throwing the performer's body clock. Performers rarely go on stage with a full stomach and tend to eat late at night. As a result, gastrooesophageal reflux is common.
Performance anxiety Environment Numerous old theatres are dusty, especially in the wings, off stage and in the curtains during change of scenes. A recent performer was seen in the clinic who was found to be allergic to feathers but, unfortunately, for his part of Captain Hook in Peter Pan, was required to wear a large feather in his hat. Artificial smokes and fogs used for special effects are also known to have an irritant and drying effect on the voice. The acoustics of sound are also important and although modern theatres are built with better acoustics it is well known that one of the newest theatres in London is particularly bad for this. As a result, many require amplification in the form of a microphone. The microphone should never be placed directly in front of the lips and indeed, should be 20 cm
The voice is the window of the soul and has an emotional as well as a mechanical and technical component (Figure 168.1).8 The larynx has the greatest innervation of any organ of the body (greater than that of the face and also the hand). Its neuromuscular physiology is complex. It also has abundant hormonal receptors. It is known that there is a slight amount of vocal fold oedema immediately before menstruation and female performers were often given grace days because of this. The condition is known as laryngopathia premenstrualis and is now well recognized. 9 Almost all performers have a certain amount of stage fright due to the effects of adrenaline. Standing on the podium with a dry mouth, sweaty hands and heavy legs is a normal reaction of the body to stre'ss and adrenaline production. Indeed, in some cases, this small amount of adrenaline is beneficial
Chapter 168 The professional voice
I 2213
SURGERY ON THE VOCAL TRACT Emotional factors
Muscle misuse
Figure 168.1
Organic disease
Interacting aetiological factors in dysphonia.
as it primes the performer for action. If this performance anxiety becomes a greater problem then there are three recognized management strategies; deep breathing exercises, an emotional support (the 'magic feather'), or cognitive psychotherapy. Beta blockers have been used by musicians and athletes to prevent tremor but they have had no benefit for the voice. 10 Anxiety can help produce a world class performance and beta blockers have no role in the management of anxiety in the performing voice.
Confidence Many of the best phonosurgeons are either musically trained or have a musical background themselves. This not only reflects their interest in this area but also allows them to be more compassionate and understanding to the performer. To the scientist, the use of modal voice with falsetto at the upper range and vocal fry at the lower range will mean very little to a performer who would rather discuss head and chest voices and persaggio. A laryngologist who understands these terms will inspire confidence in his or her diagnosis, which is essential for the performer. Education of voice users has improved greatly with many presentations and articles by laryngologists in musical journals. A professional voice user would expect to be 'seen in a voice clinic with a full range of equipment which includes a stroboscope and, indeed, it is almost impossible to make an accurate diagnosis without it. It is desirable that a speech therapist and also a singing coach are present when performers are seen. Many performers now also demand a record of their voice either from a video or a video print and also a quantitative record. It may be the recommendation from the voice clinic that the performer returns to his theatre and asks to sing a less demanding part or a different range and it will require a great deal of confidence in the voice clinic for the performer to be able to do this and not feel that their career is threatened in any way.
We have already mentioned the importance of resonance and the formants of voice and specific vocal quality. Vocal tract surgery can be more catastrophic than surgery on the vocal folds themselves. A laryngeal mask should be used rather than an endotracheal tube as an endotracheal tube by definition will cause some oedema of the vocal folds which, in the vast majority of cases, is temporary but potentially could be permanent. Most professional singers have a good musical ear and can vary their technique to accommodate for vocal tract surgery but it is still a high risk situation. Patients should be warned of the risk and, ideally, quantitative measures should be taken pre- and post -surgery for each individual surgeon. Surgery on the vocal folds is dealt with in Chapter 170, Phonosurgery.
ACUTE ILLNESS Performers live in dread of developing an upper respiratory tract infection at anytime, but especially during a performance. It is known that an internationally famous female singer would move to a different area of the house a week before a performance and avoid using any of the crockery of her family to prevent an upper respiratory tract infection. It is important to differentiate between an upper respiratory tract infection with or without laryngeal involvement. An upper respiratory tract infection can be managed conservatively with adequate hydration and steam inhalations. 11 If there is laryngeal involvement and the performance is a career make or break situation then steroids may have a role. 12 If there is evidence of a laryngeal infection, however, it is recommended that the concert is postponed and antibiotics also used. In the acute emergency, if it is the phonosurgeon who says the performance should be cancelled, then quantitative measures are important as large sums of money may be involved and records called upon. Aspirin is associated with vocal fold haemorrhage by its action on the platelets and is something that should be avoided at all times by the professional voice user.
KEY POINTS • The laryngologist mustbe sensitive to the career needs of this group of patients and their special circumstances. • Characteristics of the performing artist include: - .personality: flamboyant, high achiever, 'drama queen'; assume personality of role; voice abuse, altered configuration of vocal tract;
2214 I PART 16 THE UPPER AIRWAY
.,",-, demands: long, hours; conflict with directors;costumes~ ,different singing styles; environment: dust" smoke; allergies;· poor acousticsrabsent' auditory feedback; - lifestyle/travel: flights: dehydration, jetlag, high noise; indigestion: ,. due to irregular eating habits; - performance anxiety: larynx highest innervation and' many hormonal receptors; management: deep breathing, emotional support, cognitive psychotherapy; -' need for confidence in voice ' clinic services: stroboscopy, ,speech and language therapist, singing coach,laryngologist with a' special interest, voice recording equipment. • Full' examination with stroboscopy is essential. • Quantatitive voice analysis is desirable for all cases. • Steroids may have a role during, an acute illness but are best avoided.
With laryngeal involvement, proceed with steroids if it is a career make or break situation, but if there is evidence of laryngeal infection, antibiotics should be given and the performance postponed. Avoid aspirin at all times in these patients as aspirin can cause vocal haemorrhages.
Deficiencies in current knowledge and areas for future research This topic has very few evidence-based recommendations - partly because of the small number of performers seen in most practices, but also due to the fact that many performers do not wish to take part in any trial - it is their livelihood after all! They often do not want other performers/employers to know that they have needed medical advice or treatment for fear of being labelled as having a problem which might compromise future employment. A specific professional voice clinic where all performers can have a regular and comprehensive voice analysis and laryngeal 'MOT' may help overcome this.
The professional voice user is a potentially demanding patient. Patients expect to be seen immediately and laryngologists caring for these patients must be prepared to put aside a significant amount of time
REFERENCES
for this consultation. The laryngologist must be sensitive to the career
1.
Sundberg J. The science of the singing voice. DeKalb,
2.
Sundberg J. Vocal tract resonance. In: Sataloff RT (ed.).
Illinois: Northern Illinois University Press, 1987.
needs of this group and their special circumstances. The care of these patients may not appeal to all
Professional voice; The science and art of clinical care. San
laryngologists as little surgery is generated during
Diego: Singular Publishing Group Inc., 1998: 167-84.
consu Itations. 3.
Patients have high expectations, are well educated in
formant'. Journal of the Acoustical Society of America.
voice physiology and have the right to a stroboscopic
1974; 55: 838-44.
examination by a suitably qualified and interested 4.
laryngologist.
with dysphonia. In: Kirchner JA (ed.). Vocal fold
rumours of various voice problems. Patients do not
histopathology: A symposium. San Diego: College Hill,
want the fact that they have had previous laryngeal ,( Successes will frequently forget you. Equally, should
Mossallam I, Kotby MN, Ghaly AF et al. Histopathological aspects of benign vocal fold lesions associated
Discretion is essential as careers can be ruined with
surgery to become common knowledge.
Sundberg J. Articulatory interpretation of the 'singing
*
1986: 65-80. 5.
Sataloff RT. Patient history. In: Sataloff RT (ed.). Professional voice; The science and art of clinical care. San
phonosurgery not be beneficial then, unfortunately,
Diego: Singular Publishing Group Inc., 1999: 193-201. This
failures in this area may live with you forever.
book is the definitive guide to the management of the
For performing artist with acute upper respiratory infection
professional voice. 6.
Otolaryngology - Head and Neck Surgery. 1984; 92:
,/ Assess clinically to ascertain if evidence of laryngeal involvement and document photographically and voice
Feder RJ. The professional voice and airline flight.
251-4. 7.
Raphael BN, Scherer RC. Repertory actors' perceptions of
quantitatively if major performance or litigation risk ..
the voice in relation to various professional conditions. In:
Without laryngeal involvement, adequate hydration
Lawrence V (ed.). Transcripts of the fourteenth symposium:
of the professional voice. New York, NY: The Voice
and steam inhalation are sufficient and the performer
Care
can proceed if well enough.
Foundation, 1985: 124-30.
Chapter 168 The professional voice
8.
Morrison M, Rammage L. Approaches to voice therapy. In: Morrison M and Rammage L (eds).
performance. Annals of Otology, 1985; 94: 570-4.
The management of
voice disorders. London: Chapman 8: Hall Medical, 1994:
11.
80-97. 9.
Abitbol J, deBrux J, Millot G
Rhinology, Laryngology.
Sataloff RT, Lawrence VL, Hawkshaw MJ, Rosen DC. Medications and their effects on the voice. In: Sataloff RT
et 01. Does a hormonal vocal
(ed.).
syndrome in voice performers by videostoboscopy
Vocal Arts Medicine. New York: Thieme, 1994:
216-25.
cord cycle exist in women? Study of vocal premenstrual 12.
Sataloff RT. (ed.). Common infections and inflammations
1989; 3: 157-62.
The science and art of clinical care, 2nd edn. San Diego: Singular
Gates GA, Saegert J, Wilson N, Johnson L, Shepherd A,
Publishing Group Inc., 1997: 429-36.
glottography and cytology on 38 women. 10.
I 2215
Journal of Voice.
Hearne 3rd. EM. Effects of beta-blockade on singing
and other conditions; Professional voice.
169 Speech therapy in ENT practice: scope. sCience and evidence for intervention
ALISON PERRY
Introduction
2216
Hyperfunctional voice disorders
2225
Functions of the larynx
2217
Psychogenic disorders
2225 2226
Production of sound for speech
2217
Pitch disorders: puberphonia; transsexual voice
Parameters of voice and their anatomical relationships
2217
Laryngeal cancer: rehabilitation of voice after total
Normal versus abnormal voice
2217
Speech therapy intervention,' evidence for efficacy
2218
2227
laryngectomy Key points
2230 2230
Speech therapy: how does it 'work'?
2218
Best clinical practice
Nonorganic dysphonias
2219
Deficiencies in current knowledge and areas for future
Organic dysphonias: benign mass disorders
2220
Voice disorders of neurological origin
2222
2230
research
2230
References
The data in this chapter are supported by a search of the following databases: Medline, PubMed, CINAHL) ClinPSYC, Database of Abstracts of Reviews of Effectiveness (DARE), Evidence Based Medicine (EBM Reviews), The Cochrane database of systematic reviews and the Cochrane Controlled Trials Register. Refereed articles were reviewed using the key words: dysphonia, dysarthrophonia, voice disorders, and focusing on assessment, diagnosis and management. The journal articles included have at least a level 3 evidence in support of the comments made and, in the section on Speech Therapy Intervention, only those articles which have a level 3 evidence and at least two published articles in support of the particular treatment approach have been included in this review. Convention: 'speech therapy' has been used as the generic term in this chapter for intervention by clinicians who are termed speech and language therapists in the UK, speech pathologists in Australia and in the USA and logopedists across much of Europe.
INTRODUCTION
evidence
has
placed
increasing
pressure
on
speech
pathologists. The purpose of this chapter is to examine The role of speech pathologists in ENT practice has
the literature on evaluation and treatment of voice
become increasingly complex in recent years. With the
disorders in the context of evidence-based health care.
advent of new(er) computerized technology for assess
The chapter will focus on disorders of phonation and the
ment and intervention, what was earlier seen as the 'art' of
evidence for the intervention thereof by speech pathol
speech therapy has increasingly become more science
ogists. Voice assessment in detail is covered elsewhere.
based and, as with other branches of medical practice) the
Disorders of speech, resonance and language are not
need for clinical intervention to be underpinned by
evaluated in this chapter, and speech therapy for people
Chapter 169 Speech therapy in ENT practice: scope, science and evidence for intervention I
2217
undergoing phonosurgery will be covered elsewhere. For a
the vocal folds and their operation during phonation that
fuller discussion on the evidence base for the manage
functional care and management decisions regarding
ment of individuals with voice disorders, the interested
voice production can be determined. Most benign laryngeal lesions, such as vocal fold
reader is directed to Carding1 and/or Oates.2
polyps, nodules and cysts, develop in the superficial layer of the lamina propria.4
[***]
FUNCTIONS OF THE LARYNX The three most important functions of the larynx are as follows. 1. Protection of the airway: the larynx is a complete
sphincter that acts to protect the upper airway from saliva and food.3 The extrinsic muscles of the larynx are important for positioning the larynx upwards and forwards during swallowing, under the base of tongue and retroflected epiglottis, thereby providing the airway with protection from the swallowed bolus. The
PARAMETERS OF VOICE AND THEIR ANATOMICAL RELATIONSHIPS The three main parameters of voice are quality, loudness and pitch and all are related to the function of the vocal folds. The quality of voice relates to the extent of symmetry and completeness of the vocal fold vibration. Vocal loudness is influenced by subglottic air pressure, glottal resistance and amplitude of vocal fold vibration. Pitch (the psychological correlate of the frequency of sound produced) is influenced by alterations in the
intrinsic muscles of the larynx control the opening and closing of the vocal folds, which forms another mechanism which operates during swallowing to protect the airway.4 2. Pressure valving: the larynx functions to close off
the airway to prevent the inlet or outlet of air,
length, tension and cross-sectional mass of the vocal folds. The speed of vocal fold vibration is faster when the vocal folds are shorter, thicker and more lax.4 Increased tension and stiffness in the vocal folds translates into higher vocal pitch.
which is crucial for the protective act of coughing. The forced laryngeal closure allows a build-up of subglottic pressure, which when released, is a forceful expulsion of air.3 This is important for expelling any food or fluid that has inadvertently entered the airway. 3. Production of sound/voice: this is primarily the
function of the laryngeal muscles, which act to regulate the mechanical properties of the vocal folds and thus cause vibration which, in turn, create sound.3
NORMAL VERSUS ABNORMAL VOICE There is no accepted definition of normal voice in the literature. This task is made difficult as the variety of voices is immense and standards are broad as cultural, environmental and individual factors all contribute to the development of the human voice.7 Traditionally, voice has been termed disordered when the production of one or more of its perceptual aspects (pitch, loudness, quality and resonance)
are audibly
dissimilar to those of people of the same sex, age and culture.S,9 An alternative definition is that voice is disordered when it no longer meets the requirements 0
PRODUCTION OF SOUND FOR SPEECH
previously attained by the individual speaker. 1 The critical event that is essential for voice production is the vibration of the vocal folds and, in one study, it was agreed among voice scientists that, more than any other scientific
advancements
in
voice
studies,
Prevalence studies
Hirano's5
description of the vocal fold structure accelerated the
Data on the prevalence of voice disorders have been scarce
understanding of normal and pathological voice produc
and have ranged from 0.65 to 15 percent in the general
tion.
population.
[**] Further, as much of the evidence for anatomical
2 The data presented are dependent on the
11, 1
and physiological mechanisms of the larynx has arisen
measures used and one study concluded that prevalence
from cadavaric dissection and basic science, the facts have
varied from 7 percent when the judgement of voice
not changed from more than 20 years ago.
disorders was based on perceptual judgements of experts
[**] Each vocal
fold has been described as a five-layered structure which
to
includes the epithelium, the superficial layer of the lamina
symptoms.12
propria, the intermediate layer of the lamina propria, the deep layer of the lamina propria and the vocalis muscle.6
17
percent when it was based on self-report of
Prevalence
[***] data
for
professional
voice
users
(e.g.
teachers, singers, actors) are more readily available. It
The top four layers, known collectively as the mucous
has been reported that, in many areas of the UK, up to 34
membrane, are controlled by passively slurring vibration.6
percent of the caseload of speech pathologists consists of
I t is through an understanding of the layered structure of
teachers with voice problems.13 Russell et al.14 reported
2218
I PART 16 THE UPPER AIRWAY
that 'studies of voice production in teachers have reported vocal pathology prevalence rates to be as low as 4.4
practice, so the interested reader is directed towards these 1, , 1, , 2 2 22 23 Examining the literature in voice therapy,
texts.
percent while studies that have taken a symptom based
there are few reports of efficacy at level 1 evidence.
approach have found up to 90 percent of teachers with
Reviews have been comprehensive, but not systematic,
vocal dysfunction.' One study of the prevalence of voice
and one review found only 12 of 87 published studies
disorders undertaken on a large sample of adults in I [***] Australia reported a prevalence rate of 4 percent. S
controlled trials (RCTs). 2
which
provided
level
1
evidence
from
randomized
Women are twice as likely as men to report vocal
The remainder of this chapter examines the evidence
problems, but there has been a shift over time with regard 1 ,1 to the prevalence of sex ratios. 4 6 Certain laryngeal
for speech therapy treatment in the people who are
diseases (e.g. cancer, leukoplakia) are more prevalent in 1 men than women. 7 Prevalence data for young people and
disorders.
referred
from
ENT
practices
with
common
voice
children are notably lacking in the literature.
SPEECH THERAPY: HOW DOES IT 'WORK'? Symptoms and signs of abnormal voice
There has been an idiological shift in health care from
Abnormal voice has been described as being:
everyday activities'.24 The International Classification of Function from the World Health Organization2S presents a
'curing' disease to 'minimizing the impact of illness on
•
reduced in volume, to a level where normal hearing listeners would have difficulty in hearing;
common language, classifying health into three domains:
•
excessively loud, which may also be considered a
•
at a pitch level that is deemed to be incongruent for
•
lacking iIi flexibility to alter pitch or loudness,
impairment (of body structure, function); activity limita
quality of abnormal voice; the age and sex of the speaker;
flattened or excessive; characterized by a quality that draws attention in an unpleasant manner.
tion
(difficulty
in
the
execution
of
activities)
and
participation restriction (problems involved in real life situations). It is clear from the literature that a successful
resulting in fluctuations that may be inappropriately •
holistic model of health and offers a framework for using a
IS
outcome from intervention must incorporate more than just a description of the change in body structure or function (impairment level). We cannot assume that this will have an effect on the other domains of health - there is no
direct linear relationship between impairment,
These are all considered abnormal features. In reality,
disability and handicap and
abnormal voice rarely relies on one of these dimensions;
impairment may not translate to gains in the other
usually it is a combination of these and of different proportions. IS Symptoms (complaints) about voice only
an improvement in
an
domains.26,27 Speech pathologists need to record all areas which may be relevant to therapy, including the limitations
provide one aspect of the picture and may often be
in activity caused by the impairment, the social con
misleading whereas signs (observed, testable character
sequences and the emotional wellbeing of the client.27,2s
istics) are, usually, more objective.
Speech therapy is thus directed not only to the impairment
There is no internationally accepted classification of vocal problems; the traditional approach has been to use a 1 classification of 'functional' versus 'organic' dysphonia 9 or,
more recently,
a
classification
system
has
been
suggested that incorporates a combination of symptom
domain (i.e. the larynx), but usually assists the patient to address the participation, activity limitation and distress which arise from the underlying impairment.26 Goal-based
outcomes
(described
as
'content-free'
measures) involve the clinician recording the client' s
and aetiology.20 Four categories were suggested: discreet
progress relative to the goals set for therapy. These goals
mass lesions; distributed tissue changes; organic move
can be tailored specifically for each patient, and can be set
ment disorders; and nonorganic disorders.20 Inconsistent
in consultation with the client and/or carer, making the
terminology and the multifaceted nature of many voice
measure both sensitive to change and relevant to the
disorders, as well as variability in the vocal assessment
needs of the client.29 However, 'two clients/patients can be
techniques
treated to achieve the same goal, but achieve different , outcomes .30 For example, someone having speech
used,
still
contributes
to
the
confusion
surrounding acceptable terminology and classification.
therapy
for
dysphonia
may
experience
changes
in
laryngeal dryness and/or control of laryngeal movements
SPEECH THERAPY INTERVENTION: EVIDENCE FOR EFFICACY
ability to change pitch or to be heard on the telephone
There have been comprehensive reviews of the treatment
anxiety (wellbeing/distress) as a result of speech therapy.
evaluation studies in the field of voice, and voice therapy has been well reviewed in the context of evidence-based
(impairment level), while another may experience the (activity level)
and
another
will
experience
reduced
In terms of addressing a voice problem (dysphonia), speech therapy may be broadly described as a behavioural
Chapter 169 Speech therapy in ENT practice: scope, science and evidence for intervention
treatment, usually involving addressing: the faulty 'mechanics' of voice production; the environmental aspects which may be contributing to the vocal problem (such as dryness, pollution, noise, smoke, etc.) and the psychological aspects of the problem - the effects of stress and tension on voice production. Assessing, and correcting where necessary, the 'mechanics' of voice involves some, or all, of the following domains: posture; respiration; coordination of respiration and phonation; phonation, i.e. pitch, quality, loudness, resonance. Suprasegmental aspects of voice in speech, such as intonation and prosody, may also need attention. Insight and understanding of the problem is a prerequisite for vocal change to occur. Speech pathologists aim to assist with the 'whole' problem for the person, rather than just changing the impairment domain.
NONORGANIC DYSPHONIAS Infections. chronic conditions Many infections, chronic illnesses and trauma have been found to contribute to laryngeal disease. 31 When auditing causal factors for voice problems, one study reported that, in people with inflammations and infectious conditions, laryngopharyngeal reflux (LPR) was present in 55 percent of cases, chronic tobacco use in 25 percent and upper respiratory tract infections in 15 percent of people referred to the Centre for Voice Disorders. 32 [***] Infections targeting the upper respiratory tract can lead to inflammation of the larynx with dryness and swelling of the mucosal membranes and edges of the vocal folds and this can be acute, lasting no more than ten days, or chronic. 33 Acute laryngitis may be caused by either viral or bacterial agents and the voice is often affected (usually a husky, hoarse quality). Although most people with acute laryngitis do not present for laryngeal and voice evaluation,34 speech therapy advice 1S sometimes sought, especially by professional voice users. This is usually directed at \eaching conservation of voice and techniques to minimize voice abuse and misuse whilst the problem is medically treated. The evidence for bacterial infection as a causal agent in acute laryngitis has been supported in one study.35 [***] An absence of bacterial infection in the mucosal secretions of people with chronic laryngitis has been found. 36 [***] Causal factors that have been proposed as contributing to chronic laryngitis include: laryngopharyngeal reflux; allergic rhinitis; trauma; vocal abuse; smoking; thermal, chemical or caustic irritation; drying medications and rhinosinisitis. 31,34 In one study, 74 percent of patients who had been referred with posterior laryngitis displayed LPR which resulted in chronic vocal abuse. 37 Several other studies support this finding and more recent papers documented
I 2219
common symptoms of chronic laryngitis as being: hoarseness, reduced voice quality; dysphagia, chronic throat-clearing and cough; excessive mucous and oedema; globus sensations. 38 ,39 [***] Speech therapy for chronic laryngitis is often focused on the effect of the voice problem, rather than just addressing the impairment with 'voice exercises'. In reality, 'people with disabilities are primarily concerned with outcomes at the levels of functional limitation, disability and societal limitations, because it is in these dimensions that they experience their medical condition'.27 Generally, patients do not present to speech pathologists describing the cause of the problem 'chronic laryngitis' - but rather describing the effect of the problem - voicing complaint and frustration relating to the signs and symptoms of misuse and abuse of (their) voice - habitual patterns which may have arisen secondary to the underlying disease. Speech therapy is therefore directed at both alleviating symptoms (such as throat -clearing, coughing, excessive dryness or excessive mucus production) and improving signs (hoarse, husky voice, excessive and strained vocalization). If hyperfunction is noted, then a behavioural programme may be instigated to reduce vocal fold contact, to reduce laryngeal and pharyngeal muscle tension and to change vocal patterns (see evidence for therapy below under Hyperfunctional voice disorders). There are data supporting the proposition that vocal hyperfunction and emotional factors can lead to voice disorders.2, 40 [**** /***] Although there are no level 1 or 2 examples of prevention programmes being effective in the literature, speech therapy for people with laryngitis, directed at detecting and alleviating voice problems, may be beneficial. There is a low level of evidence for effectiveness of vocal hygiene programmes in groups such as school children, teachers and cheerleaders in preventing voice disorders. 41 [**]
Effectiveness of speech therapy In many studies evaluating the effectiveness of voice therapy, treatment of people with nonorganic dysphonias has been examined. RCTs of voice therapy have compared two treatment methods;42,43 a treatment with no treatment or a placebo;44 or two treatment methods and no treatment in the same study.45, 46 There has been good evidence provided by these studies that symptomatic! behavioural voice therapy is effective in perceptually improving voice, in patients who present with nonorganic dysphonias. [****] The Accent method of voice therapy employs rhythm and intonation (accent), abdomino-diaphragmatic breathing exercises and body and arm movements designed to achieve better control of speech and voice production and to manage two opposing functional deficits - the state of glottal waste and the state of
2220
I PART 16 TH E U PPER AIRWAY
excessive glottal tightness.47 The exact mechanism for readjusting vocal physiology is yet to be understood, but it is thought to be achieved by enhancing the Bernoulli effect at the glottis through better pulmonary support. Using an RCT design, albeit with small subject numbers (n 42), the benefit of the Accent method when combined with vocal hygiene over vocal hygiene alone has been demonstrated.42 [****] [Grade B] Vocal hygiene is an encompassing term to describe techniques which are routinely incorporated into most voice therapy programmes. It includes, for example, reducing the amount of talking, reducing loud, effortful talking, eliminating vocal abuse and manipulating the environment to be optimal for voice production. Few studies into the efficacy of voice therapy have used double blinding, as this is not feasible in most investigations of patients with dysphonia. =
ORGANIC DYSPHONIAS: BENIGN MASS DISORDERS Vocal nodules
Vocal nodules are a frequent disorder in children and adults. They present as benign, localized lesions, appear ing as a densely packed collection of cells, distinct from neighbouring tissue.48 Typically, nodules arise (either unilaterally or bilaterally) on the edges of the vocal folds, at the junction of the anterior third and posterior two thirds of the vocal folds and always, when bilaterally occurring, symmetrically on both cords. This junction is found to be the site of maximum force at adduction during phonation.49 People with vocal nodules often present with restricted pitch range and voice breaks. Vocal nodules originate from a combination of over use and incorrect use (sometimes termed 'misuse and abuse') of the voice. If detected early they can be cured, or significantly reduced, by minimizing the use of the voice while learning to use the voice properly. 50 There is valid evidence of the effectiveness of speech therapy in studies investigating treatment methods with people who have vocal nodules, using both empirical case studies and prospective controlled studies without randomization.51, 52 [***] Although the sample size was small (n = 6), a double-blind study into an evaluation of hydration against placebo as a treatment for vocal nodules was also convincing. 53 [***] The treatment of choice for people with vocal nodules is remains re-education of the voice by a suitable training programme that motivates the patient to practise outside the clinic to change faulty vocal habits and eliminate vocal misuse and abuse. There is no evidence for advising complete voice rest in treatment and, indeed, the reality is that this is usually too difficult to adhere to, as patients
would need to take leave of absence from work and seclude themselves. 54 Although vocal nodules may indeed disappear with no vocal use, the question remains as to what will happen once normal life - and habitual voice use - is resumed. Unless the incorrect vocal habits that led to the nodules are addressed, then there is a high probability that the nodules will recur. Similarly, where treatment includes surgical removal of the nodules alone, without vocal re-education and change of habit, there is little chance of surgery, by itself, eliminating the problem. Indeed, a case controlled nonrandomized study indicates that treatment by voice therapy and laryngology review is preferable to treatment by surgery followed by therapy. 50 [***] [Grade B]
Cysts of the vocal folds
Vocal fold cysts usually develop in Reinke's space below the squamous epithelium.49 Cysts may cause trauma to the opposing vocal fold as well as causing mass and stiffness changes in the vocal fold cover. Two vocal fold cysts which are important in voice disorders are mucous retention cysts (intracordal) and epithelial inclusion cystS.54 Both may result from laryngitis and can interfere with the function of voice to a greater or lesser degree, depending on the site of the cyst. Usually, cysts arise halfway along the membranous part of the vocal fold cover, so vocal symptoms may be considerable as there is a reduction or absence of a mucosal wave over the area of the cyst.4 In a study of 26 women with cysts, hoarseness was a symptom reported 79.1 percent of the time.55 Cysts are usually surgically removed and afterwards, a period of voice therapy may be necessary to correct any faulty vocal habits which formed while the cyst was present. There have been no published studies examining the efficacy of voice therapy with this population; rather the studies have concentrated on perceptual, acoustic and physiological affects of cysts on the voice and examination of surgical outcome. 56
Granuloma
Granulomas are rare, benign, inflammatory masses which may be unilateral or bilateral and are found at, or slightly cranio-posterior to, the vocal processes, in the cartilagi nous part of the glottis.57 Researchers are still debating whether these should be considered along a continuum with contact ulcers. 53, 58 Contributing factors to granulomas have included: • •
• •
intubation;58, 59 laryngeal surgery; both on its own and after radiotherapy;58 vocal abuse;58, 59 gastroesophageal reflux.6 0
Chapter 169 Speech thera py in ENT p ra ctice: scope, sci ence a n d evidence for i n te rve n ti o n I
The effect on voice is usually that of low pitch, monotony, vocal fry (creak) and hyperfunction. Hoarseness is not a common symptom as the granuloma usually sits on the cartilaginous part of the glottis and seldom affects vibration.61 [***] Chronic irritation caused by hiatus hernia and gastric reflux has been cited as the basic problem which, in turn, causes chronic coughing and harsh frequent throat clearing. It is these abusive behaviours, excessive coughing and throat-clearing, that then initiate contact ulcers and granuloma formation.62 In one study, response to medical treatment was successful in 21 of 22 cases63 and thus medical evaluation and treatment for a possible gastro intestinal reflux condition needs to be part of the total treatment protocol. [***] Voice therapy is appropriate in order to eliminate laryngeal abusive behaviours. [Grade C]
Papillomatosis of the larynx
Papilloma is a benign epithelial tumour, presenting as a warty epithelial mass on one of the cords. Papillomas usually enter the superficial layer, but may on occasion involve the intermediate and deep layer of the lamina propria of the vocal fold.49 It is caused by the human papilloma virus (HPV ) types 6 and 11 and there is reportedly a link between genital warts and laryngeal papillomas.64 Papillomas are reportedly most common in children between two and four years old and are comparatively rare in adults.64 In adults, surgical removal of the tumour is unlikely to be followed by a recurrence, although there has been a recurrence of papillomas reported in two patients after 44 and 47 years respec tively.65 [**] In children, howeve:.;, these tumours tend to recur and multiple papillomas may occur on both true and false vocal folds, extending onto the epiglottis and some occasionally extend to the trachea and bronchi. As prognosis improves with age, the chance of extension and recurrence becomes less with attaining adulthood.54 The quality of voice then becomes reasonable, provided that multiple operations have not caused permanent scarring or stenosis. Surgical treatment needs to ensure the damage to the growing larynx is avoided and that subepithelial layers are preserved. Voice therapy in children, teaching nontraumatic use of the voice, may be important so that continuous trauma due to incorrect voice use (which might stimulate growth of the papillo matous tissue) is avoided. No study exists that system atically compares voice therapy with watchful waiting.
Vocal fold oedema and polyps
A polyp is a well-differentiated, ,hyperplastic, benign pathological structure of the mucous membrane.66 A thin layer of connective tissue separates the epithelium of the vocal folds from the underlying ligament and muscles.
2221
The potential space under the epithelium is called the subepithelial space of Reinke, or Rienke's space. Accu mulation of fluid in this space results in vocal fold oedema ('Reinke's oedema' ) and if the accumulation is concentrated at one end and balloons th� epithelium out in front of it, this is known as a vocal fold polyp.54 Oedema usually affects both sides of the vocal folds symmetrically. It often occurs after laryngitis, especially when overuse of the voice, and possible excessive coughing, has occurred during the inflammatory phase. In many patients it is associated with heavy smoking. Voice quality is often harsh; pitch is deeper than usual and achieving high tones and falsetto become almost impossible. Slight oedema will resolve with time and speech therapy is directed towards encouraging the patient to avoid overuse of the voice, eliminate laryngeal abuse such as occurs with shouting, smoking, etc. When there is a colloidal mass beneath the epithelium, however, resorp tion may take a long time and patients may prefer to have the swollen mucosa surgically incised and the excess fluid aspirated. Voice therapy to assure good vocal habits and to eliminate misuse and abuse of the larynx is strongly advised in order to prevent recurrence. As with vocal fold nodules, vocal fold oedema is the effect of laryngeal misuse - and the causes need to be addressed with speech therapy. Symptomatic treatment alone (surgical aspira tion of the Reinke's space) will rarely be sufficient to prevent recurrence. A vocal fold polyp never resolves with therapy alone and should be surgically removed. In one study of 24 subjects with polyps, 48 percent of patients exhibited a moderate degree of dysphonia and this was more severe in patients with polyps than in subjects with any other laryngeal lesion who were examined.67 [***] Voice therapy postoperatively aims to assure good vocal hygiene and identification and elimination of laryngeal misuse and abuse which may have led to the problem.
Epithelial hyperplasia and dysplasia
The term 'epithelial hyperplasia' refers to any condition in which hyperplastic thickening of the epithelium is the primary lesion.7 When the lesion is associated with atypical cells, the term epithelial dysplasia is used. Lesions referred to as leukoplakia, hyperkeratosis, keratosis with cellular atypia and dyskeratosis fall into this category. This epithelial lesion causes hyperplastic thickening (an abnormal growth) which is visible on the vocal folds as an irregularly shaped white patch (as a consequence of the thickening of the squamous epithelium covered by excess keratin) . These lesions are often regarded as precancerous and clinically it is often difficult to differentiate carcinoma in situ or very early invasive cancer from epithelial hyperplasia. As the hyperplasia is I
2222
I PART 16 T H E LIPPE R AIRWAY
on the glottal margin, the resultant voice quality is usually breathy, with reduced loudness and overall dysphonia?' 49 [***] Gastro-oesophageal reflux disease (GERD) has been implicated in the manifestation of epithelial hyperplasia, with pepsin identified as the principal injurous agent of the reflux.37 Severe laryngeal damage can occur even when the pH of the refluxate is at 4.0. [***] Speech therapy alone will not resolve hyperplasia, although it has been stated that, 'in principle, all secondary organic afflictions of the vocal cords, even those with epithelial hyperplasia, are reversible if all causal factors are removed'. 54 However, it was also acknowledged that a new regimen, stopping smoking and drinking and learning new voice habits, 'is rarely practised and most patients prefer phonosurgery combined with voice correction'. 54
Laryngeal webs
Voice difficulties may arise from either central or peripheral neuropathies. To cover all neurogenic disorders in which voice problems may coexist is beyond the scope of this chapter. Hence, speech therapy intervention here has only been included where evidence exists with respect to efficacy. Speech therapy with people who have damage to the vagus (X) nerve, resulting in vocal fold palsy and dysphonia; therapy for those with spasmodic dysphonia and for people with Parkinson's disease exemplify three voice disorders of neurological origin which have most research evidence attached to them.
Vocal fold paralysis
The detailed anatomy of the vagus nerve is covered elsewhere (see Chapter 162, Anatomy of the larynx and tracheobronchial tree). The problem has been described as follows: Nerve lesions arising above the level where the various
A laryngeal web is a band of connective tissue (which may vary in length) which joins the two vocal folds at the anterior commissure? They may be congenital - due to the vocal membrane failing to separate in embryonic development or acquired - usually this is related to internal or external trauma occurring on the vocal fold edges.9 A neonate may present with cyanosis, stridor and dysphonia; but this will vary with the extent of laryngeal webbing.68 They may also have feeding problems and weak phonation. Voice quality in adult patients may be shrill and pitch high as the web tethers the vocal folds and prevents optimal vibration. There may also be varying degrees of breathiness and hoarseness, due to vibratory irregularity and glottal air leak. 69 Primary treatment is surgical, and in one study of ten subjects, seven with acquired and three with congenital webs, normal voice was achieved postoperatively in five subjects.69 [***] Voice therapy postoperatively may then be needed to re establish good voice where habitual patterns (arisen from accommodating to the existence of the web) have resulted in nonoptimal voice production.
VOICE DISORDERS OF NEUROLOGICAL ORIGIN
The central nervous system (CNS) is the essential system for the starting and stopping of a motor activity as speech and damage to the CNS may have an effect on voice production. Speech pathologists use the term 'dysarthro phonia' for disorders incorporating aspects of both speech and voice. With many progressive neurological diseases, such as Parkinson's disease, pseudobulbar palsy and multiple sclerosis, people may encounter profound communication deficits as CNS damage results in both voice and motor speech dysfunction.
nerve branches separate from the vagus (Xth nerve) affects all of the branches and therefore the muscles innervated by these nerves will be adversely affected .... Lesions of the Xth (vagus) nerve above the point of bifurcation of the pharyngeal nerve branch result in: (j) an inability to elevate the soft palate and constrict the muscles of the pharynx because of the pharyngeal branch involvement;
(ij) an inability to stretch the
thyroarytenoid muscles (via the action of the cricothyr oid muscle) because of superior laryngeal nerve (SLN) involvement and (iii) an inability to tense the intrinsic laryngeal muscles for the purpose of adducting the vocal folds
because
of
recurrent
laryngeal
nerve
(RLN)
involvement (hence the paralysis is called the adductor type).33
Symptomatically, dysphonia due to a unilateral lesion of the vagus nerve above the level of the pharyngeal branch is characterized by: mild to moderate hypernasality (due to the soft palate elevating only on one side); nasal emission (due to incomplete velopharyngeal closure); palatopharyngeal gag reflex reduced or absent (due to sensory deficit caused by the lesion above the superior laryngeal nerve origin). Vocal fold palsy may arise from more central lesions (posterior fossa and jugular foramen), where the vagus nerve emerges from the brain stem and leaves the skull. With posterior fossa and jugular foramen lesions, cranial nerves IX, X and XII may also be affected and a large number of laryngo-pharyngeal-palatal palsies associated with lesions of these nerves have been named. They are termed posterior fossa syndrome and jugular foramen syndrome. Clinically, people with these syndromes have a resultant problem in vocalization and swallowing (often with aspiration). Skull base surgery for removal of glomus jugulare tumours often has the sequelae of voice and
Chapter 169 Speech th e ra py in ENT p ractice : scope, science a n d evidence for i n te rve n ti o n I
swallowing problems as damage may occur to the IX, X and XII cranial nerves during the surgery to remove the tumour. Hence, the risk of aspiration (especially of fluids) is a real one for many such patients in the immediate perioperative period and short-term alternative feeding (e.g. percutaneous endoscopic gastronomy (PEG) ) may need to be considered. An experienced clinician often suspects a vocal cord paralysis from the sound of the voice. Voice quality will be severely breathy or whispered (due to unilateral paralysis of the intrinsic laryngeal muscles preventing the vocal fold on the affected side from adducting to the midline); hoarseness (due to asynchrony of the normal and paralysed vocal fold vibrations); reduced loudness (due to inefficient glottal closure and resultant air wastage) and low pitch with possible pitch breaks.70 [***] Dysphonia due to a bilateral lesion of the vagus nerve above the level of the pharyngeal nerve branch is characterized by: moderate to severe hypernasality (both sides of the palate being unable to raise for velophar yngeal closure); nasal emission (from incomplete palatal closure) ; the palatopharyngeal gag reflex reduced or absent (as vagal nerve lesions above the level superior laryngeal nerve separating can cause sensory deficits). Voice quality will be whispered or very breathy (due to both vocal folds not approximating in the midline; thus the airflow via the glottis has little or no resistance); a bovine cough or weak glottal attack (due to nonapprox imation of the vocal folds); markedly reduced loudness and aphonia will result if the bilateral paralysis is total. Breathing problems on rapid inspiration (audible stridor) will occur if the cords are in the paramedian position. Vagus nerve lesions below the pharyngeal nerve branch, but above the level where the superior laryngeal nerve separates from the vagus, results in adductor paralysis with no associated palatopharyngeal paralysis. A Xth cranial nerve lesion at this level affects all intrinsic muscles of the larynx. Vagus nerve lesions affecting only the SLN (isolated paralysis of SLN) may occur. In this type of paralysis, the soft palate and all the intrinsic muscles of the larynx function normally but the cricothyroid muscle is paralysed. The thyroid cartilage therefore cannot be tilted with respect to the cricoid cartilage, and the stretching and tensing of the vocal folds is impaired. Mild to moderately breathy voice may result and the ability to change pitch is affected; however, this may only be noticable when singing. Vagus nerve lesions that affect only the RLN (abductor paralysis of the larynx) may occur, with left RLN paralysis being ten times more frequent than right sided. This type of lesion results in paralysis of all the intrinsic muscles of the larynx except the cricothyroid muscle (which is innervated by the SLN) . There is an inability to abduct and adduct the vocal folds. However, the cricothyroid muscle still functions and acts to contract, stretches and pull on the vocal folds until they are drawn to the midline position. Once they reach the midline the paralysed
2223
abductor muscles are unable to pull the folds apart; hence the term 'abductor paralysis' of the larynx. In reviewing the selection, diagnosis and management of 390 patients with unilateral or bilateral vocal fold palsy, one large study demonstrated that the most common cause of unilateral palsy was trauma (37 percent) with the severing of the RLN during thyroid surgery being the most common cause of bilateral vocal fold palsy (46 percent) .71 [***] Speech therapy is usually combined with surgical management in cases of unilateral and bilateral vocal fold paralysis. Medicosurgical management of unilateral vocal fold palsy will depend on the aetiology (known or unknown) and the status (temporary or permanent) of the problem and the health status of the patient, remembering that people with a vocal fold palsy can experience moderate to severe dysphagia (swallowing problems) resulting in aspiration, as well as dysphonia. Surgical intervention (phonosurgery) is usually de layed until 9-12 months have elapsed to allow for spontaneous recovery, but there may be situations which change this time frame - for example, if the patient is audibly aspirating food or fluids to a significant degree and/or is very sick or terminally ill, such that commu nication is important but the effort/distress in producing voice is unacceptable. In these instances, temporary vocal fold augmentation may be considered to reduce the problem. Figure 169.1 diagrammatically explains the clinical decision making and options for intervention when managing people with unilateral vocal fold paralysis during and after the first 9-12 months post-onset. Voice therapy with someone who has a unilateral fold paralysis traditionally has used 'pushing' exercises, the theory being that one may encourage the mobile cord to over-adduct, across the midline, to meet the paralysed vocal fold. This involved forced adduction exercises such as pushing down against resistance (on a desk or chair, for' example) and phonating simultaneously with sharp, expiratory grunts. There is no evidence that the approach has the desired affect of making the mobile cord 'over compensate.' In a study evaluating a pushing exercise programme to correct glottal incompetence resulting from paralysis in three subjects, it was shown that any voice 'improvements' in the clinic could not be carried over into connected speech and 'normal' voice was not achieved with any of the subjects.72 [***] Therapy has been advocated that involves: •
•
educational information regarding phonation and vocal hygiene; avoidance of hyperfunctional compensation and progressive development of optimal breathing and diaphragmatic/abdominal support with gentle improvement of intrinsic laryngeal muscle strength and agility. [Grade C] The recommended exercises were isotonic and analogous to exercises to build limb strength, tone and endurance?3
2224
I PART 16 THE UPPER AIR WAY Known permanent aetiology Unknown aetiology >9 month duration Healthy patient,
Sick patient, with or wlo aspiration
with aspiration
Phonosurgery
Temporary or unknown aetiology <9 m onth duration
no aspiration
with orwlo aspiration
need for voice
. ."j 1.
-
(b)
Sick patient,
Healthy patient, with
aspiration Qf strong
Healthy patient,
········
I J
Temporary augmentation
1
I I
Definitive phonosurgery
as pushing and, furthermore, they state that pushing exercises 'must be avoided or monitored very closely (and) used with extreme caution'. Their study of 19 and 22
men
I
I
Figure 169.1
showed
that
perceptual
voice
outcomes for patients who had surgery were better than
Cli nical opti o n s for
a
person
w i th
a u nilateral vocal fo ld palsy (a) before nine mo nths; (b) after ni ne months.
© Hodder Nnold I Scott-Brown 7E
Heuer et al.73 warn against the use of forced exercises such
women
I
I
After 9 months
Abductor spasmodic (or spastic) dysphonia is char acterized by intermittent episodes of breathy dysphonia, drops in pitch and vowel prolongation. It has been said
that this presents as the mirror image of adductor spastic dysphonia.
IS
Treatment for adductor spastic dysphonia has included
those who had no surgery, although subject satisfaction
counselling,
was the same, and women displayed greater improvement
surgery. 78
hypnosis,
Unfortunately,
medication
biofeedback,
and
there are few good studies
in voice therapy than men in the group receiving voice
demonstrating voice therapy as being effective. More
treatment alone.73
recently) botulinum toxin (Botox)
[***]
adductor spasmodic dysphonia.
The effect of Botox injection fonowed by voice therapy
This disorder has achieved much attention over the last 12-15 years, out of proportion to its incidence. It is a
relatively rare disorder
with onset commonly in middle
aetiology
and
age and it seems to occur equally across gender? The unclear
some
authors
suggest
a
psychological origin74•75 whereas others imply a neuro logical
origin.76•77
This medico-surgical
approach is considered elsewhere.
Spasmodic dysphonia
is
has been used to
reduce or eliminate the spasm and tightness found in
Adductor
spasmodic
(or
spastic)
dysphonia is characterized by struggle and strain
ill
or no therapy has been examined in a cohort study with 27 patients who had adductor spasmodic dysphonia.79
The patients were not randomly assigned, but elected to undertake therapy after Botox injection or not, and thus was prone to selection bias. However, the study supported the value of voice therapy in maximizing the duration of vocal improvement [Grade
foHowing
Botox
injections.
[***)
C]
talking. and marked intermittent stoppages of voice.
Associated symptoms include hoarseness, harshness and vocal
tremor.
Others have presented with creaking,
Parkinson1s disease
choked, tense or squeezed voice with extreme tension noted in the entire voice production system.
Parkinson's disease (PD) is a disease of the extrapyramidal
ruptions to voicing, tension, loudness and pitch fluctua
specifically, the substantia nigra. Patients usually have
Perceptual signs include strain/struggle, sudden inter
tions and pitch breaks.
nervous system involving the basal ganglia or, more
voice problems - monotony (due to monopitch), reduced
Chapter 169 Speech th era py in ENT p ractice: scope, sci ence a n d evi d e n ce fo r i n terve n tion I
loudness and harshness. In a study of 200 patients, 87 percent had laryngeal dysfunction and 45 percent presented with laryngeal dysfunction as their only symptom.80 [***] The Lee Silverman Voice Program, devised by Ramig and her associates specifically for patients with Parkin son's disease, aims to increase vocal fold adduction.43 It includes intensive therapy (16 daily sessions per month) , using high phonatory effort exercises to increase vocal adduction, maximize pitch range and respiratory support. Additionally, patients are trained to self-monitor their speech production. The literature examining voice therapy for such patients is extensive. Well-designed RCTs have offered convincing evidence that the Lee Silverman Voice Program is effective in perceptually improving the voice. Further, the voice gains made during therapy seem to be extended post-intervention.43, 81, 82, 83, 84, 85 [****] [Grade A]
HYPERFUNCTIONAL VOICE DISORDERS
For clear, resonant voice to occur, there needs to be a balance between subglottic breath pressure, breath flow and glottic resistance (the degree of firmness of vocal fold closure). Hyperfunction occurs when the glottis closes too firmly, or when there is excess ventricular fold or pharyngeal level constriction. Prolonged use of improper vocal habits may result in the vocal folds adapting to the strain by forming nodules, oedema and various forms of hyperplasia. Thus hyper function/nodules might be viewed as a continuum of voice misuse/abuse leading to pathological change. Voice therapy to treat and manage hyperfunction is similar to that for treating patients with vocal nodules. Therapy includes approaches to reduce vocal fold tension, to reduce muscle tension in the laryngeal and pharyngeal regions and to restore normal tone to speech muscles and obviate the need for surgery.82 The three most common techniques which offer levels of scientific evidence to validate their use are: 1. the Accent method; 2. electromyographic (EMG) biofeedback training; 3. Stemple's vocal function exercise programme.
The Accent method has been described earlier (see above under Nonorganic dysphonias) and (has been applied in clinical practice for decades,.83 Two studies provide convincing evidence as to the efficacy of the Accent method in improving perceptual, aerodynamic and physiological aspects of hyperfunctional voice produc tion. The limiting factor in both these studies was the lack of either comparative (with other therapy) or control (no therapy) group.82, 83 [**] EMG biofeedback from the laryngeal region provides monitoring of excessive laryngeal function.86 Biofeedback
2225
is a technique that uses a physiological signal to control the amplitude, frequency and duration of a feedback signal that is presented to the subject either acoustically or visually.86 It may be viewed as an operant conditioning technique, or as an aid to learning. The literature describes slightly different techniques in the procedural use of EMG. Generally, however, EMG activity is recorded from the laryngeal area using bipolar surface electrodes placed on the cricothyroid region, 1 cm each side of the midline of the larynx, with a third (indifferent) electrode on the ear lobe. Visual and auditory feedback may be given together; usually a biofeedback needle providing visual information. The subject is instructed to reduce general laryngeal muscle tension while speaking by, for example, reducing vocal loudness. Sources of variation occur in EMG activity that renders it less than consistent from session to session. Skin resistance and site of electrode placement may be variables that are difficult to contro1.86 Several well-controlled studies testify to the effectiveness of EMG as a useful biofeedback to control hyperfunction87,88 and, in a comparative study, improve ment in frequency range (pitch) in the patient group who had EMG over a group who had progressive relaxation therapy' without biofeedback was demonstrated although both had improvement in voice quality and benefits were retained for three months in both groupS.87 [***] [Grade B] Stemple's (Voice Function Exercise Programme' is a series of voice manipulations, designed to strengthen and balance airflow to muscular effort and balance laryngeal musculature.89 One study demonstrated that 35 gradu ates, who were women with hyperfunctional voice disorders, benefited from vocal function exercises for improving voice production. In a further study, with 20 university graduate-level voice majors, vocal function exercises improved acoustic and videostroboscopic mea sures.89, 9 0 [***] Neither study used subjects with laryngeal disease or a history of voice disorder, so this procedure has yet to be demonstrated on patients with dysphonia and/or laryngeal disease.
PSYCHOGENIC DISORDERS
A psychogenic voice disorder occurs when vocal control over pitch, loudness, quality or resonance is disrupted sufficiently to impede communication because of psy chological disequilibrium. Such disequilibrium can result from unrealistic fear, anxiety, depression, anger, unre solved conflicts, personality abnormalities, psychosexual confusion, conversion reactions, interpersonal relation ship disruptions, poor self-confidence and puberty adjustment difficulties, as well as neuroses and psy choses.9 1 Convincing data have been offered for the place of voice therapy in the treatment of psychogenic voice disorders.92 [***]
2226
I PART 16 TH E U PPER AI RWAY
From analysing their comparative cohort study, using an experimental group ( n = 30) and a control group ( n = 10), Andersson et al.92 comment that 'persistent conflict situations related to family and work predomi nated as a factor possibly precipitating psychogenic voice disorders'. The chances of recurrence are high if the causes of the stress (and resulting disarray) are left untreated.54 In such cases, symptomatic voice therapy which is usually focused on achieving a rapid return of voice (with aphonic patients) or achieving optimal voice production through vocal exercises (with dysphonic patients) may only be partially effective and the patient may then need referral to an appropriate form of counselling or psychotherapy to address the underlying conflict. This needs a preparedness on the part of the patient to examine the (often painful) emotional causes of failure of voice function and this may, in turn, need 'strengthening of his or her self-reliance'.54
PITCH DISORDERS: PUBERPHONIA; TRANSSEXUAL VOICE
structure of the vocal folds and optimal, lower, pitch production. A therapy programme using an electrolar yngograph (which gives visual traces from external electrodes either side of the larynx, at the level of the vocal folds, recording pitch) for visual feedback has been successful, albeit in only two patients who had incomplete mutation. These changes were achieved with six and eleven sessions of therapy respectively.93 [***] Prolonged mutation and mutational falsetto voice, on the other hand, may be treated effectively in one or two sessions. Therapy involves manipulation of the position of the larynx - and thus lowering the pitch - by applying pressure on the Adam's apple while the patient phonates. The change to normal voice may be abrupt, not gradual. The use of coughing, clearing the throat and grunting to achieve a lower pitch and then extending this from a cough into production of vowel /a/ has been advocated. 33 This leads to producing vowel-laden words, phrases, etc. Once voice is achieved, therapy may then be directed to assisting the patient to consolidate the voice and then to adjust and carry-over this 'new voice' to the world outside the clinical setting.
Puberphonia (incomplete vocal mutation) in Transsexual voice adult males unusually high pitched voice persisting beyond puberty
When a boy is between 12 and 15 years old, the voice changes at the start of adolescence. Normally, this ensues over a period of six months or so, and then settles in the lower register. It is only when the duration of these changes last for over a year and the voice problems show no sign of decreasing, that the termed puberphonia or prolonged pubertal mutation would be used. This then is a problem specific to men. Although psychosocial factors are often cited, such as difficulty with male identification or acceptance of adulthood, in reality there is no evidence that this is the case.7 Pitch breaks at puberty can be frequent and extreme, and in an attempt to control this by 'holding on' to the voice that is known (the child voice) , the production of the adult voice may be inhibited. There are three mutational disorders: mutational falsetto voice (where the person speaks continually in a falsetto voice); prolonged mutation (where the heavy and light registers alternate, such that the voice constantly fluctuates in pitch and timbre); and incomplete mutation (where the mutation has proceeded imperceptibly; but the voice is pitched too high; timbre is dull but there is no split register).54 Abnormal use of the voice during puberty may contribute to incomplete mutation. Examples, such as continued singing in a boys' choir while undergoing pubertal voice change, and the contribution of asthma to tense breathing patterns - and therefore incomplete mutation - has been noted. 54 Therapy for incomplete mutation may involve many months, training more supple vocal folds and the
A female transsexual is a female who wants to transform herself into a male
The ratio of female to male transsexuals is lower, although prevalance data are difficult to obtain.94 Female transsex uals usually rely on the virilizing effect of testosterone (androgens) on the vocal folds, thereby thickening the folds and deepening the voice. This is an irreversible effect, so the person must be certain they do, indeed, wish to change gender as, once applied, the vocal deepening does not revert if there is a change of mind and testosterone intake is ceased. The most common presentation of a transsexual person with a voice problem to a speech therapy service is that of a male to female transsexual who now finds their (male) voice is unacceptable in terms of pitch and quality to their new (female) body/persona. This is a highly specialized area of speech therapy and should not be undertaken by an uninformed practitioner without access to more experienced support. Ideally, this should be from staff in a gender dysphoria programme with whom the speech pathologist can obtain advice and assistance. [Grade C] Much has been developed in terms of phonosurgery in order to raise pitch, although available data are limited and there is no high-level evidence showing that surgery gives a better outcome than therapy, nor vice versa. Transsexuals undergoing phonosurgery for pitch change - thyroplasty (see Chapter 170, Phonosurgery) will usually need voice therapy postoperatively to optimize the surgical results. The evidence for speech therapy alone remains somewhat equivocal. Data are available, albeit with small numbers of subjects, regarding the effective ness and efficacy of speech therapy in achieving pitch
Chapter 169 Speech thera py in ENT p ractice : scope, science a n d evid ence for i n te rvention I
change in the clinic.95 However, data regarding long-term change, and whether changing fundamental frequency (pitch) alone is sufficient to be identified as female, remains to be provided.96 The interested reader is directed to the chapter by Challoner97 for a full description of techniques for raising pitch in male to female transsexuals. As with many habitual changes in voice, success from speech therapy demands an expertise in the voice disorder (from the therapist) ; commitment to voice change (from patient and therapist); compliance (from the patient) and specialist training and experience (from the therapist).
LARYNGEAL CANCER: REHABILITATION OF VOICE AFTER TOTAL LARYNGECTOMY
The prognosis for cancer of the larynx may be better than many other forms of cancer54 but total laryngectomy is mutilating surgery which leaves the patient adjusting to a changed body image and lifestyle alteration, as well as needing to develop a substitute for voice. The full investment needed from a speech pathologist when rehabilitating people who have undergone this 'function ally destructive procedure'98 is beyond the scope of this chapter, as here we are discussing post-laryngectomy 'speech options', but the reader is directed to detailed laryngectomy texts for a fuller description of the psychosocial needs of this population. These may include, for example, dealing with stoma humidification, return ing to swimming, restoring sense of smell and taste, as well as psychological adjustment.98, 99,100 There are no data that show that a preoperative visit from another person who has undergone a laryngectomy is beneficial, although this remains routine practice in some settings. Clinicians need to be sensitive to the preoperative state of the person about to undergo a laryngectomy. If wishing to illustrate the type of future voice which might be expected, in order to raise the patient's expectation, it may be preferable to use a videotape or CD-ROM examples of voice, when the tape or CD may be paused if there is evident distress, rather than insisting that the patient meets a stranger and be exposed to a traumatic face-to-face realization of what is about to ensue.101 A total laryngectomy removes the vibratory source for voice (vocal folds) when the larynx is removed. If he wishes to communicate verbally, rather than mime, gesture and/or write for the rest of his life, then the (usually male) laryngectomized patient is left with essentially three options of rehabilitating voice after this surgery. l.
Using a tracheo-oesophageal 'puncture' (TEP) procedure: a surgical-prosthetic approach, either undertaken at the time of the total laryngectomy or some months (or years) later. This can restore
2227
near-normal speech to the patient in terms of loudness and fluency, but can be slightly restricted in vocal (pitch) range. The procedure is reversible. 2. Oesophageal speech: this is a technique whereby the patient is taught to semi-swallow (or 'inject') air into the upper oesophagus and regurgitate this to produce a 'burp' -like speech. It may eventually provide a fluent, hands-free mode of communication, but is limited in range and loudness. 3. Artificial larynges: these may be electronic or pneumatic in type and these devices may be regarded as easy to use. They provide intelligible speech, although they are often perceived as monotonous and always demand the use of one hand as they need manual operation. Table 169.1 offers a comparison of laryngeal voice, TEP voice, oesophageal voice and voice with an electrolarynx.
Physiological prerequisites for acquiring alaryngeal speech
Both oesophageal speech and TEP speech demand a tonic pharyngo-oesophageal (PE) segment to provide a vibra tory source for voice. Clear data now exist that PE opening pressure is a key factor in success or failure to acquire both oesophageal and TEP voice. Neither the length nor the shape of the reconstructed PE segment is a predictor of speech; the only physiological variable which has been shown consistently to be important in acquiring voice, post-laryngectomy, is the opening pressure of the PE segment needed for speech. 102, 103, 104, 105, 106 [***]
TEP speech
This is an extremely skilled area of rehabilitation practice and no clinician should be attempting post-laryngectomy TEP speech rehabilitation without subspecialist training, preferably by attending postgraduate courses. In the UK and USA there is a plethora of such courses. Training is needed as a TEP procedure is not simply a matter, as one ENT surgeon has said, of 'making a hole from the trachea and the oesophagus, bunging in a "valve" and seeing if it would work. After all, we can always pull it out if it doesn't'. Successful use of TEP speech demands a tonic PE segment (see Table 169.1) and convincing data exist to illustrate that the tonicity of the PE segment depends on the nature, type and extent of the initial laryngectomy. Specifically, the way in whiS;h the pharynx is reconstructed after the larynx has been removed will allow, or deny the patient postoperative speech and the importance of undertaking a pharyngeal constrictor neurectomy or
2228
I PART 16 T H E UPPER AI RWAY
Table 169.1
A compar ison of laryngeal, trachea-oesophageal. oesophageal voice and voice with an artificial larynx.
Physical
Laryngeal voice
,,[rachea-oesophageal voice
O�s()phageal voice
Artificial larynx
Moving col u mn of air from
Moving column of ai r from
Moving column of air from
Air in oral cavity/pharynx
requirements Initiator
the l u n gs
the l u ngs Vibrator
the oesophagus
Pha ryn g o-oesophagea I (PE)
Vocal folds
Pharyngo-oesophagea[ (PE)
segment Resonator Articu lators
Vocal tract (i.e. pharynx,
Vocal tract (i.e. pharynx,
nose and mouth)
nose and mouth)
nose and mouth)
nose and m outh)
Tongue, teeth, l ips, soft
Tongue, teeth, l ips, soft
Ton g u e, teeth, l ips, soft
Tongue, teeth , l ips, soft
palate
palate
palate
myotomy has now been clearly demonstra ted by surgeons with experiences in excess of 400 laryngectomy proce 107 108 ,
Vocal tract (i.e. p harynx,
Vocal tract (i.e. pharynx,
palate
dures.
Tone from artificial larynx
segment
[***]
The scope of advantages, problems and complica tions is beyond the scope of this chap te r)
but Figure 169.2
illus trates some decision-making paradigms which exist
During a primary TEP (i.e. undertaken at the time of
when using TEP. This is reproduced in an endeavour to
total laryngectomy), the fistula is used for placing a
persuade clinicians to attend postgrad uate training to
voice
improve success rates with this procedure if these are
prosthesis is not inserted un til the patient is e a ting and
lower th an the reported best practice results of 85-90 108 0 percent succes S. 1 3,
tracheo-gastric
feeding
tube
and
the
silicon
swallowing well (usu all y eigh t to ten days postoperatively after
straightforward
a
total
with
laryngectomy
no
complications). At tha t time, the feeding tube is removed and a correctly sized and type of silicon voice prosthesis is inserted.
109, 110
Voice therapy then begins.
In reality, voice therapy should be straightforward with
someone who has a primary TEP, as the driving force for speech is
Oesophageal speech
similar to laryngeal voice, being lung-powered
air. Speech therapy involves teaching the patient (and possibly family) how to clean, change and manage the silicon voice prosthesis in an ongoing manner, as well as how to use the prosthesis to speak.
To generate oesophageal speech, the patient first has t o learn to take air in (inject or inhale) to the upper
oesophagus. When, immediately after intake) the air is
returned, it vibrates at the PE segment and results in a
deep, vowel-like sound, resonating in a wide pharyngeal
and oral cavity 54, 1 .
0 1
Speech therapy is initially directed to teaching
Direct voice therapy involves teaching the following:
manoeuvres to inject Cpump') with tongue or lips or
valvi ng (closure of the tracheostome with fi nger, thumb
inhale Csuck') by rapid inhalation of air into the upper
or outer valve to direct air for speech); articulation (shape and speed of lip teeth and tongue movements); rate (of ,
closure/
upper oesophagus and then to vibrate on air return, to
opening of the tracheostoma with onset to/stopping of
produce sound for speech. Once sound is achieved, the
speech) voice)
and as
phrasing
well
suprasegmen t al s.
as
(coordination
improving
lll, 112
of the
oesophagus.IOI Physiologically, this demands a ton ic PE
segment sufficient to relax and allow air to enter the
pitch,
intensity
and
Prima ry TEP offers a rapid vocal rehabilitation and
eventually near-normal voice and communication for
next step is to achieve consistency of voice without effort,
and then to shape this sound into single syllables) words, 54 116 and, eventually) conversational speech. .
phrases
In reality, hypertonicity and spasm or a stricture at percent of
patients with whom it functions well and who wish to
the PE segment means that only
learn
patients can achieve success with this mode of speech 7 production.54,11
to use it and there is evidence that reduced 3 complications occur with primary TEP.11 [***] Nevertheless,
this
mode
of
speech
rehabilitation
demands patience and skill and evidence exists that rehabilitation should not be offered in centres where less than five laryngectomies are undertaken each
[***/**]
initial
laryngectomy
and
may
often
involve
more direct speech therapy as the patient may have to ) unlearn voice patterns that have been previously been ,
<
tried and been unproductive when attempting oesopha geal speech.
The artificial larynx
year.114, 115
Secondary TEP may occur months, or years, after the
30-60
No data exist to show that the use of an artificial larynx prevents learning or reduces m otivation) in a patient who ,
wishes to produce either TEP or oesophage al speech.
Indeed, this myth should now be laid to rest, as such evidence which does exist shows the opposite - that the
use of an artifrcial larynx may enhance communication in
p atients early postoperative days and reduce frustration '
Chapter 169 Speech therapy in ENT practice: scope, science and evidence for intervention I Remove 14 Fr catheter
DilateTEP up to "8 Fr
Open tract voir,;e?
Relaxed
2229
Size and
'VOIce
Insert 1 B Fr low pressure: 'Vahle
Effort ul voloe?
Size and insert 6 r low pressure vaive
TEP unde 10mm iIloppy/mobie?
Voice?
Size anti insert, 16 Fr low pres&lfe valve
Atrange videofluorosc.opy and insufflation
Dia\eTEP
up to:22 Fr
Open lract voice? Replace catheter
01
insoo
20 F.- standard 1O't'l pressLlre I,fj3.�/e
Arrange \!ii:::lOOfllIOl'OSCOPY and insuHlal.ion
�
- ----, Se 20 r standard 10\;'1 pressure vaNe
.---S - z e
Keep tMJI. arraf'lge ooooiluorosccpy cllKi insufflatIOn
Or insert :20 Fr
iOO'i'l811Wlg valve
Keep af'l(l review/change in 6 monUlS or lNhen leaks
Keep and review/Change
in 6 monlhs
Of'
vmen leakS
eN keep anci teacil
;0 sell-change
© H odder Arnold I Scott-BroNn 7E Figure 169.2
Surg ical voice decision-making flowchart
©
2001 (2001).
P. Kromer
pe rmission of P. Kromer, based on lectures and notes by Y. Edels
at this stage, which can be a time of both isolation and 1l3 depression. [**] The artificial larynx may be welcomed, either as a short-term measure by patients who are learning another
(updated
2003).
This schema is printed with kind
mode of speech, or when used permanently by patients who have no capacity for developing such alternatives due to physiological barriers, such as PE segment spasm, or
who have an aversion to using other modes of speech.
2230
I PART 16 TH E U PPER AI RWAY
Artificial larynges may be classified as either electronic
./ Post-laryngectomy, voice restoration i s best a chi eved
(battery powered) or pneumatic (lWlg powered, driven by
with a pri ma ry tracheo-oesopha g ea l ' pu nctu re',
respiratory airflow from the tracheostoma) . The electro
inserting a feed i n g tu be tracheo-gastrica l ly. A voice
nic larynges are further divided into neck type, or trans
prosthesis i nsertion and instructi o n on · its u se sho u l d
cervical (such as the Servox) , or mouth-type or intraoral
co m men ce as soo n a s ora l feed ing i s re-esta b l i shed .
(such as the Cooper-Rand ) . Most devices have controls to
alter pitch and loudness but, in reality, electronic artificial
larynges are fu nctionaUy mono-pitch and mono-loud
as
few patients have the linguistic skills and knowledge to conversation.
Defi c i e n ci e s i n cu rre n t kn ow l e d g e a n d a reas fo r fu tu re resea rch
pl as t ic) , inside which sits a rubber membrane, or reed,
> U n iversal co n se n s u s o n a categorizati o n of voice
results is then transmitted, via an external tube, to
» The effect o f vocal exercises o n preven ti n g voice
raise and lower pitch controls during connected speech in
The pneumolarynx consists of a stoma cover (usually
that vibrates as res p iratory air crosses it. The tone which
d isorders is l ackin g .
the inside of the mouth, and the patient articulates
da ma g e in professiona l voice u sers (te a chers, singers,
around t his tone to produce speech. An example of a
etc.) need s more research.
pneumatic larynx is the DSP-8 (used in Australia and in
)- The effect of l a ry ng ea l hydrati o n on voice d i sorders -
the USA) or the Tokyo ot Osaka pneumolarynges ( as used
thi s is often reco mmen d ed as part of 'voca l hyg iene',
in Ja p an) . IOO P it ch can be varied, rendering this device
but the evidence fo r its benefit i s sparse.
suitable fo r use when speaking tonal languages; how
ever, the external pipe from tracheostoma to mouth is
obtrusive so people need a certain degree of confi
dence when using this type of artificial larynx. All artificial larynges demand good manual dexterity and all have the
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Perry A. Preoperative trac h eoeso p h a g e a l voice restoration
Stem p l e J , Lee L, D'Am ico B , Picku p B. Efficacy of voca l
exercises in the p ractice reg imen of sing e rs. Journal o f 91.
M c ivor J, Evans PF, Perry A, Chees m a n AD. Radiological assessment of post- l a ryn gectomy speech. Clinical
A l l en K, Bernste i n B, Chait D. E M G biofeedback treatm e nt Therapy and Experimental Psychiatry. 1 99 1 ; 2 2 : 97- 1 0 1 .
B l o m ED, S i n g e r M I , H a m a ker RC. An i m proved esoph agea l i n sufflation test. Archives of Otolaryngology. 1 98 5 ; 1 1 1 :
rel axation in the treatm ent of hyperfu n ctional dysphonia.
88.
I 2233
*1 08.
H a m a ke r RC, Cheesm a n AD. S u rg ica l m a n a gement of
t h i rty patients. Journal of Voice. 1 99 8 ; 1 2 : 96- 1 06.
p h a ryngea l constrictor m uscl e hyperto n icity. I n : Blom ED,
Carlson E. E lectro l a ryngog ra p hy i n the assess m e nt a n d
S i n g e r M I , H a m a ker RC (eds) . Tracheoesophageal voice
treatment of incom p l ete m utation (puberphonia) in a d u lts.
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European Journal of Disorders o f Communication. 1 99 5 ;
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Tracheoesophageal voice restoration following total
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1 99 8 : 1 -8. Ede l s Y . Pseud o-voice : Its t heory a nd practice. I n : Edels Y
Diagnosis to rehabilitation. Lon d o n : Croo m - H e l m , 1 98 3 :
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Croom - H e l m , 1 983 : 1 07-42. S a l m o n SJ. Artific i a l l a rynx d evices and t h e i r u se. I n : Sa l m on SJ (ed.). Alaryngeal
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461 -6. *1 03.
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Com m u n i cation Sci e n ces web site ; 2000. 1 02 .
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98.
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Speech a n d H ea ri n g . Auckl a n d , N ew Zea l a n d , 1 996. Venereology. 1 99 7 ; 1 0 : 1 78-87.
97.
1 1 0.
1 1 6.
restoration fo l l owing tota l l a ryn g ectomy. I n : Myers E N ,
Eva n s E. Working with laryngectomies. B iceste r : W i n sl ow, 1 990.
B l o m ED, H a m a ke r RC. Tracheoesophagea l voice 1 1 7.
Perry A, Edels Y. Recent adva n ces in the assessment of
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fa i l ed oeso p h a g e a l spea �e rs. British Journal of Disorders o f
Sa u n d e rs, 1 99 6 : 8 39-52.
Communication. 1 9 8 5 ; 20: 229-3 6.
170 Phonosu rgery MEREDYDD HARRIES
I ntrod uction
2234
Best c l in i cal practice
2244
Micro l aryngoscopy
2234
Reinnervation procedures
2244 2244
Key points
2238
Key po ints
B est clinical practice
2238
Def i cienc i es in c u rrent knowl ed,ge and areas for fu t ure
Vocal fold injection
2239
Key points
2240
Laryngeal framework surg e ry
2241
I
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2246
research
2246
References
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The data in this chapter are supported by a Medline search using the key words voice, larynx, vocal fold and focusing on phonosurgery and results.
INTRODUCTION
a multitude of factors such as smoking, alcohol, voice abuse (both speaking and singing), gastro-oesophageal
Laryngeal surgery was initially concerned merely with
reflux:
the diagnosis and removal of malignant disease from the
reasonable trial of therapy for these factors attempted.
and
voice
misuse
should
be
assessed
and
a
larynx, whereas benign disease and its effect on the voice
Conservative treatment with medication and expert voice
was considered to be of secondary importance. The last
therapy or postural adjustment can often promote the
50 years has seen an increased awareness and emphasis
healing of benign mucosal disease without resorting to
on vocal results and the expansion of phonosurgery,
surgery. It is also important that these measures should be
which is defined as 'any surgery designed primarily for the
continued postoperatively to prevent recurrence, as surgery
improvement or restoration of the voice'. Complete assessment of a patient with a voice disorder should now include video laryngoscopy, stroboscopy and other laboratory recordings including laryngeal electro
can often temporarily remove the pathological lesion without addressing its underlying aetiology. [Grade Cl Phonosurgery
includes
a
wide
range
of
surgical
techniques such as rnicrolaryngoscopic surgery, vocal fold
myography and quantitative voice measurements. The
injection, laryngeal framework surgery, nerve grafting and
fonnation of multidisciplinary voice clinics allows an
neuromuscular surgery.
academic and scientific approach to voice disorders and an attempt at evidence-based laryngology. Stroboscopy is essential in the assessment of the mucosal wave of the vocal fold and electromyography can aid in the localiza tion of lesions
in the vagus/superior laryngeal/recurrent
laryngeal nerve network and identify signs of reinnerva tion in a paralyzed vocal cord. [Grade C]
Before considering a patient for surgery, the under lying cause of the vocal abnormality must be ascertained;
MICROLARYNGOSCOPY
History Although M�nuel Garcia 1 is often credited with the first
description of mirror indirect laryngoscopy, Bozzini2 was
Chapter 170 Phonosurg ery I
actually the first to report on mirror visualization of the larynx and indeed described the first indirect laryngo scope for surgery on the vocal folds. Indirect laryngo scopic surgery was the norm at the beginning of the nineteenth century and may have played a role in the well-documented tale of Morell McKenzie and the transoral management of laryngeal cancer in Crown Prince Frederick. At that time, there was fear that transoral laryngeal biopsies could induce cancer of the larynx and as a result laryngeal diseases, such as tuberculosis and syphilis, were often treated by an open procedure with or without a tracheostomy. These were associated with a high morbidity and even mortality and there is postulation that Virchov purposely misdiagnosed Prince Frederick's carcinoma because he was aware of Van Bergman's (the prince's surgeon) abysmal survival statistics following total laryngectomy.3 Horace Green described the first direct laryngeal surgical case, which was the removal of a laryngeal polyp in an II-year-old gir1.4 Due to the fact that in a child the larynx is in a high position, Green was able to use a bent tongue spatula and sunlight to obtain direct vision and remove the polyp. Since this first procedure, numerous developments and modifications have taken place but all demonstrate the fundamental phonosurgical principles as detailed below.
Anatomy
A knowledge of the anatomy of the larynx, specifically the micro architecture of the vocal folds and location of the lesion is essential (Figure 170.1). The layered structure of the vocal fold and its different mechanical and physical properties allows the superficial layer to
2235
oscillate independently for phonation. This cover/body theory explains the vibratory dynamics of the mucosal waves seen on stro boscopy. Detailed work by GrayS has shown that the basement membrane of the squamous epithelium is an important site in the development of benign disease of the vocal folds and research suggests there maybe a genetic predisposition for damage in this area. The poor lymphatic drainage of the lamina propria predisposes it to collect tissue fluid (Reinke's oedema). [****J
Instrumentation
Proper instrumentation with a range of laryngoscopes and micro-instruments is required. Instruments need to be fine, sharp and well-maintained to allow precise removal of the lesion with minimal scarring. Wrenching and tearing of the mucosa leads to excessive scarring. Benign disease is usually located in the mucosal layer or in the superficial part of the lamina propria. Surgery should, therefore, be superficial, staying out of the vocal ligament, with limited mucosal excision only. There is currently no role for stripping of the mucosa of the vocal fold for benign disease. A selection of endoscopes with a wide proximal end and distal illumination is desirable and internal distension of the larynx by using the largest laryngoscope possible is recommended.
Exposure
A flexed neck and extended atlanto-occipital joint is now the universally accepted best position for surgical access,
Figure 170.1
Intra corda l cyst approa ched via
cordotomy and m u cosa l flap.
2236
I PART 16 THE LIPPER A I RWAY
and in difficult cases is improved by flexing the neck to its maximum range. External laryngeal counterpressure, which can be done either with an assistant's fingers or with a specifically designed strap, will also improve exposure of the vocal folds. (Chest support systems by definition put pressure on the maxilla and, therefore, should be termed torsion fulcrum laryngoscopy as true suspension involves using a gallows to lift the patient upwards along the base of tongue and lower teeth.) [**]
Microlaryngeal surgery
Microlaryngoscopy has the following advantages over direct laryngoscopy: •
•
•
•
•
binocular vision; magnification; better illumination; the ability to use bimanual instrumentation; the ability to use the carbon dioxide laser.
Microlaryngoscopy concentrates mainly on the glottic area in cases where the diagnosis is already established and, unlike direct laryngoscopy, is not primarily con cerned with other areas of the larynx which should have been assessed preoperatively.
Laser and alternative dissecting instrumentation
Laser versus microsurgical instrumentation? The laser is not merely a precise surgical knife and the surgeon must have an understanding of the effects of spot size, wattage and mode (pulsed or continuous), their soft tissue interaction and the important hazards linked to their use. Although some experimental studies initially de scribed different healing rates, this has not been the case clinically. Benninger6 described a prospective study on patients using the CO laser and microsurgery and came 2 to the conclusion that in a trained laryngologist's hands, both are excellent tools in the management of phono surgical disorders. In many ways, laser and cold instru ments should be considered as synergistic tools rather than in direct opposition. It is, therefore, a personal choice but the author prefers to limit laser to vascular lesions or those that bleed on removal, such as papillomatosis or granulomas, or to the removal of cartilage and when excising large areas of tissue. Laser plume in the management of papillomas can be considered a potential risk of infection to both surgeon and hospital staff and there is a theoretical risk of seeding of laryngeal disease further into the tracheo--bronchial tree during jet ventilation, although no case report for this exists. Some surgeons now advocate the use of power instrumentation, such as the laryngeal microdebrider, as it eliminates many of the risks of laser listed above. The
With microdebrider has been used for various laryngeal lesions including papillomas and there is an early report using subjective methods that patients have less postoperative pain and a quicker return to a usable speaking voice.? Others have used the debrider for polyps, Reinke's oedema and also for removing tumours at both glottic and subglottic levels. Once again, one must be aware of the microanatomy of the vocal folds and the principles of phonosurgery and whether accurate depth of resection can be made with this tool. A suction collection pot must also be used to confirm histological diagnosis but margins and orientation of the specimen are lost with this technique. [**1**1***]
Anaesthesia
In the UK, general anaesthetic is the norm for micro laryngeal surgery although there have been some articles describing indirect phonosurgery under a local anaes thetic with stroboscopic control. 8 This technique has not been universally accepted, especially when we are dealing with fractions of a millimetre for surgery (depth of the superficial lamina in the middle third is only 0.14 mm in women and 0.30 mm in men) . Direct laryngoscopy under a local anaesthetic is also possible with topical anaesthesia and laryngeal nerve blocks but is not commonly practised in the UK. Ventilation during phonosurgery can either be via an endotracheal tube, which may be laser proof, or via jet ventilation. Jet ventilation gives the best exposure of the larynx but drawbacks include damage to the subglottis while lasering and vibration of the free edge of the vocal folds during jetting. This technique also necessitates good teamwork with the anaesthetists as the surgeon is also in control of the airway as well as the surgical field.
Voice rest
Although there are no control studies looking at the role of voice rest in recurrence and healing, it is now a generally accepted rule that 48 hours of absolute voice rest following a phonosurgical procedure is essential. This is followed by ten days of relative voice rest where the voice is used sparingly. [Grade D]
Pathology NODULES
These are bilateral lesions of functional aetiology and usually respond to voice therapy. They are found at the midpoint of the vocal folds (membranous vocal cord) and are confined to the superficial squamous epithelium. Histopathological studies show thickening of
Chapter 170 Phonos u rg e ry I
the basement membrane together with areas of haemor rhage, fibrin deposits and hyalinization. Their aetiology is associated with phonatory strain and a stroboscope can be useful in distinguishing between hard (usually require surgery) and soft (usually respond to speech therapy) nodules. The centre of the nodule is held with grasping forceps and pulled medially towards the opposite cord. Microscissors are then used to cut the mucosa close to its base, thus preserving normal mucosa, keeping a straight vibratory edge and preventing secondary notching. The opposite nodule can then be removed in a similar fashion, taking care not to damage the mucosa of the anterior commissure. There is no contraindication to removing both nodules at the same time using this precision technique. Postoperative voice rest for 48 hours is recommended and correct technique of voice production is essential to prevent recurrence.
POLYPS
These are usually unilateral, localized areas of oedematous tissue although some may be angiomatous and contain areas of haemorrhage. The site of the lesion is again superficial to the vocal ligament and careful examination may show a contact response on the contralateral vocal fold. Gentle, steady traction is applied by grasping forceps towards the opposite cord and the base of the polyp cut with microscissors. Preservation of mucosa is essential, too little resulting in reformation of the polyp, too much resection giving a notched, scarred cord with tethering of the layers of the vocal fold. Voice rest for 48 hours is recommended as is correction of any predisposing factors.
2237
Providing care is taken in the region of the anterior commissure, there is no contraindication to operating on both folds at the same time. Voice rest and attention to underlying causes are again essential.
INTRACORDAL CYSTS
These may be mucosal retention or epidermoid cysts, and stroboscopy has greatly increased the ease of diagnosis. The mucous retention cyst is found in the cover of the vocal fold and can be removed either with cold instruments or with the laser, but again remaining superficial to the ligament. An epidermoid submucosal cyst can be approached via a lateral microflap where an incision is made on the superior surface of the vocal fold away from its medial edge. The flap is then elevated from lateral to medial, the lesion excised and the flap replaced (Figure 170.1). There are good quantitative results in phonosurgery following this approach although some debate as to whether there is damage to the basement membrane when elevating the flap. Blood vessels have been identified in the flap and would suggest that the plane of dissection should be deep to the basement membrane, therefore, objections of greater damage to the basement membrane may not be founded. As a result of this work, however, Sataloff devised a mini microflap, which involves elevating a small section of epithelium directly over the lesion via a medially based incision. He also reports good results both subjectively and quantitatively using this method. Fibrin glue or welding microspot laser may be used to replace the lateral microflap. [**]
VOCAL FOLD VARICES REINKE'S OEDEMA
This is a bilateral diffuse condition where there is a collection of polypoidal tissue in the superficial layer of the lamina propria. There is poor lymphatic drainage of the vocal folds as a result of the different embryological origins of the supra and subglottic areas. This poor lymphatic drainage, however, is also advantageous by giving a good prognosis for small glottic tumours. A cordotomy incision is made on the lateral aspect of the superior surface of the vocal fold with an arrow-headed knife or laser. The median vibrating edge of the vocal fold is, therefore, preserved. Mucosa is then elevated with a blunt dissector and myxomatous contents either aspirated or removed with cupped forceps. Care must be taken to avoid damaging the vocal ligament or traumatizing the overlying mucosa with excessive suction. Following removal of the contents, the mucosal flap is replaced and any excess epithelium trimmed with microscissors. The mucosal flap can be laid on the surface and left to heal by surface tension, suturing or tissue glue (auto logous or, commercial) used to hold this in place.
These are often considered a potential source of haemorrhage but in most cases, if lying in a longitudinal orientation, can be left and treated conservatively unless recurrent haemorrhage occurs. The presence of vessels lying at 90° or at a different orientation may indicate underlying disease and require further investigation. Recurrent haemorrhage from these vessels can be dealt with either by lasering the blood vessel or needle cautery to ablate the vessels.
ANTERIOR WEBS
If these are small and thin, they can be divided either with a laser or with cold steel. A microweb is frequently associated with vocal cord nodules1o and can be removed at the same time. Thick webs have a 50 percent chance of recurring following laser excision and may require insertion of a keel, either endoscopically or via an open procedure to prevent recurrence. A local mucosal flap covering the exposed tissue on one side has also been reported. 11
2238
I PART 16 THE UPPER AIRWAY
use of adjuvent treatments, such as retinoids, alpha
GRANULOMAS
These are located on the vocal process of the arytenoid cartilage lesions.
and
are usually unilateral, sessile,
Aetiology
includes
endotracheal
bilobed
intubation,
trauma, gastro-oesophageal reflux and hyperfunctional
voice disorders.
Granulomas frequently recur and a
combination of surgery to confirm histological diag
nosis together with postoperative gastro-oesophageal reflux treatment, injection of steroids into the base,
interferon, ribavirin, cyclooxygenase 2 inhibitors, and cidofovir is recognized more in America than in the UK.
Photodynamic therapy is also in its experimental stage. 14
Some individual patients have gained benefit from the use
of adjuvant homeopathy but, due to the small number of adult patients with papillomas, a randomized controlled
study is difficult and there is a case to be made for a national trial in the future.
[**]
oral prostaglandins, speech therapy, osteopathy for neck
manipulation and even botulinum toxin injection into
the lateral cricoarytenoid muscle to decrease the force of
VOCAL SULCUS
granuloma is a self-limiting process that will burn itself
into three types; the first is a physiological or pseudo
adduction have been tried. There is also an opinion that a
This is a groove along the mucosa and can be classified
out when the arytenoid cartilage scleroses.12 The author's
sulcus often associated with reflux, the second is a sulcus
laser excision to cover the exposed cartilage. Recent work
the lamina propria, and the third is a sulcus vocalis
this is being used in a prospective study for subglottic
a theory that a sulcus is related to ruptured congenital
preference is a local mucosal rotational flap at the time of with mitomycin C has shown a decrease in scar tissue and
vergeture, which goes down to the superficial layer of
going down to the deeper layers of the ligament. There is
paediatric stenosis. There are some early reports of its use
cysts and may well be more common in the Indian
published data.
dysphonia following puberty. Numerous phonosurgical
in the prevention of recurring granulomas but, as yet, no
subcontinent. They frequently present with persistent
approaches have been suggested from excising the sulcus to injecting collagen or fat to boost the underlying layers.
Pontes1S advocates a technique involving parallel mucosal
PAPILLOMAS
These are due to the human papilloma virus (subtypes 6
and 11) and frequently recur. They are often found at
areas of constriction in the upper aerodigestive tract
where there is increased air turbulence, drying and
incisions of varying lengths running in a cephalad to
cordal direction to break up the linear scar of the vocal
fold. A lengthy postoperative recovery time may be
required, sometimes up to a year. [Grade D]
cooling of mucosa, and at the change of ciliary to
squamous epithelium.13 CO2 laser excision is the treat
ment of choice with minimal trauma to surrounding
tissue (that may contain dormant virus). An endoscope
;-�:
with a smoke evacuation channel is useful and the
been discussed. Settings of four watts on super-pulsed
laser (0.1 seconds) with a spot size
0f
0.3 mm is used and
specific laser masks for protection are essential. Single
papillomas are grasped gently as they may be friable and
the laser is used to excise the base. Surgical techniques
for multiple papilloma include using injection of saline
( + /- epinephrine) submucosally (hydrodissection) and
excising the mucosa en-bloc. This gives a lower recurrence
_
.
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presence of live virus in the laser plume and the possible
use of power instrumentation in the future has already
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less likely to give scarring by better
have reported success of different treatments by the
frequency of repeated lasering but there are now many established scoring systems taking into account the
distribution and appearance of papillomas in recognized areas
of
the
larynx.
This allows a
more scientific
and quantitative approach to future treatments. There
is encouraging work looking at an immunodeficiency of
T-cell lymphocytes in patients with papillomas and the
'-
'. '" t h�, .effec,t of sP9tisiz�)� w�t�ag(!, iP6d�:.. �0fj: <" ,' "":'�' .��. " .·�.ifi$ll� ·int.�ractiQlls banq hazards,;: , ' " .,.J,\, ;if); ' : , . �':�.::;. <5Qi 1as�r." and coJ�l: dis,$e�:tio}1. "ar�:·,c;:qWvaj¢l),t "
rate than surface ablation. It is also (by addressing the the ligament)
,
.
principles of phonosurgery and remaining superficial to
definition of tissue planes. Many case reports in the past
> .
'i ".:j:.}··.�.(..::r��>. f ->\'J'-�'" �.'�'
Use , of CO2, las�r� requiies understa'IjJihgc'9f
•
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,1,:.1' 1o�:'. ,. .;,t' ',,; _ "" � J l·� , _ , . -. , ..
Best clinical practice Nodules .!
Soft nodules are managed by speech and language therapy whilst hard nodules are managed by surgery and speech therapy.
./' Surgical.removal involves grasping the centre of a nodule, pulling it medially and then using
1.
.'
-
Chapter 170 Phonosurgery I
microscissors to cut m u cosa close to the base, t h u s preserving norm a l m u cosa a nd k e e p i n g a straig ht vibra tory edge.
./ Both sides can be done s i m u l taneous ly.
Polyps ./ D u ring su rgica l re mova l , a p p ro p riate preservation of m u cosa is essentia l: too l ittl e resu lting in reform a tion of the polyps, too m u ch in sca rring of the vocal folds.
Reinke's oedema ./ S u rgica l d ra i na g e invol ves: m a king a cordotomy incision on the superior a spect of the voca l fold (preserving the median vibrating edg e); - el evation of the m u cosa and asp i ration or remova l of the myxoedematous contents; m u cosa l fl a ps are then re p l aced and excess e p ith e l i u m is tri m m ed; fl a p is l a id onto su rfa ce and l eft to heal by su rface tension.
./ Th e re is no contraindication to opera ting on the second side p rovided there is no tra u m a to the anterior com m issu re.
Papillomatosis ./ Pa pil lomas a re excised using either a CO2 l aser or a m icrodebrider.
.,/ Sing l e p a p i l lomas a re excised at the base. ,/ For m u ltip l e p a p i l lom as, exci sion is facilitated by su b m u cosa l injection of sa l ine
(+/-
adrena l ine).
./ Fu rther studi es req u i red to address best fre q u ency of treatm ent.
./ Adj uvant treatm ents include retinoids, a l p ha interferon, ribavarin, cyclo-oxygenase 2 inhibitors and cidovir, but these are more recognized in the U SA than in the UK.
2239
component is absorbed in the first few weeks and its volume is partially replaced initially by an acute inflammatory reaction and later by a localized chronic inflammatory response, which encapsulates the remaining Teflon. This is, in effect, a localized granuloma but the difference in the initial volume injected and the final space occupying lesion is unpredictable, which may cause a good immediate result to deteriorate with time. If Teflon is incorrectly placed superficially and erosion of the overlying mucosa occurs, this can lead to a granuloma on the surface of the vocal fold, and a 36 percent incidence of granuloma production has been reported. Teflon particle sizes in the paste are sold as 50-100 microns, too large for immediate lymphatic spread since macrophage lymphatic cut-off is 40 microns. Studies on a commercial preparation of Teflon, however, have found particles of 4-40 microns which must lead to the question of distal spread. A study on Teflon injection into the peri urethral areas has shown spread to both regional and distal organs via venous channels, but although local spread to lymph nodes and the thyroid gland has been demonstrated with laryngeal injection, no distal spread has yet been documented. Long-term studies regarding Teflon have found migration locally into the superficial layers of the vocal fold leading to absent mucosal wave on stroboscopy and, therefore, poor long-term voice results.IS Teflon is, however, still useful in giving a good initial result in patients who have a unilateral vocal cord paralysis and a short life expectancy. The material is of high density and needs to be inserted deep into the thyroarytenoid muscle. Removal of Teflon with a CO2 laser gives high thermal damage and the vocal fold is scarred to such an extent that poor voice is almost guaranteed. As a result, excising the Teflon via an external approach and using a local muscle flap has been described with good results.19 [Grade C]
FAT
VOCAL FOLD INJECTION
BruningsI6 was the first to describe injection of the vocal folds in 1911 when he injected paraffin via a direct laryngoscopic approach under local anaesthesia. It is Arnold17 in 1962, however, who popularized this technique and the introduction of Teflon. Since then, numerous materials have been introduced and some of these are listed below.
Materials TEFLON
This is a polymer of tetrafluoroethylene and is sold as a paste consisting of 50 percent glycerine. The glycerine
This autogenous material has numerous advantages: it is easily harvested, readily available and does not give a foreign body reaction. There is no unified technique for its harvesting with some authors recommending , liposuction (which can lead to up to 30 percent cell destruction and an increased hypersensitivity reaction) whilst others harvest through a larger incision followed by irrigation with saline and soaking in insulin. It is reported that 30-50 percent of this fat will be absorbed within the first month and long-term studies also suggest a decrease in volume with time. 20 As a result of its absorption, many suggest overcorrection at the time of injection. The material is of high density and requires insertion deep into the vocal fold. Encouraging quanti tative voice results have been reported post-injection. [Grade C]
2240
I PART 16 THE U PPER A I RWAY
an atomical posi tion
GLY CERINE
This can be used as a temporar y material as it is absorbed within the first two to six weeks. It is compl etely reversible and fre quently combined with laryngeal electromyo gra phy (EMG) in cases of a temporary par al ysis . The EMG can be used prognostically to look at reinnervation of the vocal fold and the glycerine by augmenting the paralysed fold allows glott ic closure. Once again, i ts site should be deep within the muscle of the vocal fold.
of the neck, difficu lt y in ga ining access to the larynx in patients with cervical spine probl ems or other anatomical factor s preventing direct laryngoscopy and, most s ig nificantl y, lack of p atie nt feed back via phonation dur ing i nj e ction. This last factor pla ys an essential role in deciding the amount of material to inject at the time of su rg ery in patients undergoing procedur es under local anaesthesia. LOCAL ANAESTH ESIA Th e ind irect
COLLAGEN
This protein is a natural
constituent of the lamina propria of used in dennal a ugmentation, it has been p opularized by Ford et al. for use in the larynx where it becomes incorporated and even assimilated by new host tissu e .21 GAX-collagen (Zyplast) is bovine collagen cross linked by the addition of glutaraldehyde. A cross-linkage ensures better stability and reduces the rate of hypersensi tivity which is < 1 percent. Skin testing preoperatively is reco�ended before the collagen is inj ected superficially into the vocal ligam en t. It is a ch allenging p ro ced ure with blanchi ng of the vocal fold mucosa if too superficial. Altho ugh excellent results are repor ted by Ford, others have found this technique difficult and noted irregularity in its mode of absorptio n and replacement [Grade C]
the
vocal fold. Widely
SILICONE
Bi o plastiqu e is a silicon gel
consisting of vulcanized particles r anging from 150-600 microns susp ended in hydrog el. After an initial acute inflamm atory reaction, the material develops a fibrous capsu] e22 and alth o ugh, not used in the USA, has increased 'in popularity in Europe over the last year. Location of the material should be deep within the body of the voc al fold but so far there are few long-tenn results on the quality of voice or any comp lications with migration. polydimethylsial-oxane
laryng osco pic t echnique wi th strobosco pic been described in Europe, although many find the techruque difficult to master. The head pos i tion is still abnormal and due to the l ength of the i nstru men ts it is d iffi cult to assess the depth of penetration into the fold. Transcut an eo us techniqu es maintain the benefit of being p ro ce dures that can be carried out in the outpatient setting and have the great advantage that the head can be placed in a neutral, more anatomically correct, position. Penetration should be through the infe r ior half of the thyroid cartilag e but diffic ulty can occur when the c artilage is ossified or the needl e bore is blocked with cartilag e. Pene trat i ng the cricothyroid me m bran e is becoming a more familiar technique now that bot ul inum toxi n inje c tions into the thyroaryt e n oid muscle for adductor spasm odic dysphorua are increas ing " The injection needle can ei th er pass d ir ec tly into the cord without enter ing th e la ryn g eal lumen or pass initiaUy into the lumen and then penetrate the fold w hilst being visualized via a nasendoscope (Figure 170.2).23 control has
KEY POINTS • • •
Selection of operative methods These maybe subdivided as follows: • gene ral anaesthesia: direct laryngoscopic • loc al anaes t h esia:
•
method;
- di rect laryng osc opic method; - indirect laryngoscopic method; - transcutaneo us rout e through the - transcutaneous route through
the thy roi d car tilage .
GENERAL ANAESTHESIA
This is t he commonest method in
•
cricothyroid
membranes;
the UK. Drawbacks include visualization problems due to the anaesthetic tube or some other means of ventilation, the abnormal
Inject iblc glycerine,
•
incl ude Tenon, collagen and silicon.
materials
fat,
All provide inunediate resuhs. A\!I can ideally be carried out under local a,nacsthctlc. j,n the normal anatomtc�l position \·{ith the par�ent sitting up by injecting through the cricothyroid memhrane to obtain th e most reliable voice outcomes. -r"hese products delnonstra�e a range of rcversih�lity with glycerine being [ o l ally revcrs�blc, foLlowed by fat and "teflon being totally i rrc\'ersible. All except collagen ilre straighlifonvard to inject. All carry the potent ial cJ)Illplic<1t ions of over injection) airway c01!lp"ror,n;se .�vnd under
. . , � s t: : � l f � l l i i i � i i . �;Cli�� .
to
llseJt' i::I".- -: :':' ��� -'�-
�./:�::..�;
-"
,-
"
Chapter 1 70 Ph onosu rg e ry I
Figure 1 70.2
2241
Transcu taneous tech niq ue with
nasendoscopic control.
LARYNGEAL FRAMEWORK SURGERY
Payr, 24 in 1915, is credited with the first description of laryngeal framework surgery. This has been refined over many years by other surgeons but Isshiki25 was the first to describe using an alloplastic material (Silastic) and also to stress the benefits of carrying out the procedure under a local anaesthetic using the patient's voice for feedback. His name and the classification of laryngeal frame work surgery into four types of thyroplasty remains. 25 Koufman26 has done much to popularize the technique in America and new modifications of the original techni que are continuing to emerge. It is the Isshiki type 1 thyroplasty (now also called medialization laryngoplasty) that is commonly practised in the UK, although it may be combined with other modifications as mentioned below. Laryngeal framework surgery allows the size of the glottic aperture, plane of closure of the vocal folds and vocal fold length to be modified. Laryngeal framework surgery also maintains the laryngeal dynamics without invasion of the vocal folds and alteration of their mass or stiffness.
Selection of patients
Medialization laryngoplasty can be performed in any patients with a unilateral vocal cord paralysis. Waiting
12 months in idiopathic cases is still recommended, although if there is severe aspiration or in exceptional cases where the vocal needs of the patients require early intervention, surgery may be carried out sooner as an alternative to repeated glycerine injections during laryngeal EMG monitoring. Medialization laryngoplasty can also be used in cases of unilateral or bilateral bowed vocal cords caused by ageing and may be useful to correct soft tissue defects in the vocal fold as a result of previous surgery.
Techniques
Thyroplasty type 1 essentially involves medialization of the vocal cord by its inward displacement with an implant placed through a window in the thyroid cartilage (Figure 170.3). The operating technique is well estab lished 23 but some of the finer details are included below. In the original description, the cartilage window was preserved but many now remove this island of cartilage believing it can be displaced or absorbed leading to later complications. There are specific instrument kits available for medialization laryngoplasty which are not essential but can help to reduce the time of the procedure and ideally 30-40 minutes for a routine thyroplasty is adequate. Many authors believe it is likely that the inner perichondrium is torn whilst inserting the implant and as
2242
I PART 16 THE UPPER AIRWAY
a result, some authors advocate incising the inner perichondrium and preserving the thyroarytenoid fascia. This keeps the implant out of the body of the vocal fold which allows the fold to vibrate and a mucosal wave to be seen. This, therefore, is an advantage over any injected material which, together with a later foreign body reaction at the site of the injection, will stiffen and increase the mass of the cord. Although other authors have reported thyroplasty to be reversible, fibrosis around the silastic prosthesis makes it unlikely that this
*
x
=
=
critical pt 120 10)?
Y = 50
is a truly reversible procedure. A range of materials is available for medialization laryngoplasty and these are shown in Table 170.1. Interestingly, one should preserve the outer perichondrium when using Gortex as this will need to be sewn back to close the defect (window) in the thyroid cartilage. Design of the implant also varies, some preferring to insert the implant in halves, others use partial. incisions so that the implant will snap into place (Figure 170.4) and others have a long posterior flange in an attempt to close the posterior glottic chink. It is still not certain whether a posterior glottic chink can be closed with a medializa tion thyroplasty alone and research on the anatomy of the cricoarytenoid joint suggests that when the paralysed cord is on a different vertical plane to the normal one, then a medialization laryngoplasty is insufficient for full closure. [****/*] Poor results following medialization laryngoplasty are usually due to inaccurate preoperative assessment. The thyroid compression test is useful as a preoperative prognostic indicator as to the success of surgery although in older patients where the thyroid cartilage is calcified, medial displacement may not be possible. It is important to look not only at the posterior glottic area but also at any difference in the vertical levels of the vocal folds.
4)?
Figure 170.3
D i m ensions and location of window in thy roid
Developments
cart i la g e.
Table 170.1
Materia ls c u rrently used for media lizat i on
laryngopla sty. I
j"'"
.---
,MateriaL
-."
'- ·CQst
. Surgical skill
Si l a stic
Low
Moderate
Hyd roxya patite
Hig h
High
Gortex
Moderate
Low
Figure 170.4
Isshiki27 described an arytenoid adduction procedure for patients where there is a large posterior gap and the paralysed cord is at a different vertical level. Good results have been reported, both initially for a competent larynx and long term for voice production.28 [Grade C] A modification of this technique is the arytenoid fixation and cricothyroid subluxation as described by Zeitels.29 With an extended incision, the arytenoid cartilage is exposed, its attached muscles divided and the arytenoid
Insertion of sil a stic prosth es i s for m edia l disp l ace m ent of pa ra l ysed vocal cord.
Chapter 170 Phonosurgery I
2243
Figure 170.5 Suture gives tension to the paralysed vocal cord with the arytenoid cartilage fixed medially.
cartilage is fixed in a midline position. Tension of the paralysed cord is obtained by a suture between the inferior horn of the thyroid cartilage and the cricoid cartilage anteriorly (Figure 170.5). This· is usually combined with a medialization thyroplasty and allows correct positioning of the arytenoid cartilage and gives tension and bulk to the paralysed vocal cord. Although technically challenging, it is the author's personal choice for patients with a large posterior glottic chink. Common problems with thyroplasty include inserting a prosthesis that is too small or inserting a prosthesis in the incorrect place. Revision thyroplasties have shown that many insert the prosthesis too high as they do not define the lower border of the thyroid cartilage (Figure 170.3). The vocal cords are found deep to the inferior half of the the thyroid cartilage and inserting the prosthesis too high will displace the false cord and not allow glottic closure. Laryngeal EMG is useful in diagnosing an atrophic vocal cord. In these patients (only 9 percent of vocal cord paralyses are atrophic whilst the others are synkinetic), it is easy to perforate the laryngeal mucosa when lifting the inner perichondrium due to the thin sometimes non existent muscle bulk. This is also seen in patients who have received radiotherapy in the past and others who have had a high vagal neuroma excised. This atrophy of the muscle may also explain why long term voice results may worsen as the muscle bulk decreases. In these patients, the use of a local sternohyoid strap muscle flap to insert healthy tissue and prevent the implant from extruding inwards is useful (Figure 170.6). It is, therefore, essential to know preoperatively whether a strap muscle flap is required as occasionally, for exposure of the thyroid cartilage, the strap muscles need to be divided. This
Figure 170.6 Insertion of local strap muscle to provide bulk to atrophic/scarred vocal fold.
should therefore be avoided if possible or if necessary be divided superiorly to allow later rotation of the muscle flap in patients with an atrophic vocal fold.
2244 I
PART 1 6 THE UPPER A I RWAY
Muscles that produce low tension over a sustained time
Best cJ inrcal practice
period will have a high concentration of type
./ Carti lage w i n d ow now usu a l ly removed to prevent ri sks of late com p l i cations.
fibres. A high concentration of type
muscles that contract rapidly generating high tension over
a short time. The intrinsic muscles of the larynx differ in
./' Specific i nstrument kits not essenti a l but help to
their constitution of muscle fibres but the thyroarytenoid
reduce operati n g t i me.
muscle ( part of which is the vocalis muscle of the vocal
./' Some advocate divid i n g i n ner perichon d ri u m a nd prese rv i ng thyroarytenoid fascia to kee p i m plant out of body of vocal fo l d .
./' Thyro p l asty not tru ly revers i b l e due t o fi brosis a ro u nd si l i con prosthes i s.
fold) has a fast contraction time ( 1 4 milliseconds) and
< 36 percent type 1 muscle fibres. The strap muscles,
however, have a higher percentage of type
(66 p ercent) and a contraction time of
the intrinsic laryngeal muscles and the strap muscles are
G ortex.
./ I m pl a n t des i g n va ries to accom modate mod ifications in i nsertion tech n i q u e and m a x i m ize some effects.
.I U n l ikely to be a ble to close poste rior g l otti c ch i n k w i th thyro p l asty a l on e .
./ Poor resu l ts usua l ly d u e t o i n adeq u a te p reope rative assessment
also different with a diffuse pattern in the thyroarytenoid
but a typical skeletal muscle distribution in the strap
muscles where they form a narrow band at the midpoint.
This gross difference in the histochemical and contractile
properties of these muscle groups and their nerve supply makes them poor recipients and donors for nerve transfer.
It is proposed that the unfavourable synkinesis that occurs in
damaged recurrent laryngeal nerve with mixed partial
a
axonal
regrowth
is
replaced
by
. l'I S . synkinesis from the ansa cervlca
nerve
anastomosis
was
initially
that this was a successful technique but with no objective evidence to support their conclusions. Recently, Crumlel1 popularized the
technique
more
favourable
described using a block of omohyoid with its branch from
described in 1 90 9 by Horslelo and further work suggested
has
a
[****/**]
M uscle nerve pedicle reinnervation has also been
R EI N N E RVATI O N PRO CE D U R ES laryngeal
1 muscle fibres
50 microseconds .
The distribution of neuromuscular endplates in each of
.I I m p l a nts a re m a d e of s i l a stic, hydroxya patite or
Recurrent
1 muscle 2 fibres will be seen in
of ansa cervicalis to
recurrent laryngeal nerve anastomosis. [ Grade D 1
the ansa cervicalis, although some surgeons are now combining neural anastomosis with laryngeal framework
surgery as it appears that neural anastomosis alone does
not give a good result in a lateralized cord. In the author's
opinion, there is currently no convincing clinical or scientific evidence that the reinnervation techniques give better or equal results to either injection, medialization or
laryngeal framework surgery in the management of a
unilateral vocal cord paralysis. Table 170.2 shows the
N e u ro m u scu l a r p hys i o l ogy
advantages
The recurrent laryngeal nerve is a mixed nerve containing afferent,
sympathetic,
parasympathetic
and
500- 1 000
and
disadvantages
of the most common
p ro cedures currently used for the rehabilitation of a
patient with a unilateral vocal cord paralysis.
[H /*]
motor axons in an adductor to abductor ratio of 5 : 1 .
The ansa cervicalis, however, contains efferent fibres from
the first three cervical nerves to innervate the strap
muscles . Whereas the intrinsic laryngeal muscles are
KEY POI NTS
co ntrolled to contract at specific times, the strap muscles
have not been shown to have any p hasic action in istics of its supplying nerve, and the selection of the donor nerve should take into account the muscle fibre
composition of the muscle to be reinnervated.
[**H]
Muscle fibres can be divided into specific types based
on the histochemical and contractile properties. There are
three basic groups.
1 . Type 1: slow contractile period and aerobic
metabolism.
2. Type 2B: fast contractile period and anaerobic metabolism.
3. Type 2A: intermediate contractile period and both aerobic and anaerobic metabolism.
The u n derlying aetiology of tJ1e vocal abnormality must be established and addressed before surgery. t,c·"G�mwJ.���,, ��§�§��ent with videostroboscopy i��� �·" ffg�rt{t���;vr�M:��s urem en t s p re� and
•
the p rimate. Reinnervated muscle takes on the character
'·
\';:. � ; :�;"�1:�j,� p-6st::'sorg,ery are de�irable.
of the �natomy and ·· '��i',': KnO;'YJe4ge: ' : " �i � -,niici() s ttii�'iur� ·6-fdle vocal cords and
__
i.
,'.
,;�;{, �;����t;l��::���!�d' :�fo��pl�)njec�i���' ��.;���.,:r._: t
. . . " replacing
Teflon' for vocal fr
" are ,
ne
r
.
;
'
'
;>:�� -aud i�ol�Y
..��. ::�� .�, �.� �_ ��, . -
"
�
� ' ' ·' \ ,
��; ,t:;k�!�-feed:�a<;�,-� ::J;�;�J::;��h��;����i?;�l �:;�_ �. ;. . I
:'
. �:;�: �. �••�;:.: <:._�;;}:.; )
-_ �
-- Table 1 70.2 "
Com parison of p roced u res c u rrently used for t h e reh a b i l itati o n of a p a t i e nt w ith u n i l a te ra l vocal fo l d p a ra lysis.
' ' Procedure 1,
Teflon i njection
Time taken
Res u l t s
Anaesthetic
Reversible
( m i n u t es) 1 0-30
Loca l/g e n e ra I
I m med iate
No
Demand on
Changes in vocal
technical ski ll
fold
M o d e rate
G ra n u l o m a w ith i n
C.om p l ications
Cost
U n d e r- i njecti o n
Chea pest
body of fo l d
Ove r- i njecti on
(n onvi bra t o ry)
Airway c o m p romise Misplacement of Tefl on Mi gratio n G ra n u l o ma fo r m a t i o n
F a t i njection
1 0-30
I m med i ate b u t
Loca l/g e n e ra l
Yes
M o d e rate
None
U n d e r- i nj ect i o n
30-500/0 and i n
Ove r- i nj ec t i o n
1 / 1 2 good voice
Ai rway c o m p ro m ise
F ree-eas i Iy ' h a rvested
res u lts G lyce r i n e i njecti o n
1 0-30
I m med i ate
Loca l/g e n era l
Yes
M oder ate
None
U n d e r- i njection
M o d e ra te
Ove r- i njection Ai rway com p rom ise Co l l ag en i njecti o n
1 0-30
I m m e d i a te
Loca l/g e n e r a l
?
High
None
U n d e r- i njection
M o derate
Ove r- injec t i o n Ai rway co m p romise 5il i cone i njection
1 0-30
I m m ed i ate
Loca l/g e n era l
?
High
None
U n d er-injecti o n
M o d e ra te
Ove r- i njec ti o n Ai rw a y c o m p ro m i se La ryng e a l fra mework
3 5- 7 5
Loca I/g e n eral
I m m e d i a te
Yes
M o d e ra te
s u r g e ry
I m p l a nt l ateral to
Wou n d i n fecti o n
Opera t i n g
body of fo l d
Haematoma
theatre
(Red u ced
Ai rw a y co m p ro m ise
time
m u co s a l wave)
Mucosa l perfora t i o n D i s lo dg e m e n t a n d/o r extru s i o n
Re i n nervation
60- 1 2 0
2-3 m o n t h s
(+
G e n e ra l
Yes
M ost
R eturn of m u cosa l
Wou n d i nfection
Operating
G e l fo a m/
wave, b u t no
Hae m a t o m a
theatre
G lycerine
voca l fo l d
Loss of a bn o r m a l syn k i n e t i c
time
i njectio n)
move men t
tone ( F l a cc i d fo ld)
2246 • .•
I PART 16 TH E U P P ER AI RWAY
!v1 edialization bryngoplasty using Gortex is' -ardnt ively simple technique . .
"
8.
New techniques, such as arytenoid fixat'i ori
with cri cothy ro i d subluxation, can improve " ,
results when the vocal cords are at
diff�rent '
9. -
vertical levels. •
LDcal muscle flap i nse rtiDn can be used
in
atrophic vocal folds to. p reven t extrusiDn Df the implan t.
•
1 0.
'
There is no. convi nci n g clinical Dr scien tific evidence that rein'nervation teclinique�- gi've ,
2000 ; 3 3 : 1 087-96. Sataloff RT, Sp i eg el J R, H e u re r RJ, Baroody MM, E m e rich KA, Hawks haw MJ et al. La ry ng eal m ini-mi c rofl ap s : a new techn ique and reassessm en t o f t h e mi c roflap saga. Journal of Voice. 1 99 5 ; 9: 1 98-204. Bouchay e r M, Co rn ut G. Instrumental m ic roscopy o f b enign l es io n s o f th e vocal fold s. I n : Ford C , Bless D (eds). Phon osurgery: assessment and surgical management of
voice disorders. New York: Rav en P ress, 1 99 1 : 1 43-65. M atushek KJ , Bjo rl ing DE. A m u cosal fl ap t ech n ique fo r correction of l a ryngeal webbing . Results in fou r dogs. Ve terinary Surgery. 1 98 8 ; 1 7 : 3 1 8-20. 1 2. Benj a m in B, Roche J . Vocal granulo m a , including scl e rosis of the a rytenOid c a rtil age : radiog raph i c find ings. Annals of Otology, Rhinology, and Laryngology. 1 99 3 ; 1 0 2 :
better Dr ,equal - results to injection or': laryngeal frameWDrk ' su,rgeiy.
11.
Defici e nc i e s i n cu rre nt k n ow l e d g e a n d a re a s fo r fut u re re sea rch Phonosurgery would benefit fro m : » i mp roved stand a rd s o f measuri ng vocal results fo r
756-60. Kashi m a H , Mounts P , Lev enth al B , H ruban R . Sites of p red il ect ion in recu rrent respi rato ry pap illo m atosis. Ann als of Otology, Rhinology, and Laryngology. 1 99 3 ; 1 0 2 : 580-3. * 1 4. O rlo ff L A La ryng ea l recu rrent resp i rato ry p ap illomatosis. 13.
m ea n i ngful aud it;
Curren t Opinion i n Otolaryngology and Head a n d Neck
� increased av a il a b il ity o f l a ryngeal EMG fo r mo re
Surgery.
accurate diag nosi s; >- id entifi cat ion of safe adj uv ant treatmen t fo r s uccessful m a n ag em e n t of resp i ratory p ap illo m ato sis.
revie w of the condition and different modes of treatmen t.
1.
2.
3.
G arcia M. Observations on the h u m an v oice. Pro ceedings of the Royal Society of London. 1 855 ; 7 : 3 97-4 1 0. Bozzin i P. Der Lichtl e i ter oder Besch reib ung einer einfachen Vo richtung, und ihrer Anwendung z u r erl e u ch t ung inhere r Hohlen, u nd Zwischenrau me des lebenden a n i m aschen Korpers. Weimar, 1 807 . Zeitels SM. The histo ry and dev elop m ent o f
pho no m icrosurgery. Professional voice; the science and art of clinical care, 2nd ed n. Singul a r Pu bl ish ing Grou p, I nc. 1 997 ; 48 : 5 8 1 -602. 4. G reen H. Morbid growths within the larynx. New Yo rk : GP Pu tnam, 1 852. 5.
6.
Gray SD, H a m mond E, Hanson D F. B enign p a thologi c responses of the l a rynx. Ann als of Otology, Rhinology, and Laryngology. 1 995; 104: 1 3 -8. Ben n ing e r MS. M i cro d i ssectio n or m icrospot CO2 laser for li m ited vo cal fol d benig n lesio n s : a p rospective random ised trial . Laryngoscope. 2000; 110 ; 1 - 1 7. An excellent comparison of two techniques for benign vocal fold lesions by the same surgeon.
7.
Pa tel R S , MacKenzie K. Powered l a ry ngeal sh av e rs and l a ryngeal papil lom atosi s : a p rel i m inary report. Otolaryngology. 2000; 2 5 : 3 58-60.
Clinical
2000; 8 : 485-8.
An up to date comprehensive
(n o t on pubmed).
Po n tes P, Beh l a u M. Trea t m e nt of sul cus vocal i s : a ud i to ry pe rceptual and a co ustic a na lysis o f t h e sl icing mu cosal s u rg ical t echn ique. Journal of Voice. 1 99 3 ; 7 : 365-76. 1 6. Bruni ngs W. U b er eine n e u e behandlungs methode d e r Reku rhenslah mung. Verhandlungen des Vereins Deutscher La ryngologen. 1 91 1 ; 8 : 93 - 1 5 1 . 1 7 . Arnold G E. Vo cal reh a b il ita tion of pa ralytiC dysphon i a : IX; technique of intracordal inject ion. Archives of Otolaryngology. 1 962 ; 7 6 : 358-68. 1 8. G a rd ener G, Parnes S. S ta tu s o f the m u cosal wav e post vocal co rd injection versus thy roplasty. Journal of Voice. 1 99 1 ; 5 : 64- 7 3 . Confirms the benefit of th yroplasty for 1 5.
REFERENCES
*
Rosen CA. Pho no surg ical vocal fold injectio n : procedures a nd ma terial s. Otolaryngologic Clinics of North America.
*
preseNa tion of the mucosal wove. (n o t indexed on pubmed).
1 9.
Nettervi l ie J , Coe Iman J , Chang S et 01. Latera I l a ryngoto my fo r the removal of Teflon g ran ulo m ata. Ann als of Otology, Rhinology, and Laryngology. 1 99 8 ; 1 07 : 73 5-44. 20. Sh aw GY, Szewczy k MA, Searl e J e t 01. Autologo us fat i njection i n to the vocal folds : technical co nsideratio ns a nd long-term follow up. Laryngoscope. 1 997 ; 1 07 : 1 7 7-86. 2 1 . Fo rd C, Bl ess D , Loftus J . Rol e o f coll age n in th e treat ment of glottic insuffici e n cy : a study of 1 1 9 patie nts. Ann als of , O tology, Rhin ology, a nd Laryngology. 1 99 2 ; 10 1 : 23 7-47. 22. Tsuzuki T, Fu kud a H , Fuj io ka T. Response of the hu m a n l a rynx to silicone. American Journal of O tolaryngology. 1 99 1 ; 1 2 : 288-9 1 . 23.[. H a rries M, Mo rrison M. P honosu rg ery and m i crol a ryng ea l su rge ry. In : Bl each N, Mil fo rd C, Van H assel t A (eds). OperatilJe otorhinolaryngology. Chapter 45, Oxfo rd : Bl ackwell Science , 1 997 : 3 1 5-25.
Chapter 1 70 Phonos u rg e ry I
24.
Payr
E.
Plast i k am sch i l d knorpel zur B e h e b u n g der Fo l g e n
* 29.
* 2 5.
1 9 1 5 ; 43 : 1 265-70.
l a ry n g o p l asty, a n d cri cothyroid s u b l uxa t i o n .
I ssh i ki I'J, M o rita H, O ka m u ra H, H i rom oto M. Thyro p l a sty
Otolaryngologic Clinics of North America.
a s a new p h onosu rg ica l tech n i q ue. Acta Otolaryngology.
841 -54.
1 974; 7 8 : 451 -7.
Koufm a n JA. La ry n g o p l asty for vocal cord m ed i a l isa t i o n : a n a l ternative t o Tefl o n . Laryngoscope.
2 7.
cords on differen t planes.
30.
1 986; 9 6 : 726-3 1 .
H o rs l ey J . S u t u re of t h e recu rre nt l a ryng e a l n e rve w i t h re port of a case. Transcriptions from the
I ss h i ki N, Ta n a be M, Sawada M. Arytenoid a d d uction for
South Surgical Gynecological Association.
u n i l a te ra l voca l cord p a ra lysis. Archives of Otolaryngology.
1 61 -70.
1 978 ; 1 04 : 555-8. 28.
2000; 33 :
Based on phonosurgical principles this
introduces an excellent technique for paralysed vocal
In troducing laryngeal frame work
surgery and its benefits for restoring voice physiology.
26.
Zeitels S M . l'J ew p roce d u res for p a ra lytic dys ph o n i a : a d d uction a ryte nopexy, Goretex m e d i a l isation
e i n s e i t i g e r Sti m m ba n d l a h m u ng . Deutsche Medizinische Wochenschrift.
2247
31.
1 909 ; 22 :
Cru m l ey R. New perspectives i n l a ryngea l rei n
Woo P. Aryte noid a d d uction and m e d i a l isation
n e rvat i o n . I n : B a i l ey BJ , B i l l e r H F ( eds) . Surgery
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1 3 5-47.
1 98 5 :
171 Acute infections of the larynx ANDREW C SWIFT
Introduction Cl inical features of acute laryngeal infection Acute laryng i t i s Acute laryng itis and the professional voice Best c l i nical practice Adult epiglottitis Best clinical pract i ce laryngotracheobronchitis or croup Best c l inical practice Pertussis Best clinical practice Diphtheria
2248 2248
2249
2249
2250
2250 2251
2251
Best clinical practice Infectious mononuc l eosis Best clinical practice Mycotic laryngitis Best c l inical practice Laryngopyocoele Best c lin ical practice Key pOints
2252
Deficiencies in current knowledge and areas for future
2252
References
2252
research
2253
2253
2254
2254 2255
2255
2256
2256
2256 2256
2252
The information and data in th is chapter were compiled after a Medline search via Ovid. The key words used were laryngitis, epiglottitis, croup, laryngotracheobronchitis, per tussis whooping cough, and diphtheria, laryngocoele, laryngopyocoele. The search was limited to the English language. ,
INTRODUCTIO N
The larynx is in a unique pOsltlon in being a major component of the upper respiratory tract and also lying just anterior to the upper end of the digestive tract, It is therefore vulnerable to various causes of inflamma tion, not all of which are infective. Gastro-oesophageal reflux disease (GORD/GERD) is now a well-defined clinical entity that is associated particularly with posterior glottic and arytenoid inflammation. Inflamma tion affect ing the vocal cords can be induced by vocal misuse/abuse, exposure to irritants and allergies. The larynx may also be affected by chronic inflammatory noninfective condi tions, such as sarcoidosis and Wegener's granulomatosis. Laryngeal infection can also OCcur as a rare complica tion of a neck space infection, such as a p arap haryngeal or retropharyngeal abscess and Ludwig's angina.
CLINICAL FEATURES OF ACUTE lARYNG EAL IN FECTIO N
The general clinical features tha t should be so ugh t from a patient with acute laryngeal infection include the following: • • • • •
change or loss of voice; d if fi c ult y in breathing/stridor; sore throat and o t al gia; difficult or painful swallow; tender larynx with/without cervical l y m phadenop athy
.
Laryngeal i nfect ion usually presents with a weak breathy rough voice or aphonia. Stridor occurs if there is significant airway narrowing and is therefo're Inspiratory stridor occurs with narrowing of the
Chapter 1 71 Acute infections of the larynx I
2249
supraglottis or glottis. Expiratory stridor implies narrow ing of the subglottis. Indirect laryngoscopy with a mirror is possible in most adults but flexible fibreoptic nasendoscopy is far superior and is recommended wherever possible. The specific features of note are the presence of inflammation and swelling of the supraglottis, glottis and subglottis; the space between the vocal cords and cord mobility; pooling of saliva in the hypopharynx.
ACUTE LARYN GITIS Acute laryngitis is a common inflammatory condition that affects the vocal folds and supraglottis. The usual cause is a virus associated with an upper respiratory tract infection,
but
laryngitis
may
also
be
secondary
to
infection of the tonsils or the chest. Inhalation of dusts and fumes or underlying allergy can induce laryngeal inflammation and may facilitate the development of acute laryngeal infection.
Pathophysiology
Figure 171 .1
© Hodder Nnold I Scott-Brown 7E
Typical appearance of severe acute l a ryng it i s as
seen with a flexible nasendoscope.
Antibiotics should be reserved for more severe forms of bacterial laryngitis, persistent laryngeal inflammation, or
Why acute laryngitis occurs only in some and not all patients with a common cold is not fully understood. It
in specific patients who rely on their voice professionally. Penicillin has no effect, but erythromycin, which is active
has been suggested that Moraxella catarrhalis is involved
against Moraxella catarrhalis, is associated with less vocal
in the pathogenesis.! The incidence of Moraxella catar
disturbance and reduced coughing at one to two weeks
rhalis in the nasopharynx of patients with acute laryngitis
but no other significant effects.l
is significantly higher compared to controls and the
Residual problems such as aphonia, hoarseness Or
pathogen is spontaneously eliminated one to two weeks
throat discomfort sometimes occur but the larynx may
after the infection has resolved. [****]
look surprisingly normaL The likely explanation is that the residual dysfunction is due to persistent inflammation
Clinical fea tures
within the internal laryngeal muscles. Speech therapy is indicated if the problem persists. [Grade AJ
Acute viral laryngitis is normally a self-limiting infection that resolves after a few days. Patients will have a rough, deep voice of variable pitch that often disappears in mid sentence and they may, on occasions become aphonic.
ACUTE LARYNGITIS AN D THE PROFESSIO NAL VOICE
Voice changes are usually preceded by the symptoms of a common cold and a sore throat.
Although professional singers present for urgent treat
Examination will show erythema and oedema of the
ment of their acute voice disorders, not all have acute
vocal cords and there may be excess secretions. Changes
laryngitis and differentiation is important with regard to
can, however, be subtle and not nearly as bad as the
subsequent management.2 Patients with acute laryngitis
symptoms may suggest.
show early glottic contact at the mid-portion of the
Bacterial superinfection will induce a more severe degree of laryngitis that may persist and become chronic
(Figure 171.1).
membranous vocal fold. [**J Management of professional voice users with laryngitis includes systemic steroids, antibiotics, mucolytics1 vocal rest and attention to hydration. There are) however, no definitive studies on the efficacy of steroids in such
M anagement
patients. With regard to antibiotics, a full course and high
Acute laryngitis usually resolves completely over one to
mycin and tetracycline are
dose is recommended.3 Amoxicillin, ampicillin, erythro two weeks and investigation is unnecessary. Basic therapy includes vocal rest, avoidance of irritants and steam.
all suitable. Antiviral agents are
not considered to be as effective as antibiotics and have significant side effects. [Grade D 1
2250
I PART 16 THE UPPER AIRWAY
patients will often complain of an acute painful sore throat, dysphagia and odynophagia.lO, 12 Examination usually reveals a red swollen epiglottis
.I Acute l a ryngi t is is generally se l f- l imiting and shou l d b e managed b y vocal rest and
ma inta ining
and the larynx is extremely tender. Cervical lymphadeno
good
pathy is common. Drooling, respiratory distress and
hydration.
hoarseness and oedema of the palatine arches and uvula
.I An t i b i ot i cs should be reserved for severe cases where
may also be seen. Stridor is uncommon but tachycardia
bacte rial superinfection is thought to have occu rred.
that is disproportionate to the pyrexia is an important 14
sign that precedes airway obstruction.l3,
ADULT EPIGLOTIITIS
Investigations
Epiglottitis, or supraglottitis, is an acute infection of the supraglottis that
affects
primarily
the
epiglottis
Investigations should include blood culture and a throat
but
swab culture but they are often negative. Nasopharyngeal
includes other sites such as the lingual tonsiL aryepiglottic
swabs have been considered but are of limited value. The
folds and false cords. The incidence in adults is estimated to be
100,000
and 6-23 per
100,000
1-9 cases
white cell count is important and significant elevation is
per
likely
in children.4 An increasing
findings are not consistent.S,
(**]
marked
decrease
in
phy
to
cases.
as
[***/**]
This ratio has been
much reduced and even reversed where the Hib vaccine
M anagement
has been used.s,9 Before the introduction of vaccination in Sweden, epiglottitis was declining in children but remained stable in adults at
(CT) scans are useful if there is a complication such
an epiglottic abscess, but they are not necessary in most
prevent childhood meningitis. Prior to the introduction
3:1.7
(Figure 171.2).
the epiglottis (the thumb sign) and absence of a deep well
of vaccination, the ratio of epiglottitis between children and adults was estimated to be
airway
defined vallecula (the vallecula sign). Computed tomogra
epiglottitis since the introduction of vaccination against
1985
impending
able, methods of improving their diagnostic accuracy have 15, 16 Specific features include thickening of
paediatric
Haemophilus inJluenzae type b (Hib vaccine) in
with
been described.
progresses very rapidly and compromises the airway. a
patients
Although radiographs have been considered to be unreli
Epiglottitis affects all age groups. The main difference
been
in
if flexible nasendoscopy is not available
in children compared to adults is that acute epiglottitis has
occur 13
A plain lateral soft-tissue radiograph of the neck is useful
predominance has been described in adults but these 6, 7
to
obstruction.
incidence, a seasonal increase in autumn and a male
There
(**]
2.3/100,000
per year.9
Once suspected or diagnosed, the patient should be
(**]
admitted
and
observed.
There
is
some
controversy 12 Airway
regarding when airway intervention is necessary.
obstruction is potentially life threatening and intubation
M icrobi ol ogy
should be considered before the airway becomes seriously
Prior to vaccination programs, Haemophilus inJluenzae type
b was
the
commonest
pathogen,
especially
/� ' ."
in
i '4t -. t '.,� /, ,
children. A wide range of pathogens has been described in adults
and
these include
Group A
Streptococci,
Streptococccus pneumoniae, Staphylococcus aureus and 10 Klebsiella pneumoniae. Recently, Neisseria meningitidis has
been
recognized
as
a
cause
of
fulminant
:,� ' �.'
life
�hr.eatening supraglottitis.11 Unusual organisms are likely In lmmunocompromised patients. Epiglottitis due to viral
.. -
.
' �' :. '"'f ,
...�, 4��
infection is rare, particularly in adults. In many patients,
pathogens are not isolated, either from throat or blood
cultures.
. �.- ,
.
.
.
[****/*]
'... �' .
Clinical features Adult epiglottitis differs from the familiar presentation in children: airway obstruction may not be present and
.
Figure 171.2
' 5 oft-tiss ue lateral neck radiograph of an adult
with acute e p ig l ottit is.
'
Chapter 171 Acute infecti ons of the larynx I
2251
compromised.17 Tracheostomy has its proponents but
responses of T helper and B-Iymphocytes from previous
airway management can only be determined by the
exposure in childhood. Adult croup is rare and impaired
expertise and monitoring facilities that are available in
immunity should always be considered.
The characteristic feature of this specific form of
individual units. Treatment should be with intravenous antibiotics and
laryngitis is subglottic oedema. Why the swelling affects
100 percent humidified oxygen. The antibiotics of choice
the subglottic mucosa rather than the adjacent glottis is
are second- and third-generation cephalosporins. Ampi
unknown. This dilemma has been studied
cillin was often prescribed but resistant H. inJIuenzae are
model using rats infected with Sendai virus that is
now emerging. [Grade C]
in an animal
structurally and serologically related to parainfluenzae type 1. The infl amm atory response and migration of dendritic cells, neutrophils and lymphocytes is much greater in the subglottis compared to the glottis.2o
Complications
[****/*] The main complication is death from respiratory arrest due to acute airway obstruction. This is much more likely in patients with rapidly progressive disease and occurs within hours of the onset of the illness.14 Other complications are rare but include epiglottic abscess, pulmonary oedema secondary to relieving airway obstruction, and thrombosis of the internal jugular vein (Lemierre's syndrome).
[**j*]
Clinical features Adult croup presents in a similar way to childhood croup but it is a more severe illness in adults?l This difference may be due to children with less severe infection being admitted to hospital and adults with mild subglottic oedema not seeking medical advice. The illness usually presents with a cough, sore throat,
Best clinical practice ./ Adu lts w ith su spected acute ep iglottitis should be admitted and the airway closely monito red.
.I Patients should be treated with i ntravenous second or th i rd-generation ce phal osporins and 100 pe rcent
malaise and mild fever for two to four days. Deterioration can be rapid and signs include shortness of breath, stridor and inspiratory retraction of the soft tissues of the neck. The endoscopic appearance of the larynx will show a normal epiglottis, inflamed vocal cords and subglottic oedema extending into the trachea.
[*]
humidified oxygen.
v' A irway obstr uction should be treated early, idea l ly by intubation.
I nvesti g ati 0 n Direct viral antigen detection by sampling mucus from the nasopharynx may be helpful in identifying the viral
LARYNGOTRACHEOBRONCHITIS OR CROUP Croup is an old Scottish word for sore throat with harsh
pathogen. Microorganisms are not often identified from tracheal aspirate cultures. A plain neck radiograph may show narrowing of the subglottis.
breathing that is now used to describe an acute illness with hoarseness, a barking cough, stridor and varying degrees of airway distress.
M anagement
Croup affects mainly young children, aged six months
to three years, in which subglottic oedema leads to early
Because of the risk of rapid deterioration, adult croup
respiratory distress and biphasic stridor. In contrast, adult
should be suspected and recognized early.
croup is an uncommon condition that was first reported
The principles of management are similar to those in
in 1990.18 It is a community-acquired acute laryngo
children. Oxygen, steroids and nebulized epinephrine
tracheitis in otherwise well patients and differs from
should be administered. The airway and oxygen satura
acute bacterial tracheitis that often results in rapid
tion should be monitored and intubation considered if
death.19
the airway is impaired. Broad-spectrum antibiotics are
Laryngotracheobronchitis (LTB) is usually caused by a viral infection. The paramyxoviruses, para-influenza virus
advisable to cover secondary infection, but there is no evidence to support antiviral agents.
type I and type II are commonly implicated but in adults
At present, there is no means of preventing infection
infe'ction may also occur from herpes simplex, cytome
but recent research is focussed on the way the virus binds
galovirus and influenza virus. The difference in pathogens
between adults and children is probably due to memory
to cells resulting in a cascade of molecular events that 2 [Grade ND 1
leads to the virus entering the cell. 2
2252
I PART 1 6 THE UPPER AIRWAY
is recommended, but this does not change the character of
the cough
Alternative
,/ Ad u lt croup is rare but can be rapidly progressive and
and
cause significant airway obstruction. Once suspected,
or clinical course of the disease.23,26
options
are
clarithromycin,
trimethoprin-sulfamethoxazole.
azithromycin
Fluoroquinolones
are also likely to be effective in adults but there is no
patients s h o u ld be a d m i tted and cl osely m on itored.
supporting data of effectiveness. The cough should be
.! T h e l a rynx and s u bglottis should b e inspected by a
treated symptomatically with cough suppressants. There
flexib l e endoscope or b ronchoscope.
is no systematic review of the use of steroids, adrenergic
,/ B road-spectrum ant i b i ot ics are a dvisa b l e to p revent
agonists or pertussis-specific immunoglobulin.
bacteria l infect i on.
Erythromycin is thought to prevent patients from being
.! If the airway deteriorates, th e pa t ien t sho u l d be
infectious and is recommended as prophylaxis in affected
intubated and ventilated.
households, but the effect has been described as modest
compared
with good
quality vaccination.27 [Grade A]
PERTUSSIS Whooping cough, or pertussis, is an acute illness that usually caused by
is
Bordetella pertussis. The bacteria produce
endotoxin and exotoxins that induce
an
.! P e rt ussis should be considered in pat i ents of any age
inflammatory res
p resenting with a prolonged acute spasmodic cough
ponse, stop cilia from functioning and cause epithelial cell
of three or m ore weeks durat i on.
necrosis. It is a notifiable communicable disease that affects
./ Once recog n ized, treatment with a 7 -14-day cou rse
all age groups and is transmitted by coughing and sneezing. infants.
of e rythromycin s h ould be commenced.
Pertussis is most severe in children, particuJarly
Adults generally have a milder disease and less severe cough.
Despite vaccination, there are 20-40 million cases per
year worldwide,
90
percent
occurring in developing
countries. There are still 200,000-300,000 deaths per
DIPHTHERIA
suggests an incidence of 4 per 100,000, but there is
Diphtheria was endemic in the UK until approximately 50
year.23
In
England and Wales,
statutory
notification
evidence to suggest that the diagnosis is substantially higher and should be considered in all patients presenting with a prolonged acute spasmodic cough?4,25
[****/**]
years ago when mass immunization was introduced. However, the disease is still prevalent in the developing world and there has been a resurgence in Eastern Europe. The ease of world travel facilitates the transmission to
Clinical features Whooping cough presents with symptoms of a runny nose, dry cough and mild pyrexia, similar to a common cold. The cough occurs in prolonged paroxysms after one to two weeks and is followed by gasping and the characteristic whoop in children. The disease is generally milder in adults and presents as protracted cough rather than the characteristic 'whooping cough' of children. Consequently, the diagnosis may not be considered.
countries where doctors will probably not have seen a case
and
the
diagnosis
may
considered. The disease is caused by
therefore
not
initially
be
Corynebacterium diptheriae
and spreads by droplets from the upper respiratory tract of
an
affected
individual.
It
affects
nonimmunized
children and susceptible adults, particularly the elderly. The usual site of infection is the tonsil and fauces, but it can also occur in the nasal cavities or spread to the larynx.
Investigations
Clinical features
The diagnosis should be confirmed by serum serology and
The disease causes a severe sore throat, malaise, pyrexia
chain reaction (PCR).
of the throat shows a characteristic grey membrane in
nasopharyngeal aspirate culture and assay by polymerase
and nasal discharge if the nose is affected. Examination
the oropharynx and this may spread to affect the larynx. The cervical lymph nodes will also be enlarged and
M anagement
tender.
Pertussis is usually not diagnosed until the cough has
develops a severe illness depends on the host response and
developed. However, a 7-14-day course of erythromycin
Whether an infected patient becomes a carrier or virulence and toxigenicity of the organism.
----- ------ -" ��.'�.-.......<..-,.......
Chapter 171 Acute infections of t h e larynx I
2253
Investigation
Clinical features
If oropharyngeal diphtheria is suspected) a swab from the throat and/or nasopharynx should be obtained. A sample of the grey membrane, if present) should be sent for screening. Since Corynebacterium diphtheriae is not easily identi fied) throat swabs from all patients with sore throats should be specifically screened. In the UK, positive isolates should be sent immediately to the reference laboratory for detection of the potent exotoxin.28 [****]
The characteristic features include an acute sore throat with large red infected tonsils, cex:vical lymphadenopathy with grossly enlarged bilateral lymph nodes, pyrexia and general malaise. There may also be palatal petechiae) oral ulceration) splenomegaly and hepatomegaly.
M anagement
Treatment is with benzylpenicillin and antitoxin. Acute airway obstruction should be managed accordingly, ideally with intubation. Close contacts and relatives should be immunized.
Complications
The diffusible exotoxin has a predilection for cardiac and renal tissue and causes myocarditis, arrhythmias and possible death. Neurological complications due to the exotoxin may develop a few weeks after the acute infection: the most frequent is soft palate paralysis but paralysis may also affect the diaphragm and the external ocular muscles. Other long-term sequelae include scarring of the oropharynx and nasopharynx due to fibrosis and adhesion formation.
Investi gation
A full blood count and serology should be carried out. The heterophile antibody test is highly specific and if negative should be repeated. If still negative) specific EBV serology should be requested) together with serology for HIV) cytomegalovirus) rubella and toxoplasma.
M anagement
Medical management includes intravenous fluids and analgesia. There is no specific treatment for infectious mononucleosis. However) in serious infection) antibiotics, systemic steroids and acyclovir should be considered. An -antibiotic active against oral anaerobes is most suitable) but ampicillin and amoxicillin should be avoided for fear of inducing a maculopapular rash. Steroids will theore tically enhance viral replication but this has to be balanced against their effect on limiting the effects of inflammation and oedema.
Complications
./ In pati ents p resenting with severe sore throat and m a l a ise, a throat/nasoph aryngeal swab sho u l d be o btained and screened fo r diphtheria.
./ If diphtheria i s s u spected or d i agnosed, benzyl penici llin and antitoxin s hou l d be ad m in istered.
./ The airway should be monitored an d if obstructed, intu bation should be considered.
INFECTIOUS M ONONUCLEOSIS
Infectious mononucleosis is a common disease that is often subclinical or mild. It is caused by the Epstein-Barr virus) a herpes virus that has a special affinity for B lyniphocytes. Spread is usually by transfer of infected saliva during kissing and the condition is therefore most likely seen in adolescents and young adults.
The disease is often mild and self-limiting and this can give a false sense of security. However) this is 'not always the case) and serious life-threatening complications can ensue. These include airway obstruction, splenic rupture, a myriad of central nervous system (CNS) complications such as encephalitis) meningitis and cranial nerve palsies) haemolytic anaemia, granulocytopaenia and total systems failure. Immune deficiency and HIV must be considered if such serious disease ensues.29 Approximately 9 percent of patients develop a disabling chronic fatigue syndrome. Gross swelling of the tonsils and post-nasal lymphoid tissue (adenoids) causes airway obstruction) but inflam mation and ulceration can also extend to the larynx. The severity of the laryngeal involvement may be masked by the upper airway obstruction and awareness of this possibility is therefore of crucial importance (Figure 171.3). Steroids may help to alleviate airway obstruction but if there is any element of doubt) tracheostomy and or intubation should be considered. The author favours the latter because of the disastrous complications that result if the patient has a tracheostomy and deveJops a bleeding disorder as well. [*]
2254
I PART 16 THE U P PER AI RWAY
© Hodder flrnold / Scott-Brown 7E
Figure 171.3
fro m candida and aspergillus are widespread but coccidioidomycosis, blastomycosis and histoplasmosis are endemic to specific geographical regions. The larynx is probably affected by candida more often than realized. In immune-competent patients, the most common predisposing factor is recent treatment wi th antibiotics. Other predisposing factors include inhaled steroids, diabetes, chemotherapy, radiation therapy, smok ing, acid reflux and inhalational or thermal trauma. Often there is more than one predisposing factor present. The characteristic finding in the larynx is a white pseudo membrane or adherent white plaque that looks the same as leukoplakia. It can also appear as diffuse erythema, with oedema and ulceration in severe infection.3o Invasive aspergillosis is an opportunistic infection that occurs mainly in immunocompromised patients with haematological malignancies. Primary laryngeal aspergil losis is very rare, but recognition is important as steroids could have an adverse effect in affected patients with airway distress.31
Infectious mononucleosis in a 24-year-old man
wit h massive enlargement of cervical lymph nodes and severe
Investigation
upper airway obstruction from gross tonsillar enlargement.
Best clinical practice .; If infectious mononucleosis \s suspected, a
I
heterophile antibody test should be requested and, if negative, additional specific serology for EBV and other possible virus infections should be arranged.
./ If the infection is severe, the patien t should be admitted and the airway monitored.
./ In pa tien ts with airway obstruc tion steroids may give ,
relief, but airway control by intubation or a tracheostomy should be considered.
Pulmonary fungal disease should be excluded and all patients with mycotic laryngitis should have a chest radiograph. Direct laryngoscopy and biopsy may be necessary to confirm a diagnosis of fungal laryngitis. It is of note that the more chronic variety of fungal infections, such as blastomycosis, can masquerade as a laryngeal tumour and is only differentiated by laryngeal biopsy. Tissue samples should be sent for special fungal stains, such as methenamine silver and periodic acid-schiff, to identify the fungal hyphae. However, histology will not differentiate the specific fungal species and special cultures will be necessary. Management
MYCOTIC LARYNGITIS
Most fungal infections of the larynx .are caused by inhalation of the fungus associated with a breakdown in the normal tissue defence mechanisms. Cl inical featu res
--------------------�----------� .. -------
Mycotic infections of the larynx are rare in patients with normal immune function and when they do occur they present as subacute or chronic infections. In contrast, patients with compromised immune systems, and parti cularly those with haematological malignancy, are prone to acute infection from these opportunistic pathogens. Mycotic laryngitis, with the exception of superficial candida infection, usually causes ulceration. Infections
Systemic antifungal therapy is necessary for immuno compromised patients. Antifungal agents only suppress fungal growth and recurrent infection is therefore likely unless the underlying predisposing factors are addressed and corrected. Similarly, recurrence will also occur if the agent is used for too short a period or in an inadequate dose. Suitable agents include fluconazole, ketaconazole, itraconazole and amphotericin B. Each agent has its own characteristics: itraconazole is particularly effective for aspergillus infections at a dose of 100-400 mg daily, monitored by regular blood levels; fluconazole for three to four weeks is the preferred agent for candida infection; ketaconazole is the agent of choice for histoplasmosis and blastomycosis. Amphotericin B needs to be administered intravenously and also has significant adverse effects on the kidney, heart and liver. [Grade D]
Chapter 171 Ac u te infections of the larynx I 2255
obstruction. A laryngocoele can also induce hoarseness,
Best clinical practice
dysphagia and a sensation of a lump in the throat.
.; Patients with a d i agnos is of fungal laryng itis should
Examination of the larynx will show a swelling of the supraglottis on the affected side
An
h ave a chest radiog raph. .; If ac u te mycotic laryngitis is suspected,
association
has
been
(Figure
noted
171.5a
between
and
b).
laryngo
coeles and squamous cell carcinoma of the larynx and
im munod eficiency should be considered and
the
invest iga ted. .; A d i rect laryngoscopy and biopsy is recommended.
laryngeal
ventricle
should
always
be
examined
endoscopically.
Sa mples should be sent for h istol ogy and specific fungal cultures. .; A su ita ble course of a spec ific antif ungal medica tion
Investigation
shou Id be ad min istered and p red isposing factors
The sac contents can be differentiated by ultrasound. The
shou l d be addressed and corrected.
extent is displayed well by CT magnetic resonance
(MR)
(Figure
171.6),
but an
scan will delineate the lesion
much better if the sac contains mucus or in the presence of infection.
LARYNGOPYOCOELE A laryngocoele is an abnormally large laryngeal saccule that contains air or mucus and has an opening that connects with the airway in the laryngeal ventricle. They can be internal within the laryngeal skeleton, external or combined. Presentation can be at any age but the peak incidence is in the sixth decade, most commonly in men. If the laryngocoele contains mucus, stasis will predis pose to bacterial infection and a laryngopyocoele.
Clinical featu res An external! combined laryngocoele presents as an inter mittent neck swelling that can be inflated by the patient with
raised
manoeuvre
expiratory
(Figure
pressure
171.4).
during
a
Valsalva
Compression may empty air
and fluid into the larynx (Bryce's sign). Distension of an internal laryngocoele - due to infection may cause airway
© Hodder }\.rnold I Scott-Brown 7E
Fi g u re 171.4
A combined rig h t-s i d ed l a ryngoco e l e after
inflation fol l ow ing a Va l sa lva manoeuvre.
Fig u re 171.-5
(a) Appea rance of a right-sided l a ryngoco e l e as
seen with a flex i b l e laryngoscope. (b) Endoscopic appea rance of rig h t-sided l a ryngocoe le � t the time of surgery.
2256
I PART 16 T H E U P P ER A I RWAY
KEY POINTS
Most patitmt.s with acute infecti�,ri�:�'6f';�h� :� ".; have acute viral larYl1'gj.ti,s;�$� . �.�Jf-li.miting disease: .,';<'!" :; , " ..<� ';,,:\':.-:.:, (, ;' > 7f); �,:. -· . ., iTh�te a'r� s peci fie f0 rnji· C?f; laryn@ti�'Jha tare ' rare in ad 1l.lt�, and. P9teI!tially lif� :- �hretlt
larynx
.
,
.
.
-
_
Figure 171.6
CT scan of a right-sided combined laryngocoele.
,
,'
-�
Management The main reason for recommencling sUIgery is that 10
p e rcent
of
laryngocoeles
laryngopyocoele
should
present
be
treated
with
with
infection.
A
intravenous
antibiotics. If cellulitis progresses to form an abscess,
aspiration or drainage will be necessary and airway
Deficiencies in current knowledge and areas for future research » Further research is required on the pathophysi o l ogy
obstruction may require tracheostomy. Once the acute
and detai ls on the clinical outcomes of acute
infection has resolved, the laryngocoele should be excised
(Figure 171.7). Traditionally, excision has been by an external approach but this may be combined with
laryngitis. )- The reasons why the subglottis is primarily affected in croup need further e l ucidation.
endoscopic surgery. Recently, complete endoscopic exci
internal and external components with the aid CO2 laser has been described.32 [Grade B]
sion of the
of a
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E liasson I, Kamme C, Schalen C. Erythromycin in
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Mishra S, Rosen CA, M urry T. 24 hours prior to curtain. Journal of Voice, 2000; 1 4: 92-8.
3.
Sataloff RT. N onsurg i cal management of the professional voice. Current Opinion in Otolaryngology and Head and Neck Surgery. 1995; 3: 135-48.
4.
Figure 171.7
Kucera CM, Silverstein MD, Jacobson R M , Wollan PC, Jacobsen SJ. Epiglottitis in adults and children in Olmsted
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Operative view of the external component of a
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Nakamura H, Tanaka H, M atsuda A, Fukushima E, Hasegawa M. Acute epigl ottitis: a review of 80 patients. Journal of Laryngology and Otology. 2001; 11 5: 31-4.
6.
.I A laryngopyocoele should i nitial ly be treated with
Wu rtele P. Acute epig lotti.tis in child ren an d adu Its: a large-scale incidence study. Otolaryngology - Head and Neck Surgery. 1990; 103: 902-8.
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8.
Frantz TO, Rasgon B M . Acute epigl ottitis: changing epidemio logic patterns. Otolaryngology - Head and Neck
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Surgery. 1 993; 109: 45 7-60.
or endoscopical ly acco rding to the extent of the lesion and preferred surg ical technique.
Ru�ppi P, Nuutinen J, Kari A. Changed clinical
a 12-year experience. Laryngoscope. 1994; 104: 1503-6 . 7.
obtained to del ineate the extent of the lesion before
./ Once the acute infection has resol ved, the sac shou ld
T,
course and current treatment of acute epiglottitis in adults
intravenous antibiotics and possible aspi ration/drainage.
.I An M R scan, o r CT if MR is not available, should be
Torkke li
9.
Hugossoh S, Olcen P, Ekedahl C. Acute epiglottitis aetio logy, epide miol ogy and outcome in a population
Chapter 171 Acute i nfections of the larynx
before larg e-scale Haemop h i l us infl u e n zae type b
22.
11.
Carey MJ. Epig lottitis in adults. American Journal of
h e mag g l utinin - n e u ramin idase. Nature Structural Biology.
Emergency Medicine. 199 6; 1 4 : 421-4.
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Schwam E, Cox J . Fu l m i nant m e n i n g ococcal s u p rag lottitis:
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An emerg i n g infe�tious syndrome? Emerging Infectious Diseases. 1999; 5: 464-7. 12.
14.
* 15.
Reviews. 2002. 24.
J E , E l l iott TS. Serolog i cal evide n ce of pertussis in
Barrow H, Vastola AP, Wang RC. Adu lt su prag lottitis.
patients presenting with cou g h in g e n e ral practice in
Otolaryngology - Head and Neck Surgery. 1993; 1 09 :
Birm i n g h am. Communicable Disease and Public Health.
474-7.
2000; 3 : 132-4.
Deeb ZE. Acute s u p rag l ottitis in adu l ts: early i n di cators of
25.
Se nzi l et lD, H a l perin SA, S p i ka J S, Alagaratnam M, Morris
ai rway obstruction. American Journal of Otolaryngology.
A, Smith B. Pertussis is a frequ e n t cause of prolonged
199 7; 1 8: 112-5.
cou g h i l l n ess in adu l ts and adolescen ts. Clinical Infectious Diseases. 200i; 32: 1691-7.
D u cic Y, H e b e rt PC, Maclach lan l, Ne ufe ld K, Lamot h e A. 26.
of Emergency Medicine. 1997; 30: 1-6.
1275-82.
This paper
identifies a simple but effective method of interpreting
Kerr J R, Preston I\JW. Cu rre n t pharmacotherapy of pertuss is. Expert Opinion on Pharmacotherapy. 2001; 2 :
radiolog ic sig n i n the diag nosis of adu lt e pig lottitis. Annals 27.
Dodh ia H , M i lle r E. Review of the evide n ce for the use
plain lateral neck x-rays to diagnose acute epiglottitis.
of erythromycin i n the manag e m e n t of persons exposed
N e mzek WR, Katzberg RW, Van S lyke MA, B ickley lS. A
to pertussis. Epidemiology and Infection. 1998; 1 20 : 143-9.
reappraisal of the radiologic fin di n g s of acute inflam mation of the epig lottis and s u p rag lottic stru ctu res
17.
Mil l e r E, Fleming D M, Ashworth LA, Mabbett DA, Vurdien
Otolaryngology. 199 8 ; 27: 332 -6.
Descri ption and eval uation of the val l ecu la s i g n : a new
16.
Pillay V, Swin g l er G. Sym ptomatic treatment of the cou g h
i n w h oop i n g cou g h . [ Protoco l] Coc h rane Acute Res piratory I nfections G roup. Cochrane Database of Systematic
Solomon P, Weisb rod M, I rish J C, G u l lane PJ . Adu lt e p i g l ottitis: the Toronto Hospital experien ce. Journal of
13.
Cre n n e l l S, Taki moto T, Port n e r A, Taylor G. Crystal stru ctu re of the m u ltifu n ctional paramyxov i rus
vacci nation. Clinical Otolaryngology. 1994; 1 9 : 441-5. 10.
2 8.
Efstratiou A, E n g l e r KH, Mazu rova IK, Glush kevich T,
in adu lts. American Journal of Neuroradiology. 1995; 1 6 :
Vuopio-Varkila J, Popovic T. Cu rre n t approaches to the
495-502.
laboratory diqg nosis of dip h t h e ria. Journal of Infectious Diseases. 2000; 1 8 1 : S 13 8-45.
Ames WA, Ward VM, Tranter RM, Street M. Adu l t e pig l ottitis: an u nder-recog n ized, life-th reate ning
29.
Nye F. I n fectious monon ucleosis: not always
condition. British Journal of Anaesthesia. 2000; 8 5 : 795-7.
what it seems. Hospital Medicine. 2001; 62 :
18.
Deeb ZE, E i n horn KH. I n fectious adu lt crou p.
388-9.
19.
Ton g MC, Ch u I\I1C, le i g h ton SE, van Hasselt CA. Adu lt
Laryngoscope. 1990; 1 00 : 455-7.
* 20.
30.
91-5.
crou p. Chest. 1996; 1 09 : 1659-62. J ecker P, Mann WJ, McWil liam AS, Holt PG. Den dritic ce l l
Forrest LA, Weed H. Candida laryng itis appeari n g as l e u koplakia and G ER D . Journal of Voice. 1998; 1 2:
31.
Florent M , Aj ch e n bau m-Cymbalista F, Amy C, Rio B, Mol i n a T, Audouin J et al. Dysphon ia and dysp hag ia as
infl ux differs betwee n t h e s u b g l ottic a n d g lottic m u cosae d u ri n g acute laryngotracheitis i nduced by a b road spectru m
primary manifestations of invasive asperg i l losis. European
of sti m u l i. Annals of Otology, Rhinology, and Laryngology.
Journal of Clinical Microbiology and Infectious Diseases.
2002; 1 1 1 : 567-72.
This paper describes on-going
research into the reasons why the subglottis is affected in croup. 21.
I 2257
* 32.
2001; 2 0 : 441-2. Devesa P M , G h ufoor K, Lloyd S, Howard D . En doscopic CO2 laser manag e m e n t of laryngoce le. Laryngoscope. 2002;
Woo PC, You n g K, Tsang KW, Ooi CG, Peiris M, Yu e n K.
1 1 2 : 1426-30. Excellent long-term clinical study of a less
Adu lt crou p : a rare but more severe co ndition. Respiration.
invasive technique for treating external and internal
2000; 67: 684-8.
components of laryngoceles.
172 Crlronic laryngitis KENNETH MACKENZIE
Definition and aetiology Clinical presentation Key poi nts Assessment Key poi nts Processing of m i c rolaryngeal speci m ens H i stological features of chronic l aryng i tis Nonspec i fic laryngitis Key poi nts Reinke's oedema Key point Laryngea I polyps
2258 2259
2259
Key point Relapsing polychondritis Amyloidosis
2259
Chroni c granulomatous disease
2261
Radiation-induced chronic I a ryng itis
2261
Key paints
2261
Chronic laryngit is in an immunocomp romised host
2264
Deficiencies in current knowledge and areas for future
2265
References
2262 2264 2265
Best clinical practice research
2266 2266 2266
2266
2268 2268
2268
2268 2269
2269
T he data sea rc h in this c h apter was carried out in c onjunction with the clinical effectiveness librarian, North Gl asgow NBS Trust, Glasgow Royal I n firm ary, and supported b y a Medline and Embase search using the key words and MESH terms laryngitis and chronic disease.
DEFINITION AN D AETIOLOGY
Chr onic l aryngiti s is chronic inflammation of t he laryn
geal str uc t u res , most commonly the laryngea l mucosa.
The infla mmatory process can be either in fectious or noninfectious, with a br oad spectrum of aetiologies ranging from nonspecific diffuse hyperplastic laryngitis (Figure 172.1) associated with various irritants such as smoking or voice abuse to extremely rare infective conditions such as his top lasm osis . In 1976) Stell and McLoughlin commenced the debate aroWld the aetiology of chro nic la ryngitis and conclud ed from their case-controlled series that occupational effects had only a little influence, smoking was no greater than in their control group, but infection of the upper and lower respiratory tract was of signifi can ce.1 There have been
reports in various case series of the re la t i onship between occupation and chronic la ryngi t is; with excess noise at occupational work,2 exposure to atmospheric pa r t icles in as be stos causes workers3,4 and cement workers,5 to solvents in a shoe 6 wor ker and hairdressing.7 In t er e stingly, when the aet io lo gical factors in an aluminium plant were assessed, there was no statistical association with occupation but a highly significant association with both age and smoking.s Around the same time as Stell) t he concept of allergy and chronic laryngit is was r aised in a case report by Pang.9 In an updated discussion on this association in a series of 17 pat i ents, J ac ks on - Men ald i et ai.tO advocated the multi discipl in ary app roa ch to those with c h ronic laryngitis and allergy. To determine if th e re was a bacterial infective t1 process in chronic laryngitis) Eben felt and Finizia examined the l a ryngeal secretions in a c hronic laryngitis
Cha pter 1 7 2 C h ro n i c l a ryn g i tis I
2259
i mpairment, and subsequ ent disab ility and handic ap. 1 3
This is refl ected by the quality of life repo rts in dysphonia.
It is cl ear from these that there is a significant effect on
' th e qual i ty of life with assessment tools su ch as the SF36
demo nstrating that conditions res ul ting in dysphonia can .
0f
14 IS
I' ts d omams. · o utcome measures for
a: allect many
centred
Th e use
0f
p atient-
quality of life
both
and handicap associated with dysphonia has increased
significan tly in the last two decad es . I 6 Given the com
plex ity of voice assessment, it wo uld appear that some fo rm
o f patient
when assessing
report wo u l d be highly appropriate
an
intervention fo r l aryngeal disease such
as chronic laryngitis.
Figure 172 , 1
© Hodder Arnold / Scott-Brown 7E
Nons pec i fic d i ffuse hyperp l astic l a ry n g i t is .
of
l i fe.
�flS' a 'sig,irincant effect "
in chronic
laryngitis . In 1 9 72, Del ah u n ty l 2 devel oped the concep t
ASS ESSM E NT
confirmed reflux, the reflux was treated and the chronic
Outpati e n t setti n g
eight
patients
i n whom
barium
swallow
laryngitis resolved.
It would therefore appear that although the aetiology o f
chronic laryngitis i s freque n tly mul tifactorial,
b ably has a role
G O RD pro
in a s i gn i ficant nu mber o f patients.
[**1*]
How best to approach th is sp ectrum of disease is
difficult and so the chapter wi ll be co nsidered in two main
sections, firstly that of general d i ffuse laryngitis, non
specific hyperpl astic
laryngitis,
and
'
��� ed " "
on
,� �:,':. .�: �.:
: q.t;1alitY, "
' �,, ' ; " , '
is.]'' '
:
'.
'
_
.
' " ' ',�'" .'� : ,'l: -;':' '."
"
reflux
(GORD) and chronic laryngitis. I n a small case series
of around
>,
y
and little phagocytosis, res ulting in the concl usion that
gastro-oesophageal
Dys p ho n ia
'
so
,' ; , -pa,tient,.,centr�d , omcome's " are _ appf6Iniate 'f6r ; :, aS$essfu.ent- o,f:'tn/ d sphonia as,s,o d�tecl�Willi, chro ruc:laiingitis " rGra d e �
some o f the affected group, the re were few ne utrop h ils
of the associat ion between
,\S
• t.
were very large numbers of bacteria in the secret i ons o f
, there was no bacteriological infectious p ro cess
'��; ��s��:!�;1 ���h�,�s
', .
and a control group and observed that although there
[H 1*]
secondly specific
fo rms of chronic la ryng itis with recogn i zed aetiolo gies and characteristics.
Having presented primarily to an o to rhinolaryngolo gist,
most patients complaining of dysphonia will proceed to
some fo rm o f visualization o f their larynx ' once the
atten ding clinician has completed a detaile d history. This
is usu ally perform ed by flexible nasolaryngoscopy under
local anaesthesia . Some centres now omit the use of local anaesthesia following a rando m ized controlled trial
(ReT) by the Inverness group who demo nstrated there
was
no
difference in the reported
discomfort
levels
when com p a ring topical anaesthesia and simple lubricant
j elly. 1 7
[****]
I f a more detailed examination o f t h e structure of t h e
CLINICAL PRESENTATION The symp tom complex associated with chronic laryngitis
has invariably a principal sym ptom of alteratio n o f voice
vocal cords i s required then t h e rigid laryngosco p e, with
or wi tho ut strobosco py, is required. The p rincipal aim o f
these examinations is t o identify the presence o f any
q u ality ( dysphonia), but may also include var i o us other
significant intralaryngeal structural abnormalities which
in
Although the findings can vary considerably if there are
laryngopharyngeal
sympto ms :
a
sensation
o f some
thing being in the p harynx (odynop hagia ) , diffi culty
swallowing ( dysp hagia ) , painful speaking ( o dyn ophonia) ,
persistent cough, throat clearing, halitosis, bitter taste, waterbrash
and
otalgia.
These
sympto ms
help
the
clin ician to o rgan i ze the i r app roach to a patient in terms
may require
fu rther assessment u nder general anaesthesia.
any localized or discrete abnormal areas, either in shape
or colour, then rnicrolaryngoscopy is required. Equ ally, if there is any doubt about the clinical diagnosis with regard 1 8, 1 9 . · 1 aryngoscopy IS man d a to ry. malIgnancy, mIcro
to
.
of whether they th i n k that the patient may, or may not,
Frequen tly, however, there are o nly vague, nonspecific,
has the greatest overall e ffect on the patient's vocal
combination
have a m al i gnancy. It is the dysphon ia, ho wever, which
'
,
--...
diffuse, o edem atous, alterations in col o ur and fo rm, the o f which may result
in
a
p rovisional
i_ .
_ _�
2260
I PART 1 6 THE U P PER AI RWAY
diagnosis of chronic laryngitis. The abnormalities may
lesions such as a granuloma, the degree of inter- and
affect complete subsections of the larynx, e.g. all of the
intra-observer error could be such that accurate, repea
true vocal cords, or be restricted to specific areas. Clinical
table, recording may not be possible. If such a system,
experience suggests that there is considerable inter- and
or alternative, is to be recommended, then repeatability
intra-observer variability when assessing the larynx. In a
studies would have to be p erformed.
case series of 85 patients with multiple b enign laryngeal
Inconsistency in the accuracy of diagnosis of laryngeal
al. 20 reported that there was
disease is well recognized and is of a particular problem
frequent inter-observer error in relation to the diagnosis
when subtle legions, such as sulcus vocalis, are involved,
conditions,
Pontes
et
of each of the conditions involved.
[H 1*]
either alone or in combination with other conditions.
To attempt t o standardize the recording of the assessment of the larynx, several workers have suggested a descriptive grading of chronic laryngitis. This has been developed and
This was demonstrated clearly by Pontes et al. 20 who used a panel-based gold standard when assessing the diagnoses
made by an experienced team using videostro boscopic
reported primarily in the assessment of the laryngeal
equipment. They found that in approximately two-thirds
appearances in relation to GORD
of the cohort
(Table
172. 1 ) ?1, 22
[**1'*1
Although this is useful in attempting to standardize terminology, and to have some degree of gradation of assessment, it does not reflect the broad spectrum of
(n 85) =
there was an inaccurate diagnosis of
a minor structural abnormality, or associated condition, such as chronic laryngitis. In an attempt to try and quantify the degree of
abnormality within the larynx, Hanson et al.24 used a
findings in chronic laryngitis. Prior to this, Feehs and Koufman2 3 used a descriptive system which reflected the
system of quantitative colour analysis based on digitized
spectrum of findings but without any numerical grading
videolaryngoscopic images. They reported that it was
component:
possible to demonstrate a significant change in colour in
• •
red arytenoids and piled up inter-arytenoid mucosa; diffuse oedema, including Reinke's space, mucosal thickening but possibly minimal erythema;
•
diffuse erythema with granular friable mucosa;
•
discrete gianuloma(s), with or without oedema and erythema.
['* 1
response to
treatment.
Despite this it is
clear that
irrespective of the level of sophistication in the equipment used to assess laryngeal disease, ensuring high inter- and intra-observer repeatability is difficult.
[H 1*]
Operati ve assessment
In an attempt to maximize the benefits of description and gradation the
systems is
The initial outpatient assessment establishes if there
Although such a system may seem appropriate, it
or polyps and, if not, whether the diffuse changes are
may b e that in practice, unless there are clear discrete
uniform, such as Reinke's oedema, or nonspecific and
T a b l e 1 7 2.1
findings have been categorized, the next stage is either
suggested in
combination
Table
172.2.
[*]
of these two
possibly irregular, as in chronic laryngitis. Once the Gra d i ng of ch ronic l a ryng itis.
G rade G ra d e I
M i l d e ryth e m a , stri ng s i g n ,3 loss o f l i g h t reflex,
G ra d e I I
Mod e rate e ryth e m a , g ra n u l a r m u cosal su rface, ulcer
Grade I I I
Ma rked erythema, granuloma form ation
a String sign is described as the stringing of m ucus between the vocal processes.
i��i�e
G rade I
initiation of treatment, e.g. voice therapy by the speech and
stasis of secretions
Ta ble 172.2
are any discrete lesions, such as leukoplakia, nodules
language
therapists,
or
further
assessment
by
microlaryngoscopy.
Although described in detail elsewhere (Chapter 1 94,
Tumours of the larynx), the management of an early suspicious lesion probably requires some standardization of approach. If the lesion is discrete, excision biopsy, if at
all possible, should be carried o ut (Figures 172.2 and 172.3 ) . It can be seen that on the right true vocal cord
there is a lesion involving the anterior two thirds, with the Fo u r- p o i n t g ra d ation of chro n ic l aryng i tis.
proposed area of resection mapped out by arrows in
Figure 172.2. In these early subtle
and delicate lesions it is
better to use (cold' instruments to dissect the lesion M i ld eryt h e m a, stasis of secretio ns, string s i g n ,
p i ling u p of i nter-arytenoid m u cosa
G rade I I
D i ffuse oed e m a a nd m u cos a l th icke n i n g , but w i th
G ra d e I I
D i ffuse eryt h e m a, with gran u l a r fri able m u cosa or
G rade IV
D i screte gra n u l oma (s) with or w i thout oedema
l i ttle erythema u l ce ration
a n d erythema
carefully from the underlying structures with minimal trauma. If diffuse, e.g. in a possible early laryngeal cancer, then a representative 4 mm cupped biopsy should be
taken prior to definitive treatment by either radical radiotherapy or endoscopic excision. If it is not possible to excise the lesion completely, then a biopsy as described above should be taken.
In a cas� series of 68 patients, Andrea et al.25, 26
have reported the
use of contact endoscopy during
Cha pter 1 7 2 Chronic laryn g i ti s
I 2261
PROCESSING OF M ICROLARYNGEAL SPECI M ENS The difficulties with assessment of microlaryngeal speci mens histologically are that they are frequently very small, suffer shrinkage artefact and are difficult to orientate with respect to the residual laryngeal structures. As these may range from being a simple benign lesion through early in
situ
changes
to
frankly
invasive
squamous
cell
carcinoma, it is imperative that appropriate orientation, processing
and
subsequent
sectioning
is
performed .
Attempts have been made to orientate these by, for example, using needles to pin them to cork, however this Fi g u re 1 72.2
Proposed exci sional biopsy.
tends to destroy the tissue by interfering with its margins.
Murray et aI.27 described the technique of mounting the resected
specimens on dehy drated cucumber mounts
using histoacryl
(Figure 172.4), with
appropriate section
ing thereafter. [*]
HISTOLOGICAL FEATURES OF CHRONIC LARYNGITIS Considerable attention has been p aid previously to the histological characteristics of chronic laryngitis and the need for a robust classification system. The principle behind this is that a certain proportion of patients who have chronic laryngitis have a disease which may have Fig ure 1 72 .3
Excision biopsy.
microlaryngeal surgery to aid in diagnosis. Following the staining of the vocal cords with methylene blue and using the microcolpohysteroscope, it is possible to observe the cells, nuclei and
cytoplasm of the superficial layers.
Although the reports appear convincing, the uptake in the use of the technique as a routine integral part of the microlaryngeal process has been slow. [H]
characteristics suggestive of potential malignant change. The implication being that there is a cohort of patients who may need more aggressive treatment or closer follow up. The grading classification for chronic laryngitis is shown in
Table 172.3.
use
several years,
for
Although this system has been in Gale
et
al?8 reported in a
retrospective case series the Ljubljana classification of laryngeal lesions and the relationship to malignant
transformation.
subsequent
The hyperplastic
laryngeal
KEY POINTS •
Signi ficant in ter- and i n t ra- observer va riabillity when assessing the laryn.x in the outpatient set L i ng. If there is a ny doubt about the diagnosis,
mandatory. of recording lar yngeal fi ndi ngs is s uggested in Table 1 72.2. [Grade C/DJ If laryngeal lesion is discrete, then it should be excised if possible . I f this is not possible, a cupped biopsy shouM be performed a nd t reat.me n t pla nned thereafter. r Grade D 1 microla ryn goscopy is
Method
© Hodder Arnold I Scott-Brown 7E
Fig u re 1 7 2.4
M oun ting a resected specimen on de hyd rated
cucu mber mount using hi�toacryl.
I �
._
- �
-
-.-
-
2262 I
PART 16 T H E U PPER A I R WAY
Tab l e 17 2.3
Histopathological
C h ro n i c laryngitis g radi n g classification ( normal
matu ration) .
G rade I
T h i cke n ed e p i th e l i u m, hyperkeratosis, reg u lar
G rade I I
' Li m ited' disorganization of mat u rat ion process,
CA-In situ
Severe dysplasia, epithe l i u m has squamous ce l l
mat u ration reta i n ed ce l l u lar atypia, ab normal m itoses carci noma c han g es b u t without i nfi ltration t h roug h the base m e n t m e m b rane
lesions (n 4574) were graded into simple, abnormal, atypical hyperplasia (risky epithelium) and carcinoma in-situ. Malignant transformation in the atypical hyper plasia was 1 1 .6 percent, whereas in the benign group, simple and abnormal, it was 0.3 percent. The conclusion being that this classification was of value with regard to malignant transformation. Although it should therefore be possible to categorize the biopsies into 'at risk' groups, it still remains that there has been no assessment of the principle in a large prospective cohort. Even if it is assumed that such an assessment is repeatable, there has not been any sugges tion of a strategy of observation or monitoring for those patients who have lesions in the atypical hyperplasia groups, nor indeed in the carcinoma-in-situ group. [ ** ] I n practice, the cellular maturation process is histo graphically categorized into mild, moderate or severe dysplasia. Management of this condition, following excisional biopsy, is based generally on the clinical appearance of the affected mucosa, the area involved and the smoking status of the patient. The following conditions will be discussed on the basis that at least a provisional clinical diagnosis has been made. =
N O N SPECIFIC LARYNGITIS Nonspecific laryngitis is an extremely common condition which may present with a wide spectrum of signs, symptoms and severity. Patients invariably present with a degree of dysphonia and may have associated symptoms such as throat discomfort, awareness in the throat, e.g. globus type symptoms, throat clearing, halitosis or otalgia. The most common aetiological factors are smoking, voice abuse and GO RD. Although the first two of these have been addressed for many years, it is only in the last ten years that the evidence in support of an association between GORD and chronic laryngitis has evolved. In 1 972, Delahunty12 described inflammation of the poster ior third of the vocal cords, barium swallow confirming
GORD and subsequent successful symptomatic treatment with antacid. This possible association between GORD and chronic laryngitis was initially known as 'acid laryngitis'. In an observational series in 1 982, Ward and Berci29 described a group of 86 patients with chronic nonspecific laryngitis which they hypothesized was due to local irritation by chronic coughing and throat clearing, which in turn was secondary to hiatal hernia and gastro oesophageal-pharyngeal reflux. [ ** ] This hypothesis was tested further, and much more 'invasively', in a surgical series by Deveney et al.30 In a cohort of 1 3 patients with chronic nonspecific laryngitis and confirmed GORD, the performance of a 'Nissen' fundoplication resolved the laryngeal problems in 1 1 patients (73 percent) . The study group was very carefully selected in that each patient had ceased smoking for at least six months and so the conclusion was that correction of GORD in a select group of patients will resolve the laryngeal problems. [ ** ] Hanson e t al .31 developed the theory further b y using medical treatment in a 'stepwise' fashion to improve laryngeal function. In a group of 1 82 patients, 93 (5 1 percent) improved with simple nocturnal antireflux precautions alone. A further 48 with famotidine (H2 antagonist) at night and a further 34 with omeprazole (proton pump inhibitor) . With relatively simple methods, 96 percent of the group had resolution of the nonspecific laryngitis. This study is useful as it demonstrates the incremental approach to the treatment of the GORD and in particular the potential role of lifestyle modification. Other case series at around the same period reported the beneficial effect of a proton pump inhibitor (PPJ) on both conditions,32 with Jaspersen et al.33, 34, 35 confirming this with nasolaryngoscopy and oesophagoscopy at fortnightly intervals. This evidence would suggest an association between the two conditions. [ ***/**] There are two principal theories to explain the patho Reflux Laryngitis physiology. Firstly, the direct theory with the refluate from the stomach and oesophagus crossing the upper oesophageal sphincter and causing an inflammatory effect on the laryngopharynx. Secondly, the indirect theory where chronic repetitive throat clearing and coughing is caused by a vagally mediated response secondary to acid in the lower oesophagus. Iil a review article on upper gastro-intestinal disorders and respiratory symptoms, Schiller36 suggests that it is not only the gastric acid which is of relevance, but all the gastric contents, and supports this by the observation that prokinetic drugs are more efficacious than acid reducing medication (H2 antagonists) . Borkowski et al.37 raised the question of the possible role of Helicobacter pylori infection in the process. In their series of patients with chronic hoarseness (n 35) , six ( 1 7 percent) were urease positive and following H. pylori eradication, the clinical signs and symptoms resolved. Although they suggested a possible role 6f H. pylori, this hypothesis would have to be tested more fully as part of the treatment regimen was the =
Chapter 1 72 C h ronic laryng itis
prescription of a PPI which could itself be the active component. [ ***/**] If these theories were correct, then there should be an increased prevalence of laryngeal disorders in patients suffering from oesophagitis. In a large case-controlled series of patients with erosive oesophagitis (n = 1 0 1 ,366) El-Serag and Sonnenberg3 8 reported an association with laryngitis (odds ratio 2.0 1 ; 95 percent confidence interval 1 .53-2.63 ) . This would strongly support this hypothesis. [***] Conversely, if there is a significant prevalence of oesophagitis in patients with laryngitis, it would be expected that empirical treatment of laryngitis with anti reflux medication, such as a PPI, would result in an improvement in a significant proportion of patients. Such a theory and strategy is supported by Weber et al.39 who, in a prospective study of 50 patients suffering from chronic laryngitis of unknown aetiology, reported an improvement in symptoms in 72 percent of the patients. This strategy was taken a stage further by treating patients who not only had chronic laryngitis but also had other gastropharyngeal symptoms. In this case series (n = 29), a course of pantoprazole resulted in a significant (p < 0.05) recovery in hoarseness, globus pharyngeus, sore throat, heartburn and coughing.32 The association between chronic laryngitis and GORD has been reiterated by Kendall and Lee40 and Ahuja et al.41, 42 [*** /**] Intuitively, it would seem appropriate to investigate if there is any reflux into the pharynx prior to commencing gastro-oesophageal treatment.43 The 'gold standard' is 24-hour pH monitoring, however its regular use prior to treatment would probably be impractical on a population basis.44, 45 More importantly, it has been argued that pH monitoring is unnecessary and may be misleading in that some who have reflux would not be identified by the investigation and so would not be treated. Hanson et al.46, 47 have reported that this false-negative rate can be as high as 50 percent. [ **] Bearing these two aspects in mind, it would appear that the development of clinical practice has been along the strategy of empirical prescription of PPIs in patients with laryngopharyngeal symptoms, with or without ** gastro-oesophageal reflux symptoms. 2 1, 32 , 48 [ * ] To test the validity of this treatment strategy, EI Serag et al.49 carried out an RCT of PPI versus placebo in a group of patients (n = 22) with chronic laryngitis. Following confirmation of their disease status by upper gastrointestinal ( GI) endoscopy, 24-hour oesophageal pH monitoring, laryngoscopy and symptom question naires for both GORD and laryngitis, the patieHts were randomized to receive either lansoprazole 30 mg twice a day or matching placebo for three months. The principle outcome of complete resolution of laryngeal symptoms was reported in six (50 percent) of the lansoprazole group compared with one ( 1 0 percent) of the placebo group (p < 0.05 ) . The authors conclude that empirical treatment with lansoprazole is efficacious in relieving symptoms of
I 2263
laryngitis compared with placebo, but have a cautionary note that their study was carried out in a patients with a high chance of having GO RD and would have to be repeated in the general population if it was to be universally applied to all patients presenting with laryngeal symptoms. [****] This association between GORD and chronic laryngitis has been reported to be aggravated further by activity during sleep, the hypothesis being that the increased effort involved with snoring or sleep apnoea induces an intensive gastrolaryngeal reflux. 50 [**] The prevalence of upper GI disease in patients with laryngopharyngeal reflux has varied in reports. Koufman et al.5 1 reported that in their cohort, 60 percent had no heartburn and concluded that patients with laryngo pharyngeal reflux uncommonly have oesophagitis. Con versely, Tauber et al.52 reported a high prevalence of both hiatus hernia (43 percent) and H. pylori-positive antrum gastritis (23 percent) with laryngopharyngeal symptoms and with a high resolution rate for medical anti-reflux treatment. From the evidence, it would appear that there is a frequent coexistence of laryngopharyngeal disorders and upper GI tract abnormalities. [ ***/**] How best to manage a patient presenting with a combination of laryngopharyngeal symptoms remains unresolved, but the consensus of opinion would be in favour of an initial form of empirical treatment in the algorhithm (Figure 1 72.5) . Further treatment of the upper GI tract could theoretically be of value, an example being in the report by Hamdan et al.53 who described a benefit of dual prescription of PPI and prokinetic agent, pantoprazole and cisapride, respectively. Despite the level of evidence to date, there is clearly a future requirement for controlled studies not only between GORD and laryngitis but also with other extraoesophageal conditions such as asthma. 54 [ ***/** ] When treating patients with laryngopharyngeal symp toms with a 'PPI' strategy there are a range of additional treatments which can be offered, including: •
• • •
•
lifestyle changes: - avoiding late evening eating and drinking; - reducing evening alcohol intake; - avoiding foodstuffs giving reflux symptoms; - raising the head of the bed; antacids; H2 antagonists; e.g. ranitidine 1 50 mg twice daily; proton pump inhibitors; e.g. omeprazole 20 mg twice daily for at least eight weeks; fundoplication.
Although lifestyle modifications are a very sensible and rational starting point, the pragmatic approach would still be to use some form of medication for acid suppression. 55 Although the influence of the treatment of GORD on chronic laryngitis is copsiderable, the other two treatment
2264 I
PART 1 6 T H E U PPER AI RWAY
Laryngopharyngeal symptoms
Trial of PPI for eight weeks
+
Relief of symptoms
./
�
Stop treatment
No recurrence
Observe
Recurrence
Further treatment
+
No relief of symptoms
./
�
pH monitoring
Normal
Abnormal
�
�
Investigation
areas which must be considered are those of voice therapy by speech and language therapists (SLT) and strategies for the cessation of smoking. Voice therapy (see Chapter 169, Speech therapy in ENT practice: scope, science and evidence for interven tion) is designed by the SLT to modify aspects of lifestyle and voice use by, for example, discussing vocal hygiene, and addressing the dysfunctional components of voice production. This subtle combination of history taking, diagnosis, treatment planning and execution, and 'ad hoc' psychotherapy has been recognized in the past to be of value clinically. There had, however, been little evidence in support of its use except for some level 3 evidence from short case series where voice therapy had been used in specific conditions, such as vocal cord nodules or Reinke's oedema.56 MacKenzie et aI. I5 and Dunnet et aI.57descri bed the first randomized controlled trial of the use of voice therapy in a heterogeneous group of patients. The combination of diagnoses in this group of 200 patients were those which one would normally expect to receive some benefit from voice therapy, for example vocal cord nodules, functional dysphonia and chronic laryngitis. The principal outcome from the study, patient self-report, was significantly better in the group who received voice therapy when compared with the control group of observation only. The voice therapy used in the treatment limb was based on the consensus on treatment by UK SLTs on a group of laryngological disorders, one of them being chronic laryngitis. It would appear that referral to the SLT team would be appropriate and potentially of benefit in those patients with chronic laryngitis. [ ****] Cessation of smoking, and its effectiveness, is more difficult to assess. Intuitively, it would appear sensible to advocate the cessation of smoking, however, there is little evidence of the effect of this alone on the resolution of chronic laryngitis. The use of nicotine replacement patches and bupropion hydrochloride in the cessation of smoking in patients with chronic laryngitis needs clarification.
Figure 1 72 . 5
Manag i n g a pati e n t p rese n t i n g
with a combi nation o f laryngopharyn g eal
I ncrease dose
symptoms.
How best to incorporate each of these measures into the treatment of laryngeal disorders, and in particular chronic laryngitis, needs further evaluation. The progression of chronic laryngitis into dysplasia, carcinoma-in-situ and ultimately invasive squamous cell carcinoma has been widely debated for many years,58 and more recently in patients who have both chronic laryngitis and GORD. 59 In the latter study, the hypothesis is supported by the association between chronic laryngitis in nonsmokers, or long-standing ex-smokers, and clinically or radiographically proven GORD in a cohort of 23 patients. It is clear that a proportion of patients who will have been diagnosed initially as having chronic laryngitis will progress to squamous cell carcinoma. It could well be, however, that this has coexisted with early dysplastic changes, with the latter subsequently transforming into frankly invasive malignancy. These could therefore be regarded as coexistent conditions rather than malignant transformation from chronic laryngitis. [**]
KEY POINTS • •
• • •
Aetiology is generally multifactorial. Main aetiogical factors are voice abuse, smoking, GORD and environmental factors. Empirical treatment with PPI is -advised. Voice therapy is advised. Stopping smoking and lifestyle modifications would appear appropriate. [Grade AlBIC]
R EIN KE'S O E D E M A This i s a distinct form of chronic inHammation o f the larynx and s o theoretically falls into the category o f
Chapter 1 72 Chro n i c l a ry n g i t is
chronic l aryngi tis. Patho logically, there is a ch ronic state of oedema i n the m e mbrano us portion of both vocal
methods
have
been
practised
wide ly,
there
I 2265 is
little
evidence in support of one rat her t ha n the other. I n a
cords fro m the anterior commissure to the vocal process
case series of 36 patients , Lumpkin et aI. 6 1 compa red
degeneration o r hypertrop hy, have been used.
this small observatio nal cohort they co ncluded that the
(Figure 1 72.6), hen ce other terms, s uch as polypoid The co-aetiol ogical fac tors of smoking and voice ab use
res u l ts in a p redilection for women in middle age and
CO2
'stripping',
laser
the
and
Hirano
t ech niq ue.
In
Hirano technique was p referab l e. Alt hough there have b een advocates of the use of m icrod ebriders in t h is
a res u l tant specifi c signs and symptoms co mplex. The
situation, there is little s ub s t ant ive comp arative evidence
majo rity o f the
invariably
in its favour. Overall, to satisfy the o riginaJ aim of the
present with dysp honia with an overa l l reduction in the
surgery, the use of micro laryngeal cold instrume ntation is
p i tch of their voice, but rarely with obstructive symp toms.
advocated.
patients
are smokers
and
O n flexib l e nasolaryngosc opy or rigid l aryngoscopy, the
vocal
cords
a p p ear
uniformly,
diffusely
swollen,
l **]
I f the patien t i s a smoker, a s i s frequently t h e case, i t is strongly
advised
that
one
of the
stopping smoking
with this b u lbous appearance tending to move on quiet
strategies is adopted. Hoj slet et aI.62 described a case
resp iration or phonatio n .
series of 2 9 p a tients in whom a s topp ing smoki ng s t rategy
Comb i ned
modality
treatment
of
surgery,
voice
therapy and smoking cessation is required to have any
was
strongly
supported.
This
consisted
o f nicotine
chewing gum being freely ava ilable a nd gro u p counselling
(28 perce n t )
chance of resolution of the condition. The pathological
supervised by a psyc h o l ogist. Eight of them
changes within the vocal cords need surgical treatment.
refrained from smoking and, a l t hough the disco m fort was
The inflammatory process resu lts in an accumulation of
reduced, none of the voices ret u rned
fl uid witlUn Reinke's sp ace, the potential space between
ad dition ,
the vocal ligament and the overlying m ucosa. The aim of
reso lved, the laryngeal oedema persis ted .
surgical treatment o f th is is to remove the fluid and
although
the
to
normal . In
d i ffuse la ryngitic
app earances
To reh abilitate t he conseq uences of voice abuse and
reduce the excess mucosa with minimal damage to the
poor vocal hygiene, a course o f voice t herapy should be
u nderly ing laryngeal architecture. This technique was
under t aken .
described i n i tially by Hirano.60 An incision is made
in
the la ryngeal mucosa overlying the superior aspect of the
If left untreated, the concern is that there m ay be malignant trans fo rmation. There has been l i ttle rep orting
t rue vocal cord in its long axis. Reinke's sp ace is entered,
o f such a p heno m enon, and fro m clinical experience
the subm ucosal fluid contents aspirated and the excess
it would seem more l ikely that the converse is the case)
m ucosa t rimmed. The technique can be carried out either
i.e. that the presence of bilateral sy m met rical Reinke's
by using cold techniques or CO 2 laser (see Chap ter 58, Laser princip les in otolaryngology, head and neck
oede m a wo uld s u ggest . that
su rgery) . The t heoretical disadvantage of the CO 2 laser
wou ld be in the case of unila teral
it
is
very u n likely
that
malignancy is p resent. The exception to t his observation
is the inj urious thennal effect on the s urround ing tissues.
clearly such a fi nding could be oedema associa ted with
Although
a deeply centred malignancy, s u c h as a lesion in the
this
may be
the
case
in
other
laryngeal
disorders) it cou ld be argued that the fluid in Reinke's
laryngeal ventricle.
space is sufficient to absorb the heat. A further potential
[**1*]
d isadvan tage is that the resected specimen may be either severely carbonized or nonexistent. Dissection of the excessive mucosa can be relatively easily carried o ut with
KEY POI NT
mini mal trau m a using 'col d techniques'. Although both •
Treat ment should he c o l d s �rgery
of the voj�_� :
laryngeall lesi"on, smoking :cessation a nd therapy. [ Orade D ]I
-
-
-
lARYNGEAL POLYPS
If there are inflammatory changes res tri cted to a small
area o f the vocal cords, fo r exam ple after some form of vocal traum a s u ch as shouti ng} there may be resolution
into polypoidal cha nges on the vocal cord in the form of
vocal co rd p olyps. These p a t ients p resent with a history of persistent Figure 1 7 2 . 6
Re i n ke's oed e m a .
dysphonia, tend to be men mo re often
than women,
2266
I PART 1 6 TH E U PPER AI RWAY
a p p roxi mately
50 perce n t of cases. The inflammato ry results in dysp ho n i a , dysp hagi a
reaction in the lar ynx:
and pa i n in the throa t . Treatment is ma i nte n ance of a safe a i rway, p oss i bly by tracheos tomy, and cor ticosteroids and i m m u nos u p ress an ts.
[*J
A MYLOIDOS IS Amylo idos is can a ffect the la rynx as part of a pri mary or seconda ry process o f systemic a myl oid osis . The dep osits
o f a mylo i d , p ro teina ceous aggregates, have a high fluid conte n t and can occu r as a diffuse submucosal process or Figure 1 7 2.7
as small subepithelial masses. The patients p resent with
Vocal cord polyp.
dyspho nia beca use of the p resence of the depos its in the
smokers more than nonsmokers, and are in the young to middle-aged group. On nasolaryngoscopy, vocal cord polyps appea r as discrete lesions arising from the true vocal cords, and tend to be in the anterior
two- thirds (Figure 1 72.7 ) . To resolve
the p roblem , surgical excis ion of the polyp (s) is required
and is generally by microlaryngoscopy under general anaesthesia using cold instrumentation techniques. There is a plane of cleavage a t the base of the polyp between the
polyp and the vocal ligament. Following top ical applica tion of adrenaline polyp can be held
( 1 in 1 000) to the vocal cord polyp, the in microfo rceps, retracted medially and
dissected fro m the mucosa over lying the vocal ligam ent with preservation of its integrity. This latter aspect is imperative if the normal function of the vocal cord i s to be resto red. Once the lesio n has been excised, a period of
voice rest for at least 48 ho urs is generally a dvoca ted. The
evidence in support o f both the type and du ration o f alteredlreduced voice use is scan ty. Intuit ively, however, it
wou ld seem hi ghly appropriate to arrange a co u rse of voice therapy to correct any habits o f voice misuse in the
patien t, given that it is high Iy like ly it was vo i ce misuse
va rious subsites of the la r yn x and their subsequent effect
on t he vocal cord m obility. U ltimately, there may also be an effect o n the airway. The m ainstay o f treatment is microlaryngeal surgery to remove t he deposits while
m i n i mizing the laryngeal damage and this can be by either cold techniques or by CO2 laser. The use of CO2 l aser
tends
to
be effective because
vapourize the high D iagno si s
is
of its
ability to
fluid co ntent within the deposi ts .
con fi r med
h istolo gically because
of the
a ffini ty o f the amylo id fo r Co ngo Red. [ * ]
CHRO NIC GRAN U LOMATOUS DIS EAS E These are a gro up of rare sys temic conditions which may have a specifi c effect on the l a rynx. The aim of this section is
s u m mar iz e
to
the
clinical
findings
which
sho uld
p rompt the clinician to cons ider the diagnosis in patients
in wh o m the chro nic i ty o r clin ical findi ngs are somewhat out
of
the
occu rrence)
ordinary.
es peci ally
Alth ough
in
the
their
rare,
potential
i m mu nocompromised
pa tient, s h ou ld always be bo rne in mind.
which was the cause of the polyp i ni ti a lly. [ * ]
Tuberculosis Invariably tuberc ulosis (TB) occurs with the p ulmo nary vers i on of the disease, wit h the p atient complaining o f dysp hon i a, p ai n o n sp eakin g a n d swallowing and o talgia .
: . ' - -V6 �al - c� rd polyps are tr� ated' by su rgical excis19n and voice therapy.
There is a di ffu sely reddened and oedemato us larynx
I*]
p r edo m i nantly affect ing the pos terior one-third of the glottis
( Figure 1 72.8 ) . There m ay be also be ulceration
and the appearances can be confused with s quamous cell carcinoma. D i agn osis is made by biopsy of the laryngeal tissues. H i stologi cal examin ation demonstrates gr an u lo
RE LAPSING POLYCHON DRITIS This is
a
diffuse, fluctu at i ng, autoimmune, inflammatory
co ndition of t he la rynx,
chronic in nature but with acute
exacerbations, and ultim ately with progression to fibrosis and chondronecrosis. Classically, i t
a ffects
the cartilages
in the ears and n ose, with the la rynx bei ng affected
in
mas with caseating necrotic centres, Lan gh ans - typ e giant
cells and acid-fas t bacilli. Treatment is to secure
an
airway
followed by an tit uberculous drugs . If timely, there should
be resolu tion o f the laryngeal and pulmo nary disease and if not there
will be the effects o f chronic inflammation
with s tenosis and vocal co rd fixatio n.
63
[*1
Cha pter 1 7 2 Chronic l a ryn g i t is I
2267
Diagnosis is by bio p sy and is essentially the exclusion of other l aryngeal inflammatory p ro cesses . Treatment is ensuring
a
safe
airway>
either by laser excision
or
tracheostomy> and systemic corticosteroids. [ * ]
Wegener's granulom atos is This i s a systemic disease affecting the upper and lower respiratory tract and kidneys with necrotizing granuloma and vasculitis. In up to
25 percent of p atients>
the larynx is
affected with the appearances of an acute inflammatory reaction initially. Eventually granulomatous ulcers develop> Fi g u re 1 7 2 .8
principally affecting the subglottis in the long term.
Tu bercu losis.
The anticytoplasmic autoantibody C-ANCA is specific fo r Wegener's with biopsy findings showing necrotizing granuloma and vasculitis. Treatment is with corticoster
Syp h ili s
oids or cyclophosphamide and possibly tracheosto my. [ * ]
in this condition. Although
The larynx is rarely involved
each of the stages may occur> the secondary and tertiary stages of the disease are more common. Hoarseness and dysphagia are common b ut pain is rare. There are diffuse erythematous
papules
(secondary
stage)
and
nodular
infiltrates coalescing into painless ulcers ( tertiary stage),
with the epiglottis and aryepiglottic folds being princip ally involved. Appearances are similar to those of TB and carcinoma, however) the diagnosis is made by positive syphilis serology. Treatment is
with high-dose penicillin.
[*]
Cand idiasis Laryngeal candidiasis is due to the opportunistic infec tion by the oroph aryngeal associated
with
Candida albicans. It can be
immunocompromised
patients,
fo r
example due to cytotoxic chemotherapy or AIDS. In addition> it can o ccur in those patients who have received broad spectrum antibiotics> prolonged inhaled or sys temic corticosteroid use. or radical radiotherapy. In the latter case> the laryngeal findings are a diffuse erythema of the mucosa with an irregular friable white exudate which
Lep rosy Leprosy
is superficial. In the immunocompromised patient) the is
also
known
as
> Hansen s
disease.
As
in
tuberculosis) laryngeal involvement in leprosy occurs only when there is concurrent systemic disease. Invariably there will be cutaneous lesions which may have been present for several years with the nasal cavity frequently being affected. In the larynx, the principle area involved is the supraglottis. in particular the epiglottis. and so the dysphonia is of a muffled voice quality. There is an oedematous,
nodular supraglottis with
mycobacterium leprae from the tissues. Treatment is with diamino diphenylsulfone> rifampicin and clofazimine and which. if severe. may necessitate tracheosto my.
dysphonia) but little else. treatment i s with nystatin o r fluconazole and i s generally successful. In the deeply infe cted)
and potentially ulcerated.
there is pain on
speaking and swallowing in addition to the dysphonia. More intensive treatment is required and in this case 64 amphotericin B may be required. [*]
ulceration
and diagnosis is by biopsy of this area with isolation of
may have to be long term. Healing can result
inflammatory reaction is much deeper, possibly with
ulceration. In the superficial case> there is a degree o f
in fibrosis
[*]
Histo plas m os i s This i s a systemic mycotic disease caused b y histo p lasma capsulatum. There are nodular granulomas which can affect the anterior larynx and epiglottis and may ulcerate.
Th e clinical picture is very similar to TB and squamous cell aarcinoma.
The
p resentation
is
dysphonia with
S arcoid os i s
varying degrees of pain and dysphagia. Diagnosis is by > culture of the organisms on Sabouraud s agar from the
Sarcoidosis i s a slowly p rogressive disease with the larynx
laryngeal ulcers and the complement fixation test. As
involved in less than 5 percent of cases. The laryngeal
laryngeal involvement effectively only occurs in patients
appearances are very similar to those of TB and fungal
with the disseminated fo rm of the disease. a useful
infection> with the supraglottic structures being primarily
guide to the diagnosis is the presence o f multiple small
involved. The larynx is rarely involved without clinical or radiographic
evidence
of pulmonary involvement.
calcified opacities on a chest radiograph . Treatment is by 64 [ *J
amphotericin B and securing a safe airway.
2268
I PART 1 6 TH E UPPER A I R WAY
B l a stomycosis
RADIATION-IN DUCED CHRONIC LARYNGITIS
This is a fungal disease caused by Blastomyces dermatiditis
One o f the commonest causes of chro nic laryngi tis in a
individ uals in North America with p rolonged exposure in
radio therapy. When a course o f radical rad i o t herapy is
which affects multiple organs. Those at increased r isk are
head and neck practice is following a course of radi cal
wooded areas. Although skin is the next most commonly
being delivered, there is an incrementally increasing acute
there are granular erythematous cha nges which may
laryngit is. Although to a certain extent the reaction is
affecting the vocal cords. The princi p al co mp laint is
individual response to the treatm ent. Having mini mized
affected site after the lungs, when the larynx is involved progress
to
ulceration
dysphonia and,
and
as with
micro abscesses,
other
chronic
p ri marily
inflammatory
d iseases, there may be co nfusion with squamous cell carcinoma. Diagnosis is by identification of the fungus from the microabscesses. Treatment is by i t raco nazole or ketoco nazole and amphotericin B in advanced cases.64
[*]
inflammatory
reaction
which
develops
the anaerobic bacteria Actinomycoses bovis or Actinomycoses Israeli. The larynx b ecomes involved following invo lve
ment o f the soft tissues of the cervical o r subma ndibular regions, possibly with abscess o r s inus tract format io n,
with progression into the paralaryngeal re gi on. The larynx
the
the amount of potential trauma during del ivery of the radiotherapy,
laryngitis
is
the
based
treatment
of the
resulting
o n similar p rin ciples
to
chro nic
t hat
of
no nsp ecific laryngitis. Invariably in this group of pa tients
t here is a high prevalence of smoking. To increase both
the efficacy of the radical radiotherapy and decrease the
s trategies sho uld be
This is a systemic chronic supp urative disease caused by
chronic
dose dependent, there is considerable variabili ty in
severity of the chronic laryngitis,
Actinomycosis
into
employed.
smoking cessa tion
Voice therapy would
intuitively seem to be appropriate , however there is little
evidence in favour of it. There has been sign ificant debate
regarding the role of GORD
in the develo pment of
laryngeal cancer and, whilst this has no t been resolved)
acid s upp ression would seem appropriate in this group of
patien ts .
[*]
is diffusely erythematous, swollen and wo oden. D iagnosis is by identification of classi cal 'sulphur granules' in the
b iopsy material and culture of the micoorganisms. Treat ment is with penicillin or tetracycline.64. 65
(*]
Col onization and infection of the larynx with Candida albicans may occur in patients who become im muno
Rh i noscl ero ma This is primarily a chronic infecti o n of the nasal cavity
caused by Klebsiella rh inoscIeromatis but may involve t he larynx. It has three s tages, firstly cata rrhal,
purulent
CHRON IC LARYNGITIS I N AN I MM U NOCOM PROMIS ED HOST
rhino rrhoea,
secondly
with marked
granulo matous,
with
small p ainless granulomas , and finally sclerotic, with
sclerosis of the larynx. This sequence has only been postulated and can take a varying amount of time to
compro mis ed as a result of developing AIDS or second ary to
treatment
on
a friable
such
as
chemotherapy
or
lo ng-term
co r t icosteroid treatment. The larynx has white patches erythematous
mucosa a nd
diagnosis
Treatment is by nystatin) amphotericin B or fl uconazole .
[* ]
occur. The glottis and subglottis are the main areas wh ich
are involved. Diagnosis is by histological identification of
Mi kulicz's cells, fo amy vacuolated histiocytes and Russell
Best cl i nical practice
c ult u re o f the orga nis ms . Treatment
.I Ch ron ic l a ryngitis frequently has a mul tifacto rial
bod ies , birefingent red inclusions and bacteriologically by
cephalosporins or tetracycline.66
[*]
i s by
arninoglcoside,
aetio logy.
.I The main aetio log i ca l factors a re smoking, voice a buse and gastro-oeso phage a l reflux d i sease.
. KEY J,:�r��� , , ;;,'< ; ;, 5; " '} ; ::'c , ; . ,;
./' Fo l l owing clin i ca l diagnosis, t reat w i th proton pump inhib i to r, vo ice therapy and smoking cessation
.
, the rapy.
" : !���C:'f����i*s:t� •
The laryn ge aL. aJ')pe��'Ces ��'- be_-io�fused
with thos� ��{ ���;��· ���; �:�t��ma :s
.
. ._ v
.
.I S u rgery should be u sed fo r d iscrete lesions only.
.I Any intervention for chroni c l a ryngitis has to be assessed by so m e fo rm of outco me, probably patient ce n t red.
�:
'� �_ . .
./' Ch ronic infectious processes in the l a rynx a re ra re
_
is
made by culture of the laryngeal plaques and secretions.
and f req u ently m i m i c squa mous ce l l ca rcinoma.
Cha pter 1 72 C h ro n i c l a ry n g itis
Defici enci es in cur rent knowl e dge and areas for future research >- Sta n d a rd izati o n of l a ry n g e a l assess m e n t a n d
16.
I 2269
H o g i kya n N D, Rosen CA. A review of o utco m e m easu rem e nts for voice d isord e rs. Otolaryngology Head and Neck Surgery. 2002 ; 1 26 : 562-72.
17.
Ca i n AJ , M u rray DP, IVl cCLy m o n t LG . The use of to pica l n a�a l a n a esthesia before fl ex i b l e nasendosco py : a d o u b le
i m prove m e n t o f i n te r- a n d i ntrava ri a b i l ity.
b l i n d , ra n d o m ized co ntro l l ed tri a l co m pa ri n g
>- To re peat, in a l a rg e m u lticentre study, the e m p i ri ca l
co p h e n y l ca i n e w i t h p l a cebo. Clinical Otolaryngology.
use o f PPI i n t h e trea t m e n t o f c h ro n i c l a ry n g itis.
2002 ; 2 7 : 485-8. 18.
Cupic H , Krusl i n B, Bel icza M . Epith e l i a l hyperpl astic l es i o n s of the l a rynx i n b i o psy speci m e n s. Acta Oto Laryngologica-Supplement. 199 7 ; 5 2 7 : 103-4.
19.
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173 La ryngea I tra u ma a nd stenosis
LISA PITKIN
2284
Laryngeal trauma
2271
Best clinical practice
Key pOints
2276
Deficiencies in current knowledge and areas for future
Chronic laryngea I stenosis
2276
Key points
2283 .
t I
,
j
"t
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. �.
,
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.
.-.}_ f
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• ••
2284
'
• '.
•
2284
research References
,
.
� ...
.. •
. I.
\
.
•
The data in t his chapter are supported by Medline searches using the following key words: laryngeal fracture) laryngeal trauma, neck injury, hyoid fracture, clothes line injury, management of laryngeal trauma, laryngotracheal reconstruction, laryngeal stent, laryngeal keel, supraglottic, glottic, subglottic and tracheal stenosis, intubation injury,
CO2 laser,
microdebrider, CT imaging of the larynx, laryngeal transplantatio n Results were stored using reference manager software .
(Endnote), which also allowed searches to be combined without duplication of results.
4 room visits, and of which) one patient out of 137,000
LARYNGEAL TRAUMA
requires hospitalization and
Incidence and epidemiology
there is also a risk of associated injuries occurring) namely,
Damage to the larynx results from penetrating injuries or from blunt trauma that is either of high or low velocity. High-velocity
impacts
tend
to
result
in
advent
of
seatbelt
laws)
speed
limits
and
improvements in vehicle safety features has reduced the incidence of laryngeal trauma in car drivers and their passengers.
On the other hand, motorcyclists are still as
much at risk of clothes line-type injuries. In recent years, gun-related injuries have become more frequent Women should
be
more
susceptible
intracranial
(8
(13
percent incidence), cervical spine fracture
percent) and oesophageal injuries
(3
percent) ?
[**]
compound
injuries, whereas low-velocity impacts usually do not. The
furt her treatment.2 [**1*]
When a patient has sustained trauma to their larynx,
to
.
1
laryngeal
injury because of their longer and thinner necks than
Classification Laryngeal trauma can be classified either by region
( supraglottic,
glottic and subglottic) or by the type of
tissue affected ('skeleton' or soft tissue). Different modes of management are recommended depending on the site and nature of the injury and these are discussed under
l
Medica management
.
men. However, this is not statistically borne out, as men tend to participate more in 'violent' sports and activities - there is an approximate predominance 2 .
3:1
male to female
[**]
In the UK, there are no specific figures regarding the inCidence of laryngeal injury. Data from t he USA estimate 3 that less than 1 percent of all trauma involves the larynx, with it accounting from one in 14,000-42)000 emergency
Biomechanics of injury PENETRATING WOUNDS
In general, the penetrating object finds the path of least resistance, sliding off the laryngeal skeleton to .pierce either the thyrohyoid membrane superiorly or
2272
I PART 16 THE UPPER AIRWAY
cricothyroid membrane inferiorly. Injury involving the thyrohyoid membrane causes bleeding into the paraglottic space, and sometimes produces supraglottic stenosis. There is usually no voice change. Injury involving the cricothyroid membrane is associated with surgical em physema as air escapes into the soft tissues. Haemorrhage into the airways can cause respiratory obstruction.5 BLUNT TRAUMA LOW-VELOCITY INJURY
Low-velocity injury usually results in bleeding into para glottic tissues, swelling of the tongue base, dysphagia, bleeding into Reinke's space and bleeding into the inter arytenoid space causing airway compromise and ultimately stenosis� The hyoid bone can be fractured, but, in general, the thyroid and cricoid cartilages are not damaged. BLUNT TRAUMA HIGH-VELOCITY INJURY
High-velocity trauma usually fractures the laryngeal skeleton. The type of injury pattern that occurs is determined by the degree of thyroid cartilage calcification. If an uncalcified thyroid cartilage is pushed back onto the cervical spine, it should have enough inherent elasticity to spring back into place causing little damage. Rarely, is the force so extreme that the tendon of the anterior commissure and petiole of the epiglottis is detached. The epiglottis then falls backwards and the vocal cords roll in on themselves.5, 6 [*] Direct high-velocity trauma to a calcified larynx: will cause either displaced or comminuted fractures of the thyroid cartilage. High-velocity impact can result in the arytenoids being compressed together, producing either bleeding and subsequent swelling of the interarytenoid space or displacement and fixation of the arytenoids. Disruption of the cricoid causes stenosis, which has implications on airflow as a consequence of Pouseille's law, that relates airflow to the fourth power of the radius of the airway. The final soft tissue injury (as a result of high-velocity trauma) takes the form of separation of the trachea from the cricoid, which will result in fairly imminent death if recognition and treatment are delayed. This injury is the result of a shearing force produced by severe and sudden deceleration causing a tear of the relatively weak cervico tracheal junction. Also, it is usually accompanied by bilateral pneumothoracies.6 [*] Pathological consequences of injury
T hyroid cartilage
Fracture can result in chronic stenosis and downgrading of laryngeal function. Even minimally displaced fractures will cause changes in glottic resistance.7 Therefore, only nondisplaced fractures should be treated conservatively and allowed to heal by fibrous union. Displaced fractures need to be reduced and fixed. Cartilage injuries
If cartilage is separated from its perichondrium, for example by blood, it will be absorbed. If cartilage is left denuded of mucosa, inflammation and granulation will ensue.5
SOFT TISSUE
All laryngeal injuries cause oedema to a certain extent. Usually, this resolves completely, apart from in Reinke's space where polyp formation may develop.5 Haematoma organization may cause problems - supraglottic and interarytenoid expansion can cause obliteration of the airway and, ultimately, cartilage erosion. Abrasions of the mucosa in the anterior vocal cords or anterior commis sure can lead to web formation.
GLOTnC COMPETENCE
The sphincter, airway and phonatory functions of the larynx are also affected by: • • •
fixation of the arytenoids in a suboptimal position; recurrent laryngeal nerve damage; subglottic trauma.
Treatment principles
The main treatment principles are first and foremost airway protection and, secondarily, successful manage ment of the phonatory function of the larynx. Fundamental to a successful outcome is early recogni tion of the injury, accurate evaluation and the instigation of appropriate treatment. Timing is essential. If surgical treatment is required and performed within 48 hours 91-94 percent of patients will have a good airway and 69-74 percent will have a good voice.8 [**] Delays in intervention result in both a poorer voice and airway outcomes.3 [*] A successful conclusion is considered to be no tracheostomy in the long term and no (or minimal) dysphonia.
LARYNGEAL SKELETON INJURIES
Hyoid
ASSESSMENT
Fractures of the hyoid tend to heal without complica tion. Occasionally, the fractured ends will form a bursa resulting in malunion and requiring surgical excision.
All upper airway InJuries should be considered in any patient with a' history of neck trauma. Dysphonia and dyspnoea are the main features that should highlight
Chapter 173 Laryngeal trauma and stenosis I 2273
suspicion that a moderate-to-severe injury has been sustained. Dysphagia and pain are less precise indicators.
EXAMINATION
Surgical emphysema is pathognomic of an airway breach, as is the loss of anatomical landmarks. Haematoma and echymosis may be seen and haemoptysis might develop. It is important to be aware that the great vessels and cervical spine may also be injured, as up to 8 percent of moderate to-severe cases of laryngeal trauma can have associated cervical spine fractures.2 [**] Accurate flexible nasendoscopic examination of the injured larynx is crucial. Local anaesthetic spray should be avoided if there is any doubt or suspicion that the airway is critical as a loss of sensation can cause paroxysms of coughing and precipitation of airway collapse - a slow gentle endoscopic technique with copious amounts of aqueous jelly is readily tolerated. Nasendoscopy allows diagnosis of mucosal oedema, cartilage exposure, vocal cord paralysis and avulsion and arytenoid dislocation.
INVESTIGATIONS
seemingly mild-to-mod�rate injury with no airway . compromIse. In these CIrcumstances, judicious use of CT can guide the proper management of these patients and prevent unnecessary surgical exploration.9, 10 [**] Magnetic resonance imaging
In the acute setting there is no indication for magnetic resonance imaging as this procedure requires a signi ficantly longer period of time (up to 40 minutes) and imposes increased physical demands on the patient by requiring breath holding. Also, it does not assess skeletal structural damage. Strobovideolaryngoscopy
Kennedy et al.ll performed a 20-year retrospective review of strobovideolaryngoscopy (SVL) on ten patients who had been admitted with blunt laryngeal trauma and in whom the airway was not obviously compromised. They concluded that SVL was a better technique for assessing vocal cord function and integrity than nasendo scopy with/without direct laryngoscopy, and it should be used as an adjunct in investigation to identify patients who would benefit from a microlaryngoscopy and vocal cord repair.
Standard radiographs
A lateral plain radiograph is a quick and useful 'screening investigation' to exclude a fractured hyoid and concurrent cervical spine fracture. Free air can be seen, as can significant mucosal oedema. A chest radiograph should show any mediastinal emphysema or a pneumothorax. Computed tomography scanning
Spiral computed tomography (CT) is the mainstay of post-traumatic laryngeal imaging. It is very quick (a larynx can be scanned in less than 20 seconds) and can produce two-dimensional axial and reconstructed coronal and sagittal images. It is able to show mucosal oedema, structural disruption of the thyroid cartilage, the cricoarytenoid joint and the cricothyroid joint. It is excellent for assessment of the cervical spine and provides evidence of any vascular abnormalities, such as carotid artery dissection and false aneurysm. In recent years, there has been growing interest in three-dimensional CT scans which enable image recon struction giving a 'virtual endoscopy' - in the acute trauma setting; its benefits have still to be fully assessed. Not all patients who have had laryngeal trauma need to undergo CT scanning. If they have evidence clinically of just a minor injury and have minimal symptoms with no evidence of airway compromise then CT is unlikely to produce new information that would alter treatment. Alternatively, if the patient has obvious airway com promise with apparent laryngeal disruption, then they will need immediate surgical airway securing and exploration - again, CT will not alter their manage ment.9 [**] CT is useful for those patients who have
minimal / mild injury = no CT obvious injury = no CT
TREATMENT
In discussing the management of laryngeal trauma, patients can be classified into groups (I-IV ) depending on their symptoms and signs; this is known as the Schaefer classification and its use is widespread in the literature. In general, it also gives guidance on the appropriate management of these patients and it is summarized in Table 173.1.
PROGNOSTIC INDICATORS
Normal vocal cord mobility is a good prognostic sign. Immobility suggests dysfunction secondary to recurrent laryngeal nerve injury or arytenoid subluxation. If present, only 17 percent of patients will have a 'normal' voice long term. Penetrating trauma is prognostically more favourable than blunt trauma. In the long term over 90 percent will be successfully decannulated (compared with 68 percent in those who sustained blunt trauma) and 70 percent will have a 'normal' voice (compared with less than 40 percent of patients with blunt trauma).12
Medical management
Patients who do not require surgical intervention need close clinical observation for up to 48 hours after the injury. They should be put on bed rest with the head of the bed elevated to 30°. Voice rest is recommended to minimize oedema, and humidified air will reduce crust
2274 I PART
16 THE UPPER AIRWAY
Table 173.1
The Sch�efer classification of l�rynge�1 trauma and its management.
· Signs:' ·
. Synlpt6mS ...
-
Minor airway symptoms
Group I
Management
Minimal haematoma
Observation
Small lacerations
Humidified air
No detecta ble fractu res
Head of bed elevation +/ - Steroids
Group II
Airway compromise
Oedema/haematoma
Direct laryngoscopy
Minor mucosal disruption
Oesophagoscopy
No cartilage exposure
+/ - Tracheostomy +/ - Steroids
Group III
Airway compromise
Oedema
Tracheostomy
Mucosal tears
Direct laryngoscopy
Exposed cartilage
Oesophagoscopy
Vocal cord immobility
Exploration/repair
Massive oedema
Tracheostomy
No stent necessary Group IV
Airway compromise
Significant mucosal tear
Direct la ryngoscopy
Exposed cartilage
Oesophagoscopy
Vocal cord immobility
Exploration/repair
Stent required
formation and improve temporary ciliary dysfunction. Supplemental oxygen is usually not needed.9 [**] Initially, a clear, liquid diet is recommended for patients and some will require additional nutritional
Following open exploration, broad-spectrum anti biotics should be given for five to seven days, and if a stent has been positioned they should continue until the time of its removal.
support. Nasogastric feeding can be used providing the placement is carried out directly with the aid of a flexible nasendoscope or radiographically to avoid further trauma.
ANTIREFLUX MEDICATION There is no randomized control trial specifically for laryngeal trauma. It is known that using either H2-
CORTICOSTEROID USE
receptor antagonists or proton pump inhibitors can help
Although there is no randomized control trial on the
tracheal stenosis. Gastro-oesophageal reflux is a common
benefits of systemic corticosteroid use after laryngeal trauma in patients, it is common practice to prescribe either
intravenous
dexamethasone
or
hydrocortisone
post-injury with the intention to impede inflammation
to reduce granulation tissue formation and subsequent factor in the majority of patients with recurrent granulo ma formation.16 [*] It is advisable that these medications should be used to the end of the convalescent phase.
and fibrosis and to prevent granulation tissue formation. There are conflicting animal studies on the effect of dexamethasone following deliberate internal laryngeal injury, with Kil Kryzer
et al. 14
et al.13
showing no benefit, whereas
Surgical management of acute laryngeal trauma
found the reverse. If corticosteroids are
used, it should be noted that they are only of use in the first few days after the injury - after that their potential
side effects outweigh their benefits.
TRACHEOSTOMY There is controversy regarding the correct time to perform a tracheostomy. Schaefer tracheostomy
under
et a1
.
local anaesthetic
9 10 believe that ,
is appropriate
ANTIBIOTICS
for stabilization of the airway in all patients who have
The use of antibiotics is not necessary in the treatment of
Advanced trauma life support manual recommends a trial
minor laryngeal trauma in which cartilaginous fractures are not identified. However, in compound fractures of the larynx, systemic antibiotics should be used to reduce
the high risk of local infection and perichondritis, which may delay healing and promote airway stenosis.1 5
evidence of airway compromise. The sixth edition of
of intubation, but the surgeon and anaesthetist should
be aware that this might worsen a pre-existing injury. 2 In Jewett's series only 33 percent of patients had a tracheostomy'whereas Bent
required one. [**]
et al.8 showed that 72 percent
Chapter 173 Laryngeal trauma and stenosis
I 2275
As a general guideline, the decision to W1dertake tracheostomy should be made on the basis of the clinical state of the patient.17 Following this, it should be clear whether intubation is possible and if it is
likely to
exacerbate the injury. If intubation is successful and after formal rigid endoscopic airway assessment
(with or
without neck exploration), it is often necessary to perform an 'elective' tracheostomy as prolonged airway protection is often required and long-standing intubation can have deleterious effects on an already oedematous larynx. In terms of the tracheostomy site, a lower position than normal should be used. In other words, the incision in the trachea should be placed below the third/fourth
tracheal ring as this will avoid further i nj ury to the larynx
Figure 173.1
Diagram showing AO miniplate system used to
fix a comminuted laryngeal fracture. The plates are bent to conform to the shape of the thyroid cartilage.
and its supporting structures.
would bend and this would cause angulation of the fragments and subsequent loss of reduction. In the last
DIRECT LARYNGOSCOPY AND OESOPHAGOSCOPY All patients in whom surgical intervention is deemed necessary should have the injury carefully assessed by direct laryngoscopy to ascertain the degree of internal disruption and to decide on the need for open repair. Up to 3 percent of patients who require a general anaesthetic assessment will have concurrent oesophageal damage2
decade,
alloy
metal
adaptation
miniplates
with self
tapping screws have been advocated as a better way to shape the larynx back to its preinjury state, and they have provided a method of fixation of comminuted fractures (they allow titanium alloy mesh to be positioned and so any defect is bridged )
(Figure 173.1) .18, 19 [**]
and this should be recognized and addressed with the help of a cardiothoracic surgeon if necessary.
& oesophagoscopy
[**]
LARYNGEAL STENTS In the acute trauma setting, stents are used to:
OPEN OPERATIVE INTERVENTION
•
p rovide internal support as a complement to fixation
•
maintain the lumen of the larynx and diminish
This is required if spontaneous resolution of the laryngeal injury is unlikely. In general, displaced or comminuted fractures
of
the
laryngeal
skeleton
are
intrinsically
unstable secondary to the muscular forces on the larynx and should be repaired by open reduction and internal 9 fixation. Vocal cord disru ption or avulsion should also be repaired via an open approach. In general, in penetrating s trauma, the larynx will need to be debrided and repaired. The larynx is approached via a skin crease incision at the level of the cricothyroid membrane. Subplatysmal flaps are raised
(superiorly
to the
hyoid bone
and
inferiorly to the first tracheal ring) and stay sutures
applied. The strap muscles are then retracted laterally. The
l arynx is then opened by a midline thyrotomy to expose the endolarynx in its entire ty.
All mucosal lesions should
be repaired and no cartilage should be left exposed (if there are denuded areas, these should be covered by a mucous membrane or skin graft which should be sutured into position). Vocal cord injuries should be repaired usi ng 5/0 or 6/0 absorbable Vicryl Rap ide (with the aid of a microscope or loops)
and,
of the laryngeal skeleton;
if avulsed, should be
resuspended to the external perichondrium in
an
attempt
to try and reconstruct the anterior commissure.
adhesion formation; •
maintain the scaphoid shape of the anterior commissure, which is essential for vocalization.
Stents should not be used as a substitute for mucosal repair and reduction and fixation of laryngeal fractures.2o There is controversy concerning the use of stents. Outcome measurement is
difficult
as those patients
requiring stent placement have, by definition, more severe injuries (Schaefer
grade
IV). Also,
it s h o u ld be noted that
stents may lead to further problems as they can increase the risk of infection and granulation tissue formation.
In general, stents should be considered if there is widespread endolaryngeal mucosal laceration, disruption of the anterior commissure or a comminuted fracture is unstable despite using plates and titanium mesh. Different
stent
types
are
discussed
later.
Schaeffer
advocates that stent� are held in place using prolene sutures and attached to the skin of the neck using buttons. Stents are usually kept in place for 10-14 days
and should be removed under a general anaesthetic.
If the cartilage has a displaced fracture, this should be reduced and fixed. Traditionally, wire sutures were used, but at times these were inadequate owing to the load
FOLLOW UP
exerted by extra and intralaryngeal musculature during
After moderate-to-severe laryngeal injury, pa ti ents should
swallowing and neck movements. In some cases the wire
be closely monitored by repeated nasendoscopy in the
2276 I
PART 16 THE LIPPER AIRWAY
outpatient clinic.
.·as.this will avoId further: disruptive injury to
Complications of laryngeal trauma
including granulation tissue formation, web formation
the larynx and facilitat : e··furthetmanagement.
and stenosis should be looked for. Granulation tissue
•
Earlyrecognition, accurateevaluatiQnand
o f the · appropriate treatment (with
formation should be managed by serial debulking as
instigatlori
intralesional steroids and long-term use of stents have
repair within 72 hours. if required) is
limited success. The use of mitomycin C to prevent traumatic granulation and scarring has yet to be formally
•
fundamental to a successful· outcome. A Illminal stentshould be considered if there is
evaluated. Management of webs and stenosis are covered
a
massive en.dolaryngeallaceration,
disrllptionof the anterior corhmissure or
III
considerable detail under Chronic laryngeal stenosis.
a
commiI1uted fracture isunstable despite fixation.
,:. - lnjuryto thelaiyPx is
a relatively. rare .
CHRONIC LARYNGEAL STENOSIS
"pheil6i11enol1 (less�thanl percent of all
'-t�auma'inv(jlves the
laryrrx:).
,
_
Th�reisa risk' of other injuriesoccur�ingat - ': T'theiimeoflaryngeal trauma: intracnlnial (13 . p�rcent in�idence), cervical spine (8 percent) " oesophag4S(3 perc�nt). _�l_ 'a •
ijd
'.j'-
Yrgeal·�rauma, the. m�in
�ainvay protection and, .• secondarilYl succes�ful . management of the phonatory ro l(Qfth e larynx. , , . ' .. . ,. . . . In lar .
'
'
.
.
•
.
'
"
'
'
'
.
- , defined ijls 'l,i2 ,tracheostomy ,in· the long term . and no 'cor'll1iIilll1al) dysphonia. , ' Upper ajrW�y) t1ryshould be considered in
Ii)
any patienfWith'.'a history of neck trauma.
stYSPI1:9� are Jhe, main ;wh.icn,shoUIsl highlight suspicion
Dysphonia ancl ' _
featur,es
, that a moderate-to-s'evere injury has taken
place� , .' CT is usefuLfor those patients who have ,- iseerninglymild-to'-moderatelaryngealinjury . ' _-'�'avoid umiecessary surgical. exploration� •.:,CorticOsteroids.
inthe .fir�tJewdays after laryngeal' injury,. after '':', w�i<::h,- their side. effects outweigh their
are only of
use
'
benefits.
•
; 'Int6inpoundfractures -
,.
ofthe larynx,
Laryngeal stenosis.
The predominant cause of chronic laryngeal stenosis is trauma, occurring either subsequent to the failed treatment or nonrecognition of acute trauma, secondary to
prolonged
intubation
or
as
a
complication
of
Other less common causes include systemic diseases such as Wegener's granulomatosis or relapsing polychon dritits.A summary of the causes of laryngeal stenosis can be seen in Table 173.2. It should be noted that patients with coexisting diseases, such as diabetes or congestive cardiac failure, have a greater risk of developing stenosis following intubation and they should probably be considered for early tracheostomy if they require prolonged ventilatory support or pulmonary toilet.ll [*] Gastro-oesophageal should be managed by the appropriate use of proton pump inhibitors or H2 antagonists. As the subglottic region is the narrowest part of the larynx, it is the most common site of laryngeal stenosis.
stenosis is usually caused by endotracheal intubation,
integrity of the supporting structures. Acquired subglottic secondary to either the mechanical trauma of placement of an endotracheal tube or its contact pressure. Mucosal
inhibitorshelRJo redllce granulation . tissue-f()rmati onand.· • slllYs.¢quen
necrosis. These changes have been observed within hours
If atracheostomyisrequiiedfollowing
perichondrium of the cricoid cartilage. Infection of the
laryngeal injury, a.lower. position than
normalshould heusedCi.e.the incision is . p laced below the thir4/ fourth tracheal ring)
, ,- " withnQai
reflux is known to be a potentiator of stenosis and this
pen(:l1ondritts;whichmay delay healing and promote ,�irway;stenosis.
.
ynge
tracheostomy.
Associated soft tissue narrowing usually reflects a lack of
H2-recer
..
Aetiology
sY$tei11i��ntihiotic:s should be used to reduce '
th� llighdsk,of local,infection and
stenosis�
•
and its management is fully discussed in Chapter 89,
Following·lal'
treatmentj:>rinciples are first and foremost
-
This section covers chronic laryngeal stenosis of the adult
type. Paediatric laryngeal stenosis is a different entity
oedema and hyperaemia will possibly progress to mucosal of
intubation
and
can
result
in
exposure
of
the
perichondrium then results in a subglottic scar. These events will be 'hastened if an oversized endotracheal tube has been used.
t9
Chapter 173 Laryngeal trauma and stenosis
Table 173.2
I 2277
Causes of adult laryngotracheal stenosis.
Cause
Result
External laryngotracheal trauma
Penetrating tissue injury
Internal laryngotracheal trauma
Endotracheal intubation
Blunt force neck trauma: high velocity impact, low velocity impact Post-tracheostomy Post-microlaryngoscopy and resection Post-radiotherapy Endotracheal burn: chemical, thermal Tubercu losis
Infection
Scleroma Fungal histoplasmosis Sarcoidosis
Chronic inflammatory disease
Wegener's granulomatosis
Co llagen vascular disease
Relapsing polychondritis Neoplastic disease
Benign: squamous papillomas, chondromas
Extrinsic compression
Thyroid: benign multinodular goitre, malignancy
Malignant: squamous cell carcinoma, lymphoma, sarcoma
Pathological considerations
Treatment principles
Soft tissue damage causes mucosal loss, the formation
Many patients with chronic laryngeal stenosis have an
of adhesions and the organization of haematoma within
indwelling tracheostomy.
the paraglottic, the pre-epiglottic and interarytenoid
establish a 'satisfactory airway' and allow decannulation.
The goal of surgery is to
It is important to discuss with patients the likely outcome
space. Glottic competence can be affected by the formation
and to compare it with their expectations - it is possible
of a web, by arthrodesis of the arytenoids into an
that they may never be decannulated and it is unlikely
unsatisfactory position and recurrent laryngeal nerve
that they will ever regain normal voice if their glottis
damage (the latter being a result of the original trauma or
has been damaged. If the stenosis involves the glottis
iatrogenically in the ensuing treatment).
or supraglottic larynx, procedures performed to try and
If the cartilage framework has been disrupted, it will heal with fibrous tissue formation - this tissue contains
improve airway function can compromise the other laryngeal functions.
fibrocytes that' have directional memory. Owing to this
There is universal dissatisfaction with the treatment
memory, merely incising and separating scar tissue will
of systemic conditions causing subglottic stenosis and
only lead to tissue trying to replace itself in its original
long-term decannulation rates are poor. Some can be
scarred state. Reconstruction, therefore, has to be more
successfully managed by dilatation (with adjunct intra
sophisticated,
particularly of the cricoid ring, where 2 If the
lesional steroids). What is certain is that surgical resection
interruption indisputably will cause narrowing?
by laser or reconstruction should be limited to those
framework has been disrupted, grafting will be required
patients who are in remission and require no immuno
to re-establish structural support.
suppressive therapy for at least a 12-month period?3 [*]
Unfortunately, an ideal graft tissue does not exist, although many have been described and are in current use. These include rib, hyoid, thyroid cartilage and auricular and nasal septal cartilage. There are advantages and disadvantages to all - the choice essentially depends
ENDOSCOPIC RESECTION VERSUS EXTERNAL APPROACH RESECTION
on the amount of graft tissue required and the tensile
Compared with open procedures, endoscopic approaches
strength needed.
are attractive because of decreased morbidity, a shorter re-established,
hospital stay and (if necessary) tolerance of repeated
the second prerequisite is the institution of an intact
Once
structural
support
has
been
procedures. Endoscopic division of glottic webs was
epithelial lined lumen. In chronic stenosis, the scar
originally described in the 1940s, but it was not until 1972 2 that Strong and Jak0 4 first reported the endoscopic management of laryngotracheal stenosis with the CO2
tissue should be excised with preservation of as much overlying mucosa as possible. If the defect is large, then epithelial grafts (either skin or buccal mucosa) can
laser.
be used.
instrumentation, rigid telescopes, digital imaging and
In recent years,
refinements of microlaryngeal
2278 I PART
16 THE LIPPER AIRWAY
Streptomyces caespitosus.
the ready ability and clinical know-how of the CO2laser mean many laryngeal lesions are resected endoscopi 2 cally. 5
properties. Its antineoplastic properties derive from its
ment of laryngotracheal stenosis is variable.
ability to cross-link DNA. In addition, mitomycin C has
Studies
report varying success rates from 40 to 70 percent (in 2 most it is actually closer to 50 percent). 6 Regardless of the technique used, the most frequent cause of failure is scar formation and restenosis.
is an antimetabolite produced by
It possesses both antineoplastic and antiproliferative
in vivo in vitro. At present, no randomized control trials have
been shown to inhibit fibroblast proliferation both and
2 been performed. Perepetlitsyn and Shapshal published a retrospective cohort study on the management of non systemic chronic laryngotracheal stenosis, comparing the
CO2 LASER There is a growing feeling that chronic laryngeal stenosis should be treated by CO2 laser excision initially and that open repair should be reserved for those cases that fail to 2 respond to endoscopic management. 7 However, if the initial stenosis is severe, it is probable that multiple endoscopic approaches will be required and that they may never be successful. In these cases, an initial open approach is more likely to lead to an early successful outcome. The advantages of the CO2 laser over cold steel, are that the CO2laser: •
enables mucosal preservation;
•
allows for a more controlled resection; 2 achieves haemostasis. 8
•
There is delayed formation and maturation of collagen in laser wounds. In theory, this allows for re-epithelialization before scar tissue can be formed. The disadvantage of CO2 laser use (over cold steel) is the potential for thermal damage.
efficacy of CO2 laser incisions and dilatation versus CO2 laser and dilatation followed by steroid injection into the stenotic area, and finally, versus CO2laser and dilatation followed by topical application of mitomycin C. Although it was a small study with only 47 procedures performed on 20 patients, they concluded that there was a signifi cant increase in the success rate of endoscopic treatment of acquired laryngotracheal stenosis in those who had additional topical mitomycin C. They found no advan tage in the use of intralesional steroids as an adjuvant treatment.
KEELS Keels are sometimes used to prevent adhesion formation, subsequent restenosis and web formation. After glottic surgery, keels can be used to 'hold open' both the anterior and posterior commissure (as required). There are many different designs in various materials - all are inert material and are long enough to extend from the cricoid membrane to 2-3 mm above the posterior commis sure. The superior portion should make a 1200 angle
LARYNGEAL MICRODEBRIDER Microdebriders have been in use for nearly two decades in orthopaedic arthroscopic procedures and their general use in ENT began in the 1990s for assisted nasal polypectomy. In 1996, a laryngeal microdebrider was designed for the removal of recurrent respiratory papillomatosis and it is becoming the method of choice over the CO2 laser for 2 treating this disease in the laryngotracheal region. 9 [***] The microdebrider incorporates a suction device that
to minimize granulation formation at the petiole and the posterior wing should not touch the posterior commissure. Keels can be placed either endoscopically or through a minicricothyroidotomy and are held in place with a heavy suture through the cricothyroid membrane. They are left
in situ
for two to four weeks, and then
removed endoscopically under a general anaesthetic so that any resulting granulation tissue can be managed at 2 the same time. 5
enables the user to pull the obstructing granulation tissue away from healthy underlying tissue, making it easier to remove any diseased or scarred tissue. Fibrous lesions can be removed with a tricut (usually 4 mm) blade. Haemos tasis is achieved using a 1: 10,000 adrenaline pledget or
bipolar diathermy can be used. Advantages of micro
STENTS Stents are more substantial than keels and are designed to support tissue and prevent its collapse. Use of stents is not without problem - local infection, mucosal ulceration
debrider use in comparison to the CO2 laser include no potential for secondary scarring and stenosis as a result of
and granulation tissue formation are all common. These
pain.30,31 [*]
absolutely necessary and for the minimum duration
MITOMYCIN C
rized as:
In recent years the usefulness of mitomycin C in the
•
thermal damage, and significantly reduced postoperative
complications, however, are directly linked to duration of 2 use.3 [*] It is sensible, therefore, only to use a stent if required. The indications for internal stenting can be summa
prevention of restenosis has been evaluated. Mitomycin C
maintenante of the lumen following reconstruction if there is inadequate cartilage support;
Howeve
2279
Chapter 173 Laryngeal trauma and stenosis I
•
provision of support for cartilage and bone grafts;
incorporated
•
separation of opposing surfaces during the healing
a tendency to migrate. Expandable metal stents are
into
the
mucosa.
However,
they
have
meshed and will become incorporated into the mucosa,
process. If a stent is being used only to allow mucosal healing or allow a graft to take, it can be removed after two to three weeks. If it is being used for splinting, it should stay in for six to eight weeks. Prolonged stenting (i.e. for more than 12 months) is required if the laryngeal framework is deficient and scar formation needs to develop around the inert stent. Many types of laryngeal stent are available. In general, firm stents are used if splinting is required, a solid stent is used if aspiration is a problem and a soft hollow stent is used if phonation is desired. The ones in most regular use are the Montgomery and Aboulker stents.
which makes removal extremely difficult. Metal stents are more distensible and conform better to the airway than silicone stents, especially if the airway is somewhat tortuous.35 Metal stents are easier to use in the distal trachea and
bronchi
obstruct
because
primary
into contact
or
they
are
secondary
with the side
mesh
and
bronchi
do
that
of the stent.
not come
There are
many types of stents available and these include the Palmaz
and
metallic
Streker
stents)
and
stents the
(both balloon-expandable
Gianturco-Z
stent
(a
self
expanding metallic stent which has 'memory' that allows a return to normal shape after compression for place ment in the airway). Available silicone stents include the
Aboulker stent This was introduced in the 1960s and is the design most commonly used for stability following laryngotracheal reconstruction in children. The Aboulker stent is cigar shaped and composed of Teflon, which is less likely to
Montgomery T-tube and the Dumont stent, which can be inserted through a bronchoscope. In terminal patients the latter is the most
widely used tracheobronchial
silicone stent.
cause irritation, however, the base of the epiglottis can be irritated and granulation tissue tends to form in this area.33
ASSESSMENT
Acquired stenosis of the larynx is usually diagnosed
Montgomery stent
within a year following the initial 'injury'. Most patients
The Montgomery T-tube is a silicone stent with a long
will have one or more of the following symptoms:
central lumen and a smaller lumen projecting from the side of the stent at either a 90 or 75° angle
(Figure 173.2).
Its prototype was first described in 1965. It is used to stent the larynx and trachea after reconstruction for areas of malacia and stenosis. It is a soft stent and can be left in place for periods in excess of 12 months. Its main advantage is that the patient can speak. It is prone to crusting and to counteract this it is best to plug the side lumen as much as possible and intermittently perform proper suctioning to prevent blockage. It is not used in children less than two years of age as the small size of stent required has too narrow an internal diameter and can easily become blocked.
•
dyspnoea (which may be on exertion or at rest -
•
stridor;
•
hoarseness;
depending on the severity of stenosis);
•
nonproductive cough;
•
recurrent pneumonia (aspiration).
Sadly, a number of patients will have been diagnosed with asthma or chronic obstructive pulmonary disease (COPD) before the true cause is realized. A high index of suspicion is warranted with the onset of respiratory symptoms following intubation, regardless of the dura tion of intubation.
Silastic sheet (Swiss roll) Evans first described this stent in 197734 and used it for
EXAIVIINATIOI\l
laryngotracheoplasty. The silastic sheet is rolled up and
Fibreoptic nasendoscopy should be performed in every
inserted into the larynx and upper trachea, where it is
patient, and a note made of any anatomical abnormality,
fixed in place by a suture. The roll has a constant tendency
the presence of pooling of secretions, vocal cord mobility
to unravel, producing steady pressure on the mucosa.
and the degree
This pressure effect obliterates any dead space and allows
subglottic stenosis.
of
supraglottic,
glottic
stenosis
and
mucosal regeneration to take place. INVESTIGATIONS TRACHEOBRONCHIAL STENTS
Tracheobronchial stents can be broadly divided into metal or silicone stents. Silicone stents were developed
Radiology
Computed tomography scanning
in the mid -1960s and can be left in place for several
Spiral
years. They are easy to remove as they do not become
dataset through the larynx in less than ten seconds,
CT scanners
can
rapid . ly
2280
I PART 16 THE UPPER AIRWAY
Figure 173.2 (a) A sagittal CT scan showing thick total suprastomal occlusion of the airway. (b) Exposure of the suprastomal stenosis. (c) A laryngofissure has been performed and the stenosis is being resected. (d) A free cartilage graft is harvested from the superior part of the thyroid alar maintaining the pericondrium. (e) A cartilage graft has been secured in place and the Montgomery tube inserted as a stent. (f) The Montgomery tube in situ j ust prior to wound closure.
limiting the time during which the patient needs to remain motionless. Images can then be reconstructed to
create
overlapping
sections.
If
required,
coronal,
intraoperative findings 36 37 tracheal stenosis. ,
m
patients with laryngeal or
sagittal and even three-dimensional images are then
Pulmonary function testing with fiow volume loops
generated from the same dataset. With special software,
This
the creation of a continued overview on the inner
limitation. It enables determination of the severity of
surface of a hollow viscera on a monitor is possible;
the
these images are similar to endoscopic views. These
improvement: It is able to provide objective serial airflow
virtual endoscopic images have been compared with the
measurements in the postoperative period.
is
a
useful
measurement
obstructing lesion
and
the
of
respiratory
degree
flow
for potential
Chapter 173 Laryngeal trauma and stenosis I
Endoscopy
GLOn-IC STENOSIS
This is performed to evaluate the extent of the laryngeal damage, ascertain the degree and lower extent of the subglottic stenosis, and test the state of the tracheal cartilage.
This
procedure
is
best
carried
out
using
i.v. anaesthesia and Venturi jet inhalation as this will ascertain
2281
the
degree
of
tracheomalacia.
Finally,
the
arytenoids have to be palpated to see if they are fixed or not. Oesophagoscopy is mandatory in all cases as it will diagnose or exclude coexisting abnormalities.
Anterior glottic web Anterior glottic stenosis develops after thyroid cartilage fractures, from internal laryngeal trauma (as a result of an endotracheal tube) or from overzealous surgical removal of the anterior edges of both vocal cords at the same time. Only a 3-4-mm extension of a web along the vocal cord is needed to cause significant dyspnoea. (Airway obstruction will occur if it is thicker or if there is further posterior extension.) Endoscopic management using either cold steel or the CO2 laser can be performed providing that the posterior
Laryngotracheal stenosis classification
commissure is normal and the inferior edge of the vocal cord is not affected. A keel needs to be left in place for
A number of classifications have been proposed. The most simple relies on the description of the level at which the stenosis occurs, namely, supraglottic, glottic, subglottic and tracheal. Each has different management strategies and these are outlined in Table 173.3.
Laryngeal inlet stenosis causes posterior displacement the
hyoid
bone
and
any greater than previously described or when endoscopic measures have failed, a laryngofissure approach should be performed, the scar tissue resected and any defect grafted.40 A short-term stent/keel is left in situ, again, for 2 two to four weeks. 5
Posterior glottic stenosis
SUPRAGLOTIIC STENOSIS
of
two to four weeks.38, 39 If the anterior glottic stenosis is
epiglottis.
Endoscopic
CO2
laser excision can be successful but, in general, serial procedures are usually required and tracheostomy cover is advised. Alternatively, the thyrohyoid membrane is divided in the midline through a laryngofissure. The submucosal
Posterior glottic stenosis is most commonly caused by endotracheal intubation and is manifested by scar tissue lying between the arytenoids which may be accompanied by fixation of one or both of them. Bogdasarian and Olson41 have classified the extent and severity of posterior glottic stenosis into the following four types.
scar tissue is removed (via an inverted V-shaped wedge)
•
Type. I: vocal process adhesion.
and the remaining mucosa is quilted back against the
•
Type II: posterior commissure stenosis, with scarring
laryngeal framework. Areas of denuded mucosa should be
in the interarytenoid plane and internal surface of the
grafted.
posterior cricoid lamina.
Table 173.3
Management summary of laryngeal stenosis.
Site of stenosis Supraglottic
Possible causes
Managern�nt
Traumatic posterior displacement of hyoid bone and
CO2 laser (often. needs serial excisions and tracheostomy
epiglottis
cover) Laryngofissure
Anterior glottic
Thyroid cartilage fracture and mucosal disruption
CO2 laser/cold steel plus keel. (If web does not extend below inferior edge of vocal cord and if posterior commissure is normaL)
Endotracheal intubation Excessive surgical removal of mucosa from anterior
If web larger - laryngofissure with scar excision ± ssg and keel for 2-4 weeks.
edge of both vocal cords Posterior glottic
Interarytenoid scar tissue ± arytenoid fixation caused by endotracheal intubation
Subglottic
CO2 laser plus keel If larger-laryngofissure ± keel for 2-4 weeks
Endotracheal intubation
If soft - dilatation ± intralesional steroid
Vascular CT disease
CO2 laser/microdebrider Anterior cricoid decompression plus graft Laryngofissure and post-cricoid split plus graft Partial cricotracheal resection'
2282
•
•
I PART 16 THE LIPPER AIRWAY
Type III: posterior commissure stenosis with
for expansion of the airway, combining the use of
unilateral cricoarytenoid joint ankylosis.
laryngeal and cricoid splits, cartilage and bone grafts,
Type IV: posterior commissure stenosis with bilateral
and stenting. Anterior cricoid decompression with cartilage grafting
cricoarytenoid joint ankylosis. Posterior commissure stenosis can be managed either endoscopically with CO2 laser excision or via an open laryngofissure. In general, the stenosis should be excised and the arytenoids kept separated with a modified keel. It should be noted that to keep the posterior glottis open, both arytenoids must be mobile and capable of achieving glottic competence - if an arytenoid is not mobile, then it should be removed and the vocal cord stitched laterally.
is
used
for
anteriorly
based
subglottic
stenosis.
A
combined laryngofissure with posterior cricoid split is the method of choice for dual posterior glottic and subglottic stenosis, moderate subglottic stenosis with loss of
cartilaginous
support,
and
complete
glottic
and
subglottic stenosis. The most commonly used autogenous grafts are costal cartilage, nasal septal or auricular cartilage and thyroid cartilage - all require stenting. Stenting is necessary for a minimum of four weeks for thyroid, septal and
SUBGLOTrIC STENOSIS
The most common cause of subglottic stenosis is from endotracheal intubation (either secondary to prolonged intubation, an incorrect size tube or incorrect cuff pressure).
Subglottic stenosis classification system Cotton and Myers42 devised a classification scheme from I to IV for grading circumferential subglottic stenosis. This grading system applies mainly to circumferential stenosis and does not apply to other types of subglottic stenosis or combined stenosis (although it can be used to obtain a rough estimate). •
Grade I: less than 50 percent luminal obstruction.
•
Grade II: 50-70 percent luminal obstruction.
•
Grade III: 71-99 percent luminal obstruction.
•
Grade IV: complete luminal obstruction.
As with all the other types of laryngeal stenosis, subglottic stenosis can be managed either endoscopically or via an open procedure.
Endoscopic approach This can be attempted for grades I and II stenosis and for stenosis less than 1 cm in length. Soft subglottic stenosis (as commonly seen in Wegener's granulomatosis) can undergo serial dilatation. For fibrotic stenosis, either the
auricular cartilage and up to eight weeks for costal cartilage to allow the graft to be resorbed and replaced by firm mature scar tissue. If a smaller area needs to be reconstructed a hyoid sternohyoid muscle interposition graft can be considered. This is a pedicled graft and has a high success rate. The advantage of this graft is that stenting is not usually required.25 In cases of severe circumferential subglottic stenosis, partial
cricotracheal
resection
can
be
performed
(Figure 173.3). The cricoid can be mostly removed with only the posterior lamina being left (on which sit the arytenoids). The larynx can then be dropped and the trachea mobilized and elevated - the upper tracheal margin is brought up to lie on the remaining cricoid cartilage and held in by sutures (to the cricoid remnant posteriorly and to the lower end of the thyroid lamina anteriorly). To avoid damage to the recurrent laryngeal nerves dissection is carried out in the subchondrial plane, first described by Gerwat in 1974.43
TRACHEAL STENOSIS
Endotracheal intubation is again the most common cause for tracheal stenosis. The second most common cause is a complication of tracheostomy.
CO2 laser or the microdebrider with a 4-mm tricut blade can be used. If the stenosis is circumferential, two radial incisions can be made and then gentle dilatation performed. If the stenosis is greater than 4 mm in length, tracheostomy
cover is advised.25
In general, endoscopic treatment is not successful in cicatricial scarring, exposed perichondrium or cartilage (after use of the CO2 laser) and combined laryngotracheal
stenosis.
Part of cricoid resected
Posterior lamina of cricoid left behind
External approach Open repair is indicated for failed endoscopic manage ment or for grades III and IV subglottic stenosis. A tracheostomy is frequently required as an adjunct to definitive open surgical repair. Multiple techniques exist
Figure 173.3
Partial cricotracheal resection.
Chapter 173
lZSI-
!
c=J Tracheal stenosis
I
Removed
1
Laryngeal trauma and stenosis
I
2283
Larynx released
Elevation Defect closed ---+
Right mainstem bronchus detached from biforcation
Figure 173.4
Right mainstem reattached to left mainstem
Barclay's (or Grillo) procedure for extensive stenosis.
Three types of tracheal stenosis exist, namely, cica
The
pre-epiglottic
space
is
entered
through
the
tricial (essentially defined as a connective tissue scar),
thyrohyoid membrane, the thyroid cartilage is distracted
anterior wall collapse and complete stenosis.
from the hyoid and the middle constrictor is removed from the posterior lamina of the thyroid cartilage. Both
Cicatricial tracheal stenosis
the superior and recurrent laryngeal nerves should be
Providing the cartilage is normal and intact, granular or
identified and avoided. The resulting elevated trachea is
fibrous stenosis can be managed by CO2 excision with judicious use of dilatation. If it is circumferential, it is
sutured onto the cricoid or the first tracheal ring with
better to stage the procedure to prevent the formation of a complete circle of denuded cartilage, which will restenose.
nonabsorbable suture. If
the
stenosis
is
still
too
extensive,
a
Barclay' s
procedure, first described by Grillo over 40 years ago, can be considered. A right thoracotomy enables removal
Anterior wall collapse
of the right main bronchus from the carina. It is then
Anterior wall collapse is most commonly the complica
joined onto the left mainstem bronchus at a lower level;
tion of tracheostomy placement following removal of a
this will give a few centimetres of extra length and,
cartilage
surprisingly, does not result in stenosis further down
'window'. If the
patient is complaining of
dyspnoea only on exertion, this is suggestive of tracheo
(Figure 173.4).5
malacia - be considerate of surgery as reconstitution of the weak wall can potentially damage the recurrent laryngeal nerves. Attempts to strengthen the tracheal wall with mesh are usually not successful.5 The anterior wall
KEY POINTS
can be restored by mobilization of the sternohyoid muscles to cover the defect or repair with a cartilage
•
The predominant cause of chronic laryngeal
graft. The lumen will need to be stented with either a
stenosis
Montgomery or Aboulker stent.
happening as a result of endotracheal
is trauma, with the majority of cases
intubation.
Complete tracheal stenosis
•
The average length of the adult trachea is 11 cm (range 10-13 cm) with between 14 and 20 rings. Hyperextension
The subglottis is the most common site of laryngeal stenosis.
•
Gastro-oesophageal reflux is known to
of the neck results in approximately 50 percent of the trachea being brought into the neck.42 Up to 5 cm of the
managed
trachea can be excised to rejoin the trachea back onto the
prophylactic proton pump inhibitors or H2
cricoid or the first tracheal ring.44
potentiate stenosis and this should be
[***]
by the appropriate use of
antagonists.
The mediastinal trachea can be pulled up with ease,
•
Patients with chronic stenosis are often
similar to a concertina, but the same pulling force will
misdiagnosed as having asthma or COPD. A
be exerted downward after the anastomosis. Dropping
high index of suspicion is warranted with the
the larynx can counteract this; the superior cornu of the
onset of respiratory symptoms following
thyroid cartilage is cut on both sides thus releasing the
intubation, regardless of the duration of
pull
intubation.
of
the
stylophayngeus,
palatopharyngeus.
salpingopharyngeus
and
2284 I
PART 16 THE UPPER AIRWAY
,/ Only nondisplaced fractures of the laryngeal cartilage should be treated conservatively and allowed to heal by fibrous union. Displaced fractures need to be reconstituted. Following laryngeal trauma early recognition, accurate evaluation and instigation of the appropriate treatment is fundamental to a successful outcome. ,/' Flexible nasendoscopy is pivotal in the examination of laryngeal trauma. It facilitates diagnosis of mucosal oedema, cartilage exposure, vocal cord paralysis and avulsion and arytenoid dislocation. If there is any doubt about potential airway compromise, local anaesthetic spray should be avoided as this can cause paroxysms of coughing and subsequent precipitation of airway collapse. As a general guideline, the decision to undertake tracheostomy following laryngeal trauma should be made depending on the nasendoscopy finding following this, it should be clear whether intubation is possible and will not exacerbate the injury. All patients in whom surgical intervention is deemed necessary should undergo a formal endoscopic assessment to ascertain the degree of interna I disruption and to decide on the need for open repair. ,/' The indications for stenting following treatment of laryngeal stenosis are - maintenance of the lumen following reconstruction if there is inadequate cartilage support; - provision of support for cartilage and bone grafts; - separation of opposing surfaces during the healing process.
»
REFERENCES
Deficiencies in current knowledge and areas for future research )- Laryngeal transplant. In 1998, Strome et al. 45 in Cleveland, USA, performed the first successful laryngeal transplant on a patient who was aphonic (despite reconstructive attempts) following a motorcycle accident. [*J Subsequent reports suggested good results in phonation and the airway. The outcome in this patient showed that laryngeal transplantation is feasible and potential candidates for transplantation could include patients with aphonia caused by laryngeal trauma, patients with large benign chondromas requiring laryngectomy, and patients who have undergone laryngectomy for cancer and remain disease free after five years. )- Rapid referral to specialized centres following the diagnosis of laryngotracheal trauma once the airway has been stabilized. Laryngotracheal trauma is a
relatively rare occurrence and it is well documented that outcome is best if corrective surgery is performed within the first 48 hours - specialized units should be established and promoted so that appropriate treatment can commence earlier. Mitomycin C. Further randomized controlled trials are needed to prove unequivocally its efficacy in laryngeal stenosis and to determine the optimal dose for treatment.
*
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Chapter 173 Laryngeal trauma and stenosis
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15.
Kryzer TC, Gonzalez C, Burgess LP. Effects of aerosolised
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in the treatment of recurrent respiratory papillomatosis:
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an alternative to the laser? International Journal of
Pediatric Otorhinolaryngology. 2004; 68: 0.3.19
Pancholi S, Desai A. Laryngeal trauma. In: Schweinfurth J, 31.
CWo Predictive factors of success or failure in the
Havas T, Priestly J, Lowinger DS. A management strategy
endoscopic management of laryngeal and tracheal
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stenosis. Annals of Otology, Rhinology, and Laryngology. 1982; 91: 384-8.
Fuhrman GM, Stieg FH, Buerk CA. Blunt laryngeal trauma: 32.
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with miniplates: indications and extended indications in 33.
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Evans IN. Laryngotracheoplasty. Otolaryngologic Clinics of
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Zalzal GH. Use of stents in laryngotracheal reconstruction
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Schaefer SD, Close LG. Acute management of laryngeal trauma. Update. Annals of Otology, Rhinology, and
in children: indications, technical considerations and
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Volpi D, Lin PT, Kuriloff DB, Kimmelman CPo Risk factors for
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Rhinology, and Laryngology. 1987; 96: 684-6. Eliachar I, Roberts JK, Levin HL, Tucker HM.
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imaging of laryngeal and tracheal stenosis by spiral-CT:
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Strong MS, Jako GJ. Laser surgery in the larynx. Early
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Cummings CW, Haughey BH, Regan Thomas J, Harker L, Robbins K, Schuller D et al. (eds). Cummings
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Bogdasarian RS, Olson NR. Posterior glottic stenosis.
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Shapshay SM, Beamis JF, Hybels RL, Bohigian RK.
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Otology. 1984; 5: 360-8. 43.
Gerwat J, Bryce DP. The management of subglottic laryngeal stenosis by resection and direct anastomosis.
Friedman EM, Healy GB, McGill TJ. Carbon dioxide laser
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management of subglottic and tracheal stenosis.
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Cotton RT, Myer CM. Contemporary surgical management of laryngeal stenosis in children. American Journal of
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Parker DA, Das Gupta AR. An endoscopic sialastic keel for anterior glottic webs. Journal of Laryngology and Otology.
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Dedo HH. Endoscopic Teflon keel for anterior glottic web.
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otologie. 2000; 79: 584-90. Gluecker T, Lang F, Bessler S. 2D and 3D CT imaging correlated to rigid endoscopy in complex laryngo-tracheal
Alaani AA, Hogg RP, Drake Lee AB. Wegener's granulomatosis and subglottic stenosis: management of
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Rodel R, Rodenwaldt J, Hommerich CPo Inner surface
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McClay JE. Laryngeal and tracheal stents. In: Rosen CA, Talavera F, Slack CL, Meyers AD (eds). Em edicin e. August,
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Thomas GK, Stevens MH. Stenting in experimental laryngeal injuries. Archives of Otolaryngology - Head and
and Neck Surgery. 1992; 3: 159-64. de Mello-Filho FV, Carrau RL. The management of laryngeal fractures using internal fixation. Laryngoscope.
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Perepetlitsyn I, Shapshay SM. Endoscopic treatment of
Woo P, Kellman R. Laryngeal framework reconstruction 27 cases. Operative Techniques in Otolaryngology, Head,
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Simpson GT, Strong MS, Healy GB, Shapshay SM, Vaughan
for vocal process granulomas. Laryngoscope. 1999; 109:
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Pitkin L, Maani T, Daya H. The use of powered instruments
dexamethasone on subglottic injury. Annals of Otology,
Kass E, Slack C, Meyers A (eds). Emedicine. May, 2005. 16.
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Whited RE. A prospective study of laryngotracheal
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Hall RR. The healing of tissues incised by a carbon-dioxide
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Pasquale K, Wiatrak B, Wooley A, Lewis L. Microdebrider vs
Braun W et al. Laryngeal transplantation and 40-month
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Strome M, Stein J, Esclamado R, Hicks D, Lorenz RR,
174 Upper airway obstruction PAUL PRACY
Introduction Symptoms and signs Assessment
2286 2286 2287
Treatment Key points References
2288 2291 2291
The data in this chapter are supported by a PubMed, Medline search using the key words upper airway obstruction and treatment. This was supplemented by a hand search of the references contained in those articles and in the reference lists of major textbooks. The evidence for the contents of this chapter is predominantly levels 3 and 4 with some level 2 evidence. The clinical recommendations are predominantly Band C.
INTRODUCTION This chapter reviews the options available for the management of upper airway obstruction. The aim should always be to secure the airway using the least invasive method possible while providing the greatest control of the airway. While this approach sounds relatively straightforward, the decision as to which is the most appropriate intervention can be obscured by the overall clinical circumstances and coexisting medical problems. The most obvious example of these problems would be airway obstruction in a person suffering multiple trauma following a road traffic accident, being dealt with at the roadside. The circumstances are far from ideal for making a complete assessment of the cause and level of the obstruction. It may also be difficult to ascertain fully the potential for further injury resulting from a particular form of airway intervention.
SYMPTOMS AND SIGNS The symptoms of upper airway obstruction are fairly nonspecific and may on their own, or in combination, be found in conjunction with a wide range of respiratory conditions. The commonest symptoms are cough, dyspnoea and voice change, which may be associated with
local pain or dysphagia. The most important of these symptoms is dyspnoea which, if it is progressive, is indicative of imminent complete upper airway obstruction.
Stridor Stridor is the cardinal sign of upper airway obstruction and is noisy breathing resulting from narrowing of the larynx or trachea. The noise tends to be high pitched. Obstruction or collapse of the pharyngeal airway causes a low pitched noise, as heard in snorers, which is called stertor. Stridor can be inspiratory, expiratory or biphasic. The timing of the stridor in relation to the phase of breathing is useful clinically, in that it aids in the localization of the level of obstruction. • Inspiratory stridor is heard in association with obstruction at or above the level of the glottis. • Expiratory stridor is heard in association with obstruction of the intrathoracic airway. • Biphasic stridor is heard in association with tracheal lesions. During respiration, the extrathoracic airway has a tendency to 'collapse on inspiration and to increase in diameter on expiration. Consequently, the effect of any
Chapter 174
reduction in diameter is more marked during inspiration. In addition, oedematous or pedunculated lesions of the supraglottic airway will tend to be sucked into the glottis on inspiration and blown clear during expiration. The same effect is seen in stertor owing to pharyngeal obstruction. The opposite is true for the intrathoracic airway, which is influenced by the changes in intrapleural pressure. During inspiration, the negative intrapleural pressure exerts an outward force on the intrathoracic airways and thus causes an increase in diameter. During expiration, the opposite applies and the positive intrapleural pressure causes a relative collapse of the intrathoracic airway, which in turn, exacerbates any narrowing. The trachea is protected from these fluctuations during the respiratory cycle by its cartilage rings, and so any narrowing results in stridor which tends to be heard equally in both phases of respiration.
Hoarseness Hoarseness is the result of abnormal vibration of the vocal folds. Vibration may be impaired as a result of a wide range of injuries leading to vocal cord paralysis, oedema, mucosal tears, laryngeal disruption or greatly reduced airflow through the glottis. As a rule of thumb it should be remembered that the greater the degree of hoarseness the greater the severity of the laryngeal damage. Aphonia is almost always associated with very severe injury.
Suprasternal retraction As the inspiratory effort increases to overcome the airflow obstruction, so the accessory muscles of respiration are used. This maximal effort on inspiration results in suprasternal retraction, intercostal recession and flaring of the nostrils.
Restlessness Restlessness may be the result of anxiety or may be indicative of hypoxia. The hypoxia may be the result of an associated medical problem such as haemorrhagic shock or parenchymal lung damage. In a patient who has been restless, an apparent calming down should not be assumed to be indicative of improvement. As the patient starts to tire from the extreme respiratory effort, so they will become less restless, which may precede complete respiratory failure. A patient showing signs of restlessness and suprasternal recession requires urgent respiratory support.
Drooling and bleeding Drooling is usually the result of pain, where the patient avoids the painful stimulus of swallowing, and is
Upper airway obstruction I 2287
indicative of trauma or infection. Both trauma and infection can also result in neuromuscular dysfunction which will further hamper deglutition. Bleeding is indicative of mucosal trauma; careful thorough examination, with adequate lighting and suction, will usually allow identification of the source. However, in a patient suffering from multiple trauma it may not be possible to find a specific source or there may be multiple sources.
Fractures and subcutaneous emphysema Upper airway obstruction may result from fractures of the trachea, larynx or the maxilla and mandible. All of these structures should be carefully palpated to exclude a possible fracture. Subcutaneous emphysema may be seen in association with fractures of the laryngeal skeleton or trachea and implies a disruption of the aero digestive tract, with escape of air into the soft tissues. In severe cases it may be that the subcutaneous emphysema is responsible for the airway obstruction rather than being an associated sign.
ASSESSMENT As with all medical emergencies, the initial assessment of a patient with upper airway obstruction is of paramount importance. The assessment must of necessity be rapid, but there must be no compromise on the thoroughness of the examination. The patient must be examined to exclude any immediately reversible causes of airway obstruction, the breathing and circulation must be checked and any necessary resuscitation instituted. Following this, a full assessment of any other injuries or medical conditions should be made. If at any stage of this preliminary assessment there is any doubt as to the immediate safety of the airway then the airway must be secured by the least invasive technique available, without delay. A careful assessment of the symptoms and signs will, in most cases, provide sufficient information for a decision to be made as to the further management of the problem. If the airway is stable but the underlying cause of the obstruction is not obvious then further assessment may be warranted. The most useful investigation is probably fibreoptic examination, which is better tolerated than indirect laryngoscopy and provides valuable information as to the site and degree of any obstruction. If there is any question regarding trauma to the cervical spine then cervical spine radiographs should be obtained as this may have a direct bearing on the method of intervention. The positioning of the neck is crucial in both conventional endotracheal intubation and tracheost0my and so other techniques, such as fibreoptic intubation, may need to be considered for a patient who has had their neck immobilized. Other radiographs rarely provide useful information in the acute phase of management, but once stabilization has been achieved
2288 I PART 16 THE UPPER AIRWAY consideration should be given to soft tissue radiographs of the neck and chest. Facial views, barium swallow and arteriography may, on occasions, be indicated. If there is evidence of a significant disruption of the aero digestive tract then careful endoscopy under general anaesthesia is indicated.
TREATMENT As previously mentioned, the intervention required will depend on the results of the assessment and the experience of the clinician. The interventions described may be used as a single definitive treatment or may need to be used in combination, particularly if the obstruction progresses in spite of treatment. As is the case with most medical emergencies, the worst thing to do is to vacillate and put off making a decision regarding definitive treatment. When coming to a decision regarding the most appropriate form of intervention, certain basic principles should be remembered. 1 • The most straightforward and least invasive method of adequately securing the airway should be the treatment of choice. • The method selected must achieve control by securing the airway below the lowest level of the obstruction. • Careful consideration must always be given to pre- or coexisting medical conditions which may have an effect on the choice and potential complications of the intervention selected. • Once the airway has been adequately secured any other medical problems should be addressed.
Medical management and noninvasive procedures While it should always be borne in mind that 'The time to do a tracheostomy is when you first think of it', there are frequently times when minor trauma, infection or tumours cause airway obstruction which is moderate in severity and stable. Under such circumstances it may be reasonable to institute a period of close observation, while supportive and therapeutic measures are started. This option is only suitable when staff are available who have experience in the management of patients with airway obstruction, and facilities are available for immediate intervention by intubation or tracheostomy should the condition of the patient suddenly deteriorate. This being the case, the most appropriate place for such observation is probably an intensive care unit. It cannot be emphasized enough that this period of observation must be considered as potentially dangerous and should only be entered into if the patient is otherwise stable. There must also be a clear understanding among the staff
involved that any sign of deterioration is an indication for immediate intervention to secure the airway. During this period of observation, nonsurgical treatments can be used to improve the airway. HEIMLICH MANOEUVRE
If the acute airway problem is due to laryngeal obstruction by a food bolus, the acute problem can be managed by a Heimlich manoeuvre in conjunction with a sharp blow to the back of the patient. Hugging the patient from behind so as to apply pressure in the region of the xiphisternum, uses the residual air in the lungs to expel the bolus from the glottis. 2 If the procedure fails then a cricothyroidotomy should be carried out. The Heimlich manoeuvre is not without complications, which include pneumomediastinum, pneumopericardium, surgical emphysema 3 and gastric rupture. 4 With these complications in mind it is important that patients in whom an obstruction has successfully been relieved should undergo a period of observation before discharge. In spite of these potentially fatal complications there is some evidence that the death' rate from inhaled foreign bodies has fallen since the introduction of the Heimlich manoeuvre. 5 OXYGEN AND HELIOX
The administration of humidified oxygen via a face mask or nasal cannulae can increase the inspiratory oxygen levels and will help to relieve hypoxia. Some patients with upper airway obstruction develop pulmonary oedema which exacerbates the hypoxia. The humidification helps to break down secretions and makes them easier to clear. Helium has a relatively low density and high viscosity and so is less prone to turbulent flow than air or pure oxygen. Heliox is a mixture of 80 percent helium and 20 percent oxygen and has been used in the management of a variety of respiratory disorders since the 1930s. 6 The patient experiences reduced resistance during breathing with heliox and this is of proven benefit in the obstructed patient. 7 There is some evidence that the benefit is more pronounced the more severe the degree of obstruction. 8 STEROIDS
Steroids have a significant role to play in the reduction of inflammatory, infective or traumatic oedema. The main problem with their use lies in underdosing rather than overdosing. 9 There is as yet no evidence of a detrimental effect of steroids in the presence of an infection, provided the steroids are given as an intravenous bolus as a shortterm measure. ANTIBIOTICS
Antibiotics should be given infection is suspected and
III III
any case where acute cases where there is
Chapter 174 Upper airway obstruction
I 2289
evidence or strong suspicion of a mucosal injury. Highdose intravenous penicillin is usually adequate but cephalosporins may also be used.
Alternative airways If the airway problem is not stable or is deteriorating, then a decision will need to be made as to what is the most suitable alternative airway. The decision must be based on the premises mentioned previously; the airway chosen should be the least invasive that will adequately bypass the obstruction for the required amount of time. In addition, consideration must be given to the experience of the individual carrying out the intervention. It is obviously inappropriate to carry out some of the more complicated interventions for the first time when confronted with an acutely obstructed patient.
Figure 174.1
Oral airway.
Figure 174.2
Nasopharyngeal airway.
ORAL AIRWAY
Patients who are obstructed owing to a loss of consciousness or as a result of nasal injury or obstruction can be managed by the insertion of an oral airway (Figure 174.1). The semi-rigid airway is easy to insert and can bypass obstruction in the oral cavity or nose. The patient must still have a normal ventilatory drive and normal airway anatomy beyond the oral cavity and nasopharynx. The airway is not tolerated in patients who are alert and is easily dislodged. However, it is simple, maintains the airway well and facilitatates suctioning. It can also be used in conjunction with a face mask and ambubag to assist ventilation. NASOPHARYNGEAL AIRWAY
A nasopharyngeal airway (Figure 174.2) can be used in patients whose problem lies at the level of the oropharynx. If the tongue base has been pushed posteriorly by infection (e.g. Ludwig's angina) or trauma (e.g. facial fractures), an oral airway will not reach far enough to act as a conduit to the undamaged airway. Nasopharyngeal airways are soft and so are well tolerated. While they are simple, easy to insert and an aid to suctioning the airway, injudicious insertion can cause epistaxis and may result in further airway problems. As with the oral airway, a normal respiratory drive is needed.
ENDOTRACHEAL INTUBATION
If oral or nasopharyngeal airways are inappropriate or have been tried and failed, endotracheal intubation should be carried out. Endotracheal intubation is the intervention of choice where there has been a loss of respiratory drive necessitating assisted ventilation, or in cases of progressive upper airway obstruction. There should be a range of endotracheal tubes available, a
bougie, a laryngoscope with an adequate light source and good suction equipment. The commonest method of intubation is trans oral; however, there are some relative contraindications to transoral intubation. • Fractures of the cervical spine: hyperextension of the neck might result in exacerbation of an unstable or incomplete spinal cord injury. • Severe facial trauma: copious bleeding, swelling, trismus, mucosal damage and bony instability may all contribute and prevent a view of the larynx. • Laryngeal trauma: passage of a tube through an injured larynx may exacerbate the existing damage. These are all relative contraindications and very dependent on the experience of the individual. Where transoral intubation is felt to be inappropriate, transnasal intubation can be attempted. Traditionally, this was carried out as a blind procedure which required great skill and experience, but it should be regarded as a dangerous procedure because of the high chance of further traumatizing the airway. Since the introduction of flexible fibreoptic endoscopes, it is preferable to carry out transnasal intubation under endoscopic control. The endotracheal tube is passed over the flexible endoscope (Figure 174.3), a transnasal laryngo bronchoscopy is carried out so that the tip of the endoscope is passed into the trachea, and the endotracheal tube is then passed over the endoscope into position. The use of the endoscope converts blind nasal intubation into a much safer procedure carried out under direct vision of the airway. However, it requires additional equipment and no less skill or experience. In patients with a large amount of secretions or bleeding, poor visibility _of the larynx may preclude fibreoptic intubation.
2290 I PART 16 THE UPPER AIRWAY TRANSTRACHEAL CANNULATION
this way, CO 2 is not cleared effectively. Alternatively, the cannula can be connected to a jet ventilation system using Luer-Lok connectors to deliver oxygen under pressure.
In the emergency setting, the trachea can be cannulated via the cricothyroid membrane using a large-bore intravenous cannula. An airway can then be maintained by connecting the cannula to an ambubag using a syringe with a 7-mm endotracheal tube adaptor inserted in the barrel (Figure 174.4). This should allow enough time for the patient to be taken to theatre for a formal tracheostomy to be performed. It should be remembered that while adequate tissue oxygenation can be achieved in
In cases of complete upper airway obstruction cricothyroidotomy is the intervention of choice. It can be performed rapidly with a minimum of equipment (Figure 174.5) and is associated with fewer complications
Figure 174.3
Figure 174.4
Fibreoptic intubating laryngobronchoscope.
CRICOTHYROI DOTOMY
Apparatus for transtracheal cannulation.
Figure 174.5
Minitracheostomy kit.
Chapter 174 Upper airway obstruction
than tracheostomy. However, the risk of laryngeal trauma is high in inexperienced hands. Once the airway has been secured, a formal endoscopy should be carried out and the cricothyroidotomy should be converted to a tracheostomy if prolonged ventilation is required.
I 2291
REFERENCES
*
1.
Weymuller E. Acute airway management. In: Cummings CW, Frederickson JM, Harker LA (ed.). Otolaryngology head and neck surgery. St Louis, MO: Mosby, 1998: 2368-81.
2.
Fioritti A, Giacotto L, Melega V. Choking incidents among psychiatric patients: retrospective analysis of thirty-one
TRACHEOSTOMY
Tracheostomy is the definitive management for upper airway obstruction, but is often hazardous in the emergency setting. The patient is often very agitated and is only comfortable if they are able to sit upright to use the accessory muscles of respiration to relieve their air hunger. An emergency tracheostomy is best performed using a vertical incision, under local anaesthesia, to avoid bleeding as far as possible while still providing good access.
cases from the west Bologna psychiatric wards. Canadian Journal of Psychiatry. 1997; 42: 515-20. 3.
Nowitz A, Lewer BM, Galletly DC. An interesting complication of the Heimlich manoeuvre. Resuscitation.
1998; 39: 129-31. 4.
Majumdar A, Sedman Pc. Gastric rupture secondary to successful Heimlich manoeuvre. Postgraduate Medical Journal. 1998; 74: 609-10.
5.
Ross GL, Steventon NB, Pinder OK, Bridger MW. Living on the edge of the post nasal space: the inhaled foreign body. Journal of Laryngology and Otology. 2000; 114: 56-7.
6.
Khanlou H, Eiger G. Safety and efficacy of heliox as a treatment for upper airway obstruction due to radiation-
KEY POINTS
induced laryngeal dysfunction. Heart and Lung. 2001; 30:
146-7.
• Careful assessment of the severity and level of obstruction must be. carried out. • Comorbidities must be borne in mind. • Action should be decisive. • The least invasive intervention which will bypass the level of lowest obstruction should be used. • Any intervention should be carried out by someone who is experienced in the use of that technique.
7.
Ho AM, Dion PW, Karmakar MK, Chung DC, Tay BA. Use of heliox in critical upper airway obstruction. Physical and physiologic considerations in choosing the optimal helium: oxygen mix. Resuscitation. 2002; 52: 297-300.
8.
Smith SW, Biros M. Relief of imminent respiratory failure from upper airway obstruction by use of helium-oxygen: a case series and brief review. Academic Emergency Medicine. 1999; 6: 953-6.
9.
Hawkins DB, Crockett OM. Corticosteroids in airway management. Otolaryngology and Head and Neck Surgery.
1983; 91: 593-6.
175 Tracheostomy
PAUL PRACY
2300
Definition
2292
Com pi ications
Effects
2293
Decannu lation
2302
Indications
2293
Key points
2302 2303
Techniques
2294
Best clinical practice
Percutaneous versus surgical tracheostomy
2297
Deficiencies in current knowledge and areas for future
Tube types
2298
Postoperative management
2300
,
.
�
:���':<_.,
<:
'"
2303
research
2303
References
.&
_'
,"
,.�"_
"
',,
'
, "
T he data in this chapter are supported by a Medline search using the key words tracheostomy and percutaneous tracheostomy, focu sing on indications , techniques and comp li cations . This was supplemen ted by a hand search of the
references contained in those articles and in the reference lists of major textbook s The evidence for .
the contents of this
chapter is predominan tly levels 3 and 4 with some level 2 e v idence and a single level 1 study. T he clinical recommendations are p r edo min antl y B and
C.
DEFINITION
growth of such techniques, particularly that of percuta neous tracheostomy in the past ten y ea rs has meant that
Trac heotomy is the term used to describe the surgical
the s urgic al management of upper airway
opening of the 'trachea. Tracheostomy is used to describe
longer the exclusive province of the otolaryngologist.
the creation of a stoma at the skin surface which leads into
result is that more and more health care professionals are
the
trachea.
Tracheostomy,
which
was
performed
ancient Egypt, is one of the oldest surgical
and is
in
procedures 1
included in many ancient medical texts ? Prior to the
being confronted
obstruction is no The
with the problems associated with
t racheos tomy care and decannu1ation procedures. Tracheostomy may be either temporary or permanent.
introduction of antisepsis and improved anaesthesia at the end of the
nineteenth century
it was
an
extremely
hazardous procedure and was undertaken with a good
Temporary tracheostomy
deal of trepidation on the part of both surgeon and patient.
twentieth century the principles of
Temporary
the operation were described by C hev ali er Jackson3 and
emergency.
At the beginning of the
these remain the principles of the operation to the present
tracheostomy
may
be
either
elective
or
An elective temporary tracheostomy may be part of a
day. In recent years, with the improvements in endo
pla n ned procedure
tracheal tube technology, an increased n umber of upper
operation, fonowing which postoperative swelling might
airway emergencies can be managed
with nasotracheal or
orotracheal intubation, or percutaneous trach eos to m y_ The
,
such
result in upper airways
as
a major head and neck
obstruction, or for prolonged
respiratory support in a ventilated patient.
I 2293
Chapter 175 Tracheostomy
An emergency temporary tracheostomy is fortunately
that whatever intervention is used the whole of the
a rare procedure and may be indicative of an under
problem is dealt with by a single procedure. It should
breathing
always be remembered that a patient with an airway
difficulties. In most instances, other than severe trauma,
estimation
of
the
severity
of
a
patient's
problem may have coexisting medical problems that
it should be possible to carry out an urgent tracheostomy
contribute to their breathing problems and may require simultaneous management.5
under controlled circumstances using local anaesthesia. In extreme cases it is usually possible to gain control of the airway via a cricothyroidotomy and maintain ventilatory support
using
a
large-bore
cannula
until
a
formal
Upper airway obstruction
tracheostomy can be carried out. This is no longer the most common indication for tracheostomy. Owing to improvements in the design of intubating laryngoscopes and the development of alter
Permanent tracheostomy
native Permanent tracheostomy is an elective procedure carried out as part of an operation involving removal of the larynx, such as a laryngectomy or laryngopharyngectomy, or as part of a
diversion procedure
for
the pharynx and the proximal end of the trachea is sutured to the skin. A temporary tracheostomy may be in use permanently; however, it differs from a permanent tracheostomy in that there is still a communication between the pharynx and lower
airway
via
the
larynx.
In
a
strategies,
such
as
the
use
of
unusual to be presented with a patient for
whom
tracheostomy is the first option.
aspiration
problems. The trachea is permanently disconnected from
the
management
nasopharyngeal airways or fibreoptic intubation, it is
permanent
tracheostomy the only access to the lower airway is via the tracheostome.
Removal of secretions As secretions accumulate in the lower respiratory tract, gas diffusion within the alveoli deteriorates resulting in respiratory failure. Once a tracheostomy has been carried out secretions can be aspirated with minimal upset to the patient. In addition, the reduction in respiratory dead space
makes
it
easier
for
the
patient
to
breathe.
Conditions which tend to result in such an accumulation of secretions are congestive cardiac failure, infection, pulmonary oedema and bulbar palsy.
EFFECTS Tracheostomy may result in the following effects. •
Laryngeal bypass.
All of the normal laryngeal
functions are lost, the patient is unable to cough or phonate. •
A reduction in respiratory dead space.
•
A redundant area is created between the tracheal opening and the larynx in which mucus tends to accumulate and then fall back into the lungs.
•
The filtration of particulate matter and humidification of inspired air by the nasal mucosa is lost.
• •
An increased risk of infection.
The tracheostomy tube will act as a foreign body causing local inflammation, and as it tends to move during swallowing and with normal neck movements, may cause abrasions along the length of the track.4
Prolonged ventilation In cases where prolonged, continuous or intermittent, positive pressure is required, tracheostomy provides the safest means of assisting ventilation. The tracheostomy tube is more secure than a nasotracheal or orotracheal tube
and
the
reduction
of
respiratory
dead
space
facilitates the process of weaning the patient off the ventilator. The introduction of low-pressure cuffs for endotracheal tubes has led to an increase in the length of time a patient can remain intubated, and so, the timing of the tracheostomy has yet to be defined.6 While some studies demonstrate a marked increase in post-intubation laryngotracheal stenosis if patients are intubated for greater than ten days? others have argued that anything up to three weeks is acceptable.8 There is emerging evidence that the introduction of percutaneous tracheost
INDICATIONS In the management of all airway problems it is as well to
omy may lead to a reduction in the length of time patients remain intubated as well as doubling the number of patients undergoing tracheostomy.9 While it can be argued that the problems associated with organizing an
remember certain basic principles. The simplest, least
open surgical tracheostomy in most UK units in the past
invasive technique which will secure the airway ade
may have resulted in an underutilization of tracheostomy,
quately should be the intervention of choice. Considera
it is equally likely that the enthusiasm of intensive care
tion must be given to the lowest level of obstruction so
specialists for a new technique that they can perform
2294
I PART 16 THE UPPER AIRWAY
themselves has lead to circumstances in which, for reasons
Once air is aspirated, the needle is angled in a caudal
of expediency, tracheostomy is now overperformed. Early
direction and the cannula is passed over the needle into
tracheostomy has been shown to reduce the duration of O ventilation and hospital stay in trauma patientsI and it is
the trachea. An airway
possible that this finding could be duplicated for general
with a 7-rom endotracheal tube adaptor inserted in the barrel
intensive care patients.
can then be maintained by
connecting the cannula to an ambubag using a syringe
the
(Figure 175.1). This should allow enough time for
patient
to
be
taken
to
theatre
for
a
formal
tracheostomy to be performed. It should be remembered that while adequate tissue oxygenation can be achieved in
Part of another procedure
this way, CO2 is not cleared effectively.
As previously mentioned, a temporary tracheostomy is an integral part of many head and neck procedures. In circumstances
where
postoperative
swelling
can
be
predicted, and particularly when the underlying medical condition of the patient is not good) then a temporary tracheostomy should be carried out. This should be regarded as mandatory for all major resections involving the oral cavity or pharynx, and where there is any doubt then a tracheostomy should be performed as it is the safest option. The tracheostomy is not only to guard against airway obstruction due to swelling,
but also
against aspiration of blood in the event of postoperative haemorrhage, and facilitates the administration of any further anaesthetic if required in the event of major
In these cases, the cricothy roidotomy can be carried
(Figure 175.2). It should be taken into consideration that
out using one of a number of commercial kits
cricothyroidotomy is probably not a very good elective procedure, as the position of any tube used to maintain the airway, for even a short period of time,
is likely to
cause some trauma to the cricoid cartilage with the risk of subsequent subglottic stenosis. One of the commonest uses of elective minitracheostomy is for the removal of bronchial secretions following thoracic surgery, however, no study has looked at long-term sequelae. One study comments that there were no 'long-term' airway pro blems
in
their series
of patients
followed
up at a
minimum of four weeks. 13
complications. It should be borne in mind that a patient who has had a major resection with or without a complex
reconstruction) who has significant postoperative swell ing, is not a good candidate for reintubation.
It is
probably safer to perform a surgical tracheostomy rather than be tempted by a percutaneous tracheostomy in these .
CIrcumstances.
11
In percutaneous tracheostomy, the pre-
tracheal tissues fit tightly around the tracheostomy tube; early displacement of the tube, before any fibrosis has taken place, results in collapse of the tissues and sudden closure
of
the 12
tracheostome
with
potentially
fatal
consequences.
TECHNIQUES Figure 175.1
Cr i cothyro i doto my1M in itracheosto my In an emergency,
Cannula. syringe and endotracheal tube adaptor
assembly.
rapid entry to the airway can be
achieved through the cricothyroid membrane. Once the cricothyroid
has
been
breached
the
airway
can
be
maintained either with a minitracheostomy tube or a large-bore cannula. The patient lies supine with the neck extended over a pillow. Having ascertained the correct anatomical land marks by palpation the surgeon infiltrates the skin with local anaesthetic and adrenaline. The thyroid cartilage is gripped between the thumb and middle finger of the nondominant hand; in this position the index finger can be used to palpate the cricothyroid membrane. In an emergency the airway is entered using a needle and cannula attached to a lO-mL syringe half
full of saline.
Figure 175.2
Minitracheostomy kit.
racheostomv
I 2295
an,nomy should be marked on the skin the position of the lower border of the
tracheostomy
H.L�,HH�HL
invasive
Percutaneous tracheostomy provides a
increas-
and has
alternative to open
populari ty over the past ten years. The technique was first described in the late 1950S14 and the 1960s15 but has only
received
widespread
following
the
and the suprasternal notch. The hor izontal incision is sited midway between these landmarks It is useful in elective cases to infiltrate the
cricoid
incision line with adrenaline to aid haemostasis. In a true emergency tracheostomy it is useful to employ a midline
vertical incision and cut down directly onto the surface of
introduction of commercial kits based on well-defined , 7 techniques.16 1 Each kit requires a slightly modified
the
technique. The most common technique is the dilatational technique described by et aI.16
cervical skin and is less likely to heal
The
is positioned as for a formal tracheostomy,
with the neck extended and the shoulders square. A the trachea
needle and cannula are used to
below the first tracheal ring. The correct positioning of the needle and cannula is checked
of air
the
into a syringe half filled with saline. The needle is then withdrawn and a guide wire is inserted into the trachea through the cannula
the
The
cannula is withdrawn and a single dilator or multiple graded dilators are used to create a passage wide enough to receive a
tube. The tracheostomy tube is III
of the dilators and is
over the
the trachea. The tracheostomy tube is then secured in PO:SltlOn with tapes or sutures. of the
There is some evidence that the
procedure are reduced if the tracheal lumen is observed during the puncture, dilatation and tube
'YH,,, ..
f-,n.n
thus
rapid control of the
an
unsightly scar as the wound contracts, and is only recommended
in
emergency
there is little or no evidence of this in the literature and some authors dispute it.19 The
skin
and
subcutaneous
tissues
are
divided
horizontally to the depth of the strap haemostasis is achieved with vicryl ties and vertically by blunt
The strap muscles are
dissection in the midline. At this point the thyroid isthm us is
and this should be divided between
clamps and the ends oversewn
The
isthmus is sometimes retracted rather than divided but this
hazardous as the tube may
is
and reintubation could be
subsequently become
haIllOered by the isthmus springing back into position. UH'�'VV''''''
division of the
isthmus, the trachea
is visible, at which point it is useful to identify the cricoid each of the
cartilage and
a flexible bronchoscope.18
A
vertical incision cuts across the lines of election in the
tracheal
rings to to be
determine the best position for the made.
Before
opening
the
trachea
the
choice
of
tracheostomy tube should be made. The tube, its cuff and all connections to the anaesthetic equipment should be checked. Once the surgeon is satisfied that all of the There are many different techniques described in the
appropriate
described in this chapter is the one
The preferred
the author; however, variations will be wherever possible, be carried
out in an operating
under sterile conditions. It is,
of course, possible to carry out the
at the
bedside, however, the width of most intensive therapy unit beds is much
trachea is about to be opened. In general, the incision should be through the second to fourth tracheal
mentioned and discussed briefly. The procedure
of equipment are available and work the anaesthetist should be informed that the
literature. All are minor variations on the same theme.
table
than that of an
calLSlfLg any
It is
to refrain from
in the region of the cricoid cartilage
as this may result in an increased incidence of to this rule is
stenosis. An
operative when a
has a laryngeal malignancy,20 and under should be
these circumstances the
which makes access more difficult. If intubation is not
so as to allow resection of the tracheotomy site at the
possible or deemed too hazardous, the procedure can be
time of laryngectomy. The incision through the tracheal
undertaken using
wall should cause as little
and adrenaline to provide
local anaesthesia. The on
the
operating
table,
with
a
to the trachea as
possible. A vertical, midline incision between silk stay
should be positioned the
sutures,
either side of the incision line, is ideal
shoulders for neck extension. It is important at this stage
(Figure
The stay sutures allow the tracheotomy to
to ensure that the
be held open if the tube needs to be resited
under
shoulders lie square on the
table so that the position of the midline structures of the neck is maintained throughout the Extension of the neck may further compromise the airway in a patient
the procedure under
local anaesthesia and a
position may have to
be used without full neck extension.
formation
of
a
good
track
and
the
to of
the
tracheostome can be pulled up to the skin to facilitate the tube change. If a
window is removed there
may be an increased risk of subsequent tracheal stenosis or tracheomalacia.21 Some authors have the use of a superiorly or
based flap, in which
2296
I PART 16 THE UPPER AIRWAY
� ':- -----"'" �..I,--
-
-
- .:..: .
Figure 175.3
Skin incision.
Figure 175.4
Division of thyroid isthmus and
f
exposure of trachea.
the edge of a tracheal window is stitched to the skin edge. These procedures are designed to facilitate tube changes;
In a patient
with a short fat neck a cricoid hook can be
used to elevate the trachea to aid appropriate siting of the
however, it is said that there is potential for the flap to
tracheotomy? 4 The hook should be used
become displaced and block the tracheostome during
caution to avoid trauma to the cricoid cartilage.
with some In elderly
recann ulation and that there is an increased incidence of
patients the tracheal rings may be calcified and heavy Mayo
tracheocutaneous fistula following decannulation. These
scissors may be needed to cut through them. Under these
disadvantages are compelling in theory but are not backed
circumstanc�s) it may be better to resect a cartilage window
up by the literature.23
rather than outfracture the heavily calcified tracheal rings.
Chapter 175 Tracheostomy I
Figure 175.5
2297
Opening into tracheal lumen
between stay sutures.
Prior to the trachea being opened, the anaesthetist should remove any tapes used to secure the endotracheal
complication
rate)
and
that
the
small
incision,
in
conjunction with minimal tissue trauma, result in reduced
tube and prepare to withdraw the tube slowly under direct
wound complications associated with the percutaneous
vision by the surgeon. Once the trachea has been opened
techniques. However, the dearth of recent publications on
the endotracheal tube should be withdrawn so that its tip
surgical tracheostomy means that the complication rates
if problems arise over the
quoted are often from series of patients treated anything between 20 and 40 years ago.25,26,27 Where randomized
introduction of the tracheostomy tube. The tracheostomy
trials have been conducted comparing the two techniques,
is just above the superior edge of the tracheostome; this allows easy reintubation
tube having been inserted, the endotracheal tube can be removed and the ventilator can be connected to the
the evaluation has not been blind and there is little if any 8, 29, 30 of long-term complications?6, 2 In a
mention
tracheostomy tube. The incision should be closed loosely
double-blind randomized study) 11 the authors found that
with
the overall complication rate) with either technique, was
sutures
emphysema,
to and
prevent the
the
formation
tracheostomy
of
tube
surgical
should
be
low and that the complications which did happen were
sutured in position. The suturing of the tube may be
minor
thought
frequently
differences between the two groups) in that the percuta
become soiled with blood and are changed on the
neous group developed more perioperative complications,
unnecessary;
however,
the
tapes
and nonlife-threatening.
However,
there
were
patient's arrival back on the ward. This early period
while the surgical group developed more postoperative
following insertion of the tracheostomy tube has great
complications. These results correlate with those from a
potential for problems. The tube is irritant to the trachea
meta-analysis carried out by the same authors31 which has
and the patient will cough excessively if the tube is being
received much criticism from pro-percutaneous authors
manipulated, thus it is all too easy for the tube to become
because of the heterogenous group of procedures included
misplaced, with potentially fatal consequences.
in the percutaneous studies/2,33 the variable definition of what constitutes a complication32,34 and the lack of consideration for the learning curve in percutaneous procedures.34
PERCUTANEOUS VERSUS SURGICAL TRACHEOSTOMY
As yet there is no clear advantage for either procedure overall, and probably all that can be concluded is that
The literature on tracheostomy over the last ten years has
more studies are needed to compare the two techniques in
been dominated by reports, reviews and studies discuss
appropriately
ing the use of per cu taneous list
the
numerous
tracheostomy.
perceived
benefits,
Th e se papers
catalogue
the
matched
populations.
However,
there
appears to be a consensus that the safest form of
percutaneous tracheostomy is the dilatation technique 11,18, 5 3 There is little doubt
complications that arise with percutaneous tracheostomy
under bronchoscopic controL
and, more recently, attempt to compare the technique
that this technique is safe for the majority of cases, if
with standard surgical tracheostomy. Such has been the
properly selected. Percutaneous tracheostomies are less
impact of percutaneous tracheostomy that there has been very little published on conventional tracheostomy over the same period.
is available, it seems likely that the present state
The advocates of percutaneous tracheostomy argue that surgical
tracheostomy
expensive to carry out and tend to be quicker to perform
than surgical tracheostomies.36 Until compelling evidence
has
an
unacceptably
high
will
persist, in which the majority of noncomplicated patients undergo
a percutaneous
procedure,
while
the
more
2298
I PART 16 THE UPPER AIRWAY
surgical
straight and orientated at 90° to the trachea. The cannula
tracheostomy. This has some implications for surgical 9 training and so it is important that surgical trainees
the tip passes in a caudal direction. The inflation device is
patients
complicated
are
referred
for
open
gain experience in percutaneous techniques and take advantage of every opportunity to carry out surgical
is rotated and then pushed back into the trachea so that attached so that the cuff can be inflated and the cannula is secured by a flange.
A nonrandomized prospective study comparing trans
tracheostomies.
laryngeal
and
dilational
percutaneous
tracheostomy
found both techniques equally safe.38
Translaryngeal tracheostomy In children and young adults, percutaneous tracheostomy is not advised. The increased elasticity of the tracheal cartilages means that they are easily compressed and this can lead to temporary loss of oxygenation as well as trauma to the posterior tracheal wall. To counteract these problems a technique of translaryngeal tracheostomy has 37 been described. In this technique a needle is inserted into the trachea from outside under rigid tracheoscopic controL The needle is pointed in a cranial direction so
TUBE lYPES A great number of tracheostomy tubes is available. They are made from a wide variety of materials and there are many different designs to overcome some of the problems associated with tracheostomy
(Table 175.1 and Figure 175.6). The selection of a specific tube depends on the indication for the tracheostomy and the postoperative
needs of the patient.
that the tip passes into the beak of the tracheoscope. A guide wire is passed into the tracheoscope via the needle and is withdrawn th.cough the proximal end of the
Features
tracheoscope. The tracheoscope and the needle are both withdrawn and a catheter with a low-pressure cuff is positioned in the distal trachea to allow for continued ventilation. A cone-shaped dilator, which is attached to a specially designed cuffed tracheostomy cannula, is loaded onto the oropharyngeal end of the guide wire and secured by a knot in the guide wire which is attached to a cotton thread. Traction is applied to the neck end of the guide wire and thus the cone-shaped dilator is drawn into the mouth, through the glottis, and comes to rest with its tip abutting
the
anterior
tracheal
wall.
At
this
point,
countertraction is applied to either side of the guide wire as it emerges through the neck, which allows more sustained traction on the dilator to pull it through the
CUFF
Cuff-type tubes can be inflated to prevent the aspiration of blood or saliva from above and form a seal to prevent the leakage of ventilating gases during anaesthesia or prolonged mechanical ventilation. It is important that the pressure in the cuff is high enough to give an adequate seal
without
occluding
the
circulation
in
mucosal
capillaries. For the most part, the use of modern high volume low-pressure cuffed tubes will achieve this aim. Owing to the potential risk of subglottic stenosis with cuffed tubes, uncuffed tubes should be used unless there is a
risk of aspiration or the need for supported ventilation.
anterior tracheal wall and the soft tissues of the neck. As the tip of the dilator emerges, small releasing incisions are made to free up constricting bands of soft tissue which impede the passage of the dilator. Once half of the tracheostomy cannula has been delivered, the cone is detached. A rigid endoscope is passed into the lumen of the cannula and the cannula is gently withdrawn under
INNER
TUBE
An inner tube projects 2-3 mm beyond the end of the
outer tube so that secretions
or crusts,
which will
inevitably collect, collect in the lumen of the inner tube which can be removed for cleaning without disturbing the
endoscopic control until the posterior wall of the trachea
main tracheostomy. The frequency with which the inner
becomes visible. The cannula should now be completely
tube
Table 175.1
Make
needs
to
be
cleaned
will
vary.
In
the
early
Features of different tracheostomy tubes.
Material
Inner tube
:� S�'���tH:�.c;�ffed
,Speaking
Fenestration
�alve
Armoured
F.lexibility. Rigid
Portex
Polyurethane
No
Both
Unfenestrated
Yes
No
Shiley
PVC
Yes
Both
Both
Yes
No
Rigid
Tracoe
Polyurethane
Yes
Both
Both
Yes
No
Rigid
Bivona
Silicone
No
Cuffed
Unfenestrated
No
Yes
Flexible
Moore
Silastic
No
Uncuffed
Unfenes trated
No
No
Flexible
Negus
Silver
Yes
Uncuffed
Both
Yes
No
Rigid
•
Chapter 175 Tracheostomy I
Figure 175.6
2299
(a) Cuffed, nonfenestrated tube with inner tu be
and introducer; (b) cuffed, armoured, single lumen tube with adjustable flange to alter tube length;
(c)
noncuffed, soft silastic,
long tube with inner tube and introducer.
postoperative period it may need cleaning every couple of hours. If this need for frequent cleaning persists beyond the first few days. attention should be given to improving tracheobronchial toilet and humidification.
FLEXIBILl1Y
In some circumstances the anatomy of the patient's airway may
preclude the use
of a
rigid tube, which will
have a fixed curvature. The rigid tube may lie at an angle that tends to cause an abrasion or may result in tube obstruction as the lumen abuts the posterior tracheal walL
FENESTRATION
A softer more flexible tube will tend to conform more
to the patient's anatomy and because it is softer
Sited at the point of maximum curvature, the fenestration.
readily
which may be a single large hole or mul ti ple
small holes,
will cause less abrasion. However, the softness may lead to
allows air to pass through the tube and up through the larynx to increase the volume of air available for phonation.
the tube kinking and so becoming obstructed. In these circumstances it is useful to use an armoured tube.
2300 I
PART 16 THE UPPER AIRWAY
reaches the trachea. Following a tracheostomy the air
ADJUSTABLE FLANGE An adjustable flange allows the length of the tube to be
varied to suit the depth of the stoma and can be used to bypass intratracheal obstruction lying distal to standard length tubes. The tube placed at the time of the procedure will need to be cuffed to prevent blood from the operative site trickling into the trachea, and it must be possible to connect
it
to
anaesthetic
equipment
for
continued
ventilation. Ideally, the tube should have an inner tube to facilitate cleaning in the immediate postoperative period. Once the risk of aspiration has passed and there is no need for a cuff, the tube can be changed for an uncuffed fenestrated tube with a speaking valve to allow the patient to phonate properly. Speaking valves that are
enters the trachea directly via the tracheostomy and is irritant to the trachea thus resulting in an increase in the production and viscosity of secretions. By warming and humidifying the air using hot water-bath humidifiers or nebulizers, the
incidence
of crust formation can be
reduced. In the early postoperative period the patient will require frequent suction to clear secretions. This need will gradually settle as the trachea becomes accustomed to the presence of the tracheostomy tube and the patient learns to clear the secretions by coughing. Even when the patient app�ars to be coping well with the problem of secretions, there will still be a need for suction equipment to be available and scrupulous cleaning of the area around the stoma and of the tube to avoid the build up of crusts.
incorporated into the mechanism of the inner tube are, in general, easier to use than those which attach to the tube externally, as these have a tendency to blow off when the patient coughs.
Swallowing Swallowing problems are common following tracheost omy, even if the patient was swallowing normally prior to the procedure. There are two main causes: the tube has a
POSTOPERATIVE MANAGEMENT When
a
patient
returns
to
the
ward
tendency to limit the normal movement of the larynx following
a
tracheostomy they will require specialist nursing by a nurse who is familiar with the problems encountered by tracheostomy patients. The patient should have been told preoperatively of their inability to talk in the immediate postoperative
period
and
there
should
be
writing
materials available for them to use.
during swallowing and overinflation of the cuff can cause the sensation of pressure in the upper oesophagus. If there are doubts regarding the position of the tube within the
trachea or as to whether
the
lumen is
obstructed, a flexible nasendoscope can usually be passed through the tube to visualize the distal end. Using this technique it is possible to see any granulations forming on the tracheal wall at the level of the tube tip and also ensure that the shape of the tube is not causing the tip to abut
Tracheostomy tube The tracheostomy tube should be secured with sutures until the first tube change, which should usually be on the third postoperative day or later. When the tube is changed
the posterior wall, resulting in intermittent obstruction. Most of these problems can be addressed by altering the type of tube to a longer or more flexible tube. If the tube needs to be changed in the first 48 hours it is advisable to carry out the change over a flexible anaesthetic bougie.
the sutures can be changed for tracheostomy tapes and the wound sutures can be removed. The tracheostomy tapes should be fastened using a secure knot on both sides of the neck, and the neck should be in a neutral position. If the tapes are secured with the neck in extension then the tapes will be too loose and the tube may become
dislodged.
The cuff should only remain inflated for as long as there is a risk of aspiration. In spite of the introduction of low-pressure cuffs there is still a risk of perichondritis and subsequent tracheal stenosis. After an uncomplicated procedure, the cuff rarely needs to be inflated for more than the first 12 hours.
COMPLICATIONS The complications of tracheostomy fall into the following categories: •
Immediate: - anaesthetic complications; - haemorrhage: •
thyroid veins;
•
jugular veins;
•
arteries.
- air embolism; - apnoea;
Humidification and removal of secretions
- cardiac arrest; - local damage: •
thyroid cartilage;
The nose and pharynx, under normal circumstances, are
•
cri'coid cartilage;
responsible for warming and humidifying the air before it
•
recurrent laryngeal nerve.
Chapter 175 Tracheostomy I
•
2301
Intermediate:
into the venous system in large quantities and pass into
- displacement of the tube;
the right atrium. The complication is best avoided by
- surgical emphysema;
good surgical technique and meticulous haemostasis at
- pneumothorax/pneumomediastinum;
the time of surgery.
- infection: perichondritis; - tube obstruction by secretions or crusts; - tracheal necrosis;
LOCAL DAMAGE
- tracheoarterial fistula;
One of the most important tenets of tracheostomy
- tracheo-oesophageal fistula;
technique is that it is vital to confine the dissection to
- dysphagia. •
the midline. Inexperienced operators who stray from the
Long term:
midline may inadvertently cause damage to the carotid
- stenosis;
artery, the oesophagus or recurrent laryngeal nerves. In
- decannulation problems;
patients with emphysema the domes of the lungs may
- tracheocutaneous fistula;
extend into the lower neck and lateral dissection may
- disfiguring scar.
result in a pneumothorax.
Complication rates quoted in the literature range between 4 and 31 percent for percutaneous tracheostomy and
between 6 and 66 percent for surgical tracheostomy.39 Most of these complications should be avoidable in the majority of cases. Meticulous attention to the details of the technique reduces the complication rate to almost zero in elective noncomplicated cases carried out by an experienced team.19 However, the complication rates are two to five times more common in emergency cases.40 It
If inadequate exposure has been obtained then damage to the anterior or posterior wall of the trachea becomes more likely. If the operative field is further obscured by poor haemostasis then damage to the cricoid or first tracheal ring are also more common. The integrity of the cricoid ring is very important and if damage is identified at the time of surgery then the tracheostomy should be relocated lower in the trachea and the edges of the cricoid laceration repaired.
is important to emphasize that the most crucial members of this team are usually the nurses who will be responsible for the management of the patient in the first 48 hours.
Intermediate E XTUBATIOI\I OR TUBE OBSTRUCTION
Early
Accidental extubation is best avoided by the correct siting of the tracheostome and securing the tube in position
HAE MORRHAGE
with
sutures.
Displacement
of
the
tube
into
the
Haemorrhage is perhaps the most common complication
pretracheal space often goes unnnoticed as the patient
of tracheostomy and is the commonest fatal complica
continues to breath while the soft tissues gradually
tion.41 As previously stated, when the tracheostomy is
prolapse around the tracheal opening which slowly seals.
carried out under controlled circumstances, with meti
The patient becomes increasingly dyspnoeic, and by the
culous attention to detail and the maintenance of a
time the severity of the obstruction becomes apparent the
bloodless field throughout the procedure, the rate of
tube may be extremely difficult to replace. It is essential
haemorrhage
that the
should
be
very
low.
However,
in
an
patient
is
cared for
by
nurses
who
fully
emergency tracheostomy, when the prime consideration
comprehend the potential complications and are experi
is the establishment of an airway, scant regard is paid to
enced enough to identify early warning signs.
haemostasis until the tube is secured in position, and
The tube lumen may become obstructed within the
under these circumstances there may be considerable
lumen of the trachea either as it impinges on the posterior
bleeding. The usual sources of bleeding are the anterior
wall or if there is a degree of tracheomalacia and the
thyroid vessels and the isthmus of the thyroid. If there is
posterior wall prolapses in to obstruct the lumen. The
significant bleeding at the end of the procedure then the
patency of the lumen can be checked by the passage of a
wound should be re-explored and the vessels responsible
flexible endoscope through the tube to observe the distal
ligated. Packing of the wound is widely practised in the
end during respiration. If the angle of the tube means that
presence of haemorrhage but should be regarded as little
the tip is impinging on the posterior wall then the tube
more than a temporary procedure prior to re-exploration.
can be changed for one of a different type, or a longer tube may be required to bypass an area of tracheomalacia.
AIR E MBOLISM
Air embolism is a life-threatening complication, which
SUBCUTANEOUS E MPHYSE MA
thankfully, is rare. If large neck veins are inadvertently
If the tracheostomy tube or trachea are obstructed then
opened in the course of the procedure, air can be sucked
air will be expressed into the neck; if the skin incision has
2302
I PART 16 THE UPPER AIRWAY
been tightly closed rather than loosely approximated then
who
the air will be trapped in the subcutaneous tissues,
However, the incidence can be reduced if a completely
have
had
a
tracheostomy
for
many
months.
resulting in surgical emphysema. The subcutaneous air
airtight seal is used following decannulation. If a fistula is
can track up as far as the lower eyelids and down into the
the result of granulation tissue then silver nitrate cautery
upper chest. In the most severe cases the tube may
to the granulations can effect closure of the fistula. In
become dislodged by the massive swelling, necessitating
persistent cases the tract should be excised and the wound
immediate opening of the wound and repositioning of the
closed properly in layers. An unsightly wound can be
tracheostomy tube. In percutaneous tracheostomy, surgi
revised at the same time if necessary.
cal emphysema has been reported in association with posterior tracheal wall laceration.42 TRACHEAL STENOSIS
The main causes of stenosis following tracheostomy are
INFECTION: PERICHONDRITIS
damage to the cricoid cartilage or first tracheal ring at the
If infection is present in the lower airway at the time of the
time of tracheostomy or damage to the tracheal wall from
tracheostomy, antibiotics should be given in the post
a poorly positioned tube which rubs against the mucosa
operative period and the secretions should be cultured
causing inflammation.
regularly. Adequate suction of secretions using an aseptic technique, together with adequate humidification and standard wound management, should prevent secondary infection. A poor technique with cartilage damage at the time of tracheostomy will predispose to infection and this in turn may lead to perichondritis and tracheal necrosis.
DECANNULATION Decannulation
should
be approached
in
a
stepwise
fashion. In most cases, particularly if the initial cuffed tube has been changed for an uncuffed, fenestrated tube, there should be enough airflow around the tube to allow the patient to breath easily with the tube lumen occluded.
FISTULAE
A tracheo-oesophageal fistula results from severe damage to the posterior tracheal wall at the time of surgery or from the persistent rubbing of a poorly positioned tube against the posterior wall in the postoperative period. The fistula may make itself known if the patient starts to aspirate food and saliva in spite of the presence of a cuffed tracheostomy tube. Tracheoarterial fistulae often present
as
a sudden massive
haemorrhage without any premonitory signs. They happen most commonly in previously irradiated patients in whom a low tracheostomy has been carried out. The commonest vessel to be affected is the brachiocephalic artery, although there are reports of tracheocarotid fistulae.43,44 The survival rate is poor and only those patients who receive immediate surgical treatment survive. It is thought that the fistula develops as a result of mucosal necrosis secondary to pressure from the elbow, cuff or tip of the tracheostomy 5 tube.4 In the presence of any haemorrhage the tube should
In this case the tube can be blocked off with some form of obturator, during the daytime initially, and then for a full 24 hours, followed by decannulation. If the patient is
unable to breath around the tube then the tube can be downsized, to allow more room for airflow around the tube, prior to the decannulation sequence. Once the tube has been removed the stoma must be occluded with an airtight dressing. In most cases several gauze swabs covered with an occlusive dressing will be sufficient. It is important to change the dressing whenever an air leak becomes apparent to avoid a persistent tracheocutaneous fistula. In patients who have been tracheostomy-dependent for a long period, decannulation may be difficult, due to a degree of psychological dependence. In these cases a much slower sequence of tube occlusion should be followed with decannulation taking place over the course of several days or a whole week.
be changed for a cuffed tube and the cuff should be inflated to protect the lower airway. Pressure should be applied to the artery via the tracheostomy, the patient should be appropriately
resuscitated
and
the
wound
should
be
explored to ligate the bleeding vessel.
Late TRACHE OCUTANEOUS FISTULA
With time, all tracheostomies epithelialize and a persis tent tracheocutaneous fistula is more common in patients
KEY POINTS •
•
AssessITlen - t. 'part of asystematic; reviewofairway breathihg.-and
The assessment shoulddeterminethe level.of airway obstruction.
•
Action should be decisive.
•
Problems
from comorbidities must be
considel'ed, particularly in cases of multiple -trauma.
Chapter 175 Tracheostomy I
•
. The.
'
techniq'ue. to effect tracheo.$tomy sh9Utd .
6.
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�:�:
'
--
'
,-� £ -� ,)�T.:.-�: -�- �. ,.:t:'��1�.��� :'
-• .
Hefner JE. Timing of tracheostomy in mechanically ventilated patients. American Review of Respiratory
. :.:·�" �Jti�F�!����!�2:��:�:�:��•···· · : r
2303
7.
Whited RE. Posterior commissure stenosis post long-term
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Watson CB. A survey of intubation practices in critical care
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�
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II
494-501. 9.
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:
Simpson TP, Oay CJE, Jewkes CF, Manara AR. The impact of percutaneous tracheostomy on intensive care
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unit practice and training. Anaesthesia. 1999; 54:
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172-97.
partlcula r preserve carti lage.
10.
.I In the postoperative period, the patient should be nursed by nursing staff who are fully conversant with
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11.
.I Regular review of the patient should be undertaken
Gysin C. Oulguerov P, Guyot J-P, Perneger lV, Abajo B. Chevrolet J-C. Percutaneous versus surgical tracheostomy.
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tracheostomy i n critica l l y i l l patients. Chest. 1 99 3 ; 1 04 :
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Friedman Y, Fides J , M i zock B , Samuel J , Patel S, Appavu S
1 3 99-402. 37.
et 01. Com p a rison of percu ta neous a n d su rg ica l
28.
G a u k roger M C, Al it-G raham J . Percutaneous d i l atation a l
Medicine. 1 99 7 ; 2 3 : 3 8 6-92. 38.
tracheostomy : A cl i n ical com p a rison of d i l atati o n a l
Surgery. 1 99 4 ; 3 2 : 3 7 5-9.
( C i ag l ia )
H azard P, Jones C, Ben itone J. Comparative cl i n ica l tri a l of
and Analgesia. 1 999 ; 89 : 9 3 8-43. 39.
Thompson JA et 01. Posterior tracheal wa l l perforation d u ri n g percutaneous d i l ation a l tracheostomy. Chest. 1 999 ;
1 1 5 : 1 3 83-9. 40.
surgery. Ph i l a de l p h i a : W B. Sa u n ders, 1 99 3 : 2 5 7 -74.
H o l d g aard H O, Pedersen J, Jensen RH, O u tzen KE, M i d tg a a rd T, Johansen LV et 01. Percutaneous d i l atati o n a l
41 .
H a rdy KL. Tracheostomy : I n d ications, tech n ics, and tu bes.
42.
Dou g l as WE, F l a b o u ris A. S u rg ica l emphysema fol low i n g
The American Journal of Surgery. 1 9 73 ; 1 2 6 : 3 00-7.
tracheostomy versus convention a l su rg ical tracheostomy. A cl i n ica l ra n dom ised study. Acta Anaesthesiologica Scan din a vica. 1 99 8 ; 42 : 545-50.
percuta neous tracheostomy. Anaesthesia a n d Intensive
D u l g uerov P, Gysi n C , Perneger T, Chevrolet J .
Care. 1 999 ; 2 7 : 69-72.
Percu ta neous or su rg ica l tracheostomy : a meta- a n a l ysis.
43.
Primorac 0 et 01. Tracheo- i n nom i n ate a rtery fistu l a after
Friedma n Y, M izock BA. Percuta neous versus su rg ica l
tracheostomy. Anesthesia and An algesia. 1 999 ; 8 8 :
Critical Care Medicine. 1 999 ; 2 7 : 1 684-5.
34.
Ka p u ra l L, S pru n g J , G l u n ic I , Ka p u ra l M , Ande l i ovic S,
Critical Care Medicine. 1 999 ; 2 7 : 1 6 1 7-25. tracheostomy: Proced u re of choice or choice of p roced u re.
33.
Rei l l y H , Sasaski CT. Tracheotomy com p l ications. I n : Krespi YP, Ossoff R H (eds) . Complications in head and n eck
Anaesthesia. 1 99 5 ; 42 : 7 7 5-9.
32.
Trottier SJ , H azard P B, Saka b u SA, Lev ine JH, Troop BR,
C rofts S L, Al zeer A, McG u i re G P, Wong DT, Cha rles D. A in i n tensive care patients. Canadian Journal of
* 31.
a n d tra n s l a ryngeal ( Fa n to n i ) methods. Anesthesia
tracheostomy. Critical Care Medicine. 1 99 1 ; 1 9 : 1 0 1 8-24. com pa rison of percutaneous a n d operative tracheostomies
30.
Westpha l C, Byhahn C, W i l ke H -J , Lischke V. Percutaneous
tracheostomy. British Journal of Oral a n d Maxillofacial
sta n d a rd operative tracheostomy w ith percutaneous
29.
Fa nton i A , Ri pamon ti D. A non-derivative, non-su rg ica l tracheostomy: the tra nslary n geal method. In tensive Care
tracheostomies. Chest. 1 99 6 ; 1 1 0 : 480-5. 27.
Hei kki nen M, Aa rnio P, H a n n u ka i nen J. Percuta neous
Friedman Y, lVIayer AD. Bedside percutaneous
532-5. 26.
Nates J L, Cooper J , Myles P S, Schei n kestel CD, Tuxen DV.
3 4 : 42-6.
7 7 7-80. 44.
T u n gekar M F. Tracheoca rotid a rtery fist u l a i n fected w i th methici l l i n - resista nt Staphylococcus aureus.
Ba rraco R, B rathwaite CEM, B reb b i a JS, Perez J M , Sm i th
TR. Percuta neous versus open tracheostomy : Is it a fa i r
The Journal of Laryngology and Otology. 1 999 ; 1 1 3 :
com p a riso n ? Critical Care Medicine. 2000 ; 2 8 : 3 3 7 1 .
689-9 1 .
Va n Heurn LWE, Ramsay G. Is su rg ica l tracheostomy rea l ly
45.
Wood D E , M ath isen OJ . Late com p l ications of
su perior to percuta neous tracheostomy? Critical Care
tracheotomy. Clinics in Chest Medicine. 1 99 1 ; 1 2 :
Medicine. 2000 ; 2 8 : 3 3 6 9 .
597-609.
176 Physiology of sleep and sleep disorders JOHN FLEETHAM
Introduction Sleep and respiration Sleep disorders Key points
2305 2306 2307 2311
Best clinical practice Deficiencies in current knowledge and areas for future research References
2311 2311 2311
The data in this chapter are supported by a Medline search using the key words sleep, respiration, obstructive sleep apnoea/hypopnoea syndrome, nonrespiratory sleep disorder and focussing on pathogenesis.
INTRODUCTION This chapter summarizes the current knowledge concerning sleep and its impact on normal respiration. It reviews in detail the pathogenesis of obstructive sleep apnoea/ hypopnoea syndrome. The pathogenesis and clinical aspects of nonrespiratory sleep disorders such as narcolepsy, periodic limb movement disorder (PLMD) and idiopathic hypersomnia are also briefly discussed. Sleep is a temporary state of unconsciousness that can be interrupted by external stimuli. It is not a uniform state, but is organized into a cyclic pattern of sequential stages. The stage of sleep is defined by a combination of electroencephalographic (EEG), electromyographic (EMG) and electro-oculographic criteria. Two separate phases of sleep are generally recognized: 'quiet' or nonrapid eye movement sleep (non-REM) and 'active' or rapid eye movement sleep (REM). During non-REM sleep, the EEG waves progressively slow down and increase in amplitude. Non-REM is divided into four stages, representing progressively deeper stages of sleep. In stages 1 and 2 the EEG voltage is low and the frequency is mixed. In stages 3 and 4 the EEG voltage is high and the frequency slow, and consequently, these two stages are often referred to as slow wave sleep (SWS). Stage 2 sleep is
the predominant sleep stage and usually accounts for about half of an adult's sleep. During REM sleep the EEG is desynchronized with low voltage and high frequency. REM sleep has been characterized into two patterns, tonic REM associated with muscle tone depression and phasic REM associated with periods of rapid eye movements and twitching movements of the face and limbs. Most dreams happen during REM sleep and there is also increased autonomic activity with marked fluctuations in blood pressure, heart rate and respiratory rate. Increasing age, alcohol and other sedatives all tend to decrease REM sleep. A typical sleep usually starts with stages 1 and 2 of nonREM sleep which often alternate with wakefulness prior to entering the deeper SWS. REM sleep occurs for the first time approximately 90 minutes after the onset of sleep and then recurs between four and six times during a nights sleep. REM sleep accounts for 25 percent of the total sleep time and as sleep progresses the REM periods become longer and the non-REM periods shorter. Arousals are brief neurological awakenings and are a normal feature of sleep. They may be either cortical or subcortical and the sleeping individual is usually not aware of them. They may happen either spontaneously or in response to various external stimuli, such as sound or internal stimuli, such as periodic leg movements or sleep apnoea. [**/*]
"
__1__
-~
2306 I PART 16 THE UPPER AIRWAY The physiological basis of sleep is poorly understood but appears to depend on the interaction between the intrinsic sleep drive, ultradian REM sleep rhythm, adaptive sleep drive and circadian rhythm. 1 The intrinsic sleep drive increases with the time spent awake and decreases as soon as sleep occurs. The ultradian REM sleep rhythm has a 90-minute cycle during both wakefulness and sleep and is independent of the intrinsic drive. The adaptive sleep drive is influenced by a variety of behavioural responses to the environment, and reflex responses to sensory stimulation by factors such as light, noise, temperature, exercise and food. Sleep, temperature and hormone secretion all have circadian rhythms with a 24--25 hour cycle, which can be influenced by external factors. These circadian rhythms are controlled by the suprachiasmatic nuclei in the hypothalamus, which respond to changes in light stimulation. The sleep circadian rhythm keeps the sleep/ wake cycle in sequence with environment time but is not responsible for sleep onset. Cerebral cortical activity determines when sleep or wakefulness take place but does not initiate sleep. The reticular activating system in the brain stem promotes wakefulness when it is active and permits sleep when it is inactive. It controls the intrinsic sleep drive and the reflex component of the adaptive sleep drive. The neurochemistry of sleep and wakefulness is complex and poorly understood. The primary neurotransmitters involved in the control of sleep and wakefulness are amines, amino acids and peptides. These neurotransmitters playa major role in the intrinsic sleep drive and reticular activating system activity. Melatonin is an important neurotransmitter that is released by the pineal gland in response to darkness. It promotes sleep and acts on the suprachiasmatic nuclei to change circadian rhythms and reduce body temperature. [**/*]
Cortical stimulation
The majority of adults sleep seven to eight hours a night, but approximately 10 percent sleep less than five hours and 2 percent sleep more than ten hours. The optimal sleep duration is eight to nine hours a night and although many individuals appear to function on less sleep there is increasing evidence that this is associated with impaired daytime performance. Sleep pattern changes with age. Total sleep time is around 16 hours in full-term infants and 50 percent of this is REM sleep. There is a progressive decrease in total sleep time with increasing age and a reduction in the proportion of REM sleep to 25 percent by middle age. The elderly are more prone to daytime naps but the total amount of sleep each 24 hours is often similar to younger individuals. Poor sleep hygiene is the commonest cause of impaired sleep and a consistent sleep and waking time are important for good sleep quality. Shift work and time zone changes are common reasons for an irregular sleep/wake schedule. Depression and anxiety frequently cause difficulty in initiating or maintaining sleep. Medical conditions, such as backache or nocturia, and medications can also reduce sleep duration and quality. Sleep may also be impaired because of a bed partner's sleep disorder such as sleep apnoea or periodic limb movement disorder. [**/*]
SLEEP AND RESPIRATION Sleep has a variety of normal physiological effects on both the upper and lower respiratory systems (Figure 176.1). These effects usually have no adverse impact in normal subjects but may cause a respiratory sleep disorder in individuals with a narrow upper airway or underlying respiratory or neuromuscular disease. Normal respiration
Intercosta~
Chemical drive to breathe
muscle activity
t
Lung volume
t
V/O mismatching
Hypoventilation +/Hypoxaemia Hypercapnia
Figure 176.1
The effect of sleep on respiration.
I
t
Upper airway dilating muscle activity
Upper airway narrowingl collapse
t
Lower airway resistance
Chapter 176 Physiology of sleep and sleep disorders
is regulated by the respiratory centre which has both afferent input and efferent output. Respiratory rhythmicity originates from the respiratory centre that is in the medulla. The respiratory centre receives afferent impulses from central chemoreceptors sensitive to changes in pH, peripheral chemoreceptors sensitive to changes in P0 2 and pH and mechanoreceptors in the airway, lungs and chest wall. The respiratory centre is also influenced by input from the cerebral cortex and other brainstem centres. The cerebral cortex is only irregularly active during REM sleep and inactive in non-REM sleep so the respiratory centre is largely under reflex control during sleep.2 Sleep is associated with reduced chemical and mechanical drives to breathe and these changes are most marked during REM sleep. [**1*] The respiratory efferent output is via the phrenic nerve nucleus and other motor nuclei to the spinal cord, peripheral nerves and respiratory muscles. Respiration in the supine position is principally dependent on the diaphragm. During non-REM sleep, diaphragmatic activity remains unchanged and there is an increase in intercostal muscle activity. This results in expansion of the ribcage and an increase in diaphragmatic efficiency. Intercostal muscle activity is decreased and diaphragmatic activity is increased during REM sleep. 3 The loss of intercostal muscle activity while normal diaphragmatic activity continues during REM sleep causes a reduction in lung compliance with an associated decrease in lung volume and exacerbation of ventilation and perfusion mismatching. It also results in an increase in the abdominal contribution to breathing during REM sleep. Minute ventilation is maintained in response to a mechanical load during wakefulness. This ventilatory compensation to mechanical respiratory loads is lost during sleep, which also contributes to a reduction in ventilation. These normal physiological changes during sleep result in hypoventilation which may be associated with mild hypercapnia and hypoxaemia. Metabolic rate is also reduced during sleep by 10-25 percent, secondary to motor activity inhibition and a decrease in body temperature. 4 In normal subjects, the degree of hypoventilation during sleep is greater than the decrease in metabolic rate and arterial PC0 2 increases by approximately 0.5 kPa. Arterial P0 2 decreases by 0.5-2.0 kPa during sleep because of hypoventilation and increased ventilation and perfusion inequality. Hypoventilation during non-REM sleep is largely due to a reduction in tidal volume, 5 whereas the changes in tidal volume and respiratory frequency are more variable in REM sleep. The hypocapnic apnoeic threshold is more sensitive during sleep. Hypocapnia following periods of hyperventilation during sleep is a major cause of central apnoea. It may also contribute to the development of obstructive apnoea by reducing upper airway dilating muscle activity. Respiratory-related arousals can occur secondary to a wide variety of stimuli including hypoxaemia,
I 2307
hypercapnia, coughing and swallowing. The arousal threshold for respiratory-related stimuli increases during sleep and is highest in REM sleep. [**/*] Upper airway muscle activity normally decreases during sleep with an associated increase in upper airway resistance, which predisposes to partial upper airway obstruction. 6 Snoring is the low frequency sound produced by vibration of the upper airway walls during partial upper airway obstruction. These vibrations usually take place in the soft palate, but in approximately 30 percent of nonapnoeic snorers they may also be present at other sites including the tonsils, epiglottis and the base of the tongue. 7 Theoretical modelling has shown that at critical inspiratory flow rates, the upper airway becomes unstable with repetitive partial airway collapse, which generates the sound of snoring. 8 The critical inspiratory flow rate, which causes snoring, is dependent on upper airway size, shape, compliance and resistance. Normal individuals also have a circadian variation in lower airway resistance with mild nocturnal brochoconstriction. Peak expiratory flow rates during the night decrease by 8 percent in normal subjects and up to 50 percent in patients with asthma. [**/*]
SLEEP DISORDERS Sleep disorders are very common and up to 20 percent of the adult population have some form of sleep disorder. At least 90 different sleep disorders have been described, and these are defined in the widely used International Classification of Sleep Disorders produced by the American Sleep Disorder Association. 9 Sleep disorder medicine is the subject of several large textbooks,l, 10 and is often practiced in speciality clinics. Sleep disorders can be grouped into respiratory and nonrespiratory disorders.
Respiratory sleep disorders Respiratory sleep disorders are composed of four distinct syndromes: 1. 2. 3. 4.
obstructive sleep apnoea/hypopnoea (OSAH); central sleep apnoea/hypopnoea; Cheyne-Stokes breathing; sleep hypoventilation.
Each syndrome has a definition, symptoms, associated features and a differential diagnosis. 11 This review will only discuss OSAH, as this is the condition seen most commonly by otolaryngologists. OSAH is characterized by recurrent episodes of partial or complete upper airway obstruction during sleep which are usually terminated by an arousal. It is important to understand both the pathogenesis of the upper airway obstruction and the mechanism of apnoea termination. The hypoventilation associated with the upper airway obstruction causes
2308 I
PART 16 THE UPPER AIRWAY
hypercapnia and hypoxaemia with their related sequelae. The severity of the hypercapnia and hypoxaemia is determined by the duration of the hypoventilation and the baseline arterial peo 2 and P0 2 prior to the upper airway obstruction. The recurrent arousals result in sleep fragmentation and the symptoms of sleep deprivation such as excessive daytime sleepiness. The site of the upper airway obstruction is either in the velopharynx behind the soft palate, the oropharynx behind the tongue or some combination of both sites (Figure 176.2).
PATHOGENESIS
The patency of the upper airway is determined by its compliance and the balance of forces across it (Figure 176.3).12 The upper airway is more prone to collapse if there is upper airway narrowing, decreased intraluminal pressure or if either its compliance or the extraluminal pressure are increased. The upper airway dilator muscles are normally activated during inspiration,
palate
(a)
Hypopharynx
Figure 176.2
Oropharynx
Nasopharynx
Upper airway: (a) awake and (b) asleep.
Patency
which reduces intraluminal pressure, and consequently decreases the tendency to upper airway collapse. The upper airway collapses when the force generated by these muscles is exceeded by the negative airway pressure produced by the inspiratory muscle activity. Measurement of the critical pressure (Pcrit) required to collapse the upper airway has been performed in humans undergoing general anaesthesia and complete neuromuscular paralysis.13 Patients with OSAH had a positive Pcrit, with the airway collapsing at atmospheric pressure, and required positive pressure to relieve the obstruction, whereas normal control subjects required a negative pressure to collapse the upper airway. [**/*] Abnormalities in both upper airway size and muscle activity appear to contribute to the pathogenesis of OSAH. The majority of patients with OSAH have no specific upper airway abnormality. However, a range of different imaging techniques including cephalometry, computed tomography, magnetic resonance imaging, nasopharyngoscopy and acoustic reflection have demonstrated narrow upper airways in both awake and asleep patients with OSAH compared with control subjects. I4 Upper airway size is determined by a variety of factors. Obesity is a major risk factor for OSAH, and upper body obesity results in fat deposition around the airway and in the related soft tissues. Gender is an important risk factor for OSAH and sex hormones influence upper body obesity. This is probably why OSAH is less common in premenopausal women than postmenopausal women or men. Increasing age is associated with narrower and possibly more collapsible upper airways. IS Finally, individual variations in mandibular, tongue and soft palate size and position contribute to upper airway size. These individual variations have both endogenous and exogenous causes. They are, in part, genetically determined, and up to 40 percent of the variability of OSAH may be explained by familial factors. I6 It has also been suggested that adenotonsillar hypertrophy during childhood may cause abnormal craniofacial development which results in a narrow adult upper airway. [**/*] There are a large number of upper airway dilating muscles which include muscles that influence hyoid position (e.g. geniohyoid), tongue position (e.g. genioglossus) and palate position (e.g. tensor palatini) .17 The geniohyoid and genioglossus are two of the upper airway dilating muscles that have phasic inspiratory activity during inspiration which is maintained during non-REM
Collapse Decreased intraluminal pressure
Dilating muscle activity Increased extraluminal pressure Large upper airway
Increased compliance
Figure 176.3
patency.
Factors influencing upper airway
Chapter 176 Physiology of sleep and sleep disorders
sleep. They stiffen the upper airway and oppose the negative airway pressure generated by contraction of the diaphragm. In contrast, the tensor palatini has predominantly tonic activity which decreases during nonREM sleep. This decrease in tonic muscle activity, which becomes even more marked during REM sleep, is the primary cause of the increase in upper airway resistance observed in normal sleep. The upper airway dilating muscles are activated by negative airway pressure stimulating nasal and laryngeal receptors. 18 Upper airway dilating muscle activity is impaired by recurrent hypoxia similar to that seen in patients with OSAH. 19 Progesterone increases upper airway dilating muscle activity which may help protect women from developing OSAH. 20 The relative importance of upper airway dilating muscle activity is dependent on upper airway size. Minimal upper airway dilating muscle activity is required to maintain a large upper airway patent whereas considerable muscle activity may be necessary to maintain the patency of a small upper airway. The upper airway muscles of patients with OSAH are hypertrophic21 and contract more powerfully during wakefulness compared with normal subjects. 22 This is probably to compensate for the narrow upper airway present in these patients. This neuromuscular compensation probably develops in response to upper airway negative pressure stimulation and may be impaired in some patients with OSAH. There also may be a delay between the upper airway muscle activity and diaphragmatic activity during inspiration in some patients with OSAH, which would result in a negative intraluminal pressure while the upper airway dilating muscles are relatively inactive. 23 Serotonin is thought to be an important mediator of upper airway dilating muscle activity and is reduced during sleep in patients with OSAH. [**1*] Additional nonmuscular factors may also play a role in the pathogenesis of OSAH. Sleep position contributes to upper airway collapse. In the supine position, posterior displacement of the tongue and mandible occurs secondary to the loss of upper airway tone and the effect of gravity. This is more marked in REM sleep when upper airway muscle hypotonicity is greatest. Upper airway size is smaller at low lung volumes. This is especially relevant in supine obese subjects who have low end expiratory lung volumes because of the effect of abdominal weight on diaphragmatic movement. 24 Upper airway shape may also influence upper airway collapsibility. Patients with OSAH have a more oval upper airway, which may impair upper airway dilator muscle function. This upper airway shape may be an important factor in the pathogenesis of OSAH or may occur secondary to fat deposition in the lateral walls of the airway. Chronic vascular over perfusion may also contribute to upper airway oedema. Changes in upp'er airway mucosal adhesiveness and tracheal traction have also been proposed as contributing to the pathogenesis of OSAH. [**1*]
I 2309
There are a variety of factors which help to continue the upper airway collapse in OSAH once it has developed. Magnetic resonance imaging14 and histolo25 gical studies have demonstrated that patients with OSAH develop upper airway oedema secondary to the mechanical trauma associated with snoring and recurrent upper airway obstruction. This upper airway oedema then further reduces the upper airway size and tends to perpetuate the upper airway obstruction. Animal studies have shown that upper airway muscle damage may occur in OSAH in response to the increased workload. 26 This muscle damage is consistent with overuse myopathy and may impair the ability to dilate the upper airway. Finally, the chronic sleep deprivation associated with OSAH may also impair upper airway dilating muscle activity.27 [H/*] Apnoea termination is associated by a brief cortical or subcortical arousal. Upper airway muscle activity increases at the time of the arousal, which results in relief of the upper airway obstruction. This is usually associated with a loud snort and a short period of compensatory hyperventilation. Resumption of sleep then causes a loss of upper airway muscle activity and recurrence of upper airway obstruction. Hypoxaemia, hypercapnia, increased respiratory effort and negative airway pressure have all been proposed as the arousal stimulus. 28 A variety of studies has been performed which appear to confirm that respiratory arousal happens in each individual at a relatively fixed respiratory effort irrespective of the respiratory stimulus. Hypoxaemia and hypercapnia may cause arousal by increasing respiratory effort or by a direct stimulation between the respiratory centre and the reticular activating system. The arousal threshold is higher during REM sleep and this is responsible for the longer apnoea duration during REM sleep. Arousals result in increased sympathetic activity with vasoconstriction, tachycardia and increased systemic blood pressure. [H/*] In summary, the primary cause of OSAH is a narrow upper airway. Increased upper airway dilator muscle activity compensates for the narrow upper airway during wakefulness. Sleep onset is associated with decreased upper airway muscle activity, which then results in upper airway collapse and hypoventilation. Hypoventilation causes hypercapnia and hypoxaemia which stimulate increased respiratory effort. At a certain arousal threshold the patient awakens. This results in a resumption of normal upper airway muscle activity and relief of the upper airway obstruction. Ventilation resumes with correction of the hypercapnia and hypoxaemia. The patient then returns to sleep and the cycle starts again. The hypoventilation and sleep fragmentation associated with this sleeplwake cycle are responsible for the symptoms and long-term consequences of OSAH (Figure 176.4). The clinical aspects of snoring and sleep apnoea are discussed in Chapter 177, Obstructive sleep apnoea: medical management.
2310 I
SI!ep onset
PART 16 THE UPPER AIRWAY
~
Upper airway collapse
~
------~) Arousal~
Apnoea! Hypopnoea
t
Hypoventilation
/
t Catecholamines
Hypoxaemia
HyperrPnia Pulmonary hypertension
1
Systemic hypertension
"'" ~
Sleep fragmentation
1
Daytime sleepiness, impaired cognitive function and quality of life
Nonrespiratory sleep disorders The majority of patients presenting to otolaryngologists complain of snoring or have a suspected respiratory sleep disorder. However, many patients will also present with excessive daytime sleepiness and may have a nonrespiratory sleep disorder. Excessive daytime sleepiness has a broad differential diagnosis. It should not be assumed that a sleepy patient with loud snoring always has OSAH, and all physicians dealing with patients who snore or who have suspected OSAH should be aware of the different causes of excessive daytime sleepiness. In addition to lack of sleep and medications, these include narcolepsy, periodic limb movement disorder and idiopathic hypersomnia. Excessive daytime sleepiness requires investigation which, in addition to clinical assessment, may include completion of a sleep diary, subjective and objective tests of sleepiness and polysomnography.
NARCOLEPSY
Narcolepsy is primarily a disorder of REM sleep in which REM sleep intrudes into non-REM sleep and wakefulness,z9 It is associated with human leukocyte antigen (HLA) types DR2 and DQ1.30 These HLA types do not necessarily result in narcolepsy as they are present in up to 35 percent of the normal population. HLA testing has no positive predictive value but has an excellent negative predictive value. A patient without the HLA phenotype DRB1 *1501-DQB1 *0602 is very unlikely to have narcolepsy. The combination of a genetic predisposition and abnormal neurochemical status is the probable cause of narcolepsy. The association of narcolepsy with certain HLA types has led to the speculation that it may have an autoimmune basis with destruction of hypocretinproducing cells. There is impaired hypocretin production in the majority of patients with narcolepsy and this may be the neurochemical basis of narcolepsy. It affects men and women equally and occurs in approximately one in 2000 of the population. It is a familial condition and up to 10 percent of patients may have a relative with narcolepsy. It may present during childhood and almost always presents before the age of 40 years. It characteristically presents with excessive daytime sleepiness, hypnagogic hallucinations (dreams shortly before sleep), sleep
Figure 176.4
Consequences of OSAH syndrome.
paralysis (inability to move shortly before sleep) and cataplexy (sudden loss of awake voluntary muscle tone after emotion), although some of these features are often absent. 31 The diagnosis is usually made clinically based on the characteristic combination of symptoms. This may be more difficult in the approximately 10 percent of patients in whom cataplexy is absent or atypical. A polysomnogram often demonstrates sleep-onset REM (REM sleep within 20 minutes of onset of sleep). A multiple sleep latency test may be more helpful and usually reveals a sleep latency of less than eight minutes with sleep-onset REM in at least two of the four to five tests. [**/*]
PERIODIC LIMB MOVEMENT DISORDER
Restless leg syndrome (RLS) and PLMD are separate conditions, but frequently coexist and probably have a similar aetiology. RLS occurs during wakefulness and is characterized by abnormal sensation and both voluntary and involuntary movements in the legs. PLMD takes place during sleep and is defined polygraphically as periodic activation of the flexor muscles of the lower limb. The muscles usually affected are the toe or ankle flexors. More rarely, the knee, hip and arm flexors are involved. The muscle usually studied is the anterior tibialis and the activation should be between 0.5 and 5 seconds and happen in a series of at least five activations separated by between 5 and 90 seconds. PLMD is diagnosed if at least five activations take place per hour of sleep. The limb movements mayor may not be associated with arousals. PLMDs are believed to be caused by a central oscillator which overcomes the motor inhibition during sleep. They are more common in stages 1 or 2 of non-REM sleep when motor inhibition is less pronounced. RLS is associated with low iron levels but does not appear to improve with iron therapy. PLMD usually presents with excessive daytime sleepiness, difficulty initiating sleep and frequent nocturnal aWakenings. 32 They are frequently not associated with sleep disruption or excessive daytime sleepiness, so should not always be considered to be pathological. 33 [**/*]
IDIOPATHIC HYPERSOMNIA
Idiopathic hypersomnia is generally considered to refer to a heterogeneous group of patients with objectively
Chapter 176 Physiology of sleep and sleep disorders I 2311
confirmed excessive daytime sleepiness in whom all other diagnoses have been excluded. A more limited definition refers to patients with excessive daytime sleepiness that usually presents between the ages of 15 and 30 years and is frequently associated with difficulty awakening, unrefreshing daytime naps and a positive family history.34 This occurs in approximately one in 25,000 of the population. No abnormal neurochemical activity has been determined for this condition and it is believed to be caused by an increase in the intensity of the homeostatic control of sleep. As this is a diagnosis of exclusion, completion of a sleep diary, subjective and objective tests of sleepiness and polysomnography are mandatory. [**1*]
Deficiencies in current knowledge and areas for future research ). The neurochemistry of sleep and wakefulness is poorly understood. The physiological changes that cause upper airway collapse during sleep requires additional study. The stimulus for respiratory-related arousals remains largely unexplained. The long-term consequences of OSAH syndrome need further research.
REFERENCES KEY POINTS • Sleep' is a temporary state of unconsciousness that can, be interrupted by external stimuli. • Sleep has a variety of normal physiological effects on both the upper and lower respiratory systems. • Respiratory sleep disorders are composed of four ,distincLsyndrom~s:, OSAH, .central' sleep apnoea/hypopnoea, "Cheyne-Stokes breathing ·and sleep hypoventilation. • OSAH syndrome is, characterized ,by recurrent episodes of partial or complete, upper airway obstruction during. sleep which are usually terminated bY',an arousal. • Abnormalities in' both upper airway' size and muscle activity appear to contribute to the pathogeriesis of OSAH syndrome. ,. Excessive daytime sleepiness has a broad differential diagnosis. • Narcolepsy is primarily a disorder of REM sleep 'in which REM sleep intrudes 'into nonREM sleep and wakefulness. • PLMD 'usually presents with excessive daytime sleepiness, difficulty initiating sleep and frequent nocturnal awakenings.
* *
Shneerson JM. Handbook of sleep medicine. Oxford: Blackwell Science, 2000. Recent comprehensive textbook on sleep and sleep disorders. 2. Phillipson EA. Control of breathing during sleep. American Review of Respiratory Disease. 1978; 118: 909-39. Definitive review of control of breathing during sleep. 3. Tusiewicz K, Moldofsky H, Bryan AC, Bryan MH. Mechanics of the ribcage and diaphragm during sleep. Journal of Applied Physiology. 1977; 43: 600-2. 4. White DP, Weil J, Zwillich CWo Metabolic rate and breathing during sleep. Journal of Applied Physiology. 1985; 59: 384-91. 5. Stradling JR, Chadwick G, Frew AJ. Changes in ventilation and its components in normal subjects during sleep. Thorax. 1985; 40: 364-70. 6. Weigand L, Zwillich C, Weigand 0, White DP. Changes in upper airway muscle activation and ventilation during phasic REM sleep in normal men. Journal of Applied Physiology. 1991; 71: 488-97. 7. Quinn SJ, Daley N, Ellis PDM. Observation of the mechanism of snoring using sleep nasendoscopy. Clinical Otolaryngology. 1995; 20: 360-4. 8. Gavriely N, Jensen O. Theory and measurement of snores. Journal of Applied Physiology. 1993; 74: 2828-37. 9. American Sleep Disorder Association. International classification of sleep disorders. (Revised). Diagnostic and Coding Manual. Rochester: American Sleep Disorder Association, 1997. 10. Kryger MH, Roth T, Dement W. Principles and practice in sleep medicine, 3rd edn. Philadelphia: WB Saunders, 2000. 1.
* 11. It should not be assumed that a sleepy patient with loud snoring always has OSAH syndrome. Excessive daytime sleepiness requires investigation that may include completion of a sleep diary, subjective and objective tests of sleepiness and polysomnography.
* 12.
American Academy of Sleep Medicine Task Force Sleep Related Breathing Disorders in Adults. Recommendations for syndrome definition and measurement techniques in clinical research. Sleep. 1999; 5: 667-89. Consensus
report on respiratory sleep disorders. Remmers JE, deGroot WJ, Sauerland EK, Anch AM. Pathogenesis of upper airway occlusion during sleep. Journal of Applied Physiology. 1978; 44: 931-8. Classic paper on pathogenesis of obstructive sleep apnoea.
2312 I 13.
PART 16 THE UPPER AIRWAY
Isono S, Remmers J, Tanaka A, Sho Y, Sato J, Nishino T.
obstructive sleep apnea. Journal of Applied Physiology.
Anatomy of pharynx in patients with obstructive sleep apnea and in normal subjects. Journal of Applied 14.
1990; 69: 443-50. 24.
Physiology. 1997; 82: 1319-26.
dependence of pharyngeal cross-sectional area in patients
Fleetham JA. Upper airway imaging in relation to
with obstructive sleep apnea. American Review of
obstructive sleep apnea. Clinics in Chest Medicine. 1992; 13: 399-416. 15.
Respiratory Disease. 1984; 130: 175-8. 25.
and obesity. Journal of Applied Physiology. 1985; 58: 365-71.
Anastassov GE, Trieger N. Edema in the upper airway in patients with obstructive sleep apnea syndrome. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics. 1998; 86: 644-7.
White 0, Lombard R, Cadieux RJ, Zwillich CWo Pharyngeal resistance in normal humans: influence of gender, age
16.
Hoffstein V, Zamel N, Phillipson EA. Lung volume
26.
Petrof BJ, Pack AI, Kelly AM, Eby J, Hendricks
JC.
Redline S, Tischler P, Tosteson TO, Williamson J, Kump K,
Pharyngeal myopathy of loaded upper airway in dogs with
Browner I et al. The familial aggregation of obstructive
sleep apnea. Journal of Applied Physiology. 1994; 76:
sleep apnea. American Journal of Respiratory and Critical
Care Medicine. 1995; 151: 682-7.
1746-52. 27.
Leiter JC, Knuth S, Bartlett
o.
The effect of sleep
17.
White OP. Pathophysiology of obstructive sleep apnea.
deprivation on activity of the genioglossus muscle.
Thorax. 1995; 50: 797-804.
American Review of Respiratory Disease. 1985; 132:
18.
Wheatley JR, Mezzanotte WS, Tangel OJ, White OP. Influence of sleep on genioglossal muscle activition by
1242-5. 28.
negative pressure in normal men. American Review of
ventilatory effort on arousal from sleep. American Review
Respiratory Disease. 1993; 148: 597-605. 19.
McEvoy RO, Popovic RM, Saunders NA, White OP. Effects
of Respiratory Disease. 1990; 142: 295-300. 29.
Aldrich MS. The clinical spectrum of narcolepsy and
30.
Rogers AE, Meeehan J, Guilleminault C, Grumet FC,
idiopathic hypersomnia. Neurology. 1996; 46: 393-401.
of sustained and repetitive isocapnic hypoxia on ventilation and genioglossal and diaphragmatic EMGs. 20.
Journal of Applied Physiology. 1996; 81: 866-75.
Mignot E. HLA OR15 (OR2) and 00B1*0602 typing studies
Popovic RM, White OW. Upper airway muscle activity in
in 188 narcoleptic patients with cataplexy. Neurology.
normal women: influence of hormonal status. Journal of
Applied Physiology. 1998; 84: 1055-62. 21.
1997; 48: 1550-6. 31.
clinical diagnosis of the narcoleptic syndrome. Journal of
Leclerc J et al. Physiologic, metabolic and muscle fiber
Sleep Research. 1998; 7: 41-52. 32.
Coleman RM, Pollack C, Weitzman ED. Periodic movements
hypopnea syndrome and in snorers. Journal of Clinical
in sleep (nocturnal myoclonus): relation to sleep-wake
Investigation. 1995; 95: 20-5.
disorders. Annals of Neurology. 1980; 8: 416-21.
Mezzanotte WS, Tangel OJ, White OP. Waking genioglossal
33.
Nicolas A, Lesperance P, Montplaisir J. Is excessive daytime
electromyogram in sleep apnea patients versus normal
sleepiness with periodic leg movements during sleep a
controls (a neuromuscular compensatory mechanism).
specific diagnostic category? European Neurology. 1998;
Journal of Clinical Investigation. 1992; 89: 1571-9. 23.
Parkes JO, Chen SY, Clift SJ, Oahlitz MJ, Dunn G. The
Series F, Cate C, Simoneau JA, Gelinas Y, St Pierre S, type characteristics of musculus uvulae in sleep apnea
22.
Gleeson K, Zwillich C, White O. The influence of increasing
Hudgel 0, Harasick T. Fluctuation in timing of upper airway and chest wall inspiratory muscle activity in
40: 22-6. 34.
Bassetti C, Aldrich MS. Idiopathic hypersomnia: a series of 42 patients. Brain. 1997; 120: 1423-35.
177 Obstructive sleep apnoea: medical management
DEV BANERJEE
2313
Introduction
2313
The spectrum of sleep-disordered breathing Epidemiology, risk factors and associated medical
2314
conditions Symptoms, clinical examination and assessment of
2315
excessive daytime sleepiness
2315
The diagnosis of obstructive sleep apnoea
2320
Treatment
2322
Follow-up and legal i ssues
2322
Conclusions
2322
Key points
2322
Best clinical practice Deficiencies in cu rrent knowledge and a reas for future research
2323
2323
References
The data in this chapter are supported by a Medline and PubMed search of peer-reviewed articles. Key words used include obstructive sleep apn(0 )ea, obesity, coronary artery disease, cerebrovascular disease, diabetes mellitus, polysomnography and continuous positive airway pressure.
wakefulness-promoting drugs in OSA, is reviewed else
INTRODUCTION
where.2 Obstructive sleep apnoea (OSA) can be regarded as a condition
characterized
by
repetitive
upper
airway
obstruction leading to sleep fragmentation, cardiovascu lar stimulation and oxygen desaturation during sleep. Together,
these lead to symptoms such
THE SPECTRUM OF SLEEP-DISORDERED BREATHING
as snoring,
unrefreshing sleep, excessive daytime sleepiness (EDS),
Any individual may oscillate within a spectrum of sleep
and the increased risk of cardiovascular disease, hyperten
disordered breathing from intermittent simple snoring, to
sion, insulin resistance, cerebrovascular disease and road traffic accidents. With the current growth of obesity, ear,
nose and throat (ENT),
hypertension, obesity, diabetes as
well as sleep clinicians are witnessing a large increase in
the prevalence of OSA in their practices. T his chapter describes the medical management of OSA, especially continuous positive airway pressure (CPAP) , relevant to the work environment of
ENT specialists. Mandibular
chronic
heavy
snoring,
to
upper
airway
resistance
syndrome (UARS), to mild OSA, to moderate OSA, to severe
OSA or to obesity hypoventilation syndrome
(ORS). OS A is characterized by complete breath-holds (apnoeas)
and
partial
breath-holds
(hypopnoeas)
-
scientific physiological definitions will follow in this chapter. Upper airway resistance syndrome applies to individuals with increased inspiratory efforts (as identi
devices are not discussed in this chapter. Readers are
fied by oesophageal pressure measurements) with fre
recommended to refer to a recent review of such devices
quent arousals, as measured from electroencephalography
in OSA.! Pharmacotherapy for EDS, including the role of
(EEG),
during diagnostic overnight polysomnography
2314 I
PART 16 TH E U PPER AI RWAY
(PSG) but without overt apnoeas and hypopnoeas. The fragmented sleep results in increased subjective and objective daytime sleepiness. Few clinical centres measure respiratory effort using oesophageal probes and therefore UARS is probably an underdiagnosed condition. How ever, overnight noninvasive respiratory monitoring for apnoeas and hypopnoeas is easier, in practice, and diagnosing OSA is relatively straightforward. It is standard practice to regard EDS in the presence of OSA as obstructive sleep apnoea/hypopnoea syndrome (OSAHS). Obesity hypoventilation syndrome describes daytime respiratory failure in the presence of obesity (body mass index (BMI) > 30 kg/m2) in the absence of airways obstruction from respiratory spirometry.3 The exact definition of daytime respiratory failure in OHS varies from centre to centre but our sleep centre regards this as a PaC02 > 6.0 kPa (45 mmHg) and Pa02 < 9.3 kPa (70 mmHg). Not all obese subjects with OSA will develop o HS but some subjects with mild, moderate or severe OSA may develop it. The exact mechanism is not totally clear but it is probably a combination of reduced lung volumes as a result of a restrictive spirometry, upper airway obstruction (i.e. OSA) and abnormal central ventilatory responses to CO 2.4 E P I DEM I O LOGY, RISK FACTORS A N D ASSOCIATED ME D I CAL CO N D IT I O N S
Earlier studies of the prevalence of OSA in society (Wisconsin Sleep Cohort Study) estimated that 4 percent of men and 2 percent of women had OSAHS.5 However, since then, the prevalence of obesity has increased in all age groups. A more recent analysis of the epidemiology of OSA has suggested the prevalence of OSAHS is approxi mately 5 percent in a given population,6 but it is likely that this will increase with time. The exact incidence of OSA without EDS is unclear as this population is less likely to seek medical input in the primary care setting. The difference in prevalence between men and women is intriguing and the exact reason for why OSA is more common and more severe in men is not fully understood. Various mechanisms may exist including body fat distribution, craniofacial differences and the role of female hormones, over and beyond simply BMI? There is increasing evidence that ethnic differences exist, and subjects of Chinese origin have a greater risk of developing OSA at a lower level of obesity compared with Caucasian subjects. Craniofacial differences may explain this phenomenon.8 There is little information, however, on the prevalence of OSA in the South Asian population in the UK compared with the indigenous population in South Asia. Obesity is recognized as an important risk factor for OSA. The exact relationship between obesity and OSA is not well understood, and is probably multifactoriaL Factors including BMI, neck soft tissue mass, parapharyngeal and
lingual adipose deposition, and body fat distribution all play a role. Any weight gain is not necessarily wholly adipose and an increase in soft tissue mass around the airway may be more cruciaL Other factors such as pharyngeal muscle tone and the biophysical compliance relationship between airway patency and critical closing pressure remain unsolved. Obstructive sleep apnoea is associated with cardiovas cular disease,9, 10, 11 and clinicians treating and dealing with subjects with OSA are becoming more and more involved in modifying cardiovascular risk in their practice. As shown in population studies, OSA is associated with an increased risk of hypertension. In the Sleep Heart Health Study,12 conducted in over 6000 people aged between 40 and 97, the odds ratio for hypertension in patients with severe OSA after adjusting for BMI was 1 .37 (95 percent confidence interval 1 .03- 1 .83; p 0.005 ) . There is growing evidence that CPAP treatment will decrease blood pressure, and even modest falls in blood pressure may translate into significant modification of cardiovascular risk. Associated co-morbidities such as obesity, diabetes and smoking history may cloud any direct causal relationship between OSA and cardiovascular disease, and further larger longitudinal studies assessing the impact of CPAP therapy on cardiovascular outcomes, particularly coronary artery disease, are warranted. There is growing evidence that sleep apnoea is also associated with cerebrovascular disease,13 with the recogni tion that some subjects with strokes also have sleep apnoea. It is possible that sleep apnoea may become an important modifiable risk factor for cerebrovascular disease. In a cross-sectional analysis, subjects with moderate-to-severe OSA had increased odds for stroke (odds ratio, 4.33; 95 percent confidence interval 1 .32- 14.24; p 0.02) compared with those without OSA after adjustment for known confounding factors.14 In the four-year follow-up data, the odds ratio for having a stroke was raised but not significant after adjusting for age and BMI ( 3.08; 95 percent confidence interval, 0.74- 1 2. 8 1 ; p 0 . 1 2) . The term 'metabolic syndrome' has been increasingly used and described in relation to OSA.15 Metabolic syndrome encompasses a cluster of features related to obesity, diabetes and hypertension. These include waist circumference, triglyceride and glucose levels, and hyper tension. There is an increased incidence of metabolic syndrome in subjects with OSA.16 With increasing evidence that OSA is associated with insulin resis tance,17,18 it is becoming more apparent that OSA will play an important role in metabolic syndrome. In a cross sectional and longitudinal analysis performed in 1 387 participants of the Wisconsin Sleep Cohort, up to 1 5 percent of those with moderate-to-severe sleep apnoea had diabetes mellitus (defined as an abnormal fasting sugar or diabetes diagnosed previously by their physi cian).19 The 'odds ratio for having diabetes mellitus with moderate-to-severe OSA versus those with no OSA was =
=
=
Chapter 1 7 7 Obstru ctive sleep a p n oea : med ica l ma nagement
2.30 (95 percent confidence interval 1 .28-4. 1 1 ; p 0.005) after adjustment for age, sex and body habitus. [***/**] =
SYMPTOMS. CLI N I CAL EXAM I NATI O N AN D ASSESSME NT O F EXCESS IVE DAYriME SLEE PI NESS
The symptoms associated with OSA are: •
•
•
•
•
•
•
• •
•
snoring; fatigue; witnessed breath-holds; gasping and choking; EDS; fragmented sleep; unrefreshing sleep; reduced alertness; mood changes; nocturia.
Clinical assessment of OSA entails a detailed history, ideally with the partner present during the consultation. The partner may be able to describe the breath-holding, associated gasping, movement arousals (associated with the apnoeas) , and may possibly display a raised level of anxiety. Many couples may express marital strife and hence it is prudent for the clinician to regard their issues with compassion. Even if the subject with possible OSA is banished to the next bedroom, the witnessed apnoeas are still present by the pauses in the audible snoring. Some patients may have had OSA for many years and therefore have become accustomed to their EDS and consequently may underestimate their symptoms. An appreciation of their sleep patterns is important as one of the commonest causes of EDS is sleep deprivation rather than sleep fragmentation (i.e. �SA) . Shift work-related sleepiness is also a well-recognized phenomenon and may coexist with OSA. Some will relate how EDS may affect their working lives, especially those who work with heavy machinery or drive buses, lorries and trains. A history of road traffic accidents, therefore, is vital as individuals with OSA are at higher risk of them, at considerable cost. 2 0,2 1 Although individuals may not have had crashes as a result of falling asleep at the wheel, subtle clues such as drifting across lanes, clipping the kerb or a history of being honked at by other drivers, are part of the detailed history assessment. A physical finding that is particularly relevant during an OSA consultation is the presence of central obesity. A BMI greater than 28 kg/m2 should increase the suspicion for OSA. Neck circumference is a useful measure; above 43 cm ( 1 7 inches) may be predictive. Other important examination features include a detailed nasal and oropharyngeal assessment including the Mallampati score, 22 the presence or absence of retrognathia, cranio facial abnormalities and tonsillar hypertrophy. Associated medical conditions such as hypertension, diabetes and
I 2315
hypertriglyceridaemia should always be looked for during the consultation. Unfortunately, the assessment of history and clinical findings have been shown to lack sensitivity and specificity in diagnosing OSA. It is estimated that history and examination can only predict OSAHS in 50 percent of patients, 2 3 and that the male sex, snoring and BNII were found to be useful predictors of OSAHS. 2 4 The measure ment of EDS may be subjective and objective. The commonest subjective questionnaire used is the Epworth Sleepiness Scale (ESS), named after the Epworth hospital, Victoria, Australia (see Table 177.1) . 2 5 A score above 1 0 (out of 24) may indicate EDS but the ESS lacks sensitivity and specificity, therefore, in an individual, the ESS may not on its own be very useful, but only a guide. This author does not recommend clinical decisions based purely on the ESS. Objective measurements of EDS include the multiple sleep latency test, which measures how quickly an individual can fall asleep, and the maintenance of wakefulness test, which measures how long an individual can stay awake. However, such diagnostic tests can only be measured if full PSG, including EEG, are available. [**]
THE D IAG NOSIS O F OBSTRU CTIVE SLEE P APNOEA
As the sensitivity and specificity of clinical examination to diagnose OSA in the clinic setting is poor, other tools are necessary. These can best be described as domiciliary single channel (overnight oximetry) , domiciliary multi channel (respiratory and oximetry signals) and in hospital full PSG, which includes measurement of respiratory, oximetry and sleep architecture assessment using EEG, electrooculography (EOG) and electromyelo graphy (EMG). The merits of each tool are discussed next. Table 1 7 7. 1
The Epworth Sleep i n ess Scale a ssesses the
li ke l i hood of a n i n d ividual dozing off i n the fo l lowing situations. Score
Activity
Sitti n g a n d rea d i n g Watch i n g television Sitt i n g , i n a ctive i n a p u b l i c place (e.g. a theatre or a meetin g )
As a passenger in a ca r for an hour without a b rea k Lyi n g down to rest in the afte rnoon when ci rcumsta n ces perm it Sitting and ta lki n g to someone Sitti n g quietly a fter a l u nch without a lcoh o l I n a ca r, w h i le sto p ped fo r a few m i n utes i n traffic Score:
0 = never; 1
=
slight chance; 2
=
moderate chance; 3
=
high chance
of dozing. Adapted from Ref. 22., with permission from the Associated Professional Sleep Societies,
LLC.
2316
I PART 16 TH E UPPER AI RWAY
Overnight oxi metry This device measures oxygen saturation and provides pulse rate data. It assumes that when an individual has an apnoea or hypopnoea, the oxygen saturation falls. Once the apnoea or hypopnoea is relieved, the oxygen desaturation recovers. The falls and rises are regarded as 'oxygen dips'. The gadget is sited at the end of the digit, with a (wristwatch' device that the patient wears during the night. This is where the data are collected. The device can be worn at home. Some software products provide pulse rate variability (e.g. the number of pulse rises of over six beats per minute averaged per hour) which reflect autonomic cardiovascular changes during arousals as a result of apnoeas and hypopnoeas. However, pulse rate variability can only be analyzed in the presence of sinus rhythm rather than in subjects with atrial fibrillation. In the UK, some sleep clinicians use oximetry alone as a screen for OSA. It is standard practice that a dip of 4 percent oxygen saturation, for example from 94 to 90 percent, is regarded as more meaningful than a 2 or 3 percent dip. An oxygen desaturation index (ODI) (i.e. the number of times the oxygen saturation falls by 4 percent averaged out per hour) of over 15 per hour may be suggestive of OSA. The presence of other associated features that may tend towards a diagnosis of OSA include ESS > 10, obesity (BMI > 28 kg/m2) and co morbidities, for example hypertension, coronary artery disease, metabolic syndrome and diabetes mellitus. However, an ODI > 15 per hour can only be used if the resting saturation of oxygen is above 90 percent and there is an absence of obstructive airway disease. Figures 1 77.1 and 1 77.2 show a classic case of repetitive oxygen desaturation, typical of OSA. Unfortunately, studies using overnight oximetry as a screening tool for OSA have shown good specificity and positive predictive value but poor sensitivity and negative predictive value?6 In other words, overnight oximetry may miss subjects with OSA who do not desaturate, but in the presence of a positive result oximetry can be a useful screen. However, an abnormal ODI may under estimate the true severity of OSA, as demonstrated in
Figures 177.3 and 1 77.4. In general, it is accepted that young, less obese subjects may not have oxygen desaturations in the presence of apnoeas and hypopnoeas and therefore will not be identified by oximetry. The reasons why some patients desaturate and some do not are unclear but may be related to lung volumes, functional residual capacity or central respiratory re sponse to apnoeas (i.e. if an arousal response to airway obstruction is blunted then the individual is more likely to hypoventilate and desaturate). If the ODr is less than 15 per hour but there is the presence of EDS, obesity or existing co-morbidity, then the author would recommend those clinicians who use oximetry to screen for OSA to refer further to clinicians where multichannel assessment of respiration is available. The author would not advocate a trial of CPAP in those patients where the diagnosis and severity of OSA is in question due to a negative oximetry study. [Grade B/C/D]
Home multichan nel testing The advantages of home, overnight respiratory monitor ing over in-hospital studies are multiple and include better patient comfort, cost savings, prevention of hospital admission and speed of analysis data. Disadvan tages include sensor failure at home and loss of signal (which may lead to repeat studies). Fewer signal channels will mean less information is available. However, home monitoring without EEG will not determine when the patient is asleep during the night. Sleep-disordered breathing occurs during sleep, and it may be possible that without an assessment of exact sleep time, home monitoring may underestimate the severity of OSA. Some home, portable kits also include EEG probes to determine sleep architecture. However, in the UK, the multichannel kit that utilizes nasal/oral flow (by use of pressure cannulae), chest and abdominal movements (by use of a Velcro belt) and pulse oximetry (end of the digit), are most popular (see Figure 177.5). A classic example of repetitive apnoeas is demonstrated in Figure 177.6. The chest and abdominal belts allow the assessor to determine
Spo2 100 80 60 40 20
Figure 17 7.1
A su bj ect with an 001 of 55 4 percent oxygen dips per hour. This trace shows the whole night's data. Minimum oxygen
saturation is approximately 45 percent.
Chapter 1 7 7 O bstructive s l eep a pnoea : medica l m a n a ge m ent
I 2317
Start time + Date. 22.41.00 06/09/2003
Y-axis from 70% to 100%
Hour
r-��----���-����77��'---��
2
3
4
5
6
7
Figure 1 7 7.2
The sa m e patient as in Figure 177.1, showing the oxyg en d i ps in d eta i l . X-axis is one hour. Y-axis is 70-100 percent
saturations. Note the ma rked repetitive desaturations of oxyg e n , typical of OSA. Th ere are occa s i o n a l d i ps below 70 percent.
Sp 02
100
Saturation f�������"��'' '��''' -�-- �����'������
80
60
40 20
Figure 1 7 7.3
Th is s u bject has an O D I of 22 4 percent oxygen d i ps per h o u r, B M I is 36 kg/m 2 a n d ESS score is 6, a n d not as m a rked as
the exa m p l e i n Figure 177.1. The m i d-rea d i n g s i g n a l to zero is a n artefact.
whether the apnoeas and hypopnoeas are related to respiratory effort (during the apnoea or hypopnoea, the chest and abdominal signals still display movement) and, therefore, obstructive in nature, as opposed to central sleep apnoea where there is no chest or abdominal movement (no effort) during apnoeas. As the name describes, central sleep apnoea originates from the central respiratory drive centre of the brain and occurs occasionally in subjects with cerebrovascular disease. One form of central sleep apnoea known as Cheyne Stokes respiration ('crescendo-decrescendo' chest and abdominal movements) is more common in patients with hea'rt the origin of the apnoeas (i.e. obstructive versus central) in such patients.
Patients are taught how to apply the gadgets, either at home or in the hospital physiology department. The patient either goes home already set up or they prepare themselves later in the evening. The portable kit is returned the next day and the data are analyzed. The kits allow automated analysis of the data, but the author recommends that a trained clinician or technician scores the data, thus avoiding the possibility of the software incorrectly scoring apnoeas and hypopnoeas. An apnoea is regarded as a completed cessation of airflow for at least ten seconds regardless of whether there is an associated oxygen desaturation or arousal. The definition of hypopnoeas (partial breath-holds) varies from centre to centre but the author regards them as a reduction in airflow (amplitude of signal) of between 50
2318 I
PART 16 TH E U PPER AI RWAY
Start time + Date: 23: 13:00 05/10/2005
Y-axis from 70% to 100%
Hour ������==��N\i��
2
3
4
5
6
7
8
o
Figure 177.4
10
20
30
40
50
60
Shows close up of oxygen d i ps from Figu re 177.3. X-axis is one hour a n d Y-axis is 70-100 percent oxygen saturations.
Repetitive but i nterm i ttent oxygen desaturations were seen, pa rticu l a rly 2 and 3 percen t d i ps. The patient underwent a dia gnostic PSG s howing severe OSA, a pn oea/hypopnoea index of 73 per hour. Therefore, i n this case, the overn ight oximetry on its ow n underesti mated the true severity of OSA.
and 90 percent (with or without a 3 percent or more oxygen desaturation and/or EEG arousal) or a reduction in airflow of less than 50 percent, which must be accompanied with a 3 percent or more oxygen desatura tion and/ or EEG arousal. If the airflow signal is missing due to mouth breathing or displaced oronasal cannula, amplitude changes in the thoracic and abdominal wall movement signals can be used to determine whether apnoeas or hypopnoeas are taking place (see Figure 177.6). It must be pointed out that the respiratory kit actually measures change in pressure rather than strictly changes in flow within the oronasal cannulae, and a pressure transducer detects this. The changes in pressure signal are proportional to airflow and any change in signal can be regarded as a change in airflow. [Grade D] Overnight polysomnography
The disadvantages of in-hospital overnight PSG com pared with domiciliary multichannel testing have been stated above. However, there are some patients whose assessment is more complex than straightforward OSA and they may need further respiratory monitoring, such as transcutaneous CO 2 testing, particularly if OHS is suspected. Other patients, such as those with neuromus cular disorders, may need in-hospital assessment,
especially if assisted ventilation is considered. Tertiary sleep centres will experience a variety of sleep disorders where the EEG, EOG and EMG component of the PSG is essential, for example narcolepsy, parasomnias, periodic leg movement syndrome, etc. A sleep technician will prepare the individual in the evening. The patient stays overnight at a sleep centre, most of which have video monitoring throughout the night. In some centres the technician observes the signals from a central computer room during the night. This allows for any troubleshoot ing, such as disconnected leads, but also allows more complex assessments, for example trials with assisted ventilators or titration with CPAP machines. In some centres, whether the technician stays overnight is dependent on staffing and funding. In cases where the PSG is unattended, should leads become disconnected with a subsequent loss of signal, a repeat may be necessary. [Grade D] Which test should be used?
The issue of whether a PSG should be regarded as the 'gold standard' is highly debated in the sleep medicine fraternity. The Standards of Practice Committee of the American Academy of Sleep Medicine have indicated that PSG should be the investigation of choice to diagnose
Chapter 1 7 7 Obstructive s l eep apnoea: medical m a n agement I
sleep-disordered
breathing.27
However,
other
2319
centres
hotly debate this and, in reality, not all ENT clinicians will have access to tertiary centre PSG facilities?8 Local availability of services as well as health resources and funding will determine the
route of the diagnostic
procedure. The author recommends that if oximetry alone is used to screen for OSA, then borderline or uncertain cases should be referred for more detailed respiratory monitoring. The key to accurate diagnosis and management
is adequate training in assessing sleep
disordered breathing with expertise in sleep physiology analysis so that the clinician is aware of the limitations of each
diagnostic procedure. [Grade Dl
Criteria for the diagnosis of obstructive sleep apnoea The number of apnoeas and hypopnoeas averaged per hour of sleep is regarded as the apnoea/hypopnoea index (AHI). Some centres use the term respiratory disturbance index,
which
incorporates
the
number
of apnoeas,
hypopnoeas and respiratory effort-related arousals. The latter are diagnosed by EEG arousals associated
with
respiratory effort (from intraoesophageal pressure mea
Figure 1 77.5
The author demonstrating a home respi ratory
monitoring kit, includ ing oronasal ca nnulae, thoracic and
abdomi nal bands, and finger oxi metry probe. The kit can b e programmed t o switch o n and o ff a t set times.
surement) in the absence of apnoeas
and hypopnoeas.
However, as intraoesophageal pressures are seldom used, the term AHI is more reflective of clinical practice and is popularly used. If home respiratory monitoring testing is carried out, an estimate of the number of hours slept by the individual is necessary. A common mistake is to calculate
Figure 1 77.6
the total number of apnoeas and hypopnoeas
A cl assic exa mple of OSA w ith repetitive apnoeas. X-axis is five m i nu tes. The t op trace is the oronasal cannulae flow,
the second the thoracic band, the third the abdomi nal band, the fourth trace is oxygenation a n d the fifth is pulse rate. Note the marked d esaturations of oxygen w ith each apnoea, which recovers once the ap noea has ended, and becau se of lag time effect, the nadir of oxygen saturation a lways follows the ap n oea.
2320 I
PART' 6 THE UPPER AIRWAY
and then divide this number by the total number of hours of respiratory recording and not sleep time. The severity of OSA has been arbitrarily defined as: • • • •
no evidence of OSA if the AHI is less than five apnoeas and hypopnoeas per hour; mild OSA if the AHI is five or more and less than 15 apnoeas and hypopnoeas per hour; moderate OSA if the AHI is 15 or more and less than 30 apnoeas and hypopnoeas per hour; and severe OSA if the AHI is 30 or more apnoeas and hypopnoeas per hour.
It is important to note that these criteria do not take into account the desaturation index nor the length of apnoeas and hypopnoeas.
TREATMENT When to treat
When to treat varies from centre to centre. Our centre would not treat mild OSA without EDS and/or existing co-morbidities (i.e. hypertension, cardiovascular disease, coronary artery disease, diabetes mellitus) with CPAP. Lifestyle changes such as weight loss (particularly if the BMI is greater than 25 g/m2) and/or treatment of any troublesome rhinitis are recommended. However, if subjects have mild OSA with EDS and/or co-morbidities, or moderate-to-severe OSA with or without EDS and co morbidities, then treatment with CPAP therapy would be considered. [Grade C/D]
How to treat CONTINUOUS POSITIVE AIRWAY PRESSURE
First described in 1981,29 CPAP is regarded as the mainstay of OSA treatment,30 and has been of particular benefit in technological advances. The mode of action can be regarded as a 'pneumatic splint', whereby blowing air via a tube and mask through the nasal and/or oral passageway, will support the pharyngeal and palatal walls, preventing collapse of the airway. [****] The equipment
Continuous positive airway pressure machines provide either a constant blowing pressure (fixed pressure) or vary pressure depending on the presence of apnoeas. The latter system, delivered by autoCPAP machines, relies on an algorithm set in the machine mechanics, whereby a cessation of flow (i.e. apnoea or hypopnoea) is detected by the machine and results in the machine blowing the appropriate flow (and therefore pressure) to overcome the apnoea or hypopnoea. This assumes a closed system between the machine and the patient (i.e. no leaks) . The
autoCPAP may confer more comfort to the patient but no trials have suggested that clinical outcomes of autoCPAP are superior to fixed pressure machines. The masks may essentially be nasal or full face. Patient preference will determine which mask is chosen, but those patients choosing a nasal mask must ensure no mouth leaks occur. Sometimes, chin straps to keep the mouth closed are used. Most masks are kept in place by Velcro straps. All masks must have an expiratory port to prevent reinhalation of expiratory air. All patients are reminded to clean their masks and strappings regularly to ensure prolonged longevity. The newer machines are smaller and lighter to allow portability. All new machines have an internal mechanism enabling voltage switching between 220 and 110 volts depending on where the user is in the world. The ease of using CPAP on planes is variable among different airlines.31 The use of an inverter mechanism will allow a CPAP machine to be driven from a DC battery pack. Those who suffer from nasal congestion can use a humidifier. [Grade D] Setting up on continuous positive airway pressure
Centres differ in how a subject with OSA is set up on CPAP. All centres should have comprehensive education programmes to ensure that patients have a better understanding of their illness and to guarantee acceptable long-term CPAP compliance. Some centres undergo group video workshops. A trained technician who understands the technology and appreciates where problems may arise should carry out the CPAP set-up. Patients differ as to what level of pressure is necessary to eliminate the vast majority of apnoeas and hypop noeas. The method of determining this opening of airway pressure differs from centre to centre. Some use a mathematical equation and one example that has shown reasonable correlation with titration studies is predicted pressure (cm H 0) (0.16 x BMI) + (0.13 x NC) + 2 (0.04 x AHI) 5.12, where NC is neck circumference (cm) . 32 Another method of titration is to admit a patient for overnight diagnostic PSG, and halfway through the night, when the severity and the diagnosis of OSA have been confirmed, to commence CPAP for the second half of the night. This is referred to as a split night. The process must have a supervising technologist, and a big disadvantage may be that the true severity of OSA may not be determined by half a diagnostic night. There is, however, the bonus that both diagnostic and CPAP titration are performed on the same night, therefore, saving an extra admission. The CPAP titration technique is carried out by a technician from the central computer room, linked up electronically to the subject's bedroom and CPAP machine. The starting pressure is usually approximately 4 cm H 0 and the pressure is increased 2 quickly until all apnoeas and hypopnoeas are eliminated. The majority of centres will reach the required pressure to eliminate most 'apnoeas and hypopnoeas within an hour, and the rest of the night is spent fine-tuning and =
-
Chapter 1 7 7 O b structive s l eep a pnoea: medical ma nagement
troubleshooting, for example mask leaks or the need for supplemental oxygen in some cases. Another technique increasingly used is to send the subject home with an autoCPAP machine. Most auto CPAP machines will collect data on compliance, leaks and pressure profile. A trial of between 7 and 14 days may allow better adjustment to the concept of CPAP rather than an autoCPAP trial of one night. In general, autoCPAP machines are more expensive than fixed pressure machines (£450 versus £250) and, as a result, in the UK, funding from primary care trusts (PCTs) is predominantly for fixed pressure machines. In our centre, the set fixed pressure is the 95th centile pressure (i.e. the blowing pressure to eliminate 95 percent of apnoeas and hypopnoeas) , as determined by the autoCPAP data. The funding for CPAP machines is variable throughout the UK, and is usually dependent on the individual PCT. Our centre, for example, has set up a 'volume-demand' contract with individual PCTs, however, unfortunately not all patients that the centre covers will have readily available funding. Some patients decide to self-fund to bypass waiting lists. Currently, there are no guidelines on CPAP therapy as recommended by the National Institute of Clinical Excellence. However, the Scottish Intercollegi ate Guidelines Network has produced useful recommen dations on the management of OSAHS in adults.33 [Grade D] Side effects
Most side effects are related to the nasal/face mask (the interface) . Claustrophobia can be a problem for some patients, and increasing the choice of mask from full-face, to nasal, to an interface that sits on the nostril edge (nasal pillows) may be one solution. However, with patience, education and reassurance (an experienced technician is key here) , we manage to alleviate most claustrophobia issues. Nasal stuffiness is a common troublesome side effect, and although interface technology has greatly improved recently, it can lead to poor compliance. Coryzal illnesses can also lead to poor usage in those patients with nasal masks. The use of heated humidifica tion is recommended as one solution.34 Cold and dry air may provoke mucus production and vasodilation in the nasal mucosa and humidification can potentially address this. Although nasal corticosteroids and/or corrective surgery for mucosal thickening and polyps might be considered, the author believes that a full-face mask may be a simpler solution. Other side effects include skin abrasions and leaks and both are usually related to poorly fitting masks. Leaks can be a nuisance especially if directed towards the eyes. lll fitting masks can even lead to ulceration of the bridge of the nose. The patient has to be reminded that a good fit rather than a tight fit is more likely to be successful in eliminating leaks without skin and eye trauma. Other problems include air swallowing and pulmonary baro traumas, although the latter is very rare. Air swallowing
I 2321
may be more likely if the pressure delivery is greater than physiological oesophageal sphincter pressure. [Grade C/D] Treatment failure
Despite the intensive support there are patients in whom treatment has clearly failed, the usual cause being poor tolerance to CPAP. Treatment failure can therefore lead to continued symptoms plus a continued risk of co morbidities, particularly cardiovascular, cerebrovascular diseases and diabetes. The sleep apnoea physician must convey the risks attached to nontreatment of OSA, in particular, the relevance of driving safely. Other alter natives, such as weight loss therapy in those who are overweight should be considered as well as mandibular devices or other forms of surgery, as discussed else where. The author feels that tracheostomy should be regarded as a last resort in very exceptional circum stances. [Grade D] Compliance and troubleshooting
Compliance or CPAP usage is dependent on many factors. It is expected that by three years 1 2-25 percent of subjects will have discontinued treatment.35 Compliance to CPAP has been defined arbitrarily in the literature as use of CPAP for over four hours for at least five nights per week. The biggest factors to determine long-term compliance are the improvement of symptoms after commencing CPAP therapy and how severe the OSA is in the individual. 35 What is unclear, when faced with an individual about to commence CPAP therapy, is whether four hours for five nights per week is enough to reduce the risk of road traffic accidents or future co-morbidity. Therefore, at our centre, all patients are encouraged to use CPAP for at least seven hours, seven nights per week. Adequate education, close follow-up by an experienced technician and motivation of the patient will all influence the long-term use of CPAP, similar to any new treatment process, such as inhaler therapy in asthma. When CPAP failure does occur, addressing side effects and the possibility of coexisting sleep disorders, such as shift work-related sleepiness, narcolepsy, psychological illness or drug-induced conditions, should be considered. It is not uncommon for an individual to have two coexisting sleep disorders. It has been suggested that one advantage of autoCPAP over fixed pressure CPAP is an improvement in long-term compliance because pressure can be altered as appropriate to the apnoea severity during the night, and also the average pressure can be reduced throughout the night. However, although autoCPAP may increase comfort, there is no evidence to suggest that compliance or symptoms of EDS, compared with fixed pressure CPAP, are improved.36 Until there are definite cost benefits shown for autoCPAP over the fixed pressure CPAP machine, there is no justification to provide autoCPAP machines on the National Health Service (NHS) in the UK. [Grade A/C/D]
2322
I PART 16 THE UPPER AIRWAY
FO LLOW- UP A ND LEGAL I SS UES
cessation of breath using multichannel equipment. The treatment of sleep apnoea has evolved from only treating
At the time of diagnosis of OSA, the individual is recommended to inform the Driver and Vehicle Licensing
snoring and breath-holding to treating the symptoms and modifying cardiovascular risks. The role of OSA in road
Authority (DVLA), Swansea, UK, of the diagnosis. The
traffic accidents continues to provoke emotions within
diagnosis, and the emphasis to do so is placed on the
medical community to raise the profile of sleep apnoea in
subject with OSA and not the sleep clinician. In reality,
UK politics.
many subjects do not inform the DVLA as treatment for
treatment but emphasis must also be placed on lifestyle
OSA (Le. CPAP) is not available for up to a year in many
changes such as weight loss strategies.
DVLA, according to UK law, must be notified of the
the media, and there is a drive from the sleep apnoea CPAP remains the mainstay of medical
parts of the country. There is little incentive, therefore, for a patient to notify the DVLA and then be told that, potentially, their license will be withdrawn for up to one
KEY POI NTS
year until CPAP therapy is established. Improved funding for
CPAP
machines on the NHS will improve this
•
situation. However, those patients deemed to be a genuine threat to the public by continuing to drive while sleepy may be considered for notification by the sleep physician,
•
despite potentially breaking rules of patient confidentiality. Follow-up CPAP clinics aim to determine compliance, minimize intolerance, improve symptoms (e.g. reduced
•
sleepiness) and continue to modify cardiovascular risk factors. Follow-up P SG with CPAP is not necessary. Some
•
centres repeat overnight oximetry with CPAP, but an abnormal tracing may not necessarily differentiate poor
•
compliance from inadequate treatment pressure. A sig nificant increase in weight over time may lead to snoring with the mask on and an increase in the fixed CPAP
•
pressure may be necessary. Mask components wearing out may cause leaks around the mask, but if the mask is well
•
looked after it should last for up to a year. CPAP machines that are provided on the NHS must be electrically serviced
•
and checked by an engineer on an annual basis by law. The equipment technically belongs to the centre providing the machine and therefore it is the responsibility of that centre to ensure that it is electrically safe. During servicing, the
The incidence of obstructive sleep apnoea will grow as the prevalence of obesity increases in aU age groups. . Sleep apnoea is associated with co morbidities such as cardiovascular disease, diabetes mellitus and cerebrovascular d,isease. Subjects widi) sleep apnoea arc at a higher risk of road traffic accidents. Body mass index and male sex are important risk factors. History and clinical examination is not a
sensitive or specific
apnoea.
way of diagnosing sleep
Further investigation including muftichannef
is the key to diagnosis. is the mainstay of treatment tD sleep apnoea. The aim to minimize intolerance, improve symptoms of sleep apnoea and modify cardiovascular risk factors is essential in all CPAP clinics. respiratory testing
CPAP
engineer will routinely download usage data from the machine and this will provide useful compliance informa
tion. Subjects with moderate-to-severe OSA who have poor
compliance are a challenge to the sleep clinic. Reasons for noncompliance are addressed but if the subject refuses treatment with CPAP then other solutions, such as weight
I
Best clinical practice
-
�.
"
...
"
,
�: ' .
.1.'
./ Managing a p ati ent with OSA should not focus only
loss, mandibular devices, surgery, etc., may be considered.
on the upper airway but consider other co
The subject should be reminded of the issues of driving
morbidities such as obesity, cardiovascular disease,
with OSA without treatment. [Grade D]
diabetes. road traffic safety and social disharmony.
./ Initial investigation for OSA must include some
objective evidence of physiological derangement
CO N CLUSIO NS
suggestive of it, e.g. repetitive oxygen desaturations
Obstructive sleep apnoea is increasing in prevalence and
abdomen movement changes.
and/or airflow cessation with concomitant thorax and
more patients are presenting to the ENT physician with snoring and sleep apnoea. Obtaining information, in particular the symptoms associated with OSA as well as
./ The treatment of choice for moderate-to-severe OSA is CPAP treatment.
./ To ensure adequate compliance to CPAP early in the
the presence of EDS and other co-morbidities, should be
treatment process, troubleshooting by skilled
routine in the consultation. Diagnostic strategies may
technicia�s, I.e. mask fitting, leaks, discomfort and
vary between different departments but the fundamental
claustrophobia, is essential.
basis of diagnosis of OSA rests with the demonstration of
Chapter 1 7 7 Obstructive sleep apnoea: medical m a nagement
a p n ea, a n d hyperten sion in a l a rge com m u n i ty-based study. Sleep Heart Health Study. Journal of the American
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Mohse n i n V. Is sleep a p n ea a risk factor for stroke? A
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1 78 Th e s u rg i ca l m a n a g e m e n t o f s n o ri n g
M A R C E LLE MACNAMARA
Defi nitions and e p i dem iology of adu lt snori ng
2325
N onsu rg ical trea tments of snori n g
2333
C l i n ical presentation
2326
Concl usions
2333
Preoperative i nvestig ations
232 6
Key poi n t s
2334
Ind ications for surgery
2329
Best cl inical practice
2335
Su rgical techniques
2 329
Deficiencies i n cu rre n t knowledge and areas fo r future
Posto perative care
2332
Compl ications
2332
Ackn ow l edge m ents
2335
Short- and long-term o u tcomes
2332
References
2335
The data in epidemiology,
research
2335
this chapter are s upported by a Medline search using the key words adult snoring surgery, snoring snoring
aetiology, snoring cli n i cal presentati on,
sno r ing s u rgery p reoperative investigations,
sleep
nasendoscopy, sno ring imaging, snoring su rgery indications, snoring su rgery techniques, sno ring surgery postoperative care, snoring surgery complications, snoring surgery outcomes and nonsurgical treatments fo r sno ring. Evidence is based
at levels
2 and
3.
DEFI N ITIONS AND E PI DEM I O LOGY OF AD U LT SNORING
with repetitive partial ai rway collapse which" generates the
S imple snoring is defined a s snoring with o u t obstructive
compliance and resistance.
so u nd of s n oring. The critical insp i ratory flow rate that causes snoring is dependent o n upper a i rway size, shape,
apnoeas, frequent a ro usals or gas exchange abnorm alities. It
is generally considered
growing evidence
ben ign,
however, there
is
in children, but not adults, that i t is
not as innocuous as is usually believed (see Chapter 85,
Simple snoring is part of the sp ectrum of sleep disordered breathing ranging from intermittent snoring, through obstructive sleep apnoea/hypopnoea syndrome, to obes ity hypoventil ation syndrome. Recently, i mproved
Obstructive sleep ap noea i n ch ildhood) . Snoring is the
definiti o ns
low frequency sound p roduced by vibration of the upper
allowed clearer clari fication of the syndromes within this
airway walls during partial u pper airway obstruction ( see
spect r u m . l
These vibrations usually occur in the soft palate, but
tl0 n,2 active and passive smoking,3 obesity,4 reflux/ male
Chapter 1 76 , Physiology of sleep and sleep diso rders ) .
approximately
30
in
percent of non apnoeic snorers they may
also be p resent at other sites
inclu cti ng the
tonsils,
epiglottis and b ase of th e tongue. Theoretical
modelling
has
shown
and
better
monitoring
techniques
have
Aggravating factors may include alcohol consu mp gender4 and i nc reasing age.4 [ * * * ] I t is not known whether persistent paediatric risk factors, s uch as low socio eco nomic status, nasal obstruction, previous tonsil and
th at
at
critical
inspiratory flow rates the upper ai rway becomes u nstable,
adenoid su rgery, a re relevant i n adul ts . Although mild-to moderate
sleep
apnoea
is
frequently
a
progressive
2326 I
PART 1 6 TH E U PPER AIRWAY
condition, there are no studies in the literature which address this question in simple snorers.
- there is a long redundant soft palate with swollen uvula; - the palatine ± lingual tonsils are enlarged; - the tongue base is prominent; - there is a large floppy epiglottis; - there is bilateral vocal cord palsy or Shy-Drager syndrome; - there is dental malocclusion and or a large tongue.
CLI N I CA L PRESE NTATION
Before considering a patient for surgery for snoring the following clinical categories need to be addressed.
History
When taking the patient's history the following questions should be asked. •
• •
• •
•
•
•
•
Does the patient snore? Is the patient or their partner troubled by the snoring problem? How severe is the snoring? Audible if: - in the same room? - in an adjacent room? - downstairs/anywhere in the house? - next-door neighbour? Is the snoring positional or does it occur in all sleep positions? For how long has the patient been snoring? Are there clinical features suggestive of obstructive sleep apnoea (OSA) : - regular multiple apnoeic episodes most nights? cerebrovascular complications of OSA such as stroke, hypertension, myocardial infarct? - endocrine complications or co-morbidity such as diabetes mellitus or hypothyroidism? Are there any aggravating factors: - alcohol, how many units per week? - smoking how many per day? Passive smoking? - current weight and whether this is increasing? - previous tonsil and adenoid surgery as a child? - other upper aerodigestive tract abnormalities? Have any conservative treatments been tried, such as weight loss, mandibular advancement splints (MAS) or nasal valve dilators? Does this patient represent an anaesthetic risk: - is the airway anatomically difficult? - does the patient have cardiovascular, respiratory or cerebral disease that would significantly increase risks of anaesthesia?
Examination
The patient should be examined and certain measure ments taken. •
Examine the nose, oropharynx, hypopharynx and larynx to establish whether: the nasal airway is patent; the postnasal space is small; _
Examination can be carried out easily with a flexible nasendoscope apart from the oral cavity, which requires direct inspection. Often, this proves to be normal in the awake patient, or it may demonstrate relative narrowing or obstruction at any level. The Mueller manoeuvre does not satisfactorily predict the level of airway obstruction during sleep. • •
Measure height, weight to calculate body mass index and collar size. Examine the cardiovascular and respiratory system to establish potential OSA complications.
At initial consultation the Epworth Sleepiness Scale (Figure 1 78. 1 ) is usually completed, although this cannot reliably distinguish between patients with simple snoring and OSA7 as patients can maximize and minimize their symptoms. Also, poor sleep quality may be attributable to microarousals in relation to loud snoring, and the snoring sound itself may also contribute. A combination of clinical history, Epworth sleepiness score and body mass index can be used to screen out nonapnoeic snorers with a sensitivity of 93 percent and specificity of 60 percent.8 The criteria for defining apnoeic status on clinical assessment are: • •
• •
•
•
•
symptoms of obstructive sleep apnoea/hypopnoea syndrome; nocturnal choking; daytime sleepiness; witnessed apnoeic events during sleep; morning headaches or waking with a sensation of heavy head with no alcohol consumption the previous night; Epworth sleepiness score 2:: 15; body mass index 2:: 28 kg/m2•
PRE O PE RATIVE I NVESTI GATI O N S
A number of techniques are used t o evaluate patients who snore. These include: • •
• •
• •
•
videoendoscopy; sleep nasendoscopy ± video; polysomnography; oesophageal manometry; cephalometry with Mueller manoeuvre; fluoroscopy; three-dimensional computed tomography (CT);
Chapter 1 7 8 The surg i ca l management of snoring
I 2327
EPWORTH SLEEPINESS SCALE How likely are you to doze off or fall asleep in the following situations in contrast to just feeling tired. Use the following scale to choose the most appropriate number for each situatio n :
o
=
Would never doze
1
=
Slight chance of dozing
2
=
Moderate chance of dozing
3
=
High chance of dozing
Situation
Chance of dozing
Sitting and reading Watching television Sitting inactive in a public place (theatre or meeting) As a passenger in a car for an hour without a break Lying down for a rest i n the afternoon Sitting and talking to someone Sitting quietly after lunch without alcohol
Figure 1 7 8. 1 In a car while stopped for five minutes in traffic
The E pworth Slee p i n ess Sca le.
Ada p ted from Ref. 6, with perm ission from the Associated Professional Sleep Societies, LLC.
•
•
•
dynamic ultrafast magnetic resonance imaging (MRI); acoustic analysis; nasal spray test.
These techniques should be used to address four questions. 1 . Is snoring present and how severe is it? Can OSA be diagnosed and ruled out? 3. Can the site(s) of snoring be identified? 4. Is there relevant co-morbidity? 2.
Is snori ng prese nt a nd how severe is it?
Acoustic analysis of snoring is helpful in determining the volume and duration of snoring but is only of limited use in detecting the site of snoring.9 A simple tape recording made by the patient may be sufficient evidence. It may also be a useful research tool to evaluate the impact of various environmental and patient factors on the severity of snoring. 1 0, 11 [ ***/** ] Using the Glan Clwyd snore box, a simple device developed for objective measurement of the loudness and duration of snoring, it has been shown that the severity and duration of snoring is greater at home than in hospital, thus making home screening important. 1 2
CAl\! OBSTRUCTIVE SLEEP APNOEA BE D IAG NOSED A N D RU LED OUT?
Full polysomnography remains the gold standard and is discussed in detail in Chapter 1 77, Obstructive sleep apnoea: medical management. Various factors including high cost, length of time and need to perform in a sleep laboratory have stimulated the development of home screening machines. None of these dev�ces has sensitivities or specificities approaching 1 00 percent therefore sig nificant numbers will be missed. The choice of screening oximeter may also affect the apnoea hypopnoea index. 1 3 A recent systematic review1 4 discusses methods of comparing the results of portable monitoring with polysomnography. When using portable sleep monitors for home use, clinicians need to be clear how they plan to use the information obtained in order to: 1 5 • • •
confirm the diagnosis of suspected sleep apnoea. identify patients with a high clinical probability of disease. stratify patients into correct priority for polysomnography.
In centres in which full polysomnography is not readily available, a clinical decision algorithm, which incorporates a clinical prediction rule with the use of portable monitors, can guide clinicians towards institution of therapy or
2328 I
controversial
PART 16 TH E U PPER AI RWAY
further investigations.16 A recent Australian study suggests that a clinical prediction rule can be used on its own to prioritize polysomnography without screening sleep/home studies.1? [***] This was based on five variables: age, sex, body mass index, snoring and stopping breathing during sleep, which were found to be significantly associated with sleep apnoea. Patients who have failed or who have equivocal home sleep studies, and those with negative studies but persistent symptoms should have full poly somnography. Intuitively, this approach could reduce waiting times for polysomnography and delays in diagnosis but additional evidence for the validity and cost effective ness of this approach is required. Incomplete or incorrect diagnosis of the severity of sleep-disordered breathing can have significant medicolegal implications. I ? [**]
CAN THE S ITE O F SNORI N G BE I DENTI FI ED?
Both endoscopic and imaging approaches have been used to answer this question. Endoscopic approaches include sleep nasendoscopy ± video recording of findings, and oesophageal pressure monitoring. Imaging approaches include cephalometry with the Mueller manoeuvre, fluoroscopy, three-dimensional CT scanning and dynamic ultrafast MRI. Sleep nasendoscopy
Sleep nasendoscopy, which is the most widely used technique to evaluate the site of snoring in the UK, was first described by Croft and Pringle in 1 99 1 .1 8 [**] It involves sedating the patient with propafol to a level of sleep sufficient to induce snoring, i.e. a target-controlled propafol infusion. 1 9 The operator then examines the upper aero digestive tract, in the supine position with a nasendo scope, to determine the level(s) of obstruction. Levels of obstruction can be graded as shown in Table 1 78. 1.20 [**] This procedure should be carried out with an anaesthetist present to monitor the propafol infusion, and with cardiac monitoring as well as full resuscitation facilities. Respira tory stimulants can be used to encourage snoring. Oxygen saturation should be monitored throughout the procedure and oxygen administered as appropriate. Only one study in the literature has compared sleep nasendoscopy in
snorers without sleep apnoea and nonsnorers, and showed that snoring could be produced at sleep nasendoscopy in 45 percent of nonsnorers but could not be produced in 1 8 percent of snorers? 1 [***] The inability to obtain snoring in 1 8 percent of snorers is explained by an inconsistent sedation technique, i.e. that the relatively narrow propafol titration window to result in snoring. However, this argument cannot be applied to the presence of snoring in nonsnorers unless the histories were not properly documented. A recent publication comparing sleep nasendoscopy results in sleep apnoea patients with nonsnorers showed no snoring or airway collapse at any level of propafol infusion in the asymptomatic group.22 [***] The distribution of sites of snoring in snorers without sleep apnoea is shown in Table 1 78.2. A controlled study comparing sleep nasendoscopy in nonsnorers, nonapnoeic snorers and in patients with OSA would be useful to address this dilemma. Comparison of sleep nasendoscopy with some form of continuous monitoring of the site of upper airway obstruction during normal physiological sleep would help provide reassurance that sleep nasendoscopy is measuring something of physiolo gical relevance. Video recording of sleep nasendoscopic findings is helpful for documentation purposes?4 Oesophageal manometry
Oesophageal manometry has been used in conjunction with screening sleep studies to diagnose apnoeas and hypopnoeas.25 In addition, it has been used to evaluate the relationship between reflux and o SA. 26 Adaptation of the manometry devices might allow more precise localization of sites of upper airway obstruction. This could then be used as a technique to validate sleep nasendoscopy. Magnetic resonance imaging
Ultrafast MRI can be used in awake and asleep patients to assess the site of upper airway obstruction. Midline sagittal sections and cross sections at various levels are the most useful images?? [**] There are significant differences in the pattern of dynamic airway motion in patients with OSA and those with no sleep-disordered breathing?8 [***] In the awake patient there is very close correlation between the sites of upper airway narrowing in patients with OSA, Table 1 7 8.2
Table 1 7 8. 1
Sleep nasendoscopy g ra d i n g .
G rade Obstru ction
1
Si m ple pa l ata l level snori ng/pa l ata l fl utter
2
Si n g l e level pa lata l o bstruction
3
Pa l ata l l evel o bstructio n with i n termittent o ropharyngeal i nvolvement
Sites of snori ng at sleep n a sendoscopy i n
n o n a p noeic snorers. Site
Pa lata l fl utter o n ly
Percentage
70
Pa latal fl utter + oth e r site
20
S u pra g l ottic
10
Tonsi l
8
4
Susta ined m u ltiseg menta l o bstruction
Ton g u e base
2
5
Ton g u e base leve l o bstruction
Ton g u e base only
8
6
I so lated epig lottic i nvolve m enta
Epig l ottic
2
a
Author's addition.
Reprinted with permission from Ref. 23.
Chapter 1 7 8 The surg ical ma nagement of snori ng
as defined by digitized video endoscopy and MRI,29 but these data are not available in the asleep patient for OSA or for either state in the simple snorer without OSA. MRI is not widely used in the UK for the investigation of snoring and sleep apnoea because of the high cost and significant time taken as well as the lack of normative data for both simple snoring and OSA populations. Also, short periods of sleep in an MRI machine may not be representative of normal sleep patterns. A useful research tool might be to try and quantify the surgical tissue volume reduction necessary to achieve resolution of snoring or OSA. Three-d i m ensi o n al computed to m ography
Three-dimensional CT measurements may be useful to eva luate upper airway patency in patients with sleep disordered breathing. The retropalatal space is the most relevant anatomical concept. Modifications of palatal surgery techniques to increase the lateral dimensions of this space may help to improve the success rate of this type of surgery.3 0 Cephalom etry
Cephalometry should be considered in the preoperative evaluation of patients considered for uvulopalatophar yngoplasty (Uppp ) 3 1 and patients in whom treatment with MAS is contemplated.3 2 Nasal spray test
This test involves using a topical nasal decongestant on alternate nights and comparing the severity of snoring and apnoea. If the decongestant results in improved symptoms it may be worth treating nasal abnormalities to help in snoring.33 I N D I CATI O N S FOR S U RGERY
Surgery is indicated in the following groups of patients. •
Patients with severe, antisocial snoring: - without OS A; - localized obstruction at one level in the upper airway, usually at palatal level; - multisegmental obstruction with predominant obstruction at palatal level.
This usually involves palatal surgery and, although individual approaches vary, they should involve proce dures with minimal morbidity, such as radiofrequency tissue volume reduction (RFTVR) , before considering laser-assisted uvulopalatoplasty (LAUP) or UPPP. •
Patients with mild-to-moderate sleep apnoea: - with severe antisocial snoring; - failed or inadequate response to continuous . positive airway pressure (CPAP ) ; - localized obstruction at one level in the upper airway, usually at palatal level.
I 2329
This usually involves palatal surgery and, although individual approaches vary, they should involve proce dures with minimal morbidity, such as RFTVR, before considering LAUP or, finally, UPPP. •
Patients with moderate-to-severe sleep apnoea: - with severe antisocial snoring; - failed or inadequate response to CPAP; - multisegmental obstruction.
This may involve a combination of procedures on the palate, tongue base and lateral pharyngeal walls, possibly with tracheostomy cover in severe cases. The RFTVR technique may be conveniently applied at multiple levels but other combinations have also been shown to be effective. Again, the choice of procedure should be governed by both prospects of success as well as associated morbidity. S U RG I CAL TECHN I QUES Uvulopalatopharyng oplasty
This technique was first described by Ikematsu in the 1 950s but was popularized by Fugita in 1 985 and involves resecting a strip of soft palate and uvula in combination with tonsillectomy. The tonsillar pillars are then sutured together. The effect of this is to stiffen the soft palate by scarring and to increase the space behind the soft palate to minimize obstruction. It is performed as a single-stage procedure, usually under general anaesthetic. It is most effective for treating patients with severe antisocial snoring of palatal origin but is also used in the treatment of OSA. It is associated with significant complications, which are increasingly regarded as unacceptable. The incidence of serious nonfatal complications is 1 .5 percent and the 30day mortality rate is 0.2 percent.34 Forty-two percent of patients having UPPP have complaints about their treatment postoperatively and 14 percent may not be satisfied with the outcome of their surgery.35 The specific complications include severe postoperative pain,36 hae morrhage ( 2- 14 percent) , respiratory events such as airway obstruction due to laryngospasm, postoperative pulmon ary oedema and hypoxia (2-1 1 percent) ,37, 38 nasal regurgitation ( 1 3 percent) due to excessive palatal resec tion, velopharyngeal stenosis,39 dry throat due to loss of pharyngeal lubricating function of the uvula, excessive pharyngeal hypersecretion ( 10 percent), swallowing pro blems (9 percent), voice changes (7 percent)36, 40, 41 and taste disturbances. Short-term success rates are quoted as ranging from 76 to 95 percent in well-selected patient groups, however, unfortunately, long-term successes fall dramatically to approximately 45 percent.4 2 The significant potential for serious complications and the declining success rates over time have encouraged surgeons to devise alternative approaches. Preservation of the uvula eliminates nasal regurgitation and minimizes pharyngeal dryness, globus-type symptoms, hypersecretion and swallowing
2330 I
PART 1 6 TH E U PPER AI RWAY
difficulties. It also appears to improve the outcome of surgery. 43 Eliminating the pharyngoplasty part of the UPPP operation, i.e. not suturing the tonsillar pillars after tonsillectomy, can reduce morbidity when there is thought to be no redundant tissue in the lateral pharyngeal walL44 Laser-assisted uvulopalatoplasty
This procedure was originally introduced by Kamami in France, in 1 993, as an outpatient procedure under local anaesthesia. Lignocaine with adrenaline is injected above the base of the uvula and 1 cm lateral to the midline in the inferior portion of the soft palate. Bilateral vertical incisions are made in the soft palate followed by partial vaporization of the uvula with a CO2 laser. There are numerous techniques and modifications of this procedure. Each patient requires between one and five laser procedures spaced approximately one month apart to complete treatment. It may also be carried out as a single stage treatment. The principle behind the operation is to stiffen the soft palate and thereby minimize snoring due to palatal flutter. Variations in technique involve the extent and distribution of palatal laser vaporization, the amount of uvula removed and whether the tonsils are laser ablated. Usually, a CO 2 laser is used but alternatives include the Nd Yag laser. Complication rates are generally lower than after UPPP but depend on the degree of vaporization. Notably, there are no reports of significant postoperative nasal regurgitation after LAUP. Globus-type symptoms are more common after LAUP than UPPP, probably because of the greater area of insensate palate.45 Pain levels are not necessarily better than after UPPP and may in fact be worse, and are probably proportional to the amount of laser vaporization. Fungal infections of the lasered palatal mucosa have also been described. Short- and long-term results are similar to UPPP, in that there is a significant decline in benefit over time with early success rates of 79 percent and later ones of 55 percent.46 Two randomized controlled trials of LAUP in the treatment of simple snoring and mild OSA suggest that it had minimal impact for either condition when compared with no treatment or treatment with placebo. 47, 48 [***] In a considerable number of patients the procedure may lead to mild OSA and worsening in nasal breathing in previously simple snorers owing to increased palatal fibrosis and contraction of the velophaIJ'1:lgeal space.49 [***] Laser-assisted uvulo palatoplasty has no significant impact on middle ear pressures4 9 or smell and taste.5 0 [***] Radiofrequency tissue volume reduction! thermal ablation
The principle behind this is similar to diathermy, but uses lower power and lower tissue temperatures with a current working at a frequency of 460 kHz (Table 1 78.3) . The
Table 1 7 8.3
Com p a rison of somnoplasty device with d iathermy.
Feature
Somnoplasty
Diathermy
Patient part of circuit [kHZ)
460
> 600
Tissu e tem pera t u re (OC)
60-90
7 50-900
Power (W)
2- 1 0
> 1 00
Volts
80
Up to 800
Reprinted with permission from Ref. 51 .
device applies thermal injury to specific submucosal sites in the soft palate resulting in fibrosis of the muscular layer and volumetric tissue reduction. 5 1 The main advantages of this technique are that it can be carried out as a day case or outpatient procedure under local anaesthetic and causes significantly less postoperative pain and other complications than UPPP or LAUP for simple snoring. The short-term efficacy depends on the number of lesions performed and how often they are repeated. Single- and multilesion groups showed significant improvement in snoring following treatment. The multilesion group required fewer treat ments than the single-lesion group and was more than twice as likely to be cured after two treatments. There was a trend towards improved clinical outcome with increased number of lesions and total energy per treatment when patients with one, three and four lesions were compared. The four-lesion group had the most pronounced improvement in snoring, the lowest number of treat ments required for cure and the greatest number of patients cured after two treatments. There was minimal relapse in the multilesion group at 16 months. In addition, delivery of increased numbers of lesions was found to be safe and not associated with increased levels of complications. Pain was significantly greater in the multilesion group but was considered minimal by patients and was controlled by the use of nonprescription analgesics and did not result in unplanned time away ' from work. 5 2 [***J Multilevel, temperature-controlled radiofrequency therapy of the palate, base of the tongue and tonsils in adults with OSA was effective in 33 percent of patients. 53 Three types of radiofrequency devices have been used with similar results. These are the Somnus unit,5 1 Celon device, 53 which has the additional advantages of a bipolar electrode tip, auto stop application and reduced proce dure time, and the Coblator unit. 54 The latter has lost favour because of its larger electrode tip and thus increased risk of complications. One study specifically addresses the question of complications reporting a rate of 2 percent, which includes ulcers of the tongue base or soft palate, dysphagia necessitating hospital admission, temporary hypoglossal nerve palsy and an abscess at the base of tongue.55 Radiofrequency volumetric tissue reduction in' the soft palate has no adverse impact on voice quality. 56
Ch a pter 1 7 8
The su rg ical management of snoring I 2331
both these studies are interesting, a controlled study in
Nasal obstru ction a n d n asal s u rge ry in the pathoge nesis and t reatment of sno ri ng a n d obstr u ctive s leep a pnoea
p atients with recorded nasal obstruction assigned to either
nasal surgery or no nasal surgery followed by further o bjective documentation of the OSA pathway) as in the
Clinical
reports
document
nasal
obstruction-induced
snoring and OSA57, 58, 59 but the exact role of the nasal airway in its pathogenesis is unclear. The reduced nasal cross-sectional area promotes increased nasal resistance to airflow and promotes inspiratory collapse of both the oro 60 Controversial data exist regarding the
and hypopha rynx:.
role of improved nasal breathing in managing OSA. If
nasal
obstruction
correction
contributes
o f the obstructed
to
OSA
development,
airway should
result of nasal surgery alone on OSA showed no significant
(RDI) or
lowest oxygen saturation levels but CPAP levels required to correct
OSA were
reduced.
Patients with mild
OSA
RD I but lowest oxygen
showed significant worsening of
saturation levels improved in patients with moderate OSA. In patients with severe OSA neither RDI or lowest oxygen saturation levels changed but CPAP levels required to alleviate o bstruction after surgery were reduced.61
[**]
A
further objective study on the polysomnographic effects of nasal surgery for snoring and OSA showed a significant improvement in the
RD 1, apnoea index and oxygen
saturation index as well as a decrease in duration o f sno ring; however, snoring and O S A were only completely relieved in
Table
178.4
2 1 patients.62
19 percent of
[***]
encouraged as p art of the overall management plan for antisoci al snoring and OSA.
Occasio n al p rocedu res fo r s no ring and o bst ru ctive s lee p a pnoea
improve
OSA. The first study tha t objectively investigated the impact on the respiratory disturbance index
above studies, would be more convincing. In the mean time) proper management of nasal obstruction should be
Although
Occasional procedures for snoring and OSA are summar ized in
Table 1 78.4. Of the various palatal procedures
described, most are pilot studies of new techniques and most
report
subjec tive
criteria
only.
': f, -' : � ��. � �:) .. .';� .� ;X}t:.. :'��·r : :i; '
.
r
.
_
.
Palatal
Latera l pha ryng ea l wa l l Tongue base
are
no objective outcome criteria. Owing to their po tential low morbidity) the inje ction snoroplasty technique66 and the outpatient uvulopalatal flap68 may be of possible interest. Palatal implants may be interesting because the benefit may not decline with time.69 For
the
tongue
base
and lateral pharyngeal wall,
radiofrequency ablation appears to be the technique with the
lowest
morbidity
although,
again,
there
are
no
comp arative studies. Therapeutic nightly stimulation of the
hypoglossal
nerve
moderate-to-severe
during
sleep
sleep
apnoea
�
'." ,; ,'
."l� " '1:
.
'- '�
::: :., ".J,,':,.'�.• �.·.T�i�;_h. .� fl. i�J�,'.\ ':,�, ,' ,•.••
-
.
�
,,,
.
Z-pharyngoplasty Vertical fu l l thickness cuts from the upper pole of the tonsil through soft palate and posterior pil l a r I njection snoroplasty Mod ified U PPP with extended uvu lopalatal flap Outpatient uvu lopalata l flap Pa lata l implants lateral pha ryngoplasty RFlVR
Laser m idl ine g lossectomy and lingua l plasty Tongue suspension sutu re Li ngual tonSillectomy RFIVR
Epiglottis Trachea Max i l loma n d ibula r procedu res
Hyoid myotomy and suspension Max i l loma nd i b u l a r osteotomy and advancement
-
trials
in patients
markedly
with
diminishes
Occasional procedures for snori ng and obstructive sleep apnoea.
,
' -=-=
No
compared with more standard techniques and there is
Hypog lossa l nerve stim u lation Endoscopic epig lottectomy Temporary tracheostomy Designed to e n l a rg e and sta b i l i ze the retro l i ngual airway by adva nci ng the insertion of the genioglossus or gen iohyoid muscle w ithout moving the enti re mandible or teeth Adva nces the hyoid and epiglottis a n teriorly Aims to move the max i l la a n d mandible as fa r forward as possible
literature 63, 64 65 66 67
68 69
70
53
53 71
72, 73
74, 7 5
2332 I
PART 1 6 T H E U PP E R AI RWAY
apnoea severity without waking patients.71 This might be better tolerated than an oral appliance, tongue surgery or CPAP. The Repose tongue base suspension suture provides another interesting alternative for increasing the dimen sions of the retrolingual space with relatively low morbidity but, again, no comparative studies are available in the literature?6, 77 Laser midline glossectomy and its modifica tions, as well as laser lingual tonsillectomy, are rarely performed because of the relatively high complication rates (25 percent) that include bleeding, taste change, odyno phagia, dysphagia and tongue oedema. Despite this, in appropriately selected cases, good results can be obtained.78 Only two reports in the literature refer to treating snoring/�SA due to epiglottic collapse with epiglottect o my, and in total, five cases have been described.72, 73 Two studies report the role of temporary tracheostomy in the management of OSA.74, 75 Tracheostomy reliably eliminated all grades of OSA severity in 79 patients and 20 percent were decannulated eventually, but there was a 2.5 1"\ t>�'rt> �' T tracheostomy-related mortality?4 In the other series of 17 patients who had a tracheostomy for OSA, ten were carried out in a planned fashion and a further seven as an emergency. Planned tracheostomies are indicated for tongue base procedures such as genioglossus advance ment or laser midline glossectomy.75 It may also be appropriate in those rare patients where maxillomandib ular procedures are considered appropriate.
POSTO PERATIVE CARE In most units patients undergoing surgery for snoring or OSA are admitted for an overnight stay. For UPPP surgery this is still generally the case, although two recent publi cations that in selected patients without co-mor bidity same day discharge may be appropriate, even when combined with tonsillectomy and or nasal surgery. 79, 80 Laser-assisted uvulopalatoplasty is a staged procedure that was designed . for day-case use. Postoperative pain, which has usually been the limiting factor in outpatient manage ment, often does not reach its greatest extent until 48 hours postsurgery. Radiofrequency ablation seems to be associated with significantly less postoperative pain, making it much more suitable as an outpatient or day-case procedure. Peri operative pain and salivation during LAUP under local anaesthesia are well controlled with a combination of morphine and scopolamine.8! (***J Postoperative pain after UPPP and LAUP may be difficult to control, particularly if performed in conjunc tion with tonsillectomy.82 Concerns have been raised about both the use of opioids, because of the risk of sedation and respiratory depression, particularly in patients with OSA, and the use of nonsteroidal antiinflammatory drugs, on account of the risk of bleeding. However, one of them or a combination of both is required in more than 40 percent of patients; the total dosage may be minimized by giving it as a continuous infusion. The need for patient-controlled
intravenous rescue fentanyl analgesia was twice as great after UPPP than after tonsillectomy alone.82 [***] Pain after discharge from hospital may remain a significant problem, requiring oral nonsteroidal and opiate analgesia in most patients for about 5 days, but in up to one-third of patients, it may remain a disturbing issue for more than two weeks.83 [*** J Glossopharyngeal nerve block is helpful after UPPP but not following simple tonsillectomy.84 [***J Perioperative systemic corticosteroids do not reduce morbidity following Uppp.85 [***J
CO M PLI CATIO N S The complications o f individual techniques are discussed under the relevant sections with the incidence of reported complications varying widely. Table 178.5 lists the range of complications for all procedures in the literature. Only one study compares the complications between the three major palatal procedures, and this confirms the impres sion that RFTVR is associated with fewer complications than UPPP and The numbers in each group are too small to provide a picture of complications associated with each procedure. Palatal surgery for snoring and OSA is associated with a small but significant mortality, as shown by a survey of British otolaryngol ogists.86 Six intra- and postoperative deaths, related to both bleeding and airway obstruction, were reported by a total of 371 otolaryngologists. A large multicentre study comparing complications of the three most frequently performed procedure would be useful.
S H O RT- AN D LO N G -TERM OUTCOM ES For UPPP early success rates of between 65 and 100 percent87, 88 for management of simple snoring have been quoted but longer-term studies have shown that these results deteriorate over time with results at two to five years being 45-60 percent.42 Causes for late deterioration include increased body mass index and loss of palatal stiffening owing to resolution of palatal scar tissue. In patients with OSA only 41 percent showed significant improvement in objective response criteria.88 A long-term survival study of 400 snoring patients from Sweden, of whom 256 had OSA, showed that there was no increase in mortality compared with controls.89 [** J The results of LAUP operations are similar to those of being UPPP with success rates from 60 to 90 1 quoted in the literature.90 , 9 , 9 2 The favourable subjective and objective results deteriorate over time from 79 to 57 percent in 1 2-1 8 months, and the procedure can cause mild OSA in previously nonapnoeic snorers.93 A six-year follow-up study showed that most of the failure rate occurs in the first two years but long-term failure is still evident at 79 ' months. 94 LAUP is only successful in the management of OSA in 20-30 percent of cases.92, 95 [**J
Ch a pter 1 7 8
Table 1 78 . 5
The surg i cal man agement of snori ng . 2333
Complications following pa lata l snoril1g surgery. late
Early Pain occu rs after a l l procedu res but is least severe and of the shortest duration after RFTVR Haemorrhage occurs after both UPPP (2- 1 4010) and LAUP (0-9010) but has not been reported for RFTVR Airway problems have been described after both UPPP and LAU P but not after RFTVR. For UPPP this includes laryngospasm, posto perative pul monary oedema and hypoxia but for LAU P only delayed OSA deve lopment d u e to palatal stiffen ing Temporary pal atal incompetence occurs after U PPP in up to 2 5% but may be equally frequent after LAU P. It has not been described after RFTVR. Significant permanent pa latal incompetence has only been described after U PPP Wound infection can occur after a l l procedures but is most common after UPPP. Abscesses at the site of RFTVR probe insertion have been described Wou nd dehiscence only occu rs after UPPP. Ulceration at the RFTVR probe insertion site has been described Dysphag ia due to pa in is a sign ificant ea rly problem after U PPP and LAUP but not RFTVR
Postop erative po lysomnography revealed that LAUP may lead to deterioration of existing apnoea in up to 30 p ercent
Dry th roat, excess pharyngeal secretions, dysphagia and taste disturbances seem to be related to loss of the throat lubricating effect of the uvula in U PPP and LAUP Sme ll and taste disturbances have been described after UPPP and LAUP but not following RFTVR Globus-type symptoms are most marked after LAU P and appear to be related to loss of pa lata l sensation
Voice changes have only been d escribed after U PPP
Velopharyngeal stenosis has been described after both U PPP and LAU P but not RFTVR Velo pharyngeal fistula has only been described after RFTVR Temporary hypoglossal neNe pa lsy has only been described after RFTVR
study has shown significant objective improvements in OSA. I 06 [ **] Similar to CPAP, MAS can improve b lood
[***]
of p atients, p robably related to velopharyngeal narrowing
pressure. 107
and progressive palatal fibrosis by the laser beam.96
are the relative simplicity of the treatment, its reversibility
subj ective and objective improvement in 5 0-85 percent o f p atients,97 9B, 9 9 and are p robably slightly worse than
nonsurgical alternative to patients who cannot tolerate l B CPAP or who rep resent a poor surgical risk O Forty
UPPP and LAUP but do not share the high morbidity of
percent of MAS users will develop some minor complica
Results of RFTVR for simple snoring demonstrate ,
The main advantages of these devices
and cost effectiveness, and that it provides a genuine
these pro cedures. Similar to other treatments, results
tions of the jaw, with mouth or tooth pain, and some 26
deteriorate with time and in one series success deterio
percent of long-term users may experience painless b ut
rated from 72 to 52 percent in an average of 14 months.9B Results
for
O SA
are
conflicting,
with
irreversible changes in dental occlusion even with two piece adjustable devices. 1 09 A longitudinal observational
one report l suggesting benefit in 65 percent of p atients OO while
study of 1 00 adults with OSA treated with MAS showed
others suggest no benefit. l o l
significant craniofacial
changes
in maxillomandibular
Few studies comp aring different surgical techniques
relationships an d bony dimensions on lateral cephalo
exist, but those that do suggest that initial s uccess fo r laser
metric radiographs. It was postulated that changes in
UPPP has a longer sustained benefit than laser surgery l 03
minimum.
surgery is similar to UPPP fo r simple snoring102 or that .
One prospective trial compares LAUP with
RFTVR b ut
the numbers recruited are too small to state that LAUP outcomes are better than RFTVR. 104
overbite could be lessened by k eeping bite opening to a 1 10 A recent cephalometric studyl l l has shown
that better treatment responses with adjustable MAS can
be obtained in patients who are younger, have a lower
body mass index, a longer maxilla, a smaller o ropharynx,
smaller overj et, less erupted maxill ary molars and a large
ratio of vertical airway length to cross-sectional area of
N O N S U RG I CA L TREATM ENTS OF S N O RI N G
the soft palate. Trials comparing MAS with surgical interventions and CPAP sho uld be performed to assess
Apart from weight loss, cessation o f alcohol and smoking,
the relative efficacy of these treatments.
the only other nonsurgical treatment consists of the MAS, which by bringing the tongue base fo rwards increases the dimensions of the upper airway. A randomized controlled
CO N CLU S I O N S
trial of a MAS versus placebo for simple snoring showed s ubjective improvement in snoring frequency and seve l S rity in 76 and 84 percent, respectively. O [ ***] A recent
mandibular advancement splints
I n the preoperative assessment o f the snoring patient the
main difficulties still arise in the precise localization of the
2334
I PART 1 6 TH E U PPER AI RWAY
site of snoring. Sleep nasendoscopy as a technique requires further validation. Ideally, the site of obstruction should be assessed during normal physiological sleep and then further research to develop an appropriate technique is required. From a surgical point of view the three main palatal procedures produce fairly similar results that all deterio rate with time. The main factors determining the choice of operation are the high risk of complications associated with UFPP and the associated pain with LAUP. Radio frequency tissue volume reduction seems currently to be the choice with least morbidity although the results may be slightly less goo d and the benefits may decline more quickly than the other two procedures.
•
�; >r-)�: ' . " ' ,: _'" . Simpi,e'snoring j,s part. ;�f ,t�� 'sp�c�� .of " , ' . . . sleep-disordered breathi.�g; �angll:lg:!wnt: " . " '"
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In �,� :11,1< , sleep nasendqsc0PV:} & l the )n<;>st · , wideIytus.ed,:tec:lh�i'quel' t(') �val:U�tej�e '�site, · of · ' ' snQftng. �lt .!iilVO l'�s, � e4�ting · th¢ .'p.atient.with
pro:pafob��ci�.n� .to/inci:uce':shorirrg·,;'ie; a" targe.t�,�m�r9��9 'Br.qpaf91 ,�f4.#on. t;he ,
oper;it'D� ilieri ex�ln�i ��e;.�pper: , '+'.'." " ' aerodilgestive t ract,:���:p:�- .s�'R�e,,, p,p.S!ti�lil _ ", . wrth a nase:nd; ' ", ,�. � � :<, � ' • MruJ� :not , j�ri4�W:::'4sed in " the ,UK jor;,tbe -'
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g b;\:jUse.{ �f�th�,:higp, �:�ep�'
investi ati�n o{ snQr�g and '·sleep apnoea cost and significant , " le�gt4�_,?f �we as well a-s �ack- .9f , �,:, : ;;' : noiiuattve3t�M;·:f?r' both ,si�ple. s,norlI)g; an4 OSA
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The mai�'r·,w di4:ti.o.n.:.fdr!·· sp!geri�fQ'r . sriormg , in the U K': � J-severe aptisocial . snor.ing withput
�th single, well�defined 'site of ,·)i;;,!;Q�st�rtio��:.'us��y at palatal levei. '
·: -':��\�,.·:OSA , a:n4
a
.:;': -;'Tlie eff�0trp(�PP · is to stiffen the soft palate .
J/ '))Y" s'e�g"�{btq-incr�ase the space behind · �,:��· .�the )�o.fi�,pal:a;te 't(r tniniinize obstruction. .It is
" , assGJd�1icl,WiW: :� '�iW Qcant profile of.
compli�a,iiops·/wllit�· :a�e being increasingly regaraed as ·uDa�ce table. The spe�ific complicatio1)� include severe: postoperative pain, haemorrhage (2...:. 1 4' percent), respiratory . events such � 'airways obstruction due ' to laryngospasm, PQstoperative pulm.onary · oedema an4. hypo�a , (2"':1 1 perce�t), nasal , .
p
,
'
the
;; :' r�.�;��iij}t?,�P'y-��;q�fi�iti�9.,hs.�a�,� �e!1er m0q,itQring for 'dear�r,
, . ' regl:1rgita�on .c l 3 persent), velopharyngeal . - ·steno�i�, dry, throat, excessive pharyngeal " hypersecretion CIa percent), Swallowing ' � . p,robJems. (9 percent), yo�ce ch anges (7 . percent) ' and tast.e disturban'ces. • Complication rates fo r LAUF are generally lower than after UPPP bU,t depend on the degree ofvaporization. Notably, there are nq r eports of ,signifiCant postoperative nasal . , ,regurgitati.op after: LAUP. Globus-type symptol)1s are IJlore common after LAUF . ' . thaI?- UPPP, i,prci�abiy beca).lse of the greater area of h:isensate palate. Pain levels are not , necessarily bette,r than after UPPP and may . in fact be wQ.rse, and ,are probably , proportional ' to. �he. amount of laser :. v.�porizatiOI}., . , i:h�, m ain advailtages 9f RFTVR are �hat. �t ; ,.san be, carrie� o ut as a �d�y C?ase or o,+tpatient � , p� q.ce q ur e· J:lp de r lo�al ,�aestheti� and causes . ' ,s�:gnificanJly le$s p6stoperati�e pain. and , other 'complications �han vPFP Dr ,LAUP .fqr , sim'ple SI1oring.' Th.e �hort-tenp. effrca,cy depends , on number of lesions performed and .how .often they are repeated. . . Reduced 'nasal:cro�s�sectional area. promotes ' ' . \ ",��creased. nasal· resistance to airfl,ow and " .� · .promotes inspiratDiy .collapse of both th� , oro-, and , ,lJ.ypopharynx . . . ' ' f : , . 'PDstoperative pain after UP P P and LAUP � '. :"'. IT).ay , be difficult to control, particularly if , - p erformed in conjunction with tonsillectomy. ' . . Concerns have 'been raised about both the 'use, ofopioids, because of the risk of se d atio n and respiratDry :depression, -particularly in " patients With obstructive sleep apnoea and the use of nonsteroidal antiinflammatory drugs) on account of the risk of bleeding. However, one of them or a com.bination of both is required in more than 40 perc,:ent of : .' . patients; the total dosage may be minimized by giving it as a continuous infusion. . • RFTvR is associated with Jewer complications than UPPP and LAUP. • Palatal surgery for snoring and OSA is associated with a small but significant mortality. • The outcomes of palatal surgery for snoring are all fairly similar and all deteriorate over
. �
_
<
,�
•
•
time.
Adjustable MASs are an important
component of the treatment of severe antisocial snoring and OSA. With appropriate fitting to minimize bite opening, pain and changes in dental occlusidn can be avoided .
Cha pter 1 1 8
Best clinical practice .; Deta iled clinical evaluation of snori ng patients by history, physical exam ination, body mass index and Epworth sleepiness score can be used to screen out nonapnoeic snorers with a sensitivity of 93 percent and specifi city of 6 0 percent and thus prioritize fu rther investigations. (Grade C) .; This initial assessment can take place in an ENT or resp i ratory medicine clinic but probably should be carried out to standard protocols to avoid later d u p l ication or omissions. [G rad e 0] .; Although there are sign ificant concerns about how relevant the results of sleep nasendoscopy are to rea l sleep, it remains the only read i ly available and cost effective tech nique to identify the site of snori ng and therefore the decision wh ich site of surgery to offer. [Grade 0] .; Standardization of tech niq ue is vital in improving results and the test is best offered in u nits where the techn iq ue is practiced regula rly. [Grade B] ./ The test should be used until a better a l ternative is avail able. (Grade D) .; MRI is not widely used in the UK for the investigation of snoring and sleep a pnoea due to the high cost and sign ificant time taken as well as lack of normative data for both simple snoring and OSA populations. [Grade D] .; The main indication for snoring surgery in the U K is severe a ntisocial snoring without obstructive sleep a pnoea a nd w ith a single well defined site of obstruction usua l ly at palatal level. [G rade D) ./ More complex indications should probably be managed in a multidisciplinary setting of respiratory physici ans, ENT surgeons and sometimes maxillofacial surgeons as well as appropriate techn ical support to ensure the full range of site indications can be managed a nd appropriate surgical experience developed. [Grade 0] ./ I n view of the Significant risk of complications this procedure shou ld not generally be offered as fi rst l ine surgical treatment for simple palatal flutter. [Grade C] .; lAUP is a more proportionate procedure for simple pa latal snori ng than U PPP but is by no means free of probl ems i n that success is often associated with severe postoperative pa i n. [Grade C] ./ RFlVR would be the author's current choice for management of simple palatal snoring but this may cha l1ge as techniques evolve. [Grade 0] .I Despite the lack of controlled studies com pari ng the effect of nasal surgery with no nasal surgery on future managemen t snori l1g and OSA, proper management of nasal obstruction includ i ng surgery should · be offered early on as part of the comprehensive management of antisocial snori ng and OSA [Grade D] .; Apart from the very rare emergency tracheostomy for very severe OSA at tongue base leve l, occasional
The surgical management of snori ng I 2335
surgery should be done by surgeons who are part of mult i d isciplinary teams and a re eva luating their outcomes carefu l ly. (Grade 0] .; Training for such occasional procedures is currently not widely available in the UK and is probably best obta ined at larger American centres. (Grade D] .; Postoperative pain after U PPP and lAU P may be difficu lt to control particularly if performed in conj u nction w ith tonsillectomy. [Grade C] .; Concerns have been raised both about the use of opioids, because of the risk of sedation and respiratory depression, pa rticularly in patients with obstructive sleep apnea and the use of non-steroidal anti-inflammatory drugs, on account of the risk of bl eeding, but one or a combination of both is required in more than 40 percent of patients and the total dosage may be minimized by giving it as a continuous infusion. [Grade D]
Defi cien cies i n cu r re n t kn ow led g e a n d a reas fo r futu re resea rch > » �
.> >»
Is s i m ple snoring a progressive condition that eventually becomes OSA? A controlled study looking at sleep nasendoscopy in nonsnorers, nonapnoeic snorers a nd OSA. A comparison of sleep nasendoscopy with conti nous pharyngea l and oesophageal pressure manometry du ring sleep. National audit of complications of non palatal surgery for snoring and OSA. Randomized study on outcomes after va rious su rgica l techniques. Trials of adjustable mandibu lar advancement splints against su rgery for snori ng and OSA.
A CKN OWLEDG E M E NTS The author would like to aclmowledge the advice of David Morgan, Consultant Otolaryngologist at Binning
ham Heartlands Hospital, who has a special interest in snoring surgery.
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PART
17
HEAD AND NECK TUMOURS EDITED BY JOHN HIBBERT
179 Epidemiology of head and neck cancer
2343
Randall P Morton and Mark E Izzard
180 Aetiology of head and neck cancer
2351
Nicholas D Stafford
181 Staging of head and neck cancer Nicholas J Roland
2359
182 Data collection in head and neck cancer
2372
Richard Wight
183 Prognostic indicators and serum markers Andrew S Jones
2378
184 Skin cancer of the head and neck
2395
Garrick A Georgeu and Michael Gleeson
185 Mucosal malignant melanoma Andrew S Jones
2406
186 Nasal cavity and paranasal sinus malignancy
2417
Brent A McMonagle and Michael Gleeson
187 Juvenile angiofibroma
2437
Michael Gleeson
188 Nasopharyngeal carcinoma John Kong Sang Woo and C Andrew van Hasselt
2445
189 Benign salivary gland tumours
2475
Michael Gleeson and Roderick Cawsont
190 Malignant tumours of the salivary glands Andrew S Jones
2493
191 Tumours of the parapharyngeal space Andrew S Jones
2522
192 Oral cavity tumours including the lip
2543
Keith Webster
193 Oropharyngeal tumours Patrick J Bradley
2577
194 Tumours of the larynx
2598
Martin A Birchall and Layson Pope
195 Rehabilitation after laryngectomy Andrew J Parker
2623
196 Tumours of the hypopharynx and oesophagus Andrew 5 Jones
2633
197 Thyroid cancer
2663
James Ramsden and John C Watkinson
198 Management of the patient presenting with neck lymphadenopathy and an unknown primary carcinoma
2702
Jawaher Ansari and John Glaholm
199 Metastatic neck disease John C Watkinson
2711
200 Developments in radiotherapy for head and neck cancer
2753
John Glaholm
201 Quality of life in head and neck cancer
2766
Randall P Morton and Hisham Mehanna
202 Palliative care for head and neck cancer
2781
Charles Diamond and Claud Regnard
203 Medical negligence in head and neck surgery Arnold GD Maran
2803
179 Epidemiology of head and neck cancer RANDALL P MORTON AND MARK E IZZARD I ntrod uction
2343
Principles of epidemiology
2343
Aetiological review of major head and neck cancer sites
2346
Key points
2349
Deficiencies in current knowledge and areas for future research References
2349 2349
Computer searches were performed of the Medline database and Embase. The following search strategy was implemented using the key words epidemiology, head and neck neoplasms, case-control studies and focussing on causality.
INTRODUCTION
PRINCIPLES OF EPIDEMIOLOGY
different causation. It is important to recognize this because grouping of tumours of different sites leads to diluting effects of causative agents if sites are included that are not susceptible to the putative agents of interest. Moreover, many risk factors impact to a variable degree on anatomically contiguous but epidemiologically and oncologically distinct head and neck sites. Thus it is that wood dust is important in sinonasal cancer (SNC) but not in nasopharyngeal cancer (NPC). The relative rarity of tumours of many head and neck subsites leads to the problem of small numbers, which in many epidemiological studies is managed by the grouping together of tumours from different sites. While this may increase the power of the study, it has the effect of obscuring important effects that may be present for one site, but not another. The combination of sites 'middle ear' and 'nose' and 'sinuses' in early cancer registries is an example of inappropriate grouping. Equally inappropriate is the combination of oral cancer with pharyngeal and laryngeal cancer, as occurs in many clinical reports and case-control studies. Multicentre studies can overcome the problem of recruiting sufficient numbers. [*]
Head and neck cancer-specific issues
Causality
Head and neck cancer is uncommon; it comprises a heterogeneous group of tumours, each with rather
Current thinking on the origin of adult human cancer is that cancer is a phenotypic manifestation of accumulative
Epidemiology is the study of the distribution of disease in populations, with a view to establishing causality and providing a basis for the introduction of preventative programmes. The clues to causation can be found in population studies of variation in tumour occurrence by person, place and time. This is referred to as descriptive epidemiology. Any hypothesis generated by descriptive epidemiological research can be tested by retrospective comparisons of exposure to risk factors among cases and controls, known as case-control studies. A cause-effect relationship may be confirmed by interventional studies where avoidance or protective measures are taken. The first part of this chapter summarizes the principles of epidemiology as applied to head and neck cancer. The second part provides a brief outline of risk factors for disease at each major head and neck cancer site. A specific discussion of tumour aetiology accompanies each chapter relating to individual head and neck cancer sites. [*]
2344 I PART 17 HEAD AND NECK TUMOURS genetic changes in normal cells. Environmental (chemical, viral or radiation) factors probably contribute more than 80 percent of such changes. The progression to cancer is a multistep process, each step an essential and important event in a complex matter that takes place in an environment of variable host ability to recognize and repair subcellular damage as it occurs. Owing to the generally long period between initial exposure to a causative (carcinogenic) agent and the first appearance of the tumour (known as the latent interval), it is difficult to establish beyond doubt those factors that have been operative in any single patient. The inappropriateness of 'experimenting' with carcinogens in patients and the logistic problems of population-based interventional studies means that most information relating to causation comes from observational studies. Real associations are thus difficult to quantify and many studies carry considerable potential bias that may compromise the results. This bias may come from participants in the study or those conducting it (observer bias). Any study attempting to identify causality can reduce bias by: • ensuring a population size sufficient to generate a statistically meaningful result (power); • matching variables such that populations to be compared are, in as many respects as possible, alike; • taking the latent interval into account. When seeking a causal relationship between carcinogen and disease there should be a statistical association between the factor and the disease that is unlikely to be due to chance. Moreover: • any bias as far as possible should be accounted for; • a dose-response relationship should be demonstrated; • in vitro or animal studies should support the association; • a reduction in the exposure to the agent should be associated with a reduction in incidence of disease.
Study design There are three types of study design. 1. Descriptive studies consider variance of disease in
respect of time, place and person. 2. Analytical studies explore the odds of developing a cancer according to exposure to specific risk factors. These are often further subdivided into prospective or retrospective. 3. Interventional studies attempt to demonstrate cause-effect relationships through altering the natural history of the disease by an intervention aimed at reducing or eliminating exposure to a putative carcinogen.
DESCRIPTIVE STUDIES
These studies generally provide the first aetiological clues which can be further explored In more elaborate (analytical) studies. Within a defined population, the incidence of a disease is the number of cases occurring within a specific time frame, while the prevalence is the number of cases present at anyone time within that population. Comparison of geographical variance with agematched populations - for example, nasopharyngeal carcinoma in the Cantonese of southern China versus the Mandarin of central China - provide clues to causality. Tracing these population groups as they emigrate and diversify is interesting as they carry their 'relative risk' with them. Descriptive studies also provide economic and health statistical information about tumour burden in any given population, and identify occupational and social class groups that carry a higher risk of specific tumours. A descriptive epidemiological study of head and neck cancer can be found in a paper by Ramadan et al.,l in which the changes in laryngeal cancer in England and Wales were described according to time and gender and correlated with corresponding changes in the consumption of such risk factors as tobacco and alcohol. [**]
ANALYTICAL STUDIES
These may be prospective or retrospective in nature. Prospective studies, also known as cohort or longitudinal, are less common and follow groups of patients categorized in relation to exposure to risk factors of disease. The groups are followed over time and compared to identify the 'relative risk' of developing the disease if exposed to the factor being studied. Owing to the low prevalence and long latent interval of head and neck cancer, the groups must be large and followed for a long time. This leads to a costly timeconsuming study. Doll and Hill published the classical cohort study in 1954. 2 They established the smoking habits of 34,000 medical practitioners in the UK and prospectively followed their cause of death. They were able to standardize the death rate from lung cancer for men aged 45-74 years in relation to the most recent amount of tobacco smoked. [***] Retrospective studies (case control) compare groups of patients who already have the disease with a population-based group who do not. The groups are matched for age, gender and, where possible or practicable, other factors such as social class or occupational group. The exposure to risk factors is obtained retrospectively, for example from patient charts or via questionnaire. The relative risk cannot be directly calculated, as' the original population from which the patients with the disease came from is undetermined, but
Chapter 179 Epidemiology of head and neck cancer
it can be estimated by the choice of a suitable control group. The advantages of retrospective studies are that relatively small numbers of cases are needed and they are quick and relatively inexpensive to perform. Their main disadvantages lie in potential bias and the reliability of the retrospective nature of questionnaires (recall bias). A case-control study by Spitz et al. 3 reports on the effect of tobacco consumption in oro- and hypopharyngeal cancer. They found that, unlike laryngeal or oral cavity cancers, the oro- and liypopharyngeal cancers had no significant increase in risk of cancer with increasing exposure to tobacco. [***]
INTERVENTIONAL STUDIES
These are prospective studies that follow at-risk population groups whose risk of developing the disease is altered by some form of intervention. There may be more than two groups and there should be a control group against which to measure the intervention. The gold standard interventional study is the randomized controlled trial, where allocation of patients to an intervention is randomized to remove bias. Epidemiological interventional studies aim to reduce exposure or the effects of exposure, by altering the environment in some way, of one population group. A control group comprises another population in whom a similar exposure exists. It is, of course, ethically difficult to assign people randomly to carcinogen exposure in order to confirm a possible risk of a cancer developing.
Cancer prevention The principle aim is to identify measures that can impact on the incidence of disease. The two concepts here are: 1. avoidance of risk factors (primary prevention); 2. screening and early intervention (secondary prevention) .
PRIMARY PREVENTION (RISK AVOIDANCE)
Education aimed at reducing exposure to tobacco is perhaps the best example of risk avoidance. Prevention of occupational exposure to asbestos (larynx),4 or wood dust (nose, paranasal sinus)5 are other examples relevant to head and neck cancer. [*** /**]
SECONDARY PREVENTION (SCREENING)
The principles of screening must be understood in order to appreciate how screening for head and neck cancer might be implemented. The first essential element for a successful screening programme is the availability of a reliable,
I 2345
suitably sensitive and specific, relatively noninvasive test for the cancer concerned. The second is the identification of a proportion of the population that carries a sufficiently high risk of developing that cancer. These issues are embodied in the broader list of principles for screening. • There should be serious consequences of the disease. • Treatment should be more effective when applied early. • The detectable preclinical phase must be sufficiently prevalent. • The test should be inexpensive, convenient and noninvasive. • The test should have high specificity and high sensitivity. • There must be resources to respond to positive screening tests. • False positive tests require further diagnostic tests that waste resources and inflict morbidity. Patients should be advised that there is a risk that a negative screening test may overlook disease and certainly does not prevent future disease developing. It is an appealing notion to detect a cancer before it is clinically evident because it seems likely that earlier detection and treatment will be associated with a better chance of survival. It is not clear that this has, indeed, been achieved with screening for prostate cancer and there is ongoing debate as to whether it is so for breast cancer. As the great majority of the population being screened will in fact not have the disease, the occurrence of false positive tests will add considerably to the cost (personal and financial) of screening. Therefore, when screening programmes are being developed, tests with high specificity (the likelihood that a person classified as 'normal' is indeed free of the disease) - which minimize false positives - are to be favoured over tests with high sensitivity (the likelihood that a person with disease will be classified as having the disease). The predictive value of a screening test measures the percentage of positive screening tests that are 'true' positives. Tables 179.1 and 179.2 summarize the predictive value of screening tests according to their sensitivity and specificity in relation to the perceived risk of the population having the disease. Increased prevalence boosts the screening test efficiency (Table 179.1); increased sensitivity (for the same specificity) reduces test efficiency and increased specificity (for the same sensitivity) boosts test efficiency (Table 179.2). Cost-effectiveness of screening tests will depend on these features. An appropriate benchmark for screening tests would be for sensitivity and specificity to be 99 percent and the required subclinical prevalence to be at least 0.2 percent. Most screening tests and most head and neck cancers fall well short of these figures. One exception is the prevalence of NPC among first-order family members of Chinese patients diagnosed with NPC. The risk is increased several-fold over the general Chinese population in Hong
2346 I PART 17 HEAD AND NECK TUMOURS Table 179.1 Predictive value of screening test according to test sensitivity/specificity and prevalence of the disease. Prevalence (010) of disease in population being screened 0.1 1 5 10
Characteristic Of screening test (sensitivity/specificity) 90/90
95/95
99/99
0.04 0.08 0.32 0.5
0.05 0.16 0.5 0.68
0.09 0.5 0.84 0.92
VARIATION BY SUBSITE
There is no recognized subsite variation rates.
III
incidence
VARIATION OVER TIME
Over the years the incidence of NPC has been remarkably stable apart from in Hong Kong where there has been a decline among men in recent years.
RISK FACTORS
Table 179.2 Predictive value of screening test according to test sensitivity/specificity and the proportion of screening tests that are found to be 'positive' (many positive screening tests will in fact, in the event, be found to be negative for the disease being screened for). Proportion (010) of positive screening tests in population 10 12 15
Characteristic of screening test (sensitivity/specificity) 85/90
90/90
85/95
90/95
0.32 0.44
0.21 0.42
0.62 0.73 0.83
0.59 0.68 0.78
Kong risk of about one per thousand and justifies screening of this subset of the general population. Annual screening may also be appropriate for workers in an industry with a high exposure to a known carcinogen. Such an example may be nasal endoscopy in workers in the furniture-making industry in which there is a high risk for adenocarcinoma of the ethmoid.
AETIOLOGICAL REVIEW OF MAJOR HEAD AND NECK CANCER SITES Nasopharyngeal cancer INCIDENCE
In most parts of the world the incidence of NPC is less than one per 100,000 per year. However, in some ethnic groups, namely in Chinese, Eskimos, Pacific Island Polynesians and (North) Africans, NPC is notably more common. The highest incidence rates are found among the Chinese, particularly in Hong Kong and Singapore. 6 [**] VARIATION BY AGE AND GENDER
The age-specific incidence for both genders begins in the second decade, rises to a peak in the fifth decade and declines thereafter. The incidence is two to four times higher in men than in women. 7 [**]
Genetic
Several factors point to an inherited genetic predisposition: high incidence rates persist in Chinese migrants living in low incidence areas; familial cases (first-degree relatives) comprise about 7 percent of registered cases; specific human leukocyte antigen (HLA) haplotypes are associated with an increased (or decreased) risk of NPC; and studies based on sibling pairs have shown the presence of an NPC 'susceptibility gene' in the HLA region. 6 Occupation
Early studies implicated some occupational exposure to dust, smoke and chemical fumes but these have not been confirmed by more recent work. Tobacco
There is no consistent evidence that tobacco consumption is related to NPC. Diet
There is a marked increased risk of NPC in people who have a childhood diet that contains salted fish. 7 This is thought to be due to the high content of mutagenic chemicals such as N-nitrosamines. Other salted preserved food items have also been associated with an increased risk of NPC. The protective effect of high vitamin E intake in adulthood has been reported. Infection
The Epstein-Barr virus (EBV) is ubiquitous in human populations; it is harboured in circulating B lymphocytes or secreted in saliva and has a strong and consistent association with NPC. A positive immunoglobulin A/viral capsid antigen titre is especially associated with excess risk of the disease. EBV is capable of immortalizing human epithelial cells, and the virus' genome is present in NPC tumour cells. The marked geographical and ethnic variation in incidence of NPC and the ubiquitous prevalence of EBV argues against EBV as the sole cause of NPC. It seems likely that genetic factors (abnormal or variant HLA li.aplotypes) may render one more susceptible to incorporation of EBV into epithelial cells. 6 [***/**]
Chapter 179 Epidemiology of head and neck cancer
I 2347
Sinonasal cancer
Tobacco
INCIDENCE
No correlation between tobacco smoke and SNC has been found, and although various authors have implicated snuff, a definite association has not been confirmed.
The incidence of SNC is said to be about 3.5 per 100,000 population per year.8 Japan and Nigeria appear to have a relatively high incidence rate, and a high rate among the Coloureds from the Cape Province in South Africa is also reported. Only one of the leading ten countries is predominantly Caucasian; maybe people of non-European origin are more likely to develop SNC. [**]
Infection
Chronic sinusitis is thought to be an important causal factor but the evidence is only indirect. Sakai et al. 14 estimate that patients with chronic sinusitis have a cumulative risk of 1-2 percent for SNC. [***/**]
Oral cavity/oropharynx VARIATION BY AGE AND GENDER
Incidence increases with age irrespective of cell of origin,8 and there is usually a male predominance of about 2:1. 9 [**]
INCIDENCE
The overall incidence is lOA per 100,000 per year (males 15.7 per 100,000 per year, females 6.0 per 100,000 per year).15 [**]
VARIATION BY SUBSITE
Most SNCs arise in the paranasal sinuses rather than the nasal cavity, and the majority of paranasal tumours are reported to arise in the maxillary antrum. 8 [**]
VARIATION OVER TIME
There is evidence of a generalized gradual decrease incidence worldwide, especially in men. lO , 11 [**]
III
VARIATION BY AGE AND GENDER
The incidence increases with age, with a steep rise in the 60-65 age group. The male to female ratio is reported to vary from 4: 1 to 2: 1. Rates for black males doubled in the 1970s and 1980s but decreased in the 1990s. There has, however, been a relative increase in the number of young patients ( < 40 years) .16 [**]
RISK FACTORS
VARIATION BY SUBSITE
Nasal and ethmoid tumours exhibit a marked left -sided dominance that has been attributed to the predominance of nasal septal deviations to the left causing local deposition of airborne carcinogenic particles on that side. 9 , 12 Cancers of the maxillary antrum exhibit no such laterality, which raises the question of whether inhaled factors are operative in maxillary sinus tumours.
There is marked variation, but similar sex distribution between subsites. The most common sub site involved is the oral tongue (33 percent), followed by the floor of the mouth (28 percent), palate (12 percent), tonsil (10 percent), other pharynx (10 percent), retromolar trigone (4 percent) and buccal mucosa (3 percent).
Occupation
Leather workers, furniture manufacture and repair workers, and those exposed to cutting oils 13 have an increased risk of SNC. Nickel workers, chrome pigment manufacturers, furnace men and coal miners have a significant increased risk of SNC. Wood dust (principally of commonly used hardwoods but also softwoods 5) is the major factor that has been investigated and applies especially to adenocarcinoma of the nasoethmoid region. Social class
There is a pronounced increasing gradient for mortality fro'm SNC from Social Class I to Social Class V, especially for men and particularly for maxillary sinus tumours.
VARIATION OVER TIME
There has been a general decrease in incidence regardless of gender and race.
RISK FACTORS Smoking and alcohol
These are the two most strongly associated factors; however, difficulties in assessing independent risk factors exist due to a high correlation between habits. Risk increases with greater consumption and duration of cigarette smoking and declines after cessation, being back to normal after nine years. Alcohol demonstrates a doseresponse relationship independent of smoking. I? A synergistic effect is described by a few studies, although whether alcohol or smoking has the more significant
2348 I PART
17 HEAD AND NECK TUMOURS
effect is not clear. I? Other tobacco, such as cigars, snuff and smokeless tobacco, also carry increased relative risk. Occupation
Increases are seen in the textile industry, especially in carpet installers due to the use of formaldehyde, and also in those involved in fossil fuel, semiconductor manufacture and heavy machinists. 18 The association between farming and lip cancer has been attributed to ultraviolet exposure. Infection
The role of viruses is still unclear; however, human papilloma virus (HPV) is 4.7 times more likely to be found in patients with oral cavity carcinoma than controls. Genotype HPV 16 appears to be specifically implicated, and patients tend to be younger and nonsmoking with low alcohol intake. 19 Syphilis and erosive lichen planus have also been implicated. Oral cavity hygiene
Chronic inflammation from poor dental hygiene has been implicated, with the loss of 11 or more teeth without replacement carrying an odds ratio of 2.7. 20 Chewing betel nut and reverse smoking, prevalent in the Indian subcontinent, are associated with a high relative risk. Diet
Dietary deficiencies have been causally linked to oropharyngeal cancer, in particular, vitamins A, C and E, and iron deficiencyanaemia. 21 [***/**]
Larynx INCIDENCE
This accounts for approximately 1.7 percent of all new cancer diagnosis, 25 percent of all head and neck malignancies and in 90 percent of cases is squamous cell carcinoma. 22 [**]
VARIATION BY AGE AND GENDER It is mainly a disease of middle-aged men, with peak
incidence in the seventh decade. Women affected tend to be younger, with a peak incidence before the age of 60 years. 23 [**]
VARIATION BY SUBSITE
Classically divided into supraglottic, glottic and subglottic, subglottic being rare, the glottic to subglottic ratio is reported to be 2: 1. There appears to be marked geographical variation with supraglottic being more common in regions of France, Italy and Spain.24 [**]
VARIATION OVER TIME
Although there are exceptions, such as Finland, rising incidence trends have been reported worldwide, particu1arly in women and in black Americans. 1S [**]
RISK FACTORS
Smoking
Tobacco has been identified as the main causative agent in laryngeal cancer,2S with up to 98 percent of patients being smokers. Smoking also exhibits a dose-response relationship, current consumers having up to a 40-fold increase (pipes and cigars 22-fold) when controlled for alcohol. This declines markedly when smoking is stopped, albeit with a three-fold higher than normal risk for some ten years. 26 The type of tobacco and method of delivery are also important, dark tobacco being more harmful than light and hand rolled worse than factory made. Alcohol
In nonsmokers, alcohol may increase the relative risk of laryngeal carcinoma five-fold and has been particularly implicated in supraglottic carcinoma. The effect of . . 2S smoking and alcohol appears to b e synergIstIC. Occupational
Occupations involving exposure to dust and gas compounds or polluted work environments seem to be most at risk. Those working with asbestos, wood dust, cement dust and tar seem to have an increased risk, compared with controls, for developing laryngeal carcinoma. Diet
Poor nutritional status is related to increased relative risk of laryngeal carcinoma. Fruit and vegetables appear to have a protective effect, which may be related to their high vitamins A and C content. 2? Laryngopharyngeal reflux
Acute or chronic laryngeal inflammation caused by reflux may be a carcinogenic cofactor, analogous to Barrett's oesophagus. Kaufman and Burke28 reported a marked increase in abnormal pH studies in patients with early laryngeal carcinoma. There is also a subgroup of nonsmokers in whom reflux appears to be the only risk factor. Viral
HPV subtypes 16 and 18 appear to be implicated in laryngeal carcinoma, and may be identified in up to 40 percent of cases. 29 Cummins reported that up to 20 percent of patients with laryngeal papillomas went on to develop squamous cell carcinoma of the upper aerodigestive tract. 28 [***/**] Table 179.3 provides a summary of the evidence relating to commonly identified risk factors, by subsite.
Chapter 179 Epidemiology of head and neck cancer
Table 179.3
I 2349
Summary of the evidence relating to commonly identified risk factors, by subsite.
Subsite Oral cavity larynx Pharynx Nasopharynx Sinonasal
Alcohol
+ + ++
Tobacco
+ ++ +
Genetics
Viral
? ? ?
?
+
++
+++
?
?
Reflux
+ +
Occupation
Diet
+ +/-
+ + + + +
+++
?, suggestive/implicit evidence; -, no useful information available.
KEY POINTS • Cancer causation is multifactorial. • Carcinogenesis. isa. multistep process. • A long interval exists between first exposure to ca.rcinogen and appearance . ()f canCer. • Descriptiveepi
3.
4.
5.
6.
7. 8.
Deficiencies in current knowledge and areas for future research
»
More analytical studies are needed for specific head and neck cancer subsites. A highly specific, highly sensitive screening test for head and neck cancer is needed. Stronger molecular biology evidence for the role of viruses in causation is needed. More high quality evidence of the impact of diet in causation/protection is needed. More studies on genetic/HLA associations with head and neck cancer are needed. More evidence that interventions are effective in prevention are needed.
9.
10.
11.
12.
13.
14.
REFERENCES 1.
2.
Ramadan MF, Morton RP, Stell PM, Pharoah PO. Epidemiology of laryngeal cancer. Clinical Otolaryngology and Allied Sciences. 1982; 7: 417-28. Doll R, Hill B. The mortality of doctors in relation to their smoking habits. British Medical Journal. 1954; 1: 1451-5.
15.
Spitz MR, Fueger JJ, Goepfert H, Hong WK, Newell GR. Squamous cell carcinoma of the upper aerodigestive tract. A case comparison analysis. Cancer. 1988; 61: 203-8. Imbernon E, Goldberg M, Bonenfant S, Chevalier A, Guenel P, Vatre R et al. Occupational respiratory cancer and exposure to asbestos: a case-control study in a cohort of workers in the electricity and gas industry. American Journal of Industrial Medicine. 1995; 28: 339-52. Acheson ED, Pippard EC, Winter PD. Mortality of English furniture makers. Scandinavian Journal of Work, Environment and Health. 1984; 10: 211-7. Goldsmith DB, West TM, Morton R. HLA associations with nasopharyngeal carcinoma in Southern Chinese: a metaanalysis. Clinical Otolaryngology and Allied Sciences. 2002; 27: 61-7. Morton RP, Benjamin CS. Nasopharyngeal carcinoma, salted fish, and Polynesians. Lancet. 1989; 2: 1210-1. Muir CS, Nectoux J. Descriptive epidemiology of malignant neoplasms of nose, nasal cavities, middle ear and accessory sinuses. Clinical Otolaryngology and Allied Sciences. 1980; 5: 195-211. Robin PE, Shortridge RT. lateralisation of tumours of the nasal cavity and paranasal sinuses and its relationship to aetiology. Lancet. 1979; 1: 695-6. Vianna NJ, Ulitsky G, Shalat SL. Epidemiologic patterns of frontal and maxillary sinus cancer. Laryngoscope. 1982; 92: 1300-3. Acheson ED, Pippard EC, Winter PD. Nasal cancer in the Northamptonshire boot and shoe industry: is it declining? British Journal of Cancer. 1982; 46: 940-6. Morton RP, Sellars SL. laterality of sinonasal cancer and its aetiologic implications. Clinical Otolaryngology and Allied Sciences. 1988; 13: 193 -6. Roush GC, Meigs JW, Kelly JA, Flannery JT, Burdo H. Sinonasal cancer and occupation: a case-control study. American Journal of Epidemiology. 1980; 111: 183-93. Sakai S, Shigematzu Y, Fuchihata H. Diagnosis and TNM classification of maxillary sinus carcinoma. Acta Otolaryngologica. 1972; 74: 123-9. Gloeckler Ries LA, Miller BA, Hankey BF, Kosary Cl, Harras A, Edwards BK (eds). SEER cancer statistics review, 19731991. Bethesda, MD: US Department of Health and Human Services, Public Health Service, National Cancer Institute, 1994. Report no. NIH-94-2789.
2350 I PART 17 HEAD AND NECK TUMOURS Schantz SP, Yu GP. Head and neck cancer incidence trends in young Americans, 1973-1997, with a special analysis for tongue cancer. Archives of Otolaryngology - Head and Neck Surgery. 2002; 128: 268-74. 17. Kabat GC, Chang CJ, Wynder EL. The role of tobacco, alcohol use, and body mass index in oral and pharyngeal cancer. International Journal of Epidemiology. 1994; 23: 1137-44. 18. Huebner WW, Schoenberg JB, Kelsey JL, Wilcox HB, McLaughlin JK, Greenberg RS et al. Oral and pharyngeal cancer and occupation: a case-control study. Epidemiology. 1992; 3: 300-9. 19. Sugerman PB, Shillitoe EJ. The high risk human papillomaviruses and oral cancer: evidence for and against a causal relationship. Oral Diseases. 1997; 3: 130-47. 20. Garrote LF, Herrero R, Reyes RM, Vaccarella S, Anta JL, Ferbeye L et al. Risk factors for cancer of the oral cavity and oro-pharynx in Cuba. British Journal of Cancer. 2001 ; 85: 46-54. 21. Gridley G, McLaughlin JK, Block G, Blot WJ, Gluch M, Fraumeni Jr. JF. Vitamin supplement use and reduced risk of oral and pharyngeal cancer. American Journal of Epidemiology. 1992; 135: 1083-92. 22. Parkin OM, Pisani P, Ferlay J. Global cancer statistics. CA: A Cancer Journal for Clinicians. 1999; 49: 33-64. 23. Rothman KJ, Cann CI, Flanders 0, Fried MP. Epidemiology of laryngeal cancer. Epidemiologic Reviews. 1980; 2: 195-209.
Stephenson WT, Barnes DE, Holmes FF, Norris CWo Gender influences subsite of origin of laryngeal carcinoma. Archives of Otolaryngology - Head and Neck Surgery. 1991; 117: 774-8. 25. Tuyns AJ, Esteve J, Raymond L, Berrino F, Benhamou E, Blanchet F et al. Cancer of the larynx/hypopharynx, tobacco and alcohol: IARC international case-control study in Turin and Varese (Italy), Zaragoza and Navarra (Spain), Geneva (Switzerland) and Calvados (France). International Journal of Cancer. 1988; 41 : 483-91. 26. Falk RT, Pickle LW, Brown LM, Mason TJ, Buffler PA, Fraumeni Jr. JF. Effect of smoking and alcohol consumption on laryngeal cancer risk in coastal Texas. Cancer Research. 1989; 49: 4024-9. 27. Mettlin C, Graham S, Priore R, Marshall J, Swanson M. Diet and cancer of the oesophagus. Nutrition and Cancer. 1981; 2: 143-7. Kaufman JA, Burke AJ. The aetiology and pathogenesis of 28. laryngeal carcinoma. Otolaryngologic Clinics of North America. 1997; 30: 1-19. Excellent review of causation of laryngeal cancer. 29. Brandsma JL, Steinberg BM, Abramson AL, Winkler B. Presence of human papillomavirus type 16 related sequences in verrucous carcinoma of the larynx. Cancer Research. 1986; 46: 2185-8.
24.
16.
*
180 Aetiology of head and neck cancer
NICHOLAS D STAFFORD
A molecular and genetic progression model of head and
Introduction
2351
Tobacco and alcohol
2351
Viruses
2352
Key points
Environmental factors
2353
Deficiencies in current knowledge and areas for future
Occupational and dietary factors
2353
Cancer as a genetic disease
2354
neck squamous carcinoma
research References
2356 2356 2356 2356
Familial predisposition to head and neck squamous cell carcinoma
2354
The data in this chapter are supported by a PubMed search using the key words head and neck, squamous cell carcinoma, aetiology, viruses, tobacco and alcohol. The evidence levels are 3 and 4.
INTRODUCTION Aetiology is that part of medical science which investi gates the causes of diseases. The collective term head and neck squamous cell carcinoma (HNSCC) encompasses more than 95 percent of all head and neck cancers, therefore, this chapter will place particular emphasis on this histopathological group. However, the aetiologies of less common head and neck malignancies will also be covered in those instances where there is at least some understanding of them.
TOBACCO AND ALCOHOL Tobacco and alcohol appear to play a far greater role in the aetiology of HNSCC than does any inherited genetic predisposition. They are the two strongest aetiological factors for the development of HNSCC, both indepen dently· and synergistically.)·2 Although most of the evidence concentrates on the link between tobacco and
laryngeal squamous cell carcinoma (SCC) it also exists for other upper aerodigestive tract (UADT) sites, such as oesophagus and lung. One study reported that exposure to alcohol and tobacco increased the risk of laryngeal cancer 50 percent more than might be expected from a purely additive effect.3 In two separate studies, 96.5 and 97.2 percent of patients with laryngeal squamous carcinoma were smo kers.4,5 In a further study, the relative risk of laryngeal cancer was 4.4 for smokers of up to ten cigarettes per day, rising to 34.4 for smokers of over 40 cigarettes per day, demonstrating the dose-dependent relationship between smoking and incidence of HNSCC.6 While stopping smoking leads to a reduction in risk, heavy smokers who had quit at least ten years prior to the inclusion in one study had a persistent three-fold risk of developing laryngeal cancer when compared with lifelong nonsmo kers.7 Relative risk is also dependent upon the quality of tobacco used. Light tobacco is flue-cured, while dark tobacco is air processed. Use of the latter type is associated with a relative risk two to five times higher
2352 I
PART 17 HEAD AND f\IECK TUMOURS
than that associated with the former.s Tobacco smoke
type of alcoholic beverage is relevant in considering risk,
consists of a potent mix of more than 4000 chemicals, 43
and not simply the total intake of ethanol. A more
of which have, to date, been identified as carcinogens and
recently
include polycyclic hydrocarbons, nitrosamines and radio
published
study
examining
the
association
active polonium-210. There is a link between the HNSCC
between different alcoholic drinks and UADT cancer ? was a Danish population-based study of 28,180 people. I
subsite and the method of tobacco use (i.e. smoking,
Compared with nondrinkers, subjects who drank 7-21
chewing and reverse smoking). In many Asian countries
units per week of beer and/or spirits but no wine had a
chewing tobacco, or its derivatives, is more common than
relative risk
smoking it. For example, in Bombay a mixture of chewing
oesophageal cancer. However,
of
3.0
of
developing
oropharyngeal
or
tobacco called pan (consisting of betel nut, catechu,
similar amount but who also drank wine as > 30 percent
subjects who drank a
tobacco and areca nut) is very popular and is believed to
of their total alcohol intake had a relative risk of 0.5. For
contribute to the high incidence of HNSCC of the oral
subjects who consumed > 21 units per week the relative
cavity and hypopharynx. These cancers make up 50
risks, including and excluding wine, were 5.2 and 1.7,
percent of all cancers in Bombay but account for only 3
respectively. Therefore, while there is a strong association
percent of all cancers in the West where smokeless
between beer and spirit consumption and UADT cancer,
consumption of tobacco is much less popular.8 HNSCC
those who drink a similar quantity of wine are at a lower
of the hard palate, uncommon in most of the world, is
risk, while moderate wine drinkers may be afforded an
another example of the link between the method of
overall degree of protection, compared with their teetotal
tobacco use and cancer site. A high incidence of hard
counterparts. The incidence of metachronous squamous
palate cancer is seen in parts of India, Venezuela and
cell cancer of the UADT is reported to be between 5 and
Panama where the practice of reverse smoking (in which
35 percent. 18
the burning end of the home-made cigar is held inside the
phenomenon of 'field cancerization' which, in turn, is
This high
figure is attributed to
the
mouth) is prevalent.8, 9 Cannabis smoking also appears to
explained by the panmucosal carcinogenic influences of a
confer a higher risk of HNSCC than tobacco smoking.
variety of environmental factors such as tobacco and
This is probably due to the higher tar burden and greater
alcohol.
concentrations
of
aromatic
hydrocarbons
found
in
Alcohol,
a
knowledge, the incidence of smoking in the UK has begun
per se, but it is thought to potentiate
to increase again after dramatic falls in the late 1970s and
tobacco-related carcinogenesis synergistically. The major
1980s. Public education by surgeons and health care
carcinogen
or
more
Head and neck cancer is most common in male tobacco users aged between 50 and 65 years. Despite this
marijuana smoke.lO accurately,
ethanol,
is
not
ity of patients with head and neck cancer are heavy
workers appears to have failed to educate individuals
drinkers and smokers. Ethanol, in its role as a solvent,
choosing to put themselves at risk. This may reflect the
may exert its inHuence by enhancing the contact of
failure to provide a medical or scientific explanation for
tobacco carcinogens with the mucosa of the UADT.9
the fact that many smokers and drinkers do not develop
During the Second World War, in France, the fall in
cancer. The risks posed by tobacco and alcohol use are
incidence of laryngeal cancer reHected a fall in alcohol
likely to depend on the degree of exposure (duration
consumption, in spite of there being no change in tobacco
more than intensity) and the inherent susceptibility of the
use. 1 1 In the same country it has been reported that the
individual.
risk of developing supraglottic SCC is greater for alcohol
explanation for the interindividual differences in suscept
users than for tobacco users.I2
of
a
molecular
or
genetic
ibility to carcinogen exposure would allow for closer
The biological mechanisms of the ethanol effect are still unclear, although recent
Identification
in vitro experiments have
monitoring of patients at risk of developing cancer, as well as for more int1uential health education programmes.
demonstrated the induction of proliferation and down regulation of the p21 cell cycle inhibitor in HNSCC cell lines treated with this solvent.I3 However, the explanation
VIRUSES
that alcohol exerts its effect purely as a solvent does not explain the persistence of risk elevation several years after
Human papilloma virus (HPV ) is believed to play a
cessation
its
central role in the aetiology of SCC of the cervix and has
influence by interfering with the synthesis of retinoids,
recently been implicated in HNSCc.I9 HPV genotypes
of
drinking.I4
Ethanol
may
also
exert
derivatives of vitamin A, implicated in the chemopreven
have been classified into three risk categories for the onset
tion of HNSCC. Other groups have implicated nitrosa
of malignant phenotypes: high (types 16, 18), medium
mines (also present in tobacco), which are present in high
(types 31, 33) and low (types 6,
levels in beer, lower levels in distilled spirits and negligible
recurrent respiratory papillomatosis, caused by infection
levels in wine.Is The picture has been further complicated by the recent discovery of resveratrol in grapes and wine, and the subsequent demonstration of its cancer chemo preventive activity.I6 It has, therefore, emerged that the
l1)?O Adult onset
with low-risk HPV types 6 and 11, is associated with a small chance (3 percent) of malignant transformation to veruccous SCt?I Using polymerase chain reaction-based analysis, DNA of the high risk HPV types 16 and 18
Chapter 180 Aetiology of head and neck cancer I
has been detected in HNSCC at a frequency of 35-60
HNSCC subsites in terms of
percent, with the highest frequency in tumours of the oral
behaviour.
cavity.22, 23 Another study demonstrated that the presence
2353
tumour aetiology and
of HPV 16118 DNA was associated with an increased risk
of
head
and
neck
cancer
formation,
with
an
ENVIRONMENTAL FACTORS
odds ratio of 4.32.24 Two protein products of HPV 16118 DNA encoded by exons 6 and 7 (E6 and E7) have
Exposure to sunlight increases the risk of developing
been shown to inactivate the tumour suppressor gene
squamous carcinoma of the facial skin and lips.34 Melanin
products p53 and pRb (retinoblastoma protein), thereby
pigmentation provides a protective effect and an explana
potentiating cell immortalization.25 Rather than acting
tion for the differential incidences in different racial
as a major independent risk factor for recent review of the literature
HNSCC, a
concluded
that
HPV
groups. Other than lip cancer two further associations are also known to exist between radiation and carcinoma of
infection is more likely to play a synergistic role with
the UADT. These are paranasal sinus cancers related to
behavioural risk factors, such as cigarette smoking and
radium watch dial painting and thorotrast ingestion, and thyroid cancers related to radiotherapy.35 Thyroid cancer
alcohol consumption.26 The most compelling evidence of a viral aetiology
can be induced by exposure to radiation, the relative risk
exists between Epstein-Barr virus (EBV) and nasophar
estimates ranging between 7 and 69 among various age
yngeal carcinoma (NPC) and includes the following.
groups, ethnic groups and in different studies.
•
An association between radiotherapy for thyrotoxicosis
Higher EBV antibody titres (especially 19A) in
or tuberculous lymphadenitis and the subsequent devel
patients with NPC compared with controls. •
opment
EBV antibody levels rise with tumour burden irrespective of different geographical locations and Finding the EBV genome in both undifferentiated
•
Demonstration of EBV DNA in dysplastic and
thyroid
in situ lesions
SCC
has
also
been
reported.
cancers, an increased relative
proportion
of
follicular carcinomas and a larger number of giant and
and well-differentiated NPC tumours. carcinoma
laryngeal
deficiency are associated with an increased incidence of
ethnic groupS.27 •
of
Geographical areas where there is a relative dietary iodine
spindle cell undifferentiated carcinomas of the thyroid gland.
of the nasopharyngeal
mucosa. This suggests that there is a clonal proliferation from a single EBV-infected cell before
OCCUPATIONAL AND DIETARY FACTORS
expansion of the malignant cell clone.28 •
The virus is linked to the development of several
Nickel and chromate refining workers have an increased
human cancers and can cause lymphoma in
incidence of laryngeal squamous cancer, while hardwood
immunocompromised patients. An association
dust has been identified as an aetiological factor in
between EBV and NPC is strong and persistent.29 •
The inability to detect EBV in normal nasopharyngeal mucosal biopsies from patients at high risk of
the development of adenocarcinoma of the paranasal sinuses.36 The majority of the evidence regarding asbestos exposure supports an association with the development of
developing NPC or in normal mucosa adjacent to
laryngeal SCc. However, some studies have been flawed
EBV-positive NPCs.30
by not taking into account the confounding effects of
Therefore, the evidence that EBV is an important causal
tobacco
factor
strong.
consequence, there has been an argument against an
However, the ubiquitous nature of EBV infection world
association,37 but the majority of published work, where
in
the
development
of
NPC
is
very
smoking
and
alcohol
consumption.
As
a
wide, in contrast to the marked geographical variation in
such issues have been taken into account, points to the
the development of NPC, excludes EBV as the sole
relative risk for developing laryngeal cancer as being
causative factor of the tumour. EBV is a herpes virus
between 1.8 and 9.38,39 A recent French studlo supports
ubiquitous in all human populations. Infection is always
associations
accompanied by seroconversion and the establishment of
epilaryngeal and hypopharyngeal cancer.
between
asbestos
exposure
and
both
There is an association between Paterson-Brown Kelly
permanent immunity to reinfection. In South East Asia, where NPC is endemic, the EBV
syndrome (iron deficiency anaemia, glossitis, koilonychia
genome is consistently detected in tumour cells.31 The
and upper oesophageal webbing) and postcricoid carci
EBV genome not only encodes oncogenic proteins itself
noma. The underlying iron deficiency in this condition
(e.g. EBNA-LP) but also includes host expression of
may explain the relative preponderance of postcricoid
proto-oncogenes (e.g. bcl-2, bcl-10 and
carcinoma in females. Paterson-Brown Kelly syndrome,
junlfos).32
In
cidentally, the consumption of nitrosamines in salted fish,
which can be reversed with iron replacement and vitamin
whIch is a dietary standard in China, has also been
B
identified as an independent risk factor for NPC.33 It
improvements, and so its importance as a risk factor for
should be emphasized that NPC is quite different to other
therapy, is
becoming
less
common
postcricoid carcinoma is diminishing.41
with
dietary
2354 I PART 17 HEAD AND NECK TUMOURS The association between a salted fish diet, particularly
few as six critical genetic alterations thoughout the entire
in childhood, and the later development of NPC in
genome to allow a cell to overcome the mechanisms that
Chinese individuals with EBV has already been men
tightly control cell proliferation and invasion.
tioned. Certainly, traditional southern Chinese foods have
Theodor Boveri recognized that such growth advan
been shown to contain carcinogens. Such salted fish
tage could be passed on to the daughter cells following
contain volatile nitrosamines, principally N-nitrosodi
mitosis. In 1914, this led him to propose the 'somatic
methylamine and N-nitrosodiethylamine, both of which
mutation theory' of cancer, which postulates that the
have been shown to be carcinogenic in animal studies.42
mode of transmission of the malignant genotype is via
Epidemiological data suggest a protective role of dietary carotenoids and an inverse association between
mitotic
replication
of
permanent
mutations
in
the
genome.50 Extension of this concept gives rise to the
the consumption of fruit and vegetables and the incidence
clonal evolution theory of tumours, whereby continued
of head and neck cancer.43 Vitamin A has been shown to
proliferation of the genetically identical daughter cells
have an inhibitory effect on the development of epithelial
leads to tumour formation.51
tumours by controlling cell differentiation. Retinoic acid
Second-generation Chinese who have emigrated from
treatment has brought about regression of laryngeal
high-incidence to low-incidence areas in western coun
leukoplakia44
of
tries retain a high risk of developing NPC.52 This, along
Over the last three decades laryngopharyngeal reflux
in first-degree relatives in diverse populations, 53 high
and
a
reduction
in
the
incidence
subsequent second primary HNSCCS.45
with the observation of multiple cases of NPC occurring
(LPR) has received significant attention as a possible
lights the likelihood of an inherited genetic predisposition
factor in laryngeal carcinogenesis. Given its association
to the disease. Specific haplotypes of the human leukocyte
with Barrett's oesophagus and oesophageal malignancy;
antigen (HLA) loci on the short arm of chromosome 6
attempts have been made to establish a link between LPR
have been associated with an increased risk of NPC. The
and the subsequent development of laryngeal carcino
HLA
ma.46 As yet such an association has not been firmly
between Chinese and Caucasian populations.54 It is
established.
haplotypes
associated
with
NPC
are
different
believed that patients with one specific gene haplotype are rendered unable to mount a specific cellular-mediated immunity to infection caused by the EBV.
CANCER AS A GENETIC DISEASE The development of a head and neck cancer involves the progressive loss of homeostatic control of cell growth and
FAMILIAL PREDISPOSITION TO HEAD AND NECK SQUAMOUS CELL CARCINOMA
death. There is some evidence that this loss is, at least in part, determined genetically.47 The regulation of the
To a great extent, head and neck cancer is a preventable
growth and proliferation of the 30 trillion cells in the
disease, with the vast majority of cases occurring in
human body is tightly controlled by the 40 or so known
individuals with a history of exposure to the carcinogens
proteins that regulate the cell cycle. These proteins are the
mentioned above. However, not all HNSCC patients have
products of proto-oncogenes and tumour suppressor
been exposed to environmental carcinogens and, indeed,
genes. Under normal conditions, the coordinated expres
some
sion of these genes leads to an equilibrium between
tobacco and alcohol habits and never develop the disease.
individuals go through life enjoying extensive
growth promoting and growth restraining signal trans
First-degree relatives of head and neck cancer patients
duction, and natural cell loss, such that cell turnover is
appear to have a higher incidence of UADT cancer than
appropriate to the tissue and physiological circumstance.
do the relatives of cancer-free controls, an observation
Mutations may produce an imbalance of these factors,
that
through proto-oncogene activation and tumour suppres
environmental exposure alone.55 This evidence suggests
cannot
convincingly
be
explained
by
similar
sor gene inactivation, which leads to an unbalanced
that genetic factors are likely to contribute to HNSCC
mitogenic signal and consequent aberrant cell prolifera
risk.
tion. A variety of mechanisms produce mutations (i.e. a
The majority of ingested carcinogens are not danger
change in the sequence of genomic DNA) including point
ous themselves. It is the intermediate metabolites, created
mutations, deletions and amplifications of segments of
as the body attempts to metabolize the compounds,
DNA, and chromosomal rearrangements, where chromo
which are carcinogenic. Therefore, the manner in which
somes in part or in whole are lost, translocated or
the individual manages the removal of toxic compounds
reduplicated. The accumulation of these genetic altera
is crucial in understanding the risk posed. Detoxification
tions underlies the progress from a normal cell to a cancer
of these carcinogenic intermediates requires an efficient
cell, and is referred to as multistep carcinogenesis.48 It has
enzyme system. If a particular intermediate is allowed to
been estimated that between 6 and 11 specific mutations
accumulate, due to insufficient levels of a particular
are required for the development of HNSCC.49 Thus,
enzyme in the metabolic pathway, then it is free to exert
acquisition of the malignant phenotype may require as
its effects in the local environment. The active metabolites
-
Chapter 180 Aetiology of head and neck cancer I 2355
of many chemical carcinogens can covalently bind to
Polymorphism in several members of the GST family of
DNA, causing the formation of DNA adducts leading to
detoxifying enzymes has been analysed in HNSee and
genetic mutations. Polymorphism (the presence of subtly
putatively
different versions of one enzyme in different individuals)
identified. Preliminary studies have indicated that the
of
GSTMI AB genotype may be associated with a lower risk
several
enzymes
involved
in
the
metabolism
of
protective
and
risk
genotypes
have
been
carcinogens has been examined.56 A study on a series of
for all HNSee, while the GSTM3 BB genotype and
Japanese patients with oral sees identified an increased
GSTP 1 AA genotype are specifically associated with a
risk for individuals with a particular polymorphism of
lower risk of laryngeal and
N-acetyltransferase 1. This enzyme is responsible for
respectively.56 Individuals lacking the GSTMI gene (the
oral/pharyngeal
cancers,
acetylating a variety of carcinogenic aromatic amines. A
(null' genotype) have been shown to be at an increased
variety of polymorphic genotypes has been identified with
risk for all types of HNSec. 59 Genetic
differing rates of metabolic activity. Katoh et al. identified
polymorphism the
key
increased
detoxification
enzymes
NAT 1 *10 allele.57
mutagens exhibited by lymphocytes from HNSee patients
Another important enzyme involved in the detoxifica
may explain
within
a significantly increased risk of oral sec associated with
susceptibility
to
when compared with healthy controls.60 The abnormal
tion of carcinogenic nitrosamines and aromatic amines
sensitivity to bleomycin-induced chromosomal damage
found in cigarette smoke is glutathione S-transferase
in vitro in the lymphocytes of HNSee patients has been
(GST). Four enzyme families have been identified: GST rJ."
postulated to reflect an inherent chromosomal instability
(P) and 8 (T), all of which catalyse the
in the genomes of cancer patients.47 The influence of
conjugation of carcinogens to glutathione.58 The meta
GSTMI genotype on the induction of bleomycin-induced
bolism of these carcinogens shows considerable inter
DNA breaks has been examined and a higher frequency of
individual variability related to genetic polymorphism.
chromatid breaks and gaps was suggested in the GSTM 1
Jl
(M),
TI
Normal mucosa
D
-<�====::JIDD
EGF, EGFr Overexpression
-<�====::JI 0 0
9p loss, 3p loss
Hyperplasia
p53 mutation, 11q13 amplification
17p loss DYSPLASIA (Mild ......f--.
D
---+..
---
Moderate
. ......f---
---+..
---
Severe)
��====::JDD 17p13, 3p25, 3p14, 8q, 13q 14q loss
Carcinoma in-situ
D
-=:::::::�====::JI 0 0 4q, 6p, 8p, 18q loss, 3q amplification
Invasive carcinoma
D
Metastases
-<�====::JI 0 0
Matrix metalloproteinase overexpression (MMP-2, MMP-9)
Figure 180.1
Progression of normal mucosa to
invasive disease and metastatic HNSCC are shown in association with genetic events. Adapted from Ref. 48, with modification by Frank Agada and Leon Fletcher, University of Hull, UK, 2006.
2356
I PART 17 HEAD AND NECK TUMOURS
null group. However, the small study cohort
(n
=
18)
rendered this finding statistically nonsignificant.61 This
ns hip
relatio
between
enzyme
incidence may also explain,
variants
and
cancer
in part, the increase in relative
risk identified in first-degree relatives (who will share
of
terms
targeted
screening
to
detect
p rem alignan t
transfo rma tion and early detection of tumour recurrence.
Figure 180.1 shows, least is known about the
As
molecular and genetic events underlying the transition between invasive sec
and metastasis .
many of the same ge n es) of patients with multiple head
and neck cancers. Identification of genetic polymorphism
associated with differing levels of DNA adduct formation may eventually allow clinicians to predict an individual's
K EY· POINTS
.
.
response to exposure to these carcinogens and identify individuals at increased risk of cancer. a large
In
retrospective
case-controlled study the
for first-degree rela t i ves of patients with HNSeC , rising to 7.89 in fir st-degree relatives of patients with multiple
HNSec.62 A5 mentioned, GSTs catalyse the conjugation of carcinogens to glutathione. 58 GSTPl, an important member of this family, is polymorphic in humans, with
allelic variants differing in theit catalytic activities towards 3 a range of carcinogens.6 The GSTP 1 AA genotype is
thought to confer relative resistance to mutagens, and has been
found
at
a
significantly
lower
frequency
in
individuals with oropharyngeal and laryngeal cancers. 56
.
.
·
- .
a djust ed relative risk for HNSCC development was 3.79
·
t� ba-ccO is-the
mO $t.
.
im p o rt a nt aetiolQ. gicil
the aet19Iogy'" of,HNSeX;:. :Alcohol., prQbablY.-potentiates. tobacco-related ' " carcinogeneSis synergisticaily. :;, '" �HPV- is' .31so- more--like1y to. phiy a syne rgis t ic '-.' '- role-�. rather'- than: tepres,erit?-n indep e n d en t ,�;< fadOI-i1L
_
<'1
.::
·
. ,.�
. '
risk fador.
,
'
,-. EEV 'p4ys an j,mportant causal role in the , ";�'�- ,.: develop:ment of NPC. ' �d., �,:�etween 6 and It specific genetic mutations ::
.' _
,-� are
�O\lght' to;-be 'requi�.ed:for- -the,
'.i'dev�lo.prnent of ?lNSCC ..
Variants of cytochrome-p45064 and N-acetyltransferase57 have been associated with an increased risk of UADT and
oral sce, respectively.
Cytochrome p450, the gene that encodes for aryl
hydrocarbon hydrozylone, imitates a multienzyme path way that activates polycyclic aromatic hydrocarbons.
Deficiencies in current knowledge and areas for future research
Of
50 patients with oral and pharyngeal cancers, 26 exhibited
>- While the understanding of the aetiology and the
high aryl hydrocarbon hydrozylone activity, as compared 65 with a prevalence of 8.6 percent in a normal population .
causal mechanisms of HNSCC is a rapidly developing topic, the precise way in which these tumours develop is still poorly understood. Hopefully advances in this area of research will allow the development of therapeutic strategies that can block what is currently
A MOLECULAR AND GENETIC PROGRESSION MODEL OF HEAD AND NECK S QUAMOUS CARCINOMA
a relentless progression from gene mutations to the development of overt cancer. Such therapies could well be available within the next five years.
The pioneering genetic progression model for colorectal tumorigenesis was proposed by Fearon and Vogelstein in
1987. Specific genetic alterations were assigned to each
step
of
the
well-established
adenoma-carcinoma
se
quence.66,67 Several authors have atte m pted to construct
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181 Staging of head and neck cancer NICHOLAS J ROLAND
2359
Limitations of T staging
2367
2359
Limitations of N staging
2368
History of staging
2360
Limitations of stage grouping
2368
General rules
2360
Key points
2369
Stage grouping
2361
Deficiencies in current knowledge and areas for future
M ethod
2362
Sites in the head and neck region
2363
Introduction Aims of the
staging system
TNM
2370
research
2370
References
The data in this chapter are supported by a Medline search using the key words staging of head and neck cancer. The authors also consulted the International Union Against Cancer booklet TNM classification of malignant tumours, 6th ednl
an d AlCC cancer staging manual, 6th edn.2 The nature of staging has meant that the data to support the concept have been largely drawn from retrospective and observational st udies (level 3). Much of the systems development has been through the opinion of expert panels using these data (level
4).
INTRODUCTION
followed by spread to the regional lymph nodes (N) and eventually spread beyond these nodes to distant meta
(M). The stage at diagnosis in the life history of
There are many aspects which affect the outcome of
static sites
patients with a malignant head and neck tumour. These
an individual cancer is numerically assigned a TNM
relate to the tumour (the anatomical site and the clinical
classification. These individual TNM classifications are
and pathological extent of the disease), the host (age,
then assembled into four groups - stage groups (stages
general condition and any intercurrent disease of the
I-IV), each with similar survival outcomes based on the
patient) and management (treatment options, expertise
observation that better survival is anticipated for cancers
available, patient preference). Concurrently, there are also
with less extension.
many proposed systems that try to evaluate these factors and predict outcomes for an individual patient. Staging of head and neck cancer is a system designed to express the relative severity, or extent, of the disease. It
is meant to facilitate an estimation of prognosis
and provide useful information for treatment decisions.
Classification
by
anatomical
extent
of
the
disease,
as determined clinically and histopathologically (when possible),
is
that
with
which
the
tumour,
nodes,
AIMS OF THE TNM STAGING SYSTEM There are many benefits to staging) but one of the principal purposes is to provide
a
method of conveying
clinical experience to others without ambiguity. The objectives of staging are:
metastases (TNM) system primarily deals. The concept
•
to aid the clinician in the planning of treatment;
is that an orderly progression of disease takes place with
•
and invasion by the primary tumour (T)
•
to give some indication of prognosis;
enlargement of
to assist in evaluation of the results of treatment;
2360 I •
•
PART 17
H EAD AND NECK TU MOURS
to facilitate the exchange of information between treatment centres; to contribute to the continuing investigation of human cancer.
The strengths of the TNM staging system are its simplicity, low cost, relative accuracy, objectivity, universal accep tance and lack of need for special technology; however, the system is not without limitations. Inconsistencies, observer variability and differences in stage method contribute to potential bias. Uniformity in the method of data collection, knowledge of the current TNM system and accurate application of the correct stage are therefore pivotal if meaningful information is to be derived.
addition to this, data from state cancer registries are also used on occasion. Review of the literature has been p erformed to incorporate new information and/or new data, which may impact upon revisions on the staging process. In the current ( sixth) edition of the AJee cancer staging manual, published in May of 2002, the outcomes data presented reflect the information from the NCDB.2 The current (sixth) edition of the UICC contains rules of classification and staging that correspond exactly with those appearing in the sixth edition of the AJee cancer staging manual and has approval of all national TNM 1 committees. ,2
GENERAL RULES HISTORY OF STAGING The TNM staging system has developed with contribu tions from both sides of the Atlantic. In Europe, Pierre Denoix developed the TNM system for the classification of malignant tumours between the years 1943 and 1952.3 During the 1950s the International Union Against Cancer (UICC) appointed a Committee on Tumour Nomenclature and Statistics. Agreement was reached on a general technique for classification by anatomical extent of the disease, using the TNM system. In 1958, laryngeal and breast cancer were the first cancers to be assigned recommendations on clinical stage and presentation of results.4 A decade later, the first TNM booklet, the Livre de poche, was published. 5 Over the years, series of meetings have been held to update and unify existing classifications as well as to develop new ones. In the USA the initial staging system proposed by the American Joint Committee on Cancer (AJCC) in the late 1960s and implemented in the mid-1970s was simply based on 'consensus' of leaders and experts in the specialty who were members of the working group of what was then called The American Joint Committee for Cancer Staging and End-Results Reporting. They reviewed the available literature of that time and added their own experiences to devise the initial staging system. Subsequent revisions were also implemented based on the observations of the committee members on informa tion available in the literature and from institutional expenences. In 1983 The American Joint Committee for Cancer Staging and End-Results Reporting became the now familiar AJCC. Since 1996, the current AJCC Head and Neck Task Force has utilized the data from the National Cancer Data Base (NCDB) . This is maintained by the Commission on Cancer of the American College of Surgeons and supported by the American Cancer Society as well as data from Surveillance, Epidemiology, and End Results Reporting (a database maintained by the National Cancer Institute which represents 14 cancer registries). In
The TNM system for describing the anatomical extent of the disease (Tables 181.1, 181.2 and 181.3) is based on three components: • •
•
T - extent of the primary tumour; N - absence or presence and extent of regional lymph node metastases; M - absence or presence of distant metastases.
All cases should be confirmed microscopically. Two classifications should be documented for each site, Table 181.1
Extent of the pri m a ry t u m o u r.
Ddinitlc)n TX
,... ....
Primary tumou r ca n not be assessed No evidence of pri m a ry t u m o u r Carcinoma i n situ I ncreasing size a nd/o r loca l extent of the p rimary tumour
TO Tis T 1 , T2, T3 , T4
Reproduced from Ref.
1 , with permission.
Table 181.2
Absence or presence a nd extent of region a l lym ph node metastases. �.
NX NO N 1 , N2, 1\J3
Definition
M
MX MO M1
.
.;
�.
"
r '.
Reg i o n a l lym p h nodes ca n not be assessed No evidence of region al lym ph node metastases I ncreasing i nvolvement of region a l lymph nodes
Reproduced f �om Ref.
Table 181.3
..
1, with permission.
Absence or presence of dista nt m etastases. Definition
Dista nt metastasis ca n not be assessed No d i sta nt metastasis [).ista nt metastasis
Reproduced from Ref.
1, with permission.
Chapter 181 Staging of head and neck cancer I
namel y :
clinical TNM (pretreatmen t) (cTNM) and TNM (postsurgica l his top athol og i cal ) (pTNM ) . The clinical stage is essential to select and evaluate t her apy, whi le the p athologi cal stage provide s the most pr ecis e d ata to es timate prognosis and c alcul ate end results. It s hould be remembered that if there is doubt conce r ning the cor rect T, N or M category to which a particular case should be allotted, then the lower (i.e. less advanced) category should be chosen. After assigning the cTNM and pTNM categories, the pa ti en t should then be classified in a stage group. Once established this must remain u nc ha nge d in the medical records . 1
Table 181.4
pa tholo gic al
2361
Definitions of the G histopathological categories.
G
Definition
1 �,: •
GX
Grade of differentiation cannot be assessed
Gl
Well differentiated
G2
Moderately differentiated
G3
Poorly differentiated
G4
Undifferentiated
Reproduced from Ref. 1, with permission.
tumour, when classified after a disease-free interval is
prefix 'r'. The prefix 'a' indicates that cl assi ficatio n is first determ i ne d at autopsy. The certainty factor, or C factor, reflects the valid ity of c lassification ac co rding to the diagnostic methods em ployed (C1-CS). CI is evidence from standard diagnostic means whereas CS is evidence from autopsy. Generally speak ing , p re thera pe ut ic cli ni cal stag ing of head and neck cancers should be based on a C2 factor. That would be evidence obtained by spec ial dia gnostic means such as radio graphic i mag in g (e.g. computed to mograph y (CT), magnetic resonance imaging (MRI) or ultrasound scan), endoscopy, biopsy and cytology. 1 identified by the
Histopathological grading The
histol og ic al grading
squamous cell carcinoma patholog ist of the expected biolog ical behaviour of th e n eoplasm . It has been suggested that such information in co nj unction with other characteristics of the primar y tumour would be useful in the rational approach to therapy.6 Others have reserved doubts as to the validity of the method because of its subjective nat ure? ,8 Al though grading of squamous cell carcinoma of the upper aerodigestive tract mucosa is a common practice, it has not evolved as an important factor in planning therap eutic strategie s. In a s yste matic review of 3294 pa tie n ts, it was found tha t 46 percent of patie nts with poorly differentiated tumours had a nodal metastasis at presentation co mpared with only 28 pe rcen t of differentiated tu mour s . Distant metastases at pres enta tion were found in 3.4 percent of poorly differentiated tumours compared with 1.8 percent of well-differentiated tumours. Primary and nodal recurrence rates ros e and survival fell significantl y for poorl y differentiated tumours.9 In another retrospective review of over 1000 patients, g rad e and dis tant metastases were considered. It was found t hat pat ie nts with well� differentiated tumours are at low risk of metastases and patie nts with poorly differentiated tu mours are at hig h risk of distant metastases. It was suggested they should be considered for systemic chemotherapy. to Al thoug h histo logical differentiation is subject to inter- and intraobse r ver er ror, it is still wo rth wh il e in clinical prac t ic e and , the re fo re , remains an adj un cti ve part of t he TNM of
represents estimation by the
system.I,
STAGE GROUPING A tu mour with four deg re es of T, three degree s of Nand two deg rees of M will have 24 p ote nt ial TNM cate go ries. I t has, theref ore, been felt nec essa ry to condense these into a convenient number of TNM stage groups (Table 181.5). The g rou p ing adopted is desig ne d to ensure, as far as poss ible , that each group is more or less homogenous in respect of survival and in addition, that the survival rates of these groups for each cancer site are distinctive. Carcinoma in situ is c atego riz ed as stage 0, cases with distant metastases as stage IV. The exce pt i on to this grouping is for nasopharynx and carcinoma of the thy ro id (Tables 181.6 and 181.7).1,2 Table 181.5 Stage
T
2
t h e G catego ri es a pply to all h ead and neck sites apart from thyroid. T h ey are illustrated in Table 181.4. The definitions of
treatment may
of
residual
tumour
after
be de sc ribed by the symbol 'R'. A recurrent
�
".
�'.
"
M.'
T1
NO
MO
NO
MO
II
T2
NO
MO
III
T1, T2
N1
MO
T3
NO, N1
MO
Tl, T2, T3
N2
MO
T4a
NO, Nl, N2
MO
Any T
N3
MO
T4b
Any N
MO
Any T
Any N
Ml
IVb
presence
�-
T1
When s entinel lymph node biops y is atte m p ted , d es ign a tion is now applicable using the suffix 'sn' after N stage. or
.. N .,";�::..
I
IVa
absence
,-
0
Additional descriptors
The
Stage grouping.
IVc
Reproduced from Ref. 1, with permission.
2362 I
PART 17 HEAD AND NECK TUMOURS
Table 181.6
METHOD
Stage grouping for nasopharynx.
Stage
.
:"�M�':}
N ..-
T . -.' .�. .
:,.'- �
0
Ti s
NO
MO
I
T1
NO
MO
lIa
T2a
NO
MO
lib
T1
N1
MO
T2a
N1
MO
T2b
NO, N1
MO
T1
N2
MO
T2a, T2b
N2
MO
III
T3
NO, N1, N2
MO
IVa
T4
NO, N1, N2
MO
IVb
Any T
N3
MO
IVc
Any T
Any N
M1
The aim is to define in each patient all of the factors relevant to the natural history and outcome of the relevant disease, thereby enabling a patient with cancer to be grouped with other similar cases. The sex and age of the patient. the duration and severity of symptoms and signs. and the presence and severity of intercurrent disease should all be documented .
For further information.
refer to Chapter 163, Assessment and examination of
the upper respiratory tract and Chapter
and imaging of the neck.
138, Examinatio n
CT and MRI are now established as the mainstay
investigations in the preoperative work-up of patients with head and neck cancer. Not every patient requires a scan but they are useful in delineating the extent and
Reproduced from Ref. 1, with permission.
size of the primary tumour, determining the presence (particularly when risk of occult nodes is > 20 percent),
Table 181.7 ': Sta,ge'"
.
number and position of cervical lymph nodes, searching Stage grouping for thyroid carcinoma, , -" --'
......
. I
.,.,.-
,.,.
( u n der 45
.- ;.....,.:.-�
.
r':',:,,;, : ·�:C .>.i -: +,'
Papillary or follicular
II
.
--
.
"
'·-<':'·N < ,
. _,
'I
\F: 'o, 'M'
Any N
MO
Any N
Ml
(positron emission tomography) CT scan is of use in the identification of a primary of unknown origin. Several studies have suggested that a CT scan should be obtained in preference to a plain chest radiograph as this may miss
years and older) and medullary
T1
NO
MO
II
T2
NO
MO
III
T3
NO
MO
T1, T2, T3
N1a
MO
Tl, T2, T3
N1b
MO
IVA
screening for synchronous tumours and distant metas tases is particularly important in advanced tumours. PET
Any T
(45
or distant metastases (particularly the chest). Appropriate
years)
Any T
Papillary or follicular
for an occult primary and locating a synchronous primary
..-. ..... . ' .'I"""-""""':"' �..-- .•
"" -
T4a
NO, N1
MO
IVB
T4b
Any N
MO
IVC
Any T
Any N
M1
significant lung disease.
13.14
Scans to evaluate the primary site should be performed prior to biopsy to avoid the effect of upstaging from the oedema caused by biopsy trauma. Endoscopy and biopsy should be performed by a senior surgeon and in aU cases by the head and neck surgeon responsible for any future procedure. For each tumour this should include a description, diagrammatic representation and preferably also photographic docu mentation. Routine panendoscopy (oesophagoscopy and
Anaplastic (all cases are stage IV) IVA
T4a
Any N
MO
IVB
T4b
Any N
MO
IVC
Any T
Any N
M1
bronchoscopy) is contentious. Proponents point out that these procedures require very little time, and may be performed easily during planned, direct laryngoscopy. A large meta -analysis found a small advantage to pan endoscopy
Reproduced from Ref. 1. with permission.
in
detection
of second
primary
tumours
during analysis of multiple prospective studies.Is Oppo nents point out that the appropriate use of symptom
Related classifications
directed investigations
in
addition
to
routine
chest
radiography have a similar detection rate compared The World Health Organization (WHO) has developed a
with screening endoscopy and avoid unnecessary risk
series aimed at classification of tumours. The
and
international classification of diseases for oncology
panendoscopy is only recommended for symptomatic
WHO (lCD-O)
expense
in
asymptomatic
patients.16
Therefore,
is a coding system for neoplasms by topography and
patients or patients with primary tumours known to have
morphology and for indicating behaviour (e.g. malignant.
a significant risk of a second (synchronous) primary
benign) .11
tumour.
This
coded
nomenclature
is
identical
in
the morphology field for neoplasms to t he Systemized nomenclature of medicine
(SNOMED).12
It is recom
mended that the WHO classification of tumours be used
for classification and definition of tumour types and that the ICD-O code be used for storage and retrieval of data.
There is a natural desire to confer a stage on the tumour at presentation in the clinic and, certainly, after endoscopy. This should be avoided. It is better to rely
on descriptive text to avoid changing the stage as more information becomes available. The cTNM classification
J
Chapter 181
based on examination, imaging, endoscopy and biopsy should be clearly documented in the case file only when all of the above information is collated. The VICC book should be available in every theatre and clinic to assist in applying the correct stage.
Table 181.8
SITES IN THE HEAD AND NECK REGION
N2a
The TNM classification applies only to carcinomas and the following sites are included: lip and oral cavity, pharynx ( oropharynx, nasopharynx, hypopharynx) , lar ynx, maxillary sinus, nasal cavity and ethmoid sinus, salivary glands and thyroid gland. Each site is described, with rules for classification, anatomical sites and subsites where appropriate, the cTNM classification, the pTNM classification, G histopathological grading, stage grouping and a summary. The main aspects are described here, but specific details can be found in the most recent VICC/ 1, 2 AJCC TNM booklets.
Regional lymph nodes The status of the regional lymph nodes in head and neck cancer is of such prognostic importance that the cervical nodes must be assessed for each patient and tumour. Lymph nodes are described as ipsilateral, bilateral, contralateral or midline; they may be single or multiple and are measured by size, number and anatomical location (Table 181.8). Midline nodes are considered ipsilateral nodes apart from in the thyroid. Direct extension of the primary tumour into lymph nodes IS 1, 2 classified as lymph node metastasis. Imaging for node detection and delineation IS advisable if the neck is being scanned as part of the evaluation of the primary tumour, if there is a high chance of occult disease (e.g. supraglottic primary) , to assess the extent of nodal disease, to define any deep
Table 181.9 Level
II III IV V VI VII
N
NX NO N1
N2b N2c N3
Sta g i ng of head and neck cancer I 2363
I\J stage.
D�finition Regional lym ph nodes can not be assessed No reg ional lym ph node metastasis Metastasis i n a single ipsil ate ra l lym ph node, 3 c m or less in g reatest di mension Metastasis i n a single i ps i late ra l lymph node, more than 3 cm b u t not more than 6 cm in g reatest dimension Metastasis in mUlti ple i psilatera l lym ph nodes, none more tha n 6 cm i n g reatest dimension Metastasis i n b i l atera l or co ntra lateral lymph nodes, none more than 6 cm in g reatest dimension Metastasis in a lym ph node more than 6 cm in g reatest di mension
N, regional lymph node. Reproduced from Ref. 1, with permission.
nodal fixation, or if clinical detection is difficult because of a short, fat or previously irradiated neck. Lymph nodes are now subdivided into specific anatomical sites and grouped into seven levels for ease of description (Table 181.9). The pattern of lymphatic drainage varies for different anatomical sites. However, the location of the lymph node metastases has prognostic significance. Survival is significantly worse when metas tases involve lymph nodes beyond the first echelon of lymphatic drainage. I? It is particularly poor for lymph nodes in the lower regions of the neck, i.e. level IV and level V (supraclavicular area). The sixth edition of the VICC booklet alludes to the importance of levels in some sites, but does not present any definitions. The AJCC cancer staging manual gives a much more thorough account. It recommends that each N staging category be recorded to show, in addition to the established parameters, whether the nodes involved are located in the upper (V) or lower (L) regions of the neck, depending on their location above or below the lower 1, 2 border of the thyroid cartilage.
Nomenclatu re of the an atomica l sites of Iyrnph nodes. Definition
Conta ins the s ubm ental a nd s u b m a ndibu l a r triang les bou nded by the posterior bel ly of the digastric m uscle, the hyo id bone infe riorly a nd the body of the m a ndi ble su periorly Conta ins the u p per jug u l a r lymph nodes a nd extends from the level of the hyo id bone inferiorly to the sku l l base su pe rio rly Contai ns the m iddle j u g u l a r lymph nodes from the hyoid bone superiorly to the cricothyroid m e m brane i nferiorly Conta ins the lower j u g u l a r lymph nodes fro m the cricothyroid m e m brane su perio rly to the clavicle inferiorly Contai ns the posterior triangle lymph nodes bou nded by the anteri or border of the tra pezi us posteriorly, the posterior border of the sternocleido mastoid m uscle a nteriorly and the cl avicle i nferiorly Contains the ante rio r com pa rtment lymph nodes from the hyoid bone superiorly to the s u p rasternal notch inferiorly. On each side the medi a l border of the carotid sheath forms the lateral border Contai ns the lymph nodes inferior to the s u p rastern a l notch i n the u pper mediasti n u m
Reproduced from Ref.
1 , with permission.
2364 I
PART 17
HEAD AN D N ECK TUMOURS
The definitions of the N categories (Table 181.8) for all head and neck sites, apart from the thyroid (Table 181.10) and nasopharynx (Table 181.11) are the same. The natural history and response to treatment of cervical nodal metastases from the nasopharynx are different, in terms of their impact on prognosis, thus they justify a different N classification. Regional lymph node metastases from well-differentiated thyroid cancer do not signifi cantly affect the ultimate prognosis and, therefore, also warrant a unique system.
Lip and oral cavity The oral cavity extends from the skin-vermilion junction of the lips to the junction of the hard and soft palate above and to the line of the circumvallate papillae below (Table 181.12). The anatomical sites and subsites are as follows: •
•
Pathol ogical cl assification The pT, pN and pM categories correspond to the T, N and M categories. The extent of the tumour in terms of the location and level of the lymph nodes should be documented. In addition, the number of nodes that contain tumour and the presence or absence of extra capsular spread of the tumour should be recorded. Histological examination of a selective neck dissection specimen usually includes six or more lymph nodes; a radical or modified radical neck dissection specimen 2 includes 10 or more lymph nodes. i ,
Table 181.10
NX NO N1 N1a N1b
N stqging for thyroid ca rcinoma.
Regional lymph nodes cannot be a ssessed No region a l lymph node metastasis Regional lymph node metastasis Metastasis in l evel VI (pretrachea l , prelaryngeal, para laryngea l) nodes Metastasis in other u nilatera l, bilateral o r contra lateral cervica l or u pper/su pe rior mediastina l lym ph node(s)
Reproduced from Ref.
lip: - external upper lip (vermilion border); - external lower lip (vermilion border); - commissures; oral cavity: - buccal mucosa; - mucosa of the upper and lower lips; - cheek mucosa; - retromolar areas; - bucccoaiveolar sulci, upper and lower (vestibule of mouth); - upper alveolus and gingiva (upper gum); - lower alveolus and gingiva (lower gum); - hard palate; - tongue: • dorsal surface and lateral borders anterior to vallate papillae ( anterior two-thirds), inferior (ventral) surface; - floor of mouth.
Pharynx The pharynx is divided into three regions: nasopharynx, oropharynx and hypopharynx. Each region is subdivided into specific sites as summarized by the following. OROPHARYNX
The oropharynx is the portion extending from the plane of the superior surface of the soft palate to the superior
1, with permission. Table 181.12
Table 181.11
N·
NX NO 1\J 1 N2 N3a N3b
TNM Cli nical classification for lip a nd o ra l cavity.
N staging for nasopharynx.
Definition .,
.
:
Regional lymph nodes ca nnot be assessed No regional lymph node metastasis Unil atera l metastasis in lymph node(s), 6 cm or less in g reatest dimension, above the su praclavicu l a r fossa Bilateral metastasis in lymph node(s), 6 cm or less in g reatest dimension, above the su praclavicular fossa Metastasis in lymph node g reater than 6 cm in dimension Metastasis in lymph node in the s u p racl avicu l a r fossa
Midline nodes are considered ipsilateral nodes, and the supraclavicular triangle is defined by the lines joining the following three points: the
T1 T2 T3 T4a
T4b
Tu mou r 2 cm or l ess in g reatest di me nsion Tu mou r more tha n 2 cm but not more than 4 cm in g reatest di men sion Tu m o u r more than 4 cm in g reatest dimension Lip : t u m o u r i nvades th rough cortical bone, infe rior a lveo l a r nerve, floor of mouth o r ski n (chin o r nose) Oral cavity: tu m o u r invades through cortical bone, i nto deep/extrinsic m u scle of tongue, maxil lary s i n u s or ski n of face Lip or ora l cavity: tu m o u r invades m a sticator space, pterygoid p lates or sku l l base, or encases inte rnal ca rotid a rtery
superior margin of the clavicle at its sternal and acromial ends, and the
Superficial erosiol1 alone of bone/tooth socket by gingival primary is not
point where the line of the neck meets the shoulder. Reproduced from
sufficient to classify a tumour as
Ref.
1, with permission.
perm ission.
T4. Reproduced from Ref. 1, with
Chapter 181 Staging of head and neck cancer
surface of the hyoid bone (or floor of the vallecula)
181.13).
(Table
It includes:
Tab Ie 181.14 ·
•
anterior subsites (glossoepiglottic area);
•
base of tongue (posterior to the vallate papillae or posterior third);
I 2365
Classification for the nasopharynx.
Definition
T
T1
Tumour confined to nasopharynx
T2a
Tumour extends to soft tissues of oropharynx and/or
T2b
Tumour extends to soft tissues with parapharyngeal
•
vallecula;
•
lateral subsites;
•
lateral wall;
•
tonsil;
T3
Tumour invades bony structures and/or paranasal sinuses
•
tonsillar fossa;
T4
Tumour with intracranial extension and/or involvement of
•
tonsillar pillar;
cranial nerves, infratemporal fossa, hypopharynx, orbit
•
posterior wall;
or masticator space
•
superior subsites;
•
inferior surface of soft palate;
•
uvula.
nasal cavity without parapharyngeal extensiona extenslona
3 Parapharyngeal extension denotes posterolateral infiltration of tumour beyond
NASOPHARYNX
The
the
pharyngobasilar
fascia.
Reproduced
from
Ref.
1, with
permission.
(Table 181.15). It includes the piriform sinuses, the
nasopharynx
begins
anteriorly
at
the
posterior
choana and extends along the plane of the airway to the level of the free border of the soft palate
(Table 181.14). It
includes the following:
postcricoid area and the lateral and posterior pharyngeal walls. •
Postcricoid area (pharyngo-oesophageal junction) extends from the level of the arytenoid cartilages and
•
superior wall;
connecting folds to the inferior border of the cricoid
•
posterior wall: from the level of the junction of the
cartilage, thus forming the anterior wall of the hypopharynx.
hard and soft palates to the superior wall; •
lateral wall: including the fossa of Rosenmuller;
•
floor: superior surface of the soft palate.
•
fold to the upper end of the oesophagus. It is bounded laterally by the thyroid cartilage and
The margin of the choanal orifices, including the posterior margin of the nasal septum
medially by the hypopharyngeal surface of the
is included with the nasal
aryepiglottic fold and the arytenoid and cricoid
fossa.
cartilages. •
Posterior pharyngeal wall extends from the superior level of the hyoid bone (or floor of the vallecula) to
HYPOPHARYNX
The
Piriform sinus extends from the pharyngoepiglottic
hypopharynx
is
the level of the inferior border of the cricoid cartilage that
portion
of
the
pharynx
and from the apex of one pyriform sinus to the
extending from the plane of the superior border of the
other.
hyoid bone (or floor of the vallecula) to the plane corresponding to the lower border of the cricoid cartilage Table 181.15 Tab Ie 181.13
Classification for the oropharynx.
�ro!:- �S:_ 'D�-ti�'itio�:;-
:�I;
T1
Tumour 2 cm or less in greatest dimension
T2
Tumour more than 2 cm but not more than 4 cm in
;i\��;��·:i:��nW�i�:,':;: �;: �-s�t�
T1
Tumour limited to one subsite of hypopharynx and 2 cm
T2
Tumour invades more than one subsite of hypopharynx or
or less in greatest dimension an adjacent site, or measures 2-4 cm in greatest
greatest diameter T3
Tumour more than 4 cm in greatest dimension
T4a
Tumour invades any of the following: deep extrinsic muscles of the tongue (genioglossus. hyoglossus,
dimension, without fixation of hemilarynx T3
Tumour measures more than 4 cm in greatest dimension,
T4a
Tumour invades any of the following: thyroid/cricoid
or with fixation of hemilarynx
palatoglossus and styloglossus), larynx, medial
cartilage, hyoid bone, thyroid gland, oesophagus,
pterygoid, mandible and hard palate T4b
Tumour invades any of the following: lateral pterygoid muscle, pterygoid plates, lateral nasopharynx, skull base; or encases the carotid artery
Reproduced from Ref. 1, with permission.
Classification for the hypopharynx.
central compartment soft tissuea T4b
Tumour invades prevertebral fascia, encases carotid artery or invades mediastinal structures
3Central compartment soft tissue includes prelaryngeal strap muscles and subcutaneous fat. Reproduced from Ref. 1, with permission.
2296 I
PART 16 THE UPPER AIRWAY
ses y and paranasal sinu u sites and subsites are:
(Table 181.19):
'.$ , I
" �
(Table 181.20); (Table 181.19).
tes and subsites are as follows (Table
I
/
Supragiottis
� � n n
Back to Ca Larynx
TI Tumor limited to one subsite of supraglottis with nOlTI1al vocal cord 110bility T2 Tumor invades mucosa of more than one adjacent subsite of supraglottis or glottis or region outside the supraglottis (e.g. mucosa of base of tongue, vallecula, medial v.all of pyrif onn sinus) without fixation of the larynx
----
land;
T3 Tumor limited to larynx with vocal cord fixation and/or invades any of the follO\�ing: postcricoid area, pre-epiglottic tissues, paraglottic space, and/or minor thyroid cartilage erosion (e,g., itiller codex) T4a Tumor invades tlU'ough the thyroid cartilaae anellor invades tissues beyond the laryn.x (e.g. trachea, soft tissues of neck itlcluding deep extrinsic muscle of the tongue strap muscles, thyroid or esophagus) T4b Tumor invade preve11ebral space, encases carotid artery, or invades mediastinal Sllllctures
)athological types are: �.
papIllary carcinoma ( includi ng those with follicular foci);
2. 3. 4.
follicular carcinoma (inclu di ng so-called Hurthle
cell carcinom a) ;
medullary carcinoma ; undifferentiated ( anaplas t ic) carcinoma (Table 181.22),
Stage grouping
papillary and follicular, medullary, and undiffere ntiated carcino mas (Table 181.7). Separate stage groupings are recommended for
Reproduced from Ref. 1, with permission.
Ta ble 1 81 .17
Classification for the glottis.
T1 a
Tumour limited to one vocal cord (may involve anterior or posterior commissure) with normal mobility
T1 b
Tumour involves both vocal cords (may involve anterior or posterior commissure) with normal mobility
T2
Tumour extends to supraglottis and or subglottis, and/or with impaired vocal cord mobility
T3
Tumour limited, to larynx with vocal cord fixation and/or invades parqglottic space, and/or with minor thyroid cartilage erosion (inner cortex)
T4a
Tumour invades through thyroid cartilage or invades tissues beyond the larynx, e.g. trachea, soft tissues of neck including deep/
T4b
Tumour invades prevertebral space, mediastinal structures, or encases carotid artery
extrinsic muscle of tongue (genioglossus, hyoglossus, palatoglossus and styloglossus), strap muscles, thyroid and oesophagus
Reproduced from Ref. 1, with permission.
Chapter 181 Staging of head and neck cancer I
Table 181.18 ;:, T
2367
Classification for the subglottis.
Definition
Tl
Tumour limited to subglottis
T2
Tumour extends to vocal cord(s) with normal or impaired mobility
T3
Tumour limited to larynx with vocal cord fixation
T4a
Tumour invades through cricoid or thyroid cartilage and/or invades tissues beyond the larynx e.g. trachea, soft tissues of neck including deep/extrinsic muscle of tongue (genioglossus, hyoglossus, palatoglossus and styloglossus), strap muscles, thyroid and oesophagus
T4b
Tumour invades prevertebral space, mediastinal structures, or encases carotid
Reproduced from Ref. 1, with permission.
Table 181.19
T
Classification for the nasal cavity and ethmoid sinus.
Definition
T1
Tumour restricted to one subsite of nasal cavity or ethmoid sinus without bone erosion
T2
Tumour involves two subsites or extends to involve an adjacent site within the nasoethmoidal complex, with or without bony
T3
Tumour extends to invade the medial wall or floor of the orbit. maxillary sinus, palate or cribriform plate
T4a
Tumour invades any of the following: anterior orbital contents, skin of nose or cheek, minimal extension to anterior cranial fossa,
T4b
Tumour invades any of the following: orbital apex, dura, brain, middle cranial fossa, cranial nelVes other than maxillary division of
invasion
pterygoid plates, sphenoid or frontal sinuses trigeminal nelVe, nasopharynx, clivus Reproduced from Ref. 1, with permission.
Table 181.20
T
Classification for the maxillary sinus.
Definition
Tl
Tumour limited to the antral mucosa with no erosion or destruction of bone
T2
Tumour causing bone erosion or destruction, including extension into hard palate and/or middle nasal meatus, except extension to
T3
Tumour invades any of the following: bone of posterior wall of maxillary sinus, subcutaneous tissues, floor or medial wall of orbit,
T4a
Tumour invades any of the following: anterior orbital contents, skin of cheek, pterygoid plates, infratemporal fossa, cribriform
T4b
Tumour invades any of the following: orbital apex, dura, brain, middle cranial fossa, cranial nelVes other than maxillary division of
the posterior wall of maxillary sinus and pterygoid plates pterygoid fossa or ethmoid sinuses plate, and sphenoid or frontal sinus trigeminal nerve, nasopharynx, clivus Reproduced from Ref. 1, with permission.
Tumours of the larynx are classified according to the
LIMITATIONS OF T STAGING For the majority of sites in the head and neck, emphasis is placed on tumour size. It is, however, well recognized that
number of anatomical surfaces involved. This has led to a
number of problems. For example, a large 3-cm tumour
of the supraglottis may still remain
TI, whereas in the be a T3. This mitigates
T stage alone is of limited prognostic significance in many
glottis this will almost certainly
head and neck carcinomas. It is a significant factor in the
against
tumours are more likely to have nodes than those
prognostic and therapeutic importance. For example, a
is explained
T la. The same tumour may be deeply infiltrating into
presence of nodes on presentation. Patients with larger
with smaller tumours. IS In carcinoma of the larynx, the poorer prognosis with increased T stage
by the increasing propensity to nodal metastases with
lar"ger tumours. If nodal metastases are removed as a confounding factor then T stage prognosis. 19
per se does not influence
supraglottic
tumours
in
terms
of outcome.
In addition, depth of invasion is not measured, but is of
superficial tumour of the vocal cord mucosa would be vocalis muscle and yet the stage will still remain Tla.
In the oral cavity, in particular the oropharynx, the size
of the tumour is not always easily measured. There is little
difficulty in defining a TI or T4 tumour, but problems
2368 I
PART 17
Table 181.21
T
T1 T2 T3 T4a T4b
H EAD A N D N ECK TU M O U RS
Sa l iva ry TN M classification.
.
�_Defr�itRm , ;�.�:�.:; . '-. . > ; . :.,
.•..
Tumour 2 cm o r less in g reatest d i mension without extra p a renchymal extensiona Tu m o u r more tha n 2 cm, but no m ore than 4 cm in g reatest dimension without extra paren chyma l extensiona Tu m o u r more tha n 4 cm an d/or t u m o u r with extrap arenchymal extension Tu m o u r invades skin, m a n d i ble, ea r ca n al or facia l nerve Tu m o u r inva des base of sku l l, pterygoid p lates or encases ca rotid a rtery
aExtraparenchymal extension is clinical or macroscopic evidence of invasion of skin, soft tissues or nerve, except those listed under T4a and T4b. Microscopic evidence alone does not constitute extraparenchymal extension for cl assification purposes. Reproduced from Ref.
Table 181.22
T
T1 T2 T3 T4a T4b T4aa T4ba
1, with permission.
Thyroid TI\I\V1 clinical classification.
. " Ddinition Tu m o u r 2 cm or less in g reatest d i mension, l i m ited to the thyroid Tu m o u r more than 2 cm, but not m o re than 4 cm in g reatest d i mension, l i mited to the thyroid Tu m o u r more than 4 cm in g reatest dimension, limited to the thyroid or a ny t u m o u r w ith m i n i m a l extrathyroid extension (e.g. extension to sternothyroid m u scle o r perithyroid soft tissues) Tu m o u r extends beyond the thyroid ca psu le an d inva des any of the fol l owing : su bcuta neo u s soft tissues, larynx, trachea , oesophagus, recurrent l a ryngea l nerve Tu m o u r invades p revertebra l fascia, mediastina l vessel s or encases ca rotid a rtery Ana pl a stic ca rcinoma only. Tu m o u r (any size) lim ited to the thyroid An a plastic carcinoma only. Tu m o u r (any size) extends beyon d the thyroid ca psu le
Multifocal tumours of all histological types should be designated (m) (the largest determines the classification) . aAIl anaplastic carcinomas are considered T4. Reproduced from Ref.
1, with permission.
can occur when the tumour measures between 1.5 and cm. Furthermore, increasing severity with a T4 tumour is reflected in deep invasion into muscle, bone or adjacent structures. There is then a reliance on the predictive power of radiographic modalities including CT and MRI. The depth of invasion of lesions of the floor of the mouth has been shown to be of prognostic significance and this is similarly difficult to assess by either clinical or radiographic means.18 Tumours of the hypopharynx are classified in terms of both their size and anatomical extent. The anatomical boundaries of the hypopharynx have been in the past contentious and it is occasionally difficult to be certain of the exact origin of some of the larger tumours. The dual listing of the aryepiglottic fold in both the supraglottis and hypopharynx sites, in p articular, invokes a problem in trying to classify the site of origin in some situations.
3
LIMITATIONS OF N STAGING The reliability of clinical examination of nodes is contentious with studies showing that observers disagree on their presence.2 0 Furthermore, palpable nodes do not always harbour tumour. During clinical examination, the size of the node should be measured with callipers, and allowance made for the intervening soft tissues. There is
considerable observer error in estimating the size of the node by palpation alone without a measuring device.21 Most masses over the size of 3 cm in diameter are not single nodes, but will represent confluent nodes or tumour in the soft tissue compartments of the neck. One of the main criticisms over the last decade has been the failure of the TNM system to provide a description of the level of nodal involvement. Various studies have confirmed the importance of this factor17 and it is now included in the current classification (engaging the Memorial Sloan-Kettering system of lymph node levels).2
LIMITATIONS OF STAGE GROUPING There are now seven stages for head and neck cancers arising at mucosal sites (0, I, II, III, IVa, IVb, IVc) and six stages for salivary gland cancers (1, II, III, IVa, IVb, IV c). Differentiated thyroid cancers also have six stages (1, II, III, IVa, IVb, IVc) with undifferentiated ( anaplastic) cancers having three, as all cases are stage IV ( IVa, !Vb, IVc) . Many authorities have concluded that problems exist with the current staging system.22, 2 3, 24,25 One of the main criticisms is that the size of some groups defined by the combinations of the TNM classifications is small, preventing accurate prediction from previous experience:
Chapter
Groome et aI.26 identified four criteria that a stage grouping scheme should meet. The subgroups defined by the T, N and M that make up a given group within a stage grouping scheme have similar survival rates (hazard consistency) . 2. The survival rates differ among the groups (hazard discrimination) . 3 . The prediction of cure is high (outcome prediction) . 4. The distribution of patients across the groups is balanced (thereby maximizing statistical power in each group ) . 1.
Compelling arguments have been advanced suggesting the different ways of grouping the same TNM categories, and how this may result in an improved system. The TANIS score combines the integers of the T and N to create a new score. Thus, a T I NO would be a TANIS 1 and T2N2 would be a TANIS 4, etc. First reported by Jones et aI. ,25 this is an easy-to-use system evaluated primarily for cancers of the oral cavity and oropharynx. It treats T and N as equivalent with respect to survival. Many authors have studied this system and recommended grouping several TANIS scores to improve hazard discrimination. In their initial report, Jones et aI. found little statistical difference between groups 1-3 and 5-7. They recommended pooling TANIS scores 1-3 together as TANIS 1, 4 as TANIS 2 and 5-7 as TANIS 3. Others have tried different groupings based on the TANIS system.27 The advantages of the TANIS score are its ease of application, ability to define a reasonable number of groups and ability to be applied retrospectively if the TNM score is known. The main disadvantage is that the concept of T and N equivalence does not hold true. Many studies have confirmed the more significant impact of N status over T status. For example, a T2NO carcinoma does not have the same survival as a T IN I at any site, although both of these would be TANIS 2. The TANIS system does not account for M 1 disease, although most would agree that any M l would automatically put the patient in the highest TANIS group. It is also apparent that by pooling groups because there is little difference in survival between them (attempting to improve hazard discrimination) , there i s a n implicit trade-off with hazard consistency. Others have also tried to improve on the current stage grouping and TANIS system with subtle variations,23, 28, 29 all claiming, more or less, that their system is an improvement on any other. It seems that excellent systems have been devised that may improve predictive power, hazard consistency, hazard discrimination and balance over the current UI CCIAJ CC T, N and M stage grouping system. Lydiatt et aI. 30 provide a review of these. They observe that one of the main disadvantages is that the systems are not intuitive and would require a chart for most clinicians to stage their patients. Analyses comparing authors' systems with other systems including
1 8 1 Sta g i ng of head a n d neck ca ncer I 2369
the UICC/AJCC are flawed, because each one is not independent of the authors' system. Therefore, because the system was created from the database, it would naturally perform well. The true test is whether the results from an independent database would yield similar results. The five major sites of the head and neck (oral cavity, oropharynx, larynx, hypopharynx and paranasal sinuses) share the same system. Arguably, they should be independent of each other. One advantage of an independent system is better groupings within each site. Different systems are in use for the nasopharynx and thyroid, which are considered to be sufficiently different with respect to risk factors, behaviour and treatment. In their rebuttal of these views the AJCC Task Force maintains the opinion that independent systems would create problems for clinicians and investigators not remembering which group was staged by which system. They are of the view that any new system should be comprehensive and easily applicable to all the major sites.30
KEY POI NTS Staging of head ah� neck cal).ce{is a .syst.em -rela:tive §-evetity, · or extent, of ·'the disease. It
designed Jo express- the
.
.
P
: biopsY t() .a\roid�tbe ,�ffett of itpst�ging fuom the '-oedema� c�used b)r:biopsy:tr?uma.. .
.
,
- . The' seX and age oftne patient" the duration -� responsible for any · future procedure; Th e clinical (pretieatmertt) clasSIfica:tion • (cTNM) based on examination, imaging, endoscopy· and biopsy should be clearly documented in the c?se . file only when
.
2370 I
PART
1 7 H EAD A N D N ECK TU M O U RS
Defi cien cies i n cu rre n t know l ed g e a n d a reas for fu tu re resea rch
et Micro biologica Scandinavica. Section A, Pathology.
9.
> The cu rrent Tf\l M system re l i es on m orphology of the
tumour (a natom ica l site and extent of d isease) w ith l ittle or no attention g iven to patient factors. H owever, the l iteratu re does suggest that sym ptom severitl 1 and co-morbiditl 2 have a sign ificant i m pact on o utcomes. It is therefore reco m m ended that these data be recorded. » Defi n itions of TN M categories may be a l te red or expanded for c l i n ical or resea rch pu rposes as long as the basic defi n itions are recorded and not cha nged. Cha nges i n the TN M classification shou l d , and w i l l , only occ u r, based on t h e a ppropriate col l ection, presentation a nd ana lysis of data, i n the foru m of the U ICC a n d AJCc.
1 0.
11.
1 2.
1 3.
> The TI\J 1\t1 system e m b races the concept of orderly
descri ption of d isease with i ncreasing size and extent. W h i le fa l li b l e, it is fou nded on sou nd princip les an d relates t h e com b i ned experience a nd data from many s u rgeons a n d centres. Many of the shortcom ings i n t h e system represent the com plexity o f the d isease of head a n d neck ca ncer.
1 4.
1 5.
1 6.
REFERENCES *
1.
Sob i n lH, Wittekind Ch. TNM classification of malignant tumours, UICC, 6th edn. New York: Wiley-Liss, 2002.
1 7.
A summary and cornerstone for accurate staging.
*
2.
G reene F, Pa ge Dl, Flem m i n g 1 0 , Fritz AG, B al ch CM, H a l ler DG (eds) . The AJCC cancer staging man ual, 6th edn. N ew York: Springer, 2002. A summary and cornerstone for
3.
Denoix PF. Note on the possible rol e of the I nternatio n a l U nion agai nst Ca ncer. Acta Unio Internationalis Contra Cancrum. 1 952 ; 8 : 92-6. U I CC Com m ittee on C l i n ica l Stage Cl assification an d
1 8.
accurate staging.
4.
App l ied Statistics.
1 9.
Clinical stage classification and
presen tation o f results, malignant tumo urs of the breast and larynx.
Pa ris: I nternation al U n ion Aga i n st Ca ncer,
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1 958. 5. 6.
7. 8.
U I CC. TNM classification of malignant tumours. Geneva : I nternational U n ion Aga i nst Ca ncer, 1 968. McGavra n M H , Bauer WC, Ogura J H . The i ncidence of cervica l lym ph node m etastases from e p idermoid ca rci noma of the l a rynx an d thei r relations h i p to certa i n characteristics o f t h e primary t umo ur. Cancer. 1 961 ; 1 4 : 55-66. M ichaels L. Ear, nose and throat histopathology. New York: Spri nger-Verlag, 1 98 7 : 387. G raem N , Helwig-la rsen K, Keiding N . Precision of h istologica l grading of m a l i g n a ncy. Acta Pathologica
21 .
2 2.
23.
1 980 ; 83 : 307- 1 7. Rol a n d NJ, Cas l i n AW, Nash J, Stel l PM. The va l u e of g rad ing sq u a mous cel l carcinoma of the head a n d neck. Head and Neck. 1 99 2 ; 1 4 : 224-9. Fortin A, Couture C, Doucet R, Al bert M , Al lard J, Tetu B. Does h istologic grade have a rol e i n the m a nagement of head and neck cancers. Journal o f Clinical Oncology. 2001 ; 1 9 : 41 07 -1 6. Fritz A, Percy C, Jack A, Sha n m ugaratna m K, Sob i n l, Pa rki n OM et al. (eds) . WHO international classification of diseases for oncology ICD-O, 3 rd edn. Geneva : W H O, 2000. SNO M ED I nternational. The systemized nomenclature of h uman and veterinary medicine. Northfield, I l: Col l ege of Am erican Patholog ists. Ava i la ble from www5nomed.org Rei ner B, Siegel E, Sawyer R. The i m pact of routine CT of the chest on the d iag nosis a n d ma nagement of newly diag nosed squamous cel l carcinoma of the head a n d neck. AJR. American Journal of Roentgenology. 1 997 ; 1 69 : 667-71 . Houg hton OJ, H u g hes I\t1l, Garvey C. Role of chest CT sca n n i n g in the management of patients presenti ng w ith head and neck cancer. Head and Neck. 1 998; 2 0 : 61 4-8. H a ug hey B H , Gates GA, Arfken Cl, Harvey J. Meta a n a lysis of second m a l ig n a nt t u m o u rs i n head and neck cancer: the case for an endoscopic screening protocol. Annals o f Otology, Rhinology, a n d Laryngology. 1 992 ; 1 01 : 1 05- 1 2. Davidson J, G i l bert R, I rish J, Witterick I, Brown 0, B i rt 0 et al. The rol e of panendoscopy in the m a nagement of m ucosa l head a n d neck m a l ig na ncy - a prospective eva l uation. Head and Neck. 2000 ; 2 2 : 449-54. Jones AS, Roland NJ, Field J K, Ph i l l i ps D E. The level of cervical lym ph node metastases : their prog nostic relevance and relationship w ith head and neck squamous ca rcinoma pri m a ry sites. Clinical Otolaryngology and Allied Sciences. 1 994; 1 9 : 63-9. H i b bert J, M a rks NJ , Wi nter P J, Shaheen O H . Prog nostic factors in ora l squamous cel l carcinoma and thei r relation to cli n i ca l stq g i ng. Clinical Otolaryngology and Allied Sciences. 1 983 ; 8: 1 97-203. Ste l l PM. Prog nosis in l a ryngea l ca rci nom a : t u m o u r factors. Clinical Otolaryngology a n d Allied Sciences. 1 990 ; 1 5 : 69-8 1 . Watki nson JC, Joh nston 0 , Jones N , Coady M , laws 0, Al len S et al. The rel i a b i l ity of pal pation i n the assessment of t u m o u rs. Clinical Otolaryngology and Allied Sciences. 1 990 ; 1 5 : 405-9. Alderson 0, Jones T, Roland NJ. I ntra and i nter observer error i n assessm ent of cervica l lym p h nodes. Head and Neck. 2001 ; 2 3 : 739-43. Am b rosch P, Kron M, Freuden berg lS. Clin ica l sta g i ng of oropharyngea l ca rci noma. A critica l a ppraisal of a new stage-grou ping proposa l . Cancer. 1 998 ; 8 2 : 1 61 3 -20. H a l l SF, G roome PA, Rothwell 0 , Dixon PF. Using TNM sta g i ng to pred ict s u rviva l i n sq u a mous cel l ca rci noma of head a nd neck. Head an'd Neck. 1 99 9 ; 2 1 : 30-8.
Chapter
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* 25.
Piciri l l o J F. Pu rposes, problems, a n d proposa ls for prog nosis in ca ncer stag i ng . Archives of Otolaryngology Head and Neck Surgery. 1 995; 1 2 1 : 1 45-9. Jones GW, B row n m a n G, Goodyear M , M a rce l l u s D, Hodson DI. Com pa risons of the a d d itions of T and N i nteger scores with TN M stage g rou ps i n head a n d neck ca ncer. Head and Neck. 1 993 ; 1 5 : 497-503. The first
28.
29.
description of an integer score which has become a standard for other novel studies.
* 26.
* 30.
Groome PA, Sch u lze K, Boysen M. A corn pa rison of p u b l ished head a n d neck stage g ro u pings i n ca rci noma of the oral cavity. Head and Neck. 200 1 ; 23 : 61 3-24. An
27.
Synderm a n CH, Wag ne r RL. Su periority of the T a n d N i nteger score (TANIS) stag ing system for sq u a m ou s ce l l ca rci noma o f the ora l cavity. Otolaryngology and Head and Neck Surgery. 1 995; 1 1 2 : 691 -4.
H a rt MM, M a k-Kregar S, H i lgers FJ M . The i m porta nce of correct stage g ro u pi n g i n oncology: resu lts of a n ationwide stu dy of oropharyngea l ca rcinoma i n the Netherl a n d s. Cancer. 1 996; 77: 587-90. Ki ricuta I e. The i m porta nce of correct stage g rou ping in oncology: resu lts of a nati onwide stu dy of oropharyngea l ca rci noma i n the Netherl a n d s (letter). Cancer. 1 996; 7 7 : 590. Lyd iatt WM, Shah J P, Hoffm a n HT. AJCC stage g rou pings for head a n d neck ca nce r : shou ld we look at a lternatives? A re port of the Head a n d Neck Sites Task force. Head and Neck. 200 1 ; 23 : 607- 1 2. A refutation of some of the opinions in the review by Groome et 01.
excellen t review and opinion on current systems of stage grouping.
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31.
Pugliano FA et 01. Sym ptoms as a n i ndex of biologic behavio u r i n head a n d neck ca ncer. Otolaryngology and 1 99 9 ; 1 2 0 : 380-6. Piciri l l o .I F. I m porta nce of com orbid ity i n head and neck ca n ce r. Laryngoscope. 2000; 1 1 0 : 593-602. Head and Neck Surgery.
32.
182 Data collection In head and neck cancer RICHARD WIGHT
Introduction What are data? Why collect cancer data? Historical data collection methods Why a minimum data set? How to develop cancer data collection Structure of a computerized database Confidentiality-secure data Coding classifications
2372 2372 2372 2373 2373 2373 2374 2374 2374
Value of national coordination National Cancer Data Set Moving to comparative audit Key points Best clinical practice
2375 2375 2376 2376 2376
Deficiencies in current knowledge and areas for future research References
2377 2377
INTRODUCTION
WHY COLLECT CANCER DATA?
This chapter describes the principles that should be followed in the capture of high -quality cancer data. These principles are equally transferable to other aspects of otolaryngology. A description is provided by the National Cancer Data Set initiative in England, as well as the National Comparative Audit in Head and Neck Cancer.
All clinicians managing patients with cancer have a responsibility to assess the quality of the care they provide. 1 This is reflected in the impact or consequences of the management and procedures they apply, to individuals or groups of patients. In order to discharge this duty the prospective collection of data on each patient, in order to derive simple outcomes, is a minimum requirement. Potential outcomes are knowledge of the range of malignancies treated, stage distribution' the types of treatment provided, complications of treatment, survival and quality of life measures. Clinicians also seek to provide a prognosis for their patients' disease. This is affected by tumour-specific factors (e.g. stage, 2 pathological features), host factors (e.g. performance status, co-morbidities) and environmental factors (including access to services, experience, the individual's particular circumstances, availability of treatments). 3 Currently, prognosis is typically anecdotebased and 'best of class from the literature', but routine data capture can (if sufficient numbers are obtained) be converted into an accurate focus. Also, bringing into play an individual's personal circumstances is becoming increasingly important, as demonstrated by the impact of co-morbidi'ty; the additional burden of other disease present at the time of diagnosis of' the index cancer. A
WHAT ARE DATA? Data are a collection of directly observed facts, and the storage of these facts in a standardized format and content comprise a database. To ensure standardization of content, data gathering requires an underlying 'skeleton' of items: a data set. The items need to have a defined meaning, standard terminology should be used, choice fields should have a consistent coding structure and use of free text should be avoided. They are the building blocks from which the construction of information subsequently takes place. If the data set has been correctly defined and is fit for the purpose, it should contain all the items needed for the outputs proposed without the need to resort to additional data capture.
Chapter 182 Data collection in head and neck cancer
series of standardized indexes is available, with the adult co-morbidity evaluation (ACE-27) having significant prognostic value. 4
HISTORICAL DATA COLLECTION METHODS There are four traditional methods of cancer data collection: cancer registries, personal databases, histopathology records and patient administration systems. Each method has delivered results but, equally, each has significant problems. Cancer registration is, traditionally, a government-run service using nonmedical staff trained in note extraction techniques as well as collating death data to produce a summation of documented cases. In the UK the data have often lacked stage information, thus limiting its usefulness, and because of the volume of data to be collated there has been a delay in report production. However, the ability to demonstrate trends in incidence and variability in treatment has proved valuable. 5 This method therefore remains the standard to match in other cancer information initiatives. Personal databases are of variable quality, timeconsuming to manage and, inherently, have site-to-site variation in fields and codes, thus limiting cross cooperation. Histopathological records are of limited value in isolation, containing little treatment and no outcome information. They do however remain an important and reliable source of information in identifying cases. Patient administration systems are difficult to examine, are financially driven and lack a link from coder to clinician.
I 2373
journey (real or near real time data capture). This reduces error and increases likely compliance by health professionals. Duplication is reduced and the data collection process can deliver added value by-products, such as referral or discharge letters. The key steps are shown in Figure IS2.1. The required outcomes should be defined at the outset and a data set created around these to encompass the minimum amount of additional data needed to support the patient pathway. Some items will be derived. For example, it is better to record date of birth and date of an event in order to calculate the age at the event than it is to enter the age as a free field item. The latter is prone to error, as well as being repetitive if a series of events require age as a factor. The minimum data set should then be defined, with a description of each item, its purpose in inclusion and any associated codes and classifications. Creation of a supporting data manual providing an expanded description is of value to support staff, institutions and software writers. For a data set to be successfully collected it requires a change in culture by all contributory professionals. A
WHY A MINIMUM DATA SET? The principles of a minimum data set are based on the smaller the volume of items, the greater the speed of entry, the higher the accuracy and the greater the likelihood of compliance in usage. This has to be balanced against the requirements of components in order to deliver the necessary outcomes, without additional data entry at a later stage. To produce a minimum data set each proposed item should be critically examined, both its definition and purpose for inclusion, and these be reviewed in the light of any modification. An ongoing recording of current status in relation to the absence or presence of the index cancer is needed, with capture of recurrence or metastasis events. This allows for the censoring of records ultimately in certain types of survival analysis.
HOW TO DEVELOP CANCER DATA COLLECTION In recording cancer data, the goal must be to collect data at the point of contact with the patient along their care
Figure 182.1
collection.
The key stages in developing cancer data
2374 I PART 17 HEAD AND NECK TUMOURS sense of ownership is needed as well as carefully focussed drives to ensure data quality on a recurring basis. After an initial period of collecting and ensuring quality, it is appropriate to validate the data. This ensures that all relevant cases have been captured within the geographical target area and that, particularly where patient care crosses organizations, a full record has been collected. Useful sources for cross-comparison are pathology and cytology records. Some patients fall outside these groups and for those who only have a clinical diagnosis alternative sources, such as clinic records, may need to be used. Via their links to the Office for National Statistics, cancer registries in the UK can provide the small number of additional death certificate only registrations. Data analysis, if appropriate, can then take place. It is mostly likely to fail if significant gaps in the data are evident. Only from high-quality data can relevant and useful information be assembled. The data set should not be seen as fixed. Its items should be reviewed on a regular basis to include any changes and confirm that their continued collection remains relevant and of value.
STRUCTURE OF A COMPUTERIZED DATABASE Each subject on the database requires a unique identifier, thus, a record of registration is created. A diagnosis of cancer produces a care spell or event, to which is then tagged each recurrence or metastasis and each treatment plan and treatment. An additional new primary creates a new care spell. A relational database tree is thus constructed. In selecting database software a number of factors should be considered. Local familiarity with the software, including the ability to write in the software to add item changes, is required. Flexibility of the software to deliver changes in relationship between events and to support different system packages is needed. Increasingly, it is necessary to be able to link to other host institutional systems for automated data capture, such as patient administration systems. The ability to export data in a number of formats is also of value.
CODING CLASSIFICATIONS Standardized nomenclature is essential to allow assimilation of data from different units and specialities and should, wherever possible, be internationally recognized (e.g. International Classification of Disease (ICD)-lO), nationally (e.g. Office Population and Censuses (OPCS)-4 operation codes, Clinical Terms read codes) or national professional (e.g. British Association of Head and Neck Oncologists (BAHNO) extension codes). Locally derived codes should be avoided. To illustrate the structure of these coding classifications some are briefly described.
ICD-l0 tumour site codes The classification of neoplasms is broken down into categories based on their point of origin and behaviour. 6 Sites for malignant neoplasms are prefixed by C and sites for in situ and benign neoplasms by D, but they are grouped into much broader categories (see Table 182.1). For each anatomical site the initial three alphanumeric code is supplemented by a decimal point and an additional digit to identify subsites 0-7, an overlapping site 8 (unless specifically indexed) or unspecified subsite 9 (see Table 182.2).
ICD-O-3 morphology codes ICD-IO includes a copy of this coding system to allow it to be used in conjunction with the above site codes, to identify histological type? Morphology codes are prefixed by M. Some histological types of neoplasm are specific to certain sites or types of tissue, and C and D site codes are shown after these. For example, M93IO/3 ameloblastoma malignant C41.0, C41.I identifies that the morphology only relates to tumours in the maxilla and mandible. The four identity digits for the histological type
Table 182.1 Code
COO-C75
CONFIDENTIALITY-SECURE DATA Patients have the right to expect that health professionals who care for them will hold information about them in confidence. Information stored in computerized or paper records must be effectively protected against improper disclosure at all times. For the majority of audit purposes anonymous data will meet requirements. If this is not the case permission should be sought from the patient.
C76-C80 C81-C96 C97 000-009 010-036 037-048
ICO-lO Tumour site codes (benign and malignant). Tl.lmour site Covers specified primary sites (but excludes lymphoid, haematopoietic and related tissues) Covers ill-defined, secondary and unspecified sites Malignant neoplasms of lymphoid, haematopoietic and related tissues Malignant neoplasms of multiple independent primary sites Relates to in situ neoplasms Relates to benign neoplasms R.,elates to neoplasms of uncertain or unknown behaviour
Chapter 182 Data collection in head and neck cancer I 2375 Table 182.2
ICD-lO Tumour site codes for the tonsil.
Code
Table 182.3 carcinoma. Code
C09 C09.0 C09.1 C09.B
C09.9
Malignant neoplasm of tonsil (excludes lingual tonsil, C02.4; pharyngeal tonsil, C11.1) Tonsillar fossa Tonsillar pillar (anterior and posterior) Overlapping lesion of tonsil, i.e. involves pillar and fossa and unclear which is site of origin Tonsil unspecified, i.e. subsite not stated or known
of neoplasm are followed by a slash, then a one-digit behaviour code:
MB070 MB070/2 MB070/3 MB070/6
ICD-0-3 Morphology codes for squamous Morphology
Describes squamous carcinoma Squamous cell carcinoma in situ Squamous cell carcinoma (not otherwise specified) Squamous cell carcinoma metastatic, i.e. in a node with an unknown primary
Table 182.4 OPCS (operation and procedure codes), salivary gland procedures. CodeProced ure
• /0
• 11 ./2 • /3 • /6
benign; uncertain benign or malignant; carcinoma in situ; malignant, primary site; malignant metastatic, or secondary site.
This system, as it applies to squamous carcinoma, is illustrated in Table 182.3. The morphology section of the Standard Nomenclature of Medicine and Clinical Terms (SNOMED CT)8 is similar to ICD-O-3 but provides a broader description of pathological terminology to aid coding.
OPCS operation codes The basic structure of the classification comprises anatomically based chapters, each of which is given an alphabetical code. 9 The next two digits describe the operation group, based on the largest operation first, descending to the smallest, followed by a decimal point and a fourth digit to identify the procedure itself. If the procedure described does not match any of these categories, then, provided the procedure is recorded, 8 for other specified or 9 for unspecified can be added after the decimal point. Within the classification, certain codes do encompass multiple procedures, otherwise the operation needs to be coded from its component parts, i.e. having defined the primary resection procedure, separate codes for type of flap and its site of harvest need to be added. Operations on the salivary glands are illustrated in Table 182.4. SNOMED CT 10 represents a joint initiative by the College of American Pathologists and the National Health Service (NHS) to provide a unified terminology. This started assessment in 2002 and will influence future coding agendas in both the USA and UK.
F44 F44.1 F44.2 F44.3 F44.4 F44.5 F44.B F44.9
Excision of salivary gland Total excision of parotid gland Partial excision of parotid gland Excision of parotid gland (not elsewhere classified) Excision of submandibular gland Excision of sublingual gland Other specified Unspecified
on registry-based systemslland in the USA registry databases feed to the National Cancer Database. 12 However, the American Head and Neck Society has now developed software to help both clinicians in the community and those in major medical centres to contribute to cancer data collection. 13 British initiatives have been led by BAHNO. In 1996, the association identified the need for a national minimum data set (NMDS) for professions managing head and neck cancer. BAHN014 stated that for every case a minimum data set should be defined for collection. The parameters should include demographic variables, clinical and pathological staging, tumour grading, diagnostic categories and a wide range of treatment options. In 1998, the Royal College of Pathologists also defined a minimum data set for histopathology reporting in head and neck cancer,15 and this was incorporated into the overall NMDS. In 1999, BAHNO introduced two data sets: 16
1. the NMDS for head and neck cancer; 2. the National Advisory Data Set for head and neck cancer. A previous audit 1? showed that 60 percent of UK head and· neck units were collecting this information on a regular basis.
VALUE OF NATIONAL COORDINATION
NATIONAL CANCER DATA SET
Increasingly, the focus for cancer data capture has been based on national initiatives. In Europe, this has focussed
In May 2000 this project was instigated to move towards standardization of cancer data sets across different cancer
2376 I PART 17 HEAD AND NECK TUMOURS site-specific areas in England. It sought to bring together performance requirements to monitor delivery of cancer care, populate the registries for epidemiological needs and match the clinical requirements to move to comparative audit. Under the auspices of the National Cancer Director and the Health and Social Care Information Centre (formerly the NHS Information Authority), the project has defined a data set with a common core for all cancers, followed by site-specific elements in a standardized fashion. The National Cancer Data Set has advantages over the previous BAHNO data sets; it is better at covering work across geographical boundaries and more comprehensively matching the patient's journey. It follows a patient pathway, within the concept of a 'cancer care spell': the continuous period of care, including assessment for care, for a patient who has been diagnosed as suffering from a single primary cancer. A recurrence of the original primary cancer at a secondary site is part of this care spell, which allows a patient to be tracked across boundaries, and to have follow-up contacts attach to the care spell. The core data set is compatible with noncancer clinical data sets and NHS data standards, and has received standards approval from the NHS Information Standards Board. It will be future proofed by the NHS and will drive the agenda for central reporting, and avoid the need for snapshot audits. The latest data set, version 4.1 ISB, is available from www.ic.nhs. uk/ our-services/improving-data-collection-and -use/ datasets/ document-downloads/ cancer. Also available is a download of the supporting cancer data manual and appendix for head and neck cancer, which defines each of the items and has jointly been developed by BAHNO and the NHS Information Authority. The aim is that the multidisciplinary team meeting is the focus for data capture, but allowing devolution to those performing treatments and interventions. In order to deliver this, the aim must be to move to real time data capture at the point of contact with the patient, by any staff member managing the patient.
MOVING TO COMPARATIVE AUDIT Both the BAHNO and National Core initiatives aim to provide a pathway to comparative audit, so that individual clinicians/clinical teams can demonstrate their effectiveness 18 and compare their performance in delivering cancer care with those in peer-matched units. In England, a partnership between BAHNO, the Health and Social Care Information Centre, Cancer Registries, Royal College of Surgeons Clinical Effectiveness Unit and sponsored by the Healthcare Commission, has led to the creation of Data for Head and Neck Oncology (DAHNO), a national comparative audit for head and neck cancer. The project has defined outcomes. 19 These may be delivered by items from the core and head and
neck specific National Cancer Data Set and deployed software infrastructure to hospitals. By autumn 2005, most hospitals providing head and neck cancer care in England had connected, and over half were submitting data. The second annual report looking at outcomes related to patients with laryngeal and oral cavity cancer was published in March 2007. 20 While comparison on waiting times, for example, is relatively straightforward, comparing surgical performance is much more challenging and the consequences of invalid performance assessment are obvious. The validity of surgical outcomes and adverse events and what are acceptable variations are, as yet, poorly understood. For the comparison to be effective, representative populations with an appropriate case mix, high-quality data collection and subsequent appropriate statistical analysis and interpretation are all required.
KEY POINTS • Data gathering requires an underlying 'skeleton' of items 2. a data set. • The items need to have a defined meaning. Standard terlIlinologyshould be used and choice fields have a consistent coding structure. • All clinicians managing cancer patients have a responsibility to assess· the quality of the care they pr()vide; To discharge this duty, the prospective collection of data on each patient to derive simpleoutcomesisa minimum requirement. • In commencing ·an initiative· to .record·· cancer data, the goal has to be to collect data at the point of contact with the patient along their care journey. • Patients have a right to· expect that information about them will be held in confidence by health professionals who care for them. • The .National Cancer DataSet for· England wasintioduced for head and neck cancer from September 2003.
The current draft measures for improving outcomes in head and neck cancer, issued by the National Institute for Clinical Excellence, support the proposition that clinicians should routinely collect data to a'ssess care.
Chapter 182 Data collection in head and neck cancer
Deficiencies in current knowledge and areas for future research
* 10.
I 2377
of Popu lation Censuses a nd Surveys, 1990. Classification source. SNOMED CT. Systematized nomenclature of medicine, clinical terms. Chicago: College of American Pathologists,
The relative rarity of head and neck cancer means that to reach statistical significance in assessing and
2002. Available from: http://snomed.com/snomedct. 11.
van der Sanden GA, Coebergh JW, Schonten U, Visser 0,
comparing results from different treatment regimens
van Leeuwen FE. Cancer Incidence in The Netherlands in
and practice requires comprehensive data collection
1989 and 1990. European Journal of Cancer. 1995; 31:
from as many units as possible across the UK. The goal must be to achieve high levels of completeness
1822-9. 12.
on a regular and systematic basis.
Funk GF, Kamell LH, Robinson RA, Zhen WK, Trask DK, Hoffman HT. Presentation, treatment, and outcome of oral cavity cancer: a National Cancer Database report. Head and Neck. 2002; 24: 165-80.
13.
Coltrera Me. American Head and Neck Society Otobase
14.
BAH NO. Provision and quality assurance for head and neck
User Guide. Seattle: University of Washington, 2002.
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Gospodarowicz MK, O'Sullivan B. Prognostic factors'
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head and neck oncology services in the UK: The Royal
cancer. Laryngoscope. 2000; 110: 593-602. Demonstrates
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Head and Neck Oncologists Preliminary Multidisciplinary
Joslin C, Rider L, Crelin A. Head and neck cancers. Cancer
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Yorkshire Cancer Organisation, 1994. WHO. International statistical classification of diseases and related health problems, 10th revision. Geneva: World
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General Medical Council. Maintaining good medical practice. London: GMC, 1998. National Clinical Audit Support Programme. DAHNO consultation document, 2003. Available from: www.DAHNO.com.
Fritz A, Percy C, Jack A, Shanmugaratnam K, Sobin L, Parkin DM et al. (eds). ICD-O. International classification
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Birchall MA, Brown PM, Browne J. The organisation of
Piccirillo JF. Importance of co-morbidity in head and neck
in Yorkshire, Cancer Registry Special Report Series. Leeds: 6.
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UlCC prognostic factors in cancer. New York: Wiley Liss,
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National Head and Neck Cancer Audit. DAHNO Second
of diseases for oncology, 3rd edn. Geneva: World Health
Annual Report. London: The Information Centre for Health
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operations and procedures, Fourth revision. London: Office
november-2006.
183 Prognostic indicators and serum markers ANDREW S JONES
Cell and molecular biology of head and neck cancer with special reference to putative rnarkers of prognosis Markers of head and neck cancer Summary
2378 2385 2385
Key points References Further reading
2392 2392 2394
The initial search strategy used Pubmed and Medline. Owing to the large number of publications in molecular and cellular oncology the search had to be quite specific from the outset. The MeSH headings were head and neck cancer with various combinations of the following: molecular oncology, cell biology, molecular biology, cellular oncology, biological markers, serum markers, urine markers, exfoliative cytology as well as cancer, carcinoma, malignancy, squamous cell carcinoma, thyroid and salivary. Back searching from review articles and book chapters revealed a number of additional references. Finally, other databases, such as the Cochrane database, the library of the British Medical Association and CHINAL, were searched. The first part of the chapter relies heavily on my own view of the fundamental oncology of head and neck cancer, with some general references for the interested reader. In all, 5769 relevant references were identified. Initially, these were selected using the title and then the abstracts. Finally, 385 original articles were used in the preparation of this chapter. The chapter also makes use of the data from much molecular cell biology work carried out by the Department of Otolaryngology at the University of Liverpool over the last two decades. This work has been greatly facilitated by access to the head and neck database. This was begun by my predecessor, Phillip Stell, and since his retirement maintained by me.
CELL AND MOLECULAR BIOLOGY OF HEAD AND NECK CANCER WITH SPECIAL REFERENCE TO PUTATIVE MARKERS OF PROGNOSIS Introduction The functional structure of living cells has been categorized into the genome and the proteome. Recently, the great importance and huge diversity of the domain of carbohydrate-protein and, to a lesser extent, lipid-protein molecules has been recognized. The genome contains around 30,000 to 40,000 genes, the proteome contains at least ten times this number of molecules and the 'glyceome' has millions of possible molecules. Twenty years ago it was a basic tenet of molecular biology that
one gene coded for one protein; evidently this is untrue. The glyceome and lipids are created indirectly from genes by protein enzymes and by chemical reactions between the proteins in their tertiary and quaternary structures with available sugar and lipid molecules. The genome is divided into exons and nonprotein coding segments known as introns; perhaps as little as 1.5 percent of the genome is made up of exons. The well-known p53 gene contains 16 exons and the equally well-known retinoblastoma gene 36 exons. Each gene possesses a controlling portion, usually at its beginning but occasionally upstream in the DNA molecule. The exons are separated by introns and the genetic code must be interpreted' by messenger RNA; this process is :J;lot necessarily purely linear. A hypothetical gene of three
Chapter 183 Prognostic indicators and serum markers I
exons separated by two introns might be transferred to messenger RNA as exon 1 + exon 2 + exon 3, but might be, for example transferred as exon 1 and exon 3, or even exon 1, exon 1 and exon 3. One of the problems during gene transcription is in the nature of the molecule itself; to contain such an immense amount of DNA the cell must adopt several strategies. One simple strategy is to break the DNA up into chromosomes (Figure 183.1). Man has 46 chromosomes but the number appears fairly arbitrary as nematodes have 2, hermit crabs 254 and the chimpanzee 48. Each chromosome is then formed of a super coil of DNA, which is itself coiled several times, and the whole structure is twisted around a rod -like basic protein, termed a 'histone'. To express or copy a gene presents problems as these may be in inaccessible parts of the coil. Enzymes termed 'topoisomerases' help untangle DNA by, for example cutting it and letting one strand pass between the breaks and then repairing the break. In cell division an interesting problem arises when a chromosome is being transcribed. End sections of the chromosomes, termed telomeres, contain repeating units of 66 base pairs; each time a chromosome divides the telomeres gradually reduce in length. This represents the 'end replication problem' and is at least one reason for the finite life of normal animal cells, which have a theoretical limit of about 70 cell divisions. Each telomere consists of thousands of repeats of the six-nucleotide sequence, TTAGGG. Cancer cells usually avoid this problem and if they become immortalized can, theoretically, be grown forever in cell culture. This occurs because they express an enzyme termed telomerase, which allows regeneration of the telomere. The basic concept of genetics is the interchange of genomic material between two organisms. Central to this process is meiosis where the diploid set of 46 chromosomes is reduced to the haploid number (23). During fertilization of the ovum by a spermatozoa, the diploid
1
-1-1-1-1- -'-I 2
3
4
-1-1-1-1 -I I-I 6
7
13
14
.a-a-
8
2379
number of chromosomes is regained, one set from each parent. Once an embryo is formed only mitosis occurs. Here, the relatively simple copying of genetic material from cell to daughter cell takes place. By this means the aero digestive tract is kept covered with mucosa. Unfortunately, also by this method, cancer cells divide. The above is true except for the sex cell producing organs, the testes and the ovaries. Although meiosis appears fairly straightforward the molecular processes involved are complex but essential for the preservation of the species. Perhaps the most important phenomenon is termed recombination. In this process genetic material is swapped between chromosome pairs at crossover points termed chiasmata. Some of the offspring will inherit a 'vigorous' genome that allows adaption to the environment into which they are born. Unfortunately, those offspring who inherit the relatively poor genome will perish or at least are unlikely to interbreed. Brutal as this mechanism sounds it does ensure that the most appropriate genes survive and also allows the species to thrive. This mechanism is not only crucial for selecting the most beneficial genes but also for, perhaps, a more sinister reason. Not only does the genome gradually accumulate mutations but it also becomes 'infected' with ancient virus-like self-replicating areas termed 'repetitive elements'. The nuclear membrane contains pores and it is through these that protein-coding messenger RNAs are transported to the ribosome. The ribosome contains two RNA structures; one larger than the other, termed ribosomal RNA and here the messenger RNA is converted into proteins by transfer RNA. Each molecule of transfer RNA contains three coding bases and each codes for one amino acid. Until recently only 20 amino acids were known, a 21st was then added and very recently a 22nd. This latter transfer RNA interestingly utilizes a triplet usually reserved as a stop signal. Gradually the transfer RNAs build up amino acids into long chains. These building block amino acids become polypeptides and
5
9
-.
16
-
17
Figure 183.1
A human chromosome spread.
Such spreads are still used in cytogenetics providing evidence of abnormal, missing or translocated chromosomes. The spreads are performed in metaphase when the chromatin is most easily seen.
2380 I PART 17 HEAD AND NECK TUMOURS then proteins. This linear protein construct then undergoes structural (but not linear) modification into a secondary, tertiary and quaternary structure. This structure is dictated by the sequence of amino acids in the chain and the main property of the protein is that it is folded, the folding held together by various chemical bonds, particularly disulphide bridges. Once synthesized these proteins are frequently modified in the endoplasmic reticulum and the Golgi apparatus forming glycoproteins, lipoproteins, etc. Apart from the DNA in the nucleus a cell also contains some DNA within the mitochondria. These are mainly concerned with the generation of adenosine triphosphate (ATP) from glucose oxygen phosphates. The ATP molecule forms the basic energy unit of the celL We only express a small proportion of our genes and some are only expressed on rare occasions. Evidently, cells from different tissues express different groups of genes. The expression of genes is related to various factors, most primitively to stress, whether this is from heat, toxins, osmolarity or desiccation. In normal physiology, gene expression is largely controlled by cell surface receptors and their respective ligands. Genes can be switched on artificially.
Oncogenes Oncogenes comprise a disparate group of genes potentially capable of stimulating cell growth and division. They include transcription factors, regulators of the cell cycle or growth factor receptors. Originally, the term was specifically applied to transforming genes identified in RNA tumour viruses and had the prefix v-. It was soon realized that the v-oncogene was in fact derived from the host cell, captured by the viral genome soon after infection by a mechanism termed transduction. The cellular counterparts of v-oncogenes are c-oncogenes or proto-oncogenes and comprise a highly conserved part of the genome. In retroviral infection, the RNA viral genetic code must be transformed to a DNA code by viral reverse transcriptase and then inserted into the host genome. If this insertion takes place near a proto-oncogene it may be rendered oncogenic. This has now happened during gene therapy of two French children, both of whom developed leukaemia. Viruses do not tend to cause most human cancers, but other mutagenic events do. Examples are inhaled carcinogens, dietary mutagens and low intake of free radical scavengers, ionizing radiation and DNA copying errors during meiosis or mitosis.
Tumour suppressor genes The set of genes with the opposite effect of oncogenes are tumour suppressor genes (TSG). As implied by their
name they are 'safety' genes that counterbalance the growth and mitotic potential of oncogenes. They are recessive genes that negatively regulate cell proliferation and promote apoptosis and differentiation. Unlike oncogenes, TSGs were first noted as genomic deletions in human cancers. The best known and first discovered is the RBI gene. If absent, familial retinoblastoma supervenes in nearly half of those affected. The tumour is otherwise extremely rare as a sporadic event. Most researchers now suspect that multiple losses or failures of TSGs happen in most cancers. TSGs are biochemically diverse and include phosphatases, kinases, cyclin-dependent kinase (CDK) inhibitors, transcription factors, cell adhesion molecules, protein degradation proteins and DNA repair molecules.
Genes controlling the function of the nucleus The mechanisms involved in gene expression are immensely complex and incompletely understood. One of the most studied areas involves a transcription factor termed AP-l. It is a member of the Jun and Fos (ATF) family of proto-oncogenes involved in the normal functioning of the cell including cell division and differentiation and responding to growth factors and cytokines. They are also important in the cells response to stress, mitogens and ionizing radiation. Finally, as proto-oncogenes they can become oncogenic, leading to neoplasia. Twenty years ago, the heterodimer Fos-Jun was identified and found to contain the viral oncoprotein, Fos. The first member of the Jun family, c-Jun is similar to Fos a homologue of a retroviral oncoprotein. At present, the Jun family includes c-Jun, JunB and JunD. The Fos family includes c-Fos, FosB, Fra-I and Fra-2. Recently, the Fos-related ATF has become regarded as a separate family which includes ATFa, ATF-2 and ATF-3. A typical transcription factor must comprise a specific DNA binding domain and a transcription activating domain. All the foregoing factors involve a highly conserved DNA binding domain, although they differ slightly and specifically.
The cell cycle We would be unable to live unless cells could divide; this is a normal part of physiology. We lose vast amounts of cells from our aero digestive tracts and from our skin every day, and vast numbers of leukocytes and other immune cells are also lost each day. In the mature mammal, one type of cell may only divide into a similar cell, thus an osteoblast will only make bone. There are exceptions and these are called stem cells; these cells are totipotent, i.e. 'they can mature into a variety of tissues. Stem cells exist in the basal layers of the epidermis and in
Chapter 183 Prognostic indicators and serum markers
the base of the crypts in intestinal mucosa; they are also known to exist in bone marrow. Traditionally, some cells such as muscle cells and brain cells do not divide (a good workout in the gym every week makes muscle cells hypertrophic, but not increase in number). In the brain vast numbers of neurons die daily from ageing or cerebrovascular accident. The increasing number and complexity of interconnections between neurons can compensate for this loss. Interestingly, central nervous system stem cells have now been identified, a finding which will force the above concept to be reconsidered. To replace cells that have died and for growth, cells must undergo cell division, known as mitosis. Essentially, mitosis is the process where one cell divides into two identical cells. During this process the nuclear material must split into two with the copying of chromosome pairs. Controlling this process is the cell cycle, a simplified diagram of which is shown in Figure 183.2. The stages of mitosis as seen by light and electron microscopy are well known to students of biology. In interphase, the cell is in the resting state or has become differentiated. However, on initiation of the cell cycle there is no visible change, but on a molecular level, G 1, S and early G2 of the cell cycle are completed. Thus, long before morphological changes take place, most of the cell cycle is complete. Regulation of the cell cycle takes place mainly at G 1 (gap) but also at G2, and DNA synthesis occurs in S phase. Towards the end of G 1 phase there is a critical point, the restriction point (R); once the cell cycle has passed this it will continue to cycle even without the presence of growth factors. The time taken by this complex process is short, little over one day, although it does vary between cell types. G 1 is the longest and most complex phase and lasts approximately 14 hours; mitosis itself only takes two hours. Most of the following discussion will deal with
continuous cell gr0
control of the cell cycle and, in particular, G 1. G2 occurs between S phase and mitosis and it is convenient to discuss it here. G2 is an important point and, if passed successfully, allows the cell to undergo mitosis. On microscopy, the dramatic morphological changes of mitosis take place here. Before a cell may enter mitosis, several criteria must be met. Most important is that S phase was completed successfully with accurate copying of the genome. Morphologically, the first event is the condensation of the chromatin and dissolution of the nuclear envelope. The nucleolus fragments halting RNA synthesis and the endoplasmic reticulum and Golgi apparatus disperse. The cell skeleton of micro filaments and tubules alter and on cell culture the cells can be seen to 'round up'. The micro tubules increase by a factor of ten and focus on the centrosomes leading to the formation of the spindle. In metaphase the chromosomes line up equatorially on the spindle, the two pairs of chromosomes separate and in anaphase move to opposite ends of the spindle, the process culminating with the final division of the cell in telophase. On the molecular level, the cyclin BlICDKl complex controls the G2 checkpoint although other cyclins are also involved to a lesser extent. The above complex gradually accumulates during S phase and early G2 but is abruptly released allowing the cell through G2. The term 'growth fraction' is used to define the proportion of cells in a tissue that are proliferating. Typically, in head and neck cancer, it is approximately 30 percent. The signals for mitosis to begin are usually growth factors, which bind to cell receptors. Cell adhesion molecules also have a role, as does the mere contact between one cell and another. A typical sign of neoplasia in cell culture is the loss of 'contact inhibition' where cells start to grow over each other.
Vvth
~
r
...... M ....
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..
.... -------' -------G2 """" ,,"
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s Figure 183.2
Diagrammatic representation of the cell
cycle. Mitosis, the most obvious part of the cycle, occupies only a couple of hours. It is S phase, the phase of DNA synthesis, which takes up the majority of the cell cycle, lasting some 16 hours.
2382
I PART 17 HEAD AND NECK TUMOURS
Q
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proteins termed 'eyclins', which are numbered in t he usual haphazard way of biology as A, B,
.
Diagrammatic representation of the
n egative feedback loop where irreparable
damage to the genome detected by p53 causes cessation
The cell cycle is controlled primari ly by a group of
01, 02 03 and E.
Cyclin C may, or may not, have a role to play. One thing common
Figure 183.3
mechanism of action of p53.
to all cyclins is that they are serine, threonine
of the cell cycle. A positive feedback lo op also exists in which p53 causes production of mdm2, which in turn inhibits further p53 activity. P53 abnormalities manifest themselves
ki nase They operate via CDK, the enzymatic activity of
demonstrated on immunohistochemis try
the cyclin only becoming active when associated with a
P53 mutation happens early in
specific CDK protein. Again, the
numbering of the CDKs
is far from logical, being COK1, 2, 4 a nd 6. Each one aligns
with a speci fi c cyelin; for
example,
most clearly as
pathological s tab ilizat i on of this protein. This is easily
(Figure 183.4). is and is even
.
ca rcinogenes
present in dysplasia where p53 posit ive cells are seen in the rapidly dividing basal layers of mucosa
cyclin D
affiliates with CDK4/CDK6. Cyelin D1 is important in the GO and Gl restriction points and also allows the cell cy ele to progress into S phase. Cyel in E has a similar function but extends further into S phase. Cyel i n A wi th COK2 is associated with the transition from S phase to, and across, G2. Cyclin A is again active bu t this time
The retinoblastoma gene This
gene
(RBl) is lo ca ted on chromosome 13 at ( 35 percen t)
q 14.1-14.2 and shares a sequence homology
associated with CDKI. In act ual mitosis cyel i n B is present. The genes coding for cyclins are themselves under the control of other genes, perhaps the most important of which is p53. This prot ein is involved in a host of interactions with other proteins
and genes (Figure 183.3). of
It is so important that it has been called 'the guardian
the genome'. P53 constantly surveys the genome and if any aberrati o ns are apparent the repair system will come into operation.
If this is not possible p53 will induce a
process, which ends in apoptosi s, otherwise known as programmed cell death. The
anticanc e r
importance of
.
this process can hardly be emphasized enough, and over half of human cancers have damage to the p53 locus to
p rot e in product will not operat e In addition, p53 itself is sensitive to ONA damaging agents, such as cytotoxi c drugs, and also to ionizing
the extent that the p53
Figure 183.4
Photomicrograph of pS3 stained (brown) by
immunohistochemistry. P53 is seen as brown staining cell nuclei
irradiation. P53 exerts its effect on the cell cycle in a
at the basal layers of this dysplastic epithelium. Such (abnormal)
production of p 16, p21 and p2 7, all of which inhibi t some or al1 of the cycli ns thus
staining is indica'tive of the role mutated p53 plays very early in
complex fashion by causing
the neoplastic process.
Chapter 183 Prognostic indicators and serum markers
with pI 07 and p 130, together known as the pocket protein family. For pRB the highly conserved region is the so-called pocket region between amino acids 379 and 792. As with p53 the most serious abnormalities affect this region, for example the viral oncoproteins, such as the SV40 large T antigen, the adenovirus EIA and the E7 protein of human papilloma virus (HPV). Similar to p53 pRB has more than one binding site (three). Unlike p53, pRB is inactivated by phosphorylation. Inactivation of pRB allows the cell cycle to enter S phase but can also facilitate apoptosis. Also similar to p53, pRB is involved in many interactions with other cellular proteins and genes, some of which are outlined in Figure 183.5. PRB allows mdm2 to inhibit p53 thus inhibiting one of the apoptotic pathways but facilitating cell cycle entry. Active (unphosphorylated) pRB causes expression of the all important transcription factor, API, allowing differentiation of the celL Other factors including myoD and NF-interleukin (IL)6 are also activated.
Apoptosis So far we have discussed cell division as the mechanism by which new cells are formed. We have also discussed some of the regulatory genes involved in the overall management of this process. We now deal with the opposite end of the life cycle of a cell, that is, cell death. Cells can die by necrosis, which usually happens in disease, by cellular catastrophe during mitosis (e.g. after ionizing radiation) or by apoptosis or programmed cell death. For the repair and remodelling of tissues, apoptosis is as important as the creation of new cells and is the physiological method by which unwanted cells are removed from a tissue. A study of apoptosis in vivo as opposed to in cell culture is difficult, in part because the
Negative growth signals
Positive growth signal
· crCDK~
I
AP-1, MyoD, -.~--NF-IL6, etc.
j Differentiation
Figure 183.5
is central.
1H Rb
Mdm2
----1 p53
1
I 2383
process is over so quickly (less than a day) leaving little evidence microscopically that the process has happened and also because light microscopic changes are relatively slight and subjective. A pathognomic feature of apoptosis is the formation of dense short fragments of chromosomal DNA, termed nucleosomes, and the presence of enzymes, known as caspases. The fragmented DNA is formed of short lengths of approximately 180 base pairs. There are various methods for the detection of apoptosis in tumour samples in practice. Most are based on the identification of double-strand breaks or, more robustly, on the identification of caspases. The most successful, and the one we use in our unit, involves in situ hybridization detection of these enzymes. The technique tends to underestimate the apoptotic fraction; this is a systematic and reproducible error and so for most purposes it is adequate. Evidently, in a tissue where cells are not being lost by any other process and which is not growing, the growth and apoptosis fractions must be equaL Perhaps up to onethird of cells in the mucous membranes of the head and neck is undergoing proliferation. Estimates of the proportion of cells undergoing apoptosis vary from 5 to 10 percent. This difference is partly explained by the fact that apoptosis is a quicker process and also, of course, because cells are being continuously lost from mucosal surfaces all the time. Apoptosis appears during the development and the remodelling of tissues and, of course, in ageing. It can be induced by chemical and physical stresses applied to a cell, such as ionizing or ultraviolet irradiation, anticancer drugs, cytotoxic lymphocytes and a number of cytokines called death factors. Obviously, the absence of crucial survival factors may also trigger apoptosis. Finally, arguably the most important role of apoptosis is the precipitation of programmed cell death in a cell whose genome is irreversibly damaged. This happens during mitosis and may indicate a faulty genome or inaccurate DNA replication. Crucial to the degradation of a cell is a group of proteases termed caspases, which derive from the histologically well-known zymogen protein. The human caspase family has 13 members and, as is usual in biology, the numbering of these proteolytic enzymes is haphazard. Caspase 8, 9 and 10 are initiators of apoptosis. The second group, caspase 3, 6 and 7 are enzymes, which degrade various cell death initiating substrates leading to apoptosis. The final effector molecule to discuss in relation to apoptosis is apaf-l. This together with cytokine C recruits pro-caspase 9 and with ATP produces active caspase 9.
E2F
Cell receptors S phase entry
Apoptosis
Apoptosis
Representation of the mechanisms in which pRb
The bi-lipid cell membrane effectively isolates the inside of the cell from the outside and this is true for extracellular ligands, including agonists and antagonists.
2384 I PART 17 HEAD AND NECK TUMOURS Owing to this the cell requires a multitude of transmembrane receptors. Part of the molecule is outside the membrane; the receptor and part of that molecule is inside, which is usually a receptor tyrosine kinase (RTK) initiating signal transduction. Specific damage to these receptors can make them oncogenic; a gene that codes for a damaged receptor is an oncogene and a gene, which can be converted to the latter, is a proto-oncogene. The whole family of RTK receptors are growth factor receptors and bind to polypeptide ligands. Examples of these receptors are the epidermal growth factor receptor (EGFR) and the closely related erb-B receptors, the platelet-derived growth factor receptor (PDGFR) and the insulin receptor. The extracellular domains frequently include immunoglobulins (Ig) and fibronectin type 3 binding regions. When a receptor binds a ligand the receptor molecule undergoes dimerization and activation of its intrinsic tyrosine kinase activity, which in turn leads to phosphorylation of the receptor. The receptor is now active in its intracellular· domain. Cytoplasmic signalling molecules, which contain certain domains, such as the phosphotyrosine binding domain, recognize the phosphotyrosine residues on the activated receptor. A complex signalling mechanism cascade then ensues. This usually involves heterotrimeric GTP binding proteins, the G proteins bind and hydrolyse GTP, and subsequently, regulation of the activity of serine/threonine kinases takes place. Finally, via the process of phosphorylation nuclear transcription factors are activated. A diagrammatic example is shown in Figure 183.6. Seven RTKs are now outlined with regard to human cancers. The genes which code for such RTKs are termed oncogenes because if for some pathological reason they
6
are left switched on cancer may develop. These growth factor receptors have been selected because they have been extensively investigated and have well-documented clinical correlates. • The Ret oncogene is associated with medullary thyroid and papillary thyroid cancer. The mechanism of activation in the former is a point mutation and in the latter is a fusion of genes. • The Trk is associated with papillary thyroid carcinoma by a mechanism of gene fusion. • The Met oncogene is associated with thyroid, gastric and colorectal cancer and the mechanism of activation is gene amplification or overexpression. • The Kit oncogene is associated with gastric cancers and haematopoietic malignancy; the mechanism is by point mutation. • The HER 2 oncogene is associated with breast and ovarian cancer and is caused by gene amplification or overexpression. • EGFR is associated with brain tumours caused by overexpression of the gene. • PDGFR is associated with dermatofibrosarcoma protuberans and with chronic myelomonocytic leukaemia and the mechanism of increased activity is by gene fusion.
Cell adhesion molecules These molecules are all transmembrane and are of five types. 1. The cadherins are calcium-dependent,
2.
Thr
654
1 •
I
G-protein (ras?) Diacyl glycerol
•
Kinase C
4J
~E:~
3.
Endoplasmic ~.....,..., ~ reticulum releases Ca2 + Phosphatidyl inositol
Figure 183.6 The proposed mechanisms involved upon stimulation of an EGFR.
.......
4. 5.
transmembrane proteins. They typically possess five cadherin repeats and cadherins bind to other cadherins on adjacent cells. The integrins. These are heterodimers consisting of an alpha and a beta subunit. They interact with members of the Ig super family, which may also be receptors themselves. Importantly, the integrins interact with the extracellular matrix (ECM), for example the macromolecules fibronectin and lamenin. The Ig-like adhesion molecules have a variable number of Ig-like subunits, and fibronectin-like molecules may also be present. They bind to integrins or to members of the Ig family. Selectins contain a calcium-dependent selectin domain that binds to carbohydrates. The proteoglycans. These macromolecules have a small protein core to which are attached long chains of negatively charged glycosaminoglycans. These receptors combine with a variety of other receptors, most importantly with the ECM.
Next, I des(ribe briefly the intracellular relations of E-cadherin; lack of space does not allow a discussion of
Chapter 183 Prognostic indicators and serum markers I 2385
the other adhesion molecules. E-cadherin has a surprisingly complex structure. Intracellularly it is attached or related to two other proteins, known as alpha- and beta-catenin, which in turn are attached to the adenomatous polyposis coli gene product. The latter protein is overexpressed, in particular, in a proportion of colonic cancers. Abnormalities of this protein will be reflected in the function of E-cadherin. Reduction and expression of E-cadherin (Figure 183.7) has been felt to be an important predictive factor for metastasis. However, work in our department on this molecule has somewhat clouded the issue, and our· latest study found abnormal expression of E-cadherin adhesion complex in all of head and neck squamous cell carcinomas (HNSCC).
The cytoskeleton and extracellular matrix The cytoskeleton is a complex network of structures that include micro filaments, intermediate filaments and microtubules. They give the cell its shape, allow movement and spindle formation and provide attachment to cell adhesion molecules. The skeleton is built of proteins. The micro filaments are formed from the motile protein, actin and the micro tubules from tubulin. Other proteins of great importance are cytokeratin, vimentin and desmin. The ECM is crucial to the understanding of cancer as it is invaded in the early stages. It is a mesh of glycoproteins, proteoglycans and glycosaminoglycans. It lies immediately beneath the basement membrane and allows attachment of the cell adhesion molecules of the adjacent cells to the matrix. Thus, cellular cell adhesion molecules bridge the potential space between the cell and the basement membrane/ECM. These attachments are not
Figure 183.7
Immunoflorescence photomicrograph of the E-
cadherin cell adhesion molecule showing its distribution at cell boundaries of normal cells in tissue culture.
merely structural; they also pass to the cell differentiation signals maintaining order and polarity to an epithelium. The ECM is all-pervading in tissues, filling the spaces between cells, and is largely formed of type 4 collagen. The chemical constituents of the ECM are highly complex but are essentially a network of protein fibres within a polysaccharide ground substance.
MARKERS OF HEAD AND NECK CANCER Markers are used for diagnosis, monitoring treatment and the early diagnosis of recurrence. For the most part they are easily found in blood serum/plasma. Cytological markers of oral cancer may be sought using mouth washings or cytological brushings although they cannot be diagnostic of invasive cancer. In practical and epidemiological terms, urine would be the ideal source of marker. Work in this field has, to date, been disappointing although the subject is in its infancy. It seems to me that no single marker will prove adequate and that a panel of markers will be necessary as the subject progresses.
Markers for head and neck squamous cell carcinoma The value of using various serum markers is presented in Table 183.1 and is my personal assessment of the value, at present, of the test. Explanations for the abbreviations used in Table 183.1 are given in Table 183.2.
SUMMARY The subject of serum markers is in its infancy. Markers for thyroid cancer and nasopharyngeal cancer are frequently used in the clinical setting, mostly in the follow-up of patients. Most head and neck units do not use any other markers for screening, follow-up or the monitoring of treatment response. It is certain that this field will become very important in the near future. Initially, I suspect, it will be important in follow-up. Later it will become a diagnostic tool. To have any epidemiological impact, screening must be available at the level of the general medical and dental practitioner. Cytological screening of mouth washings will prove crucial to the early diagnosis of mouth cancer. Blood tests, perhaps initially for fragments of cytokeratins, will allow early diagnosis of head and neck cancer of most sites. To have the greatest impact on early diagnosis and reduction of mortality, urine tests would be the ideal and, no doubt, will be feasible in the future.
Table 183.1 Typ.e
Comparison of markers for HNSCC. Molecu I~and .¢xpl~natiori
Analysis.
Effecfandcomment
Serum alkaline DNAase
Enzyme assay
DNAase increased in good treatment response
2
Serum viral DNA, EBV and HPV in NPC
PCR sequencing
EBV and the prognosis and success of treatment HPV is an early tumour marker
2
3
P53 serum antibodies in HNSCC
PCR sequencing
Act as surrogate markers for p53 abnormalities in
2
ELISA
tumour Serum p53 antibodies predict resistance to cisplatin
2
Ref.
Value
DNA Possible indicator of recurrence 2
p53
2
4
p53 Antibodies and chemosensitivity of oesophageal
and 5FU
SCC 3
5
p53 expression and antibodies in oral SCC
Saliva ELISA
Both serum and saliva p53 antibodies detects tumour p53 alterations (500f0)
4
6
Mutant p53 protein and c-erb B2 and bcl-2 in serum
INC ELISA
c-erb B2 serum levels predict poor response to
ELISA
This measures serum fragments of CK 19
IC IC
Test of no value clinically
tissue in NPC
2
treatment
Cyfra 21-1 7
Monitoring the response to radiotherapy in HNSCC with serum cyfra 21-1
2
8
Serum cyfra 21-1 in oesophageal Ca
3
9
Cyfra 21-1 in serum detection of distant metastases
ELISA IC
10
in HNSCC Prognostic value of cyfra 21-1 in HNSCC and its
4
ELISA
Good for monitoring treatment and recurrence in SCC Good predictor of recurrence and particularly distant
2 2
metastases Good marker of favourable prognosis if cyfra is
2
reduced Early detection of metastases
value in detecting distant metastases
Squamous cell carcinoma antigen 11
SCCA is used as a serum marker of SCC There are two iso-forms, 1 and 2. SCCA2 is acidic
mRNA in tissue Reverse transcriptase PCR
An elevated SCCA2/SCCA 1 mRNA ratio predicted recurrence (RR7.2)
2
ELISA
SCCA increased in serum in 700f0 of cases before
2
ELISA
clinical relapse Elevated SCCA indicates recurrence and can be used
2
and found in serum. SCCA derives from serine protenase inhibitor gene products. 30 HNSCC tumours studied for the relevant mRNA 2
3
12 13
SCCA and Ca larynx SCCA in HNSCC
to monitor treatment
(Continued over)
Table 183.1 Type
Comparison of markers for HNSCC (continued). Ref.
Moleculeand·explanatiQn
Analysis
Effect and comment
14
SCCA in inverted papilloma
ELISA
SCCA 1 may warn of recurrence
15
Serum c-erb B-1 and B-2 products in HNSCC
ELISA
No value
2
16
EGFR Glycoproteins in HNSCC. One molecule that may form the carbohydrate moiety is sialic acid
ELISA
Serum glycoproteins i for large tumours. All 1 posttreatment but only sialic acid 1 to normal. Sialic acid directly correlates with staging and recurrence
3 4
17
ELISA
Raised in all malignancies including Hodgkin's 1-acidic glycoprotein raised in HNSCC ? reliability
5
19
4
Value
Receptors, glycoproteins, ECM
18
Sialic acid in HNSCC and other sites 1-acidic glycoproteins in HNSCC HNSCC patients excrete chondroitin sulphate with low sulphation. Chondroitin is broken down by
Western blot 50S-PAGE URINE ELISA
chondroitinase into sulphated and nonsulphated
6
20
disaccharides Plasma fibronectin in cancer
1 Sulphated
chondraitinase products in urine of
2
2
patients with HNSCC. With successful treatment return to normal
1 in
i
ELISA
Fibronectin
ELISA
Both molecules present in the serum of laryngeal
HNSCC but
in breast cancer
Adhesion molecules 21
Levels of soluble intercellular adhesion molecule-1 and sialic acid in laryngeal cancer. Both,
Thiobarbituric acid method
SCC patients. Correlate with advanced stage
including sialic acid, can act as adhesion 2
22
molecules Tumour-associated tissue eosinophilia and soluble
IC and immunohistochemistry
IL-3, IL-5 and E-selectin and vascular cell adhesion molecules 1 and 2 NOT involved in this process
ELISA
All raised in NPC whereas only VCAM-1 and E-
adhesion molecules and cytokines in NPC. Blood eosinophilia may break through basement membrane and invade a tumour. To be effective certain cytokines and adhesion molecules must be repressed for inflammation to proceed
3
23
Circulating intercellular adhesion molecule 1 (lCAM1), E-selectin and vascular cell adhesion molecule 1 (VCAM-1) in HNSCC
selectin in laryngeal Ca. Only E-selectin raised in oral SCC. Difficult to make any practical use of these findings
Matrix disruption enzymes 24
Cathepsin Band L, and stefin A and B in HNSCC. These enzymes digest the ECM allowing tumour invasion
ELISA
Low cathepsin correlates with disease recurrence and death. Cathepsin Band stefins had no effect
(Continued over)
Table 183.1
2
Comparison of markers for HNSCC (continued).
25
MMP-9 activity enhanced in plasma in HNSCC
Gelatin zymogJ:aphy
i
level of MMP-9 but no correlates with tumour factors
Interleukins and other cytokines 26
i
soluble IL-2 receptor predicts
t
tumour response
to IL-2
Cytotoxic T-Iymphocyte
Plasma with IL-2R
t
i
3000 U/mL associated with
leukaemic (CTLL) cell/IL-2
50%
assay
appears that IL-2 and its receptors are not the
in tumour cell growth. However it
only factors in this effect
2
27
Serum soluble IL-2 receptor and HNSCC. Used the
CTLL cell/IL-2 assay
IL-2RX
3, 4
28 and 29
Tumour necrosis factor (TNF)-alpha, IL-6 and their
t
then reduced neck metastases. This is the
opposite finding to the above 26
alpha subgroup CTLL cell/IL-2 assay
The mediators and their soluble receptors content in
soluble receptors in serum secreted by
plasma are dependent on tumour type, clinical progression and therapy. TNF-alpha may reduce
neutroph i Is
the host response to tumour. The biological effect of the cytokines is mediated by the membranebound target cell receptors. The neutrophils secrete TNF-alpha and the soluble receptors. Neutrophils have a highly significant role in the tumour's response to TGF-alpha
5
30
Plasma angiogenic cytokines and prognosis in
ELISA
i
31
High soluble TNF receptor levels in NPC. Correlation with response to EBV replication
bFGF had no effect ELISA
i
Fluorescence-activated cell
32
HNSCC and urine and plasma bFGF
URINE and PLASMA
in TNF receptors in serum is derived from the local immune system and appears to
sorter 7
2
t Angiogenesis gave a relative risk of recurrence of 4
cytokines. Angiogenesis, endostatin and b fibroblast growth factor (FGF)
6
Endostatin gave a relative risk of tumour recurrence of 4.7
HNSCC. Studied three angiogenesis-related
t
2
host immune
response to tumour
i
FGF in HNSCC
i
FGF with tumour stage
ELISA
8
33
bFGF in advanced HNSCC
Positive correlation but not statistically robust
Tumour immunology
34
Dendritic cells transduced with normal p53 generate
Numerous methods
Normal p53 gene inserted into an adenovirus vector
antitumour cytotoxic T cells from blood of cancer
applied to cancer patients' dendritic cells. These
patients
then exposed to cancer patients' T cells. This
3
process caused the production of antitumour CD8 + cytotoxic T cells. This is therapy rather than a test
(Continued over)
I
~
..
-
Table 183.1
Comparison of markers for HNSCC (continued).
2
35
Circulating IgG response to stromelysin-3, collagenase-3, galectin-3 and mesothelin in HNSCC
ELISA IC
3
36
Antibodies to EBV Rta protein in NPC
ELISA
4
37
IC
5
38
Can mononuclear cells produce IFN-gamma in laryngeal cancer? ~2-microglobulin as a marker for NPC
Serum thymidine phosphorylase in Ca oesophagus. This enzyme is also known as platelet-derived growth factor. It involves angiogenesis in cancer Urokinase-type plasminogen activator in HNSCC Urokinase receptor i in HNSCC
ELISA
IC
This constitutes the first report of IgG to collagenase-3. Antibodies to the latter molecule were forming in 50% of cancer patients and only 10% of controls IgA andG to Rta protein correlated with the pres.ently used test of IgA to EBV early antigen Ca Larynx associated with IFN-gamma significance? Little to find, no clinical importance
2
t
Miscellaneous markers 39
2 3
40 41
4
42
5
43
6 7
44 45
8
46
9
47
10
48
11
49
i lactate leads to i risk of metastases in HNSCC. Hypoxia shifts the cell towards glycolysis and lactate formation Hypercalcaemia associated with parathyroid hormone-related protein in terminal HNSCC Detecting the above protein in serum in HNSCC Hypercalcaemia is the commonest metabolic complication in HNSCC. Most likely due to the above prote i n Anaemia and surgically treated. Larynx SE
Western blot and zymography Northern blot Bioluminescence assay
i Enzyme is associated with increased depth of tumour invasion and poor prognosis but it is not an independent prognostic factor No associations The receptor i in HNSCC but a poor marker of prognosis i lactate -+ i local and distant metastases and a poor outcome
BIOPSY IC IC BIOCHEM and IC
Parathormone may be detected by biopsy before hypercalcaemia takes place This protein is not a useful serum marker Hypercalcaemia is a survivor's prognostic sign in advanced oral cancer
Routine full blood count
Anaemia (male < 13, female < 12). Associated with high risk of treatment failure Parotid tumours iPSA. Also Ca breast, colon, ovary, liver, kidney and adrenal. Also normal breast Patients frequently show disordered oestrogen metabolism (M and F) Subgroup of intestinal metaplasia (seen in Barrett's) and all oesophageal adeno Ca express sulphomucins and aberrant Le (a). Also Le (a + b-) nonsecretor and blood group A phenotypes -+ genetic susceptibility. H. pylori present in 75% of adeno Ca
Prostate-specific antigen (PSA) expression in tumours Oestrogen and HNSCC
Immunofluorometric assay
Blood group phenotypes, sulphomucins and Helicobacter pylori in Barrett's oesophagus
Routine Clinical laboratory tests
ELISA
o o
o
2
(Continued over)
Table 183.1
12
Comparison of markers for HNSCC (continued).
50
H. pylori in HNSCC
Routine
Serum positivity in 57% of controls and 62% HNSCC
2
- no difference 13
51
Predicting HNSCC from exfoliative oral cytology
CYTOLOGY Micronuclei assay
The micronuclei cytological assay correlates with
3
smoking and drinking, confirms field cancerization and may be able to detect early HNSCC or at least indicate risk
14
52
SCCA, carcinoembryonic antigen (CEA), ferritin, sialic
Various
acid and immunosuppressive acid protein in
lAP, sialic acid and SCCA useful prognostic markers
3
in HNSCC
HNSCC 15
53
CEA, SCCA, ferritin and tissue polypeptide antigen
Various
(TPA) as markers of response to chemotherapy.
In order of sensitivity TPA, CEA, SCCA and ferritin
2
appear to be potentially very useful markers
TPA (12-0-tetradecay phorbol-13-acetate) a mitogen inducing transcription of fos, jun and ets genes 54
16
Markers of thyroid cancer
Routine clinical chemistry
Thyroglobulin for FU of differentiated thyroid Ca. Need to know thyroid-stimulating hormone and T4 replacement status to interpret. Sequential measurements mainly of use
Ret gene study
Calcitonin and Ret oncogene assays for medullary Ca also CEA In familial forms pentagastrin test useful Nothing new here but confirms our practice
.
Values: 0 = nil, 3 = excellent. All assays are performed on serum unless otherwise specified in bold capitals in the 'Analysis column'. IC, immunochemistry; INC, immunonuclear chemistry.
2
Chapter 183 Prognostic indicators and serum markers.
2391
DNA Serum alkaline
An enzyme associated with tissue necrosis
DNAase
2
EBV
Epstein-Barr virus associated with head and neck cancers and particularly with nasopharyngeal carcinoma (NPC). HPV is similarly associated
P53: This is the gene product of the gene Tp53 and has been discussed earlier 3-5
6
SCC
Squamous cell carcinoma
HNSCC
Head and neck squamous cell carcinoma
PCR
The polymerase chain reaction used to amplify small amounts of DNA for further study
ELISA
Enzyme-linked immunosorbent assay. An assay commonly used to study small quantities of Igs
erbB2
A growth factor receptor gene similar to epidermal growth factor (EGFR)
Bcl2
A gene whose protein product inhibits apoptosis. It stands for the B-cell lymphoma gene
Cyfra 21-1: Fragment of cytokeratin 19 found in patients with HNSCC 1-4
As above
SCCA: Squamous cell carcinoma antigen. It has two isoforms of highly homologous serine proteinase inhibitor genes 1-4
As above
Receptors ECM
The extracellular matrix discussed previously
Glycoproteins: ErbB1 is EGFR as above. Other molecules in this section ECM 1-4
Also described previously
As above
Adhesion: Sialic acid occurs with degradation of the ECM. Sialic acid molecule residues commonly occur on glycoproteins and have an adhesion function among others 1-3
As above
ECM: Cathepsins are powerful proteolytic enzymes Disruption MMPs have been discussed in the text. Stefin A and B are endogenous inhibitors of cysteine proteinase cathepsin (B and L). MMP-9 is the most frequently associated with HNSCC 1-2
As above
Cytokines: An array of molecules with powerful functions. The interleukins are inflammatory mediators and also ligands for certain cell receptors. For example, they can trigger apoptosis bFGF
A powerful growth factor and binds with EGFR. It has many other properties which include inducing
Endostatin
Also induces neoangiogenesis
neoangiogenesis 1-8
As above
Immunology Dendritic cells
The antigen presenting cells for the immune system. They possess major histocompatibility complex (MHC) class 2 receptors. Following processing the dendritic cell is able to 'programme' other immune cells, particularly lymphocytes to attack other cells possessing MHC class 1 receptors. These cells include neoplastic ones
2
Galectin
An animal lectin capable of binding metallic ions. Galectin-3 is the one usually associated with tumours including HNSCC. Lectins trigger cell receptors but not by the normal process,
ct.
ligands. They are
implicated in human cancers, e.g. peanut lectin and bowel cancer. Lectins are a group of animal and plant carbohydrates which may function as a receptor for a ligand (Continued over)
.1
\
2392 • PART 17 HEAD AND NECK TUMOURS
Table 183.2
Terms and abbreviations used in Table 183.1 with explanations (continued).
3 4
Rta
The product of the BRLF gene of EBV. BRLF is classed as an immediate-early gene
IFN
Interferons are well-known cytokines with antiviral and antitumour properties. Many inflammatory cells
5
Microglobulins
Frequently associated with cancers
can produce them and high levels of IFN are frequently found associated with cancers
Miscellaneous: This assorted group of molecules are well known but several require special mention 11
PSA
Prostate-specific antigen is now known to occur on other steroid hormone-stimulated cancers such as
12
Helicobacter
Thought to be carcinogenic to the upper digestive tract
13
TPA
breast and salivary glands infection Carcinogenic in laboratory experiments and induces the transcription factor relateq genes, e.g. fos, jun and ets
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of c-erbB-1 and c-erbB-2 proto-oncogene products in patients with squamous cell carcinoma of the head and neck. Oral Oncology. 2001; 37: 50-6. Bathi RJ, Nandimath K, Kannan N, Shetty P. Evaluation of glycoproteins as prognosticators in head and neck malignancy. Indian Journal of Dental Research. 2001; 12: 93-9. Kokoglu E, Sonmez H, Uslu E, Uslu I. Sialic acid levels in various types of cancer. Cancer Biochemistry Biophysics. 1992; 13: 57-64. Croce MV, Price MR, Segal-Eiras A. Association of alpha1 acidic glycoprotein and squamous cell carcinoma of the head and neck. Pathology Oncology Research. 2001; 7:
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antigen is a useful biologic marker in patients with
16.
Liu CM, Sheen TS, Ko JY, Shun CT. Circulating intercellular adhesion molecule 1 (lCAM-1), E-selectin and vascular
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cell cancer of head and neck. International Journal of 12.
Liu CM, Ko JJ, Shun CT, Hsiao TY, Sheen TS. Soluble
cancer. Anticancer Research. 2000; 20: 2241-3.
Heng P, Chan SH, Ooi EE, Soo MY, Loh KS, Wang D et al.
Pontes PA, Dietrich CP et al. Patients with head and neck
Elevated blood levels of soluble tumour necrosis factor
tumours excrete a chondroitin sulfate with a low degree
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Surgery. 2000; 122: 115-8. Gallurt P, Rodriguez P, Lorenzo A, Lopez Saez JJ, Senra A, Millan J. Plasmatic fibronectin in malignancies. International Journal of Biological Markers. 1992; 7: 240-3. Akcay F, Taysi S, Uslu C, Dogru Y, Gumustekin K. Levels of
1999; 15: 167-72. 32.
Leunig A, Tauber S, Spaett R, Grevers G, Leunig M. Basic fibroblast growth factor in serum and urine of patients with head and neck cancer. Oncology Reports. 1998; 5: 955-8.
33.
Dietz A, Rudat V, Conradt C, Weidauer H, Ho A, Moehler T. Prognostic relevance of serum levels of the angiogenic
soluble intercellular adhesion molecule-l and total sialic
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acid in.serum of patients with laryngeal cancer. Japanese
treated by primary radiochemotherapy. Head and Neck.
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Mitsuhashi M, Nagumo M. Hypercalcemia in patients with
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lymphocytes from peripheral blood of cancer patients.
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decreased local control of surgically treated squamous cell
Sampedro A, Alvarez Marcos C, Mira E et al. Circulating
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Feng P, Chan SH, Soo MY, Liu D, Guan M, Ren EC et al. Antibody response to Epstein-Barr virus Rta protein in
48.
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Schantz SP. Oestrogen metabolism as a risk factor for head and neck cancer. Otolaryngology and Head and Neck
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thymidine phosphorylase concentration in oesophageal
to predict the relative risk of cancer in the upper
squamous cell carcinoma. Cancer. 2002; 94: 1947-54.
aerodigestive tract using the MN assay. Oral Oncology. 2000; 36: 550-5.
Schmidt M, Grunsfelder P. Urokinase type plasminogen 52.
Kimura Y, Fujieda S, Takabayashi
T.
Tanaka T, Sugimoto C,
Saito H. Conventional tumour markers are prognostic
and neck squamous cell carcinoma in vitro and in situ.
Archives of Otolaryngology - Head and Neck Surgery.
indicators in patients with head and neck squamous cell
2001; 127: 679-82.
carcinoma. Cancer Letters. 2000; 155: 163-8.
Schmidt M, Schier G, Gruensfelder P, Muller J, Hoppe F.
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498-504. Brizel DM, Schroeder T, Scher RL, Walenta S, Clough RW,
Rosati G, Riccardi F, Tucci A. Use of tumour markers in the management of head and neck cancer. International Journal of Biological Markers. 2000; 15: 179-83.
Urokinase receptor up-regUlation in head and neck squamous cell carcinoma. Head and Neck. 2000; 22: 42.
Bloching M, Hofmann A, Lautenschlager C, Berghaus A,
Matsubara H et al. Prognostic significance of serum
activator expression and proliferation stimulation in head
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microglobulin (beta 2M) as a tumour marker in
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Cytobiologica. 2001; 39: 106-7.
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parameter for diagnosis. Cancer. 2001; 92: 1872-80. Rogowski M, Rutkowski R. Assessment of the ability of
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Suarez-Alvarez B, Garcia Suarez MM, Arguelles ME, IgG response to stromelysin-3, collagenase-3, galectin-3
36.
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Carbone DP et al. Dendritic cells transduced with full-
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Pichon MF, Basuyau JP, Gory-Delabaere G, Eche N, Daver A, Blanc-Vincent MP et al. Standards, options and
Dewhirst MW et al. Elevated tumour lactate
recommendations for blood tumour markers in thyroid
concentrations predict for an increased risk of metastases
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in head and neck cancer. International Journal of
Radiation Oncology. Biology. Physics. 2001; 51: 349-53. 43.
Fujikawa M, Takata Y, Okamura K, Nakagawa M, Tateishi A,
FURTHER READING
Kurokawa H et al. Hypercalcemia associated with parathyroid hormone-related protein at the terminal stage of uncomplicated squamous cell carcinoma in the head and neck region. Head and Neck. 2002; 24: 56-62. 44.
Sellers RS, Schuller DE, Sharma PK, Tannehill-Gregg SH, Capen CC, Rosol TJ. Head and neck squamous cell carcinoma: measurement of plasma parathyroid hormonerelated protein and serum and urine calcium
Cox TM, Sinclair J. Molecular biology in medicine. Oxford: Blackwell Science, 1997. DeVita VT, Hellman S, Rosenberg SA (eds). Cancer - principles
and practice of oncology. 4th edn. 2 vols. Philadelphia: Lippincott, 1993. Lodish H, Berk A, Zipursky SL, Matsudaira P, Baltimore D, Darnell J.
Molecular cell biology. 4th edn. New York: WH Freeman, 1999.
concentrations. Otolaryngology and Head and Neck
Schwab M (ed.). Cancer. Berlin: Springer, 2001.
Surgery. 2000; 123: 558-62.
Whitfield P. Evolution. London: Mashall, 1993.
184 Skin cancer of the head and neck GARRICK A GEORGEU AND MICHAEL GLEESON
Introduction Basal cell carcinoma Squamous cell carcinoma Malignant melanoma
2395 2395 2398 2399
Author's cautionary note Key points Best clinical practice References
2402 2402 2403 2404
The data in this chapter are supported by a Medline search using the key words skin cancer, basal cell carcinoma, squamous cell carcinoma, malignant melanoma, excision margins, incomplete excision, diagnosis, management, guidelines, recurrence, head and neck.
INTRODUCT~ON
The epidemic that is skin cancer is significant and continues to rise. Melanoma and nonmelanoma (basal cell and squamous carcinomas) skin cancers account for almost 50 percent of all cancers diagnosed annually in the USA. The incidence of skin cancers is estimated to have increased by as much as 20 percent over the last decade. 1,2 Basal cell carcinomas account for approximately 80 percent of all nonmelanoma skin cancers diagnosed, squamous cell accounts for the further 20 percent, with a ratio of 4: 1.
head and neck accounting for between 85 and 93 percent of all cases, of which 25 percent are found on the nose. 3 The risk of developing one or more lesions after a primary BCC or squamous cell carcinoma (SCC) is 35 percent at three years and 50 percent at five years. The estimated risk of metastasis from BCC is less than 0.1 percent, with lymphatic and blood-borne spread both reported. 4
Risk factors for BCC The risks of developing a BCC can be divided into genetic predispositions, environmental exposure and premalignant conditions (see Table 184.1).
BASAL CELL CARCINOMA GENETIC PREDISPOSITION
Jacob first described the characteristics of a basal cell carcinoma (BCC) as a rodent ulcer as early as 1827. The BCC arises from pluripotential cells within the epidermis or hair follicles. Clinically, these tumours are usually slow growing following an indolent course and may take years to develop into a significant size (Figure 184.1). BCC are found most commonly in sun-exposed areas, with the
Skin type
Sun-exposed skin is the main anatomical site for BCC and SCC. The susceptibility of the skin to sun damage is directly related to the amount of melanin. This skin phenotype classified by Fitzpatrick5 divides the skin into six types according to the melanin content, pigmentation
2396 I PART 17 HEAD AND NECK TUMOURS the disease to be located at a tumour suppressor gene on the long arm of chromosome 9. 4 • Epidermodysplasia verruciformis: A viral and partially inherited disorder resulting in the inability to resist human papilloma virus (type 3 and 5) leading to degeneration of the lesion into a BCe.
ENVIRONMENTAL EXPOSURE
Sun exposure It is well documented that the total time spent in the sun
Figure 184.1
Table 184.1 skin cancers.
Basal cell carcinoma.
Summary of risk factors for the development of
and the number of sun burns plays a cumulative risk of developing skin cancer. The UV spectrum is the only significant wavelength in the pathogenesis of skin cancer, with UVA potentiating the direct effects that UVB has on skin cell DNA. UVC is a potent carcinogen, but is filtered by ozone. Ionizing radiation
Genetic
Environmental
Premalignant lesions
Pale skin Syndromes: xeroderma pigmentosum; Gorlins' (BCC); epidermodysplasia verruciform is (BCC); albinism (SCC); epidermolysis bullosa (SCC); porokeratosis (SCC)
Su n exposu re Ionizing radiation Chemical exposure Immune suppression Sebaceous naevus of Jadassohn (BCC) Actinic keratosis (SCC)
Pale skin Syndromes: atypical mole syndrome
The most important factor in carcinogenesis is the total accumulated dose. It is recognized as an occupational hazard in radiology, mining, airline pilots and occurs in patients treated with radiotherapy. Chemicals
Certain chemicals act by direct toxic effects or potentiating the effects of UV radiation, for example, polycyclic aromatic hydrocarbons, psoralens and arsenic exposure. Immune suppression Giant hairy naevus Family history Sun exposure
Inability of the host to detect and repair damaged cells is a feature of immune suppression. This predisposes to the spontaneous development of malignant cells: 30 percent of skin cancers that develop are highly aggressive.
Dysplastic
PREMALIGNANT LESIONS
Naevus Lentigo maligna
Sebaceous naevus ofJadassohn usually presents at birth as a yellow plaque, with approximately 10 percent undergoing malignant change.
and sensitivity to sunlight. Fair skin that always burns (type 1) is at a higher risk of developing a BCC or SCC than Africo-Caribbean (type 6) skin. Syndromes
• Xeroderma pigmentosum: An autosomal recessive condition resulting in the inability of the body to repair ultraviolet (UV)-induced skin damage. Develop multiple BCC and SCC early, poor prognosis. • Gorlins' syndrome: An autosomal dominant condition characterized by a number of features including multiple BCe. Genetic analysis has found
Types of
Bee
There are several types of BCe. • Nodular: The most common type, usually arising in the head and neck. Slow-growing, fleshy or pearly coloured nodule. • Superficial: These lesions often develop on the trunk in multiple patches, contained within the epidermis with no dermal invasion, may have shallow ulcer, atrophic scar or crusting. • Pigmented: Lesion contains melanin causing confusion with melanomas.
J
Chapter 184 Skin cancer of the head and neck. 2397 • Morphoeic: These lesions are usually indurated, with irregular borders, behave aggressively and are frequently misdiagnosed and incompletely excised.
Treatment of
Bee
The treatment method is usually based on the local specialist expertise, the resources available to the clinician and can be simply divided into surgical, destructive and medical techniques.
SURGERY
Surgical excision achieves high cure rates. Epstein6 reported a 94 percent cure rate using a 2 mm margin and a 95 percent cure rate was reported by Wolf and Zitell/ with a 4 mm margin for tumours less than 2 cm. 4 Risk factors for incomplete excision include grade of surgeon; sensitive anatomical sites such as the ears, eyes and the nose; large tumours > 2 cm; aggressive histological subtypes, such as the morphoeic BCC; and young age. 8 ,9 In such situations it may be better to perform a more radical excision, cover the defect with a temporary dressing and only then proceed to a staged reconstruction of the resultant defect, once histological confirmation of tumour clearance has been given. 8 ,10 Moh's micrographic surgery (MMS), developed in 1932, involves a process of initial surgical excision of the tumour, followed by repeated tissue sampling along lateral and deep margins. These tissue samples are examined immediately under frozen section control for evidence of tumour. This process is repeated until clearance is finally obtained. Moh's reported cure rates for primary BCC are 66 percent (3 mm margin), 85 percent (5mm margin) and >95 percent (l3-15mm margins).7, 11 The disadvantages of this form of treatment include limited access to these specialist centres, the possibility of multiple operations and the need for delayed reconstruction.
DESTRUCTIVE
• Electrodessication and curettage (EDC): A reliable technique with cure rates of 97 percent reported in studies of small,· well-circumscribed, superficial lesions. 12 An overall cure rate of 74 percent relates to higher rates of recurrence with increasing tumour size. 4 , 13, 14 [Grade A] [**] Histological analysis is difficult due to the technique. • Cryosurgery (liquid nitrogen): This technique has been shown to be comparable to other techniques in the treatment of small, superficial lesions with less aggressive histological types in noncritical areas. [Grade AJ [**J Zacharin,13 a proponent of cryosurgery, formulated guidelines and obtained cure
rates of 97 percent, but less than 10 percent of the lesions treated in this study were > 2 cm. Treatment may require a number of clinic visits with reported complications of oedema, pigmentary changes, atrophic and hypertrophic scars. No histological confimation is obtained using this technique. • Pulsed CO 2 laser: This creates superficial vaporization of the skin, requiring a number of passes over the clinically apparent tumour and a healthy margin of tissue. It is a reportedly reliable technique in patients with a superficial BCC confined to the epidermis. Occasionally, poor cosmetic results are obtained from laser, including hypopigmentation and scarring. No histological confirmation is obtained from this technique. 4 ,8
MEDICAL TREATMENT
Radiotherapy is a useful alternative to surgery with reported cure rates of 92 percent for BCC and 90 percent for SCe. 12, IS This treatment modality is complicated initially by the numerous visits required for treatment and the long-term radiotherapy results of scarring, fibrosis and malignant transformation. It is a useful alternative to surgery for the elderly or medically unfit patient. The topical chemotherapeutic agent 5-flurouracil is not recommended for skin cancers, but is ideal for premalignant conditions such as actinic keratosis. It requires diligence by the patient to apply cream daily. Interferon is presently in various stages of clinical trials using intralesional injections of interferons into BCe. It is not advocated at present as the cure rate is inferior to other treatment modalities. 4 [Grade C] [***]
Recurrence THE INCOMPLETE EXCISION
There is controversy about the best form of treatment for the incompletely excised BCe. The accuracy of histological reporting has been confirmed in studies using MMS based on re-excising the primary site and finding 55 percent contain tumour. IS [Grade A] [**J Incompletely excised tumours have been shown to recur over time with the highest risk in those lesions that had both lateral and deep margins involved with BCe. 16 Rowe et al. found that 50 percent recur in the first two years, 66 percent in the first three years. Immediate re-excision is to be recommended in surgical sites where the resultant defect has been repaired with local flaps or grafts. 13 , 17 The options in the elderly or infirm patient with an incomplete excision may be for regular follow up or to refer the patient for local radiotherapy. Electrodessication and cautery for recurrent BCC has cure rates reported of 60 percent. [Grade AJ [***]
2398 I PART 17 HEAD AND NECK TUMOURS
In cosmetically sensItIve areas, such as periorbital, perinasal and periauricular regions, where deep margins are incompletely excised and there is an aggressive histological subtype (morphoeic BeC), surgery forms the only suitable alternative. This can be performed with wide local excision and frozen section control or MMS. The overall cure rate for recurrent Bee using MMS is 94.4 percent. 18
SQUAMOUS CEll CARCINOMA Squamous cell carcinoma arises from the basal layer in the epidermis. Although see accounts for 25 percent of nonmelanoma skin cancer, it has a poorer prognosis than Bee due to its aggressive local invasion of tissues and metastatic potential. It usually develops within altered skin, arising from, for example, previously sun-damaged areas such as within an actinic keratosis, or malignant change in a chronic sinus or ulcer (Figure 184.2). It arises most commonly in sun-exposed areas with 70-80 percent found in the head and neck. Overall, the risk of metastatic spread, usually via lymphatics, is 2-5 percent. see metastasis requires a multidisciplinary approach including surgery, radiotherapy and chemotherapy.4,19
Risk factors for SCC The risks of developing see can be divided into genetic predispositions, environmental exposure and premalignant conditions (see Table 184.1). GENETIC PREDISPOSITION
Syndromes • Xeroderma pigmentosum: see Risk factors for Bee above. • Albinism: an autosomal recessive condition, resulting in an increased risk of see due to the absence of melanin. • Epidermolysis bullosa: Variable genetic penetrance characterized by recurrent blistering of the skin predisposing to see with a poor prognosis. • Porokeratosis: An autosomal dominant condition resulting in abnormal keratinisation, 13 percent undergo malignant change. ENVIRONMENTAL EXPOSURE
Similar environmental risks for Bee hold true for see, including exposure to ultraviolet light, ionizing radiation, chemical exposure and immune suppression (see Risk factors for Bee above). PREMALIGNANT CONDITION
Actinic keratosis (synonyms: solar keratosis, senile keratosis), caused by sun damage, is a premalignant lesion with a malignant transformation rate of 10-l3 percent. 4,19
Types of SCC There are no different types of see, but they are graded histologically to indicate the aggressive nature of the individual tumour. Markers include the depth of tumour, degree of cell differentiation (poorly differentiating equals poor prognosis), mitotic index (high mitotic index equals poor prognosis). Occasionally, the use of immunohistochemistry and specinc dermal antibodies is needed to differentiate a poorly differentiated see from melanoma.
Treatment of SCC
Skin types For a review of the risk factors, see Risk factors for above.
Bee
The treatment method for see is similar to that of Bee and is divided into surgical, destructive and medical techniques. SURGERY
Figure 184.2
Squamous cell carcinoma.
This is the treatment of choice as the adequacy of surgery can be assessed histologically. There is no universally accepted margin of excision. An excision margin of 4 mm for low risk tumours (well differentiated, less than 2 cm) has been reported to have a cure rate of 95 percent?O [Grade A] [**] The larger the tumour, the larger the required margin to obtain cure, with a minimum of 10 mm recommended by some authors for those lesions > 2 cm. For larger tumours and/or those see which have irregular or indistinct borders, or in cosmetically sensitive and highrisk areas (lips, 'nose, eyelids, ears), MMS has a higher cure rate (95 percent) compared to surgery?1 [Grade B] [**]
J
Chapter 184 Skin cancer of the head and neck I
DESTRUCTIVE
Electrodessication and curettage has been used for low risk tumours (well differentiated, small tumours) with cure rates of 95 percent. [**J However, difficulty with histological accuracy and few long-term outcome data for larger tumours and poorly differentiated SCC must be recognized.21, 22, 23
MEDICAL
As with BCC, local radiation treatment is effective with 90 percent cure rates reported, 19,21,23 a good alternative treatment for patients refusing surgery or unfit medically. Initial drawbacks to treatment have been highlighted (see under Treatment of BCC).
Recurrence and metastasis Rowe et al. 21 correlated a number of risk factors associated with local recurrence and a higher risk of distant metastasis. They include the following. • Anatomical site: There is a higher risk of spread in the head and neck (10-20 percent) with the lip and ear predominating. • Size > 2 cm: Local recurrence rate 15.2 percent and metastasis rate of 30.3 percent (two and three times, respectively, the rates of lesions < 2 cm). • Depth of tumour: Invading > 4 mm and/or Clark's level V have local recurrence rates of 17.2 percent and metastasis in 45.7 percent. • Poorly differentiated tumours: A local recurrence and metastasis rate of 28.6 and 33 percent compared to that of well-differentiated tumours of 13.9 and 9.2 percent. • Perineural spread: There is a local recurrence of 10 percent. The clinical presentation of positive lymph nodes at the time of initial consultation is not uncommon, turning a
Figure 184.3
Melanoma: (a) nodular; (b) superficial spreading.
2399
localized skin disease into a regional and potentially distant metastatic disease with a poor prognosis (35 percent, five-year survival).19 A lymph node dissection is indicated in these situations and should be combined with the surgical excision of the primary. The treatment of distant metastasis is palliative and should be treated by a specialized multidisciplinary team where the modalities of further surgery, radiotherapy and chemotherapy can be offered to provide options for the patient's overall care.
MALIGNANT MELANOMA Melanoma comes from the Greek word melanos meaning black. Its sinister reputation relates to its unpredictable nature and variable response to conventional treatment modalities (Figure 184.3). In the USA, melanoma accounts for 3 percent of all cancer diagnoses and 1.2 percent of deaths. 2 It differs from the other skin cancers (SCC and BCC) in that although it is primarily a disease of fair skin, it occurs in all races and is not limited to sunexposed areas. Melanoma is less common than BCC or SCC (ten cases per 100,000 per annum in the UK), but its rate of increase (3-7 percent) annually matches these tumours. An increasing incidence is seen in the white population and specifically an increase of lower leg melanoma in women has been noted. There is an increasing incidence of trunk and extremity melanoma compared to the head and neck. 2,24 The lifetime risk of developing a second melanoma is 4-6 percent. 25 The head and neck account for 11-18 percent of all melanomas. Certain anatomical sites in the head and neck have different clinical characteristics. Different to the SCC, malignant melanoma (MM) of the ear has a better prognosis than the face, which is still better than the scalp and neck. If there is spread from an MM of the ear, it usually involves the parotid gland, which should be removed when a neck dissection is performed.
2400 I PART 17 HEAD AND NECK TUMOURS
Six major prognostic factors have been identified, of which tumour thickness and ulceration are the most important. 26 1. Tumour thickness: Tumour thickness is the most important determinant of survival; for example, with a 0.76 mm thick MM, survival over ten years equates to 92 percent compared to 50 percent for > 3 mm thick MM. 2. Ulceration: Ulceration is associated with an aggressive tumour and worse prognosis irrespective of depth and size. 3. Anatomical site: The survival curves are equal for the trunk. compared to the head and neck, but there is poor prognosis with the scalp versus facial MM. 4. Sex: There is better prognosis in women, possibly due to common site and lower incidence of ulceration. 5. Level of invasion (Clark's level): Survival is inversely related to level of invasion. 6. Surgical treatment.
Risk factors for MM The risks of developing MM can be divided into genetic predisposition, environmental exposure and premalignant conditions (see Table 184.1).
GENETIC PREDISPOSITION
ENVIRONMENTAL EXPOSURE
Sun exposure, especially the total accumulated dose and also the number of sun burns, has been linked in many studies to the development of melanoma, with the trunk predominating in men and the legs in women.
PREMALIGNANT CONDITIONS
Dysplastic naevus is thought by some to be a melanoma in situ, as an estimated 40 percent transform into a superficial spreading melanoma. 28 Lentigo maligna (synonym Hutchinson's freckle, senile freckle) is a precursor of lentigo malignant melanoma (Figure 184.4).
Types of MM There are four types of MM: 1. 2. 3. 4.
superficial spreading; nodular; acral lentiginous; lentigo malignant melanoma.
Two phases of growth occur, the first confined to the epidermis, called the horizontal phase, and a vertical phase. The latter phase is associated with an increased risk of metastasis. Their incidence, anatomical sites and characteristics can be seen in Table 184.2.
Treatment of MM
Skin type
Malignant melanoma primarily affects white individuals, having a greater than ten-fold incidence compared to Africo-Caribbean peoples.
The treatment of primary malignant melanoma and its subsequent management relates to the stage of disease at presentation and is classified according to a scheme by the
Syndrome
• Atypical mole syndrome: Atypical mole syndrome is an autosomal dominant condition. It is diagnosed in a patient with more than 100 naevi, where one or more have dysplastic features and are greater than 8 mm. The patient has a 10 percent chance ofMM. 25 • Giant hairy naevus: Giant hairy naevus occurs in a patient with a naevus > 20 cm, or more than 5 percent of the body surface area at birth. The estimated malignant transformation ranges from 3.8 to 18 percent. 27 Family history
A first -degree relative with MM increases the lifetime risk to 5-11 percent.
Figure 184.4
Lentigo maligna.
)
Chapter 184 Skin cancer of the head and neck I
2401
Summary of the frequency, site and clinical features of the different types of mali nant melanoma.
Frequency (Ofo) Site Clinical features
70 Any site, back (both sexes), lower leg (women) Irregular and asymmetrical borders; variable pigmentation usually > 6-8 mm in size
15 Any site, legs and trunk most frequent Rapid growth with no radial phase; raised dark papule or nodule
2-8 Soles, palms, subungal, mucous membranes Irregular shape, black or brown lesion, higher incidence in darker skin types (35-90 percent)
Table 184.3
The 2001 American Joint Committee on Cancer staging system for malignant melanoma.
la lb
< 1 mm, no ulceration < 1 mm with ulceration or 1.01-2 mm, no ulceration 1.01-2 mm, with ulceration or 2.01-4 mm, no ulceration 2.01-4 mm, with ulceration or > 4 mm, no ulceration > 4 mm, with ulceration Any thickness, no ulceration Any thickness, with ulceration Any th ickness, no ulceration Any thickness, ± ulceration Any thickness, with ulceration Any thickness, ± ulceration
2a 2b 2c 3a 3b 3c
4-10 Head and neck (nose, temple, cheeks). arms Malignant precursors, slow growth, large lesion, variable pigmentation
None
None
>90
None
None
70
Micrometastases Micrometastases . < 3 palpable nodes In-transit metastasis <3 palpable nodes > 3 nodes or matted nodes or in-transit metastasis
None
35
Yes
<2
4 Reproduced from Ref. 29 with permission from the American Society of Clinical Oncology.
American Joint Committee on Cancer (AJCC).29 This is broadly divided into four stages: 1. 2. 3. 4.
thin MM with/without ulceration; thicker MM with/without ulceration; any size MM with regional nodal disease; distant metastasis (see Table 184.3).
Local disease All clinically suspected MM should be excised initially with 2-5mm margins. [Grade B] [*] Occasionally, with a large lesion with indistinct edges, such as a lentigo maligna, or in a cosmetically sensitive area, such as the face, a single or multiple punch biopsies can be performed to make the diagnosis. Once MM is confirmed, a further surgical excision is recommended, where possible down to fascia. The· width of excision is directly dependent ·on the depth of tumour and current practice for MM below 4 mm thick is
based on two large trials. For MM < 1 mm thick, a surgical excision margin of 10 mm has been shown to be safe and effective. 3D [Grade A] [****] A study in the United States showed that for intermediate thickness MM (l-4mm), a 2 cm margin is to be recommended after it was found to be comparable to a 4 cm margin with respect to the rates of local and regional recurrence and distant metastasis. 31 [Grade A] [****] There is currently no universally accepted excision or re-excision margin for a MM thicker than 4 mm, despite their local recurrence rate of 20 percent. Eagerly awaited are the results from the UK-based trial ( 1 versus 3 cm surgical excision margins for malignant melanomas greater than 2 mm) and the Swedish trial (2 versus 4 cm excision margins for malignant melanomas greater than 2mm). Provisional results from the UK-based trial show an increased incidence of local and regional recurrence in the 1 cm arm of the trial, but no recommendations at this time could be given.
2402 I PART 17 HEAD AND NECK TUMOURS
Regional disease MM metastasis is usually via lymphatics. The thicker the original MM, the higher the risk of potential spread. Frequent clinical examinations are at present the only way of monitoring the regional lymphatic lymph nodes. The recommended appointment interval for invasive MM is three-monthly for three years followed by discharge for MM less than 1 mm and six-monthly reviews for a further two years for the rest. 24, 32 Positive clinical and/or cytological evidence of metastasis increases the stage of disease and decreases the prognosis accordingly. A radical lymph node dissection is a procedure that can be associated with considerable morbidity, but remains the only potential cure of metastatic disease. The role of sentinel lymph node biopsy (SLNB) in MM is hotly debated. The theoretical benefits are to improve the patients' prognosis by accurately identifying those patients with early metastasis not picked up on clinical examination. These patients then undergo a radical dissection of the regional lymph nodes to clear any potential residual tumour. The negative aspects of SLNB initially are the need for two operative procedures with their associated morbidity and complications. Also, and more importantly, the long-term health benefits of those patients with initial subclinical disease who had a positive SLNB followed by a radical lymph node dissection will only be known in 10-20 years' time. Sentinel lymph node biopsy's role at present is therefore diagnostic and prognostic with the possibility of it being recognized as therapeutic in time.
Distant disease Once evidence of disseminated disease is found, the prognosis is bleak with a mean survival of six to seven months and five-year survival of 6 percent. 33 Routine screening tests for the evidence of spread include chest radiograph, liver ultrasound and computed tomography (CT) scan of chest, abdomen and pelvis. These tests remain controversial as they are costly, of limited sensitivity and specificity in the early stage of spread and ultimately there is no effective treatment once spread has occurred beyond the regional nodes. 34 Treatment is therefore palliative not curative and the patients' care should be tailored accordingly, ideally within a multidisciplinary team. Various combinations of surgery, chemotherapy, radiotherapy and immunotherapy (interferon) have been used.
Recurrence A local recurrence occurs by definition within 2 em of the primary excision. Overall, for MM 1--4 mm thick, the local recurrence rate is 2.5 percent. This is true for MM less than
2.5 mm in the head and neck region, but recurrence rates climb to 12.3 percent when tumour thickness is greater than 4 mm. 35 Local recurrence has a poor prognosis with 82 percent of patients succumbing to their disease. 36 For single local and in-transit recurrence (between local recurrence and regional nodes), surgery is advocated. For managing multiple local and in-transit metastasis, isolated limb perfusion has been used, a less invasive and possibly simpler alternative is the use of the CO 2 laser.3? [Grade BJ [***/**J Elective lymph node dissection should be performed for lymph node recurrence if no previous surgery has been performed.
AUTHOR'S CAUTIONARY NOTE The efficacy of the different treatments for all skin cancers is difficult to analyze. What is discussed in this chapter is a representation of current modalities offered to patients. There are multiple variables that make comparisons between the techniques difficult. There are no prospective studies comparing techniques using comparable anatomical site, size of tumour, histological subtype, same level of expertise for each technique and uniform length of follow-up by an independent observer.
Chapter 184 Skin cancer of the head and neck. 2403
single or multiple if the lesion is large with indistinct margins. Note the biopsies should always include the leading edg~ of the tumour with a section of normal skin for comparison. (2) Excision biopsy may be performed using 3-4 mm margins for a BCC, 6 mm margins for a SCC and 2 mm margins for a suspected melanoma. This may make further treatment of small BCC and SCC unnecessary if good histological margins are obtained. In cases of incomplete or close surgical excision margins for any skin tumour, further surgery should be considered. (3) Lymph node biopsy/fine needle aspiration if clinically suspicious node is noted on examination. Specialist investigations (standard tests in preparation for treatment/specialist staging scans) including: (1) blood tests including a full blood count, urea and electrolytes, liver function tests; (2) chest x-ray; (3) ECG; (4) CT/MRI scan of lesion, regional lymph node basins, chest, abdomen and pelvis. Local guidelines may apply as to which investigation modality is preferred. ,/ Step 3. Multidisciplinary team meeting (MDT). The MDT is comprised of dermatologists, plastic surgeons, radiologist, histopathologists, radiotherapists, oncologists and skin cancer specialist nurses. Discussions take place on the best treatment modalities available for the patient after review of all Example of a skin cancer care pathway (UK guidelines from GP referral to definitive treatment in 61 days) ,/ Step 1. General practitioner (GP). Patient presents to
the investigations including histology reports and specialist scans. ,/ Step 4. Second skin cancer clinic appointment.
GP with a suspicious lesion on history and
Discussion takes place with the patient and relatives
examination. Depending on their experience the GP
firstly about the diagnosis of the tumour, its prognosis
will decide to either:
and secondly the treatments that have been offered
perform an urgent biopsy incisional (single/multiple)
after discussion of their case at the skin MDT.
or excision (3-4 mm for BCC, 6 mm for SCC, 2 mm
Definitive treatment is then planned according to the
for a suspected MM). Once the histology report
patients' wishes and may involve management of:
confirms a skin tumour, an urgent referral to the
local disease: observation following national
local skin cancer specialist centre is made; or
guidelines may be all that is needed if excision is
send immediate urgent referral fax/letter to skin
complete. Further wide local excision is indicated
cancer specialist centre (ideally using local
for MM, SCC and/or incomplete excisions. MMS
standardized skin proforma). ,/ Step 2. Initial skin cancer clinic appointment. Three
required for recurrent tumour, incomplete excisions and some histological subtypes. Radiotherapy may
processes need to be undertaken or planned during
be offered in patients who, for example, are frail
this visit and they include:
or decline surgery.
Primary assessment, including lesion history, site,
regional disease: observation (as above); sentinel
size, colour, mobility, pain, crusting, involvement or
lymph node biopsy (at this stage only performed in
invasion into surrounding structures; regional
regional centres as part of clinical trials); elective
spread, assessed clinically; evidence of metastasis
lymph node dissection for positive nodal spread
on history and examination; general health with
only; palliative radiotherapy. Systemic disease:
respect to fitness for anaesthetic or medication that
Observation and regular screening with serial scans
may affect any planned procedures (e.g. warfarin).
(controversial); radiotherapy to isolated metastasis;
Histology. Confirm the diagnosis by obtaining biopsy specimens taken at this clinic visit or booked on the next available theatre list. This can occur in the form of (1) incisional biopsy either
chemotherapy; immunotherapy. ,/ Step 5. Follow up. This will be based on national guidelines for tumour subtype.
2404 • PART 17 HEAD AND NECK TUMOURS
REFERENCES
17.
Richmond JD, Davie RM. The significance of incomplete excision in patients with basal cell carcinoma. British
1.
Roth JJ, Granick MS. Squamous cell and adnexal 24: 687-703.
2.
Diepgen TL, Mahler V. The epidemiology of skin cancer.
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Shanoff LB, Spira M, Hardy SB. Basal cell carcinoma: a
British Journal of Dermatology. 2002; 146: 1-6. statistical approach to rational management. Plastic and
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Reconstructive Surgery. 1967; 39: 619-27. 4.
Zbar RIS, Cottel WI. Skin tumors, I: Nonmelanoma skin
Journal of Plastic Surgery. 1987; 40: 63-7. Rowe DE, Carroll RJ, Day CL. Mohs surgery is the treatment of choice for recurrent (previously treated) basal cell carcinoma. Journal of Dermatological Surgery and Oncology. 1989; 15: 424-31. 19. Motley R, Kersey P, Lawrence C. Multiprofessional guidelines for the management of the patient with primary cutaneous squamous cell carcinoma. British Journal of Dermatology. 2002; 146: 18-25. UK 18.
carcinomas of the skin. Clinics in Plastic Surgery. 1997;
*
tumors. Selected Readings in Plastic Surgery. 2000; 9: 5.
6.
7.
1-33. General overview. Fitzpatrick TB. The validity and practicality of sun-reactive skin types I through VI. Archives of Dermatology. 1988; 124: 869. Epstein E. How accurate is the visual assessment of basal cell margins? British Journal of Dermatology. 1973; 89-37.
8.
of American Academy of Dermatology. 1992; 27: 241-8. 21.
10.
recurrence, metastasis, and survival rates in squamous cell
340-4.
Academy of Dermatology. 1992; 26: 976-90. Friedman NR. Prognostic factors for the local recurrence, metastasis and survival rates in squamous cell carcinoma
Telfer NR, Colver GB, Bowers PW. Guidelines for the
of the skin, ear and lip. Journal of the Academy of
Dermatology. 1999; 141: 415-23. UK management guidelines. Kumar P, Watson S, Brain AN, Davenport PJ, McWilliam U, Banerjee SS et al. Incomplete excision of basal cell carcinoma: a prospective multicentre audit. British Journal
22.
Dermatology. 1993; 28: 281-2. 23.
cancer. A statistical study of 1341 skin tumors comparing results obtained with irradiation, surgery and curettage
* 24.
Kirkland N. UK guidelines for the management of
* 25.
overview. 26.
Soong SJ. A computerised mathematical model and
Dermatological Surgery and Oncology. 1991; 17: 574-8.
scoring system for predicting outcome in patients with
Dubin N, Kopf AW. Multivariate risk scores for recurrence
DW, Sober AJ, Soong SJ (eds). Cutaneous melanoma, 2nd
localised melanoma. In: Balch CM, Houghton AN, Milton
of cutaneous basal cell carcinomas. Archives of
Dermatology. 1983; 119: 373-7. 13. Zacharin SA. Cryosurgery of cutaneous carcinomas. An 18-year study of 3022 patients with 4228 carcinomas. Journal of American Academy of Dermatology. 1983; 9: 947-56.
edn. Philadelphia: JB Lippincott. 1992. 27.
Marghoob AA, Schoen bach SP, Kopf AW, Orlow SJ, Nossa R, Bart RS. Large congenital melanocystic naevi and the risk for the development of malignant melanoma. Archives of Dermatology. 1996; 132: 170-5.
28.
Rivers JK, Kopf AW, Vinokur AF, Rigel OS, Friedman RJ,
Spiller WF, Spiller RF. Treatment of basal cell epithelioma
Heilman ER et al. Clinical characteristics of malignant
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melanoma developing in dysplastic nevi. Cancer. 1990; 65:
American Academy of Dermatology. 1984; 11: 808-14. Rowe DE, Carroll RJ, Day CL. Long-term recurrence rates in previously untreated (primary) basal cell carcinoma:
1232-6. 29.
Balch CM, Buzaid AC, Soong SJ, Atkins MB, Cascinelli N, Coit DG et al. Final version of the American Joint
implications for patient follow-up. Journal of 16.
2002; 55: 46-54. UK management guidelines. Anderson RG. Skin tumors II: Melanoma. Selected
Readings in Plastic Surgery. 2000; 9: 1-38. General
Breuninger H, Dietz K. Prediction of sub-clinical tumor infiltration in basal cell carcinoma. Journal of
15.
Newton Bishop JA, Corrie PG, Evans J, Gore ME, Hall PN, cutaneous melanoma. British Journal of Plastic Surgery.
48: 214-5.
14.
followed by electrodesiccation. Cancer. 1964; 17: 535-8.
Terashi H, Kurata S, Hashimoto H, Asada Y, Shibuya H, Fujiwara S et al. Adequate depth of excision for basal cell
12.
Freeman RG, Knox JM, Heaton CL. The treatment of skin
of Plastic Surgery. 2002; 55: 616-22.
carcinoma of the nose. Annals of Plastic Surgery. 2002; 11.
Rowe DE, Carroll RJ, Day Jr. CL. Prognostic factors for local carcinoma of the skin, ear and lip. Journal of the American
management of basal cell carcinoma. British Journal of
9.
Brodland DG, Zitelli JA. Surgical margins for excision of primary cutaneous squamous cell carcinoma. Journal
Wolf OJ, Zitelli JA. Surgical margins for basal cell carcinoma. Archives of Dermatology. 1987; 123:
*
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Committee on Cancer staging system for cutaneous
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melanoma. Journal of Clinical Oncology. 2001; 19:
Bieley HC, Kirsner RS, Reyes BA, Garland LD. The use of
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Mohs micrographic surgery for the determination of
30.
Veronesi U, Cascinelli N, Adamus J, Balch C, Bandiera D,
residual tumor in incompletely excised basal cell
Barchuk A et al. Thin stage I primary cutaneous malignant
carcinoma. Journal of American Academy of Dermatology. 1992; 26: 754-6.
melanom~. New England Journal of Medicine. 1988; 318: 1159-62.
Chapter 184 Skin cancer of the head and neck
31.
Balch CB, Urist MM, Karakousis CP, Smith TJ, Temple WJ,
35.
McGovern VJ et 01. Head and neck melanoma in 534
intermediate thickness melanomas (1-4 mm). Annals of
clinical stage 1 patients. A prognostic factor analysis and results of surgical treatment. Annals of Surgery. 1984;
200: 769-75.
Dicker TJ, Kavanagh GM, Herd RM, Ahmad T, McLaren KM, Chetty U et 01. A rational approach to melanoma follow-
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Karakousis CP, Balch CM, Urist M, Ross MM, Smith TJ,
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Bartolucci AA. Local recurrence in malignant melanoma:
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Long-term results of the multi-institutional randomised
Barth A, Wanek LA, Morton DL Prognostic factors in 1512
surgical trial. Annals of Surgical Oncology. 1996; 3:
446-52.
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American College of Surgeons. 1995; 181: 193-201.
34.
Urist MM, Balch eM, Soong SJ, Milton GW, Shaw HM,
Drzewiecki K et 01. Efficacy of 2 cm surgical margins for
Surgery. 1993; 218: 262-7.
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I 2405
37.
Hill GJ, Thomas JM. Use of the carbon dioxide
Shoaib T, Dunn R, Soutar D. UK guidelines for the
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melanoma. British Journal of Surgery. 1996; 83:
Surgery. 2002; 55: 706 (letter to the editor).
509-12.
185 Mucosal malignant melanoma
ANDREW S JONES
Introduction
2406
Recurrence and metastasis
Mucosal melanomas type and site
2407
Survival
2411
Presentation
2407
Complications of treatment and quality of life
2413
2410
Host and tumour factors
2407
Conclusion
2413
Diagnosis
2408
Key points
2413
Aetiology and biology of mucosal melanoma
2409
Best clinical practice
2414
Clinical findings and staging
2409
References
2414
Treatment
2409
The data in this chapter are supported by PubMed and Medline searches using the key words mucosal melanoma, malignant melanoma, melanoma, amelanotic melanoma, neural crest tumours, 'various appropriate treatments'; in various combinations as appropriate. The search was extended or refined as necessary. Back searching from review articles and from book chapters revealed a number of additional references. Finally, other databases were searched, such as the Cochrane database, the library of the British Medical Association and CHINAL. In all, 264 references of some relevance were identified. Initially, these were selected using the title and then the abstracts; finally, 121 original articles were used in the preparation of the present chapter. The chapter also makes use of the data from 259 patients from the University of Liverpool head and neck database. This was started by my predecessor, Phillip Stell, and since his retirement maintained by me. The database contains details on over 7000 patients with head and neck tumours and this chapter makes use of these data, not only in its preparation, but also for detailed calculations of recurrence and survival. All calculations have been carried out specifically for this chapter.
INTRODUCTION
melanoma of the head and neck,2 the data being retrieved from the Liverpool head and neck database and the
Malignant melanoma arising from the mucosal surfaces
regional database. In our study population, by far the
of the head and neck are very rare, in the American
most common site for mucosal melanomas was in
College
the nasal cavities and sinuses accounting for 69 percent, 22 percent occurred in the oral cavity and 9 percent in the
1998,1 91 percent of all malignant melanomas were cutaneous, 5 percent ocular, 2.2 percent peripheral unknown primaries and
of Surgeons
only
1.3
Commission
percent
were
Report
mucosal.
For
mucosal
melanomas, the head and neck was by far the most common site with 55.4 percent of cases, 23.8 percent were ano-rectal and the rest were urogenital. In a paper from our department, we reviewed 259 cases of mucosal
pharynx, larynx and upper oesophagus. The incidence of malignant melanoma as a whole is approximately two of
100,0003,4 and, as described above, mucosal melanoma
of the head and neck will account for less than 1 percent S of these cases. ln 1967, Lewiss and Martin reported an incidence of 0.67 percent for nasal mucosal melanomas
/
Chapter 185 Mucosal malignant melanoma I
2407
out of 2939 Caucasians with melanoma, all melanomas
appeared to be most common in Caucasians. 6 A series from Israel gives similar figures to Europe and white Americans,? the incidence of mucosal melanoma is two to three times more common in India. 8 [**]
MUCOSAL MELANOMAS TYPE AND SITE Whilst cutaneous melanomas are life threatening enough, mucosal melanomas are far more aggressive and have a much poorer outcome wherever they arise. The prognostic factors for both cutaneous and mucosal melanomas are similar but, at the time of diagnosis, mucosal melanomas have already reached dangerous limits in terms of depth of invasion and tumour thickness. In addition, mucosal melanomas are more refractory to treatment than the cutaneous disease.9 [*] Mucosal melanoma is a very aggressive tumour that is derived from the malignant transformation of melano cytes in the basal layer of the mucosa. The exact site of origin of many cases in the head and neck is difficult to determine.lo Where the site of origin can be determined, the
majority
arise in
the nasal
cavity;
by contrast
metastatic melanoma in these sites is very rare. Melano cytes in the sinonasal area are present in both Caucasians and Negros and exist mostly in the septum. Intra epithelial melanocytes occur locally and only in adult Negros.ll According to Batsakis/2 malignant melanoma of the head and neck appears to arise de
novo
without any
obvious precursor lesion, most sinonasal melanomas occur on the middle and inferior turbinates and the anterior nasal septum, these areas are not pigmented with melanin, whereas the olfactory area which is, is not associated with tills tumour. Junctional changes seen in cutaneous melanoma are rarely seen in mucosal melano ma, no doubt because of the advanced stage of this disease at the time of histological examination.13 [**]
Figure 185.1
A large polypoidal amelanotic mucosal
melanoma.
and numerous counterparts of this lesion occur on other mucosal cutaneous surfaces. All mucosal melanosis must be taken seriously because malignant melanoma cannot be excluded on clinical examination. In mucosal malig nant melanoma, me1anocytes in the basal layer tend to show bizarre atypical forms. Of interest is that primary acquired melanosis of the conjunctiva appears to be biologically different from other mucosal melanosis as it frequently progresses to malignant melanoma. [*] Mucosal melanomas tend to occur in an older age group than their cutaneous counterpart (from the fifth to eighth decade) and men are more commonly affected than women.16 Mucosal melanoma of the larynx, pharynx and I oesophagus is very rare. ?, 18, 19 In the case of the larynx and the oesophagus, dysphagia and airway obstruction occur as well as haemoptysis and hoarseness and the history is relatively short, in the region of half a year.
PRESENTATION
Mucosal melanomas at other sites have been described,
The clinical history is of little help in making the
gland. 22 [**]
including the middle ear,20 lacrymal sac21 and parotid
diagnosis. In the case of sinonasal melanoma, examina tion may show a sessile mass, a polyp or even a large obstructing tumour (Figure 185.1). Although usually
HOST AND TUMOUR FACTORS
pigmented, amelanotic lesions occur. The next common est site after the sino nasal tract is the oral cavity. Eighty
In the Liverpool series,2 which included 259 patients, the
percent are located in the maxilla, usually the palatine
mean age was 73 years, but varied from 35 to 90 years and
mucosa. Very occasionally, malignant mucosal melano
the condition was slightly more common in men. Most
mas
cases occurred in the nasal cavity with the oral cavity
form
over
pre-existing
longstanding melanosis.
Once the malignant tumour becomes clinically evident
being second, other sites contributed only a small number
it is locally invasive and tends to metastasize to the
of
cervical lymph nodes fairly late, but distant metastases are
oesophagus and multisite involvement (Table 185.1). In
q
cases
and
these
included
the
pharynx,
larynx,
fre uent.14 In a review of mucosal melanosis,15 labial
the case of the sinonasal cavities, nearly all the lesions
mucosal melanotic maculae demonstrate an increased
were on the nasal septum (usually anteriorly) or on the
number of dendritic me1anocytes along the basal layer
middle or inferior turbinate. Only 13 of 150 sinonasal
/ _.:....-..---- -
\
2408
I PART 17 HEAD AND NECK TUMOURS
Details of all patients in the study group.
Table 1 85.1
Number
Detail Total patients
259
Age range (year)
35-90
Mean age (year)
72.8
Male:female
1:0.9
Site Nasal cavity
163
Oral cavity
58
Pharynx
13
Larynx
3
Oesophagus
5
Multisite involvement
17
cavity cancers were located in the sinuses, eight were in
Figure 1 85.2
An amelanotic mucosal melanoma
(x40).
and other neoplastic cells.25 It is a sensitive test with immunoreactivity being present in 86-100 percent25.26 of
the ethmoid and five in the maxillary sinus. Of oral cavity
these tumours. The neurone-specific enolase test was
tumours, most developed on the palate and half this
popular but has been found to be unreliable.27 Identifica
number on the gingivae; the other oral cavity sites
tion of melanoma cytoplasmic antigen (using HMB45, a
contributed little to the total. Of the pharyngeal tumours
monoclonal antibody) and S 100 protein (using a poly
(which numbered 13), five were in the nasopharynx and
clonal antibody) appears to identify nearly all melanomas
seven in the hypopharynx with only one being present in
regardless of site.22 With these tests now available, the
the oropharynx. In our series, approximately one-quarter
classical methods of identifying melanin in the tumour
of patients had amelanotic melanomas and in a historical
cells is now less important.l2 Other work has demon
series these are likely to be underdiagnosed, most likely
strated the S 100 protein is divided into an alpha and a
being put into the category of undifferentiated malig
beta subunit.
nancy. Immunohistochemistry has allowed such lesions
appears to be rare in mucosal melanomas compared with
to be correctly categorized. Whilst failure and survival
cutaneous melanomas and may thus have a potential use
will be discussed later on in the chapter, the effects of
Immunoreactivity to the beta subunit
when studying metastatic melanoma from an unknown
host and tumour factors on survival cannot be ignored
site.28 Further work on the distinction between primary
here, patients aged over 60 years had a significantly
and metastatic melanoma of the mucosa has been carried
poorer tumour-specific survival than younger patients.
out by Billings et al.29 They noted that junctional activity
Those with amelanotic lesions also did particularly badly.
in the overlying or adjacent mucosa distinguishes primary
Multiple linear regression for associations of host and
mucosal melanoma from metastatic disease, in which the
tumour factors2 revealed little other than regards treat
overlying mucosa is usually intact. Whilst of interest, this
ment parameters. Older patients tended to receive no
observation is widely known by histopathologists. As may
curative treatment and patients with amelanotic melano
be expected in such a difficult field, new immunohisto
mas tended to receive radiotherapy.
chemical techniques aimed at a variety of proteins and melanoma cells are being described. A report from the Christie Hospital in Manchester30 describes the VS38 monoclonal antibody, this was recently described as a
DIAGNOSIS
marker reactive to neoplastic plasma cells and may be Whilst
amelanotic
malignant
mucosal
melanomas
useful in the diagnosis of plasmacytoma and melanoma.
occur frequently and thus almost any lesion is suspect,
Some lymphomas are also positive and
pigmented lesions, particularly of the nasal cavities or the
of benign naevi stained with this antibody, 11 percent
15 percent
oral mucosa, are particularly suspicious. Due to anato
of dysplastic naevi, in situ melanomas and 100 percent of
mical constraints, an incisional biopsy is usually regarded
primary mucosal melanomas also reacted. In addition,
as the first step in diagnosis.23 Whilst histological patterns
one clear cell sarcoma also stained. Unless other methods
do exist
have failed, it would seem that this antibody is not
(Figure 185.2), immunohistochemistry has
become a very important part of the histological diagnosis
specific enough for the routine diagnosis of melanoma.
of melanoma. The melanocytes may be dopa positive or
The
negative, in amelanotic lesions particularly, and also in
of melanoma
undifferentiated lesions immunohistochemistry is essen
the detection of vimentin, normally present only in
tial for diagnosis. Staining for the S 100 protein has been widely used,24 it is however, present in a variety of normal
Amsterdam
Group3l
underline
associated antigen
the
importance
detection
and
also
mesodermal tissue, in the diagnostic work up of this condition. [**J
I
/
/
... - ". \
. � . :.
Chapter 185 Mucosal malignant melanoma
AETIOLOGY AND BIOLOGY OF MUCOSAL MELANOMA Using a panel of immunohistochemical markers, including 5100, HMB45, NKI/C3, HLAlDR, PCNA, cytokeratin and Von Willebrand Factor, Barratt et aI.32 suggest that mucosal melanoma is an entirely separate entity from cutaneous melanoma, rather than being a subcategory of the latter tumour. Mucosal melanocytes occur normally and in a further study, Barratt and Raja investigated mucosa from the palate and buccal mucosa from 30 autopsy specimens, fresh samples of 'normal' gingiva were collected. Polyclonal antisera to 5100 stained dendritic cells throughout the epithelium but monoclonal antibodies to 5100, HMB45 and NKI/C3 labelled cells that were only restricted to the basal layer, often in clusters. HMB45 produced the clearest and most specific staining. Stains with HLA/DR showed Langhans' cells located in the basal layer, basally located dopa-positive cells were also seen as well as dopa-positive suprabasal dendritic cells, which were presumably Langhans' cells. 5100, HMB45 and NKIIC3 thus identify melanocytes normally present in all mucosa and these may be induced during normal function.33 [**J Like many tumours, therapeutic immune interven tions may be associated with neoplastic change. Mucosal melanoma of the tongue following stem cell transplanta tion for non-Hodgkin's lymphoma has been reported.34 Gene expression of several cytokines in conjunctival melanoma has been studied. It should be noted, how ever, that conjunctival melanomas have a relatively good prognosis compared to other mucosal melanomas. Messenger RNA was extracted and a reverse transcriptase polymerase chain reaction performed. The tumour expressed potent inhibitors of tumour cell growth including interleukins 2, 4, 6 and gamma-interferon. These inhibitors are not expressed by other pigment cells in the eye. The basic fibroblast growth factor gene which is known to stimulate melanoma cell growth, at least in the cutaneous variety, was not expressed in conjunctival melanoma.35 Further molecular work shows that N-ras mutation is common in cutaneous melanoma but rare in mucosal melanomas, no H-ras or K-ras mutations were detected. N-ras mutation occurred in two patients who had been exposed to UV light. In cutaneous areas not exposed to UV light, this mutation was missing and was also not present in mucosal melanomas.36 Given that UV light exposure is such an important aetiological factor in cutaneous melanoma, but obviously not in mucosal mela1loma, may partly explain immunohistochemical and molecular differences between the two cancers. Familial cutaneous malignant melanoma is known to be of genetic origin.3? Whilst mucosal melanoma undoubtedly has a genetic basis, no clearly defined syndrome has yet been identified. The antigenic profile of mucosal melanomas has been studied with regard to membrane-bound and cytoplasmic melanoma-associated antigens, adhesion molecules and receptors, as well as HLA class 1 and class 2
I 2409
antigens.38 Mucosal melanomas differed from other types of melanoma and their antigenic profile. In particular they had a higher expression of P97, CEA and NGF but a heterogeneous expression of HLA antigens was found similar to melanomas at other sites. There was a selective loss of, and abnormalities in, HLA class 1 expression and these abnormalities were greater in metastatic as opposed to primary lesions. Increased expression of high mole cular weight melanoma-associated antigen of 1l0-kDa, the P97 antigen, carcino-embryonic antigen, neuronal growth factor-R and GD2 ganglioside were found to be associated with a particularly poor prognosis. [**J
CLINICAL FINDINGS AND STAGING There are no tyPical clinical findings for malignant melanoma but obviously any type of dark tumour of the head and neck mucous membranes must be viewed with suspicion. Needless to say, one must always be aware that many mucosal melanomas will be amelanotic. Unfortunately there is no universally accepted staging system for this disease. The prognostic value at various levels of invasion as established in the Clarkes' classifica tion of cutaneous melanomas39 does not apply for mucosal melanoma because of the absence of histological landmarks analogous to the papillary and reticular demise. The VICC and AJC have yet to classify this disease,4o but the thickness of the melanoma is an important prognostic indicator as it is in the cutaneous tumour.23 The staging of Palatine has been recommended by some authors and the stage of the disease in this system does correlate with surviva1.41,42 [**J Since any chance of cure involves a major resection, if appropriate, as well as adjuvant treatment regimes, the tumour must be accurately defined anatomically and of course a careful search made for distant metastases. Work from Japan suggests that magnetic resonance imaging (MRI) may be the best imaging technique for head and neck mucosal melanomas, hyperintensity on T I-weighted images was characteristic, although not universally so, and the addition of gadolinium enhancement probably im proves sensitivity.43 Because by the time most head and neck mucosal melanomas present they are invading bone, a computed tomography (CT) scan is also required. In our department, a CT scan of the lungs and liver are carried out with a view to detecting metastases, making any curative treatment impossible.44 Because of the natural history of melanoma, a CT brain scan and an isotope bone scan are also indicated. It should be noted that bone formation can occur with a mucosal melanoma and its metastases.45 [**J
TREATMENT The mucous membranes of the head and neck contain a rich vascular and lymphatic system, both in the mucosa
2410 I
PART 17 HEAD AND NECK TUMOURS
and the submucosa. This facilitates local and systemic spread. The anatomy is further complicated by the close proximity of the sinonasal mucosa to the underlying bone, it is also close to the eye, base of skull and brain. 18 The philosophy of treatment of oral and sinonasal melanoma has largely been derived from experience with its cutaneous counterpart. There is a relatively low incidence of regional neck metastasis and a certain discontinuity within the regional lymphatic system favours a forthright attack on the primary melanoma.46 It is generally accepted that the radical excision of the primary tumour with or without adjuvant postoperative radiotherapy is the best treatment for patients with no evidence of distant metastasis.47 Mucosal melanomas initially spread radially, thus involving large areas of mucosa with margins which may be difficult to delineate.23 To be effective, surgical resection margins should be generous with inevitable aesthetic and functional deficit. [*] There has been a tendency to regard mucosal melanoma as radioresistant. However, work in 1991 on 28 patients with sinonasal mucosal melanoma demon strated that radical radiotherapy using megavoltage techniques to a dose of up to 55 Gy over three weeks was associated with complete regression of tumour in 79 percent of cases and sustained local control at 12 months in 74 percent. Before the latter evaluation, five early deaths had occurred from distant metastasis.48 These results have been subsequently confirmed by other oncologists.49,50 In 1999, the Institute of Laryngology and Otology in London assessed 58 patients receiving treatment for sinonasal melanoma, the sex incidence was equal and the ages range from 39 to 90 years with a mean age of 64 years. Twenty nine patients underwent surgery alone, 23 surgery and radiotherapy, 6 received surgery and chemotherapy and 3 patients received all regimes. Primary surgery included a complete excision, whether this involved lateral rhinotomy or maxillectomy, cranio facial resection or even endoscopic clearance. The death rate was high over the first 36 months due to local and/or systemic disease, irrespective of treatment modality. The five-year tumour-specific survival was 28 percent and the ten-year survival was 20 percent, adjuvant radiotherapy did not improve the results of surgery and nor did chemotherapy.5 1 Jatin Shah and his colleagues evaluated the results of 115 consecutive patients undergoing craniofacial resection for various malignant neoplasms and mucosal melanoma had the lowest survival of all tumours.52 The results of our department2 confirm that surgery offers the best chance of control of the disease and adjuvant radiotherapy appears to enhance this effect. This policy gave a five-year survival of 50 percent, a ten-year survival of 33 percent and a 20-year survival of 17 percent and half of the patients in this series had postoperative irradiation. [**] Chemotherapy has usually been given as a last resort to terminally ill patients. Reports suggest that chemotherapy
regimes containing dimethyl triazeno imidazole carbox amide (DTIC) may be more effective than others.53 In a recent phase two trial of tirapazanine with cisplatin in advanced metastatic melanoma from either cutaneous or mucosal origin, the overall response rate was 20 percent and the median duration of response was six months. If such treatment has any role it is, at present, in palliation only.54 The 20-year course of mucosal melanoma in some patients suggests some immune mechanism may be retarding its progress. Malignant melanoma was one of the first cancers where immunotherapy was introduced. Initially, these attempts were crude using BCG vaccina tion or DMCB treatment. In 1970, Wharton and colleagues55 examined the effect of interferon treatment together with cimetidine (an H antagonist) which 2 inhibits T suppressor cells and activates natural killer (NK) cells and the results were encouraging.56,57 More subtle treatments have been studied more recently, one used an IgG mouse monoclonal antibody combined with 3 the CD3 antigen on melanoma cells and major tumour regression was observed in three of 12 patients with metastatic melanoma.58 More recent work on this subject validated three vaccination strategies for melanoma in mice. The three vaccines essentially comprised (1) naked DNA, (2) peptide pulsed dendritic cells and (3) a mixture of peptide and the Escherichia coli toxin LTR72. The experimental results suggested that the tumour antigens were a target for immunotherapy and further, that the peptide pulsed dendritic cell based vaccine was the most promising and should be considered for a trial in human subjects.59 [***] Having described the four basic modalities of treat ment for malignant melanoma, there seems no doubt that major ablative surgery still offers the best chance of cure. In 1998, De Meerleer et al.60 emphasized that postoperative radiotherapy should be administered and offered good palliation in inoperable cases. They point out that intensity modulation techniques and local I125 seeds can be used to increase tumour dose whilst sparing surrounding normal tissue. Finally, it should be men tioned that new treatment strategies are always being developed and while most will unfortunately fail, some may be of use. In the recent literature, mention should be made of boron neutron capture therapll that is being developed for the treatment of glioma and cutaneous melanoma. By chance, it was found that the capture agents were also concentrated in oral mucosa. Studies are already underway and a new clinical facility is under construction in the UK. [***]
RECURRENCE AND METASTASIS Mucosal melanoma has a lower incidence of regional lymph node metastasis than cutaneous melanoma, both at presentation and later in the course of the disease.47 As with other cancers this is particularly true of the sinonasal
Chapter 185 Mucosal malignant melanoma I
tract. The incidence of such metastasis for oral cavity
2411
SURVIVAL
melanoma is higher, local recurrence rates however seem to be higher for sinonasal disease than for oral cavity
The five-year tumour-specific survival of the 259 patients
and pharyngeal cancer.47 In Gallagher's series,62 just over
in the Liverpool series was 44 percent, lO-year survival was
half of all patients had locoregional or distant involve
33 percent and the 20-year survival was 17 percent. The
ment within one year.62 The primary site recurrence
20-year observed survival, that is death from all causes,
rate following complete therapeutic ablation of disease
was 12 percent (Figures 185.6 and 185.7). This figure is
varies from
55 to 82 percent according to various authors.63. 64, 65, 66 The incidence of neck node failure varies from 16 to 35 percent.67, 68 Our figures for a total of 259 patients suggest a 37 percent actuarial primary site recurrence at two years, but this rises to nearly 70 percent at 12 years. As regards neck nodes, failure in the regional nodes occurred in over a third of patients after two years (Figure 185.3). Mathematical extrapolation of this statistic suggests that neck node failure will continue unabated as time goes on, probably being somewhat less than the primary site recurrence rate at 12 years. Lee
et al.69 report a local recurrence rate of 80 percent. [**] Distant metastasis
has
always been a
malignant melanoma and mucosal
feature
melanoma
of
is no
exception. The Roswell Park Cancer Institute studlO showed that of patients with complete local control, 76 percent died of distant metastases over the years (Figure
185.4). Mucosal melanoma, like other malignant mela nomas, frequently metastasizes to the brain (Figure
185.5), the median survival of such patients is 103 days.7! In a very few patients, surgical resection can significantly prolong meaningful survival. As regards bone metastases, the spine is not uncommonly involved. In a series of 133 patients72 mostly suffering cutaneous melanoma, nearly all patients had metastatic disease to other sites. Bone was very often involved with a median survival of four months and spinal metastases tended to occur late in the disease. Of practical concern is that false
Figure 185.4
Hilar metastasis from a mucosal melanoma.
Figure 1 85.5
A CT brain scan showing a melanoma
negatives from bone scanning occurred in 15 percent of patients. [**]
80 70 60
:;R � 50 o c
40 � i3 30 OJ a: 20 10 o
3 6 (Months)
Figure 1 85.3
12 18 24
I�/------� 12 years
Time
Actuarial development of recurrence at the
primary site and in neck nodes (University of Liverpool Database) *. neck nodes, site
permission.
!
,'-----�
(35 percent at two years); ., primary
(69 percent at 12 years). Redrawn from Ref. 2. with
metastasis.
I
2412 I
PART 17 HEAD AND NECK T UMOURS
similar to that seen for the tumour-specific survival and is typical of a lethal disease.16 A number of other authors note a similar disastrous prognosis.62, 66, 73, 74, 75 [**J As regards factors affecting survival, our work2 showed that those with melanotic melanoma faired better at three years than those with amelanotic melanoma (Figure 185.8). This may in part be a consequence of diagnosing the latter condition relatively late. In addition, in our series, amelanotic melanoma tended to receive radio therapy rather than primary surgery. Our results show primary surgery is associated with better survival than nonsurgical treatment; radiotherapy as the primary mode of treatment was ineffective in our series (Figure 185.9). Women fared better than men but site had no effect on survival and this observation is confirmed by other
series. 16, 76, 77 Freedom et al.64 and Snow et al.,67 however, noted that nasal cavity tumours fared better than tumours of the paranasal sinuses and the oral cavity. [**J The Liverpool series was large enough to perform meaningful multivariate analysis of factors affecting survival using Cox's proportional hazards' model.78 This mathematical technique, based on a hazard function, is the most accurate routine statistical method we have 100
80
�
100
60
Ol c .s;
.�
::J (f)
80
�
40
20
60
Ol c
:� 2:
::J (f)
40
o
48 Survival
20
Figure 185.8 on survival
60
120
180
(months)
The effect of melanotic vs amelanotic melanoma
;d =5.9231;
p=0.0149. *, melanotic (58 percent at
three years); <>, amelanotic (20 percent at three years).
o
12
24
36
48
Survival Figure 185.6
60
84
120
180
240
Redrawn from Ref. 2, with permission.
(months) 100
Observed survival. All patients (12 percent at 20
years) Redrawn from Ref. 2, with permission.
80
100
�
80
60
Ol c .s;
�
.�
::J (f)
60
40
Ol c .s;
.�
::J (f)
40
20
20 o
12
24
36
48
Survival o
12
24
36
48
Survival Figure 185.7
60
84
120
180
240
(months)
Tumour-specific survival. All patients (17 percent
at 20 years). Redrawn from Ref. 2, with permission.
Figure 185.9
xf =41.6658; at five years);
60
84
120
180
(months)
The effect of treatment on survival.
p=O.OOOl. *, nonsurgical treatment (17 percent
e:"
treatment including surgery (49 percent at
five years). Redrawn from Ref. 2, with permission.
Chapter 1 85 Mucosal malignant melanoma I
2413
for studying survival. This clearly demonstrated that
not known. There is the possibility of giving radiotherapy
advanced age had an adverse effect on survival, women
to the ipsilateral
fared
better
than
men and
melanotic
lesions
fared
better than amelanotic lesions. Site and radiotherapy
There is
NO neck but its efficacy is not proven.
considerable doubt
regarding the magnitude of
on
the
statistical
analysis
effect of therapeutic
had no effect whereas primary surgical treatment was
intervention on the natural history of this disease. Certainly
highly significantly associated with prolonged survival
nearly all untreated patients are dead within four years,2 but
(p < 0.0001). Although relatively few patients in our series
then most patients who were not treated had very advanced
had postoperative radiation, this did significantly improve
disease. The best evidence we have is that Cox's model in a
survival and is recommended. Regrettably, due to a
large series of patients, highly significantly associates
disparity in patient numbers, Cox's model becomes too
surgical treatment with an improvement in survival. With
unstable to confirm this effect although it was demon
such a rare disease as mucosal melanoma of the head and
strated on univariate analysis.
neck, it is unlikely that any controlled trials
In our
will ever be
node
carried out. It seems possible that advances in immuno
metastasis should undergo full radical neck dissection, if
modulation, antibody delivered therapy and perhaps gene
necessarily staged and bilateral, followed by irradiation to
therapy, with or without more effective chemotherapy and
series,2 patients
with regional
neck
the neck. Although in our large series we have evidence
radiotherapy,
that this is the most effective policy, Harrison felt it was
this disease. Whatever the type of novel therapy it
unjustified and he recommended simply removing the
to address the problem of distant metastases. Mucosal
enlarged nodes;79 our data do not support this view.
will form the basis for future treatments of will have
melanoma, along with malignant salivary gland carcino
NO disease
mas, are among the most distressing diseases head and neck
is a difficult one. Conley and Hamaker75 found a tumour
oncologists treat and one can only hope that more effective
The question of elective neck dissection for
specific disease-free survival of 55 percent in those who
and more humane therapies
had an elective neck dissection, compared with
particularly unfortunate group of patients.
38 percent
will soon be available for this
in those who did not; the case for prophylactic neck 80, 81 Selective
dissection is supported by other authors.
neck dissection appears to be inadequate in this disease but some type of modification of a radical neck dissection may be permissible, particularly with preservation of the 8 accessory nerve. 1 [**J
COMPLICATIONS OF TREATMENT AND QUALITY OF LIFE The main treatment modalities for mucosal melanoma of the head and neck are the same as for squamous cell cancer, with the exception of immunotherapy. Complica tions and quality of life issues are largely site specific and are discussed in Chapter
'· ��: ?����J:elr;oeJm�,er tha� an:aelanotiG lesions .'U�.JI44I"'_
ooer-third of patients. These are
�·!�IM.�.to di,agnose and a bigh ,index of �l suspicion .must be maintained F..or iqIloscic �ation. relian� must»>;
199, Metastatic neck disease.
m4d�
QJl
wtQ\ogy
or.
histology. parti�llarly
with bmnunohisto,hemistry.
CONCLUSION
•
long-term �ntrol.
Head and neck mucosal malignant melanoma has a disastrous prognosis at
When attempting. cute,: surgery is the only primary �tment mod.ality associated with
20 years, this natural history is
•
cystic carcinoma. this malignancy has
almost linear decline in tumour-specific survival over two
long �ablral history of between
decades. Therapeutic intervention appears on statistical •
probably be carried out, although whether some mod
With this
in. mind. the. aim should be fot:
function kept to a mininluml thus
by postoperative irradiation. Involved neck nodes should
enJtl
quality of life.
be treated by radical neck dissection with preservation of not strong, ipsilateral prophylactic neck dissection should
very
good locoregional control and loss of
surgery and appropriate reconstructive surgery followed
the accessory nerve if possible. Although the evidence is
a
lO and 30
years.
analysis to alter this natural history to a useful extent. Primary site disease should be treated by wide ablative
It should be rer:nemhered. howev.er, that cqre
is unlikely to be achieved; rather like adenoid
very different from squamous cell carcinoma, with an
•
:rhe twnour-specmc percent at five years, and 17 percent at
20 years.
ification or selective neck dissection would be adequate is
\
/
2414
I PART 17 HEAD AND NECK TUMOURS
9.
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10.
./ Nasal lesions must be evaluated endoscopically and
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De Meerleer GO, Vermeersch H, Van Eijkeren M, Lemmerling M, Caemaert J, De Naeyer B et al. Primary
73.
Laryngology. 1998; 107: 626-30.
74.
of Otolaryngology. 1960; 72: 432-44.
75.
Conley J, Hamaker RC. Melanoma of the head and neck.
76.
Shah PJ, Huvos AG, Strong WE. Mucosal melanomas of the
Laryngoscope. 1963; 87: 757-64.
oral mucosal tissue: implication for boron neutron capture therapy. British Journal of Cancer. 2000; 82: 62.
1764-71.
head and neck. American Journal of Surgery. 1977; 134:
Gallagher JC. Upper respiratory melanoma. Pathology and
531-5.
growth rate. Annals of Otology. Rhinology. and
77.
Laryngology. 1970; 79: 531-56.
63.
Anderson U, Berthelsen A, Hansen HS. Malignant
neck: 48 cases treated at Instituto Nazionale Tumori of
melanoma of the upper respiratory tract and nasal cavity.
Milan. European Journal of Surgical Oncology. 1993; 19:
Freedom HM, De Santo LW, Devine KD, Weiland LH.
316-9. 78.
Cose DR. Regression models and life tables. Journal of the
79.
Harrison DFN. Malignant melanomata arising in the nasal
Royal Statistical Society. 1972; 34: 187-220.
Malignant melanoma of the nasal cavity and paranasal sinuses. Archives of Otolaryngology. 1973; 97: 322-5. 65.
mucous membrane. Journal of Laryngology and Otology. 1976; 90: 993-1005.
Panje WR, Moran WJ. Melanoma of the upper aerodigestive tract, a review of 21 cases. Head and Neck
80.
Surgery. 1986; 8: 309-12.
66.
Mundth E D, Euralnick EA, Raker Jw. Malignant melanoma, a clinical study of 427 cases. Annals of Surgery. 1965;
162: 15-28.
Harrison DFN. Malignant melanomata of nasal cavity. Proceedings of the Royal Society of Medicine. 1968; 61:
67.
Guzzo M, Grandi C, Licitra L, Podrecca S, Cascinelli N, Molinari R. Mucosal malignant melanoma of head and
Journal of Ootolaryngology. 1992; 21: 180-5.
64.
Ravid JM, Esteves JA. Malignant melanoma of nose and paranasal sinuses and juvenile melanoma of nose. Archives
449-57. Morris GM, Smith DR, Patel H, Chandra S, Morrison GH, Hopewell JW et al. Boron micro-localisation in
Batsakis JG, Suarez P, EI-Naggar AK. Mucosal melanomas of the head and neck. Annals of Otology. Rhinology. and
sinonasal mucosal melanoma: three different therapeutic approaches to inoperable local disease or recurrence and a review of the literature. Melanoma Research. 1998; 8:
Gokaslan ZL, Aladag MA, Ellerhorst JA. Melanoma metastatic to the spine: a review of 133 cases. Melanoma
2651-6.
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Sampson JH, Carter Jr. .lH, Friedman AH, Seigler HF.
Ronchetti A, Moro M et al. Relevance of the tumour for melanoma. Journal of Immunology. 2000; 165: 60.
Loree TR, Mullins AP, Spellman J, North Jr. JH, Hicks Jr. WL.
81.
O'Brian CJ, Peterson-Schaefor K, Ruark D, Coates AS,
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Menzie SJ, Harrison RI. Radical, modified and selective
Snow GB, Esch EP, Van der Siooten EA. Mucosal melanomas
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and Neck. 1995; 17: 232-41.
J
186 Nasal cavity and paranasal sinus malignancy BRENT A McMONAGLE AND MICHAEL GLEESON
Introduction Epidemiology Aetiology Surgical anatomy Patterns of tumour spread Staging Surgical pathology Presentation Clinical evaluation
2417 2417 2418 2418 2418 2420 2420 2424 2425
Treatment Other surgical procedures Prognosis Key points Best cI i nica I practice Deficiencies in current knowledge and areas for future research References
2427 2431 2434 2434 2435 2435 2435
The data in this chapter are derived from a Pubmed search using the key words nose and paranasal sinus neoplasms, and focussing on the diagnosis and management of these conditions.
INTRODUCTION In this chapter we discuss the management of malignant tumours that develop in the nasal cavity and paranasal sinuses. Malignancies of the nasal vestibule and external nose are discussed in Chapter 219, Nasal reconstruction. Sino nasal malignancies are a diverse group of tumours, some of which are unique to the nose. These tumours are uncommon and account for less than 1 percent of all neoplasms. They produce little in the way of symptoms at the outset when most are mistaken for rhinosinusitis. As a result, the diagnosis is usually delayed and only made at a relatively advanced stage. The average delay between the first symptom and diagnosis is six months. By this time, erosion of bone and infiltration of sensory nerves has usually produced severe pain and sometimes a facial sensory deficit. Further extension of the tumour into the orbit, brain and infratemporal fossa has profound implications for treatment and the likely outcome. Accurate staging of nasal and sinus tumours remains difficult despite recent advances in endoscopy and almost universal access to refined radiological imaging
techniques. Current staging systems are only applicable to the maxillary and ethmoid sinuses. Surgery and chemoradiotherapy remain the mainstays of treatment. Use of topical chemotherapeutic agents is favoured by some, but is not without complication. All treatment regimens inflict considerable morbidity and for some patients this has a very significant impact on the quality of their lives. Loss of sight, facial disfigurement and interference with mastication are issues that affect many. The prognosis for patients with sinonasal malignancies has improved over the last three decades, but remains poor overall. Consequently, quality of life issues are very important when considering treatment, particularly for those with extensive disease.
EPIDEMIOLOGY Sinonasal malignancies have an incidence of 05-1 per 100,000 per year. l They account for 0.2-0.8 percent of all malignancies and 3 percent of upper aerodigestive tract neoplasms? Most develop in the fifth and sixth decades of life. The incidence in men is twice that of women. 3 In the
2418 I past it
PART 17 HEAD AND NECK TUMOURS
was considered that certain races were more
General considerations
susceptible to sinus malignancies than others, but this misconception is explicable by occupational exposure to carcinogens.
[**J
Sinonasal malignancies tend to spread by local invasion. The ethmoid and maxillary sinuses are intimately related to the orbit, separated by paper-thin bone that is deficient in places where nerves and blood vessels pass through.
AETIOLOGY
These anatomical features favour relatively early spread of
Several carcinogenic compounds have been identified.
frontal sinus is similarly thin and that of the superior part
Inhalation of these carcinogens is responsible for about
40
percent of reported sinonasal malignancies. Foremost among these occupational hazards is exposure to hard woods in the furniture industry. Acheson et
al.4 reported
higher rates of nasal cavity and sinus adenocarcinoma in the High Wycombe area than elsewhere and proposed that this was caused by exposure to wood dust. Workers exposed to hard wood have a
70 times increased incidence
of sinonasal adenocarcinoma, particularly in the ethmoid sinuses.
The
UK
Government
recognize
this
as
an
occupational risk and it is a prescribed disease under the
1959 National Insurance Regulations: Reference D6
and it is the doctor's duty to inform patients of their rights. The type of wood is a significant factor, with African
mahogany
being
the
most
dangerous.
It is
thought that biologically active compounds in wood dust impair mucociliary clearance and predispose to carcino
tumours from these sites to the orbit. The roof of the of the nasal cavity has many perforations through which the olfactory nerves pass. Thus, tumours developing at these sites tend to spread intracranially. Ohngren7 described a line running from the medial canthus of the orbit to the angle of the mandible. This line separated tumours into two groups, those that developed above it from those that developed below it. He suggested that superiorly based cancers tended to be more aggressive and poorly differentiated, whereas tumours arising from below the line were more amenable to treatment and, as a consequence had a better prognosis. This may well be the case, but it should be remembered that this classification was developed before the concept of craniofacial resection had been considered, let alone described. There have also been huge advances in radiation oncology that make this concept largely of historical interest.
genesis.5 It is this wood that is often burned by Bantu tribesmen who have the highest incidence of upper jaw cancer in the world. Interestingly, sinonasal adenocarci noma
that
develops
in
wood-workers
has
a
better
prognosis than other nasal adenocarcinomas.5 While hardwood exposure increases the risk of developing adenocarcinoma, soft wood exposure increases the risk of developing squamous cell carcinoma.
[**J
Other occupational hazards include exposure to nickel. This increases the risk of developing sinonasal squamous cell carcinoma
250 times. The interval between exposure to
nickel and the development of the tumour can be very prolonged. Pedersen et anything from
al.6 reported a latent interval of
18 to 36 years. Smoking is also thought to
play a role in the development of these tumours, perhaps in a synergistic fashion with wood dust.5 Other chemicals
Lymphatic drainage The lymphatic drainage of the nose and paranasal sinuses is relatively scant. Two lymphatic pathways have been described,
the
anterior
and
posterior
pathways.
The
lymphatics of the anteroinferior part of the nasal cavity and skin of the nasal vestibule drain via the anterior pathway to the facial, parotid and submandibular lymph nodes - the first eschelon nodes. These nodes then drain into the upper deep cervical chain. The remainder of the nose and the paranasal sinuses drain through the posterior pathway which runs anterior to the Eustachian tube to first eschelon nodes - the retropharyngeal lymph nodes, from where they drain to the upper deep cervical chain.
linked to sinonasal malignancy include chromium, poly cyclic hydrocarbons, aflatoxin (found in certain foods and dust), mustard gas and thorotrast (thorium dioxide used in paints for watch dials). Radiation, viral and genetic causes have also been proposed. There is no evidence that chronic sinusitis predisposes to cancer. The incidence of chronic sinusitis in patients with sinonasal malignancies is the same as that in the general population.2
[**J
SURGICAL ANATOMY
PATIERNS OF TUMOUR SPREAD The advanced stage of tumours at the time of presenta tion can make their precise origin extremely difficult to determine. Nevertheless, maxillary sinus tumours are the most common
(55 percent) followed by the nasal cavity (35 percent), ethmoid sinuses (9 percent) and rarely frontal and sphenoid sinuses (1 percent). Local invasion
The anatomy of the nose and paranasal sinuses is described in detail in Chapter and paranasal sinuses.
104, Anatomy of the nose
In general, sinonasal carcinomas tend to fill the sinus cavity
before
eroding
its
bony
walls.
Periosteum,
Chapter 186 Nasal cavity and paranasal sinus malignancy
perichondrium and dura seem to act as a temporary barrier and resist tumour expansion to some extent, a feature possibly explained by the fibroelastic connective tissue component of these tissues. s By contrast, the bone of the antronasal wall, canine fossa and orbital floor is very thin and easily destroyed by tumour. Only 25 percent of maxillary sinus carcinomas are contained within the antrum at the time of presentation. 9 Patterns of local spread are summarized in Table 186.1. [**/*] Maxillary sinus tumours spread medially from the sinus into the lateral wall of the nasal cavity; laterally into the cheek; superiorly through the inferior orbital fissure into the orbit; inferiorly into the palate and, posteriorly into the infratemporal and pterygopalatine fossas (Figure 186.1). Tumours that arise in the ethmoid sinus spread medially into the nasal cavity, laterally into the orbit, superiorly into the anterior cranial fossa and inferiorly into the maxillary sinus (Figure 186.2). Frontal sinus tumours extend through the posterior wall into the anterior cranial fossa and frontal lobes, as
Figure 186.1
well as anteriorly into the skin of the forehead and inferiorly into the nasal cavity. Tumours arising in the sphenoid sinus tend to spread laterally into the cavernous sinus and anteriorly into the ethmoids and nasal cavity (Figure 186.3).
Regional spread Lymphatic spread to regional nodes becomes apparent in 25-35 percent of patients at some time during the course of their disease, though only 10 percent have nodal disease at the time of presentation. Those with involved nodes almost always have locally advanced disease. The submandibular and jugulodigastric nodes are the most commonly involved. Bilateral lymph node involvement is
An advanced carcinoma of the maxillary antrum.
The tumour has broken through the lateral wall and presents as
Figure 186.2
a swelling in the cheek.
orbit and produced proptosis.
Frontal sinus
Skin
This ethmoid carcinoma has spread into the
Anterior cranial fossa,
Ethmoid sinus,
frontal lobes Ethmoid sinus
Skin
Sphenoid, nasopharynx, clivus, pituitary gland
Maxillary sinus
I 2419
Cheek, skin
Pterygopalatine fossa,
nasal cavity Nasal cavities,
Orbit
Anterior cranial
cribriform
fossa, frontal
plate
lobes
Nasal cavity
Nasa I cavity
Cheek, skin
Orbit
Palate
Middle cranial
Pituitary gland,
Nasopharynx
infratemporal fossa, temporal bone, middle cranial fossa Sphenoid sinus
Ethmoid sinuses
Clivus, pituitary gland, posterior cranial
fossa,
fossa
cavernous
hypothalamus
sinus Nasa I cavities
Skin
Sphenoid sinus, nasopharynx
Maxillary sinuses
Anterior cranial fossa, fronta I lobes
Palate
2420
I PART 17 HEAD AND NECK TUMOURS
with 50 percent developing on the turbinates. Two-thirds of septal SCC are found anteriorly in the region of the mucocutaneous junction. Transformation of Schneiderian papillomas into SCC is a recognized risk. Batsakisl3 reported a 14.6 percent incidence of SCC in a series of 322 patients with Schneiderian papillomas. Approximately 85 percent of SCC are well differentiated and keratinizing tumours. Papillary and exophytic histological patterns are also recognized.· It is said that differentiation has little bearing on the ultimate prognosis, but this probably reflects the poor overall outcome for these patients and the relative rarity of poorly differentiated forms. Macro scopically, some sinonasal squamous cell carcinomas have Figure'86.3
MR of sphenoid tumour that has spread into the
cavernous sinus and presented with diplopia caused by a Vlth
a polypoid appearance, while others are more obviously fungating, friable and keratinizing. [**]
nerve palsy.
Adenocarcinoma likely in patients with tumours that have developed near the midline. [**]
Distant metastases Distant metastases at the time of presentation are very unusuaL They develop in 18 percent of patients with adenocarcinomas, in contrast to just 10 percent of those with squamous cell carcinomas.1O When found, they are usually associated with local recurrence.II The most common sites for metastases are bone, brain, liver, lung and skin. The presence of distant metastases is obviously a grave sign and one that signifies a very poor prognosis. The occasional patient with metastatic adenoid cystic
Adenocarcinoma accounts for 9 percent of sinonasal malignancies. Like SCC, it too has a male predilection and tends to affect those in the sixth and seventh decades of life. Adenocarcinomas are generally found in the upper nasal cavity and ethmoid sinuses. They have a slow growth rate and rarely metastasize. Several histological subtypes of sinonasal adenocarcinoma are recognized, namely papillary, sessile, mucoid, neuroendocrine, in testinal and undifferentiated. Papillary adenocarcinomas tend to be locally malignant only and are the least aggressive form. The intestinal variety is most often associated with woodwork-induced tumours. Sessile and mucoid adenocarcinomas have the worst prognosis.s [**]
carcinoma in the lungs can survive for some time if the primary site remains controlled. [**]
STAGING Staging systems have only been devised for carcinomas of the maxillary sinus, ethmoid sinus and the nasal cavity. These systems are not applicable to mesodermal tumours and have no relevance to olfactory neuroblastoma for which there are separate schemes. The TNM classification
Adenoid cystic carcinoma A little less than 5 percent of sinonasal malignancies are adenoid cystic carcinomas (ACC). As elsewhere, ACC tend to grow slowly but inexorably with early perineural and vascular spread. All variants of the tumour are seen. The maxillary sinus is the most commonly affected site and patients usually present with a long history of facial pain that has defied diagnosis for many months if not years. [**]
system for the maxillary sinus (Figure 186.4), ethmoid sinus (Figure 186.5) and nasal cavity is shown in Table
186.2. The staging matrix is shown in Table 186.3.
SURGICAL PATHOLOGY Squamous cell carcinoma
Olfactor y neuroblastoma (aesthesioneuroblastoma) Olfactory neuroblastoma (OAN) arises from basal cells within the olfactory neuroepithelium. OAN represents less than 5 percent of all sinonasal malignancies.14 The incidence of this tumour has a bimodal distribution with peaks at 20 and 50 years of age, respectively. Unlike most
Squamous cell carcinoma (SCC) is the most common
sinonasal malignancies, it is more common in women
sinonasal malignancy. The highest incidence is in the
than men. OAN is a neuroendocrine tumour capable of
seventh decade of life and there is a male preponderance.
causing parAneoplastic syndromes by secreting peptides.
Most SCC arise from the lateral wall of the nasal cavity
Patients
with
OAN
causing
/
Cushing's
syndrome,
Chapter 186 Nasal cavity and paranasal sinus malignancy. 2421
(a)
(b)
(e)
(d)
Figure 186.4 TNM diagrams of maxillary sinus carcinoma (a) T1; (b) T2; (c.d)T3 (continued over).
inappropriate antidiuretic hormone secretion or hypertension produced by vasoactive peptides have been reported in the literature. Hyams et al. 1S developed a four-point histological grading system for OAN based on such features as the degree of differentiation, the tumour architecture, mitotic index, nuclear polymorphism, fibrillary nature of the matrix and tumour necrosis. This tumour can either be extremely aggressive (grade 4) or relatively indolent (grade 1). Survival for more than 20 years is not unusual, while· others are less fortunate succumbing to highly aggressive disease with widespread metastases within a
/
•
/
b"-
\
1
few months. 14 Up to 25 percent of OAN invade the dura and anterior cranial fossa. In 5 percent of patients, metastases to cervical nodes are evident at the time of presentation and distant metastases are already present in 6.6 percent of patients. 14. OAN can often be predicted from imaging characteristics, based on its location focussed on the cribriform plate (Figure 186.6). Disease-specific staging systems have been devised for .OAN. The most useful and commonly used systems are those attributed to Kadish et al. 16, 17 and Dulgerov and Calcaterra 18 (Tables 186.4 and 186.5).
!
2422 I PART 17
HEAD AND N�CK TUMOURS
Figure 186.4 TNM diagrams of maxillary sinus carcinoma (continued) (e.f,g) T4.
Sinonasal undifferentiated carcinoma
and tends to affect the elderly. The nasal cavity and the septum are usually the sites of origin. Appearances vary
Sinonasal undifferentiated carcinoma (SNUC) was de scribed relatively recently by Frierson et
al.19 It is otherwise
known as anaplastic carcinoma and can be hard to distinguish from high-grade OAN. It is a highly aggressive and
invasive
twnour
but,
paradoxically,
commonly
produces few symptoms despite its extensive nature.
metastasizes less frequently to regional cervical lymph nodes than melanoma that develops elsewhere, but more often to the lungs and brain.21
[**]
[**]
Haemangiopericytomas
Melanoma Melanoma accounts for
from a polypoid mass to an area of ulceration. While some are pigmented, others are not. Sinonasal melanoma
3.6
These are rare neoplasms that develop from pericytes percent of all sinonasal
within the outer capillary wall. They account for less than
malignancies.2o It is more common in women than men
5 percent of all sarcomas. Within the head and neck, 20
/ 1/
Chapter
186 Nasal cavity and paranasal sinus malignancy I
2423
II II
(el Figure
186.5
TNM diagrams of ethmoid sinus carcinoma:
(a) T1; (b) T2; (c) T3; (d) T4 (continued over).
percent of all haemangiopericytomas develop in the nasal
polypoid lesions. Haemangiopericytomas rarely metasta
therapy, coincidental trauma, hypertension and preg
relatively
cavity or sinuses.22 They have been associated with steroid
nancy. Macroscopically, they appear as red-grey, firm,
_• r.-Z---. _
sjze. Complete surgical excision is necessary, as they are radioresistant.
recurrence rate.
There
is
a
10--60
percent
[**J
__
I
...,-_�._ ..J-____ _
_. _._ . ___
2424 I PART 17 HEAD AND NECK TUMOURS
PRESENTATION
Figure 186.5 (continued) TNM diagrams of ethmoid sinus carcinoma: (e) T4,
Table 186.2
TNM classification.
Tumours of the nasal cavity cause progressive unilateral stuffiness and blockage, sinus outflow obstruction and have a tendency to bleed or spot nasal secretions. Distortion of the nose itself develops later. As mentioned earlier, the presentation of most sinus malignancies is considerably delayed. The sinus of origin itself is usually filled with tumour and symptoms are caused by erosion of its walls and extension beyond. Maxillary sinus carcinomas cause facial pain with or without progressive anaesthesia of the cheek by infiltration of the infraorbital nerve. Erosion of the medial wall is associated with epistaxis and obstruction of the nasolacrimal duct causing epiphora Destruction of the posterior wall and spread into the pterygopalatine and infratemporal fossa results in trismus, maxillary and mandibular trigeminal nerve deficits. Destruction of bone inferiorly leads to loosening of the premolar and molar dentition, ill-fitting dentures and ultimately ulceration of the buccal sulcus or palate. Spread of tumour superiorly into the orbit gives rise to proptosis and diplopia. A visible swelling or distortion of the cheek develops when tumour breaks through the anterolateral wall. Ethmoid sinus carcinomas usually present with unilateral nasal obstruction and epistaxes. Epiphora, orbital
back to text
Maxillary Sinus TX Prima ry tum or cann ot be assessed TO No evidence of primary tumor Tis carcinoma in situ T1 Tumor limited to the maxillary sinus mucosa with no erosion or destruction of bone T2 Tumor causing bone erosion or destruction induding extension into the hard palate and/or middle nasal meatus, e:x:cept extension to posterior wall of maxillary sinus and pterygoid plates T3 Tumor invades any of the fol lowing: bone of the posterior wal l of maxillary sinus, subcutaneous t issues, floor or medial wa ll of orbit, pterygoid fossa, ethmoid sinuses. T4a Tumor invades anterior orbital contents, skin of cheek, pterygoid plates, infratemporal fossa, cribriform plate, sphenoid or f rontal sinuses T4b Tumor invades any of the fol lowing: orbital apex, dura, brain, middle cranial fossa, crania l nerves other than maxillary division of trigeminal nerve V2, nasopharynx, or clivus. Nasal Co vity and Eth moid Sinus TX Primary tumor cannot be assessed TO No evidence of primary tumor Tis Carcinoma in situ TI Tumor restricted to anyone subsite. T2 Tumor invading two subsites in a single region or extending to involve an adjacent region within the nasoethmoidal complex, with or without bony invasion. T3 Tumor extends to invade the medial wall orfloor of the orbit, maxillary sinus, palate, or cribriform plate. T4a Tumor invades any of the fo llowing: anterior orbital contents, skin of nose or cheek, minimal extension to anterior cranial fossa, pterygoid plates, sphenoid or frontal sinuses. T4b Tumor invades any of the fol lowing: orbital apex, dura, brain, middle cranial fossa, cranial nerves other than V2, nasopharynx, ordivus ·Within the nose, four subsites are recognized. namely septum. floor. lateral wall and vestibule. Reproduced from Ref. 12. with permission.
/
I
*
AS"
Chapter 186 Nasal cavity and paranasal sinus malignancy I 2425
Tis Tl T2 Tl/2 T3 Tl/2/3 T4a T4b Any T Any T
0
I II III IVa IVb IVc
NO NO NO Nl NO/l N2 NO/l/2 Any N N3 Any N
MO MO MO MO MO MO MO MO MO Ml
swelling, proptosis and diplopia are not uncommon (Figure 186.7). Orbital symptoms and signs also prevail with frontal sinus tumours. Tumours that develop in the sphenoid sinus usually invade the cavernous sinus and infiltrate the contained cranial nerves to produce diplopia and facial pain.
CLINICAL EVALUATION Endoscopy A thorough endoscopic examination of the nasal cavity is essential in anyone suspected of having a malignancy. More thorough routine use of both flexible and rigid scopes might diagnose tumours at an earlier phase of their development. While the appearance of some tumours is quite obviously neoplastic, such as a proliferative ulcerative growth, others are less conspicuous. It is not unusual for tumours to excite a polypoid reaction in the surrounding mucosa. Some of this will be infiltrated but a casual biopsy in the outpatient or office setting may well be nondiagnostic (Figure 186.8).
Imaging A combination of both computed tomography (CT) and magnetic resonance (MR) imaging is required for all patients with sinonasal malignancies. CT alone is not sufficient for accurate evaluation and staging purposes. Indeed, many scans are adversely affected by amalgam artifact. Bone-windowed CT allows reconstruction in all planes and gives accurate detail of bone erosion and potential involvement of the skull base. Both axial and coronal views are necessary. Unparalleled information concerning the soft tissue component of tumours is derived from MR imaging. Gadolinum-enhanced MR imaging provides tumour detail that might include flow voids, suggesting that the tumour is extremely vascular. It will also detect dural or
Figure 186.6 (a) MR and (b) CT scan of a patient with a Kadish 3 olfactory neuroblastoma. The tumour is centred on the cribriform plate - characteristic of DAN. Table 186.4 Kadish staging system 16 (with Morita's modification).17
A B C D
Limited to nasal cavity Involving nasal cavity and sinuses Extension beyond nasal and paranasal sinuses cavities Tumour with metastasis to cervical nodes or distant sites
I
\ 1
L \
' ,
'
<~e.'
.
2426 Table
I
PART
186.5
17 HEAD AND NECK TUMOURS
Dulguerov staging system.
Stage T,
Tumour involving the nasal cavity or paranasal sinuses (excluding the sphenoid sinus) sparing the most superior ethmoidal cells
T2
Tumour involving the nasal cavity or paranasal sinuses (including the sphenoid sinus) with extension to or erosion of the cribriform
T3
Tumour extending into the orbit or protruding into the anterior cranial fossa without dural invasion
T4
Tumour involving the brain
plate
No
No cervical lymph node metastases
N,
Any form of cervical lymph node metastases
Mo
No metastases
M,
Any dista nt metastases.
Back to Text
Reproduced from Ref. 1, with permission.
�igure
186.7
Spread of tumour into the cavernous sinus often
results in a lateral rectus palsy.
Figure
I
186.9
MR and CT scans are complementary and help
distinguish between tumour, retained secretions and dural infiltration. This patient had an extensive tumour that had spread into the cavernous sinus, infiltrated the dura of the temporal lobe (small arrows) and the infratemporal fossa (large arrow). The MR, shown here, shows the true extent of the disease. The spread was not apparent on the CT scan, which had shown a relatively small tumour affecting the sphenoid.
Biopsy Tissue diagnosis from biopsy is a mandatory part of
Figure
tumour evaluation. A number of these tumours can bleed 186.8
Endoscopic view of an extensive SNUC.
torrentially, particularly the rarer entities, for example, olfactory neuroblastoma, melanoma and meningioma, not to mention angiofibroma. No matter how tempting it
cerebral infiltration and give an accurate assessment of
might seem to take a tissue sample in the office setting, be
orbital invasion. T2-weighted sequences make the dis
sure that facilities are available to arrest any haemorrhage
tinction between retained secretions, tumour or mucosal
that might ensue. It would seem prudent to take a biopsy
thickening
(Figure 186.9).
under general anaesthetic. In this way the chance of
Ateriography is rarely required but might be under
obtaining a nondiagnostic sample is less likely and gives
taken if preoperative embolization were considered to
the surgeon the opportunity to obtain a sample from
facilitate the removal of a vascular tumour, for example,
within the sinus itself. A Caldwell-Luc approach should
haemangiopericytoma. There is rarely a role for positron
be avoided as this will almost certainly seed the cheek flap
emission tomography (PET), the exception being to find
with tumour' and complicate a subsequent resection
the primary site when the sinus tumour is a metastasis.
(Figure 186.10).
/
Chapter 186 Nasal cavity and paranasal sinus malignancy
Figure 186.10
This patient lost 2 L of blood after a biopsy
was taken.
TREATMENT General principles It has to be accepted that most patients have very
advanced disease at th~ time of presentation and there will inevitably be some who are incurable from the outset. Surgery for these patients runs the risk ofraising hopes unrealistically and of increasing morbidity. At the jrtitial consultation, it is essential that all necessary investigations are arranged so that the tumour can be staged accurately. Most patients will be elderly and their general medical condition might preclude any major intervention. There is usually a choice between treatment for cure and palliation. In considering palliative treatment it is necessary to record the patient's symptoms and appreciate how they lmpact on their life, the extent of their disease and whether distant metastases are present. Most important, the surgeon must obtain fully informed consent from the patient and the relatives. While this might sound a little negative, it should be remembered that some tumours have a long natural history and, while treatment may only be palliative, it is often possible to achieve significant periods of good quality survival. With this in mind, some surgeons advocate local debulking of tumour with adjunctive radiotherapy as palliative treatment. This is probably best performed by experienced surgeons only. For those patients who are potentially curable, most centres recommend a combination of radiotherapy and surgery. There is still dispute as to whether the irradiation should be used before or after surgery. Preoperative radiotherapy has traditionally been advocated and is more appropriate in radiobiological terms. The criticism that it interferes with healing should Ilot be true with modern radiotherapeutic regimens. Postoperative radiotherapy may be more valuable in slow-growing tumours, such as adenoid cystic carcinoma and chondrosarcoma.
I
\ l
I 2427
The role of chemotherapy is largely undetermined. For the majority of tumours, squamous cell carcinoma and adenocarcinoma, it probably has little to offer. Undoubtedly, it has a role in olfactory neuroblastoma, rhabdomyosarcoma, lymphoma and possibly sinonasal undifferentiated carcinoma. Topical application of 5fluorouracil has been advocated by Knegt et al. 23 for adenocarcinoma of the ethmoid sinus. Surgical debulking through an extended anterior maxillary antrostomy is followed by a combination of repeated topical chemotherapy and necrotomy. Knegt et al. reported that temporary periorbital swelling develops in 40 percent, cerebrospinal fluid (CSF) leakage in 8 percent and meningitis in 1.6 percent of his cohort of patients. Adjusted disease-free survival at two, five and ten years using this technique was 96, 87 and 74 percent, respectively. Other than the stage of disease, there are relatively few contraindications to treatment. The patient's wishes, as some understandably fear facial mutilation, and poor health are probably the main factors. Local invasion of the anterior cranial fossa and skull base are not necessarily contraindications as modern skull base surgical techniques can cope with some of these. Distant metastases always indicate a bad prognosis and by definition these patients are incurable. Involvement- of the facial skin is not a contraindication to treatment and in practice many such patients do well. The involved area is best excised and repaired with either a rotation· flap or free flap. Most now advocate radical surgery for even early disease with the objective of obtaining an en-bloc clearance of the tumour. Careful imaging will have demonstrated the tumour extent and facilitates transnasal debulking before primary radiotherapy with curative doses of 60-65 Gy delivered over six weeks. Approxi- ' mately six weeks after the completion of radiotherapy, the patient should have a planned craniofacial resection to encompass completely any residual tumour. High quality prosthetic rehabilitation is essential and requires the help of a maxillofacial laboratory; With a palatal resection, the defect must be sealed with either an obturator fitted with teeth to restore both speech and normal deglutition or by a free composite flap using microvascular techniques. Orbital resections leave an obvious cosmetic deformity and the Branemark system of titanium implants has revolutionized the fitting of facial prostheses. Radiotherapy is not a contraindication to their use.
Surgery for maxillary tumours A variety of operations has been described. The choice is determined by the extent of the tumour and amount of bone that needs to be removed.
I
2428 I PART 17 HEAD AND NECK TUMOURS
PARTIAL MAXILLECTOMYbetter
refer to Cumming's
This entails partial removal of the upper jaw skeleton. Two variants are in common use. 1. Medial maxillectomy involves the clearance of the
lateral wall of the nose including the ethmoid SInuses. 2. Palatal resection along with the adjacent alveolus is used for tumours of the oral cavity that involve the hard palate. In its simplest form, this is called a fenestration. This is technically incorrect as palatal fenestration was originally described for placing radium implants into the cavity of the antrum containing tumour. Most fenestrations nowadays are closed with free flaps, but for some patients there is still some advantage with the older, less sophisticated procedure as it allows good visualization of the cavity after treatment with potential early detection of any recurrence.
TOTAL MAXILLECTOMY
mobilization of the cartilaginous nose using rhinoplasty techniques to elevate the facial skin off the middle third of the face. It gives excellent exposure to the nasal cavities, postnasal space, antra and pterygopalatine fossae. In selected cases, good exposure of the ethmoids is obtained, but for ethmoid malignancy the lateral rhinotomy incision gives better exposure. When combined with either a Le Fort 1 osteotomy or maxillotomy, it gives a very wide approach to the clivus and skull base and is of immense value for those extensive tumours which involve this region (Figure 186.13).27,28 The basic technique of each operation is well described in the standard textbooks of operative surgery, but many points require special emphasis to ensure good tumour clearance and rapid rehabilitation. The selection of the operation depends on the preoperative assessment, but generally if the palate or zygoma is involved a total maxillectomy is indicated. In most other tumours a lateral rhinotomy or midfacial degloving approach will
This entails the total removal of the upper jaw, preferably as a bony box containing the tumour.
EXTENDED MAXILLECTOMY An extended maxillectomy is required when the tumour
extends beyond the upper jaw. If this involves the skull base, the term craniofacial resection is used.
Surgical approaches To facilitate the various bone resections it is necessary to use an appropriate soft tissue approach. Three different soft tissue approaches are used.
Figure 186.11
Extended lateral rhinotomy incision to include
1. Lateral rhinotomy. This approach is usually
the lip. In most cases, splitting the lip is not necessary, but
attributed to Moure,24 but in fact was originally described by Michaux25 some 50 years earlier in 1854 and gives excellent exposure of both the nasal cavities and medial maxilla with a cosmetically acceptable incision in the lateral nasal crease (Figure 186.11). 2. Weber-Fergusson. This approach is incorrectly attributed to both Fergusson and Weber, although it was originally described by Gensoul in 1833 (Figure 186.12). It is rarely used unless there is need for an orbital exenteration. 3. Midfacial degloving. Undoubtedly this is a more cosmetic alternative to both the Moure's lateral rhinotomy and Weber-Fergusson approaches. Originally proposed by Rouge, it has recently been rediscovered by Casson et al. 26 This technique combines a bilateral sublabial approach to the anterior wall of the maxilla with a midline
additional lateral exposure can be gained in this way.
Figure 186.12
Weber-Fergusson incision.
J
Chapter 186 Nasal cavity and paranasal sinus malignancy
I 2429
OSTEOTOM IES
Figure 186.13
Mid-face degloving exposure.
usually give good access for medial maxillectomy and requires little rehabilitation. Extensive tumours require some form of craniofacial approach.
ANAESTH ESIA
Skilled anaesthesia is essential. Topical anaesthesia of the nasal mucosa with Moffet's solution and hypotensive general anaesthesia are of considerable benefit to the surgeon. Some feel that an oral endotracheal tube gets in the way when fabricating the prosthesis and so prefer a nasal tube placed in the contralateral nostril. Others prefer a preliminary tracheostomy for the same reason. If the cranial cavity is opened, brain shrinkage is helpful and best achieved by hyperventilation to lower the end-tidal pC0 2 to about 24 mmHg which induces decreased cerebral blood flow and brain shrinkage. If the anterior fossa is opened, the patient should be loaded with phenytoin at the time of induction and maintained on this prophylactically for three months.
Maxi Ilectomy SOFT TISSUE APPROACH
The maxilla is best exposed by the Weber-Fergusson incision. The transverse limb should be placed close to the lid margin to prevent postoperative oedema of the lower lid. In the medial canthal region where the potential for skin loss as a result of radiotherapy is greatest, it is helpful to curve the incision forward over the nasal bones for additional support postoperatively. An incision along the crest of the philtrum and stepped on the lip is more acceptable than a midline incision. The mucosal incision along the midline of the hard palate turns laterally at the junction with the soft palate passing behind the maxillary tuberosity and then round the alveolus anteriorly. The facial skin flap is raised and all the soft tissue incisions are gently dissected free of the bone to allow the subsequent osteotomies (Figure 186.14).
The maxilla is freed from the skull by osteotomies through the frontal process of the maxilla. The body of the zygoma, the midline of the palate and the pterygoid plates need to be freed posteriorly. The palatal osteotomy is placed in the floor of the nasal cavity and may be made either with an oscillating or gigli saw. The pterygoid plates are best separated from the maxilla with a curved osteotome and subsequently dissected free from the muscles. The final two osteotomies are made with diamond paste burr medially through the ethmoid cells and frontal process of the maxilla after dividing the lacrimal sac; laterally, the osteotomy is made through the body of the zygoma, except for those laterally placed tumours where the zygoma needs to be included in the resection, then the osteotomy is made in the lateral orbital wall below Whitnall's tubercle and through the zygomatic arch (Figure 186.15). The remaining bony attachments are the posterior ethmoid cells and posterior antral roof, and these break readily on mobilizing the maxilla. The remaining soft tissue attachments are freed with Mayo scissors and the maxilla removed. Bleeding from the internal maxillary artery is controlled initially by packing and then by application of a Ligaclip.
COMPLETION OF THE RESECTION
Following removal of the maxilla, further tissue must be resected to ensure complete tumour clearance and promote drainage from the remaining sinuses. The ethmoid cells should be exenterated completely and both the sphenoid and frontal sinuses opened widely. If there is obvious involvement of the orbital periosteum, orbital exenteration .is generally indicated. The support of the globe is complex and virtually all the medial and inferior orbital walls can be removed without the eye sinking. . However, the lateral removal of WhitnaIl's tubercle results in lack of support for the eye which is best corrected by transposing the temporalis muscle medially. Orbital exenteration is achieved by an extraperiosteal dissection and transection of the muscle cone at the apex with Mayo scissors. Bleeding from the ophthalmic artery can be stopped by applying local pressure or bipolar coagulation. Following orbital exenteration, the eyelids are preserved but the lid margins and tarsal plates are excised to give a smooth skin-lined cavity to which an onlay prosthesis can be fitted. REHABI LlTATION
Careful rehabilitation ensures a good cosmetic and functional outcome. Healing of the bony cavity is fairly rapid, but it is advantageous to apply a split-skin graft to the back of the facial skin flap. After resuturing the facial incision, the cavity should be immediately fitted with an
2430 • PART 17 HEAD AND NECK TUMOURS
(~ , " "
J,'
\
'.
(a) Figure 186.14
Classic maxillectomy: (a) Weber-Fergusson incision; (b) palatal incision.
(a) Figure 186.15
(b)
(b) Classical maxillectomy: (a) Following the elevation of the facial flap, the maxilla is freed with osteomies through the
zygoma, palate and frontal process of the maxilla; (b) freeing the pterygoid plates.
obturator to cover the palate and to restore the normal facial contours. The main problem with this type of prosthesis is its weight. To counter this, a hole is drilled in the zygomatic arch through which a wire can be passed and secured to cleats on the prosthesis.
The primary prosthesis is changed after 14 days and appropriate adjustments made. This process is repeated several times over the subsequent weeks until such time as it is judged that the cavity has healed and a final prosthesis made.
Chapter 186 Nasal cavity and paranasal sinus malignancy
Medial maxillectomy using the lateral rhinotomy approach This approach gives good access to the nasal cavities, the ethmoids, nasopharynx, sphenoid and the pterygopalatine fossa (Figure 186.16). For more extensive tumours, an enbloc resection can be achieved by combining this operation with an anterior craniofacial approach. The incision is cosmetically very acceptable as it passes along the lateral border of the nose to the upper edge of the alar margin. For more extensive resections, the incision can be continued into the nasal cavity without compromising the final cosmetic outcome. The upper end should start just above the level of the medial canthus. The upper lateral cartilage is freed from the nasal bones at the pyriform opening and the soft tissue flap is elevated from the frontal wall of the maxilla and nasal bones. The orbital periosteum is elevated as for an external ethmoidectomy and the lower part of the lacrimal sac is exposed by nibbling away the anterior lacrimal crest. The orbital contents can then be completely freed medially by dividing the sac low down and also by freeing the insertion of the inferior oblique tendon and trochlea by sharp dissection from the orbital rim. Access to the anterior nasal cavities can be increased by removing the nasal bones with little cosmetic defect. However, it is more usual' to include the lateral nasal wall and ethmoid complex in the resection. The bone is freed by osteotomies cut with a fissure burr. The first is through the anterior wall of the maxilla just medial to the inferior orbital foramen curving medially into the nasal cavity. Further osteotomies are made along the lower border of the lateral nasal wall in the inferior meatus, and across the floor of the orbit towards the foramen of the anterior ethmoidal artery. Finally, an upper osteotomy is continued forward through the frontal process of the maxilla and nasal bone then down to the pyriform aperture. This frees the whole block of the lateral·· nasal wall and ethmoid complex, apart from their posterior attachments just in front of the optic and
Figure 186.16 Medial maxillectomy approach used to remove a tumour of the ethmoid.
\
I 2431
sphenopalatine foramina. In this region the bone is very thin and easily fractured by elevating the block medially. Virtually all the mucosa of the nose can be included as a cuff with the main specimen, the posterior and antral mucosal attachments being freed by scissors. The view obtained following the removal of this main block of tissue is excellent and the resection is extended into the sphenoid and frontal sinuses or alternatively into the pterygopalatine fossa. At the completion of the procedure, the operative cavity is packed with a Whitehead's varnish pack for seven to ten days.
OTHER SURGICAL PROCEDURES Anterior craniofacial resections Involvement of the cribriform plate region has long been known to be one of the major reasons for failure to control ethmoid neoplasms. Some surgeons even considered this as a contraindication to surgery. Smith et al. 29 described a surgical approach to this region which was subsequently developed by Ketcham et al}O Clifford31 and Cheesman et al. 32 (Figure 186.17). With hindsight, it has become clear that some of these procedures are not appropriate in all patients. In particular, they tend to give poor clearance of tumours in the region of the frontonasal duct and lacrimal sac. Similarly, more extensive involvement of the anterior fossa is better managed by more· conventional combined procedures with the neurosurgeons. The appropriate selection of approach has been best summarized by Cheesman and Reddy33 who subclassified the craniofacial procedures into three types. 1. Type l.craniofacial (transorbital) resection. This procedure is essentially an extended medial maxillectomy using a lateral rhinotomy incision. The operation entails a careful exploration of the anterior nasal cavities using the operating microscope and frozen section histological control. The wide exposure allows resection and repair of both the ethmoid roof and orbital periosteum if indicated. A similar approach has been described by Draf and Samii. 34 2. Type 2 craniofacial (window craniotomy) resection. In this procedure a lateral rhinotomy approach is used for anterior access and extended superiorly in a frown line to expose the frontal bone. A small midline 'window' craniotomy is made giving access to the floor of the anterior cranial fossa. The dura is elevated from the roof of the ethmoids and cribriform plate and the area is encompassed with a cranial osteotomy. This osteotomy, in conjunction with those of the lateral rhino to my, allows the en-bloc resection of both ethmoid complexes. Involved dura can be excised and repaired with fascia lata. Involved
2432 I PART 17 HEAD AND NECK TUMOURS
Figure 186.17 CT.
Stages of an anterior craniofacial resection. (a) pre-operative CT acquired face down; (b-e) resection; (f) postoperative
Chapter 186 Nasal cavity and paranasal sinus malignancy
brain can also be excised, but cure is unlikely for disease at this late stage. The window bone flap is replaced and fixed with mini-plates and the soft tissue is closed with remarkably little cosmetic defect. The combined approach not only gives excellent visualization of the ethmoid region, but readily allows extensions of the resection into the sphenoid, the orbit, the pterygopalatine fossae and the skull base centrally. 3. Type 3 craniofacial resection. This operation is performed in conjunction with a neurosurgeon and combines a transfacial approach with a neurosurgical approach, such as a frontolateral craniotomy, to allow the resection of extensive
I 2433
tumours (Figure 186.18). Skull base surgery demands an interdisciplinary approach working in teams. There is a trend nowadays for the otorhinolaryngologist to use endoscopic techniques in order to guide the neurosurgeon from below when making his osteotomies. In some centres, four-handed techniques have been developed which are totally reliant on endoscopic nasal techniques. A team comprises a neurosurgeon and otorhinolaryngologist working together. One provides suction and visualization, while the other is able to use both hands for transnasal instruments. The scope of this technique is quite remarkable and for many a craniotomy and transfacial approach can be avoided. 35
Figure 186.18
(a) Bicoronal skin flap; (b) view from above into
the nasal cavity after the tumour has been removed; (c) view from below after the tumour has been removed and the cranial base defect repaired; (d) frontal bone flap replaced and secured; (e) closure of lateral rhinotomy wound.
2434 I PART 17 HEAD AND NECK TUMOURS
Lateral craniofacial resections
PROGNOSIS
Many antral tumours extend posteriorly to involve the infratemporal fossa. Attempts to clear the infratemporal fossa through an anterior approach have not been very successful mainly due to venous bleeding from the pterygoid plexus. A middle fossa extradural approach to the foramen rotundum allows the roof of the infratemporal fossa to be freed and an en-bloc resection of the medial infratemporal fossa is possible as part of a classical maxillectomy. The combination of this with an anterior fossa resection allows the en-bloc removal of the orbit for extensive tumours involving this region.
The overall prognosis of sinonasal malignancy is directly related to the degree of local control. 1 Absolute local control rates for all malignancies are 50 percent at five years, 31 percent at ten years and 21 percent at 15 years. 36 In the Memorial Sloan Kettering Cancer Centre series of 166 patients undergoing anterior skull base resection, patients who did experience a recurrence were most likely to fail locally (66.7 percent) followed by distant metastasis (46.4 percent), with regional failure less common (16.7 percent).3? Factors associated with prognosis are shown in Table 186.6.
Orbital exenteration Attempts to preserve the orbital contents and reduce mutilation often result in orbital recurrence. Ketcham et al. 30 clearly showed that orbital exenteration for involvement of the orbital periosteum doubled the cure rate from 32 to 62 percent, even in more advanced tumours. However, the orbital periosteum may be involved with tumour while the underlying fat and orbital are not. The use of peroperative frozen section can determine those patients whose eyes can be retained and spare them the misery of an exenteration. Medial defects in the orbital periosteum are repaired with split-skin grafts, but inferior resections must be repaired with fascia to prevent prolapse of the globe.
Table 186.6
Factors affecting prognosis.
Anatomical factors: location 1 Nasal cavity Maxillary sinus
77 62
Ethmoid sinus
48
Above Ohngren's line
Worse prognosis
Pathological factors: histological type 37 OAN
88
Adenocarcinoma SCC
68 51
Undifferentiated carcinoma
44
Mucosal melanoma
18
Tumour stage 1
T1 T2 T3
91
T4
49
Five-year actuarial survival.
64 72
Chapter 186 Nasal cavity and paranasal sinus malignancy.
2435
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,/ A combination of CT and MR scans should be acquired as part of the staging and planning process.
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Pedersen EA, Hogetrait AC, Anderson A. Cancer of the respiratory organs among workers in a nickel refinery in Norway. International Journal of Cancer. 1973; 12: 32-41.
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Ohngren LG. Malignant tumours of the maxillo-ethmoidal
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surgical margins incorporate the initial extent of the
Kraus D, Stern man BM, Levine HL, Wood BG, Tucker HM, Lavertu P. Factors influencing survival in ethmoid sinus
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515-20.
187 Juvenile angiofibroma
MICHAEL GLEESON
Introduction
2437
Surgical resection - techniques and approaches
2441
Pathogenesis
2437
Complications
2442
Presentation
2438
Key points
2443
Assessment
2438
Best clinical practice
2443
Treatment
2439
Deficiencies in current knowledge and areas for future
Preoperative embolization
2440
Preoperative chemotherapy
2441
2443
research
2443
References
The data in this chapter are supported by a PubMed search of publications focussing on the genetics, pathology and management of juvenile angiofibroma.
INTRODUCTION
PATHOGENESIS
Recognized since ancient times by Hippocrates, juvenile
Juvenile angiofibromas present as well-defined, lobulated
angiofibroma is an uncommon, benign and extremely
tumours that are covered by nasopharyngeal mucosa. The
vascular tumour that arises in the tissues within the
tumour consists of proliferating, irregular vascular chan
sphenopalatine foramen. Rarely, it is found at other sites
nels within a fibrous stroma. Tumour blood vessels
in the nasal cavity and paranasal sinuses.!
Juvenile
typically lack smooth muscle and elastic fibres, this feature
angiofibroma accounts for less than 0.5 percent of all
contributing to its reputation for sustained bleeding. The
head and neck tumours. It develops almost exclusively in
stromal compartment is made up of plump cells that can
adolescent males, though there are reports of this tumour
be spindle or stellate in shape and give rise to varying
being found in children, the elderly, young and even
amounts of collagen. It is this that makes some tumours
pregnant women. As it grows, the tumour extends into
very hard or firm, while others may be relatively soft.
the nasopharynx, paranasal sinuses, pterygopalatine and
As this tumour is almost exclusively found in adolescent
infratemporal fossa. Larger tumours can involve the orbit
boys, there has always been much speculation and indirect
and cavernous sinus. Juvenile angiofibromas are locally
evidence that sex-hormone receptors play some part in its
invasive, though a few have been reported to behave in a
development.
more malignant fashion. The vascular nature of juvenile angiofibroma has posed a significant problem for those
have been used to show that androgen receptors are present in at least 75 percent of tumours, these receptors
charged with its management. In recent years, with the
being present in both the vascular and stromal elements. A
advent of endoscopic techniques, the surgical approach to this tumour has changed. This chapter aims to summarize
much smaller proportion of tumours also have some . progesterone receptors. In contast, oestrogen receptors
current knowledge and management.
have not been demonstrated? Other factors also play their
Recent
immunocytochemical
techniques
,
/
L
"t ·
2438
I
PART 17 HEAD AND NECK TUMOURS
part in the development of this tumour. The angiogenic growth factor (vascular endothelial growth factor (VEGF)) has been found localized on both endothelial and stromal cells, perhaps indicating that both cell types play a role in tumour development.3 Vessel density and both the expression and localization of VEGF correlate with the proliferative marker Ki67.4 However, neither the prolif erative index nor VEGF expression seem to bear any relation whatsoever to the stage of the tumour at the time of presentation; in other words, its degree of aggressiveness. Overexpression of insulin-like growth factor II (IGFII) has also been found in a large number of juvenile angio fibromas. The IGFII gene is situated on the short arm of chromosome 11 and at that site is the target of genomic imprinting, expressing the paternal allele only. It is thought that overexpression of IGFII might be associated with a tendency to recurrence and poorer prognosis.5 Juvenile angiofibromas have also been reported to develop 25 times more frequently in patients with familial adenomatous polyposis, a condition that is associated with mutations of the adenomatous polyposis coli (APC) gene. As a result, it has been suggested that germline mutations in the APC gene on chromosome 5q might also be involved in the pathogenesis of sporadic juvenile angiofibromas. This gene regulates the beta-catenin pathway which influences cell to cell adhesion. Mutations of beta-catenin have been found in sporadic and recurrent juvenile angiofibromas.6 Localization of beta-catenin only to the nuclei of stromal cells has been interpreted by some to suggest that the stromal cells have a critical role in the development of these neoplasms.
ASSESSMENT
In the past, the exact nature of these tumours was suggested by the plain lateral skull radiographic appear ance that would show anterior bowing of the posterior wall of the maxillary sinus (Figure 187.1). Nowadays, the diagnosis is based on the CT and MR appearances that are sometimes confirmed by angiography. A trans-nasal biopsy is not necessary and can provoke brisk haemor rhage. The exact extent or stage of the tumour can only be determined by a combination of CT and MR imaging and this is vital when planning the surgical resection (Figures 187.2 and 187.3). Several staging systems have been proposed but that of Fisch is the most robust and practical (Table 187.1).7 It defines clearly which tumours can be resected by endonasal techniques and those that would be better tackled by more open or infratemporal fossa/neurosurgical approaches. The Radkowski staging system appeals to those involved with the management of smaller tumours as there are more subdivisions but, in reality, this adds little to its utility (Table 187.2).8 Diagnostic angiography is undertaken to evaluate the
influences cell to cell adhesion PRESENTATION
Recurrent severe epistaxes accompanied by progressive nasal obstruction are the classical symptoms of juvenile angiofibromas at the time of presentation. These tumours do not grow fast and so many months or even years may pass before it occurs to the patient or their parents that there is anything seriously amiss. In most, there is a delay of at least six or seven months between the onset of symptoms and presentation. By that time, it is usual for the youth to have other signs and symptoms of tumour growth and extension. These may include swelling of the cheek, trismus, hearing loss secondary to Eustachian tube obstruction, anosmia and a nasal intonation or plummy quality to the voice. More extensive tumour growth with invasion of the orbit and cavernous sinus may cause proptosis, diplopia, visual loss, facial pain and headache. Anterior rhinoscopy is likely to confirm the presence of abundant mucopurulent secretions in the nasal cavity that usually obscure the tumour from vision, though a few patients have tumour prolapsing from the anterior nares. The soft palate is often displaced inferiorly by the bulk of the tumour which can be seen clearly as a pink or reddish mass that fills the nasopharynx.
Figure 187.1 angiofibroma.
Typical plain radiographic appearance of an
The posterior wall of the maxillary sinus has been
bowed anteriorly (arrowed).
/
Chapter 187 Juvenile angiofibroma
Figure 187.2
I
2439
(a) Axial and (b) coronal CT images of a type
3a, right-sided, juvenile angiofibroma. There is destruction of the pterygoid plates and extension of tumour through the skull base (arrowed).
source of blood supply and as a prelude to selective embolization (Figure 187.4). [*]
Figure
187.3
MR appearances of a type 3a, right-sided
juvenile angiofibroma. It has invaded the infratemporal fossa. The operative specimen gives a more objective assessment of the tumour size.
TREATMENT
Hippocrates (470-410 Be) is said to have removed what he called a 'hard nasal polyp' through a midline, nose splitting incision and it is suggested that this was a juvenile angiofibroma. The famous surgeon, Liston, at University College London performed the first successful
Table Type
187.1
resection of an angiofibroma on a 21-year-old man from Gibraltar on 6th September 1841.9 The tumour had been present for at least three and a half years and filled the pharynx to the extent that it caused significant airway obstruction. It extended into his cheek and had eroded the alveolar process. The patient had experienced a
Fisch staging system of juvenile angiofibromas. Details
1
Tumour limited to the nasopharyngeal cavity; bone destruction negligible or limited to the sphenopalatine foramen
2
Tumour invading the pterygopalatine fossa or the maxillary, ethmoid or sphenoid sinus with bone destruction
3
Tumour invading the infratemporal fossa or orbital region: (a) without intracranial involvement (b) with intracranial extradural (parasellar) involvement
4
Intracranial intradural tumour: (a) without infiltration of the cavernous sinus, pituitary fossa or optic chiasm (b) with infiltration of the cavernous sinus, pituitary fossa or optic chiasm
!
I
•d
2440
I
PART 17 HEAD AND NECK TUMOURS Radkowski classification of juvenile angiofibromas.
la
Limited to the nose and nasopharyngeal area
Ib
Extension into one or more sinuses
lIa
Minimal extension into pterygopalatine fossa
lib
Occupation of the pterygopalatine fossa without orbital erosion
Ilc
Infratemporal fossa extension without cheek or pterygoid plate involvement
Ilia
Erosion of the skull base (middle cranial fossa or pterygoids)
Illb
Erosion of the skull base with intracranial extension with or without cavernous sinus involvement
In the years that followed it became apparent that a large number of these tumours could be removed relatively safely by open approaches but not without significant morbidity. A number of patients also died as a direct result of blood loss. Attempts were made to reduce the blood supply of the tumour preoperatively and to shrink them by chemical means. Very extensive tumours were treated by radiotherapy as were recurrences. Strategies for the surgical management of these tumours have evolved over the intervening years and never more quickly than in the last decade with the advent of endonasal endoscopic techniques.lO
PREOPERATIVE EMBOLIZATION
Figure 187.4
External carotid angiogram of a juvenile
angiofibroma demonstrating its blood supply from the internal maxillary artery which is much larger than normal.
number of severe epistaxes, losing two to three pints of blood on each occasion. Liston removed the tumour by performing a total maxillectomy through a Weber Fergusson incision without anaesthesia! The patient bore the procedure 'with remarkable fortitude'. He was discharged 24 days later able to eat a normal diet! Histopathological examination of the operative specimen showed the tumour had a 'fibro-vascular nature:
The role of preoperative embolization in the surgical management of this tumour is controversial. W hile some surgeons regard it as essential, others have less strict views or frankly disagree. There is little doubt that for small tumours the blood supply is predictable, usually the terminal branches of the internal maxillary artery, and these can be controlled easily at the time of surgery. Embolization in such cases would seem to be unnecessary. More extensive tumours acquire a blood supply from other vessels, branches of both the external and internal carotid circulations. Surgical resection of these tumours can be formidable and preoperative selective emboliza tion, some days before surgery, is prudent at the very least. It is the medium-sized tumours where the benefits of preoperative embolization are doubtful. Intraoperative blood loss after embolization is certainly less.ll The maxillary or external carotid artery can be controlled or ligated relatively easily at an early stage in any open procedure, regardless of whether embolization has been undertaken or not. [**J It might be thought that any measure undertaken to improve operative conditions might influence the ade quacy of resection and reduce the rate of recurrence. On the contrary, recurrence rates seem to be increased by preoperative embolization.12 Perhaps shrinkage of the tumour makes it more difficult to define its entirety at the bottom of a deep and bloody operative field. / /
Chapter 187 Juvenile angiofibroma
I
2441
PREOPERATIVE CHEMOTHERAPY
anaesthesia the nose is prepared with a vasoconstrictor
Other means of reducing tumour size before surgery have
anterior end of the middle turbinate is resected at the
also been evaluated. Oestrogens have been reported to
outset of the procedure
solution, 4 percent cocaine or epinephrine 1:10,000. The
induce shrinkage in some but their effect is variable and
(Figure 187.5).
An anterior ethmoidectomy together with removal of
not without complications. At the very least, oestrogen
the medial wall of the maxillary sinus gives access to the
therapy delays surgery and the secondary feminizing
posterior wall of the antrum. This is then removed to
effects are certainly unwanted by an adolescent boy. In a
achieve complete lateral exposure of the tumour (Figure 187.6). Dissection then continues into the sphenoid until
small series of patients given the nonsteroidal androgen receptor blocker, flutamide, tumour shrinkage of up to 44
its rostrwn is reached following which the tumour can be
percent was reported by Gates et
peeled inferiorly
al.!3 Flutamide is
regularly used in the management of prostatic cancer. While not without side effects, nausea, breast tenderness and gynaecomastia, these effects were only temporary and
(Figure 187.7).
A similar technique can be used to deliver the lateral extension of the tumour into the operative field (Figure 187.8). Throughout this process it is necessary to use
disappeared completely at the end of therapy. It seemed
bipolar diathermy and ligaclips to control the feeding
that this drug might have a role in the preoperative
blood vessels.2o The use of a second surgeon accessing the
preparation of patients with very advanced tumours,
nasal cavity through the contralateral nostril aids the
certainly those with intracranial extension. Unfortunately,
resection of larger tumours. The second surgeon can
in a pilot study of seven patients with stage IV disease
apply traction to the tumour and improve visibility by
undertaken by Labra et
additional suction.
al.14 the mean shrinkage achieved 7.5 percent (median 6.1 percent, range 4.8-11.1 percent) and this was considered to be insignificant. [**I*J
was
SURGICAL RESECTION - TECHNIQUES AND AP PROACHES Until
relatively
recently,
most
small
tumours
were
resected either through a transpalatal approach, lateral rhinotomy
or
mid-facial
degloving
approach.
Open
approaches can be used for tumours of all stages and certainly were the only option before the application of endonasal endoscopic techniques became more wide spread. Nowadays, stage Fisch I, 2 and some type 3 tumours are suitable for endoscopic resection using one or two surgeon techniques.1S,16,17,IB,19 There is much to be gained by endonasal endoscopic techniques, for example, reduced intraoperative blood loss, fewer postoperative complications and a reduced
Figure 187.5
The anterior end of the middle turbinate is
removed to gain access and improve visualization of the tumour.
length of hospital stay. It is difficult to know how real these claims are as no prospective trials have been undertaken and those reported are either small case series or rely on historical controls. Furthermore, the twnours resected by endoscopic techniques tend to be relatively small. Fisch type 3 tumours suitable for endoscopic resection have limited medial invasion of the infratem poral fossa. Larger tumours and those extending across or through the skull base present a very different surgical challenge
which the enthusiastic endoscopist should
consider carefully before embarking on a potentially life-threatening procedure. "'"
......... ------
Endoscopic endonasal techniques Preoperative embolization is usually undertaken, not
Figure
withstanding its doubtful benefit. After the induction of
medial antral wall is undertaken.
\
.
187.6
An anterior ethmoidectomy and resection of the
-- .--- - .
/
_ ----------
\
-
2442
I
PART
17 HEAD AND NECK TUMOURS
Figure Figure
187.7
Extraction of the tumour from the sphenoid.
187.9
A mid-facial degloving approach to the
pterygopalatine fossa. The anterior, medial, lateral and posterior walls of the antrum have been removed while preserving the infra-orbital nerve and a rim of bone around the nasal aperture.
facilitate the removal of paranasal extensions. However, the components of tumour in the cavernous sinus and any intradural disease demands adequate exposure and this can only be achieved with a subtemporal pre-auricular infratemporal fossa approach, usually combined with a
modified middle fossa craniectomy.22
Radiotherapy
Figure
187.8
Resection of the lateral extension of the tumour
and use of ligaclips to control bleeding from the feeding artery.
Several centres have reported results for the treatment of , 4, advanced disease by radiotherapy.23 2 25 External beam radiation was delivered in several fractions to achieve a total tumour dose of 30-55 Gy. All series report that regression of angiofibromas after radiotherapy is very slow indeed, often taking two to three years before
Open approaches
'radiological stabilization' is achieved. In other words,
Access for open approaches has changed over the last 20 years. Transpalatal and lateral rhinotomy approaches have largely, but not completely, given way to mid-facial degloving
and
infratemporal
popularized in the
approaches
that
were
1980s. Most surgeons now have
adopted the technique of mid-facial degloving for the resection of juvenile angiofibromas. Using the exposure afforded by this approach, the anterior, medial, lateral and posterior walls of the maxillary antrum can be removed. This produces a very large cavity
that is
confluent with the nasal cavity and post-nasal space and gives adequate access for tumour removal together with
control of its blood supply. Extensions into the inferior part of the orbit and infratemporal fossa can also be 1 removed (Figure 187.9).2 Extensive juvenile angiofibromas are better resected through skull base approaches, preferably undertaken by a combined otorhinolaryngological and neurosurgical team. It may be that the intranasal component can still be removed endoscopically or that endoscopic guidance may /
reduction in the size of the tumour takes place, but residual tumour remains. Local control rates of 80-85 percent
have
been
achieved
as
assessed
by clinical
examination. In most series, residual disease was not assessed by interval scans unless new symptoms or signs developed. The radiation oncologists relied upon mirror examination of the nasopharynx and clinical criteria rather than objective image data to determine outcome. Treatment failure was apparent, usually within the first two to three years, and surgical salvage was generally successful in all these patients. There are no reports on the efficacy of gamma-knife therapy as yet, though some patients must have been treated by this means. I**J
COM PLiCATIONS Recurrence is by far the most conunon complication encountered and is reported in up to 25 percent of patients regardless of the method of treatment. Further recurrences may develop in up to 40 percent of these
/
/
.l
....
'1 ..
• l.
Chapter patients. Not surprisingly, recurrence is more likely in
187 Juvenile angiofibroma I
2443
KEY POINTS
patients with advanced disease and in those treated by inexperienced surgeons. As stated previously, preoperative embolization is not associated with a reduced rate of
Angiofibromas should be
•
susl*idll�
a young male patient �U"UP��)O\�MI
recurrence as might be expected. The one single factor
nasal obstruction. particularly -"
that seems to correlate with recurrence is the age of the
"'f'.<;.J,.�
been experiencing epistaxes.
patient at the time of presentation. The yOJ.lnger the patient the more likely that future recurrence will develop.
The diagnosis should be made
•
imaging and not biopsy.
[HI"] From a surgical standpoint, most recurrences develop
Complete surgical resection is
•
the trea���Jl�; ���:��:� J
of choice with radiothe(apy being res.lti'e�(L
as a consequence of invasion ()f the basisphenoid. A more
for those in whom �s is not possible or
meticulous exploration of this area at the time of primary
who develop recurrence.
Surgery has been reported to have a dramatic effect on the rate of recurrent disease.26 Rather than rely on macro
•
scopic clearance of disease, drilling out the basisphenoid
•
There is a high rate of recurrence. Recurrence rates can be reduced by meticulous dissection of the sphenopalatine
ensures that no residual tumour remains in the pterygoid
foramen.
canal or cancellous bone of the sphenoid. In view of the very high incidence of recurrent disease,
Recurrence usually becomes evident within
•
two to three years of the initial resection.
prolonged clinical and radiological monitoring is neces sary for all these patients. Disease-free status five years
Response to radiotherapy is very slow, the
•
effect may not be fully apparent for one to
after primary surgery probably represents cure. The same
two years.
cannot be said for those who have experienced recurrent disease. Interestingly, few surgeons have quoted complications other than recurrence. It is unlikely that this is the only possible complication, but rather that all others pale into insignificance in comparison. Surgically induced infra orbital nerve sensory deficits are recognized as a potential complication of mid-facial degloving, as is nasal vestib ular stenosis.27 Prolonged nasal crusting is also common and this may well develop into ozaena. Regular nasal
. -:. ..
" J�.�
a
tion. With more extensive resections, ocular problems
,
.
,
•
./ Both CT and MR images should be acquired and
clinical staging made on the basis of these data. ./ Angiography and embolization is advised for those
undergoing endoscopic endonasal resection and for
douching with saline and the use of glucose in glycerine drops can do much to alleviate this unpleasant complica
'
'
those with intracranial extension. ./ Patients should have interval imaging for at least five
years before being declared disease free and cured.
may be experienced. Displacement of the globe caused by loss of bony support, ophthalmoplegia and visual loss must have been experienced by some, but perhaps not considered a complication so much as the unavoidable consequence of a complete craniofacial resection. Late complications also develop following radiother apy and are relatively common. Up to 33 percent of patients in the reported series have been affected. Growth retardation, panhypopituitarism, temporal lobe necrosis, cataracts,
radiation
keratopathy,
together
with
skin,
thyroid and nasopharyngeal malignancies were the most common problems encountered in the first 10-15 years after treatment. Some second neoplasms have developed
Deficiencies in current knowledge and areas for future research >- The preCise molecular mechanisms involved in the
development of this tumour. >- Long-term outcome data for patients treated by
endoscopic endonasal techniques. >- Outcome data for patients treated by gamma-knife or
stereotactic radiotherapy.
in the radiation field at an even later date. Whatever the success rate of radiotherapy to control disease, it has to be remembered that even 30 years after radiotherapy the patient will still be very young28 and none of these reported complications is negligible. Furthermore, it must be recognized that all patients with residual disease are at
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Windfuhr JP, Remmert S. Extranasopharyngeal
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2444 I PART 17 HEAD AND NECK TUMOURS
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Hwang HC, Mills SE, Patterson K, Gown AM. Expression of
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Klossek J-M, Serrano E et al. Exclusively endoscopic
immunohistochemical study of 24 cases. Modern
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Pathology. 1998; 11: 1122-6.
Archives of Otolaryngology - Head and Neck Surgery.
Schiff M, Gonzalez AM, Ong M, Baird A. Juvenile
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Brieger J, Wierzbicka M, Sokolov M, Roth Y, Szyfter W,
angiofibroma: when and how. Laryngoscope. 2003; 113:
Mann WJ. Vessel density, proliferation, and
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of benign tumors extending into the infratemporal fossa:
Nagai MA. Relaxation of imprinting of IGFII gene in
A two-surgeon transnasal approach. Laryngoscope. 2005;
Molecular Pathology. 2003; 12: 57-62.
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Frequent beta-catenin mutations in juvenile
nasopharyngeal angiofibroma. Laryngoscope. 2005; 115:
1073-8.
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surgical management of extensive nasopharyngeal
prevalence and treatment. Ophthalmic Plastic and
Laryngoscope. 1989; 99: 429-37.
Reconstructive Surgery. 2004; 20: 296-300. 22.
Radkowski D, McGill T, Healey GB, Ohlms L, Jones DT.
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Surgery. 2004; 130: 882-6. * 23.
Cummings BJ, Blend R, Keane T, Fitzpatrick P, Beale F,
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naspharyngeal angiofibromas. Laryngoscope. 1984; 94:
Mann WJ, Jecker P, Amadee RG. Juvenile angiofibromas: changing surgical concept over the last 20 years.
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Donald P J, Enepikedes D, Boggan J. Giant juvenile
Angiofibroma. Changes in staging and treatment. Archives
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Cruz AAV, Atique JMC, Melo-Filho FV, Elias J. Orbital
Andrews JC, Fisch U, Valavanis A, Aeppli U, Makek MS. The angiofibromas with the infratemporal fossa approach.
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Pryor SG, Moore EJ, Kasperbauer JL. Endoscopic versus
Abraham SC, Montgomery EA, Giardiello FM, Wu n angiofibromas. American Journal of Pathology. 2001; 158:
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Robinson S, Patel N, Wormald P J. Endoscopic management
Coutinho-Camillo CM, Brentani MM, Butugan 0, Torloni H, juvenile nasopharyngeal angiofibromas. Diagnostic
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Wormald PJ, Van Hasselt A. Endoscopic removal of juvenile
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Nicolai P, Berlucchi M, Tomenzoli D, Cappiello J, Trimarchi M, Maroldi R et al. Endoscopic surgery for juvenile
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Roger G, Tran Ba Huy P, Froehlich P, Van den Abbeele T,
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Reddy KA, Mendenhall WM, Amdur RJ, Stringer SP, Cassisi
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Lee JT, Chen P, Safa A, Juillard G, Calcaterra TC. The
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McCombe A, Lund VJ, Howard DJ. Recurrence in juvenile
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Gates GA, Rice DH, Koopmann CF, Schuller DE. Flutemide-
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Labra A, Chavolla-Magana R, Lopez-Ugalde A, Alanis-
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Lowlicht RA, Jassin B, Kim M, Sasaki C. Long-term effects
Calderon J, Huerta-Delgado A. Flutamide as a preoperative
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nasopharyngeal angiofibromas on maxillary growth and
invasion: report of 7 cases. Otolaryngology - Head and
dental sensation. Archives of Otolaryngology - Head and
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Howard DJ, Lloyd G, Lund V. Recurrence and its avoidance
Carrau RL, Snyderman CH, Kassam AB, Jungreis CA.
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Gold DG, Neglia JP, Potish RA. Second neoplasms following
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188 Nasopharyngeal carcinoma
JOHN KONG SANG WOO AND C ANDREW VAN HASSELT
Introduction Epidemiology Aetiology Pathogenesis Immunology and serology Pathology Histological classification Clinical features Diagnosis Staging
2445 2445 2446 2448 2448 2448 2449 2450 2452 2458
Treatment Prognosis Complications of radiotherapy Other treatment modalities Conclusion Key points Best clinical practice
2458 2464 2464 2467 2467 2467 2469
Deficiencies in current knowledge and areas for future research References
2470 2470
Apart from the standard textbooks on nasopharyngeal carcinoma, the data in this chapter are supported by a Medline search using nasopharyngeal carcinoma against the following key words: diagnosis, pathology, immunology, treatment and complications.
I NTRO DUCTION
Nasopharyngeal carcinoma (NPC) has the most peculiar geographical and ethnic variation in its occurrence. The endemic disease has a close association with the Epstein Barr virus (EBV) and is consistently of an undifferentiated or nonkeratinizing carcinoma type. The location of the nasopharynx and the wide spectrum of presentations make early diagnosis difficult, even in high prevalence areas where clinicians and the general public have an acute awareness of the disease. It is also a disease surrounded by controversy: from pathogenesis to histopathology, disease staging and related management strategies. Thus, in many ways, NPC differs from other head and neck cancers.
EPI D E M I OLOGY
The aimual incidence rates of nasopharyngeal carcinoma of different populations vary enormously. In endemic
areas, the rate can be as much as 50 times higher than that in other countries. [*H/**] The highest age-standardized incidence rate occurs in southern China amongst the Cantonese population of the Guangdong Province. In fact, in this region, NPC is frequently referred to as the 'Guangdong tumour'. I In Hong Kong, where almost 98 percent of the population is Cantonese, the age-standardized incidence rate for men was once over 30 cases per 1 00,000, the highest in the world.2,3 Emigrants from southern China retain a significantly higher risk of developing NPC, although this suscept ibility falls off in subsequent generations.4 Other South east Asian races, including Malays, Indonesians, Thais, Vietnamese and Filipinos, as well as Eskimos (in Canada, Alaska and Greenland) are also noted for a high prevalence of NPC. These populations have an average annual incidence rate between five and ten cases per 1 00,000. Certain North African populations (in Malta; Tunisia, Algeria and Morocco) also have a slightly higher I I
. .
.\
,
I
d'
2446 I
PART 17
H EAD AN D N ECK TU M O U RS
5 times less
incidence than western populations. The Japanese and Koreans, like western populations, have an annual incidence rate of less than 1 case per 100,000.5 Wide variations in the rates of NPC are observed in China. They drop sharply from south to north so that the annual incidence rate in northern China is amongst the lowest in the world with less than 1 case per 100,000. It is predictable, therefore, that in Singapore, the annual incidence rate is highest amongst the Chinese, inter mediate amongst the Malays and lowest amongst the Indian sectors of the population. The marked variation in incidence in this case, reflects a difference in ethnic susceptibility rather than a change in geography. The disease is approximately three times as common in men as women. This is generally true both in endemic and nonendemic areas; however, there is no explanation for this gender difference. The tumour occurs at a much younger age than other cancers. Its incidence starts to rise after the second decade of life and slowly reaches a plateau, for both sexes, after the fifth decade then very gradually drops with increasing age (Figure 188.1). Below the age of 50, the incidence of NPC is higher than any other cancer.6 This plateau pattern in age distribution suggests that the pathogenesis/interaction of the aetiolo gical factors of NPC are probably different from those that operate in other forms of cancer. Somehow, there must be either reduced exposure to carcinogens or susceptibility with age. It is rare to encounter NPC below the age of 20 among the Chinese. However, in certain low-risk populations, a bimodal age distribution with two maxima has been reported. For example in Tunisia, 15 percent of patients are below the age of 16. To some extent, this bimodal age distribution is also found in India (Madras and Bombay) , Uganda and east Malaysia. A bimodal age distribution suggests different aetiological factors may take turns in playing the determining role at different periods within these populations. The age-standardized incidence rate in Hong Kong has steadily declined from 28.5 cases in 1980-1984 to 20.2 10,000 ,------,
--
o
1000
Qj
100
8 8
-----
All cancers NPC
0OJ
cases in 1995-1999 per 100,000 men, and from 11.2 to 7.8 cases per 100,000 women, resulting in a total decrease of 29 percent for men and 30 percent for women over the 20-year period. In both genders, the peak incidence occurs in the 50-59-year age group, and this age distribution pattern has remained much the same throughout the 20-year period.? It is interesting to note that no significant change in the age-standardized incidence rate has been observed in other south east Asian countries, such as Singapore and Malaysia, over the same period.
AET I OLOGY
The development of NPC is the result of a complex interplay of genetic factors, early latent infection by EBV and its reactivation and exposure to environmental carcinogens. The lack of a single unique characteristic that defines a transformed NPC cell argues in favour of a multistep hypothesis. [***/**/*]
Genetic factors
Genetically determined susceptibility probably plays an important role in the pathogenesis of NPC. This view is supported by the extremely high incidence amongst southern Chinese and retained high incidence in later generations of southern Chinese emigrants who settled in areas of low incidence.4 Familial clustering amongst immediate relatives among Chinese and other popula tions is well known. The proportion of familial cases reported across major cities of southern China is relatively constant at approximately 6-7 percent. 8 Low risk populations have a low incidence despite living in high incidence areas, for example, Indians in Singapore.9 [***/**] The human leucocyte antigen (HLA) system was first associated by Simons in 1975. Many HLA haplotypes have since been described as associated with NPC. The loci involved are the HLA-A, B and DR locus situated on the short arm of chromosome 6. The HLA-NPC association among Singaporeans, Malaysians, Hong Kong and southern 11, 12 Chinese has been thoroughly studied by Chan et al.w, Some of the important findings are summarized below.
10
0:
10
HLA ALLELES AND NASOPHARYNGEAL CARCINOMA
, ,
o
10
20
30
40
50
60
70
80
Age
Age-specific incide nce cu rves for men ( 1 998- 1 999) showing the ea rly p latea u for nasop h a ryngea l ca rci noma in com p a rison to a rising tre n d with age for a l l oth er cancers. This pattern was true fo r both sexes a n d observed th roug h out the records of the H o n g Kong Cancer Registry.6 Figure 188.1
The alleles for HLA vary in frequency among different populations. Some of these alleles, for example A2, A33, B46, B58, Cwl and DR3, are frequently present in patients with NPC. The relative risk of having NPC with particular HLA alleles was calculated as being 1.5 for A2, 1.9 for B46 and 2.1 for B58. The highest relative risk of 3.4 was found for the haplotype with A2-Cwl-B46. The gene frequency
Chapter 188 Nasoph a ryngeal ca rci noma
of B46 was also found to correlate closely with the incidence of NPC, in other words being highest in southern China and decreasing with distance from that region.
HLA HAPLOTYPES AND NPC
Certain HLA haplotypes were found to be associated with the age of onset of the disease and survival in patients with NPC. The A2, Cw1, B46 haplotype is associated with an older age (> 30 years old) of onset. The A33, Cw3, B58, DR3 haplotype is slightly more common in younger « 30 years old) patients and is associated with poor survival chances. On the other hand, A2 without B46 or B58 is associated with better survival. The HLA molecules perform tasks by presenting antigens to T cells that are the central component of the immune system. The way the different HLA haplotype affects individual susceptibility to developing NPC is still open to hypothesis. It has been suggested that individuals with a certain HLA haplotype may not be able to mount specific cell-mediated immunity to infection caused by EBV.12 Genetic changes at a chromosomal level have also been reported.l3,14 Consistent deletion on the short arm of chromosomes 3 and 9 have been found on NPC biopsies, supporting the hypothesis of an NPC tumour suppressor gene locus at these sites.
EBV
The association of NPC with EBV infection was proposed by Liang as early as 1969.15 Raised antibodies to EBV in patients with NPC over controls were confirmed a year later.16 Then the EBV genome was found in NPC cells.I?,18 The missing link still needed to be clarified, however, as EBV was not known to infect epithelial cells. The discovery of EBV receptors on human pharyngeal epithelia by Young et al.19 firmly established the close association of EBV with NPC. To date, circumstantial evidence has indicated that the virus plays a critical role in the pathogenesis of NPC.20 Thus, although these undesirable consequences occur in only a tiny minority of cases infected, because the virus is so ubiquitous this minority is numerically very significant. [***1**]
Environmental carcinog ens
Epidemiological evidence clearly shows that the patho genesis of NPC goes beyond latent EBV infection in a genetically susceptible population. The ubiquitous nature of EBV and the long incubation period between infection and development of NPC, and then only occurring in a small proportion of susceptible populations, clearly
I 2447
indicates strong co-factor dependence. Supporting evi dence also comes from the NPC incidence trend in Hong Kong over the last two decades.? The age-standardized incidence rate for both genders has, over the last two decades, dropped sharply and proportionally (by ap proximately 30 percent) , while the age pattern has remained unchanged. The drop in annual incidence rate is more likely to be related to changes in the sociocultural environment, which has indeed changed significantly compared to half a century ago, rather than changes in genetic susceptibility and the pattern of EBV infection. A possible explanation might be that while the level of individual exposure to environmental carcinogens has decreased significantly, the mechanism of exposure has remained relatively unchanged. Studies of emigrants from southern China residing in different places also suggest an association with the traditional Chinese life style rather than a modern western one. [**1*] Inhalants are logically implicated as a carcinogen as they come into direct contact with the nasopharyngeal mucosa on passing through the respiratory tract. In fact, numerous potential agents have been studied including dust, household smoke, industrial fumes and tobacco smoke?I,22 However, none of these factors has been conclusively implicated in high-risk populations. In fact, the incidence of NPC in women worldwide remains constantly lower than in men, despite the rising propor tion of women smoking over recent decades. Vaughan et al.23 reported a significant risk of developing NPC with occupational exposure to formaldehyde. After adjusting for cigarette use, race and other risk factors, a trend towards a growing risk of squamous cell carcinoma formation was found for increasing duration and cumulative exposure but not for maximum exposure concentration. By contrast, there was no association between potential exposure to formaldehyde and un differentiated and nonkeratinizing carcinomas. The im portance of analysing the data with reference to the histological subtypes of NPC is well illustrated. It was H02 who shifted attention from inhalants to ingestants in the search for causative factors. He observed that the fisherfolk of Hong Kong have a higher risk of NPC but less exposure to household smoke as their cooking and cultural rituals are all carried out in the open air rather than indoors like the land dwellers. Women, on the other hand, have more exposure to household smoke as they do most of the housework and cooking. However, they have a lower risk of NPC. Supporting evidence came later from Yu et al.24 who reported a strong association of NPC with a childhood diet that contains an appreciable amount of salted fish. In Hong Kong and southern China, the highest incidence of NPC occurs in the fisherfolk, whose diet is high in salted fish and low in vitamin-rich fresh vegetables and fruits. The ungutted salted marine fish favoured by the southern Chinese contains an appreciable amount of volatile nitrosamines. They are alkylating agents and known to induce malignant nasal
2448 I
PART 17
HEAD AN D NECK TU M O U RS
tumours in experimental animals.25 Consumption of other salted preserved foods, such as vegetables and shrimp paste, was also found to be an independent risk factor.26 Emigrant Chinese and other population groups exhibiting an intermediate to high incidence of NPC commonly consume salted fish too. These dietary carcinogens perhaps only affect susceptible populations, as the Japanese also consume dry fish and preserved vegetables that contain high levels of nitrosamines. In Japan, however, NPC is rare.
PATH OG EN ESIS
The exact steps involved in the pathogenesis of NPC are far from clear. Genetically determined susceptibility undoubtedly plays a fundamental role, which is sup ported by strong epidemiological evidence. The part played by the EBV, although still unconfirmed, is likely to be critical. The EBV genome and latent gene products are consistently found in both differentiated27 and undiffer entiated28 types of NPC. Within the tumour cells, the EBV DNA has the characteristic of being homogenous and is likely to be due to clonal cellular proliferation.29 However, so far, EBV DNA has not been recovered from normal epithelial cells of the nasopharynx, nor even from nasopharyngeal biopsies of populations at high risk of NPC.30 Also, it has been shown that a single (clonal) form of the EBV genome can be obtained from a mixed population of NPC cell lines in vitro, even when they are initially infected by multiple virions with multiple formes) of the EBV genomes.31 A causal relationship between EBV and NPC can only be established when an anti-virus vaccine eradicates the cancer. Thus far, epidemiological evidence shows that an environmental carcinogen(s) has a definite role to play. However, the exact mechanism involved is much more controversial. It may help to initiate or promote carcinogenesis by enhancing the entrance of the EBV genome into the nasopharyngeal epithelium and the subsequent expression of the virion. [**I*J
I M MU N OLOGY AN D SEROLOGY
Basic knowledge of the immunological and serological response that EBV infection induces in its host is essential for our understanding of NPC. Besides adding to our knowledge of pathogenesis, this has found numerous applications in the diagnosis, monitoring and treatment of NPC. [***I**J [Grade BJ EBV is a ubiquitous human herpesvirus discovered in 1964 by Epstein and Barr. EBV infection is widespread in all parts of the world, infecting over 95 percent of the human population and earning it the nickname of 'Every Body's Virus'. Primary EBV infection usually occurs early in life and is largely asymptomatic. If primary EBV
infection is delayed until adolescence, the clinical syndrome of infectious mononucleosis may result. In any case, primary infection is followed by seroconversion and permanent immunity to reinfection but also life-long virus persistence. The virus may somehow remain 'active' and is shed in the saliva of the asymptomatic host. The virus thus released into the saliva is responsible for the horizontal transmission of the disease to nonimmune individuals. Alternatively, the virus may lie dormant in genomic form in a small population of lymphocytes, either inside bone marro�2 or peripheral blood.33 These latent viral genomes may in later life be reactivated and enter the replicative or transforming cycles of infection. The host's genetic constitution and immunity, as well as exposure to environment carcinogens, all play a part in determining the final course. The general cell-mediated immunity (CM!) of those in whom NPC eventually develops is more likely to be impaired. Although it is still unsure whether impaired CMI is the cause or effect of NPC, this impairment can be demonstrated by lymphocyte stimulation assay or by T cell cytotoxicity. The degree of impairment of CMI may actually affect prognosis.34 As carcinogenesis progresses, different components of the EBV genome become expressed. Since the humoral immunity of these patients is normal, when it is triggered it switches on a sequence of serological events. The anti-EBV serological response in NPC patients results in the production of a wide range of specific antibodies, particularly those in the immunoglobulin A (IgA) class. The titres reached by some of these antibodies may correlate with tumour burden.35 The rise in antibody titres may precede clinical onset of the tumour.36 This premalignant phase is highly variable but may last for years before progression to frankly invasive NPC. 37 Henle et al.38 reported a strong association of IgA against viral capsid antigen (VCA) and early antigen (EA) with NPC. The IgA anti-VCA appears to be more sensitive but less specific than IgA anti-EA. These antibodies are extremely useful in screening high-risk populations for NPC. 39 However, monitoring levels of these antibodies after treatment has not been found usefu1.40 A high antibody dependent cytotoxicity (ADCC) assay against EBV specific membrane antigens was found to associate with good prognosis.41 Unfortunately, the ADCC test is not generally available. A high prevalence of neutralizing antibody for EBV-specific DNase occurs in NPC patients and its level returns to normal during remission. Promising results have been obtained using this antibody as a marker in field surveys for screening of NPC and monitoring progress after therapy.42
PATH OLOGY
Nasopharynge31 carcinoma may present itself in a variety of ways. However, a mass in the nasopharynx is a constant
Chapter 188
finding in almost all patients. Thus, it will be useful for clinicians to be familiar with the possible conditions that may produce a nasopharyngeal mass. This is particularly true for clinicians practising in areas of low prevalence of NPC, as the chance of encountering other conditions is higher. The WHO classification of tumours of the nasopharynx43 is a good source of reference for this purpose (Table 188.1). The relative proportion of cancer types in the nasopharynx differs from place to place. However, nasopharyngeal carcinoma is by far the most common, irrespective of geography and race. [**] [Grade A] The nasopharynx is a relatively small anatomical region approximately the size of the terminal phalanx of a thumb. In most cases, it will be difficult to tell the exact origin of the tumour by the time the patient develops symptoms. Nonetheless, the tumour is typically eccentric, being more bulky on one side. Morphologically, the tumour mass may fall between two ends of a continuous spectrum. On the more common arm of the spectrum, it appears as a lobulated mass of varying size with well defined borders (Figure 188.2). On the other arm, it appears to be more infiltrative with an indistinct border (Figure 188.3). The former type seems to spread earlier through lymphatics and is frequently accompanied by cervical lymphadenopathy. The latter is more likely to present with locally advanced disease with skull base erosion but without cervical lymphadenopathy. When the disease is picked up at a very early stage, for example through screening, the whole tumour may still be hidden within the fossa of Rosenmuller (Figure 188.4). In very rare cases, the tumour can be entirely submucosal without any observable mass in the nasopharynx (Figure 188.5). Lee44 described precancerous changes through different stages of intraepithelial neoplasia; however, this view has not yet gained wide acceptance.
H I STO LOGI CAL CLASS I F I CATI O N
In the past, there has been considerable disagreement over the cellular origin and the histological classification of NPC. [**] [Grade A] Nasopharyngeal carcinoma was referred to as malignant lymphoepithelioma since heavy lymphocytic infiltration at the sites of the tumour was constantly found. With improved immunohistochemical techniques, the tumour cells are confirmed to be epithelial in origin, since they stain positive for cytokeratin. The lymphocytes that infiltrate the tumour sites are reactive in nature. Analysis shows that these are predominantly T-Iymphocytes and most of these are CDS positive.45,46 However, the role of these T cells and what they are reacting to is not exactly clear yet. Recent studies showed that these tumour-infiltrating lymphocytes are regulatory T cells. There is early evidence that these tumour infiltrating regulatory T cells in fact protect the NPC cells from the body's immunosurveillance.47 Other terms, including undifferentiated carcinoma, transitional cell
Table 188.1
Nasopharyngeal ca rc i n o m a I 2449
W H O classification of t u m o u rs of the nasop ha rynx.
I Epithelial tumours a Benign
b Malignant
1 2 3 4 5
1 2 3 4 5 6
Pa p i l l o m a Pleomorp h i c adenoma On cocyto ma Basa l ce l l adenoma Ectopic pitu ita ry a d e n o m a
Nasopharyngeal ca rci noma Ad en oca rc i n o m a Pa p i l l a ry a d enoca rci noma M u coepidermoid ca rci noma Ad enoid cystic ca rci noma Po lymorphous l ow-g ra d e adenoca rc i n o m a
I I Soft tissue tumours a Benign
b Malignant
1 2 3 4 5
1 2 3 4 5
Angiofi broma H a e m a ngio m a H a e m a n g iope ri cytom a N e u ri l e m moma N e u rofi b roma
6 Pa ra g a n g l i o m a
Fibrosa rcom a R h a b d o myosa rco m a Ang iosa rco ma Ka posi's sa rcoma M a l ig n ant h a e m a n g i o pericytom a 6 M a l ig na n t n e rve sheath tumour 7 Syn ovia l sarcoma
III Tumours o f bone and cartilage IV Malignant lymphomas
1 2 3 4 5
N o n - Hodg ki n's lym phoma Extra m ed u l l a ry plasmacyto ma M i d l i n e m a l ig n a n t reticu l osis H istocytic lymphoma Hodg ki n's d isease
V Miscellaneous tumours a Benign
b Malignant
1 M e n i n g ioma 2 Cra n iopharyn gioma 3 Te ratoma
1 M a l ig n a nt m e l a n o m a 2 Chord o m a 3 M a l i g n a nt g e rm ce l l t u m o u rs
VI Secondary tumours VII Unclassified tumours VIII Tumour-like lesions
1 Cysts 2 M e n i n g ocoe l e/m e n i ngoencep h a l ocoe l e 3 G ra n u lomas 4 Amyloid d e pos its 5 Others Reproduced from Ref. 43, with permission.
carcinoma and anaplastic carcinoma, have also been used to describe these tumour cells. Thus, there were alSo. different histological classifications of nasopharyngeal carcinoma in use.48 To date, the WH049 classification is
...
2450
I PART 17 HEAD AND NECK TUMOURS
Figure 188.2 through a
Figure 188.4
A typical nasopharyngeal carcinoma as seen
0° rigid nasendoscope situated inside the left nostril,
through a
A very early nasopharyngeal carcinoma as seen
30° rigid nasendoscope situated inside the right
showing a left-sided tumour with a well-defined border. By the
nostril, showing a left-sided tumour creeping out from the
time a patient presents with symptoms, the tumour is usually
depth of the left fossa of Rosenmuller. This patient has a
more bulky on one side and it may be difficult to determine its
persistently raised IgA titre for EBVs VCA and a family history of NPC. The tumour was picked up eighteen months after the
origin.
index case was diagnosed in the family.
Coincidentally, the WHO (1978) classification was revised in the same year43 into two grades: grade 1 (Figure 1 88.6) keratinizing squamous cell carcinoma and grade 2 (Figure 188.7) - nonkeratinizing squamous cell or undifferentiated carcinoma. This system is simple to follow and accurate enough to reflect tumour characteristics. In places where NPC is endemic, grade 2 tumours constitute more than 90 percent of all cases.50 These tumours are EBV-related as patients with this type of tumour typically have elevated serological titres of anti EBV antibodies. In fact, EBV-DNAs can be detected within the tumour cells as well as in the peripheral circulations of these patients. In low incidence areas for NPC, 25 percent or more are grade 1 tumours.51 These tumours are not associated with EBV infection. In general, grade 1 tumours are less aggressive than grade 2 tumours, however, they are also less radiosensitive. Overall, the prognosis for patients with grade 1 tumours is less favourable when compared stage to stage with patients having grade 2 tumours. -
Figure 188.3
An infiltrative type of nasopharyngeal carcinoma
as seen through a
0° rigid nasendoscope situated inside the left
nostril, showing a left-sided tumour with an ill-defined border and extending up the sphenoethmoidal recess. This type of tumour is usually locally advanced at the time of diagnosis.
still the one most commonly used. It divides nasophar yngeal carcinoma into three histological subtypes on the basis of the light microscopic appearance: • .
• •
Type I Squamous cell carcinoma (keratinizing): well differentiated; - moderately differentiated; - poorly differentiated. Type II Nonkeratinizing carcinoma. Now, type Type III Undifferentiated carcinoma. only
CLI N I CAL F EATU RES
_
Mc Guire and Suen48 described the WHO type II and type III subtypes as a morphological continuum.
II
The nasopharynx is simply an air passage in the upper respiratory tract. An early tumour may cause no symptoms whatsoever. Even if it does, symptoms of early NPC are often trifling and nonspecific and tend to be ignored by both doctors and patients. Moreover, as the nasopharynx is difficult to examine thoroughly, NPC remains a diagnostic challenge to clinicians. Symptoms arise in relation to the size and position of the tumour
.,1/
Chapter 1 BB Nasopharyngeal carcinoma I
Figure 1 BB.6
1)
Figure 1 BB.5
(a) A submucosal nasopharyngeal carcinoma as
seen through a 0° rigid nasendoscope situated inside the right nostril. There is only vague mucosal oedema with some
2451
High power view of a keratinizing (WHO grade
nasopharyngeal carcinoma.
Figure lBB.7 grade
High power view of an undifferentiated (WHO
2) nasopharyngeal carcinoma.
prominent vessels in the vicinity of the right fossa of Rosenmuller. This patient presented with a palpable right cervical lymph node. (b) MRI of the nasopharynx of the same patient as in (a). Although the tumour has filled up the right fossa of Rosenmuller. the parapharyngeal fat plane is intact and there is no gross tumour inside the nasopharynx proper.
within the nasopharynx, the extent of direct spread beyond the nasopharynx and the nature of distant metastasis. Complaints fall into groups depending on the anatomical structures involved. [***I**J [Grade AJ The commonest complaint at presentation is the presence of an upper neck swelling (Figure 188.8). Unilateral neck swelling is much more common although bilateral metastases are not infrequent.52 Cervical lympha denopathy is the presenting complaint in almost 50 percent of patients. A significant proportion of patients presenting with other complaints also have cervical lymphadenopathy on examination. Overall, 75 percent of all patients have palpable cervical lymphadenopathy at diagnosis.52
Figure 1 BB.B
A patient with nasopharyngeal carcinoma
presenting with cervical lymphadenopathy. Cervical lymphadenopathy is the commonest presenting symptom of NPC and is typically situated in the upper part of the posterior triangle.
/
I
2452
I PART 1 7 HEAD AND NECK TUMOURS
Thirty percent of patients present with nasal symp toms including bloodstained nasal discharge, nasal obstruction, post-nasal drip or even frank epistaxis.52 Patients who present with one or more of these complaints are easily overlooked by clinicians as these symptoms are very common in general practice. For those presenting with nasal symptoms alone, the tumour may grow to a large size before the diagnosis of NPC is made. Approximately 20 percent of patients present with aural symptoms including deafness, tinnitus and otal gia.52 A retracted tympanic membrane or otitis media with effusion (OME) is a very common clinical finding. This finding almost always correlates with the side with more bulky tumour in the nasopharynx. The cause of Eustachian tube dysfunction may be due to the mechan ical effect of the tumour or the tumour infiltrating the Eustachian tube musculature. There is a good chance (approximately 50 percent chance from personal experi ence) of spontaneous resolution of effusion after radiotherapy. Neurological complaints comprise headache or cranial nerve symptoms. Headache is a common complaint occurring in almost 20 percent of patients.52 Headache alone may not necessarily imply locally advanced disease as it may be referred pain when distal branches of the trigem.inal nasopharynx or nose. However, it can also be the result of bony erosion of the skull base. Cranial nerve symptom(s) may be isolated or multiple. In either case, it occurs late in the disease from the spread of the tumour through the foramina of the base of the skull or with parapharyngeal involvement of the last four cranial nerves. Cranial nerves V and VI are the most commonly involved among all the cranial nerves. Cranial nerves III-VI, when affected together, are indicative of cavernous sinus involvement. Horner's syndrome is rare, but if present, is typically accompanied by paresis of one or more of the last cranial nerves. Trismus, before radiotherapy, is rare and occurs only with direct infiltration of the pterygoid muscles. Ophthalmoplegia, when accompanied by proptosis, is indicative of direct tumour extension to the orbit. This occurs only in neglected cases when the tumour spreads along the lateral nasal wall into the ethmoid cells and finally breaches the lamina papyracea into the orbit. Orbital involvement was more frequently encountered in the pre-CT era, when obscure disease in the ethmoid sinus was not picked up and therefore not included in the field of radiotherapy (Figure 188.9). Systemic metastasis at presentation is rare although eventually most NPC patients die of distant failure. The bones and lungs are the most common sites for secondary deposits followed by the liver. Lung metastases are usually asymptomatic even when multiple and sizeable, and only picked up by imaging. Bone metastases usually give rise to localized pain and are readily diagnosed by bone scan. Hepatic deposits usually caUse no symptoms when small
Figure 1 88.9
(a) A patient presenting with left-sided orbital
disease six months after radiotherapy for nasopharyngeal carcinoma (despite the fact that the nasopharynx was now free from disease). Transnasal transethmoidal biopsy confirmed an undifferentiated carcinoma. This is most likely due to persistent disease in this area (geographic miss) since it was outside the original field of radiotherapy. (b) Coronal CT of the same patient in (a), showing obvious disease involving the left orbit and the ipsilateral ethmoidal sinus. Unfortunately, there are no corresponding images for comparison, as the original planning
CT did not cut through the ethmoid sinus and orbit. The paranasal sinuses and the orbit should always be studied radiologically by CT or MRI, especially for locally advanced disease.
but may give rise to abdominal discomfort as they get larger. Although ultrasonography easily identifies liver metastases, a high index of suspicion is required to initiate the investigation. It is interesting to note that haematogenous spread to the brain is extremely rare.
DIAG NOSIS
approach to diagnosis based on the resources and expertise available should be formulated and followed so as to shorten the time taken for diagnosis. Such. a guide to the diagnostic process is especially useful in areas where NPC is endemic. Figure 188.10 outlines the approach to diagnosis followed at the Prince of Wales Hospital in Hong Kong.53,54 A good history, together with a thorough clirtical examination including endoscopy of the nasopharynx, is the basis for making the diagnosis. In An
i
/
Chapter 188 Nasop h a ryngea l ca rci noma
I 2453
History and examination
Normal looking NP
Obvious tumour
Clinically
CliniCally
suspicious
not suspicious
Radiologically
Unexplained
Persistently
Suspicious
suspicious
SOM
raised IgA
neck node
�
Biopsy NP
(LA)
Biopsy NP
FNA
Follow up
(GA)
cytology
examination
NPC
Diagnosis
Other
Squamous cell or
Other
proven
uncertain
diagnosis
undifferentiated carcinoma
diagnosis
Treatment
Repeat biopsy
Other
Biopsy NP (GA)
Other
(LNGA)
treatment
+/- panendoscopy
treatment
Approach to patients with suspected naso p h a ryngea l carc i n o m a . Red rawn from Ref. 53 with perm ission. FNA, fi n e need l e aspiration ; LA , loca l a n a esthesia ; GA, genera l a n a esthesia ; NP, naso p h a rynx; NPC, naso p h a ryngea l ca rci n o m a ; SOM, serous otitis media.
Figure 188.10
the majority of patients, a tumour mass will be found in the nasopharynx and a biopsy should be taken without delay. In less than 5 percent of patients, the nasopharynx may appear normal and other investigations may then be necessary to confirm or definitively exclude the diagnosis ofNPC. [**] [Grade A] History
The presenting symptoms are diverse and, in a consider able proportion of patients, tend to be vague and nonspecific. In the early phase of the disease, symptoms, if present, are usually related to the ear, the nose or both. These include hearing loss, tinnitus, nasal obstruction and blood-stained nasal or post-nasal discharge. In adults, these symptoms should always be of concern to the clinician if unexplained, especially if unilateral. If the disease is advanced, the above symptoms may be more clear-cut or the patient may complain of a neck lump or symptoms of cranial nerve involvement or distant metastases (see above under Clinical features). Examination GENERAL EXAMINATION
A full head and neck examination is essential in all patients. Care should be taken to look for otitis media
with effusion, cranial nerve lesions and cervical lympha denopathy. When nodes are palpable, their site and size must be carefully assessed as part of the staging process. According to Ho's concept of staging, the neck is divided into three levels (one to three) by two natural horizontal skin creases, one passing through the thyroid notch and the other through the sterno-clavicular joint. The lower the neck node involvement, the more advanced the disease, the higher the neck staging. EXAMINATION OF THE NASOPHARYNX
The nasopharynx is one of the most difficult areas of the head and neck to exanline using conventional techniques. The traditional method of indirect mirror examination, although it may give an excellent view of the nasophar ynx, is inadequate. For general diagnostic purposes, transoral retrograde nasopharyngoscopy with either a 70° or 90° endoscope no doubt gives the best possible view of the nasopharynx. This technique is technically more demanding but it provides a wide-angled view of the entire nasopharynx with superb clarity. As the view obtained is from below and behind, the fossae of Rossenmuller are wide open for evaluation, allowing even minute degrees of asymmetry between the two sides to be identified (Figure 188.11). However, even in the best hands and with the most cooperative patient, the. posterior part of the nasal fossae will not be seen. On rare occasions, the tumour may remain submucosal in the
2454 I
PART 1 7 HEAD AND NECK TUMOURS
nasopharynx and only become obvious after reaching the nasal fossa. These tumours may be missed altogether. Thus, retrograde nasopharyngoscopy (direct or indirect) may on rare occasions be inadequate. Antegrade nasopharyngoscopy is preferred and should be performed under topical anaesthesia both for the patient's comfort and to enable a biopsy to be taken if necessary. Adequate surface anaesthesia is achieved by applying cotton pledglets soaked in 5 percent cocaine solution placed along the floor of the nose. Alternatively, a solution made up of 4 percent xylocaine with 1 in 1 0,000 adrenaline can be used instead of cocaine. Both sides of the nose should be prepared in order to allow a complete examination, and, in case a biopsy is to be taken, the most direct passage for the biopsy forceps can be used. A narrow (3.5 or 3.7 mm) end-viewing flexible fibrescope is most suitable for this examination. It gives
an undistorted view and provides the flexibility required to inspect the area in detail. The narrow diameter and flexible tip of the fibrescope allow accurate assessment of the entire nasopharynx, enabling small lesions to be detected and large lesions to be accurately staged. Alternatively, rigid (4 mm) 0 and 30° Hopkins rod endoscopes are also suitable for direct inspection of the nose and nasopharynx. The modern rigid nasendoscope has excellent optics and provides a wide-angle view of 1 1 0° or more and gives a better picture for photographic documentation (Figure 1 88.1 2). However, in patients with a severely deviated nasal septum or nasal polyposis, the passage of the rigid endoscopes may be difficult. The view of the nasopharynx obtained with the antegrade approach is from front to back. Thus, the depths of the fossae of Rosenmuller will be hidden by the inwardly projecting Eustachian cushions. A simple manoeuvre, by
Figure 188.12 Figure 188. 11
(a) A
normal nasopharynx as seen through a
90° rigid pharyngoscope situated inside the mouth, showing the
(a)
A normal nasopharynx as seen through
a
0° rigid nasendoscope situated inside the right nostril. Although the nasopharynx proper is well seen, the depths of the fossae of
whole nasopharynx and both fossae of Rosenmuller. (b) An early
Rosenmuller are not demonstrated clearly. (b) A normal
nasopharyngeal carcinoma as seen through a 90° rigid
nasopharynx as seen through a 30° rigid nasendoscope situated
pharyngoscope situated inside the mouth, showing a right-sided
inside the right nostril with the viewing axis turned towards the
tumour with
a
distinct border. The ipsilateral fossa of
Rosenmuller is totally filled by the tumour.
left. Note that the whole length and depth of the fossa of Rosenmuller is seen in detail.
/
Chapter 1 88 Nasopharyngeal carcinoma
I 2455
asking the patient to say 'ah' (mouth sound), 'ng' (nasal sound) and then to swallow ( opening and closing the Eustachian tube) will expose any small lesion in the fossae of Rosenmuller for inspection. 55 Biopsy of the nasopharynx
Biopsy of the nasopharynx is considered the first necessary investigation for NPC if a suspicIous lesion is found.54 Ideally, this should be carried out during the patient's first outpatient visit. The biopsy procedure is carried out under topical anaesthesia (as described above under Examination of the nasopharynx), with the patient seated. A diagnostic nasendoscopy should be carried out first, noting the site of the tumour if present. The endoscope is passed through the side of the nose where the tumour is less bulky, leaving the ipsilateral side clear for the passage of the biopsy forceps ( Figure 188.13) . This arrangement of instruments p rovides flexibility for manipulating the endoscope, while reserving the most direct route for the passage of the biopsy forceps. The biopsy should be taken under direct vision using cutting biopsy forceps with a large cup. This will avoid the need to pull on partially cut tissues and one bite on the tumour is usually adequate for diagnosis. Although some bleeding is to be expected, significant post-biopsy epistaxis is rare. Biopsies taken through the operating channel in the flexible endoscope are not recommended as the tiny forceps provide an inadequate tissue sample for diagnosis ( Figure 188.14). [**] [Grade A] In the few cases when clinical suspicion exists but the nasopharynx appears normal, or when previous biopsy specimens taken under topical anaesthesia are incon clusive, an examination and biopsy taken with the patient under general anaesthesia is mandatory. Multiple deep biopsies should be taken from the central nasopharynx and both fossae of Rosenmuller. The Yankauer naso pharyngeal speculum is a very useful aid to open up and give access to the depths of the fossae of Rosenmuller. If special histochemical staining is anticipated, the biopsy specimens, after prior arrangement, should be sent fresh to the pathologist. Differential diagnosis
The differential diagnosis varies according to the method of presentation. Some common nasal conditions, such as rhinosinusitis or nasal polyps, may coexist with NPC. Clinically, those patients with a neck node, but with no obvious primary in the nasopharynx, are the most difficult to diagnose. Pathologically, NPC should be distinguished from sinonasal undifferentiated carcinoma which has similar cellular morphology but is not EBV related in aetiology. The amelanotic melanoma may also cause confusion in diagnosis based on cellular
Figure 1 88.1 3
Biopsy of a left nasopharyngeal carcinoma
under direct visual guide. A 0° rigid nasendoscope was introduced through the right nostril while Takahashi biopsy forceps were passed along the floor of the left nostril (ipsilateral to the side of the tumour). Note the very accurate placement of the biopsy forceps.
Figure 1 88. 1 4
Takahashi biopsy forceps in comparison to
those that work through the suction channel of a flexible endoscope. Note the marked difference in size of the biopsy cups.
morphology alone and may need a series of histochemical stains to confirm its origin. Under these special circumstances, detailed imaging (see below under Ima ging) and special diagnostic tools are recommended. Delay in diagnosis
NPC is extremely radiosensitive and i� a readily curable cancer if the diagnosis is made when the disease is still at an early stage. Unfortunately, only approximately 10 percent of all cases are diagnosed really early (stage I). Delays in diagnosis are the result of a multitude of factors.
-
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2456 I
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The absence of, or the trifling nature of, symptoms of early NPC is probably the main cause leading to delayed diagnosis. Moreover, patients with NPC are mostly young, fit and healthy and the main breadwinner of the family. They tend to deny the fact that they may have a serious disease. This explains why even for those with a neck lump, it takes an average of four months before they seek medical advice. Unfortunately, to date, a cost effective mass-screening programme for early diagnosis of NPC is still lacking. Early diagnosis can only be achieved through better patient education.&A high index of suspicion among clinicians is also necessary so that the diagnostic process is initiated early.
Oth e r d iagnostic tools
The key to diagnosis of NPC is to have an accurate biopsy combined with histological examination since in approxi mately 95 percent of cases a tumour mass will be found on endoscopy. In atypical cases, however, especially where the disease is submucosal or biopsies are negative, additional investigations are indicated.
SEROLOGY
The detection of IgA antibodies to the Epstein-Barr virus specific antigens is helpful in the diagnosis of NPC. 5 6 The IgA anti-VCA titre is high although lacking in specificity, especially at low levels. The IgA anti-EA titre, on the other hand, is less sensitive but its specificity is extremely high. These tests, especially in combination, are useful for general practitioners in endemic areas, as they may provide guidelines for referral to specialists if titres are raised. They may also serve to alert the specialist to the need for further investigation and a deep biopsy under general anaesthesia, especially in patients whose clinical examination is normal.
CYTOLOGY
Fine needle aspiration cytology (FNAC) of neck nodes is extremely useful in patients with suspicious nodal enlargement but without a detectable primary tumour. FNAC readily differentiates metastatic nodal disease from tuberculosis. In NPC, the nodal disease is typically of the undifferentiated variety and can be recognized by an experienced cytologist.
I M MUNOCHEMICAL STAI NING
In endemic areas, effectively all cases of NPC are EBV related. In the case of doubtful diagnosis, special EBV specific immunochemical staining may help to confirm the diagnosis. Cytological smears from tissue biopsies or FNAC material can be stained for the presence of
Epstein-Barr virus-associated nuclear antigen (EBNA) by specific monoclonal antibodies. Its presence indicates the likelihood of NPC. 35 On the other hand, a negative result virtually excludes NPC. A more easily available test is to stain for EBV-encoded RNAs. All NPC cells expresS certain EBV-encoded latent proteins, and in the process abundant RNA is produced intracellularly. Thus again, if the cancer cells stained positive for EBV RNA, NPC is virtually confirmed. Modern technology of in situ hybridization for EBV RNA can be applied to fresh tissues as well as formalin-fixed paraffin-embedded specimens,5 7 making the test useful both as a diagnostic and as a research tool. More recently, even minute amounts of circulating cell-free EBV DNA can be detected and quantified with real-time polymerase chain reaction from serum samples of patients. 5 8 The level of circulating cell free EBV DNA has been shown to correlate with the recurrence of NPC. 5 9 IMAGING
Although imaging may occasionally be needed to identify the site for a biopsy of a submucosal tumour, its major role in the management of NPC is in the tumour staging, radiotherapy planning and post-treatment monitoring of the disease. A plain radiograph of the nasopharynx and base of skull is obsolete as it is neither sensitive nor accurate enough to have any clinical application nowa days.60 Computerized tomography (CT), magnetic reso nance imaging (MRI) and ultrasound (US) examination are commonly used and complement each other in patient management. CT is the most widely used method for primary tumour evaluation as it is more widely available. It accurately demonstrates the tumour mass (Figure 188.15), including submucosal disease, and its local extension, and it is preferred by many clinicians to demonstrate bony erosion of the skull base (Figure 188.16) or vertebral bodies. MRI, however, has the advantage of having better soft tissue resolution and multiplanar capability. To date, MRI is the most accurate method of evaluating the primary tumour and its direct local spread. It accurately differentiates parapharyngeal space distortion from infiltration by a tumour (Figure 188.17) and direct perineural spread of tumour. Although bony erosion is not directly shown, once the cortex is breached, MRI is much more sensitive than CT in evaluating marrow infiltration. The additional view in the sagittal plane improves assessment of the clivus (Figure 188.18) and better defines nodal metastases. In suspected disease involving the paranasal sinuses, MRI definitively differentiates entrapped mucus from tumour involvement (Figure 188.19). Thus, in many respects, MRI is superior to CT in local and regional staging of NPc. 6 1 , 62 However, due to its much higher cost, MRI is not easily available or affordable, especially in developing countries where NPC is endemic. US examination is useful and does not involve
Chapter 188 Nasopharyngeal carcinoma
Figure 188.15
I 2457
An axial CT of the nasopharynx showing a
tumour obliterating the right fossa of Rosenmul l er and extending medially to the midline. The contralateral fossa of Rosenmulier is normal.
Figure 188.17
M R I of the nasopharynx showing a right-sided
tumour with parapharyngeal disease. The rounded appearance and the weli-preserved tissue planes are suggestive of distortion by a parapharyngeal lymph node rather than tumour infiltration.
Fig ure 1 88 . 1 8
Sagittal M R I of the nasopharynx showing a
tumour with e rosion through the clivus and extensive infiltration of its marrow space.
Figure 188 . 1 6
A coronal CT of the nasopharynx showing a
right-sided tumour with extensive skull base erosion.
irradiation or administration of contrast media. It is less expansive when compared to either CT or MRI and is generally more easily available. However, its accuracy is very operator dependent. FNAC of neck nodes under US guidance (Figure 188.20) is the most accurate method to diagnose nodal metastases especially in the
post-irradiated neck. Due to the difficulties in instru mentation, US examination of the primary tumour of the nasopharynx has had very little application so far. Currently, the use of US examination is confined to the diagnosis and monitoring of regional or distant metastases. The detection of residual or recurrent disease at the primary sites after radiotherapy is complicated , and particularly difficult for those who are diagnosed with advanced local disease. The images obtained from the post-irradiated sites are affected by different degrees of I
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PART 1 7 H EAD AND N ECK TUMOURS
CT/MRI findings are equivocal. PET, being an extremely sensitive investigation, is useful to exclude distant metastases before major salvage.
STAGI NG
Figure 1 88.1 9 T2-weighted MRI of the nasopharynx showing a nasopharyngeal tumour extending from the nasopharynx to the right nasal fossa with secondary maxillary sin usitis.
Figure 1 88.20 An u ltrasonograph showing fi ne needle aspiration of a neck node for cytology performed under real time u l trasound guide. Note the needle track is accurately i n p lace.
In post-radiation changes; viable tumour growth may not be confidently diagnosed. As the natural course of these lesions is not fully understood, and biopsy may be hazardous, for example at the base of the skull or parapharyngeal space, serial imaging (MRI preferred) is advised. Functional scanning with the ability to differ entiate hypometabolic (post-RT oedema) from hyperme tabolic (viable cancer) tissues is a useful adjunct to the conventional imaging techniques. Positron emission tomography ( PET) based on differential uptake of F 1 8 fluoro-2-deoxy-D-glucose (FDG) and single photon emission computed tomography (SPECT) based on differential uptake of thallium have produced some promising results.63 SPECT as a whole is used when the
As a result of the unique nature and behaviour of the disease, many stage classifications have been devised, though none has yet gained universal acceptance. The modified Ho's stage classification64 has thus far been the most effective in separating patients evenly into different prognostic groups. The staging is based on the combined assessment of the tumour (T), regional nodal (N) spread and presence of any distant metastases (M), as in the other systems. The UICC/AlCC classification, however, is the one preferred for publications. The main difference between the Ho classification and that of the VICC/AlCC has always been N criteria. The former stage of the neck is based mainly on the concepts of levels of nodal involvement. Even in the latest UICC/AlCC revision,65 when the concept of nodal levels was adopted, differences still exist over the significance of the size, fixity and laterality of the nodes. The recommendation nowadays is, as far as publications are concerned, that the latest VICC/AlCC system should be used, while in places where NPC is endemic, a more refined staging scheme should be used in tandem so as to give a better correlation with prognosis. The Ho modified stage classification 1 982 (Table 1 88.2) and the VICC/AlCC classification 2002 (Table 1 88.3) are reproduced for easy reference. [**] [Grade A] Unlike other head and neck cancers, the staging procedure does not require evaluation under general anaesthesia. However, thorough physical examination, endoscopy of the upper airway and radiological imag ing by CT and/or MRI should be performed for all patients undergoing radical treatment. The basic meta static work-up includes a chest radiograph and liver function tests. Further investigations (bone scan, liver ultrasound) are recommended for patients with abnor mal functions, suggestive symptoms or advanced locor egional disease.
TREATM ENT
NPC is an extremely radiosensitive tumour and the mainstay of treatment for primary local and regional disease is invariably radiotherapy, almost irrespective of the stage of the disease. For patients with advanced disease, the addition of chemotherapy appears to enhance the overall treatment results. Surgery, at present, is only used to salvage local and regional failures. Other modalities of treatment are still experimental at the present stage. As patients are m'ainly treated according to the stage of their disease, it is more practical to look at the overall treatment )
/
/
Chapter 1 88 Nasopharyngeal carcinoma
Table 1 88.2
Mod ified Ho's classification.
Table 1 88.3
I 2459
AJCC stage classification for NPC.
Classification
Pri mary tu mou r (T)
Pri mary t u m o u r (T)
Tl Nasopharynx only T2n Nasal fossa T20 Oropharynx
TX TO Tis Tl T2 T2a
T2p Para pharyngeal region T3a Bony involvement of below the sku l l base including floor of sphenoid T3b Bony involvement of the sku l l base T3c Cranial nerve(s) pa lsy T3d Orbit, laryngopharynx (hypopha rynx) or infratem pora l fossa T3p Para pharyngeal region Reg ional lymph node (N) NO N1 N2 N3
No nodes Node(s) above the skin crease at laryngeal cartilage Node(s) below the above skin crease but above the supraclavicu lar fossa Su praclavicu lar fossa nOde(s)
M etastasis (M) MO No distant metastasis M 1 Dista nt metastasis
Primary tumou r can not be assessed No evidence of primary tumour i)" Carcinoma in situ Tumour confined to the nasopha rynx Tu mour extends to soft tissues Tu mour extends to the oropharynx a nd/or nasa l cavity without para pharyngeal extensiona Any tumour with parapharyngeal extension Tu mour involves bony structures and/or paranasal sin uses Tumour with intracranial extension and/or involvement of cranial nerves, i nfratem poral fossa, hypopharynx, orbit or masticator space
T2b T3 T4
Regional lymph node (N) NX NO Nl
Regiona l lymph nodes can not be assessed No reg ional lymph node metastasis Uni latera l b metastasis i n lymph node(sl. 6 cm o r less in the g reatest dimension, above the supraclavicu lar fossab Bilateralb metastasis in lymph node(s), 6 cm or less in the g reatest dimension, above. the su praclavicular fossa Metastasis i n lymph node(s), > 6 cm a nd/or involve the supraclavicular fossa Greater than 6 cm in dimension Extension to the supraclavicular fossa
N2
Stag i n g g ro u ping (Tl ,T2n ,T20) NOMO I i a (Tl ,T2n,T20) ( N 1 ,N2)MO l i b (T2p,T3,T3p) NOMO I l i a (T2p,T3,T3p) (N 1 ,N2) MO I l lb (Tl ,T2n,T20) N3MO IVa (T2p,T3,T3p) N3MO Ivb M 1 (any T, any N) Reprodu ced from Ref.
64. with permission.
in that fashion. In the subsequent paragraphs, the staging ( unless otherwise specified) used is the DICC/AJCC 1997 staging system. [***/**] [Grade AlB]
Primary treatment RADIOTHERAPY
Megavoltage external radiotherapy (ERT) (Figure 1 88.21 ) is the primary treatment modality of choice. This is given through two lateral opposing and one anterior field. The field design is such that the whole nasopharynx and both sides of the neck are covered (Figure 1 88.22). Elective neck irradiation is practised almost worldwide due to the high incidence of occult nodal involvement.66. 67 In Hong Kong, the territory-wide recommended tumouricidal dose should be no less than 65 Gy, and the dose per fraction should not exceed 2 Gy.68 Proper shielding of all
N3 N3a N3b
M etastasis (M) MX
Distant metastasis can not be assessed N o distant metastasis Dista nt metastasis
MO Ml
Stage g rouping Stage Stage Stage Stage
0 I
Iia lib
Stage l l l Stage IVa Stage IVb Stage IVc
Tis Tl T2a Tl -2a T2b Tl -2b T3 T4 Any T Any T
Reproduced from Ref. a
NO NO NO Nl NO-l N2 NO-2 NO-2 N3 Any N
MO MO MO MO MO MO MO MO MO Ml
65. with permission.
Parapharyngeal extension denotes posterolateral infiltration of tumour
beyo nd the pharyngobasilar fascia. bSupraciavicular fossa is a triangular area orig inally described by Ho. I t is defined by three points: clavicle ;
(2)
( 1 ) The
superior margin of the sternal end of the
the superior margin of the lateral end of the clavicle;
(3)
the
poi nt where the neck meets the shoulder. U n i lateral or bilateral lymph nodes rather than ipsi l a teral or contralateral lymph nodes are noted. as the nasopharynx is considered a m i d l i n e structu re.
!
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afterloading brachytherapy may be used to deliver the additional dose of radiation with much more acceptable morbidity. Variation in the primary treatment plan will affect the management of residuallrecurrent disease. [***] [Grade A] CHEMOTH ERAPY
Figure 1 88.21 A modern megavoltage externa l radiotherapy u n it with a pa tient i n place ready for treatment.
Figure 1 88.22 Typica l surface markings for treatment planning on a patient with nasopharyngeal ca rcinoma. Note that the field of radiotherapy extends below the clavicles.
critical structures, as well as surrounding normal tissue, is important. When indicated, a parapharyngeal boost is given to extend the postero-lateral coverage. Treatment should be delivered without interruption in five or six daily sessions per week for a total of six weeks. For early disease (stage I-II), conventional radiotherapy alone is adequate and, as yet, there is no evidence that treatment results can be further improved by adding chemotherapy. For lo�lly advanced non metastatic disease (stage III-IVB) , chemotherapy in addition to conventional radiotherapy appears to improve the overall results. The use of adjunctive chemotherapy in these advanced cases is in fact an integral part of the treatment protocol in many centres. In some, a higher radiation dose (�70 Gy) is given to the primary tumour. This may be given as standard ERT but with a risk of having a higher incidence of radiation-induced complications. Alternatively,
With respect to the timing, chemotherapy is described as neoadjuvant, concurrent or adjuvant to radiotherapy. Chemotherapy is believed to act as a radiosensitizer and helps to reduce the chance of distant metastases. Owing to conflicting results in the literature, it is difficult to assess its benefit and develop the best chemotherapy regimen. The impact of chemotherapy on long-term survival is still controversial. Studies on adjuvant chemotherapy show contradicting results. The results of cisplatin-based neoadjuvant chemotherapy are more encouraging, a trend towards improving relapse-free survival was observed by the International NPC Study group.69 The same result was obtained by the Asian-Oceanic Clinical Oncology Associa tion studies.70 However, no study so far has demonstrated any overall long-term survival benefit. Neoadjuvant chemotherapy is also used to reduce the size of bulky neck nodes so that the standard radiotherapy techniques can be applied. The most impressive results have been with concurrent (cisplatin) chemoradiation, a significant short term progression-free survival benefit, up to a mean follow-up of three years, was shown by two independent phase III studies.7l, 72 Similar results were obtained by a meta-analysis on the same subject.73 However, the experience of chemotherapy is still limited and true benefits will need longer follow-up. Complications are largely due to the effects of bone marrow suppression, sensorineural hearing loss and renal impairment from cisplatin-based chemotherapy. Theoretically, as a radio sensitizer, chemotherapy also potentially accentuates the complications of radiotherapy. [***] [Grade B] FOLLOW-UP PLAN
Close monitoring of the progress during and after treatment is necessary so that treatment failures are identified early for successful salvage. The majority of relapses occur in the first three years although late failures also occur.74, 75 After primary treatment, patients should be seen at least two-monthly for the first year and three monthly for the second and third year, six-monthly thereafter. Lifelong follow-up is needed as very late recurrence may also occur. The response of local disease is best followed up by repeated nasendoscopy. Post-treat ment biopsy is indicated if there is any residual swelling at the primary site. However, the appearance of the post irradiated nasopharynx will look quite different from normal (Figure 188.23). Experience in assessing the post irradiated nasopharynx is necessary so that an accurate biopsy can be taken and unnecessary biopsy avoided.
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/
Chapter 1 88 Nasopharyngeal carcinoma I 2461
be achieved through the joint efforts of radiation oncologists and medical oncologists, as well as otolar yngologist/head and neck surgeons. Patient benefits and disease control may be on opposite sides of the health equation. Treatment, therefore, should be considered on a case-by-case basis. Radical attempts to cure are recom mended whenever feasible. All treatment options carry inherent risks, and there are yet no data prospectively comparing the efficacy of different approaches. Risks and benefits of all possible options should be evaluated, and the patient's preference duly considered when alternative measures exist. As patients with uncontrolled local and/or regional disease also have a higher risk of distant failure/6 restaging (locoregional and metastatic workup) is essen tial before any radical measures are taken. [**] [Grade B] SALVAGE FOR LOCAL FAI LURES
The treatment of NPC with modem techniques of radiotherapy is very effective particularly in early (stages I and II) disease. However, for those with more advanced disease, the control rate is much worse. Thus, after primary treatment, the reported incidence of persistent/ recurrent local disease varies widely ( 1 5-48 percent)/7, 78 depending on the proportion of patients with advanced disease (stages III and IV) and the duration of follow-up after primary treatment. As there are subtle differences between local persistence and local recurrence in treat ment strategy, the two should be considered separately. Local persistence Figure 1 88.23 (a) The appeara nce of a nasop harynx a few years after radiotherapy as seen through a 0° rigid nasendoscope situated inside the left nostril. Note the prominent mucosal capillaries on the right side of the nasop harynx; there a re a lso patches of greenish mucopurulent crusts scattered on the left side of the nasopharynx. (b) The a ppearance of a recurrent nasopharyngeal carcinoma (arrow) two years after radiotherapy as seen through a 0° rigid nasendoscope situated inside the left nostril. There are d iffuse mucosal i rregularities over the whole nasopha rynx. Reference to the tumou r site before radiotherapy w i l l be the best guide for the site of biopsy.
Imaging (see above under Imaging) is often needed to evaluate regional disease as the post-irradiated neck may be fibrotic and difficult to examine. Annual chest radiographs in the first few years after treatment may pick up lung metastases. Otherwise, routine metastatic survey in asymptomatic patients is not warranted. [*] [Grade A]
Salvage treatment
Whereas primary treatment is relatively straightforward, salvage treatment is controversial. The best result can only
There is still no universally accepted definition of local persistent disease. It is well known that a positive biopsy at various time intervals after primary treatment has a different predictive value and that the residual tumour will become truly persistent and not regress.79 Thus, the timing of such a biopsy will affect the ultimate diagnosis of persistent disease. Persistent local disease confined to the nasopharynx can be treated with further radiotherapy or by nasopharyngectomy. The preferred option depends on the primary treatment the patient has received and the ' expertise and facilities available. A further dose of ERT may be possible if the normal tissue tolerance dose has not been exceeded during primary treatment. The trade off will be a greater chance of radiation-induced complications. Brachytherapy is preferred over standard ERT. The extra dose needed is delivered from within the nasopharynx at close range with less added morbidity. Different techniques of brachyther apy, such as transpalatal insertion of radioactive gold grains80 and intracavitary afterloading radiotherapy,81, 82 may be considered. To cover the gross tumour with a minimal margin, 1 0-30 Gy of radiation is needed. However, the effective dose of brachytherapy falls off rapidly, limiting its use to relatively small volume tumours (rT 1 , rT2a). Stereotactic radiotherapy, 83 instead of brachytherapy, should be used when the tumour is
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either too bulky or situated close to critical structures, such as the optic nerve. If the maximum radiation dose has already been given or the tumour is judged too bulky for further irradiation, salvage surgery may still be an option (see below under Surgery) .
Loca l recurrence Local recurrence less than one year after primary treatment is managed in the same way as persistent disease. Re-irradiation has been the commonest method employed to treat local recurrence. This can be given by external radiotherapy, brachytherapy or both. With special techniques such as 3D-conformal radiotherapy, re-irradiation is possible even when the recurrence is close to critical structures. A tumouricidal dose of no less than 60 Gy is recommended, 7 4, 84 and dose per fraction, again, should be no more than 2 Gy.84 However, the salvage rate for re-irradiation is unsatisfactory and the late morbidity rate is high.85 A high rT stage and a short disease-free interval predict a poor prognosis. Addition of chemother apy should be considered, especially for patients with a short disease-free interval after completion of the primary course.
Surg i ca l salvage for loca l disease Surgical salvage for residual/recurrent disease in the nasopharynx is a difficult task for many reasons. Adequate exposure of the nasopharynx and the para pharyngeal space is difficult through any approach. The procedure inevitably follows heavy doses of radiotherapy. Preoperatively, the tumour extent is difficult to define precisely either clinically or by imaging. Intraoperatively, tumour margins may be grossly indistinguishable from irradiated tissues and fro�en section may not be possible with bony margins. Wide en bloc resection is limited by the close proximity of the skull base and the carotid sheath and its content. Despite all these difficulties, in well-selected cases, salvage nasopharyngectomy has a low perioperative mortality rate, acceptable morbidity and can be curative. The best result is to be expected from those rT 1 and rT2 cases but without neck disease. Involvement of the skull base, cranial nerves, vertebral bodies and carotid sheath and its contents are absolute contraindications. Concurrent failures in the nasopharynx and neck constitute a relative contraindication since these patients are more likely to fail, not just locoregionally but also systemically.
SALVAGE FOR REGIONAL FAILURE
Surg ica l approaches to the nasopharynx
Radiotherapy with or without adjunctive chemotherapy is very effective in controlling primary neck disease. The local control can be further enhanced by a booster dose of a low-energy electron beam given to any residual disease upon completion of the primary course. However, any neck disease that remains, whether persistent or recur rent, thereafter should best be treated by surgical resection unless there is concurrent failure at other sites. Neck salvage by re-irradiation may be considered in selected patients who refuse or are unfit for surgery. The reported five-year local control rates with re-irradiation ranges from approximately 14 to 28 percent8 6 , 8 7
The centrally located position, surrounded by the facial skeleton and cervical vertebrae, abutted superiorly by the base of the skull and flanked by the great vessels and the lower cranial nerves, makes the nasopharynx relatively inaccessible. An approach that gives sufficient exposure for tumour resection and safe control of the great vessels and lower cranial nerves remains a challenge. The wide variety of different approaches to the nasopharynx described in surgical textbooks highlights the difficulties. The exposure obtained with each approach is different and the choice will depend on the tumour extent, surgical expertise and facilities available.
compared to nearly 40 to 50 percent reported for surgical salvage.88, 89
SURGERY
Surgery only plays a limited role in the overall manage ment of NPC. However, its role is complementary to the other modalities. Even when the other methods fail to control the disease, surgery for salvage can still be curative if the remaining disease involves the nasopharynx or the neck. However, careful case selection is the key to a successful outcome. It cannot be emphasized enough that all patients should be restaged beforehand with full metastatic work up to exclude lung, bone and liver metastases. For systemic metastases, PET and whole-body scan is probably the most sensitive single test. For delineation of local and regional disease, MRI is the method of choice and CT is the alternative. [**] [Grade C]
Anterior approaches Lateral rhinotomy This approach exposes the nasal fossa and choana well. It may be used alone or in conjunction with other approaches to enhance exposure and resection of an anteriorly situated tumour.
Transnasal transmaxillary When this approach is used for removing malignant tumours, a lateral rhinotomy or Weber-Fergusson inci sion is preferred. A medial or subtotal maxillectomy can be performed to give the exposure needed. The naso pharynx, the ipsilateral spheno-ethmoidal complex, pterygopalatine fossa and the medial end of the infra temporal fossa are all within reach.
,.r \
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Chapter 1 BB Nasopharyngeal carcinoma
I 2463
Midfacial degloving
This is essentially a bilateral transnasal, transmaxillary approach. The procedure is carried out through a sublabial incision leaving no visible scar. With both infra-orbital nerves safeguarded, the midface is degloved subperiosteally up to the root of the nose. Sufficient access to the nasopharynx is obtained with bilateral medial maxillectomy. The pterygopalatine fossa and the medial end of the infratemporal fossa on either side can be reached by extending the extent of the maxillectomy. The exposure to the parapharyngeal space is, however, limited. Le Fort
I
osteotomy
This approach involves a sublabial incision and transverse maxillary osteotomy through both maxillary sinuses allowing the whole hard palate and both inferior maxillae to be down-fractured. Access to the central skull base and nasopharynx is thus obtained. 90 No facial bones are resected and there are no visible facial scars, but the tumour exposed will be quite far from the surface. Maxillary swing
This is one of the most commonly used approaches that exposes the nasopharynx and the surrounding areas from the antero-lateral aspect. Through a Weber-Fergusson Longmire incision, the entire maxilla is separated from its bony foundations and swung laterally intact with the maSseter muscle and the cheek flap. 9 1, 92 Access to the opposite side is enhanced by removing the posterior part of the nasal septum. Sufficient exposure will then be obtained for dissection between both carotid arteries and allows a limited resection of the skull base. After tumour resection has been completed, the maxilla is swung back and fixed to the facial skeleton (Figure 1 88.24). I nferior approach Transpalatal
Access to the nasopharynx is gained by raising a palatal mucoperiosteal flap off the hard palate so that the soft palate is separated from its bony portion. The posterior edge of the bony palate is then removed as necessary. The greater palatine neurovascular pedicle needs to be mobilized bilaterally from its bony canal so that all soft tissues of the palate can be retracted downward during the tumour resection. Greater exposure is achieved by resecting the soft palate with at least half of the hard palate. The defect is closed using a dental prosthesis. Tumour extension outside the nasopharynx is difficult to deal with using this approach. Mandibular swing
This is essentially a trans cervical, transmandibular, trans palatal approach via a Frazier incision. Soft tissues including the skin, the masseter muscle and the parotid gland are elevated from the mandible. The middle portion of the ascending ramus including the coronoid process is
An intraoperative picture of a patient having a nasopharyngectomy through the maxillary swing a pproach.
Figure 1 BB.24
cut and removed to facilitate , exposure and to prevent postoperative trismus. The exposed lateral and medial pterygoid muscles are divided to enter the nasopharynx. Tumour involving the pterygomaxillary fossa, the para pharyngeal space anteromedial to the internal carotid artery and the soft palate including the tonsil can be resected en bloc. The dead space and mucosal defect after tumour resection needs to be repaired. A protective tracheostomy is necessary with this approach. latera l approach
Access to the nasopharynx and the adjacent areas is made through the infratemporal fossa. 93 This approach is limited by many critical structures including the facial nerve and the carotid sheath. It is used mainly when the tumour extends laterally to the parapharyngeal space. After nasopharyngectomy, irrespective of the approach, the contents of the carotid sheath and the parapharyn geal space are vulnerable to infection. It is advisable to cover the raw surface with healthy unirradiated skin or mucous membrane held in place by the balloon of a Foley catheter. The most convenient and most commonly used material is from the mucosal lining of the nasal turbinates. Different free flaps have also been described to resurface the raw areas and protect the carotid sheath and its content. Surgical salvage for neck disease
With modern radiotherapy techniques and the widely practised elective neck irradiation, isolated uncontrolled disease in the neck is uncommon.79 Patients with apparently isolated neck disease often have local and/or distant failure. 94 This may be simultaneous or sequential. Failures at more than one site are associated with a poor prognosis, therefore rigorous work up is necessary to select suitable patients for surgical salvage. However, definitive diagnosis of active neck disease is difficult even with FNAC, which has a sensitivity of approximately
" '\
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PART 17
H EAD AN D N ECK TU M O U RS
83 percene5 and the false negative rate may be as high as 39 percent.89 However, if a neck node persists in the absence of distant metastases, radical neck dissection should be performed, as the potential benefit is greater than harm. Radical neck dissection (RND) is considered necessary by most surgeons for adequate control. The different rationales for radical neck dissection include: ( 1 ) multiple nodes are frequendy involved; (2) these nodes are usually widely spread from level I to V; (3 ) the incidence of extra capsular spread outside the lymph nodes is high.9 6 When the overlying skin has to be excised due to tumour infiltration, the defect may be covered with a flap, such as a deltopectoral or pectoralis major myocutaneous flap. If it is judged that resection margins may be involved, interstitial brachytherapy catheters should be placed intraoperatively. Postoperative afterloading brachytherapy can then be applied for better disease contro1. 7 9, 97 If afterloading brachytherapy is judged not necessary based on final histological assessment, the catheters can be removed without harm to the patient. RND is well tolerated by patients with low perioperative morbidity and generally an overall neck control rate in the region of 60 percent is possible.89, 95 Overall, in approximately one third of the patients disease recurs in the neck after surgical salvage and this will usually be evident within 1 8 months. When it fails, there will normally be simultaneous failure (90 percent) at the primary and/or distant sites.95
Si m u lta neous loca l and reg ional fa i l u re There are as yet no reports that address this problem specifically. It is highly likely that these patients will eventually develop distant disease as well. Thus, any further radical attempts at treatment may turn out to be merely palliative. Combined therapy with salvage surgery including some form of postoperative radiotherapy and/or chemotherapy will be needed. However, the post-treatment morbidity may not be worthwhile. The patient's opinion should be respected in the final analysis. Studies on the quality of life of patients after radical salvage therapy are unfortunately still lacking.
Dissemi nated d i sease . It is doubtful whether patients who present with disseminated disease (stage IVC) would benefit from any form of treatment, as their average survival is only approximately six months. Symptomatic support with/ without palliative radiotherapy is often needed. Che motherapy can be considered for medically fit patients (especially if symptomatic and eager for treatment). The disease may, on rare occasions, run a protracted course and occasionally long survival can be achieved with chemotherapy.98 Those with isolated distant failure should be treated for palliation only. Exceptions are those with limited lung metastases without active disease elsewhere, where long-term survival in isolated cases has
been reported after aggressive combined surgery and chemotherapy.8l, 8 2,99
PRO G N OSIS
It is often difficult to compare results of treatment between centres as the staging systems used and treatment strategy, as well as implementation of the treatment plan are different. Nevertheless, in Hong Kong, the treatment results of NPC have improved significandy over the last two decades: the age-standardized mortality rate has steadily decreased from l 3 . 7 in 1 980-1 984 to 7.8 in 1 995-1 999 per 1 00,000 for men, and from 4.5 to 2.2 per 1 00,000 for women? Poor prognostk factors including old age, male gender, cranial nerve palsy, level and fixity of lymph nodes have been reported by Lee. lOO The average five-year survival achieved by conventional radiotherapy alone is excellent for early disease: approximately 80-90 percent for stage I and 70-80 percent for stage II. The average five-year survival achieved by conventional radiotherapy alone for locally advanced nondisseminated disease is approximately 40-60 percent for stage III, and 20-40 percent for stage IVA-B. For disseminated disease (stage IVC), the median survival is only six months. For all patients with nondisseminated disease, the overall control rate of 60 percent at five years can be expected.lOl Half of the failure group will also have distant metastases. Most of these metastases will occur in the first three years post treatment. [***/ ** 1
CO M PLI CATI O N S O F RAD I OTH E RAPY
Radical radiotherapy for NPC inevitably exposes normal tissue in the vicinity of the tumour to a damaging dose of radiation. Acute, subacute and late complications are well recognized and reported in the literature. A useful source of information on the subject can be obtained from the comprehensive review of Lee.102 As both major and minor salivary glands are well within the field of irradiation (Figure 188.25), xerostomia occurs in all patients and usually develops following the first few doses of irradiation. Symptoms of oropharyngeal mucositis (Figure 188.26), altered taste sensation, der matitis and alopecia of the irradiated area are also common early effects of radiation. These are usually very marked and happen in all patients. Apart from xerosto mia, fortunately, these early reactions will usually setde over weeks with supportive care. A significant proportion of patients will have life-long xerostomia (Figure 188.27) although the severity tends to decrease with time. Subacute complications, occurring in approximately 25-30 percent of patients, commonly affect the ear and nose. These complications may happen during or soon after radiotherapy, probably as a combined result of local radiation trauma and delayed wound healing
Ch a pter 1 88 Nasopha ryngeal carci noma .
2465
A pictu re of the mouth and oropharynx i l lustrating marked xerostomia many yea rs after radiothera py. Note the m ucosa is dry in general with telangiectasis of the mucosa of the soft palate.
Figure 1 88.27
Skin cha nges a few weeks after radiotherapy showing that both the major and minor sal ivary gla nds a re well within the fie ld of irradiation. Figure 1 88.2 5
with/without further complications such as infection. Otitis media with effusion (OME), acute otitis media and otitis extema are common complications especially the former. The treatment of OME should be conservative as current evidence shows that the use of a grommet during or soon after radiotherapy is associated with a high incidence of otorrhoea and otalgia. 1 03 Olfactory dysfunc tion, nasal crusting, rhinosinusitis and intranasal adhe sions are common complications. Olfactory dysfunction, usually transient, occurs in quite a number of patients towards the end of radiotherapy and slowly recovers over the next few months. Nasal crusting and symptoms of rhinosinusitis (thick nasal catarrh and foul smelling nasal discharge) are very common following radiotherapy. Regular saline nasal douching in the first few years after
g
A picture of the mouth and oropharynx showing marked mucositis in the early phase of radiothera py. Note the diffuse i nfla mmation and excoriation of the m ucosa. Fi ure 1 88.26
radiotherapy with courses of antibiotics may be needed for adequate control. Minor nasal adhesions between septal spurs and the nasal turbinates are quite common and need no treatment. Occasionally, marked scarring at or close to the choana (Figure 188.28) may occur, particularly in patients with more advanced local disease requiring a higher local dose of radiation through afterloading brachytherapy. Endoscopic surgery is extremely effective but should be delayed to at least six months after radiotherapy when the adhesion scar matures. Early attempts are frequently followed by reformation of adhesions. The latent interval of late complications can vary from several months to many years after irradiation. They happen when the irradiated tissues are irreversibly damaged. Tissues that have poor powers of regeneration,
Figure 1 88.28 Early intranasal adhesions after radiothera py as seen through a 0° rigid nasendoscope situated inside the right nostril. Note the ad hesions around the posterior ends of the middle and inferior turbinates and the nasa l septum. I
(
\
I
...
2466 I
PART 1 7 H EAD AND N ECK TUMOURS
such as sensory and neural tissues, are particularly prone to become affected. Apart from the total radiation dose, the dose-fractionation and timing of delivery will all affect the occurrence of late complications. 104 The reported average incidence of late complication is around 30 percent, 105 although this figure varies depending on the proportion of long-term survivors. The list of these complications is long. Trismus and neck stiffness may arise as a result of progressive soft tissue fibrosis. Osteoradionecrosis of the anterior and lateral skull base may lead to recalcitrant rhinosinusitis and otitis (Figure 1 88.29), and, in serious cases may result in ascending meningitis. Hypothalamic-pituitary dysfunction may result in a range of hormonal deficiencies requiring life long replacement therapy. The symptoms and signs of these hormonal dysfunctions are subtle and require a high index of suspicion for their diagnosis. One of the most difficult complications to be picked up is temporal lobe necrosis (Figure 1 88.30) as it may occur ten or more years after radiotherapy with subtle changes in personality and memory. The overt cases may present with epileptic attacks and in the more severe cases with symptoms and signs of raised intracranial pressure. Delayed cranial nerve palsies affecting one or more of the last four cranial nerves usually occur a few years after primary radiotherapy with progressive dysarthria and dysphagia. The hypoglossal nerve is the commonest one to be affected (Figure 1 88.3 1 ) . When patients present with delayed cranial nerve palsies, distinction from recurrence is necessary and serial MRI may be required. Radiation-induced malignancy typically presents after a long delay of ten years or more after completion of radiotherapy. The reported overall incidence is around 1 percent. 106 Osteosarcoma of the nose and sinuses and squamous cell carcinoma of the oral cavity, tongue and pharynx are amongst the most
common. The prognosis of these radiation-induced tumours is invariably poor. There are many more of these late complications, such as impairment of cognitive function, neurosensory deafness, etc. Overall, they are difficult to manage as they tend to be progressive with time. They are the main source of serious morbidity (7 percent) 1 05 and mortality (3 percent) 1 07 related to radiotherapy. Modern techniques of radiotherapy, in particular intensity modulated radiotherapy (IMRT), by evenly distributing the dose of irradiation to normal tissues,
Figure 1 88.30 Axial MRI showing temporal lobe necrosis with marked midline shift. This patient presented with symptoms and signs of raised intracranial pressure ten years after radiotherapy.
Figure 1 88.3 1
Otitis externa with osteoradionecrosis in the rig ht ear many years after radiation, as seen through a 0° rigid otoscope. Note the exposed bone that failed to heal years after radiothera py. This appears to be dose related, as it frequently occurs on the side on wh ich a booster radiation dose is given. Figure 1 88.29
A patient with u n i lateral right hypoglossal
nerve palsy developed after radiothera py. Note that the rig ht side of the tongue is atrophic and appears wrinkled as a result of fasciculation. The hypoglossal nerve is the commonest cranial nerve affected by radiotherapy and this typically occurs many years after radiotherapy.
/
Chapter 1 88 Nasopharyngeal carcinoma
has been shown to reduce acute reactions to radio therapy. 1 08, 1 09 However, their role in reducing late complications still awaits the test of time. OTH ER TREATMENT M O DALITI ES Photodynamic therapy
Experience with photodynamic therapy (PDT) (Figure 188.32) as a means of salvage for recurrent/residual NPC is limited to only a few large centres around the world. It is an attractive alternative to the standard forms of salvage treatment as it operates on a totally different principle and may still be effective when the other approaches fail. The tumouricidal effect of PDT is based on laser activation of a photosensitizer, which has been selectively taken up and retained by the tumour. The first generation of PDT worked on the combination of haematoporphyrin derivatives (HPD) and a laser light of 630 nm red light from a gold vapour or pumped-dye laser. Encouraging results were obtained in China 1 1 0 and Hong Kong. I I I The second generation combination of m-THPC sensitizer activated by 652 nm red light from a diode laser is more attractive as the treatment time required is much shorter ('"'-'2 minutes compared to '"'-'30 minutes). However, the experience with this second generation PDT in the treatment of NPC is still limited (see also Chapter 58, Laser principles in otolaryngology, head and neck surgery). [**/"] [Grade D] I m m unotherapy
Although the idea of developing an EBV vaccine that would prevent all EBV related diseases is sound and attractive, 1 I 2 it encounters enormous difficulties. Such a vaccine has to be administered to infants between 6 and 1 2 months of age when the passive immunity from the
I 2467
mother has worn off and before natural infection occurs A live attenuated whole virus vaccine is not suitable for .� virus that causes latent infection. However, for a subunit vaccine, it is difficult to decide on which subunit to use for a virus as complex as the EBY. To date, two broad approaches are currently being considered. These include either the use of EBV structural antigens or cytotoxic T lymphocyte (CTL) epitopes from latent EBV antigens as immunogens. The latter approach appears to be more promising for NPC. l l3 It is unlikely, however, that a single vaccine will be developed in the near future that is applicable to treat all EBV-associated diseases.
CONCLUSION
NPC is a disease of considerable interest and concern to both scientists and clinicians. Over the years, the amount of basic and clinical research into the disease is unparallelled by any other head and neck malignancy. With coordinated international efforts, controversies have been narrowed in certain aspects, such as histopathology and staging. In other respects, such as management, however, diversity of opinion still exists. In fact, the increasing possibilities of modern treatment modalities cause more controversy in treatment strategy than before. Although the overall treatment results have improved steadily over the last two decades, the morbidity associated with treatment is still substantial. As our knowledge of the complex and intriguing association of NPC with the EBV grows, more clinical tools for diagnosis and disease monitoring have become available.
KEY POI NTS
' Fig ure 1 88.32
A patient receiving photodynamic therapy for recurrent nasopharyngeal carcinoma. The procedure is conducted in a semi-dark room and fu l l eye protection is necessary.
I
,
---- -_ .
(
2468
• PART 1 7 H EAD AND N ECK TU MOURS
nti- VCA appears to be more sensitive, but less specific than IgA anti-EA. These antibodies ace extremely useful in screening high -risk populations for NPC. Promising results .have been obtained using this antibody as a marlcero in field surveys for screening NPC and monitoring progress after therapy. •
The pathogenesis o f NPC is far from clear. However, genetically determi ned susceptibility plays a fundamental role, and EBY is l ikely to be critical. The £BY genome and latent gene products are consistently found i n both differentiated and undifferentiated types of NPC. Within the tumour cells, the £BV DNA is homogenous and likely to be due to clonal cellular proliferation. However, EBY DNA has not yet been recovered from normal epithelial ceUs of the nasopharynx.
•
Epidemiological evidence shows that an environmental carcinogen has a definite role to play, but the exact mechani... m i nvolved is much more controversial. It may help to initiate or promote carcinogenesis by
� .�p ,bifeC:iioal � .m� " �' by �� jjl!.��Dll: � .t , f���t' irnmunity to t-.; "��!JiP," .but '; als() LifeijltOl1g virus
enhancing the entrance of the EBY genome into the n asopharyngeal epithelium and the subsequent expression of the virion. •
a
Nasopharyngeal carcinoma can present in many ways, but a mass i n the nasopharynx is
ties dormant i n
'S1nall [ '«l.pullati()R of
a fi nding in almost all patients. It is necessary to be familiar with the possible conditions that may produce a nasopharyngeal mass, for which the World H ealth Orga nization classification of tumours o f the nasopha rynx is a good reference. •
By the time patients present with symptoms, NPC typically appears as an eccen tric
'I�=::���
nasopharyngeal mass, being more bulky on one side. Morphologically, it may appear as a
(CMI)
lobulated mass of varying size with well
develops is
ill
�� :.iJ�Pi�:d1
iJ:1.LI1,""'Jj;,aJ it is still '
defined borders, or infiltrative with an indistinct border. The former type spreads
l; ��,�� (:; M I is the cause
earlier through lympha tics and is frequently accompanied by cervical lymphadenopathy. The latter is more likely to present with locally advanced disease with skull-base erosion. but without cervical lymphadenopathy. •
When the disease is detected at a very early stage. the whole tumour may still be hidden within the fossa of Rosen m iiUer. I n very rare cases, the tumour can be entirely submucosal without any observable mass in the nasopharynx.
•
In the past, NPC was referred to as malignant lymphoepithelioma because heavy
lymphocYt ic infiltration at the sites of the tumour was consta ntly found. With
/
...../
.".
/ J .
Cha pter 1 88 Nasopharyngeal ca rcinoma
improved immunohistochemical techniques,
very common clinical: finldilijfli "
the tumour cells have been confirmed to be
usually correlates WfltA
epithelial in origin, because they stain
n asopharynx that has mb�r� b1I1l1111 .1
positive for cytokeratin. The lymphocytes
The cause of Eustachian t utJe· (1fSll1D!�_
that infiltrate the tum
U�
..
Gfeai..
reacting to is no ,yet
{ 199 1 ) classification is
the most common. It divides nasopharyngeal
•
'a
IltSili!l �'I» :
after radiotherapy. •
Neurological complaints include headaches or
carcinoma into three histological subtypes on
cranial nerve symptoms. Headaches are a
the basis of the light microscopic appearance:
common complaint, occurring in almost
type I, squamous cen carcinoma
percent of patients, but they may be referred
(keratinizing);
•
Eustachian tube musculat u re. There is
chance of spontaneous resolution of effusio n
Various histological classi fications of NPC are in use, but the WHO
eft�· -«fira1'"
tumour or the tumour i nfiltrating th�
cells, but their role and- what they are •
'tM�� ii�WIJj
may be due to the mechanical
sites are reactive T
I 2469
type II, nonkeratinizing
20
pain when distal branches of the trigeminal
carcinoma; and type I II, undifferentiated
nerve are i nvaded by the tumour in the
carcinoma.
nasopharynx or nose. H owever, they can also
I n endemic a reas where NPC is closely
be the result of bony erosion of the skull
related to EBV infection, the tumours are
base. Cranial nerve symptom(s) may be
typically of the type II or I lJ variety. Stage for
isolated or multiple. In either case, it occurs
stage, patients with type II or I I I tumour
late in the disease from the spread of the
have a better prognosis than those with type
tumour through the fora mina of the base of
1 NPC as the latter is much less
the skull or with parapharyngeal i nvolvement
radiosensitive.
of the last fou r cranial nerves. Cranial nerves
The symptomatology of NPC varies
V and VI are the most commonly i nvolved.
depend ing on the stage of the d isease at
When cranial nerves I I I-VI are affected
presentation. An early tumour may cause no
together, cavernous sinus i nvolvement is the
symptoms whatsoever, and symptoms of early
cause. H orner's syndrome is rare, but i f
NPC are often nonspecific. Symptoms arise
present i s typically accompanied b y paresis o f
in relation to the size and position of the
o n e or more of the last cranial nerves.
tumour withi n the nasopharynx, the extent of di rect spread beyond the nasopharynx and the nature of distant metastasis. Complaints fall i nto groups, depending on the anatomical structures i nvolved. •
The most common complaint at presentation is the presence of upper neck swelli ng: uni lateral neck swelling is most common, but bilateral neck metastases are not infrequent. Cervical lymphadenopathy is the presenting complaint in almost
50 percent of patients. A
significant proportion of patients presenting
./' An adult with a nasopharyngeal mass is assu med to
have NPC, until proven otherwise. ./' A high i ndex of suspicion is necessary to detect early
disease. ./' Nasopharyngeal biopsy should be the first and ./
with other complaints also have cervical lymphadenopathy on examination. Overall,
75 percent of all patients have
palpable cervical lymphadenopathy at
./
diagnosis. •
Thirty percent of patients present with nasal symptoms, i ncluding blood-stained nasal d ischa rge, nasal obstruction, post-nasal drip or even frank epistaxis. For those presenting with nasal symptoms alone, the tumour may
./'
grow to a large size before the diagnosis of NPC is made. •
Approxi mately
20 percent of patients present
with aural symptoms, i ncluding dea fness, tinnitus and otalgia. A retracted tympanic membrane or otitis media with effusion is a
./
defi nitive investigation to establ ish the diagnosis. Radical radiothera py is a highly effective treatment for early (UICC stage I and II) disease w h i le concu rrent chemoradiation thera py is recom mended for advanced (UICC stage I I I and IV) disease. With the current more agg ressive treatment approach, the overa l l survival has sign ificantly i mproved ; however, treatment-related morbidities have correspondingly i ncreased. There is early evidence that i ntensity-modu lated radiation therapy (l M RD reduces radiation-induced morbidity. Close monitoring is necessary as most recurrences occur within the fi rst three years. Consideration for salvage surgery should be individualized balancing the risks and benefits for each patient. Systemic disease should be excluded before considering salvage surgery.
i
L
2470 I
PART 17
H EAD A N D N ECK TU M O U RS
Defi c i e n ci e s i n cu rre nt know l e d g e a n d a re a s fo r fu tu re resea rch If b rea kth rou g h in the fo l l owi n g aspects ca n be achieved in the n ext five yea rs, it w i l l be adva ntageous both fo r patie nts a n d c l i n icia ns. > Pathogenesis: The closer we a re with the exact i nterp l ay of g e n etics, EBV i nfection a n d envi ron ment ca rc i n ogens on pathogenesis of N PC the closer we wi II be to ta rgeted thera py. > Massive scree n i n g prog ra m m e : Early d i a g nosis i n e n d e m i c a reas ca n o n ly be poss i b l e with a massive scree n i n g prog ra m me. However, the biolog i ca l behavi o u r (ra pid prog ression a n d re latively asy m ptomatic ea rly d i sease) of the t u m o u r ma kes it d ifficult to ru n a cost-effective scree n i n g prog ra m m e at present.
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Chapter 1 88 Nasoph a ryngeal carci noma
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H EAD AN D N ECK TU M O U RS
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1 09.
1 1 0.
1 1 1 . Tong CF, van H asse lt CA, Woo J KS. Pre l i m i n a ry resu lts of photody n a m i c thera py for recurrent naso p h a ryngea l ca rci n o m a . European Archives of Otorhinolaryngology. 1 99 6 ; 2 53 : 1 89-92. 1 1 2. Epste i n MA. I m pl ications of a vacc i n e for the p revention of Epste i n - Ba rr v i ru s infection : eth ica l a n d log istic consid erations. Cancer Research. 1 97 6 ; 3 6 : 71 1 -4. 1 1 3. D u ra iswa my J, Sherritt M , Thomson S, Te l l a m J, Coo per L, Co n n o l ly G et al. Thera peutic LM P 1 polyepitope vacc i n e for EBV-associated Hodg kin's d i sease a n d naso p h a ryngeal ca rcinoma. Blood. 2003 ; 1 0 1 : 3 1 50-6.
189 Ben ign salivary gland tu mou rs MICHAEL GLEESON AND RODERICK CAWSONt
Introduction Epidemiology and distribution Aetiology Presentation Assessment
2475 2475 2476 2476 2478
Histopathology and natural history of common benign tumours
Treatment Key points Best clinical practice
2483 2490 2491
Deficiencies in current knowledge and areas for future research References
2491 2491
2480
The data in this chapter are supported by a Medline search of publications that focused on the pathology, aetiology and management of benign salivary gland tumours.
INTRODUCTION For a number of reasons, benign salivary gland tumours pose special problems for both the surgeon and their patient. First, at the outset, there is little to distinguish a benign tumour from its malignant counterpart. The diagnosis is often only made after resection and at that stage the surgeon may wish that a more extensive procedure had been undertaken. Second, preoperative tissue diagnosis by fine needle aspiration cytology can be difficult and often inconclusive. Open biopsy at any site other than the palate is contraindicated lest seeding should develop subsequently. Third, the anatomical relationship of the tumour to the facial nerve in the parotid gland is nearly always intimate and the potential for a significant cosmetic handicap makes surgery at best challenging and certainly extremely worrying for the patient. Fourth, some patients are referred following an open biopsy, enucleation, attempted parotidectomy or with frank and extensive recurrent disease. These patients are likely to develop a facial nerve deficit at the least and all are at risk of developing a recurrence later. Malignant transformation of some recurrent benign tumours is well recognized and
almost impossible to cure. In this chapter, these issues are addressed and guidelines for the management of benign salivary gland tumours are established.
EPIDEMIOLOGY AND DISTRIBUTION Salivary gland tumours are relatively uncommon. Fewer than 3 percent of all neoplasms arise in the salivary glands. At least 75 percent of these tumours are benign. There are no accurate data on the incidence of these benign tumours but estimates of three to four per 100,000 population can be deduced from the registration of malignant salivary gland disease. For most tumour types there is a slight female preponderance. All age groups are affected from birth to old age. However, as pleomorphic adenomas predominate overall, the most common age for the presentation of a benign salivary gland tumour is in the fourth decade of life. By far the majority of tumours develop in the parotid gland but a substantial number arise in the submandibular salivary gland and minor glands of the palate and pharynx (Table 189.1).
,L
iiixH
2476
I PART 17 HEAD AND NECK TUMOURS
Table 189.1
Frequency of epithelial salivary gland tumours and
Absolute No. Parotid
Frequency (%)
1756
72.9
257
10.7
7
0.3
336
14.0
54
2.2
Submandibular Sublingual Minor glands Unknown
Malignant (%)
~80% 10 <1 10
14.7 37.0 85.7 46.4
~20% 40 80 >50
0.0
would appear to be a latent period of 15-25 years after exposure before development of the tumour.
Reproduced from Eveson.
increased susceptibility was shared by both the parotid and submandibular glands. It is also established that survivors of childhood malignancies who have been treated with a combination of radiation and chemotherapy have an incidence
JW. a Cawson, RA. 1985. British Salivary Gland
of
second
primaries.
The
most
soft tissue, skin, breast and thyroid tumours. There have also been reports of salivary gland tumours in this cohort of patients. While
Frequency of primary I!pithelial salivary gland
tumours by site. Tumour type
In a later
common second malignancies are acute leukaemia, bone,
Tumour Panel Data, with permission.
Table 189.2
I. 2
study of the same population it was established that this
increased
2410
Total
hypocentre of the explosion and in those returning early to the city. As with similarly induced thyroid neoplasms there
malignancy analyzed by site.
the majority of these have been
malignant, pleomorphic adenomas have also been re corded? [****] An increased incidence of second primary tumours has
Parotid
Submandibular
Sublingual Minor
also been documented in patients with thyroid cancer treated by radioiodine (1131).4 Bone, soft tissue, colorectal and salivary gland malignancies are the most common.
63.3
59.5
0
42.9
14.0
0.8
0
0
In recent years, extreme public concern has focussed on
Oxyphilic adenoma
0.9
0.4
0
0
the use of mobile telephones and the development of
Other
7.1
1.9
14.2
11.0
Pleomorphic
[****]
adenoma Adenolymphoma
Total no of cases 1756 Reproduced from Eveson,
regional malignancies. There has always been controversy about the long-term effects of high frequency electro
monomorphics
257
7
336
JW. a Cawson, RA 1985. British Salivary Gland
Tumour Panel Data, with permission.
Pleomorphic adenoma is the commonest tumour found at any site and outnumbers all the other tumours in the major glands (Table 189.2). Within the parotid gland the majority of tumours develop in the superficial lobe, in other words, lateral to the facial nerve. In this part of the gland they usually arise in the posterior aspect where they
fill the retromandibular fossa and can be relatively inconspicuous. Less often they are found in the preauri cular region or further forward where they are far more obvious from a much earlier stage. The other major glands, submandibular and sublinguaL are relatively small and, by the time a tumour is detected and removed, much of the normal gland will have been replaced or displaced by it making the site of origin almost impossible to determine.
magnetic
fields
and this latest
debate
has
been
no
exception. All studies suffer from methodological deficien cies that include too short duration of mobile phone usage and incomplete data on exposure. It has been suggested that there is a relatively increased risk for brain tumours and uveal melanoma but, to date, an increased risk of salivary gland tumours has not been reported.5,6 The molecular events that are associated with the development
of
salivary
gland
tumours
are
largely
unknown but inroads are being made by microarray analysis and other techniques to identify and implicate genes and their products. In this way, a small set of genes has been identified that is differentially altered between normal salivary gland tissue and the common benign and malignant neoplasms. Apart from adenoid cystic carcino ma, patterns of gene expression overlap between tumour types.?' 8, 9 In pleomorphic adenomas, the gene PLAGI (pleomorphic adenoma gene 1) is activated by chromoso mal translocations at 8q12. This gene rearrangement has been
detected
in
both
epithelial,
myoepithelial
and
mesenchymal-type cells that are found in this tumour.
AETIOLOGY
This finding supports the pluripotent single-cell theory
There has been much evidence to suggest that radiation
pithelial cells evolve into the varied somatic cell phenotypes . 10 present ill t hese tumours.
which postulates that tumour-initiated, modified myoe induces salivary gland tumours. This was initially estab lished in epidemiological studies of those who survived the atomic bombs dropped in Japan during the Second World War. In this cohort of patients, the incidence of benign and
PRESENTATION
than that of a comparable nonexposed population, while
Most parotid and submandibular gland tumours develop ' in an insidious fashion, growing slowly over a long period
malignant salivary gland tumours was 2.6 times higher that of malignant tumours was ten times greater. This risk of salivary malignancy was higher in those closest to the
of time without causing any other symptom whatsoever.
/
Chapter
189 Benign salivary gland
tumours I 2477
A very small number cause discomfort by obstructing
salivary
flow.
Pain is extremely uncommon and,
if
present, usually heralds malignant change. Likewise, facial weakness or palsy is virtually never seen unless malignant change has supervened. Growth of these tumours is so slow that patients often wait many months or years before seeking attention. T he patient with a parotid tumour eventually becomes aware of a firm mass that is steadily getting bigger behind the angle of their jaw in the retromandibular region, in front of the tragus or in the cheek
(Figure 189.1). Deep
lobe parotid tumours and those arising from minor oropharyngeal glands displace the medially
and
are
often
tonsil and palate
impalpable
from
outside.
Very large parapharyngeal salivary tumours affect the quality of the patient's voice and may interfere with Eustachian tube function, for example during air flights
(Figure 189.2). Tumours arising in the submandibular gland present as swellings in the submandibular triangle which can be localized more accurately by bimanual palpation of the floor of the mouth
(Figure 189.3). It is sometimes
difficult to differentiate a tumour arising in the posterior aspect of the submandibular gland from one that is in the tail of the parotid gland. An ultrasound scan is a simple and quick method of making this distinction when doubt persists. Benign tumours in the minor salivary glands of the . oral
and
pharyngeal
mucosa
present
as
firm
submucosal swellings. Ulceration is rarely if ever seen
Figure
189.2
(a)
MRI of a very large deep lobe parotid
tumour that had caused Eustachian tube dysfunction, altered the quality of voice and resulted in obstructive sleep apnoea;
(b)
typical intraoral appearance of a deep lobe tumour with
medial displacement of the right tonsil.
Figure Figure
i 89.1
Typical presentation of a pleomorphic adenoma
of the parotid gland, a retromandibular swelling.
----�,�--
\
189.3
A very large pleomorphic adenoma of the
submandibular gland presenting as a swelling in the submandibular triangle.
.
__ ______
I
-;-_�_._..L�....� .;..
2478 I PART 17
HEAD AND NECK TUMOURS
unless there has been local trauma and, in the absence of that, an aggressive malignancy should be suspected (Figure 189.4). Recurrent tumours are often multiple and it is very easy to underestimate the precise extent of this disease. Often the tissues in the area are scarred and difficult to palpate accurately and pinpoint small foci of tumoUT. After all, a number of recurrences arise as a result of previous peroperative rupture of the tumour and seedlings may have been spread over a wide area (Figure 189.5). ASSESSMENT Imaging Detailed imaging of all salivary gland tumours is neither cost-effective nor necessary. In the majority, a thorough clinical examination y ields adequate surgical information to permit safe removal once consent has been obtained. However, for some patients imaging is necessary. The advantages of ultrasound in the investigation of salivary gland tumours are frequently extolled by
praised
Figure 189.4
Unilateral swelling of the left side of the palate,
typical of a minor salivary gland tumour.
radiologists. There is little doubt that it can be useful to confirm a clinical suspicion. However, there are very few surgeons who can operate confidently on the basis of an ultrasound scan alone. He or she will feel happier with a more visual representation of the intricate local anatomy that can only be acquired by either computed tomography (CT) or magnetic resonance imaging (MRl). There are also areas of the salivary glands that may be obscured by bone from ultrasonic assessment and it is precisely in these cases that the surgeon will want a complete picture. Similarly, positron emission tomography has little to add in the assessment of salivary gland tumours. Uptake of isotope gives little indication of malignant status and does not alter patient management. There is no doubt that the superior soft tissue definition achieved with MRl makes this the preferred imaging modality. CT is not so good in this respect and can be rendered almost unusable by dental artefact obscuring vital detail. Nevertheless, in those situations where MRI is not available, CT is still a very good substitute. There are clear indications for CT or MRI which can be summarized as shown in Table 189.3. Several studies have assessed the reliability of both CT 11 and MRl in the detection of malignant salivary disease. Neither is, nor can be expected to be, completely reliable although reasonable specificity rates are claimed for both. However, it is not for this purpose that imaging is generally required but rather for detecting suspected lesions within the salivary glands and providing surgically useful images of the extent of disease. Sensitivity rates approaching 100 percent are claimed for both modalities and image quality is influenced mainly by the generation of scanner or image protocol adopted. The majority of tumours within the major glands examined by CT give higher attenuation values than Table 189.3
Indications for CT or MR imaging.
Major glands Masses confi ned to the deep
Minor glands Tumours of the palate with suspected involvement of
lobe of the parotid gland
the nose or maxillary antra Tumours with involvement of
Any tumour with clinically ill-defined margins
both the deep and superficial lobes of the parotid gland (dumb-bell tumours) Parotid tumours presenting with facial weakness, other neural deficit or indication of malignancy Congenital parotid masses Submandibular gland tumours
Figure 189.5
MRI of multiple recurrences of pleomorphic
adenoma in the left parotid bed. The patient had previously had an enucleation and the tumour had ruptured.
with neural deficit or fixation to the mandible Recurrent disease
/
J
Chapter 189 Benign salivary gland tumours. 2479
surrounding normal glandular tissue. The resolution of soft tissue attenuation in thin slices achieved by modern generation scanners is exceptional, improved by intravenous contrast and is perfectly adequate for the examination of salivary glands (Figure 189.6). There is no longer the need for CT sialography, which was advocated at a time when scanning resolution was considerably inferior. As stated above, it is unfortunate that disruptive artefacts may be introduced by extensive dental restorations which can significantly detract from the. image quality. Occasionally, CT scanning will show calcifications in a salivary gland tumour and this strongly suggests that it is a pleomorphic adenoma. They are unlikely to be seen in conventional radiographs. MRI has proven to be equally sensitive in the detection of salivary neoplasms. Within the major glands they give low signal intensity with Tl-weighted protocols and relatively high signal intensity with T2 and balanced protocols. Although both Tl and T2 images show the margins of the lesion with equal clarity, the tumour composition is better defined with T2 sequences and the detection of subtle areas of disease by STIR sequences. 12 The use of gadolinium improves definition significantly (Figure 189.7). The quality of MRI is not influenced by the state of the patient's dentition. Occasionally also, MRI may will indicate whether a parapharyngeal tumour has originated in the parotid gland or from one of the minor phar:yngeal glands, but this distinction can rarely be reliably demonstrated. In clinical terms, therefore, there is essentially little to choose between CT and MRI for the diagnosis of salivary gland disease. The final decision will therefore be mainly influenced by the local availability of scanners, cost and personal preference.
Fine needle aspiration cytology Fine needle aspiration cytology offers at least the possibility of preoperative diagnosis of parotid tumours without the risk, associated with open biopsy, of seeding tumour cells in the incision. Its limitation, which is even greater than for frozen sections, is that of missing a critical area within or at the border of the tumour mass and thus failing to obtain a truly representative sample. Using fine needle aspiration, a small area of malignant change in a pleomorphic adenoma could easily be missed and it would not, for example, be possible to differentiate follicular from diffuse lymphomas. Aspirates of non-neoplastic lymphocytes could come from a variety of lymphocyte-rich lesions such as Warthin's tumour, tuberculosis, benign or HIV-associated lymphoepitheliallesions. Apart from special problems such as these it should be possible to differentiate malignant from benign salivary gland tumours with 80--90 percent accuracy (Figures 189.8 and 189.9).13,14 Accuracy of diagnosis may be improved by application of immunocytochemistry, but electron
Figure 189.6 (a) CT scan of a Warth in's tumour in the left parotid gland and (b) a whole mounted section of the operative specimen. Both have been cut in the same plane and this demonstrates the correlation and accuracy of the margins very clearly.
microscopy of the aspirated material is of no value for _ rapid diagnosis. [***] A more important consideration is whether fine needle biopsy is as safe as has been believed. Increasing
I
/
\ l
L
~:il';.·
2480
I PART' 7 HEAD AND NECK TUMOURS
Figure'89.8
Fine needle aspiration biopsy of a pleomorphic
adenoma (Papanicolaou stain). Glandular epithelium and faintly fibrillary myxoid tissue are seen.
•
. . /
·
•
• • . .
•
,
•
. •
..
I .
•
. . . �
·
·
• •
•
Figure'89.9
Fine needle aspiration biopsy of a Warthin's
tumour (Papanicolaou stain). The boundaries of the cytoplasm of the oncocytic epithelial cells are sharply defined. Their nuclei
Figure'89.7
(a)
Axial and
(b)
coronal MR scans of a deep
lobe tumour that has a cystic and potentially fragile upper pole
are large and have a single prominent nucleolus. Scattered lymphocytes surround the epithelium.
that could be easily ruptured on removal. In contrast, the lower
glands, there is a greater female predominance
pole is relatively solid.
(1. 7: 1) and [****J
the peak age of incidence is in the sixth decade. experience with other tumours suggests that seeding of tumour cells along the needle track is a real rather than a theoretical possibility. This has not as yet been shown in the case of salivary gland tumours, but the slow growth of pleomorphic adenomas in particular may mean that in due course such recurrences may yet be reported.
Eighty percent of parotid pleomorphic adenomas are within the superficial lobe and 20 percent arise either within the deep lobe or involve it by direct growth. These tumours frequently attain a large size and historical pictures portray tumours of gargantuan size 189.10).
Rarely,
a
pleomorphic
adenoma
(Figure
forms
in
accessory parotid tissue along the line of the duct and then may only be visible when the mouth is opened and
HISTOPATHOLOGY AND NATURAL HISTORY OF COMMON BENIGN TUMOURS
the tumour is pushed outward by the forward movement of the coronoid process of the mandible. As to other salivary glands,
11 percent of all pleomorphic adenomas
are found in the submandibular glands and a similar
Pleomorphic adenoma
proportion is found in minor salivary glands. In the minor glands, the majority of pleomorphic adenomas are
The mean age at presentation of patients with pleo
found in the palate, the next most common sites are the
morphic adenomas in the parotid gland is
46 years but
lips and the sheeks. They are also occasionally found at
they can develop at any time of life. Overall, there is a
other sites such as the tongue, retromolar fossa, pharynx
slight female predominance
or tonsil. By contrast, these tumours are exceedingly rare
(1.4:1). In the submandibular
I
/
.' ,\ ,
Chapter 189 Benign salivary gland tumours I
Figure 189.11
2481
This operative specimen demonstrates the
intraoral appearance of a palatal pleomorphic adenoma covered by mucosa as well as the typical bosselated surface of the tumour.
prognostic or behavioural features. To this end, attention has been turned to the various elements of the tumour, Figure 189.10
In former times it was not unusual to see
patients with massive pleomorphic adenomas. This example is
for example, the capsule - whether it is complete or incomplete, the nature of the stroma, the epithelial cells
taken from the Lam Qua collection in the Gordon Museum at
and their configurations and the myoepithelial cells..
Guy's Hospital. This man's tumour had been growing for 17
Although no relationship with behaviour has been found,
years. It measured 2 ft in circumference and weighed 71b. A
it is worth considering these features briefly as some have
hole had been made in it by a traditional Chinese doctor using
practical significance.
escharotics.
in the sublingual glands, but occasionally found at sites in the airways that extend from the nasal cavity to the bronchi, the middle ear and external auditory meatus and in the lacrimal glands. The clinical features of pleomorphic adenomas in the other major or minor salivary glands do not differ significan tly
from
those
in
the
parotids.
However,
pleomorphic adenomas within the mouth may have a readily palpable, bosselated surface and bluish areas may be discernable through the mucosa
(Figure 189.11). In
addition, these tumours, like any others in the mouth and
THE CAPSULE
The capsule of pleomorphic adenomas may be thick and fibrous or absent in some part. Serial sectioning of excision specimens shows that focal infiltration of the capsule is common 15 and that subcapsular clefts just within the tumour borders provided false planes of cleavage should enucleation be undertaken. The degree of encapsulation and the ability of these tumours to extend through the capsule have practical implications and have become controversial with the revival of extracapsular dissection as a method of treatment by some surgeons.
particularly those in the palate, can become ulcerated by friction or trauma. The firmness of these tumours varies with the nature and amount of the stromal component
THE STROMA
and thus ranges from soft, in the case of the more
The myxoid stroma of pleomorphic adenomas is one of
mucinous tumours, to hard in the case of tumours with
its most characteristic features. It can form the major part
an extensive chondroid or collagenous component.
of the tumour and can bulge into the normal gland
Occasionally, pleomorphic adenomas are associated
parenchyma without any capsule intervening. The almost
with another salivary gland tumour, though less fre
mucoid nature of many pleomorphic adenomas makes
quently than Warthin's tumours. The other tumour may
them extremely fragile so that they can burst very easily at
be synchronous or metachronous, in the same gland or
operation, even with the most delicate handling, unless
on the opposite side.
protected by an envelope of normal glandular tissue.
Attempts have been made to categorize these tumours on the basis of histological features in an effort to infer
.\
Rupture of the tumour inevitably seeds the operative field and can result in later recurrence.
-C-. ____ ___ .
/_/ --.",.... : ..
--,_ _ ......
___ ._
2482
I PART 17 HEAD AND NECK TUMOURS
The cartilage of pleomorphic adenomas, though often termed 'pseudo-cartilage', does not appear distinguishable in any way from true cartilage. Very occasionally it is the major component with the result that the whole tumour is very firm. The cartilage may rarely even contain true bone with fatty marrow spaces. Calcifications or bone formation are unlikely to develop in any other salivary gland tumour and may be seen clearly in scans. Their presence in a salivary gland or a parapharyngeal mass strongly suggests that the tumour is a pleomorphic adenoma. Elastic tissue can be found in greater or lesser amounts in most pleomorphic adenomas. Progressive elastosis and fibrosis can, after many years, cause the tumour to become sclerotic. This may be dismissed as mere scarring, but malignant change may be associated and examination of such tumours should be particularly thorough despite their superficially bland appearance.
Figure 189.12
Multiple seedlings are present scattered
throughout the operative field.
forms a fixed bulky conglomerate, removal of which sometimes requires resection of the facial nerve. Finally,
THE CELLS
It is widely accepted that pleomorphic adenomas are derived from intercalated duct and myoepithelial cells which clifferentiate into epithelial and connective tissue structures. The epithelial cells may be columnar, cuboidal, squamous or flattened and in sheets of greater or lesser extent but interspersed by stromal elements. Squamous metaplasia with keratinization is common and does not imply malignant change. There are no certain cellular indicators of the like lihood of malignant change. Mitoses are an occasional feature of benign tumours. High cellularity with mitotic activity, particularly if associated with increased vascu larity and areas of necrosis, are suggestive of carcinoma
the incidence of malignant change is greater in recurrent 7, 8 tumours.16, 1 1 Another problem is that of deep lobe parotid tumours and the possibility that they may have arisen in minor pharyngeal glands. W hole organ sectioning of paroti dectomy specimens has shown that extensions of a pleomorphic adenoma may only be joined to the rest of the tumour by a thin neck. It is unwise therefore to assume that a deep lobe tumour is anything other than a parotid gland tumour and to therefore attempt to remove it by a transpharyngeal approach. However, MRI may sometimes make it possible to distinguish minor para pharyngeal gland tumours from extensions of parotid gland tumours.
tous change and justify more extensive sampling of the material. A greater diagnostic clifficulty is that of areas of atypia within the substance of the tumour (intracapsular
Warthin's tumour
carcinoma). Although such changes may presage the development of frank carcinoma at some later stage, if
This tumour is also known and referred to as either
neglected, they do not seem to justify any further
adenolymphoma or papillary cystadenoma lymphomato
interference if parotidectomy has been carried out, since
sum. The latter terms are either inaccurate or clumsy and
they do not extend outside the tumour margins. Follow
tend not to be used. Warthin's tumour is the most
up, however, must be rigorous.
common monomorphic adenoma. It accounts for 14
As a result of poor encapsulation and a tendency to
percent of all salivary gland neoplasms and is the second
rupture during resection, enucleation has frequently
most common tumour. The frequency may be even higher
the recurrence of these tumours are of great practical
nodules in scans of the parotid gland, the only gland in
resulted in subsequent recurrence. Several points about
importance. First, it may take more than a decade for them to become apparent; perhaps as much as 20 years may elapse after the primary surgery before diagnosis. Claims of cures based on disease-free periods of up to ten years may therefore be misleading. Second, recurrences
as suggested by the finding of multiple asymptomatic which it develops. Those tumours that are reported at other sites may well have been misdiagnoses. [****J The peak incidence of Warthin's tumours is in the seventh decade but they have been known to develop much earlier in adult life too. Formerly, it was thought
are typically multiple, frequently in the incision scar and
that these tumours predominantly developed in men,
of recurrent tumour nodules clearly makes their manage
suggest that this was either a misconception or that the
often widely separated from each other. This multiplicity ment very difficult. Minute nodules can be hard to detect at reoperation
and further recurrences often follow
(Figure 189.12). In some cases the recurrent tumour
series quoted a 10:1 incidence ratio. More recent series sex distribution is becoming more equal with a male: female ratio of just 1.5:1. Warthin's tumours appear to be
uncommon in black people.19
/
J
Chapter 189 Benign salivary gland tumours
It is suggested that Warthin's tumours develop as a
result of neoplastic proliferation of ectopic salivary gland
ducts within intra- or paraparotid lymph nodes. The abse,llce of lymphoid tissue from other salivary glands
explains· the development of these tumours only in the parotids. Warthin's tumour consists of a characteristic,
eosinophilic,
gl':mdular
epithelial
component
and
a
stroma of lymphocytes which may form follicles and
cysts. Despite gross circumscription, there is only a thin
capsule which is incomplete in most cases or even absent in a minority. This feature makes this tumour susceptible to rupture during removal. Small foci of incipient tumour
formation may also be found in the surrounding parotid
tissue. Such multiple foci almost certainly account for the
rare recurrences that have been reported.
These tumours typically grow slowly to form soft,
and the elderly can be affected. There is no
I 2483
apparent can be
predominance in either sex and all salivary glands affected.
[****]
Oncocytoma (oxyphilic adenoma) Oncocytomas are rare tumours. They are predominantly tumours of those over middle age. Women, usually in the
seventh or eighth decade, are more likely to be affected. The parotid glands are by far the most frequent site. These
tumours are slow growing and may rarely be bilateral.
Oncocytomas are benign and excision is curative. There
have been occasional reports of recurrences and this is likely to be due to other nodules of tumour tissue in the
gland.21
[****]
painless swellings, usually at the lower pole of the parotid gland. A few may undergo rapid expansion possibly
caused by cystic change. Pain, sometimes severe and
radiating to the ear, may be experienced by a few,
particularly in those where the tumour becomes infarcted. The combination of pain and sudden increase in size of the mass may be mistaken for malignant change. The
TREATMENT Parotid gland Removal of the tLUnour within an appropriate part of the
diagnosis of Warthin's tumour is unlikely to be made
superficial lobe of the parotid gland (superficial paroti
consistency.
tumours.22 Those arising within or involving the deep
clinically, unless it is suggested by rapid changes in size or If the
mass
appears
of
Warthin's
to
be
cystic
and
dectomy)
is
adequate
treatment
for
the
majority
of
aspiration is carried out, a yield of brownish fluid is
lobe demand a total conservative parotidectomy in which ' all, or as much as possible, parotid tissue is removed
however, these tumours are treated like pleomorphic
leaving the facial nerve intact. Total parotidectomy, removal
Warthin's tumours are also more frequently asso
inevitable when treating recurrent tumours. Enucleation or
strongly
suggestive
a
tumour.
Usually,
adenomas and the diagnosis is made postoperatively.
of the entire parotid gland and facial nerve is sometimes
ciated with a second tumour than any other and the
extracapsular dissection is acceptable in those rare situa
tumour and a pleomorphic adenoma. The tumours can
the parotid gland, but not otherwise. Poor general health is
most frequent combination appears to be a Warthin's
tions when the tumour is hanging off the inferior pole of
be synchronous, metachronous, in the same gland or on
the only valid contraindication to surgery on this gland.
opposite tumours
sides.
has
Carcinomatous
only
exceedingly
change
rarely
in
been
Warthin's
reported
and may, in some cases, be secondary to irradiation. Onder et al.20 have reported a case of poorly differen
tiated
adenocarcinoma
in
a Warthin's
tumour
with
severe dysplasia of the oncocytic cells in other areas.
They have also summarized the features of 14 previous
INFORMED CONSENT
Prior to superficial or total conservative parotidectomy
the patient should be warned about the following serious or frequent complications.
reports in the English literature. These show that the
Facial weakness
carcinomas can be adenocarcinomas, squamous cell or
The risk Of temporary or permanent facial weakness must
undifferentiated.
be carefully explained as it has a very significant impact on quality of life. The risk of facial nerve damage is related to
the extent of the disease, the type of resection and the
Myoepithel ioma Myoepithelial
cells
experience of the surgeon. Neuropraxia usually recovers
are
a
prominent
component
of
within four to six weeks. More severe injuries cause some degree of degeneration and recovery may never be complete
pleomorphic adenomas. Tumours derived solely from
and take 6-12 months or even longer to take place.
sidered to be variants of pleomorphic adenoma that are
Facial anaesthesia
myoepithelial cells are rare. Myoepitheliomas are con
characterized by overwhelming myoepithelial prolifera
Anaesthesia in the distribution of the greater auricular
tumour has no distinctive clinical characteristics. The
thirds of the pinna, is unavoidable. Most patients learn to
tion. A carcinomatous variant is also recognized. This
average age at presentation is 40 years but both children
nerve, over the angle of the mandible and inferior two
accept this deficit and few are severely troubled by it.
/
2484
I PART 17 HEAD AND NECK TUMOURS
Cosmetic defects The cosmetic appearance of the incision rarely causes concern. Loss of bulk behind the ramus of the mandible may result in a mildly unsightly dent in the normal outline of the jaw.
Frey's syndrome Gustatory sweating or flushing (Frey's syndrome) is a socially
embarrassing
complication
of
parotidectomy
(Figure 189.l3). It develops in nearly all patients following surgery to some degree. The frequency of this complication is sufficient to warrant preoperative ex planation together with the reassurance that it is rarely significantly
disconcerting
and
usually
amenable
to
simple preventive measures such as the application of an anti-perspirant or botulinum toxin.23
local,
subdermal injections
of
[*)
Salivary fistula In some patients saliva continues to be produced by the parotid remnant and either collects in the parotid bed or leaks out through the wound. This can be extremely distressing and makes the patient fear eating. For the most part, salivary fistulas close spontaneously and settle down over a period of days to weeks. Quite why salivary fistulas are not more common is not known. It could be speculated
that
those
with
a
significant
volume
of
residual gland, perhaps with an extensive cut surface and
a ligated
complication.
duct This
would has
be
more
certainly
prone
been. the
to
the
author's
experience with those patients referred to him with persistent
fistulae.
Revision
surgery
to
reduce
or
eliminate any residual glandular tissue is a last resort that is not without complications. The interposition of a pedicled muscle flap derived from the sternomastoid muscle has also been used to effect.
[*)
OPERATIVE PROCEDURE
The fundamental principle of parotidectomy is exposure of the facial nerve and then removal of the gland and diseased tissue from around it. The surgeon should be aware that the branching pattern of the facial nerve can be quite varied and that the nerve may have been displaced from its normal position by tumour. Identification of the facial nerve and safe manipulation of the tissues around it can be significantly aided by the use of a facial nerve monitor
(Figure 189.14).
Superficial parotidectomy
Figure 189.13
Frey's syndrome: (a) classical facial blush
Most tumours can be removed through a 'lazy S' incision
elicited by eating flavoured crisps;
but, in some, extension of the incision into the hairline
demonstrated by painting the side of the face with iodine. After
aids exposure. Infiltration of the area with 1:200,000
this had dried the face was dusted with starch powder. As soon
adrenaline reduces haemorrhage and makes identification
as salivation 'I-Ias stimulated, sweating caused the characteristic
of the facial nerve slightly easier
starch-iodine reaction.
(Figure 189.15). Skin
(b)
/
gustatory sweating
Chapter 189 Benign salivary gland tumours. 2485
Figure 189.14
Tumours can displace the facial nerve and make surgical resection hazardous. (a) The facial nerve is adherent and
stretched across the upper pole of the tumour. (b) The appearance after resection.
Figure 189.15
Superfical parotidectomy: (a) skin incision; (b) skin flaps raised; (c) identification of the facial nerve; (d) completed
dissection.
flaps are raised which contain the subcutaneous tissue lateral to the parotid fascia. The parotid is then mobilized from the cartilage of the external auditory canal and adjacent muscles, the sternocleidomastoid and digastric muscles. It is at this point of the dissection that section of the greater auricular nerve becomes necessary. Preservation of the posterior branch of this nerve is thought by some to diminish the sensory deficit that accompanies this operation but others view this suggestion with a degree of scepticism.
The facial nerve trunk is then identified. A number of anatomical landmarks facilitate this part of the procedure: • the inferior portion of the cartilaginous external auditory canal. The facial nerve lies 1 cm deep and inferior to its tip; • the groove between the cartilaginous and bony external auditory meatus. The facial nerve lies immediately deep and inferior to this at its point of exit from the skull. This groove is very easy to feel;
2486 I PART 17
•
HEAD AND NECK TUMOURS
the anterior border of the posterior belly of the digastric muscle. The facial nerve leaves the skull immediately anterior to the attachment of this muscle. The facial nerve can be exposed by careful dissection in the area immediately anterior to the posterior belly of the digastric in the region of the mastoid process.
In some cases, for example in those with large or soft tumours immediately overlying the main trunk of the nerve and particularly in recurrence surgery, it is neither possible nor wise to access the facial nerve trunk at the skull base at the outset of the operation. In these cases it is better to locate and identify one of the major branches and dissect centrally or peripherally from there. The
Figure 189.16
mandibular branch can be found at the angle of the
gland both superficial and deep to the facial nerve has been
mandible, as it lies superficial to the facial vessels. The
removed.
Total conservative parotidectomy - the entire
cervical branch of the nerve can be located at the point where it pierces the deep fascia below the body of the
In the case of a tumour within the deep lobe, the facial
mandible. The zygomatic and temporal branches of the
nerve must be mobilized with great care. In the first
upper trunk cross the zygomatic arch anterior to, and
instance it is best to develop a plane deep to the main
within 1-2 cm of, the superficial temporal artery.
trunk. The remaining peripheral mobilization
can
be
In summary, there is a variety of landmarks that can be
facilitated by gentle elevation of the trunk with a nerve
used to aid identification of the facial nerve and its
hook. A piecemeal approach is not appropriate when there
branches. With experience, the surgeon learns how and
is tumour within the deep lobe. The tumour must be
when to use this information. The routine use of facial
removed with as much normal parotid tissue as possible,
nerve monitoring for parotid surgery also helps in this
albeit that it is usually very scant and the resection bears
process and cannot be recommended too strongly. Not
resemblance to an enucleation. Access to the tumour can
only does it predict the impending proximity of the facial
be improved by sectioning the digastric muscle and by
nerve trunk, but also helps minimize trauma to its finer
counter-pressure applied to the tumour by an assistant
branches that can be irrevocably damaged all too easily.
with their index finger in the patient's oropharynx. It is
The superficial lobe of the parotid gland and tumour
extremely easy to rupture a deep lobe tumour if care is not
are then dissected off the divisions and branches of the
taken or the tumour is soft and poorly encapsulated. At the
facial nerve. By this means the superficial lobe of the gland
very least it is possible to avulse surface bossellations.
is separated from the deeper tissues. If a tumour ruptures,
Either can be. catastrophic in the long term as multiple
the spillage should be contained and the tissues immedi
recurrences develop that are almost impossible to remove
ately deep to it removed. In this way tissue contamination
without inflicting significant morbidity.
and seeding is minimized. Haemostasis is then achieved
Other techniques for removal of deep lobe tumours
and the wound closed in two layers. Either active or passive
have been described and have their advocates. These
drains should be used. Great care should be exercised when
include both midline and angle transmandibular ap
placing vacuum drains, particularly if there are sections of
proaches. These approaches are very rarely needed for
unsupported facial nerve within the field, as they can be the
benign tumours and have significant morbidity in terms
cause of inadvertent neuropraxia. Recently, it has been
of swallowing, neural deficits and cosmesis. They should
suggested that the skin flaps are better replaced using a fine
be reserved for exceptional cases only.
mist of tissue glue. This eliminates the need for drains and some sutures.24 It is also thought to reduce the risk of reactionary haemorrhage.
Transpharyngeal approach After induction of anaesthesia, a preliminary tracheost omy is performed to protect the airway, as this approach
Total conservative parotidectomy
includes a mandibulotomy and there may be significant
Occasionally it is necessary to remove the deep lobe of the
soft tissue swelling in the immediate postoperative period
gland when either tumour has developed within it or
(Figure 189.17). The tracheostomy has the additional
extends into it
advantage of removing the endotracheal tube from the
(Figure 189.16). Spillage of tumour during
superficial parotidectomy is another indication for local
operative field
resection of the deep lobe. In the latter case, segments of
exposure.
parotid tissue deep to and in between the branches of the
and
therefore
increases
the
available
A skin crease incision is made at the level of the hyoid
facial nerve must be removed and this can be achieved in
bone and extended forwards across the chin to split the
a piecemeal fashion.
centre of the lower lip. The dissection is continued deep
/
.I
Chapter 189 Benign salivary gland tumours I
2487
(b) Figure 189.17
Transpharyngeal approach to deep lobe tumours:
(a)
outline of skin incision; (b) osteotomy and opening of floor of
mouth and parapharyngeal space (continued over). Figures drawn by Despina Sawa.
At this stage the exposure is complete and the tumour
to the submandibular gland until it is free from the surface of the
hyoglossus muscle. Attention is then
may be mobilized and removed by blunt dissection. This
focussed on the buccal gingivae which are very carefully
technique provides excellent exposure of the medial and
elevated from the underlying bone over the chin. Holes
superior aspects of the tumour which by any other
are prepared on either side of the proposed, stepped,
method have to be approached blindly.
osteotomy and compression plates fitted. It is essential
After removal of the tumour, the mucosa is closed with
that the placement of the compression screws avoids the
a single layer of interrupted 3'0' Vicryl sutures and the
roots of the underlying incisor and canine teeth and that
mandible secured with the compression plates.
the plates are accurately bent to the outline of the
external wound is sutured in two layers.
The
mandible. Once fitted, the plates and their screws are removed and placed to one side until the end of the operation. A midline mandibulotomy is then made with a
Submandibular gland
fine oscillating saw. If the lower incisors are overlapping or imbricated, it may be necessary, to extract one of them
Unlike the parotid where only a part of the gland is
to make space for the bone cut. The mandible is then
removed, total resection of the submandibular gland is
retracted laterally so that the incision can be extended
always indicated for tumours.
between the papillae of the submandibular ducts, along the floor of the mouth and up the anterior faucial pillar to the superior pole of the tonsil. During this part of the exposure the lingual and hypoglossal nerves should be identified and displaced medially, but not overstretched or cut if possible. While it is relatively simple to preserve the hypoglossal nerve, this is not the case with the lingual nerVe, which is frequently damaged. Because of this, the patient
must
be
forewarned
of
the
hemilingual anaesthesia following surgery.
, ---� �
probability
of
INFORMED CONSENT
The patient should be warned about the following serious or frequent complications. •
Damage to the marginal branch of the facial nerve. This may result in either a temporary or pef!I1anent weakness of the angle of the mouth that will be most noticeable on smiling and puckering the lips.
L
2488 I PART 17 HEAD AND NECK TUMOURS
Figure 189.17
•
•
Transpharyngeal approach to deep lobe tumours (continued).
(c)
and
(d)
repair of floor of mouth and plating of osteotomy.
Lingual and hypoglossal nerve damage. Neuropraxia
to sternomastoid muscle (Figure
of the lingual and hypoglossal nerves is unusual but
through the platysma muscle and flaps developed in the
189.18). It is deepened
possible. It is more likely to be sustained when the
fascial plane immediately beneath it. Care must be taken
gland is removed for chronic sialadenitis rather than
in development of the superior flap as the marginal
tumour as in these cases the gland is likely to be
mandibular branch of the facial nerve runs in the same
densely tethered to adjacent structures that become
tissue plane. This nerve enters the neck 1 cm in front of
more difficult to identify and preserve. This
the angle of the mandible, loops over the facial artery and
complication is a common source of litigation and so
vein 2 cm below the lower border of the body of the
must be included in the consent process. Motor
mandible before sweeping superiorly to the angle of the
dysfunction of the tongue initially impairs articulation
mouth. The mandibular branch of the facial nerve can be
and mastication but the patient rapidly compensates.
protected
Ultimately, the tongue muscles waste on that side but
manoeuvres. The facial vessels can be transected at a
from
inadvertent
damage
by
one
of
two
without further symptomatic deterioration.
low level on the surface of the submandibular gland and
Cosmetic defects. The patient should be reassured
reflected superiorly. The nerve, which lies lateral to the
that a properly placed skin incision is unlikely to
facial vessels, can then be lifted out of the operative field
leave a cosmetically unsightly scar.
by
traction
on
the
transacted
end
of
the
vessels.
Alternatively, the capsule of the gland can be opened at the level of the hyoid bone and dissection continued OPERATIVE PROCEDURE
beneath it. The elevated capsule protects the nerve in a similar fashion to the first technique. Occasionally it is
The incision is made in or parallel to a 1tatural skin crease
very difficult to identify the mandibular branch , and in
approximately 2.5 cm below the lower border of the
these cases a' nerve stimulator or monitor is extremely
mandible and extending for approximately 10 cm anterior
helpful.
J
Chapter 189 Benign salivary gland tumours.
2489
Figure 189.18 Submandibular gland resection: (al skin incision; (b) identification of the facial vessels; (e) mobilization of the deep part of the gland.
The superficial part of the gland is mobilized by either blunt or sharp dissection and retracted posteriorly in order to expose the deep portion that lies on the hyoglossus muscle and is partly covered by the mylohyoid muscle. Retraction of the mylohyoid anteriorly, together with posterolateral traction on the gland, brings the lingual nerve, duct and more proximal part of the facial artery into the operative field. The lingual nerve appears as a ribbon-like band loosely attached to the body of the gland by a few fibres - the parasympathetic secretomotor supply. Section of these fibres releases the nerve from the gland and permits it to assume a more superior relation. At this stage the hypoglossal nerve may be seen inferior and parallel to the lingual nerve but is sometimes partially covered by the posterior belly of the digastric muscle. The proximal part of the facial artery is usually ligated at this point. The gland is then further mobilized from the hyoglossus muscle and about its duct so that this may be ligated and transected as far anterior as possible. A small vacuum drain is inserted and brought out through the skin posteriorly. The wound is closed in two layers.
Management of recurrent pleomorphic adenoma This is always a most difficult situation and unfortunate condition for the patient. In most, and with the wisdom of hindsight, it would seem almost completely avoidable had the primary surgery been undertaken correctly. Patients often say that the original mass never entirely disappeared, suggesting that a subtotal resection has been achieved. The situation may have been made even more difficult if postoperative radiotherapy has been given. All too often their surgery amounted to an enucleation and it is difficult not to think that a more appropriate parotidectomy should have been undertaken. In some instances, an initial incisional biopsy will have seeded the ar~a and should not have been performed, while in others the. tumour has been ruptured and this might well have been unavoidable .
./
\
\
These patients have to be managed very carefully as it is all too easy to make their lives even more miserable by inflicting an unnecessary facial palsy. In general, recurrences tend to be either unifocal or multifocal. Unifocal recurrences suggest previously inadequate surgery while multifocal recurrences usually develop after tumour spillage following rupture. MRI will differentiate between the two in most, but some seedlip.gs are beyond the resolution of current scanners and only become apparent at operation. MRI will also give some indication of the amount of parotid tissue that remains. Further information may be forthcoming from previous operation notes or anaesthetic records. The important issue is to decide whether the previous surgeon found the facial nerve or if his operation was without reference to it. Lack of a greater auricular nerve sensory deficit suggests that an enucleation or extracapsular dissection took place. The incision scar may also give some indication, although a perfect outline is no guarantee that the rest of the operation was undertaken in a classical way. A history of temporary global facial weakness following the previous surgery is a clear indication that the facial nerve is likely to be surrounded or encased by scar tissue. Clearly, as much information must be obtained before surgery as possible so that the likely extent of any resection can be. gauged and the patient properly informed. In those patients where the primary surgery amounted to little more than a very superficial enucleation, it may be possible to remove all recurrences by completion surgery. The facial nerve will be found in virgin tissue and its anatomical and functional integrity can be preserved. It is prudent to remove as much parotid tissue as possible lest imperceptible implantation had taken place. Patients with multifocal recurrences require a thorough revision parotidectomy with removal of every scrap of the remaining parotid gland (Figure 189.19). It may be necessary to find the facial nerve at various sites in the residual parotid bed and link them together by delicate dissection. In some, sacrifice of the fadal nerve may seem inevitable and in these situations it should be· repaired imntediately by a suitable cable ,graft. The sacrifice of a fadal nerve can never be taken lightly. The patient's life will never be the same again and if, on
2490 I PART 17 HEAD AND NECK TUMOURS wise to obtain a baseline scan within six months of surgery. Interval scans are then acquired as necessary according to the patient's symptoms and signs. For those already treated for recurrent disease or whose operative field has been soiled with spilt tumour, scans at five- yearly intervals would seem to be sensible. In this way, any residual disease can be monitored and recurrent disease detected at an early stage. This attitude might also apply to those patients for whom the surgeon has concern that the initial resection was not as complete as they might have wished. There are, of course, a large number of patients in whom the tumour capsule comes to the edge of the resection. The vast majority of these patients will have no Figure 189.19
further
Total parotidectomy and facial nerve graft.
problems
but a
very
small
and undefinable
number may. For these, a warning that any mass, lump
balance, it seems a wise decision, the parotid resection must be absolutely complete to make it worth their while. Factors such as patient age and the likelihood of future
or unexplained symptoms
developing in
the region
should prompt an immediate referral for review would seem to be the best advice.
malignant change help to make this difficult decision. Postoperative radiotherapy is believed by many to delay or prevent the development of further recurrence and it is
KEY POINTS
sensible to offer this to those most at risk of further troublesome recurrence.
•
It is obvious that revision surgery is not for the clinician
been estimated at three to four per 100,000
who undertakes occasional parotid surgery or even for the
population. At least 75 percent of these
head and neck surgeon who lacks otological skills and cannot manage the facial nerve in the temporal bone. T his
tumours are benign. •
is for a highly skilled surgeon only, otherwise insult may be
pleomorphic adenomas. •
permanent facial palsy, be totally aware of the reason for drastic action and the potential consequences of malignant
Mo t tumours develop in the parotid gland
and the vast majority of these are
added to the injury already sustained by the patient. They must be made aware of the possibility of sustaining a
The incidence of salivary gland tumours has
Some salivary gland tumours are induced by previous exposure to radiation.
•
Most salivary gland tumours present in an
change. Intraoperative facial nerve monitoring should be
insidious fashion, growing slowly over a long
considered a standard of care for this surgery.
period of time with little else in the way of symptoms. •
POSTOPERATIVE FOLLOW-UP
necessary. Imaging should be undertaken in
There are no strict guidelines for follow-up after resection
an deep lobe tumours, those in which
of benign salivary gland tumours. After all, recurrent
malignancy is suspected, congenital tumours
pleomorphic adenoma can develop up to 20 years later and
and those that have recurred.
it would be both futile and inefficient to follow up all patients for this length of time. There is a group of patients, however, that
can
•
•
tumours. Areas of deficient or complete
whom the tumour capsule has ruptured at the time of
absence of capsule are not uncommon and
primary surgery. These are obvious categories and it would
this predisposes these patients to recurrence.
be extremely unwise to discharge these patients perma difficult
are
those
patients
in
whom
•
handled with care.
the capsule was incomplete or came to the margin of the gland surgeon could become swamped with unnecessary follow-up
appointments.
To
some
extent,
MRI
has
revolutionized the further management of these patients. In those at a significantly increased risk of recurrence it is
Some pleomorphic adenomas are extremely soft and fragile. These rupture easily if not
subsequent histopathological examination has shown that resection. Unless a sensible attitude is taken, a salivary
The degree of encapsulation of pleomorphic adenomas varies between and within
patients who already have recurrent disease or those in
More
Fine needle aspiration biopsy should be undertaken in all salivary tumours.
be recognized as at increased
risk of developing recurrence. Foremost among these are
nently.
Detailed imaging of all salivary gland tumours is neither cost-effective nor
•
Areas of cellular atypia and frank carcinoma can be found in some pleomorphic adenomas. As long as the tumour is containtd within the capsule it has no nificance.
/
Chapter 189 Benign salivary gland tumours.
2.
2491
Takeichi N, Hirose F. Salivary gland tumours in atomic bomb survivors, Hiroshima, Japan. Cancer. 1983; 52: 377-85.
3.
Whatley WS, Thompson JW, Rao B. Salivary gland tumors in survivors of childhood cancer. Otolaryngology - Head and Neck Surgery. 2006; 134: 385-8.
4.
Rubino C, de Vathaire F, Dottorini ME, Schvartz C,Couette JE, Dondon MG et al. Second primary malignancies in thyroid cancer patients. British Journal of Cancer. 2003; 89: 1638-44.
5.
Kundi M, Mild K, Hardell L, Mattsson MO. Mobile telephones and cancer - a review of epidemiological evidence. Journal of Toxicology and Environmental Health.
Part B, Critical Reviews. 2004; 7: 351-84. 6.
Hardell L, Hallquist A, Hansson Mild K, Carlberg M, Gertzen H, Schildt EB et al. No association between the use of cellular or cordless telephones and salivary gland tumours. Occupational and Environmental Medicine. 2004; 61: 675-9 .
./ A retromandibular fossa or cheek mass should be
7.
Maruya S, Kim HW, Weber RS, Lee JJ, Kies M, Luna MA et
considered a salivary gland tumour until proved
al. Gene expression screening of salivary gland neoplasms:
otherwise. [Grade DJ
molecular markers of potential hi~togenetic and clinical
./ Undertake fine needle aspiration biopsy on all
significance. Journal of Molecular Diagnostics. 2004; 6:
suspected salivary gland tumours. [Grade DJ ./ Never perform an open biopsy of a salivary gland
180-90. 8.
tumour unless it is situated in the palate. [Grade DJ
Batsakis JG et al. Differential expression of p63 isotypes
./ Image all deep lobe tumours, those in which
(DeltaN and TAl in salivary gland neoplasms: biological
malignancy is suspected, congenital tumours and
and diagnostic implications. Human Pathology. 2005; 36:
- those patients with recurrent disease. [Grade DJ ./ Undertake an appropriate parotidectomy every time
Maruya S, Kies M, Williams M, Myers IN, Weber RS,
821-7 . 9.
and never an enucleation. [Grade DJ
Pastore A, Carinci F, Pelucchi S. Genetic expression profiling of parotid neoplasms by cDNA microarrays. Acta
./ Use facial nerve monitoring in every case. [Grade DJ
Otorhinolaryngologica Italica. 2005; 25: 153-60. 10.
Martins C, Fonseca I, Roque L, Ribeiro C, Bullerdiek J, Soares J. PLAG1 gene alterations in salivary gland pleomorphic adenoma and carcinoma ex-pleomorphic adenoma: a combined study using chromosome banding,
Deficiencies in current knowledge and .areas for future research
»
in situ hybridisation and immunocytochemistry. Modern
Pathology. 2005; 18: 1048-55. 11.
Further epidemiological studies are required to
comparison of MR imaging and CT. Radiology. 1987; 165:
establish the influence of environmental factors in the development of salivary gland tumours.
» The molecular basis of tumour development is
183-9. 12.
tumours is required. Other specialties need to be made aware of the
Chaudhuri R, Bingham JB, Crossman JE, Gleeson MJ. Magnetic resonance imaging of the parotid gland using
beginning to be understood. Large-scale analysis of
»
Casselman JW, Mancuso AA. Major salivary gland masses:
the STIR sequence. Clinical Otolaryngology and Allied
* 13.
Sciences. 1992; 17: 211-7. Cohen EG, Patel SG, Lin 0, Boyle JO, Kraus DH, Singh B et
importance of correct initial management of parotid
al. Fine-needle aspiration biopsy of salivary glands lesions
tumours and their limitations in this field.
in a selected patient population. Archives of
Otolaryngology - Head and Neck Surgery. 2004; 130: 14.
773-8. Hughes JH, Volk EE,Wilbur DC. Pitfalls in salivary gland fine-needle aspiration cytology. Archives of Pathology and
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* 15.
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Salivary gland tumours in atomic bomb survivors,
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Sciences. 2001; 26: 134-42.
;'
\
\
_ _ _. . ,.,.....;...L_>..... ·
01-/ _: __
'''\
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* 17.
Piekarski J, Nejc D, Szymczak W, Wronski K, Jeziorski A.
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Otology. 1990; 104: 656-61. 21.
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TJ, Gleeson M, Eveson JW, Cawson RA. Oncocytic
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adenomas and oncocytic hyperplasia of salivary glands: a
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Maxwell EL, Hall FT, Freeman JL. Recurrent pleomorphic
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Clayman MA, Clayman SM, Seagle MB. A review of the surgical and medical treatment of Frey Syndrome. Annals
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Patel MJ, Garg R, Rice DH. Benefits of fibrin sealants in parotidectomy: is underflap suction drainage necessary?
Laryngoscope. 2006; 116: 1708-9.
190 Malignant tumours of the salivary glands
ANDREW S JONES
Introduction Incidence and epidemiology Key points The cell and molecular biology of salivary cancer Key points The classification and h istology of malignant salivary tumours Key points Best clinical practice H istogenesis Cancer of the sa livary glands at the three main sites
2493 2494 2494 2494 2496 2496 2502 2503 2503 2503
Key points Best clinical practice Diagnosis and investigations Best clinica l practice Treatment Best clinical practice Patterns of fail ure and survival Key points Conclusion Key points References
2505 2505 2506 2507 2507 2510 2510 2515 2515 2516 2516
The initial search strategy used PubMed and Medline with the MeSH headings salivary gland, parotid gland,
submandibular gland, sublingual gland, minor salivary glands, tumours, carcinoma, histology, mucoepidermoid, adenoid
cystic, squamous, pleomorphic adenoma, glandular and neck nodes, in various combinations. The search was extended or
refined as appropriate. Back searching from review articles and from book chapters revealed a number of additional references. Finally, other databases were searched, such as the Cochrane database, the library of the British Medical Association and CHINAL. In all,
then the abstracts; finally, the data from
8829 relevant references were identified. Initially, these were selected using the title and 688 original articles were used in the preparation of this chapter. The chapter also makes use of
326 patients from the University of Liverpool head and neck database. This was begun by my predecessor, 7000 patients with head and
Phillip Stell, and since his retirement maintained by me. The database contains details of over
neck tumours. This chapter makes use of these data, not only in its preparation, but also for detailed calculations of recurrence and survival. All calculations have been carried out specifically for this chapter.
I NTRODUCTION
neoplasms and adenoid cystic carcinoma, in particular,
O f all the cancers treated b y head and neck oncologists,
twenty-first
malignant salivary gland tumours are arguably the most difficult. Patients are not infrequently young and the cure
rates are very poor for most histological types. Indeed,
work from my unit demonstrates that adenoid cystic
carcinoma, for example, will inevitably potentially recur and eventually
kill the patient. Why malignant salivary
are so resistant to treatment is not known even with the century
explosion
in
the
techniques
of
molecular biology. The natural history of these cancers
tends to be long and patients may undergo multiple treatments in an attempt to control their disease at least.
The salivary glands are in many ways unique. They
supply a lubricant, a solvent and a dispersant for food.
Saliva
contains
antimicrobials,
immunoglobulins
and
/ --� -.
I
'
2494
I PART 1 7 H EAD AND N ECK TUMOURS
enzymes. The glands themselves respond to food and drink, fear and exhaustion. The salivary glands fall prey to many diseases but none as disastrous as malignancy. John Conley stated that 'because of their rarity [tumours], past difficulties and classification and the quandary they pose in management they [the salivary glands] have remained outside the mainstream of active scientific investigation'. The treatment of these tumours is particularly challenging, not only because they have such diversity of histological type but also because of anatomical constraints. The tumours themselves encompass some of the most malignant oncologists have to deal with and also some of the most benign. Not only is the tumour type diverse but also the involved organs from the large parotid gland to the smallest minor salivary gland, located anywhere in the head and neck mucosa.
I N CIDENCE AND EPIDEMIOLOGY An epidemiological study of malignant salivary gland tumours in Sweden studying data from 1960 to 1989 produced only 85 new cases per year, forming 0.3 percent for diagnosed cancers in Sweden. The common est site was the parotid gland (58 percent) followed by malignant minor salivary gland tumours (23 percent). There was no great variation in the incidence of submandible salivary cancer over the 30-year period but the diagnosis of adenoid cystic carcinoma and mucoepidermoid carcinoma increased.! A study in Scotland demonstrated how inaccurate epidemiological data were when an incidence of 40 per million was demonstrated for all major salivary gland tumours, which was much higher than expected. Further analysis, however, demonstrated that the incidence was probably higher than that indicated because of errors in report ing.2 Canadian Arctic Inuit peoples were surveyed from 1949 to 1974, as during these years they changed from a traditional lifestyle to one where the various benefits (or otherwise) of Western civilization impacted on them. Salivary gland and renal neoplasms were originally very common but, over the time period studied, decreased and were displaced by cancers of the lung and cervix which are now the most common malignant tumours in these people. Interestingly, nasopharyngeal carcinoma did not alter and breast cancer is still uncommon in Canadian Inuits.3[**] In Great Britain, according to the OPCS cancer statistics, the incidence of malignant salivary gland tumours of the major glands is 1.2 per 100,000.4 [**] Always of great relevance in cancer studies is the influence of environmental and nutritional factors on incidence. Similar to most cancers, salivary malignancy rises with increasing smoking and alcohol consumption. Ionizing irradiation is also a well-documented cause. The difference in registration varies between geographical
areas. Epidemiological evidence indicates that diet and nutritional habits may be important and, in particular, polyunsaturated fatty acids seem to exert a beneficial effect with an inverse relationship between the registra tion of salivary cancers and the intake of these substances.5, 6, 7, 8, 9, !O For a number of years it has been suspected that salivary gland malignancy may be related to occupation. A Danish study has demonstrated that workers involved with livestock feed processing had an increased risk of malignant salivary disease and this has been linked to imported crops contaminated by aflatox ins. These are a highly carcinogenic group of substances, particularly aflatoxin B1 that was present in relatively large amounts. This study carried out multiple compar isons and confounding factors cannot be excluded.!! In the Netherlands Cancer Institute study of irradiation induced tumours of the head and neck, 2500 patients were included of whom 0.7 percent were deemed to have post-irradiation tumours. The mean interval between irradiation and the development of the tumour was 36.5 years. Of the irradiation-induced tumours, only a small fraction involved the salivary glands, demonstrating a risk of an irradiated person suffering a salivary gland tumour of approximately 0.1 percent.12 A number of studies suggested other predisposing factors including race, diet (other than fatty acids), occupation (apart from feed workers) and Epstein-Barr virus (EBV) infection.l3, 14, !5 Various tumours can be induced in adult mice by injecting known carcinogens, such as benzopyrine and its analogues.16 Benzopyrine induces tumours of the salivary glands at the site of injection, whereas the dihydrodiol analogue induces lymphosarcomas in other organs. [****]
KEY POI NTS •
•
•
In Great Britain, the incidence of malignant salivary gland neopla..�ms is 1.2 per 100,000. Salivary malignancy increases with increased smoking and alcohol consumption. Diet. especially polyunsaturated fatty acids, race, e.g. Canadian Inuits prior to westernization, occupation, particularly livestock feeding, and EBV infection may all be predisposing factors.
THE CELL AND MOLECULAR BIOLOGY OF SALIVARY CAN CER One of the first subjects to interest cell biologists in this disease were silver stairung nucleolar organizer regions (AgNOR). It was found that an increased AgNOR cluster
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Chapter 1 9 0 Malignant tumours of the salivary glands
to nucleolus volume reflected proliferative activity in a range of normal and neoplastic tissues. Proliferation was monitored using bromodeoxyuridine labelling;17 an increase in AgNOR cluster size was correlated to some extent with the degree of malignancy. In the 1 980s there was much interest in the subject of cell kinetics using flow cytometry for assessing the proliferation rate in neoplastic tissue. In this technique various factors are measured that include labelling index, DNA content and S-phase duration. Proliferative activity assessed in this way significantly and inversely affects surviva1.18 While flow cytometry is still a useful tool in cell and molecular biology, it is by no means a panacea. [****] The workhorse of basic cell biology is the technique of immunohistochemistry (IHC). With this technique a large number of proteins including enzymes and receptors has been studied. Returning to the concept of cell proliferation, IHC has had much to offer. An antigen expressed in the nucleus of dividing cells was identified a number of years ago. The antibody that bound to it is called Ki-67 and the density of staining with this antibody gives a good indication of the proportion of cells that are proliferating in a tumour. It is expressed in all phases of the active cell cycle (except Go). Proliferating cell nuclear antigen (PCNA), as its name suggests, stains the proliferating cells and unlike Ki-67 PCNA is detectable long after cell division is completed. PCNA immuno reactivity tends to be significantly higher in malignant salivary disease than in benign salivary disease, offering a potentially useful tool in the histological diagnosis of tumours where the degree of malignancy is variable.19 Protein products of various genes have been studied by IHe. Rosa et al. studied c-erbB-2 and p53 but found no significant relation between these two protein products and salivary malignancy.2 o The influence of Ki-67 and Bcl-2 expression in salivary cancer has been investigated. Bcl-2 is a gene, which codes for a protein, which inhibits apoptosis; in addition, tumour apoptosis has been studied by in situ end labelling. Ki-67 was found to have prognostic value as regards adenoid cystic carcinoma, and Bcl-2 and the apoptotic index were found to be potentially useful as prognostic markers.2 1 Regarding further studies on this issue, the pro-apoptotic Bax must also be considered. This is closely related to Bcl-2, and whereas that molecule rescues the cell from apoptosis, Bax is pro-apoptotic. In salivary gland cancer there is a relatively low expression of Bcl-2 leading to a higher incidence of apoptosis.22 A group of proteins termed cytokeratins are expressed by epithelial cells and the cancers derived from them. Cytokeratins 5-1 7 tend to be expressed by complex epithelia such as mucosa whereas cytokeratins 18 and above are noted in simpler glandular epithelia. Cytokeratin 14, while usually considered a marker for squamous cell carcinoma (SCC) regardless of origin, is also found in the myoepithelial component of salivary gland tumours2 3 and, of course, in SCC of the salivary glands. [****]
I 2495
Cells are stimulated to divide by growth factors and in a study by Myoken et al., fibroblast growth factors 1 and 2 and fibroblast growth factor receptor 1 were studied in malignant salivary gland tumours. All the factors were overexpressed in human salivary gland malignancy.24 Recent interest in nitric oxide syntheses and the levels of nitric oxide in tissue show that this mediator has complex effects, from the relatively simple vasodilatation action to poorly understand inhibitory and tumour-promoting activity. The enzyme nitric oxide synthase has an inducible and an endothelial form. The inducible nitric oxide synthase is evident in almost all tumours studied; the endothelial form shows little relation to tumour activity and is of no value in differentiating tumour from normal tissue.25 Further work has demonstrated that the inducible form of the enzyme is present in normal salivary ducts and is probably due to expression by myoepithelial cells.26[****] In the last decade, much work has been carried out on vascular endothelial growth factor (VEGF) and its receptor. For new tumour to grow successfully to more than a couple of millimetres in size it needs to stimulate a new blood supply and this process is termed neoangio genesis. VEGF is found in normal saliva.2 7 A new antibody VG 1 has been shown to react with various isoforms of the VEGF protein in fixed specimens and may therefore be useful in the study of salivary malignancy, although no definite conclusions can yet be formed.27 In practice, most work on malignant neoplasia has been carried out using immunohistochemical antibodies to CD31 (endothelial cells) and CD34 (vascular endothe lium). [****] Some of the vast array of mucin-type carbohydrate antigens has been studied in relation to salivary cancer.28 These are the T and the sialyl-T antigens as well as the Tn and sialyl-Tn antigens. These can be studied on paraffin embedded tissue. The Tn antigen appears to be associated with early locoregional recurrence and death but the association is not strong. In normal salivary gland, metallothionein is expressed while duct or basal cells express parathyroid hormone-related peptide. Metal lothionein may be involved in the differentiation and growth of actively growing salivary cells and may be a marker of differentiation in malignant salivary tu mours.29 Oestrogen and progesterone receptors have been discovered by IHC in salivary tumours, and 25 percent of tumours expressed oestrogen receptors and 16 percent expressed progesterone receptors. It should be emphasized that not all tumours were malignant but the malignant ones tended to express these receptors more often, and sometimes both together. Evidently, this finding suggests a therapeutic opportunity with appropriate endocrine therapy for at least some tu mours.30 Many tissue markers have been studied in salivary cancer. Among these are carcinoembryonic antigen, which tends to be poorly expressed and - of no diagnostic or therapeutic value. Mucoepidermoid cancers
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I PART 1 7 HEAD AND NECK TUMOURS
tend to be positive for a variety of cytokeratins and also virnentin. Alpha 1-antichymotrypsin, usually con sidered a marker for histiocytes, was present in over three-quarters of the cases of mucoepidermoid carcino mas studied, a quarter of these carcinomas were also positive for S100 and half for the Leu-N1 antigen.3' [****] For molecular biology data, complex chromosomal changes are noted in primary squamous carcinoma of the parotid gland. In 1993, Mark and colleagues found the only consistent picture was varying morphology in markers of chromosome 6q, which was particularly evident in a case of adenoid cystic carcinoma.32 Other workers have found overexpression of a c-erbB-2. The overexpression of this oncogene in parotid cancer was seen in an adenocarcinoma (82 percent) , undifferentiated carcinoma (75 percent) and adenoid cystic carcinoma (73 percent). Expression of this oncogene did not appear to affect the natural history of the disease.33 In my department, loss of heterozygosity studies have been carried out on chromosome 17; loss at TP53 and, in particular, CHRNB1 was present in hypo pharyngeal cancer but no abnormal findings were noted in salivary gland cancer. Other more recent studies suggest other wise, and also loss of heterozygosity associated with the p53 gene. This affected roughly half of salivary carcinomas, which is approximately what one would expect in head and neck cancer in general.34 Studies of hMSH2 showed no loss or microsatellite instability indicating that these molecules may not be important in this disease.35 In a study of Mdm2 and p53 gene status in minor salivary glands,36 p53 expression was raised above 50 percent in adenoid cystic carcinoma, but polymerase chain reaction (PCR) of exons 5-8 on the p53 gene showed no alterations. Needless to say, other exons should be studied to exclude a genetic cause for the p53 protein stabilization, and exon 4 should certainly be studied. Other causes of stabilization are, for example, human papilloma virus (HPV) infection. Mdm2 expres sion has been found to be raised in all minor salivary gland neoplasms.36 [****] For a number of years EBV has been thought to be involved in salivary cancer. In 1999, Pollock et al. found an association between the presence of the EBV genome using in situ hybridization and undifferentiated carcino ma but no other tumours. They also confirmed a previously reported ethnic association.37 Other viruses implicated in this disease are HPV, human herpes virus 8 (HHV-8) and human cytomegalovirus (CMV). A recent study employing PCR found no evidence of HPV, HHV-8 and CMV DNA in any salivary glands neoplasms.3 8 Experimental work has investigated the role of herpes viral genes in tumour genesis; transgenetic mice were generated to express the StpC transformation-associated protein of lymphoma associated with herpes virus saimiri. StpC does produce tumours in various organs including the salivary glands.39 [****]
THE ClJ\SSI FICAT ION AND HISTOLOGY O F MALIGNANT SALIVARY TUMOURS To classify this disease in any logical order is eXtremely difficult. Typically, this has been carried out according to histology or according to site.40, 41, 42 Recent work in the UK attempting to rationalize the problem43 uses a modification of the 1972 World Health Organization histological classification by Seifert and Sobin.44 In this system there are seven categories: WHO 1. 2. 3. 4. 5. 6. 7.
adenomas; carcinomas; nonepithelial tumours; malignant melanomas; secondary tumours; unclassified tumours; tumour-like disorders.
Although the above list is useful, it has no particular relevance for those treating these tumours, as it is the
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Chapter 1 9 0 Malignant tumours of the salivary glands
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While this list is simple, it does not really represent a natural order in terms of tumour behaviour. The clinicopathological and natural history details of each type of tumour are now described. [*J
solid microcystic, papillary cystic and follic ular. All of these patterns may be seen in one individual tumour. 53 As acinic cell carcinoma is rare, pleomorphic and pleo trophic, the histological diagnosis is frequently difficult. The differential diagnosis includes thyroid carcinoma, mucoepidermoid carcinoma, myoepithelial carcinoma, oncocytoma and metastatic renal cell carcinoma. Although acinic cell carcinoma almost certainly has the best survival rate of any salivary cancer, similar to most of the latter it has a long natural history and it is a mistake to consider five-year survival rates as a cure. Spiro et at found that of 67 patients with this disease the cure rate at five years was 76 percent but at 1 5 years was only 55 percent,54 and other authors concur.55,5 6 Clearly, this is an aggressive tumour and treatment should reflect this. The clinical extent of the disease is the most important prognostic factor and thus early attempts at enucleation yield disastrous survival figures.57 More appropriate options range from total parotidectomy and neck dissection to a local excision of the cancer with a margin of normal parotid gland.54,5 8 The view of some of the most experienced surgeons in this field is that excision of a facial nerve is not justified unless it is grossly involved.54,58 The role of postoperative radiotherapy has not been determined in the management of this tumour. As discussed above, the tumour has generally been regarded as at the more benign end of the spectrum of malignant salivary disease, but as the quoted survival figures show, the long-term cure rate is relatively poor. As a result of this our unit gives patients with this disease postoperative irradiation to the primary site and the first echelon nodes. Our own data on a small number of patients suggests that locoregional recurrence is reduced by two-thirds, although we have no data on final outcome as yet. [**J
Acinic cell carcinoma
Mucoepidermoid carcinoma
Acinic cell carcinomas is often regarded as a low-grade malignancy. While they form some 15 percent of parotid malignancies they account for only 3 percent of all salivary gland tumours.48 Although bilateral salivary malignancy is usually very rare, acinic cell carcinoma is the most common and, in terms of salivary tumours, in general, only Warthin's tumour is more likely to follow this behaviour.49 Clinically, acinic cell carcinoma presents as a painless lump, usually in the parotid gland. It is commonly a solitary encapsulated lesion with well defined margins but multilobulation does occur. The cut surface is of variable appearance but cystic lesions are frequently seen. Histological grading is not reliable in this tumour50 but some authors have noted that the papillary cystic variety results in a high mortality.51 Unsurprisingly, this tumour probably arises from the acinic cells. Three quarters of these cancers demonstrate more than one cell type52 and the histological patterns described include
This tumour is the most common of the major salivary gland malignancies, accounting for one-third of cases.59 In particular, it is the most frequent cancer of the parotid gland, often presenting as a painless mass at the more benign end of the spectrum of this tumour to more aggressive cancers presenting with pain, swelling and facial palsy. In high-grade cancers, lymph node metastases occur in nearly three-quarters of patients at presenta tion.45 As in many salivary malignancies the tumour is formed of several groups of cells. In the case of mucoepidermoid cancer there are mucus secreting cells, epidermoid cells and intermediate cells (Figure 190.1). Batsakis maintains, however, that nearly all salivary cancers originate from a common progenitor cell, the intercalated duct reserve cell.40 Mucoepidermoid carci noma may be usefully classified histologically in terms of low grade and high grade. Low-grade tumours tend to be cystic, whereas higher-grade tumours tend to be solid
clinical behaviour of such diseases that tends to predict survival rather better than histology. Most head and neck pathologists further classify malignant tumours into three grades according to their differentiation, and this correlates well with surviva1.45 In the case of adenoid cystic carcinoma it is the histological structure that is related to survival, with three histological patterns. Cribriform is the most common, followed by solid and tubular pattern. The solid pattern has a significantly poorer survival than the other histological types.46 [**J While the parotid gland is the largest salivary gland, the combined minor glands are the second largest group. Most tumours appear in the parotid gland and most of these are benign. The incidence of malignancy is relatively higher in the submandibular, sublingual and minor salivary glands. For example, approximately 85 percent of tumours of the sublingual gland are malignant.47 [**J Histologically, carcinomas are probably best classified as below:43 • • • • •
•
• •
•
•
•
acinic cell carcinoma; mucoepidermoid carcinoma; adenoid cystic carcinoma; polymorphous low-grade adenocarcinoma; papillary cystadenocarcinoma; mucinous adenocarcinoma; adenocarcinoma; carcinoma ex pleomorphic adenoma; malignant mixed tumour; squamous cell carcinoma; undifferentiated carcinoma.
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I PART 1 7 H EAD AND N ECK TU MOURS
Figure 1 90.1 A photomicrog raph of a mucoepidermoid carcinoma. Both elements of th e tumour a re seen.
Figure 190.2 A photomicrograph of a nonsolid pattern adenoid cystic carcinoma.
with areas of necrosis and haemorrhage. The tumour was previously divided into three grades: low, intermediate and high. The clinical relevance of the intermediate grade is, at least, dubious with no prognostic relevance. Patients with low-grade tumours have a five-year survival of 96 percent whereas high-grade tumours are associated with a death rate ten times this.60 Other authors have reported similar figures with a 70 percent cause-specific survival for low-grade tumours and a 47 percent survival for high grade tumours.61 [**J The extent and grade of a tumour dictate the treatment. For the most favourable tumours a superficial parotidectomy with facial nerve preservation, if possible, is recommended, although a much more radical excision is necessary for patients with large and/or high-grade lesions. An associated elective neck dissection to include levell, 2 and 3 for the No neck would also be appropriate. With more severe neck disease a radical neck dissection is necessary. 59 In high-grade tumours there is little doubt that postoperative irradiation to the primary site and the neck must be carried out, with studies suggesting a two thirds reduction in locoregional recurrence.61
tubular. Interestingly, when the histology of all the tumours studied was re-evaluated, 15 percent of our series of adenoid cystic carcinoma, in fact, had poly morphous low-grade adenocarcinoma. These were ana lyzed separately as they have a benign outcome compared with adenoid cystic carcinoma. Solid pattern histology is associated with a poorer survival than tumours with other histological patterns.46,62 There is a feeling among experienced head and neck oncologists in Britain that a cure is never achieved in this disease. Indeed, the actuarial primary site recurrence rate in our study demonstrated 100 percent recurrence at the primary site at 30 years. The neck node recurrence rate was 23 percent at 15 years and the tumour-specific survival 40 percent at 20 years. It should be noted that even after 20 years the actuarial curve was still falling, demonstrating a very long natural history of this disease coupled with an appalling cure rate. Solid pattern histology was associated with a considerably worse prognosis than other histological types. Patients with tumours of the oral cavity minor salivary glands, particularly the hard palate, faired better than patients with tumours at other sites. Those with T3 and T4 primary site disease and with lymph nodes at presenta tion did particularly badly. Other studies have concen trated on distant metastases, particularly to the lung, which is characteristic of this disease.63 These lung metastases, although obviously alarming to the oncologist and the patient, frequently grow very slowly. In a recent Japanese study62 the records of 30 patients were analyzed: 21 had pulmonary metastases, 4 of these at presentation and 17 during follow-up; other patients in the series had not been followed-up for long enough to assess survival. A calculated cumulative metastasis rate to the lung of 70 percent at five years and 100 percent at ten years has been suggested. Of interest is that patients with early primary site disease (T1 and T2) and with tubular or cribriform histology developed pulmonary metastases a median of 20 months late; than those with more advanced disease or with solid pattern histology.64 Unfortunately, as follow-up
Adenoid cystic carcinoma A study from our department published in 199746 investigated 108 patients with this tumour who were seen over a 30-year period. Nearly one-third of all adenoid cystic carcinomas occurred in the major salivary glands, and most of the remainder involved the minor glands. Forty percent of patients had tumours arising in the oral cavity and half of these were in the hard palate. Of all tumours 41 percent were locally advanced at the time of presentation and 11 percent had distant metastases. Histological subtype is best divided into three main categories although combinations may occur (Figure 1 90.2). In our series 25 percent were of a solid pattern, 40 percent were cribriform and 20 percent were
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Chapter
accrues there is no difference in the long-term metastasis rate. The average tumour doubling time of a metastatic deposit was just over one year, which is very slow, compared with lung metastases from other cancers. This report is of particular importance as it obviously defines the lim-it of ablative surgery in the head and neck. In a further study from our department,65 data on 145 patients with tumours of the minor salivary glands were analyzed and again showed that adenoid cystic carcinoma had a particularly bad prognosis in the long term. Obviously, with a tumour-specific actuarial curve which continues to fall after 5, 10 and even 20 years, 5-year survival figures are in no way indicative of cure rate. [**] Not only are adenoid cystic carcinomas unusual in producing (it seems inevitably) distant metastases via the blood-borne route, they also have a predisposition to invade and spread along peripheral nerves (Figure 190.3). Generally, it has been assumed that tumour spreads into the nerve from the primary site, but others have suggested an embolic mechanism. Whatever the underlying cause of this behaviour spread into, and along, peripheral nerves occurs in 80 percent of cases.66 The bigger the tumour the more likely it is to involve nerves. Whether this affects survival or not is uncertain, although there is good evidence that it does.67 Carcinomas involving the larger salivary glands, in particular the parotid gland, may have as much as a four-fold better survival at ten years than those in the minor salivary glands.6 8 [**] As regards presentation, adenoid cystic carcinoma demonstrates insidious growth over many years. It also shows a tendency for local recurrence and distant metastasis despite aggressive therapy at the primary site. Some patients present with severe pain due to peripheral nerve invasion, and in the parotid gland facial nerve palsy may be evident. The most appropriate treatment for this disease is controversial. The Sloan-Kettering experience68 of 184 previously untreated patients suggests that radical primary surgery is likely to provide the best survival rates at 20 years. The case for how radical the primary surgery should be is unproven. In a study of 4 1 patients with
Figure
1 90.3
Perineural spread of sa livary cancer.
190 Malignant tumours of the sa livary gla nds . 2499
palatal lesions for small cancers with clear surgical margins and no nerve spread or bone involvement, local surgery alone was considered adequate. Larger tumours involving adjacent sites require more extensive surgery with postoperative radiotherapy.69 As long ago as 1975, John Conley suggested that postoperative irradiation should be an integral part of treatment of adenoid cystic carcinoma. Interestingly, he only reported a 3 percent incidence of regional neck node involvement and there fore did not recommend elective neck dissection.67,70 Thus, based on the few large series in the literature, prophylactic neck dissection does not appear to be warranted and this has also been our finding.46 In the Liverpool study, because of difficulties in analytical power caused by the protracted natural history of this disease, we found it difficult to make definitive treatment policy recommendations.46 It appeared that a radical operation, compared with adequate local excision, tended to be associated with a longer period of locoregional control. It did not, however, appear to alter the natural history of the disease in the long term. Our experience has been that postoperative radiotherapy should be given, although the follow-up of this group of patients was limited. [**] Pulmonary metastases have been discussed above and occur in approximately 70 percent of patients. Metastases to bone and liver are also not uncommon. The role of chemotherapy in this disease appears limited; non-cisplatin therapy is useless although some responses are seen if this drug is included.71 There is some evidence that doxyrubicin should also be included.72 [**] It is evidently essential that if radical treatment of an adenoid cystic carcinoma is considered, a full radiological work-up is essential. This would not only include magnetic resonance imaging (MRl) of the primary site, and of course the neck, but also computed tomography (CT) scans of the lungs and liver and an isotope bone scan. Owing to the high risk of bone involvement a CT scan of the primary tumour should also be considered. If no regional or distant metastases are detected, then surgical ablation of the primary tumour followed by radiotherapy is the treatment of choice. The question is how radical should the primary treatment be. Most head and neck oncologists who have dealt with this disease and are familiar with the literature are justifiably confused. We have seen young patients treated by relatively local complete excisions who later developed devastating recurrence at the primary site, with death from pulmon ary metastases. Would more extensive primary surgery have stopped such catastrophes? On the other hand, we have seen patients where super radical surgery has been carried out, with immense associated morbidity, in whom death ensued either from local invasion to vital structures or distant metastases to the lung and other sites. In our experience skip lesions in the facial nerve, several centimetres from where tumour invasion apparently terminated, both on frozen section and on later paraffin section histology, certainly take place. Following the facial
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HEAD AND NECK TUMOURS
nerve into the mesotympanum would thus appear pointless. In a disease in which there is at least more than a suspicion that treatment may not greatly affect natural history, consideration should be given to whether or not super radical surgery is justified. A large tumour is almost always going to be associated with peripheral nerve invasion when first seen. This is particularly true of the parotid and submandibular glands where large nerves are in contact or closely adjacent to the tumour. If gross or frozen section histology involvement of a nerve is found at operation, the nerve should be sacrificed and an immediate nerve graft carried out in the case of the facial nerve. We would now aim to obtain clear margins although this is not always technically feasible. It is our view that postoperative radiotherapy should always be given with or without a cisplatin- and doxorubicin containing chemotherapy regimen.72 [**]
Polymorphous low-grade adenocarcinoma
This tumour was once considered a low-grade variant of adenoid cystic carcinoma because of similar histology and its relatively benign clinical course. However, since 1983 it has been considered a different histological type, originally called terminal duct carcinoma.73 There are four histological patterns: tubular, cribriform, papillary and 10bular.74 The cellular morphology is uniform and the tumour tends not to metastasize. About three quarters of these tumours arise from minor salivary glands and major salivary gland involvement is relatively unusual. It tends to be a tumour of women and most arise on the palate. Most oncologists recommend wide local excision with clear surgical margins as adequate treatment for these cancers.75 [**]
Adenocarcinoma. papillary cystadenocarcinoma and mucinous adenocarcinoma
The literature dealing with adenocarcinoma is not large and that dealing with the particular types is sparse, but papillary and mucinous adenocarcinomas are best regarded as different histological types of adenocarcino ma. Mucinous adenocarcinoma and papillary cystadeno carcinoma are two of the five usually described variants of adenocarcinoma. The other three are trabecular, clear cell and sebaceous. Histologically, they all demonstrate either a neoplastic duct or neoplastic tubular formation but there is no evidence of pre-existing pleomorphic adeno ma. The histological grade of a neoplasm is judged primarily on mitotic rate, cellular pleomorphism and stromal invasion. These histological patterns have a bearing on survival. Mucinous adenocarcinoma and papillary cystadenocarcinoma tend to be relatively low grade whereas nonmucin-forming tumours tend to be
high grade.47,76 It is prudent to regard all adenocarcino mas as high-grade cancers, for example the salivary duct variant of adenocarcinoma has a particularly poor prognosis. Half the cases of adenocarcinoma of all types have neck node metastases at the time of presentation, and frequently distant metastases as well, with a median survival of only 2.5 years.77 Most adenocarcinomas arise in the parotid gland but constitute only a small proportion of parotid tumours; the other salivary glands are proportionally more affected. Most adenocarcinomas present as a long-standing gradually enlarging mass; less than one-quarter are painful. In the parotid gland they only rarely produce facial nerve palsy and just under one quarter of patients have nodal metastases at. the time of presentation. The disease is one of the sixth and seventh decades of life and tends to affect women more than men.78 Locally advanced disease, high-grade histology and infiltrative growth pattern are features associated with a poor prognosis.78 [**]
Carcinoma ex pleomorphic adenoma
These tumours account for up to 10 percent of all malignant salivary cancer and tend to arise in the major glands. It is very rare for such tumours to occur within a pre-existing pleomorphic adenoma (3 percent) although the risk of malignancy may increase to as much as 10 percent by 15 years;7 9 however, many would challenge this view. In the Liverpool series, most such malignant changes happened in patients who had already had a benign pleomorphic adenoma excised a number of years previously. The same has been noted by others.so Malignant transformation most commonly took place in men over 40 years of age, in tumours of the deep parotid lobe, in solitary nodules greater than 2 cm diameter and in those patients with a history of a previous operation.so The same authors also noted three histological types of this tumour: noninvasive carcinoma, invasive carcinoma and, the very rare, carcinosarcoma. In malignant mixed tumours there seems to be a very clear relationship between prognosis and depth of invasion. A depth of invasion of less than 1 cm is associated with a five-year survival of approximately 100 percent; if the depth of invasion is greater then the five-year survival is halved. Lunaso has used a different histological classification. The first is the true carcinoma in a pleomorphic adenoma, which is by far the most common variant, and if a metastasis occurs it is from the carcinomatous element alone. The second type is the carcinosarcoma in which both components of the tumour are malignant and can metastasize. The third type is a metastasizing mixed tumour, in which metastases not only contain malignant elements but also structures typical of a benign tumour. The final type is the noninvasive carcinoma or carcinoma in situ in a p re-existing benign pleomorphic adenoma. The prognosis for most patients with a carcinoma ex
Chapter 190 Malignant tumours of the salivary glands .
pleomorphic adenoma is poor: the cause-specific survi vals for this disease are 40 percent at 5 years, 24 percent at 10 years and 19 percent at 15 years according to the Memorial Hospital figures8l and they are confirmed by others.6l During follow-up one-quarter of patients developed lymph node metastases and one-third develop distant metastases.82 [**J
2501
in the aetiology of this disease.38 It is very unusual to achieve a cure in this neoplasm, which has a median survival of 30 months and a cure rate of probably less than 10 percent.8? Owing to its undifferentiated histology and similarity with nasopharyngeal cancer, irradiation should form a crucial part in treatment. [****J Lymphoma
Squamous cell carcinoma
According to Batsakis et al.,83 the incidence of primary SCC of the salivary glands is somewhere between 0.3 and 1.5 percent. SCC involving the salivary gland is much more common and, to be defined as a salivary carcinoma, certain criteria must be met. The tumour must arise from the gland itself and not from lymph nodes within the gland. There must be no regional or adjacent tumour especially of the skin and, needless to say, a high-grade mucoepidermoid carcinoma must be excluded. The Memorial Hospital, when reviewing their histology, found that squamous carcinoma accounted for only 12.5 percent of all malignant salivary gland tumours.59 Over almost a 30-year period the same group reported only 10 of these tumours in the parotid and 15 in the submandibular glands.84,85 In an analysis of 50 cases of SCCs of the salivary gland over a 30-year period, 42 cancers of the parotid gland were recorded and only 6 of the submandibular gland.86 Most patients present with a painless mass but approximately 20 percent do have pain and facial palsy occurs in around 10 percent. Nearly half of all patients have neck node metastases at the time of presentation. A locoregional failure rate of approximately 50 percent is to be expected for the parotid but is rather higher in the submandibular gland. Distant metastases occur in approximately 10 percent of patients. Shemen et al.,86 when discussing prognostic factors, noted that advanced age, tumour fixation and lymph node metas tases were associated with a poor prognosis. Whatever the treatment the cure rate for this disease is disastrous with almost no five-year survivors.8? [**J
Undifferentiated carcinoma
These tumours commonly arise from ductal reserve cells and histologically are small-cell cancers. As with other undifferentiated malignancies, the incidence of reporting this histology has decreased as IHC has become routinely used for this type of tumour. Now undifferentiated carcinoma probably accounts for little over 1 percent of all salivary gland cancers.88 Undifferentiated carcinomas of the salivary glands are microscopically identical to the undifferentiated carcinoma seen in the nasopharynx. Not only does this mean that a nasopharyngeal carcinoma must be excluded in diagnosing this salivary neoplasm, but it also suggests that EBV infection may also play a role
Batsakis and Rugezi89 suggest three criteria for the diagnosis of this disease: extraglandular lymphoma must not be present; there is histological proof that the lymphoma involves the gland parenchyma and not the intraglandular lymph nodes; immunohistochemical screening must confirm the presence of lymphoma markers. Most lymphomas involve the salivary gland as part of a regional disease. However, there are a number of important points to consider here. In general, low-grade non-Hodgkin's lymphoma (NHL) is either not treated at all or, if it is, conservative monomodal management is undertaken with drugs such as chlorambucil. High-grade lesions are usually treated aggressively with complex regimens such as VAPEC-B. Interestingly, if dealt with as above, both groups have a median survival of approximately eight years.90 [**J Malignant lymphomas arise relatively rarely in the major salivary glands.90 True extranodal involvement only happens with NHL although Hodgkin's disease may affect intraglandular lymph nodes. If lymphomas happen at all in minor salivary glands it is impossible, in practice, to assign this site to an extranodal lymphoma. Five-year survival of patients with NHL of the major salivary glands is 74 percent.90 [**J Although unusual, a patient may present with a low grade lymphoma solely involving a salivary gland; usually the parotid. Local excision or radiotherapy may offer a cure in such a patient whereas the common diffuse type of disease is indolent with a median survival of approximately eight years. The other feature which is important in salivary gland lymphoma is its association with Sjogren's syndrome; the risk of developing a lymphoma in this syndrome is said to be 40 times that of the normal population?3 Some data on lymphomas of the salivary glands are appropriate here. Almost all primary lymphomas of the salivary glands affect the parotid and these form almost 5 percent of all extranodal lymphomas.89 Approximately 40 percent of lymphomas of the head and neck are of the salivary glands and nearly all of these are NHLs and well differentiated.90,9l [**J
Metastatic disease involving the salivary glands
The major salivary glands contain and are adjacent to lymph nodes. The superficial parotid lobe contains a
2502 I
PART 1 7
H EAD AND N ECK TUMOURS
median of five nodes and the deep lobe two. Almost all metastases to the salivary glands arise from the skin of the
head and neck and involve the parotid lymph nodes.n, 93
Mucoepidermoid carcinoma •
common malignant tumour of the major
While metastatic involvement of the parotid gland may only happen in little over
salivary glands, especially in the parotid
1 percent of head and neck skin
squamous carcinomas, this does not take account of the
area drained by the parotid nodes. It has been noted that
•
whereas skin cancer anterior to these involve the parotid in only
•
such important structures as the pinna and the eyelids.
node metastases are due to cancer of the skin of the
pinna.93 Evidently, the very low rate of metastasis to the
parotid, even in carcinoma of the pinna, does not justify
elective parotidectomy. If parotid metastases are present, a parotidectomy
en
bloc with a neck dissection in continuity
with the primary lesion is indicated.95 Even with such
major surgery, five-year survival rates are little more than
the parotid lymph nodes. The incidence is unknown but is major
salivary
2 percent. Cure rates are dismal. The
glands
can
be
the
site
of
distant
metastases.96 The review of the literature by Batsakis and Bautina found only
•
Almost one-third of adenoid cystic
•
Forty-one percent are locally advanced at the
sites were the lung, breast and kidney, the metastatatic 2 Needless to say, survivors
route being haematogenous.9
from such a disease are almost unheard of.
time of presentation.
•
There are three main histological subtypes:
•
•
•
survival than other types.
This disease has a very long natural history recurrence at
30 years.
A cumulative blood-borne lung metastases
rate of 70 percent at five years and
100
percent at ten years has been suggested.
Metastases in bone and liver are not uncommon.
Patients with T l and
metastases
T2 primary site disease
•
20 months later than those with
more advanced disease or solid histology. Adenoid cystic carcinomas have a
Bilateral salivary malignancy is very rare but
pred isposition to invade and spread along
after Warthin's tumour (benign).
cases, being more probable in larger tumours
acinic cell carcinoma is the most common
peripheral nerves, developing in
Hi.<;tological grading of this tumour is not
and likely to affect survival adversely.
reliable.
Histological diagnosis is difficult and the
80 percent of
Carcinoma ex pleomorphic adenoma •
Very rarely develop within pre-existing
mucoepidermoid and myoepithelial
pleomorphic adenomas (3 percent) although
carcinoma.
percent by
carcinoma, oncocytoma and metastatic renal Although acinic carcinoma almost certainly
has the has
a
the risk of malignancy may increase up to ] 0 •
b(� su rvival of any salivary cancers it 0
only
•
or near total parotidectomy with preservation
although data on postoperative rad iotherapy
outcomes are limited.
diameter; previous surgery.
The prognosis for most patients is poor with
cause-specific survivals at S years of 40 percent,
of the facial l1erv� u nless involved, neck
d issection and postoperative radiotherapy
>40 years;
deep lobe tumours; solitary nodules > 2 em
55 percent.
Treatment should probably involve both total
15 years.
Risk factors for malignant change in pleomorphic adenomas: males
long natural history with a I S -year
survival rate
•
The solid pattern is associated with poorer
of cribriform or tubular histology developed
d ifferential diagnosis may include thyroid,
•
(25 percent), cribriform ( 40 percent) (20 percent).
and tubular
and cure is never achieved, with ] 00 percent
[ ***J
Acinic cel l carcinoma
•
presentation.
solid
KEY POI NTS
•
.
Eleven percent have distant metastases at
•
•
carcinomas develop in major salivary glands.
•
35 cases metastatic to the parotid and
1 8 to the submandibular gland; the commonest primary
patients at presentation.
Histologically. they are usefully subdivided
Adenoid cystic carcinoma
10 percent. Malignant cutaneous melanoma can involve probably less ' than
In high-grade tumours, lymph node
into high and low grades.
3 percent of cases.94 The area concerned includes
Indeed, one study suggests that well over half of parotid
glands.
metastases are present in three-quarters of
skin tumours posterior to the facial artery and vein give rise to parotid node metastases in about half of patients,
Mucoepidermoid carcinoma is the most
10
•
years
24 percent and 15 years 19 percent.
During follow-up, one-quarter of patients
develop tymph
nodal disease and one-third
devel<:)p" distant metastases.
/
Chapter
Squamous cel l carcinoma •
True primary SCC of the salivary glands is rare
(0.3-1 .5 peKent) but SCC involving the
gland is m uch more •
Poor prognostic tumour
common.
fattotS 'inClude advanced age,
fixation 4n
For this group c
5 -year survi\lt)�
Und ifferentiattd (lmi noma •
•
1 90 Malig na nt tumours of the salivary glands I 2503
./ Treatment is with radical surgery to the primary site without elective neck dissection and with postoperative radiotherapy to achieve the maximum duration of locoregional control, a lthough neither modality may i nfluence the natural history of the disease. The case for how radical the surgery should be is confusing and unproven. ./ Large tumours are almost inevitably associated with nerve involvement. If gross or frozen section h istology of nerve involvement is found at operation, the nerve should be sacrificed and immediate nerve grafting carried out. ./ The role of chemotherapy a ppears limited, with some responses possible with cisplatinum.
Metastatic disease involvi ng the sal ivary g lands •
lym phoma •
Low-grade N H L is either not treated or treated with conservative mono modal therapy such as chlorambucil.
•
H igh-grade N H L is treated aggressively with complex regimens such as VAPEC-B.
•
./ If parotid metastases from cuta neous SCC are present, a parotidectomy en bloc with neck dissection in continuity with the primary lesion is indicated but five-year survival rates are l ittle more than 1 0 percent. ./ Cutaneous melanoma metastases to the parotid rarely develop (2 percent) but radical resection, as above, yields a disma l outcome.
Both have a median survival of approximately eight years.
•
Five-year survival of patients with NHL of major salivary gland is
•
74 percent.
The risk of developing lymphoma in patients with Sjogren's syndrome is said to be
40
times that in the normal population.
Metastatic disease involving the salivary g lands •
Nearly aU metastases to salivary glands arise from skin of the head and neck.
•
mainly the
HISTOGE N ESIS We owe the basic concept of histogenesis o f salivary gland cancer to Batsakis, who with Rugezi, in
1977, put forward
the bicellular reserve cell theory, postulating that all salivary cancers arise from two types of pluripotent precursor cells. These are the intercalated duct reserve cell 97 and the excretory duct reserve cell; there have been no
pinna, and involve parotid lymph nodes.
significant challenges to this concept. Indeed, in
In skin areas drained by parotid nodes the
pleomorphic adenoma gene I -related protein was identi
incidence of sec metastases to parotid nodes is much greater than the I percent figure
200 1 , the
fied in the intercalated duct reserve cell. This adds 98 As
considerable support to the reserve cell theory.
quoted for lymph node metastases from
salivary gland tumours arise from pleuripotent cells, the
cutaneous SCC in general, i.e. approxi mately
finding that different cell types may be present in one
50 percent for tumours located behind the
tumour is easily explained.
facial artery and
3 percent for those anterior
[****]
to the facial artery. •
Lung, breast and kidney tumours occasionally spread to the parotid gland.
CA N CER OF THE SALIVARY GLA NDS AT THE THREE MAIN SITES The parotid g land Most textbooks of head and neck oncology suggest that
Adenoid cystic carci noma , ./ Diagnostic work-up should include MRI of the primary site and neck with CT of the lu ngs, l iver and possibly the primary site if bone involvement is a l i kelihood, as well as isotope bone scans for bone metastases,
one
in
six parotid tumours are malignant.
Not all
oncologists agree with this, and a much higher figure of 99 one in fou r or even one in three has been quoted. According to the Liverpool head and neck database,
24
percent of all parotid tumours are malignant. Tu mours of the main body of the gland enlarge laterally producing a
____
/
� ..J--
_ _ _ _ __ ... _ __ _ _ _
2504 I
PART
Figure 1 90.4 carcinoma.
1 7 H EAD AND N ECK TUMOURS
A swel ling due to a l eft parotid mucoepidermoid
and carotid vessels, makes surgery even more difficult. Resection of part of the temporal bone is sometimes warranted, although following tumour along the facial nerve into the mesotympanum is, as discussed earlier, usually a futile exercise, particularly for adenoid cystic carcinoma. Where the facial nerve is grossly involved it must be sacrificed and immediate nerve repair carried out. Where the nerve is not grossly involved management is controversial, some oncologists sacrifice the nerve in all 101 high-grade cancers, whereas others preserve the facial nerve unless, of course, it is grossly involved. l02 In any event, facial palsy appears to be an independent prog nostic indicator with those presenting with facial palsy having a very poor prognosis compared with those who 100, 103 The various histological types have been do not. described above but in the parotid gland the commonest malignancy is the mucoepidermoid carcinoma followed by the adenoid cystic carcinoma. In both cases high histological grade or adverse pattern affects prognosis adversely. It should be remembered that the parotid gland contains lymph nodes. From studies in our department, the superficial lobe contains between three and seven nodes whereas the deep lobe contains from nil to three nodes. Regional nodal involvement is seen at presentation 03 in approximately 13 percent of parotid cancersl but the risk of 'recurrence' or 'occurrence' in a previously 1 uninvolved neck is greater than 50 percent. 5 Owing to this finding, either a selective neck dissection clearing areas 1 , 2 and 3 or even a radical neck dissection in high-grade tumours should probably be carried out.46 Postoperative irradiation almost certainly improves loco regional control, although there are no randomized . 104 105 106 [**] contro IIed tnaIs to support thI' S view. ' ,
.
Figure
1 90.5
A massive adenoid cystic carcinoma of the
parotid.
The su bmandib u lar g l and
visible swelling (Figures 1 90.4 and 1 90.5), malignant tumours may enlarge rapidly and facial nerve paralysis is not uncommon. Facial nerve paralysis as a presenting symptom and sign appears in approximately one-third of patients.loo Pain is a symptom of malignancy. Carcinomas of the deep lobe expand medially into the pharynx. Although about 1 0 percent of parotid tumours are of the deep lobe, fortunately, malignancy is fai rly unusual at this site. In our series there is a tendency for deep lobe tumours to be benign with only 1 1 percent of tumours of this site being malignant. The surgical anatomy of the parotid gland is complex; it is in fact a unilobular gland microscopically with the facial nerve growing through it. It is said to be divided into two unequal parts by the facial nerve and thus the concept of a superficial and a deep lobe is purely one of surgical anatomy. The presence of a facial nerve within the gland obviously greatly compli cates ablative surgery, and the proximity of the external ear canal and the middle ear, as well as the mandible
It has been suggested that a tumour of the submandibular 103 gland is twice as likely to be benign as it is malignant. Data in the Liverpool head and neck database, however, suggest that 40 percent of submandibular tumours are malignant. In this gland, adenoid cystic carcinoma is particularly common (43 percent) with mucoepidermoid carcinoma and adenocarcinoma accounting for 17 and 1 1 percent, respectively.46 The tumour may cause nerve involvement, in particular the hypoglossal nerve, followed by the trigeminal nerve and then the facial nerve.loo Lymphadenopathy is seen at first presentation in one quarter of patients. The typical clinical picture is of a slowly growing swelling under the jaw or occasionally in the floor of the mouth. Pain suggests malignancy and palsy in one of the nerves described above may be present. Surgery should include a regional dissection o f the whole submandibular triangle with the gland and surrounding lymph nodes, including areas 1 , 2 and 3. Unless grossly' involved, nerve resection appears unne cessary. In the case of adenoid cystic carcinoma, nerve
j
/
Chapter
biopsy has been recommended l oO and, I'f positive, resection of the nerve should continue until further sections are negative. In our experience this is not particularly helpful as this tumour produces, and indeed spreads, by skip lesions which may have normal nerve for a couple of centimetres between involved segments. Postoperative irradiatior1 should be given for all high grade cancers, and almost certainly improves locoregional contro 1.46, 105, 106 [**J
1 90 Malignant tumours of the salivary glands I 2505
KEY POI NTS The parotid gland •
•
•
Minor salivary g lands (incl uding the s u bling ual g land)
Quoted figures for parotid malignancy """,dAl1fflltl.lll from one in three to one in six of all parotid tumours. The commonest malignancy is mucoepidermoid followed by adenoid cystic carcinoma. Facial palsy is a presenting feature of approxjmately one-third of all parotid malignancy.
The submandibular gland In the Liverpool series, nearly half of all salivary malignancy was in the minor salivary glands.65 This has not been the universal experience, however, with other authors suggesting that only 1 0 percent of salivary gland cancer arises in the minor salivary glands. 103 Most patients present with a smooth lump, usually on the palate, with no associated nerve palsies or lymphadenopathy (Figure 1 90.6). Rapid enlargement, pain or the presence of palsies is a sign of malignancy. The vast majority of minor salivary gland cancers are adenoid cystic carcinomas ( 70 percent) and most of the remainder are mucoepidermoid carcinomas ( 1 9 percent).65, 106 Half of all minor salivary gland cancers are on the palate and approximately 1 5 percent o n the lips o r buccal mucosa; tongue and floor of . 103, 106 I n our senes, mouth are reIatlve . Iy unusua I sites. ' survival was affected by histological type, the site of the primary tumour and the general physical condition of the patient. The Liverpool series showed that patients with adenoid cystic carcinoma did particularly badly as did those of any site other than the oral cavity or oropharynx; patients unfit at the time of presentation also did badly. 65 As with other sites, in spite of the lack of high-quality evidence, high-grade cancers, at least, should be given . " . Irra 105, 106 [ **J postoperatIve dlatlOn.
•
•
•
Quoted malignant to benign tumour ratio varies from 40 to 66 percent. Common malignant subtypes include adenoid cystic (43 percent) , mucoepidermoid ( 17 percent) and adenocarcinoma ( l J percent) . Nerve involvement in order of frequency includes hypoglossal, trigeminal and facial.
M i nor sal ivary g lands (including the sublingual gland) •
•
•
•
•
Malignancy figures vary widely with 1 0-50 percent of all salivary malignancy arising in minor salivary glands. Most present in isolation as a smooth mucosal lurnp. The majority are adenoid cystic carcinomas (70 percent) and of the remainder most are mucoepidermoid carcinomas ( 19 percent). Location is 5 0 percent palate, 15 percent lips and buccal mucosa. Prognosjs is affected by histology, adenoid cystic carcinoma being the worst, location of tumour and general physical condition of the patient.
The parotid g l and ./ Where the facial nerve is grossly involved it must be sacrificed and immediate nerve repair carried out. ./ Where the facial nerve is not grossly involved management is controversial, some sacrifice it in a l l high-grade tumours, others only when grossly involved . ./ Following tumour along the facial nerve into the mesotympanum is usually a futile exercise . Figu re 1 90.6 palate.
An adenoid cystic carcinoma of the right hard
./ Facial nerve palsy is an independent poor prognostic indicator.
I
_�_ ---.,- .
...,.1'--_---,'--
2506 I
PART
1 7 H EAD AND N ECK TUMOURS
.I Regional lymph node i nvolvement is seen in 1 3
percent of parotid cancers a t presentation but reg ional nodes may develop i n up to 50 percent of patients, thus at least selective level l , 2 or 3 neck d issection or radical neck d issection i n high-grade mucoepidermoid tumours should probably be undertaken. Postoperative radiation seems to i mprove locoregional control.
The subma ndibular g l a nd .I Resection of the submand ibular gland and level 1 -3
lymph nodes. Nerve resection is u nnecessary unless grossly i nvolved. .I In adenoid cystic carcinoma, nerve biopsy is recommended and, if positive, resection of the nerve should continue until further sections are negative.
DIAGNOSIS AND I NVESTIGATIONS The clinical features o f salivary malignancy have been described above. While the majority of tumours present with a slowly enlarging painless swelling, the following symptoms and signs are ominous: • • • •
pain; nerve palsy; skin invasion; neck nodes.
diagnosis is still not forthcoming then a decision regarding malignancy will have to be made on clinical and radiological grounds. If malignancy is a possibility then the patient must be taken to theatre, consented for a large resection. Appropriate flaps will have to be elevated and a frozen section biopsy taken. Depending on the results the appropriate surgery can be carried out. It is my view, however, that a head and neck oncology new patient assessment clinic in Europe or North America should always have access to fine needle cytology. A chest radiograph should be performed at the first visit because if metastases are identified there is no point in considering major ablative treatment. If this investiga tion is normal then MRI of the head and neck should be performed (Figure 190.7) 1 10 MRI is superior to CT in our experience and that of others l lO although some I I workers find MRI and CT comparable. I For MRI, enhancement with gadolinium should be used for the accurate identification and delineation of tumours. 1 1 2 I Brain invasion i s well demonstrated o n MRI I 3 and perineural spread by both imaging techniques. In certain cases a magnetic resonance angiogram will help delineate large vessel involvement and also provide an assessment of patency. I 1 4 For surgical planning, however, invasive angiography will be necessary. Particularly when major ablative surgery is contemplated, metastases should be sought by a CT scan of the chest and upper
Rapid enlargement
Following a full history and head and neck examination, the size of the swelling should be measured with callipers and any other features noted. A fibreoptic upper airway endoscopy should be carried out in every patient. The mainstay of early diagnosis (in the clinic) should be fine needle aspiration cytology of the salivary gland lesion and any enlarged neck nodes. While it is well known that salivary tumour cytology is difficult, in 1 993 we published a series of almost 100 patients with head and neck salivary swellings that had been immediately reported by a cytopathologist in the clinic. 107 The results of cytology were later compared with definitive paraffin embedded section pathology. Cytological diagnosis was incorrect in five patients, only one was a false negative result and there were no false positive results. Sensitivity was 91 percent and specificity 100 percent. 107 In the Liverpool study, cytology was carried out by a consultant cytopathologist with much experience in head and neck tumours. Other centres have not noted such good resultsl08 but accurate diagnosis increases with experi. 09 . we re1y very heaVl'ly on a ence. 1 C erta inly, III our umt, cytopathological diagnosis. [**J If cytology is unavailable this poses a dilemma as other methods of obtaining tissue carry the risk of spreading the tumour. For large gland disease a large bore biopsy needle can be used (e.g. Trucut). For minor gland disease an excision biopsy should be performed if possible. If a
Figure 1 90.7 A CT scan showing a large left parotid adenoid cystic carcinoma. The lesion is partly lobulated and not invading the paraphary� geal space although displacing structures in this area.
/ J
Chapter
iS abdomen. l If base of skull involvement is present, a CT scan of this area should also be obtained in addition to MRI. Imaging has been discussed more fully in Chapter 1 46, Imaging of the salivary glands. A bone scan is not usually necessary. The role of newer imaging techniques such as positron emission tomography and single photon emission computed tomography has yet to be determined but experience so far is very encouraging. [** 1 At this stage a definitive International Union Against Cancer (UICC) TNM stage must be assigned to the tumour 1 l 6 (Table 190. 1 ) . For minor salivary glands the site and stage is as for SCc. Full host and tumour (TNM) details are given for the Liverpool series in Table 190.2.
Table
1 90 M a l ignant tumours of the salivary g lands I 2507
1 90.2
Salivary carcinom a : the Liverpool experienc e. Parotid
%
%
Host factors Age < 60
51
60
55
Age > 60
49
40
45
Male
62
48
44
Female
38
52
56
ECOG 0
62
60
63
ECOG 1
28
24
20
ECOG 2-4
10
16
17
1 00
100
Tumour factors Site
Superficia l : 9 1 Deep: 9
Su blingual
1 90.1 Summary of U ICC TNM staging for malignant sal ivary g land disease. Table
Stage
Description
4
Larynx and pharynx
21
Hard palate
24 9
Buccal mucosa Other oral cavity
16
Maxillary antrum
9
Other nose and sinus
Pri mary
site
Tl T2 T3 T4
< 2 cm, without extraparenchymal extension > 2-4 cm, without parenchymal extension > 4-6 cm, and/or extraparenchymal extension > 6 cm, and/or base of skull or seventh nerve involvement
Nodes Nl N2a N2b N2c N3
, _. I
r
' .
•
wi t h
, .
.
"
: '�
�
.. �. � r . .....-.�� :. ....r.-
3
Histology Muc oe p i d e rm o id
23
8
19
Adenoid cystic
19
69
70
Mixed
9
4
3
Acinic
9
a
2
SCC
9
3
0
4
12
6
Adenocarcinoma
11
4
0
Undifferentiated
16
a
0
T stage
permission.
y ;�� ",",-.�.. .. � . .... .
7
Ear
Other (rare)
Single i psilateral node <3 cm Single i psilateral node > 3-6 cm Multiple i psi lateral nodes <6 cm Bilateral or contalateral nodes < 6 cm Nodes > 6 cm
Reproduced from Ref. 1 1 6,
Trachea
1
5
20
40
2
19
36
24
3
34
8
17
4
42
36
19
77
80
90
17
16
6
2
3
8
3
3
3
a
N .
stage
a
,, �
./ Pa in, nerve palsy, skin invasion and neck nodes a re ominous cli nical featu res. ./ Fine needle aspi ration cytology is the mai nstay of early d iagnosis and can have a sensitivity of 91 percent and a specificity of 1 00 percent. ./ A chest rad iograph should be performed at the first visit to rule out metastases. ./ MRI of the head and neck and brain, if a ppropriate with gadolinium enha ncement. MRI angiography may be h e l pfu l with suspected vessel involvement. ./ CT of the chest and u pper abdomen and possibly base of sku l l if a ppropriate. ./ Bone scan not usua l ly necessary. ./ Full TN M staging.
ECOG,
general condition;
0,
good ;
carcinoma; T, primary site stage;
N,
4,
bedridden.
SCC,
squamous cel l
neck node stage. Total number o f cases,
326.
TREATMENT Radiotherapy In spite of the lack of randomized controlled trials dealing with this topic and, indeed, any type of level 1 evidence, and in spite of the fact that all large studies to date are retrospective, it is almost unanimously agreed that surgical ablation should be the primary treatment
!
--- - - --- - -� --"' ---
2508 I PART 17
HEAD AND NECK TU MOURS
modality.45,5 1 ,59,65,67,84,85 In addition, in Liverpool, as in many other centres, this is followed by postoperative irradiation. The evidence for giving postoperative radio therapy in salivary malignancy is compelling, although retrospective.65, 1 17, 1 18, 1 19, 120, 121 , 122 From statistical modelling studies carried out in our department, there seems little doubt that postoperative radiotherapy significantly reduces lbcoregional recurrence by a factor of three and this has been noted by other authors.120, 121 Our own analysis suggests that although this may improve early survival, the effect on long-term survival is dubious. Two large studies disagree, 120, 121 however, and report a five-year survival of 70 percent with postoperative radiotherapy compared with 25 percent without. In a well-performed study, Shingaki et ai., 122 as indicated in the Liverpool series, were unable to demonstrate any long term survival benefit from postoperative irradiation. [**] As regards indications for postoperative radiotherapy, not surprisingly, nearly all authors recommend it if residual tumour is present 1 17 and for high-grade cancers. A positive microscopic surgical margin may be associated with a high rate of distant metastases, which may be reduced by adjuvant radiotherapy, although some suggest it is not. 12 0 There is more controversy about postoperative irradiation as part of the management plan for minor salivary tumours. It would seem that locoregional control is improved by this treatment modality65 although survival is not. It has been recommended that perineural spread of tumour is an indication for postoperative radiotherapy. Perineural spread is a sign of aggressiveness in adenoid cystic carcinoma. As skip lesions frequently occur, the probability of recurrent or residual tumour · is accordingly increased and postoperative radiotherapy should therefore be given. In our experience postoperative irradiation should also be administered to those with cervical node metastases or if the cancer is adjacent to a nerve. There is no doubt that ablative surgery for recurrent disease should be followed by radiotherapy if possible and even reirradiation and/or brachytherapy considered. As regards radiotherapy dose, most oncologists recommend a total dose of 60 Gy in fractions of 2 Gy a day. 121 , 122 The radiation dose should, arguably, be higher than this or treatment provided by an accelerated regimen. The place of chemotherapy and chemoradiation in this setting has not been resolved. As regards other types of radiotherapy, fast neutron treatment has been compared with standard photon treatment and has shown improved locoregional control. Subsequent experience with fast neutrons has been that this improvement is at the expense of potentially devastating damage to the irradiated site, including necrosis, severe fibrosis, loss of function and fistula. 123 [**]
Chemotherapy
For various reasons salivary cancer has a high rate of distant metastasis with one-fifth of patients succumbing
to it.124 It is largely for this reason that many regard chemotherapy as an essential adjuvant to the treatment of malignant salivary cancers. Regrettably, no studies to date have shown these agents to be effective. 124, 125, 12 6 Even in the area of locoregional palliation drugs have little useful effect125 although there are often good initial responses. For the adeno types, doxorubicin is effective, particularly in combination with cisplatin and perhaps 5-fluorouracil. For the squamous malignancies the latter two agents are effective in the initial stages. There is no doubt of the effect of these drugs early on in treatment, with good response rates in up to half of patients.127 While the response rates are not in question, there is no evidence in the literature to suggest that these are translated into long-term locoregional control, let alone survival. If used at all, most chemotherapy regimens are given post operatively, but at present it is unknown whether this is the correct approach and the intermediate future may lie with chemoradiation protocols. [***]
Surgery
There is strong, but by no means level 1 evidence that primary surgical ablation of salivary cancer is the treatment modality providing the best chance of cure.45,5 1 ,59,65,67,84,85 There is good, although by no means incontrovertible evidence that postoperative radio therapy should be given.65, 1 17, 1 18, 1 19, 120, 121 , 122 The role of chemotherapy is as yet uncertain but chemotherapy or some other cytocidal therapy targeted at tumour cells by antibodies and viral vectors may offer a real chance of improving the poor results of present treatment. Other treatments based on knowledge of the human genome are rapidly being developed. Gene therapy in particular, either deleting or introducing genes, or using probes to target specific areas of DNA is promising in certain malignancies and already in use in the experimental clinical setting. It is, however, probably some way from being a realistic therapeutic option in head and neck cancer because of its highly complex biology. [**] The basic concept of surgical ablation has been discussed in the relevant sections dealing with the three main sites. The close proximity of other structures including the brain may, in practice, mean that total tumour excision is impossible. This is particularly true for the parotid gland, parapharyngeal space and some other areas that may harbour minor salivary gland cancer. It is not appropriate here to discuss the general concepts of ablative surgery but, needless to say, clear margins should be aimed for, as recommended by Hippocrates in the fourth century Be. Common specific problems at the various sites, such as the proximity of the facial and other nerves, have been discussed. In the case of certain structures, modern surgical techniques can repair and replace skin and mandible with good functional and cosmetic results using free revascularized flaps. Sacrifice
Chapter
of the middle ear (Figure 1 90.8) or even the eye may be justifiable to obtain surgical clearance, although it must be remembered that survival, in general, for patients with such extensive salivary cancer is extremely poor. Likewise, although the facial nerve may be sacrificed in an attempt to obtain good tumour clearance, it must be remembered that facial nerve involvement is in itself an indicator of poor prognosis. Nevertheless, surgical ablation with clear margins offers the best chance of cure and the facial nerve is usually straightforward to repair. In our experience, however, postoperative radiotherapy severely limits func tional recovery. In parapharyngeal space tumours includ ing the deep lobe of the parotid, the carotid vessels may be encountered and if such involvement is limited the tumour can be dissected off the adventitia of the artery. If involvement of the artery is the only potentially positive margin then excision should be recommended. Unless it is the external carotid artery, repair is necessary and is relatively straightforward using a segment of long saphenous vein. Apart from the facial nerve it is rare to find lesions invading adjacent structures in a way limited enough to warrant extensive ablative surgery. Tumours involving the lateral skull base require very careful assessment. Major ablation is possible but with formid able quality of life implications. It should be born in mind that with such major local involvement one is primarily concerned with long-term locoregional control rather than increasing survival. I deal briefly now with the facial nerve and its surgical repair. The dilemma of whether or not to sacrifice the nerve has been discussed above. Essentially, there are three methods of repairing the facial nerve. The first is neurorrhaphy, which involves middle ear surgery to extend the length of the facial nerve stump, and end to-end anastamosis can then be performed. In our experience it is very rare for the nerve to be involved to such a limited extent. The mainstay of nerve repair is
Figure 1 90.8 A rectus abdomonis free flap closing a subtotal petosectomy defect. The petrous was invaded by a medium sized parotid adenoid cystic carcinoma.
1 90 M a l ignant tumours of the salivary glands I 2509
interpositional grafting. This should be carried out at the time of surgery, if only because finding the distal nerve stumps at a second operation is very difficult. The Liverpool experience is that postoperative irradiation, which is given to nearly all our patients with malignant salivary gland disease, impairs facial nerve regeneration. Of the branches of the facial nerve, the most important is the zygomatic allowing eyelid closure, followed by the buccal to allow the perioral muscles to function. The easiest donor nerve to use is the greater auricular because it is in the operating field. If it is involved with tumour or a greater length of nerve is required, it is best to resort to the sural nerve. While there is much academic discussion about which way round the nerve should be anastomosed, anatomical factors, viz. the branching of the donor nerve, usually dictate which way round it must be positioned. From the neurophysiological point of view the ideal is that the distal end of the donor nerve is anastamosed to the proximal stump of the facial nerve. This may occasionally be possible if the main trunk of the nerve has had to be sacrificed. The perhaps, simplistic reasoning behind this is that all peripheral nerves dichotomize from proximal to distal. Thus reversing the orientation of the donor nerve should, potentially, divert the randomly orientated sprouting of the original nerve stump into a smaller number of nerve fibres at the distal end of the graft. The third method is nerve transfer and the donor nerve is usually the hypoglossal. If this is successfully anastomosed to the distal facial nerve, tone can be restored to the face but not normal voluntary movement. In patients in whom major ablation leaves no opportunity for nerve grafting or in a patient who has had the nerve divided for more than two years, then some type of musculoskeletal transfer can be carried out. Other reconstructive techniques may also be useful, particularly facial slings, tarsorrhaphy and facelift. The masseter or the temporalis muscle may be used to create a dynamic sling but in our department we tend to use fascia lata strips to elevate the corner of the mouth. The final strip can be attached to the zygomatic arch and if it requires tightening at a later stage this can be carried out via a superficial incision under local anaesthetic. A facelift is carried out at the time of fascial strip insertion. A dynamic sling can be fashioned using the temporalis muscle and its attached fascia, but whether this provides better long-term function than the previously described methods is debatable. From the functional point of view, it is the eye that is at risk from a facial palsy, with severe damage to the cornea eventually happening in those patients with no Bell's phenomenon. In our department we carry out a limited lateral tarsorrhaphy and insert a gold implant of the appropriate weight in the upper eyelid. This is effective because one-third of the motor supply to the upper eyelid comes from the sympathetic nervous system via the deep petrosal nerve and is not interrupted by parotid surgery.
L
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25 10 I
PART
1 7 H EAD AND N ECK TUMOURS
Treatment of the neck This has been described with regard to tumour type and also site but a summary is appropriate here. In node negative high-grade cancer an elective neck dissection should be carried out because of the very high risk of regional recurrence. Retrospective studies suggest that a selective neck dissection encompassing levels 1 , 2 and 3 should be enough for parotid gland and submandibular disease, with of course clearance of the submental triangle in the latter case. In minor salivary gland cancer the site of the tumour dictates the level of neck dissection; half of such tumours are on the palate and a large proportion of the rest involve other areas of the oral cavity. Evidence is scarce regarding a logical treatment plan for minor salivary cancer but most authorities agree that elective neck dissection is not recommended.65 Postoperative irradiation should not only encompass the primary site but also the first echelon nodes and in the oral cavity this would be levels 1 , 2 and 3. Whether elective neck irradiation in salivary cancer is as effective as elective selective neck dissection (as is the case in SCC) is unknown. Whatever the site and histology, a patient with a salivary gland cancer with a node in the neck at presentation should have a radical neck dissection. Needless to say, a neck dissection can be modified as appropriate within the limits of good oncological treatment but postoperative irradiation should also be given. [**]
Rad iotherapy ./ Surgical treatment is the primary treatment modality followed by postoperative radiotherapy in most centres. ./ Postoperative radiotherapy reduces locoregional recurrence by a factor of 3 which may improve early survival a lthough the long-term benefits are as yet d isputed. ./ Clear-cut indications for postoperative radiotherapy include residual tumour, h igh-grade cancers and probably positive margins. ./ Less clear-cut indications include minor salivary gland tumours where it is said to i mprove locoregional control but not affect surviva l ; perineural spread or tumour close to the nerve; cervical node metastases; recurrent disease - consider reirradiation or brachytherapy as well. ./ Total dose of 60 Gy i n fraction of 2 Gy a day is recommended by most. ./ Fast neutron thera py improves locoregional control but at the expense of potentially devastating damage to the irradiated site.
Chemotherapy ./ Despite the h ig h metastatic rate of 20 percent of salivary cancers there is no evidence that
chemotherapy is effective although good initial responses are seen in u p to 50 percent of patients. ./ Chemoradiation protocols may be where the intermediate future lies.
Su rgery ./ Primary surgery is the treatment with the best
chance of cure followed by postoperative radiotherapy in a ppropriate cases. ./ Clear margins irrespective of the type and extent of resection a re vital. ./ Sacrifice of the ear and the eye may occasionally be appropriate to obtain clearance but size large enough to warrant this is an independent indicator of poor prognosis as is facial nerve involvement. ./ Tumour adjacent to the carotid in the para pharyngeal
space can be dissected off the adventitia of the a rtery. However, if the internal carotid is the only potentially positive margin then the internal carotid involved segment can be resected and reconstructed with a segment of long saphenous vein. ./ Tumours involving the lateral sku l l base can be resected but with formidable quality of life implications and only a realistic prospect of achieving locoregional control rather than increasing survival. ./ Options for facial nerve repair include: neurorrhaphy which involves middle ear surgery to extend the length of the facial nerve stu m p prior to end-to-end anastamosis; interpositional grafting at the time of primary surgery using the sural nerve but postoperative irradiation impairs facial nerve regeneration ; hypoglossal transfer which a l lows tone but not volu ntary movement to be restored ; musculoskeletal transfers, such as fascial slings, tarsorrhaphy and facelifts can be hel pful when there is no opportunity for nerve g rafti ng.
Treatment of the neck ./ I n node negative high-grade cancer, elective neck d issection should be carried out because of the very high risk of regional recurrence. ./ Selective neck d issection of levels 1 -3 should be sufficient for parotid and submand ibular disease with clearance of submental triangle in the latter. ./ In minor sa l ivary gland cancer the site dictates nodal levels to be dissected but most a uthorities agree that elective neck d issection is unnecessary. ./ Salivary cancer with nodal disease at presentation should have an appropriately modified radical neck d issection and postoperative radiotherapy.
PATIERNS OF FAIL U RE AND SURVIVAL ' This subject could be presented either with regard to tumour type or tumour site. The first is more
/
Chapter 190 Malignant tum ours of the salivary gla n d s
scientifically rigorous, whereas the latter is useful for the treating oncologist. Thus, in this section, results from both of these viewpoints are presented.
•
Recurrence rates
True actuarial recurrence rates are not well described in the literature. A major problem is the very long natural history of some tumours. For example, adenoid cystic carcinoma can be shown to have a potential 100 percent recurrence rate at 30 years independent of site.46 Conversely, with SCC the locoregional recurrence rate is approximately 50 percent and as with other SCCs most recurrences occur within the first couple of years following treatment. Mucoepidermoid carcinoma de scribes a wide spectrum of disease, both in terms of histology and natural history, from the relatively benign to the highly malignant. [**] As regards site, the primary site recurrence rate for major salivary gland cancer is 92 percent at 20 years (95 percent confidence interval 77-100 percent; own data) . The Liverpool figures are as follows. •
•
•
There is no significant difference between recurrence rates for the parotid gland or the submandibular gland. As regards the minor salivary glands, primary site recurrence rates are lower at 73 percent at 20 years (95 percent confidence intervals 64-88 percent; own data) (Figures 190.9 and 190. 1 0). Recurrence or subsequent occurrence in the neck is relatively unusual in both major and minor salivary gland cancer. For the major salivary glands the 10- and 20-year node recurrence rates were the same at 26 percent (95 percent confidence intervals 12-40 percent) but are obviously higher in patients who presented with a node (Figure 190. 1 1). For minor salivary gland cancer the neck node recurrence rate at 12 and 20 years was the same at 29
•
percent (95 percent confidence intervals 40-44 percent) (Figure 190. 1 2). As regards minor salivary glands, cancers affecting the hard palate tend to fail less often locally than cancers of the other minor sites. The natural history of various histological types of minor salivary cancer has been described previously. Locoregional failure is more likely with advanced tumours at the primary site, spread of the cancer outside the gland and the presence of neck node metastases at presentation. This has been noted by other authors.48,5 1 ,56,65, 1 02, 128 The problem of distant metastases has been discussed earlier in this chapter and is adversely affected by all the above factors but also includes recurrent neck disease and the total tumour load. 129, 1 30 [**]
Survival
Survival data are generally better reported in the literature on salivary gland malignancy than are accurate details of recurrence. Survival data are not necessarily accurate as it IS well known that death certification is not accurate, 0
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/
251 2 I PART 17
H EAD A N D N ECK TU MOURS
particularly in a disease with a long natural history. Nevertheless, in the Liverpool database death certifica tions are audited. Salivary gland cancer is a remorseless disease with a 5 1 percent tumour-specific survival at 5 years, 39 percent survival at 10 years and 32 percent (95 percent confidence intervals 2 1-43 percent) (Figure 190.13) at 20 years in major salivary glands (Liverpool data) . The corresponding data for minor salivary gland cancer is 76 percent at 5 years, 64 percent at 10 years and 34 percent (95 percent confidence intervals 18-5 1 percent) at 20 years (Liverpool data) (Figure 190.14). As discussed above, the only scientifically viable way of classifying salivary malignancy is on histology, with IHe if necessary. A simple plot of high-grade, intermediate grade and low-grade tumours can be given with the expected survival differences. Not all salivary tumours can be graded in this way and even in some that can, such as mucoepidermoid carcinoma, it is fairly subjective. For this reason this chapter presents Kaplan-Meir curves for eight major histological types although the plots are often fairly complex. The survival of major salivary cancer by histology is shown in Figure 190.15 (Liverpool data) . Adenoid cystic carcinoma has a 57 percent survival at 10 years falling to a 35 percent survival at 20 years. Mucoepidermoid carcinomas of all grades have a
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ten-year survival of 54 percent. Squamous cell carcinoma has a ten-year survival of 49 percent. The ten-year survival for undifferentiated cancer is only 7 percent. The Liverpool experience of acinic cell carcinoma confirms the views that it is not particularly benign, having a ten-year survival of 53 percent. Very rare malignant salivary tumours have been grouped together and have a ten-year survival of 28 percent. Adenocarcinoma has a particularly poor survival of 11 percent at five years and there were no survivors at ten years. The malignant mixed tumour has a ten-year survival of 37 percent. Not surprisingly, the log rank test confirms that there is a highly significant difference between the different histological types (p < 0.000 1) . The data for minor salivary gland cancer are shown in Figure 190.16. As is typical of this disease, adenoid cystic carcinoma has a relatively benign course at five years and a 72 percent survival at ten years. This falls to only 34 percent survival at 20 years. The ten-year survival for mucoepidermoid carcinoma of all grades is 5 1 percent. Other types, which could not be analyzed on their own because of the small numbers, were grouped together. They consisted mainly of adenocarcinoma with malignant mixed tumours forming most of the remain der. The 10-year survival is 67 percent but there were no 20-year survivals. There was a statistically significant difference between survival for the various types (p 0.02 17). Needless to say, the figures of one centre must be compared with those of others. Regrettably, large reviews are now quite old, dating from the mid-sixties to the mid-seventies; nevertheless, the Liverpool series compares well with other reported series with no major , 8 , 1 3 1 , 1 3 2 As differences in survival.45, 5 1 , 59 , 65 , 67 , 84 5 regards site there is no difference between the 5-, 10- and 20-year survivals for parotid gland cancer and subman dibular cancer. The 20-year survival for both is 30 and 29 percent, respectively (Figure 190.17). Minor salivary cancer occurs at any mucosal site in the head and neck, where these glands occur. Four main sites are studied and illustrated graphically in Figure 190.18. The pharynx and the larynx are taken as one group and demonstrate a 74 percent ten-year survival, the nose and sinuses 52 percent and the oral cavity, excluding the palate, a 69 percent
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1 90 Mali gnant tumours of the salivary glands I 25 13
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ten-year survival. Disease located on the palate had a 76 percent ten-year survival. These results are very similar to 10 , lOS, 106, 1 33 , 134 The the findings of other workers.65, 3 Liverpool series does a little worse for parotid cancers and rather better for submandibular cancers than other large series. 84, 85 [** 1 As regards tumour stage and prognosis, Tl cancers have a 70 percent ten-year survival, T2 cancers 4 1 percent, T3 32 percent and T4 9 percent for major salivary glands (Figure 190. 19). For minor salivary cancers the ten-year
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survival for both Tl and T2 cancers was the same at 73 percent, the survival for T3 and T4 interestingly are also the same at 50 percent at ten years (Figure 190.20) (Liverpool data). These data are little different from other published series with the exception that advanced cancer in our series, tends to do a little better. In oncology, the presence of regional nodal metastases suggests a poor prognosis and salivary gland cancer is no exception. The
25 14 I PART 17
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five-year survival for major salivary gland cancer without neck node metastases was 52 percent and for those with neck node disease the figure was 22 percent. Although ten-year figures could not be calculated due to small numbers of patients surviving in the node positive group, the difference between survivals was significant (p = 0.03 10; Figure 190.10). For minor salivary gland cancer the number of patients with neck node metastases was too small to allow product limit estimators to be calculated. Nevertheless, the figures are not significantly different from other published work previously quoted. Various methods of attempting to calculate prognostic risk have been described. 128, 129 The UICC TNM classi fication attempts this1 1 6 but it has its limitations.13s Our department at the University of Liverpool has done much work on the multivariate analysis of survival in head and neck cancer and the Liverpool series contains 253 patients with malignant salivary cancer. The accepted method of analyzing failure in biological systems (and others) is Cox's proportional hazards model fitted to a Weibull distribution.136 Using this technique only three factors were of prognostic significance in malignant tumours of the large salivary glands: age over 60, T stage 3 and 4 versus 1 and 2 and the presence of a primary site recurrence, all adversely affected survival (p = 0.0043, P = 0.049 1 , P = 0.0069, respectively). As regards minor salivary gland cancer, age over 60, poor general condition (Eastern Cooperative Oncology Group (ECOG) greater than 1 ) , the presence of recurrence at the primary site, the presence of recurrence in the neck and the presence of neck node metastases at the time of presentation all adversely affected survival (p = 0.0020, P = 0.0066, p = 0.023 1 , p = 0.0024, p = 0.0335, respectively). [**J Association between clincopathological variables for salivary gland disease are discussed here because of the importance of recurrence and its association with such variables. In an analysis of the Liverpool database of malignant salivary disease carried out for this chapter, categorical modelling showed a surprising lack of association between factors. Histology, in particular, has no association within the major or the minor salivary
cancer group of patients. There was an assoClatlOn, however, across these groups of patients in that adenoid cystic carcinoma was more common in minor salivary disease (p = 0.047 1 0 ) . Of more practical relevance is that recurrence at the primary site in major salivary cancer was more common in patients over 60 years of age (p = 0.0 1 2 2 ) . No such relation was found for minor salivary gland disease and recurrence in the neck was also not associated with any other factors. As regards multi variate survival analysis, others have found age, T stage and N stage useful indicators of prognosis. In addition, pain, facial nerve dysfunction and skin invasion are useful indicators of prognosis with the addition of perineural spread and positive margins after surgical excision. 1 18 Formulae have been constructed based on the findings of multivariate analysis of survival data 1 18 but their clinical usefulness is at least doubtful and of limited use when dealing with an individual patient. The basic problem of assessing survival data using complex statistical pro grammes is that they, of necessity, deal with probability functions, which may or may not be accurate as regards the patient. Recent work in our department using complex mathematical algorithms such as artificial neural networks and genetic algorithms with the inclusion of various molecular variables undoubtedly improves the accuracy of prediction. It is hoped that inclusion of more molecular data into the algorithm will soon allow accurate prediction of the course of the disease in a particular individual as well as indicating the most appropriate treatment. [**J
Compli cations
With the exception of certain nerve palsies the complica tions of the treatment of salivary gland cancer is the same as for head and neck cancer of the various sites. Local, pedicled or microvascular flaps are routinely used to repair skin deficit and reconstruction of the mandible is now routine using osteocutaneous microvascular flaps. Defects in the palate can be closed by this method or, more usually, by an obturator fitted to the upper teeth or denture. Deficits to the lips, tongue, pharynx and larynx are more appropriately discussed in Chapters 192, Oral cavity tumours including the lip; 193, Oropharyngeal tumours; and 1 94, Tumours of the larynx, dealing with the cancer of these sites. Local invasion of tumour into the carotid artery, if the rest of the tumour is deemed resectable, is not an absolute contraindication to surgery. The carotid artery repair is straightforward using standard vascular techniques and the saphenous vein as the replacement. The main technical problem here is the accessibility of the upper end of the resected carotid artery and poor access can make anastomosis technically very demanding. If.resection is felt to be impractical, balloon occlusion of the carotid preoperatively can be carried out and, if no neurological signs develop, the occlusion can be
Chapter
made permanent. One must, however, be aware that propagated thrombosis may gradually develop with disastrous consequences. As regards treatment of the neck, various deficits are well known and can be reduced by the techniques of modified neck dissections and selective neck dissections. These problems are dealt with in Chapter 199, Metastatic neck disease. The side effects of radiotherapy are well known. In practice, the main common sequel is poor salivary flow when the parotid glands are irradiated to any dose above 1 5-55 Gy. There are various methods of ameliorating this problem including, for example, the administration of amifostine, and they are previously discussed (see under Radiotherapy) . The almost unique problem encountered when dealing with salivary malignancy is damage to the facial nerve; in the hands of experienced head and neck surgeons a superficial parotidectomy even for malignancy should not be associated with more than a 5 percent risk to the nerve. 137 The methods of facial nerve repair are discussed above (see under Surgery). Nerves may have to be sacrificed in the removal of the submandibular gland for malignancy; nerves close to the submandibular gland are the mandibular and cervical branches of the facial nerve, the hypoglossal nerve and the lingual nerve. Normally, these lower facial branches should not be damaged unless they loop particularly inferiorly to the mandible or a wide excision of soft tissue is necessary. Damage due to over retraction of the upper skin flap is, however, the commonest cause of this problem; recovery is rare. Sacrifice of the hypoglossal nerve leads to paralysis of one side of the tongue but adaptation is good and rarely causes severe problems. Damage to the lingual nerve is less likely as it is high up behind the mandible but if damage does occur it is potentially a serious problem as the loss of sensation allows repeated trauma to the tongue from dentition. Repair tends to be unsuccessful and we had one patient who finally underwent a partial glossectomy, although obviously this would not be the first-line management. [**J A specific complication that affects patients with surgery for the parotid gland is Frey's syndrome. The true incidence of Frey's syndrome has not been accurately determined but it may be in the region of 30 percent for a superficial parotidectomy, although a rate of half this is commonly quoted.138 Frey's syndrome can be dealt with by placing fascial grafts between the skin and the gland bed or it can be treated by injections of botulinum toxin A. In any event, Frey's syndrome is rarely a problem in parotid gland cancer as postoperative irradiation is a pre requisite of adequate treatmentl38 and, in addition, is effective at inhibiting parasympathetic nerve regrowth. Occasionally, patients develop a salivary fistula; these almost always resolve spontaneously or are incidentally cured by postoperative radiotherapy. If they do not botulinum toxin may be useful. [ ***J
.1
\
1 90 Malignant tumours of the salivary gla nds I 25 15
KEY POINTS •
•
•
•
Nerve palsies: facial, hypoglossal, " U'fI§U'�1It - Facial: In a superficial paifotidect()Iri\,,,. ,&,tt; malignancy, the rate should not be than 5 percent. Excessive flap retrac�on �i):\ ;...'t� submandibular surgery is the main cause of marginal mandibular nerve loss of function and rarely recovers fully. - Loss of hypoglossal nerve function rarely presents a problem. - Loss of lingual nerve function is rare by virtue of its deep position but results in problematic accidental tongue biting. Frey's syndrome rates may be as much as 30 percent but it is t:arely a problem because of postoperative radiotherapy, which inhibits parasympathetic regrowth. It can be dealt with by applying a graft between the skin and the graft bed or by injection of botulinum toxin A. Salivary fistulae tend to resolve spontaneously or are incidently cured by postoperative radiotherapy. If they do not, botulinum toxin may be helpful. Complications related to radiotherapy. The main problem is dry mouth when the parotid glands are irradiated in doses greater than 1 5-55 Gy.
CONCLUSION Salivary gland cancer is, despite multimodal treatment, a particularly demanding tumour for both patient and oncologist. This almost always involves a radical excision, followed by postoperative radiotherapy. Even with aggressive therapy the primary site recurrence rate at 20 years is more than 90 percent for major salivary cancers and nearly 75 percent for minor salivary cancer. Survival rates for major salivary gland cancer at 5 years are in the region of 50 percent falling to only 27 percent at 20 years. For minor salivary cancer the 5-year survival is in the region of 77 percent falling to 34 percent at 20 years. As regards histology, the squamous tYPe such as mucoepidermoid cancer and SCC behave in a similar fashion to other head and neck squamous cancers with a cure at five years of 50-60 percent. Acinic cell cancer, although initially appearing to run a relatively benign course, begins to cause a significant number of deaths at approximately five years. Shortly after this time, survival falls to 53 percent but does not decrease any further. Adenoid cystic carcinoma, although apparently similar to squamous-type cancer at 5 years, continues to behave aggressively with deaths continuing to occur even after
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1 7 H EAD AND N ECK TU MOURS
30 years. In spite of these results, salivary gland malignancy is worth treating, with cure rates from the squamous-type cancer being similar to SCC of the head and neck in general and the results for the adeno-type cancers being similar at five years. Adenoid cystic carcinoma, in particular, has a slow insidious relentless capacity to recur locally in spite of adequate multimodal treatment. Deaths continue to occur after 30 years (own data), thus most patients live with the disease rather than are cured from it and eventually most will succumb to this cancer. This should be borne in mind when treating the cancer, in particular with regard to sacrificing important structures such as the facial nerve. There is no evidence that removing the nerve merely because the tumour is close to or even abutting it improves survival. Obviously, if the nerve is invaded it must be excised and immediately grafted although one must be aware that this may not confer a survival advantage. It is doubtful if super radical skull base procedures are warranted in this disease. Treatment of adenocarcinoma and undifferentiated carcinoma and certain very rare cancers of the salivary gland yield few, if any, survivors but loco regional control may be achieved for a time. Approximately half, or slightly more, patients with salivary cancer can be rendered disease free for five years. Those with squamous-type histology can then expect to be cured and those with adenoid cystic carcinoma will continue to suffer locoregional recur rences, then distant metastases and eventually die of their disease. It must be remembered that even a patient with multiple secondary deposits of adenoid cystic carcinoma in the lungs can sometimes live for five years or more (own data). The advent of multimodal therapy, that is surgery followed by irradiation, may have improved survival rates, although certain proof of this is lacking; it does, however, reduce locoregional recurrence. Distant metastases may produce a fatal outcome in at least 20 percent of patients with salivary cancer and it is doubtful whether the type of primary treatment has any effect on this.
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•
In parotid cancer, unless the facial nerve is involved microscopically, sacrifice of the nerve does not improve survival . Therefore, in resection the goal should be to preserve the facial nerve. The ten-year tumour-specific survival for glandular-type cancers is approximately SS percent falling to 3S percent at 20 years. For squamous cancers the ten-year survival is similar but falls no further after this period.
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J o h n s M E, Cou l t h a rd SW. Su rviva l a n d fo l low u p i n m a l i g n a n t t u m o rs of the sa l iva ry g l a nds.
malignant tumors, 5th e d n . New Yo rk: W i l ey-Liss, 1 99 7 :
Otolaryngologic Clinics in North America. 1 97 7 ; 1 0 :
20-46.
455-60.
Re n e h a n A, G l eave EN, H a n cock BD, Smith P, M cG u rk M .
1 32.
Th e ri a u lt C, Fitzpatrick PJ . M a l ig n a n t pa rotid t u m o rs-
Lo n g -term fol low- u p of ove r 1 000 patie n ts with sa l ivary
pro g n ostic factors a n d opti m u m treatme nt. American
g l a n d t u m o u rs treated in a s i n g l e centre. British Journal of
Journal of Clinical Oncology. 1 98 6 ; 9 : 5 1 0-6. 1 33.
S p i ro R H , Koss LG , H aj d u SI, Stro n g EW. Tu mors of the
Ka g a n AR, N u ssba u m H, H a n d l e r S, S h a p i ro R, G i l be rt HA,
m i n o r sa l iva ry g l a n d ori g i n : A c l i n i copath ologic stu dy of
J a cobs M et al. Recu rre nce from m a l i g n a nt pa rotid sa l iva ry
492 cases. Cancer. 1 973 ; 3 1 : 1 1 7-20.
g l a n d tu m o rs. Cancer. 1 97 6 ; 3 7 : 2600-4. 1 1 9.
131.
Sob i n LH, Witte k i n d C. UlCC TNM classification of
Surgery. 1 99 6 ; 83 : 1 750-4. 1 1 8.
G a l l o 0, Fra n c h i A, Botta i GV. Risk factors for d ista nt
m etastases from ca rc i n o m a of the p a rotid g l a nd. Cancer.
m a n a g e m e n t of patie n ts prese n t i n g with head a n d neck
1 1 7.
Reg i s de B rito Sa ntos I , Kowa lski CP, Cava l c a n te de Ara njo
R u b i n G D, Dake M D, Se mba CP. Cu rre n t status of t h ree-
JW, G e rl i n g e r I et al. Role of ch est CT sca n n i n g i n the
1 1 6.
Vermorken J B , Ve rwe ij .I, d e M u l d e r PH, Cog n etti F, Cl ave l M , Rode n h u i s S et al. E p i ru b i c i n i n pati e n ts w ith a dva n ced
Casse l e m a n JW, M a ncuso AA. Major sa l ivary g l a n d
masses: Co m p a rison of MR i m a g i n g and CT. Radiology.
1 1 2.
J o n es AS. Neopl astic c h e m othera py and head and neck ca ncer. Journal of Laryngology and Otology. 1 99 7 ; 1 1 1 :
M a n d e l b l att S M , B ra u n I F, Davis P, Fry S M , Jacobs LH, H offm a n J r. J C. Pa rotid masses: M a g n etic reso n a nce
111.
Jones AS, Ph i l l i ps DE, Cook .lA, H e l l i w e l l TR. A ra ndom ised
Jandu M , Webster K. The ro l e of operator expe rience in
International journal of Oral and Maxillofacial Surgery. 1 1 0.
Ka p l a n MJ, J o h n s M E, Ca ntre l l RW. C h e m ot h e ra py for
sa l iva ry g l a n d cancer. Otolaryngology and Head and Neck
Elvin A, Su n dstrom C, La rsson SG, Li n d g re n PG. U l traso u nd-gu ided 1 .2 - m m cutti ng- need l e biopsies of
1 09 .
Asg a ra l i S, Erri ngton RD, Jones AS. The treatment of
J o n es AS. Fi n e n eed l e aspi ratio n cyto l ogy of sa l iva ry
c l i n ic. Journal of Laryngology and Otology. 1 993 ; 1 07 : 1 08.
S h i n g a ki S, Ohtake K, N o m u ra T, N a kaj i m a T. The rol e of
t u m o rs o f t h e l i p a n d bu cca l m u cosa. Laryngoscope. 1 989 ; 9 9 : 6-9. 1 07.
Fitzpatri ck PJ , Theri a u l t C. M a l i g n a n t sa l iva ry g l a n d tu m o u rs. International Journal of Radiation OncologY,
A study o f 7 6 pati ents. Clinical Otolaryngology a n d Allied 1 06.
S h i d n i a H , Hornback N B, H a m a ker R, Li n g e m a n R. Ca rci n o m a of the m ajor sa l iva ry g l a nds. Cancer. 1 98 0 ; 45 :
1 02 : 1 064-9.
1 34.
C h a u d ry AP, Vickers RA, G o rl i n RJ . I ntra o ra l m i no r
ma nagement of the pri m a ry lesion i n head a n d neck
sa l iva ry g l a n d t u m o rs : An a n a lysis of 1 ,41 4 cases. Oral , Surgery. Oral Medicine, and Oral Pathology. 1 96 1 ; 1 4 :
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*1 3 7 .
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191 Tumours of the parapharyngeal space
ANDREW S JONES
Introduction
2522
The treatment of para pharyngeal space tumours and
2524
Patterns of failure
2535
parapharyngeal space
2532
other lesions
Histopathology and spread of tumours in the Metastases to the parapharyngeal space
2527
Summary
2537
The spread of tumour within the parapharyngeal space
2528
Key points
2538
Symptomatology
2528
Best clinical practice
2538
Diagnosis. investigations and staging
2529
References
2538
The initial search strategy used PubMed and Medline with the MeSH headings parapharyngeal, tumour, space, lateral pharyngeal, various appropriate histological diagnosis and treatments, in various combinations. Back searching from review articles and from book chapters revealed a number of additional references. Finally, other databases, such as the Cochrane database, the library of the British Medical Association and CHINAL, were searched. In all, 645 relevant references were identified. Initially, these were selected using the title, and then the abstracts. Finally, 319 papers were obtained for use in the present article. Data for detailed analysis were obtained from the 114 patients with parapharyngeal space lesions, identified on the University of Liverpool head and neck oncology database. Clinical recommendations are Grade D.
INTRODUCTION
detailed understanding of this space is crucial to successful
The parapharyngeal spaces (PPS), as the name implies, lie
a high degree of accuracy, particularly with regard to
laterally on either side of the pharynx. They are potential
tumours and their spread.
management. Latterly, radiologists have defined the PPS to
spaces, filled with fat and areolar tissue and bounded and
According to Basmajian,2 who uses the term the lateral
subdivided by various condensations of fascia. The space is
pharyngeal space, it is described as being lined by areolar
poorly described by anatomists; not being mentioned in
fascia, filled with fat and containing branches of the
the 37th edition of
Gray's Anatomyl
and having only an
maxillary
nerve
and
maxillary
vessels.
The
surgical
incomplete description in the 9th edition of Grant's . Method of Anatomy. 2 Although the term parapharyngeal
importance of the space is mentioned, and Basmajian
space has become generally accepted,3 there are many older
and the submandibular space, but not with the retro
names including the pterygomaxillary space, the pharyn
states that the space communicates with the parotid space pharyngeal space. As is widely and, incorrectly, known, he
gomaxillary space, the pterygopharyngeal space and the
states that the apex of the space is at the hyoid bone below
lateral pharyngeal space. The definition, description and
and arises from the base of skull and tympanic tube
general understanding of the PPS was left to surgeons,
above. He go�s on to assert that the medial pterygoid
particularly with regard to deep neck abscesses, where
muscle and the mandibular ramus are anterio-lateral to
/
Chapter 191 Tumours of the parapharyngeal space I 2523 the PPS, and the styloid process and its muscles largely
compartment of the PPS except fat and the parotid gland
separate the space from the carotid sheath. This is a
deep lobe. In addition, the masticator space also contains
standard anatomical description of the PPS, which many
the mandibular branch of the trigeminal nerve. The base of skull attachment of the prestyloid compartment is
of us learnt in the distant past as undergraduates. The following description of the PPS is derived not
narrow, as the fascia of the medial pterygoid and tensor
only from books and papers but also from clinical
palati muscles attach along the same line anteriorly and
A simplified
partially fuse. Conversely, the masticator space attaches to
Figure 191.1. The surgical descrip
a much larger area of the skull base and has the foramen
experience of 114 lesions in this location. diagram is shown in
the
ovale in its roof, allowing potential tumour spread.
constricter
Inferiorly, the masticator space terminates at the lower
tion of the space gives its medial boundary pharyngobasilar
fascia
and
the
superior
as
muscle and laterally by the ramus or the mandible. The
margin of the mandible. The distinction between the
posterior boundary consists of the prevertebral structures.
masticator space and the PPS is somewhat arbitrary. In 5 1987, Curtin formed a study employing anatomical
The styloid process with its muscles and condensations of fascia divide the PPS into a prestyloid and a poststyloid
dissection. He found a fascial layer extending from the
compartment. While the prestyloid compartment has its
medial pterygoid muscle to the base of the skull, which
apex at the hyoid bone, the poststyloid compartment
can ambiguously separate the masticator space from
continues to low in the neck.4 More accurately, the
the PPS. He confirmed that the lower division of the
poststyloid compartment is separated from the prestyloid
trigeminal nerve passed through the masticator space.
compartment
the
When he reviewed clinical cases, he found it straight
by the
tensor palati
fascial
layer;
poststyloid compartment being posterior and medial.
forward to assign tumours to the masticator, prestyloid
The main structures contained in the anterior compart
and poststyloid compartments. He also noted that benign
ment include the pterygoid and tensor palati muscles, fat
salivary
and the deep lobe of the parotid gland. From the purely
compartment of the PPS.
tumours
developed
only
in
the
prestyloid
anatomical perspective, the parotid deep lobe is not
The poststyloid compartment contains the carotid
within the PPS but separated from it by the deep parotid
sheath, with the carotid artery, jugular vein and vagus
fascia. Of some surgical importance is the relation of the
nerve. The compartment also contains the sympathetic
anterior part of the PPS to the masticator space. This
trunk, the IXth, XIth and XIIth cranial nerves and the
space is formed by the splitting of the deep cervical fascia
major part of the internal maxillary artery.
as it reaches the inferior margin of the mandible, and
These fascial subdivisions of the PPS are tedious to
there envelops the pterygoid, temporalis and masseter
remember,
muscles. The medial boundary of the masticator space is
direction of tumour spread and need to be understood
the medial
pterygoid interpterygoid fascia.
Since the
but are very
important in
dictating the
by those contemplating surgery in this area.
A diagram
masticator space contains the pterygoid, temporalis and
matic representation of the spread of a benign parotid
masseter muscles, there is little left in the prestyloid
tumour into the PPS is shown in
Mandible
Figure 191.2. In spite of
Uvula
Stylomandibular process
Parotid gland Styloid process Stylohyoideus Mastoid process Posterior belly
of digastric Styloglossus
Stylopharyngeus
Superior pharyngeal constrictor
Figure 191.1
Cross-sectional anatomy of the
parapharyngeal space.
/ . - -.- - ----.---..,-----.--('-.
..
2524 I PART 17
HEAD AND NECK TUMOURS
Superior pharyngeal Uvula
constrictor
� I
Tumour
I
Stylomandibular
I
process
Stylomandibular ligament I
Figure 191.2 Midline
this anatomical complexjty, nearly all tumours of the prestyloid compartment are deep lobe parotid neoplasms, whereas most tumours of the poststyloid compartment are either paragangliomas or schwannomas. In addition, the great majority of tumours are benign.
A benign deep lobe parotid tumour
spreading into the parapharyngeal space.
Table 191.1
Patients with P P S lesions treated at the University
of Liverpool (over a 30-year period).
Frequency
Tumour type
(n)8 Benign
HISTOPATHOLOGY AND SPREAD OF TUMOURS IN THE PARAPHARYNGEAL SPACE One of the commonest tumours to involve the PPS is nasopharyngeal carcinoma and because of this it appears frequently in citations dealing with the PPS. I deal with tumours spreading to the space later, but at this stage I am concerned only with tumours that arise de novo, within the confines of the PPS and the masticator space. Outline information is provided in Table 191.1 on those patients with PPS lesions treated at the University of Liverpool (over a 30-year period). In a review of 10 years experience (23 cases), Allison et a/.6 found that even large PPS tumours may be asymptomatic. Histologically and anatomically, the most common tumour is the parotid pleomorphic adenoma, located in the prestyloid compartment (Figure 191.3). In addition, he noted that the five patients with malignant tumours did poorly. In a review from Singapore, Stanley7 noted that PPS neoplasms were rare, forming only 0.5 percent of all head and neck tumours. He noted the varied histological types, the most common being salivary gland tumours, schwannomas and paragangliomas. In another small study, this time with 26 patients,S two thirds of tumours of the PPS were benign and one-third malignant. This report found that neurogenic tumours and soft tissue sarcomas were, respectively, the most frequently benign (one-third) and the most frequently
Pleomorphic adenoma
34
Carotid paraganglioma
17
Vagal paraganglioma
16
Schwannoma
11
Other benign salivary tumours
8
Other benign tumours
5
Meningioma
2
Neurofibroma
3
M al i gnant 5
Adenoid cystic carcinoma Mucoepidermoid carcinoma
3
Other malignant salivary tumours
4
Lymphoma
2
Carotid body paraganglioma Vagal paraganglioma
2
Other malignant tumours
"Liverpool series
n=
114.
malignant neoplasms (nearly halO; again, malignant tumours had a poor prognosis.s A further review from Singapore9 studied 31 patients with PPS neoplasms, and again noted that they accounted for only 0.5 percent of all head and neck tumours. The most common histology were the deep lobe parotid tumours, accounting for nearly half of all cases and present in the prestyloid compart ment. Eighteen percent of cases were schwannomas, but
/
J
.�
Chapter 191 Tumours of the parapharyngeal space I 2525
..... . [J'!1?: ...� "\ .� .' ,:,,'11·1
-" ,.,.
,
. .... -:
i
-i
Figure 191.3
CT scan of a deep lobe parotid tumour spreading
into the P PS.
the series contained only one paraganglioma. In a larger series of 144 cases, Biller and his colleagues confirmed the findings of the other reported series.1o Most series found computed tomography (CT) or magnetic resonance imaging (MRI) to be crucial for the diagnosis and management of these tumours, and fine needle aspiration cytology was recommended to obtain a histological diagnosis. Diagnostic methods are discussed later in the chapter under Diagnosis, investigations and staging.
Salivary gland tumours These are the most common neoplasms to involve the PPS and invariably are located in the prestyloid compart ment and almost always arise from the deep lobe of the parotid gland (Figure 191.3).11,12 A minority, however, arise from extraparotid salivary gland tissue in the PPS. Histologically, these lesions are almost always pleomorphic adenomas.13, 14, 15 Rarely, Warthin's tumour, oncocytoma and benign lymphoepithelial lesions have been described and, very rarely, malignant salivary cancers arise, which include mucoepidennoid carcinoma, malignant mixed tumour, adenoid cystic carcinoma and adenocarcinoma.16 A fuller account of benign and malignant salivary gland tumours is given in Chapter 189, Benign salivary gland tumours; and Chapter 190, Malignant tumours of the salivary glands.
in the blood gas partial pressure, particularly of carbon dioxide but also of oxygen, and is also sensitive to pH. The cells are positive for neuron-specific enolase and are classed as neuroectodermal tissue. It is generally felt probable that the relatively common neoplastic change in such a small body of cells is related to their very high metabolic rate. They also have the highest blood flow of any organ relative to their size. Paragangliomas have an interesting epidemiology. A study of 199817 compares tumours arising relatively commonly in the inhabitants of Mexico City, at an altitude above sea level of 2200 metres, with cases reported in the USA and Europe in inhabitants living below 1500 metres above sea level. Over a 30-year period 120 paragangliomas were seen, a relatively large number. While nearly all were benign, 3 percent were malignant. Tumours developing at high altitude appear to differ in a number of respects from the sporadic cases seen at low altitude. High-altitude cases have a female to male preponderance of eight to one, only a 5 percent incidence of bilaterality and a family history in only 1 percent. By contrast, those tumours developing at low altitude have a female to male preponderance of only two to one, bilaterality is relatively common (10-20 percent) and a family history is present in 7-25 percent in the lower altitude group.17 Paragangliomas have a brownish colour and are encapsulated (Figure 191.4). Histologically, they demon strate a typical appearance of epithelial cell clusters in. an extremely vascular and fibrous stroma. The clusters have been given the name zellballen. The tumours are histologically similar to the adrenal medullary
Neurogenic tumours As opposed to salivary neoplasms, these tumours involve the poststyloid compartment of the PPS. The three neoplasms that are involved in this area are paraganglioma, schwannoma, and neurofibroma; other tumours are extremely rare. 'Paragangliomas arising from the carotid bodies were previously known as carotid body tumours or chemo dectomas. The paraganglionic cell is sensitive to changes
Figure 191.4
A carotid body paraganglioma at operation.
\
I
2526 • PART 17 HEAD AND NECK TUMOURS
phaeochromocytoma and cases of catecholamine-secret
ing carotid body tumours have been reported.18 Familial
Familial and multiple paragangliomas and phaeochromocytomas
multiple paragangliomas and phaeochromocytomas.
As discussed previously, multiple paragangliomas occur
Vagal paragangliomas
nonfamilial cases.22, 24,25, 26,27 In familial tumours, the mode of inheritance is autosomal dominant.22,24,28,29,30
paragangliomas are discussed later under Familial and
synchronously in up to 50 percent of patients in familial cases, compared with
These are rare tumours of neural crest origin and less than
200 cases have ever been reported in the literature. They
are slow growing and usually occur in the PPS close to the
base of the skull involving the nodose ganglion, but can
arise anywhere along the course of the vagus nerve and its
branches, including the middle ear. In a review of nine cases, Eriksen et al.19 emphasized evaluation and treat ment of these potentially fatal tumours. Microscopically,
they have a fusiform appearance and are usually sited close to or involving the jugular foramen, and tumours
are well encapsulated. As is well known, a lesion can arise
juxtaposed to the jugular bulb itself and involve the temporal bone; it is frequently intracranial rather than
involving the PPS, doing so only as it expands. A large
jugular bulb paraganglioma (glomus jugulare) may, in
practice, be impossible to differentiate from a large nodose ganglion paraganglioma.2o A recent review of 19
patients revealed that only 3 percent of all paragangliomas were associated with the vagus nerve?! While carotid
body paragangliomas only very rarely secrete catechola
mines,!8 it is more common in vagal paragangliomas?!
Owing to the rarity of secreting tumours, some type of logical approach must be adopted to exclude metaboli
cally active lesions. First, a history of hypertension, in
particular, labile hypertension, facial flushing or tachy
cardia should be specifically sought, a serum catechola
mine estimation should be made and a 24-hour urinary
vanillylmandelic
acid
(VMA)
collection
should
be
performed. If the results are suspicious the consensus view seems to be to proceed to a metaiodobenzylguani dine scan.
MIBG
While metabolically active paragangliomas are rare, familial paragangliomas are not, forming almost
50
percent of one series.22 In almost all cases, at least one of the other tumours was sited in the carotid body.
Paragangliomas of the various sites vary with carotid
body paragangliomas, appearing in half of the nonfamilial
cases and only 30 percent of the familial cases. Although
any combination of multiple paragangliomas can happen in certain individuals, with occasionally more than four
tumours reported, the commonest synchronous tumours are carotid body and jugulotympanic tumours.30 Of great
clinical importance is the synchronous occurrence of
paragangliomas and phaeochromocytomas?2,26 As is
widely known, patients with phaeochromocytomas have
a tendency to sudden rises in plasma catecholamine levels,
leading to severe and even fatal hypertensive episodes.
Such episodes are particularly likely to happen during
anaesthesia. Thus, in spite of the rare concurrence of this
tumour with paragangliomas, screening should be under
taken. As discussed above under Vagal paragangliomas,
this should include blood pressure monitoring, preferably by continuous an1bulatory electronic monitoring, mea
surement of plasma catecholamine levels and a 24-hour
urinary VMA estimation. Whether it is justifiable to
carry out an abdominal CT scan is uncertain. Some
centres do not use 24-hour VMA measurements as, in
the clinical setting, 24-hour urine collection is rarely
complete, leading to unreliable values.
Other neuroendocrine and endocrine tumours can
happen in association with paragangliomas. These include
parathyroid adenomas, thyroid carcinomas and certain other rare neural crest tumours.28, 3!, 32
The association of phaeochromocytoma with para
ganglioma raises the possibility of a relationship with the multiple endocrine neoplasia type 2 syndromes. In 1961,
Sipple reported a high incidence of bilateral phaeochro
mocytomas associated with thyroid malignancy.33 It was
later found that these patients also suffered medullary thyroid carcinoma. Genetic studies show the disease to
be inherited in an autosomal dominant fashion, with high
Malignant paragangliomas Up to 10 percent of paragangliomas are malignant.23 In
the absence of regional or distant metastasis it is not
possible to distinguish benign from malignant lesions
on histological features alone; rather it is the surgeon
who finds evidence of clinical invasion and aggressive
behaviour and makes the diagnosis. This is certainly the
experience in our unit and since the lesions are almost
impossible to remove completely, postoperative radio therapy is then mandatory.
approximately 10 percent for
gene
penetrance.34,35
Hyperparathyroidism
was
later added and the combination of medullary thyroid carcinoma, phaeochromocytoma and hyperparathyroid ism was termed MEN -2A.
In 1966, Williams and Pollock found that some
patients in the MEN-2 category with medullary thyroid
carcinoma and phaeochromocytoma also had multiple mucosal neuromas, sometimes with marfanoid features, puffY lips, prominent jaw, pes cavus and certain other occasional abnormalities.36 In these patients parathyroid
disease was apsent. The MEN-2 gene is located in chromosome
10.37
While
no
significant
association
between paragangliomas and MEN -2 has been described,
Chapter 191 Tumours of the parapharyngeal space I 2527
it
would
seem
paragangliomas
likely,
may
or
be
at
least
involved
in
possible,
that
the MEN-2B
syndrome. Linkage analysis localizes the MEN-2B anom
aly to chromosome 10, close to the FNRB and DlOZ1 1 OCl.38,39,40 .
Whether
there is
any
association
with
the RET
oncogene is unknown, but it is located on chromosome
10q11.2 and mutations have been found in over half of
the cases of MEN-2B at M918T, exon 16. It is expressed in neuroblasts but, interestingly, it is not associated with the
adult central nervous system.41
Rare tumours of the para pharyngeal space The surgical anatomy of the PPS is complex, containing a
variety of tissues, any of which could potentially become neoplastic. Such tumours appear only sporadically as case reports. For example, lipomas have been reported47 as having various sarcomas which affect any of the tissues in
the space, perhaps most commonly nerves, but other sarcomas have also been reported.48 Probably the most
common sarcomatous change is within neurofibromas although synovial sarcomas have also been reported.49,50 The PPS contains much muscle and although muscle
tumours have been reported rarely they include rhabdo
Schwannomas and neurofibromas
myoma, rhabdomyosarcoma and leiomyosarcoma.51 As
The histological appearance of a schwannoma falls into
two groups known as Antoni type A or B. The type A
pattern is of elongated spindle cells, forming a palisade of nuclei around a central mass of cytoplasm (verocay
the PPS contains blood vessels, vascular tumours can
occur and hemangiopericytoma has been reported.52
Neurofibromas associated with neurofibromatosis are
probably the commonest tumour to undergo malignant transformation. An unusual variant, the triton tumour
body). Type B is not really a pattern but consists of cells in
is a peripheral nerve sheath tumour with a rhabdomyo
present in one tumour. Occasionally, features of the
reported in the PPS54 is Masson's tumour, otherwise
polymorphism, pleiotropism and increased mitotic fig
plasia.54
malignancy.42,43,44
gomas occur. Extracranial meningomas form only 2
a loose myxoid stroma. Inevitably, both patterns are often histological malignant phenotype are apparent with
ures. In this particular lesion these do not indicate clinical
blastic differentiation.53 Another unusual vascular tumour known
as
intravascular
papillary
This is a benign lesion,
endothelial never
hyper
undergoing
malignant change. Occasionally, parapharyngeal menin
Although the schwannoma is the commonest neuro
percent of all meningomas. The most common site for
neoplasia is only found in one-quarter of PPS tumours.
PPS.55,56 An extremely rare tumour, often diagnosed as
or vagus and are only very occasionally malignant.43
tumour of the PPS. While this tumour is benign, it has
ment although there are occasional reports of prestyloid
geal sarcoma has many similarities with rhabdomyo
Neurofibromas probably arise from Schwann cells
the PPS. Perhaps unsurprisingly, the tumour has the
genic tumour to be found in the PPS, neurogenic When they happen they arise from the sympathetic chain Almost all schwannomas are in the poststyloid compart tumours.
and are well known to be usually subcutaneous in
site; they may be multiple and are often associated with von Recklinghausen's disease. Histologically, the neuro
fibroma does not have a capsule and the nerve fibres
are within the tumour.45
Typical
cafe au lait
spots
associated with multiple neurofibromas are pathagnomic
of
von Recklinghausen's disease.
Of
crucial
clinical
importance is the risk of malignant transformation. In
sporadic neurofibromas the risk is very small but rises
to between 5 and 15 percent in von Recklinghausen's
disease.46
these tumours is probably the orbit, followed by the extra cranial meningoma, is the follicular dendritic cell considerable potential for local recurrence.57 Paramenin
sarcoma. By 2002, 29 such lesions had been reported in
potential for spread into the cranial cavity. Chemoradia
tion protocols can largely avoid this problem and yield
five-year survival rates in the region of 75 percent. It is a
disease of children in the first decade of life.58
Finally, although not tumours, branchial cleft cysts are
primary diseases of the PPS. They can present with cranial
nerve palsy, and diagnosis should be suspected in any cystic lesion in the region of the PPS. The cysts usually
arise from the third branchial cleft and are treated by . . 1 1 Simp e surglCa exclslOn.59 ' 60 .
.
Von Recklinghausen's disease is an autosomal domi
nant disorder, with an incidence of approximately one in
3000 births. Half have a positive family history. The
diagnostic criterion of five or more spots, characterized by a light-brown cutaneous macule 1.5 cm or more in
diameter, is diagnostic. Other neurological abnormalities
such as glioma may be observed. The disease is usually
METASTASES TO THE PARAPHARYNGEAL SPACE One of the particular problems with this phenomenon is
that although the PPS contains a number of lymph nodes
localized to the skin although cranial nerves may be
it is not dealt with by the standard operations for treating
bilateral lesions occur. After these two nerves the vagus is
suggested for the poor prognosis of maxillary cancer
aff�cted, most often the lInd and VIIIth cranial nerves;
the next most commonly affected.
regional neck node metastases.
One of the reasons
with neck nodes is development of metastases within the
most commonly involved CNs i
--------_�_'
2528 I
PART 17 HEAD AND NECK TUMOURS
PPS. . Reports of
surgically clearing the PPS during
appearance of a benign nerve sheath tumour. Occasion
have
ally, such lesions may enter the cranial cavity via one of
suggested that such treatment may be useful, but the
the foramina, in particular, the carotid canal or jugular
associated morbidity is very high.61 A review of this
foramen. Anteriorly, the foramen ovale can theoretically
primary
ablative
surgery
for
maxillary
cancer
work gives no satisfactory indication that clearance of the
be entered. Expansion of tumours in the poststyl6id
better option.
thus, pressure on nerves with accompanying nerve palsy is
PPS is worthwhile, and irradiation therapy would seem a A more common metastasis to the PPS is from
nasopharyngeal carcinoma. Up to 30 percent of patients with undifferentiated nasopharyngeal carcinoma develop distant metastases within five years and this is associated
compartment is limited by anatomical constraints and not uncommon, even in benign tumours. In the case of the jugular foramen itself, an expansion within it may produce one of the many jugular foramen syndromes; particularly palsies of the IXth, Xth and XIth cranial
with a very poor prognosis. For metastatic nodes above
nerves. The hypoglossai nerve may also be involved. In the
PPS is not an uncommon site for such recurrences, care
pressure on the pterygoid muscles or in the case of
the upper clavicle, aggressive therapy is suggested. As the should be taken to obtain adequate imaging of this area at regular intervals during follow-up.62 It wouid seem better
anterior compartment and the masticator space, due to
malignancy, invasion of these muscles will cause trismus. High poststyloid lesions may compress the cartilaginous
to treat the area electively at the time of the radiotherapy
part of the Eustachian tube, causing middle ear effusion
to the nasopharynx, and a boost dose of irradiation
and
(20 Gy), is said improve locoregional contro1.63
described
A final tumour in the head and neck that metastasizes
deafness.
Obstructive
when
sleep
apnoea
medial
displacement 1 pharyngeal wall is pronounced. 6, 69
of
has the
been lateral
to the PPS is thyroid cancer. Occult thyroid cancer can present in the PPS. At least two cases of occult papillary thyroid carcinoma presenting with a PPS mass have been reported,64 and occult medullary thyroid carcinoma can also present in this manner.65 Finally, it should not be forgotten that distant cancers might metastasize to the PPS, perhaps most commonly the breast.66
The PPS contains many lymph nodes, which receive
afferent vessels, either directly or indirectly from nearly all sites of the head and neck. The commonest is the nasopharynx, the nose and sinuses (particularly posterior lesions), tongue base, the parotid salivary gland and the oropharynx.
Spread of adjacent tumours to the parapharyngeal space The PPS is in close relation to a number of head and neck sites
frequently
involved
by
carcinoma.
The
most
common sites, the nasopharynx and maxilla, have been discussed but other cancers are also important. Posterior
oral cavity cancers not uncommonly invade the PPS directly. Many oropharyngeal cancers also behave in this manner. A number of such patients will have trismus but, in many, spread will only be detected by
imaging
techniques. Significant spread into the PPS by these tumours
as
well
as
maxillary
cancers
is
a
relative
indication of inoperability. Certainly, full oncological
THE SPREAD OF TUMOUR WITHIN THE PARAPHARYNGEAL SPACE The great majority of PPS tumours are benign, account 1 ing for approximately 80 percent of neoplasms. 6 The most common neoplasms are tumours of the parotid deep lobe. Large tumours of the superficial lobe of the
clearance within an extensively involved PPS is not possible.
SYMPTOMATOLOGY Symptoms of PPS lesions happen relatively late. For the
parotid may also pass into the area of the deep lobe, via
prestyloid
the stylomandibular tunnel, giving a typical dumb-bell
oropharyngeal wall or a lump behind the angle of the
shaped tumour.67 Expansion of such a tumour, in the plane of least resistance, tends to result in displacement of
compartment
medial
displacement
of the
mandible are relatively common but the lesions must be quite large and they are thus relatively late signs. In the
the lateral oropharyngeal wall and tonsil medially. For
masticator space, trismus tends to be one of the earlier
such a mass to be apparent it must be at least 3 cm in 1 diameter. 6, 68 More superficially placed lesions may
symptoms in tumour� of the poststyloid compartment. A
expand laterally to produce a lump in the neck, behind
the angle of the mandible. The apex of the prestyloid
compartment is at the hyoid and the submandibular gland and may be displaced downwards. In the post
styloid compartment, tumours typically expand upwards
towards the skull base and downwards towards the apex of the PPS, for example giving the typical fusiform
lump in the neck is one of the most common findings, particularly in the case of a carotid body paraganglioma or benign nerve tumour. Lesions in the poststyloid compartment may produce nerve palsies, as previously discussed above. Carrau et al., in 1990,7° produced a list of
presentin�
symptoms
caused
by PPS
lesions.
A
modification of this table is shown in Table 191.2. The commonest,
accounting
for
approximately
half
the
Chapter 191 Tumours of the parapharyngeal space I
Table 191.2
Symptoms and signs of a parapharyngeal space
2529
normally in the neck but sometimes as a bulge in the
oropharynx. Visualization of the larynx will show vocal
lesion.
cord palsy in almost all thos� presenting with hoarseness;
trismus will, of course, be obvious. Cranial nerve palsies should be sought. A bruit may be detectable over a carotid Neck swelling
54
Pain
11
Cranial nerve palsy
10
Oropharyngeal swelling
8
Dysphagia
6
Other, e.g. trismus, otalgia
11
body paraganglioma. As a lump is the usual presenting feature, fine needle aspiration cytology (FNAC) in the clinic with immediate reporting76 is the next investiga
tion, following measurement of the pulse and blood pressure.
Fine needle aspiration cytology
aLiverpool database.
presentations, was a neck mass. There was pain in one fifth of patients, displacement
of
12
percent had
dysphagia, medial
the
oropharynx
was
a
presenting
Fine needle aspiration cytology is essential at the head and
neck clinic and accuracy rates of greater than 95 percent are possible in a routine head and neck clinic. Rates of 88
symptom in only 10 percent and hoarseness, usually
percent have been quoted from developing countries. 77
due to vagus nerve palsy, occurred in 7 percent. The
FNAC is equally applicable for neck lumps or lumps in
sensation of a foreign body, the presence of a parotid
the
oropharynx.78
In
appropriate
circumstances
the
mass, otalgia or trismus happened relatively rarely as
accuracy can be improved even further, to 92 percent by
presenting symptoms. A history suggestive of any cranial
combining FNAC
with
CT.
Such
CT-guided FNAC
nerve palsy should be investigated by direct questioning.
procedures are essential for lesions that are not directly
Syncope has received some attention in the literature
detectable without imaging techniques?9 In some cases
in recent years and is usually due to a malignant tumour,
ultrasound guidance may suffice. Such assessment of cases
either primary or secondary, invading the glossophar
at presentation is very accurate, and in our unit provides
yngeal nerve and in particular the carotid sinus. While usually a sign of malignancy, this is by no means always
the basis for management planning. For example, an asymptomatic carotid body paraganglioma or a lipoma,
be associated with
in an elderly individual, is likely to be treated conserva
glossopharyngeal neuralgia.72 Medical treatment of such
tively, although obviously imaging will be necessary in
the
case?O,71
The syncope
may
syncope with drugs or cardiac pacing seems relatively
addition. From the point of view of the patient and the
unsuccessful, compared with surgical removal of the
oncologist this is highly satisfactory, as one-third of
tumour. 73,74 Although syncope is rare, it can be fatal.
patients will probably need no more than an FNAC and
Regrettably our department has seen one case over the last
imaging, with appropriate follow-up. There are, of course,
30 years, which possibly could have been avoided by
lesions where FNAC diagnosis may be difficult. The
surgical excision of the lesion.
commonest in our experience is in carotid body tumours,
Finally, the syndrome of inappropriate antidiuretic
where the large amount of blood aspirated in many
hormone secretion or Schwartz-Bartter syndrome, is well
may make accurate cytology impossible. However, often
recognized in head and neck cancer. Most commonly, this
such tumours are fairly fibrous and can yield suitable
is associated with cancer of the nasal cavity or larynx
cytological material. Other pitfalls include rare tumours
although occasionally PPS tumours are implicated. The
such as fibrosarcomas, which by simple sampling error
types of tumours most often associated with this syndrome
may not provide enough malignant cells for an accurate
(shown in descending order of frequency) are squamous
diagnosis to be made. Neither of these problems is
cell carcinomas, neuroblastomas, small-cell neuroendo
particularly serious
as other techniques
including
a
crine carcinomas, adenoid cystic carcinomas, undifferen
sophisticated radiological investigation, or even a surgical
syndrome are hyponatraemia, serum hypo-osmolality and
suspected. The problems lie in the false positive cases;
elevated plasma vasopressin. It is typical that these changes
fortunately false positives are extremely
tiated carcinomas and sarcomas. The key features of this
take place in the presence of normal adrenal, thyroid and renal function?5 The symptoms and signs of a PPS lesion
are given in Table 191.2.
exploration, will provide the diagnosis as long as it is rare in our
institution, in part because the cytologists are in the clinic and perform the aspiration themselves. The speci
men
is
then
quickly
stained,
fixed
and
examined
microscopically. If a diagnosis cannot be made a further
FNAC is undertaken. On some occasions a definitive
DI�GNOSIS, INVESTIGATIONS AND STAGING
answer cannot be obtained until immunocytochemistry has been completed. In addition to these advantages,
The presenting symptoms of a PPS lesion are discussed
the cytologists and oncologists will discuss each case in
above, and the majority of these present with a mass,
the clinic environment and tell the patient either the
_i ;
----
.--
----_. .-- - ----------.-----------------=
2530 I
PART 17 HEAD AND NECK TUMOURS
diagnosis or the possible diagnoses. In any event, such
discussions will allow the oncologist to make a logical decision regarding further diagnostic tests and form a
provisional management plan. The main problem with
FNAC is in patients who have been previously treated and
Now that most centres in Great Britain and Europe
have
access
to
both
imaging
modalities
the
above
discussion is perhaps somewhat redundant. In practice, both modalities provide slightly different information. CT, for example allows deep soft tissue planes to be
in whom recurrence is suspected. False positive cytologi
evaluated and is more easily correlated with the physical
not uncommon following radiation therapy due to the
helpful where bone is involved; particularly thin bone
cal diagnosis, particularly for squamous cell carcinoma, is
severe dysplastic changes that accompany this treatment
modality. Thus, care must be taken when assessing such results. Imaging is of course also difficult to interpret after treatment, whether it is surgical or by radiation, and serial imaging studies may be required. The advent of positron emission tomography (PET) scanning has proved parti cularly helpful in this area. Realistically, however, if extensive
surgery
or
radical
radiotherapy
has
been
undertaken in a malignant lesion in the PPS, there is
examination (Figure 191.3). It is, of course, especially
structures such as the pterygoid plates or the bone of the posterior wall of the maxillary sinus. Here, CT was shown
to perform better than MRI. MRI, however, possesses many advantages and has excellent soft tissue contrast,
somewhat superior to CT. In addition, the authors suggest that three-dimensional modelling is particularly useful in the PPS and is most readily achieved using MRI; however, spiral CT consecutive volume data sets are now almost as good.84
little viable chance of salvage. Benign lesions are, of
The masticator space is anatomically complex but
course, another matter. Finally, it should be mentioned
rarely involved by primary tumours, although it is not
that there are physical limitations to FNAC, particularly in the deep neck or paraspinal region.79
infrequently involved by spread from adjacent sites. Som et al. evaluated retrospectively 30 patients with primary or
metastatic masticator space tumours. The conclusions are a little difficult to interpret, but it seems that imaging in
Imaging
this area is difficult and, in particular, may be unreliable
In our department, after the above procedure we move
and also occasionally mandibular erosion.85
regarding the integrity of the medial masticator space wall on to a plain chest radiograph and subsequent MRI of
the head and neck. Following the MRI, CT scans may be requested, particularly if bone detail is required. In addition, in our experience precise anatomical detail is, at the moment, a little better with CT than with MRI. In 1995 the Free University Hospital of Amsterdam
studied 14 patients with PPS tumours using MRI. 80 They
Some
lessons
may
be
nasopharyngeal carcinoma,
learnt
from
imaging
of
which frequently involves
the upper regions of the PPS; generally, NIRI has been
shown to be very good at assessing these tumours and
also their extension into the PPS.86, 87
A major problem in all head and neck oncology clinics is the early detection of recurrence following surgical or
found that all paragangliomas were sited in the post
irradiation treatment. This is particularly so for the PPS,
styloid compartment of the PPS whereas all salivary
which is relatively inaccessible to routine examination in
lesions were in the prestyloid compartment. They found
the clinic. Our department uses MRI in patients where it
that
is felt this is worthwhile. As mentioned above, a patient
vagal
paragangliomas
showed
flow
voids
with
anterior and medial displacement of the internal carotid
with malignancy of the PPS, who has already been treated
artery. Salivary gland tumours in the prestyloid compart
radically, has little realistic chance of salvage. As one
ment showed displacement of the internal carotid artery
might expect, the interpretation of a post-treatment MRI
posteriorly but no flow voids. They found MRI to be
is difficult, particularly so following irradiation.88 The
particularly useful in the PPS as it was able to distinguish
main radiation-induced effect is oedema, which affects all
accurately between vascular and nonvascular tumours.
tissues exposed to treatment. Of note is that the bone
acquired to assess flow voids, but in vascular tumours
oedema, frequently due to osteoradionecrosis, and this
They recommend that T1 spin-echo images should be
marrow regions of the mandible themselves may show
angiography should also subsequently be carried out. In
can be confused with recurrence. Volume reduction of
enhancement. Finally, they emphasized that FNAC is
degeneration of bone marrow.88 The above description is
addition, they found gadolinium to be useful for tumour required in all solid lesions for a tissue diagnosis to
be made. Whether MRI or CT should be the primary
imaging modality is a frequent cause for confusion among oncologists, but in truth, both are very good at assessing tumours in this region.81, 82 Further evidence from a study of Miller et al.83 in 1996, involved 51
patients with PPS tumours; anatomical location was
superior with MRI (95 percent) compared with CT
(84 percent).
the parotid gland is caused by radiation, as is fatty by no means exhaustive, and even an experienced head and neck radiologist will frequently be unable to make a
diagnosis of recurrence from a set of such images. Thus,
in practice, serial images are usually obtained to ascertain the natural history of a putative recurrence. An imaging modality used more and more in this context is PET scanning. In other regions of the head and neck it has been shown to be an accurate method of detecting recurrence. Experience of PET in the PPS is limited but
Chapter 191 Tumours of the parapharyngeal space I
2531
there is no reason to suppose that it will not prove to be
addition, they are most common high in the PPS close to
of great value.
the jugular foramen (Figure 191.5). Glomus jugulare
tumours are in the jugular bulb and can be seen to be
expanding the jugular foramen. All these findings will
Angiography
be seen quite clearly on MRI and CT. Glomus lesions
Carotid angiography should not be undertaken lightly.
developments using digital subtraction techniques in
generally are vascular showing flow voids. More recent Although the risks of this technique have been greatly reduced, estimates of the risk of cerebrovascular accident may be as high as 1 percent. Without angiography, vagal paragangliomas can be difficult to distinguish radiologi cally from a carotid body paraganglioma (Figures 191.5 and 191.6). Anatomically, however, carotid body para gangliomas are characteristically located between the internal and external carotid arteries at the carotid bifurcation (Figure 191.6). Most vagal paragangliomas
association with MRI will allow accurate diagnosis in most cases. The main indication for carotid angiography is in planning surgical treatment. There is no other
method of imaging that accurately demonstrates the feeding vessels,89 and we would regard it
as
essential that
this investigation is carried out prior to surgery. In addition, cerebral blood flow measurements using the xenon CT scan techniques may be useful to show whether cerebral blood flow is compromised, prior to surgery.89
tend to displace the internal carotid anterio-Iaterally. In
Staging Some type of universally accepted anatomical staging of tumours and their regional metastases is essential for comparison of results between centres. In the present medical climate in Great Britain, this is becoming more and more important and will soon be essential practice. Apart from these practical problems, advances in cancer research and treatment are not possible without adequate staging. The fifth edition of the International Union
Against Cancer handbook published in 199790 and the
fifth edition of the American Joint Committee handbook are both in concord of worldwide comparison of staging. Equally important is histological grading, which has also become standardized. Unfortunately, neither staging system includes the PPS. As we have seen, this is a very difficult site, both anatomically and histologically, with a wide Figure 191.5
A high vagal paraganglioma on angiography.
variety of tumours making useful classification difficult. In addition, these tumours are rare. Since many of these tumours used to remain histologically undiagnosed, the routine application of FNAC in head and neck oncology clinics has become crucial and, to a great extent, has resolved the problem of tissue diagnosis. Imaging techni ques have also improved, far exceeding the expectations of their resolution capabilities 25 years ago. This has allowed very accurate anatomical localization of tumours and a highly accurate diagnosis to be made in some of these, for example carotid body paragangliomas. 'The ability of imaging to demonstrate tumour invasion, regional and distant metastases and tumour volume, again will allow comparison of one centre's experience with another. As regards an attempt at staging, the nasopharynx is the closest structure. MRI investigation of the extent of nasopharyngeal carcinomas (which do have a staging system), shows good correlation between this investiga tion and tumour stage.87 In addition, the 1997 American Joint Committee on Cancer staging system for nasophar yngeal carcinoma has been shown to be prognostically
Figure 191.6
A carotid body paraganglioma.
useful.91
. � I �
-\ -
-
/
-
x
2532
I
PART 1 7
H EAD AN D N ECK TU M O U RS
From the practical po int of view, our unit stages PPS
immunohistochemistry.
It
cannot
be
overemphasized
tumours in terms of tumour volume, greatest tumour
that incisional biopsy must not be carried out intrao rally.
diameter, evidence of local invasion, evidence o f regional
We have seen several cases of recurrent pleomo rphic
metastasis
and
evidence
of
distant
metastasis.
The
adenoma from a deep lobe parotid tumour develo ping in
location of the primary tumour is actually defined within
the
the PPS . The tissue diagnosis provided by FNAC or
cavity following such biopsies. Such a tumour should be
surgery is noted. In cases where FNAC may not yield
easily
a result, commonly in carotid body and vagal para
perfectly safe and yields the correct diagnosis in almost
gangliomas, the radiological diagnosis is used. If the
all cases.
mucosa
of the
diagnosed
oropharynx
using
FNAC,
and
posterior
transorally,
o ral
which
is
tumour is likely to be malignant then a search is made for regional and distant metastases. Our experience would suggest that all oncologists treating these tumours use this descriptive approach and we would urge it to be adopted universally.
S u rg i ca l treatment Surgery
may
diagnosis
TH E TREATM E NT O F PARAPHARY N G EAL S PACE TU M O U RS AN D OTH E R LES I O N S O nce the PPS lesion has been fully classified, a decision can be made on the appropriate treatment. For example, in the case of a carotid body paraganglioma with a stable natural history in a n elderly patient, who perhaps is suffering few symptoms, the best management is almost certainly conservative. The same is likely to be true fo r other benign lesions causing few symptoms such as a lymphoma. Equally, a symptomatic distant metastasis to the PPS from another site, such as the breast , would only be suitable fo r palliative treatment, usually by a short cou rse of irradiation. Fortunately, malignancy will o ften reveal itself by causing pain or cranial nerve palsies . It must be remembered that this is by no means always the case. Imaging will usually give an indication whether a
tumour
accurate
is
in
malignant this
regard.
and, In
fi nally, spite
FNAC
of the
is
very
fo regoing
discussion, any surgeon with a reasonable-sized oncolo gical p ractice will have been caught out, when the tumour only becomes obviously malignant at operation. We have witnessed this change within an ostensibly benign nerve tumour in vagal p aragangliomas and also carotid body paragangliomas, as well as a few other tumours such as sarcomas. I n patients where a diagnosis cannot be made with
be
and
necessary
this
to
should be
obtain
a
excisional
histological rather
than
incisional and the planned approach must be adequate fo r
a
full
oncological
resection.
The
PPS
is
very
complicated anatomically and the various app roaches to it rarely easy. Experience in carotid vessel surgery is necessary as is some experience of lateral and anterior skull base surgery in o rder to deal with the whole range of PPS tumours. The PPS is very high in the neck a nd is mostly retromandibular. In terms of access, small carotid body paragangliomas, being near the apex of the PPS ( inferior) are probably the most accessible. Our experience is that although most of these tumours can be removed relatively easily, on a few occasions major internal carotid artery surgery including excision and grafting has proved necessary. Likewise, a deep lobe parotid tumour may be undertaken via a superficial parotidectomy approach. The superficial lobe can then be reflected o r excised and the deep lobe exposed, in most cases by division of the stylomandibular ligament. A bigger tumour will require greater
access,
most
easily by
a
mandibulotomy
of
the ramus above the lingula. Even so, completed excision cannot be guaranteed and it is our practice to administer radical radiotherapy p ostoperatively as recurrence in this region is extremely difficult to deal with. This is the case even with the benign pleomorphic adenoma. Definitive surgical treatment will be considered first as this is the most common treatment modality for most PPS lesions requiring therapeutic intervention.
reasonable certainty and, in p articular where m alignancy is suspected but not proven, surgical explo ration may prove necessary. In these cases excisional biopsy following good oncological principles should be the aim. If this
D E F I N ITIVE S U RG E RY
Access to the PPS is anatomically difficult and technically
is obviously impossible because of technical reasons,
demanding as a number of crucially imp ortant structures
a n incisional biopsy will have to be made and sent for
lie
frozen section. If frozen histology is diagnostic then the
approaches to the PPS . O ne is the transparotid appro ach,
resectability of the tumour will have to be reconsidered in theatre, bearing in mind its p rognosis, potential curability
and the anatomical, functional and aesthetic deficits a
p atient may have to suffer. If a diagnosis cannot be made on
frozen-section
histology
there may be
no
alternat ive but to abandon the op eration and wait fo r full histology. In many unusual tumours this will require
in
or
near
this
sp ace.
There
are two
standard
typically used for deep lobe p arotid tumours in the prestyloid compartment. The other is a transcervical approach, p rimarily used for access to the poststyloid compartment and carotid body p araganglioma. A l amen table common appro ach is the transo ral , which provides poor access and poor visualization. It is not recom mended and is not discussed further. Perhaps the most
Cha pter 1 9 1 Tu m o u rs of t h e p a ra p h a ry n g e a l s p ace
frequent
modification
to
the
standard
approach
is
mandibulotomy fo r large salivary tumours in the anterior compartment. Apart from these, there are almost as many operations described as there are head and neck surgeons!
The main approaches that are the most useful and
that our department has direct experience of are now discussed. Finally, some new, very maj o r approaches, or approaches necessary in unusual circumstances, will
be described.
routine superficial p arotidectomy procedure, p referably preserving healthy parotid gland and with full identifica tion and preservation of the facial nerve and division of the stylomandibular ligament. This ligament, although frequently described, is more a diffuse condensation of fascia when seen at operation. Nevertheless, its division anterior
may
be
The more extensive lateral mandibulotomy approach is required fo r malignant tumours of the anterior PPS particularly with
oropharyngeal
malignant salivary gland tumours.
;
involvement or fo 93 , 9 5 For even more
extensive tumours a midline mandibulotomy may very 9 occasionally be necessary. 8 With the median mandibu loto my, realms
Small deep lobe p arotid tumours can be approached by a
imp roved
Exten d ed tra nsm a n d i b u l a r a pproaches
open transpharyngeal resections can also be 96 Such procedures obviously extend into the
carried out.
Th e tra nspa rotid a pproach
allows
2533
displacement
access. extended
Commonly, as
a
of the the
mandible
standard
transparotid
with
approach
submandibular
approach, which is indicated in larger deep lobe p arotid tumours. All that is required is that the standard modified Bailey incision fo r a superficial parotidectomy is extended beneath the mandible anteriorly over the submandibular space; the submandibular gland may then be displaced or more often excised. The greater exp osure allows more division of diffuse fascial elements, facilitating dislocation of the temporal mandibular joint anteriorly, which can almost double the surgical exp osure. A useful adjunct to this p rocedure is mandibulotomy. In the context of the present exposure, the easiest to use is the division of the mandibular ramus above the lingula, 9 93 9 preserving the mandibular nerve. 2 , , 4 Some advocate a midline mandibulotomy with extensive dissection and 9 93 9 9 96 of the hemi-mandible laterally. 2 , , 4, 5 ,
reflection
Radical mandibular approaches are discussed later.
Th e tra nscervica l approach
of
extensive
immediate
repair
composite
of bone,
resections,
mucosa
and
requiring
skin,
using
composite microvascular grafting techniques. While the technique is very rarely necessarily for benign tumours, very extensive malignant tumours may be satisfactorily resected using this method. With the exception of the latter exp osure, access to the skull base
using
the above techniques is poor.
The
exception is extensive mandibulotomy, either median or lateral, which provides a useful exposure of the lateral skull base.
The technique
can
also
be
modified to 96 In this
allow good exposu re of the anterior skull base. approach,
the
digastric
and
omohyoid
muscles
are
detached from the hyoid bone and retracted superio rly. The
mylohyoid
muscle
is
divided
and
an
anterior
mandibulotomy performed, and the lateral floo r of the mouth incised as far as the anterio r tonsillar pillar. The contents of the carotid sheath can then be exposed when the incision is continued to the maxillary tuberosity. In exceptional circumstances, a palatal flap can be elevated, allowing better exposure of the internal carotid artery as it enters the skull base and giving access to the nasopharynx.
Other exposu res of the sku l l b ase Wide field access to the skull base is required in three surgical situations. The first is when access to the most superior part of the internal carotid artery is necessary. The second is when high benign, usually nerve, tumours are invading the foramina of the base of the skull, and the
For most tumours of the poststyloid space the transcer 7 9 vical approach is adequate. 0, 2 A reasonably extensive
this area. In our experience it is unlikely that such
final indication is for resection of malignant tumours in
excision is made from a point 2 cm below the mandibular
tumours will be cured and the morbidity is usually
ramus, starting some 2 cm in front of the mandibular
extremely high. Very careful consideration should there
angle and extended backwards and upwards. The size and
fo re be given before contemplating such surgery fo r
accessibility of the tumour will dictate how large the
malignancy.
incision needs to be. Early direct access to the poststyloid
good access, p articularly anterio rly, has already been
compartment allows straightforward removal of most
discussed. Various new approaches have been described
benign nerve tumours and paragangliomas .
including combined infratemp oral fossa and transfacial 99 approaches. Typically, massive tumours within the
The incision may be extended anterio rly to expose the
Transmandibular
surgery,
which
gives
submandibular triangle. Care is obviously required to
infratemporal
p reserve the mandibular and cervical branches of the
approached via a Fisch type C procedure. This provides
facial nerve, which if damaged, rarely recover. The facial
excellent control of the internal carotid artery without
artery can be ligated and divided and the submandibular
leaving facial scars; regrettably, the app ro ach requires that
fossa
and
pterygopalatine
fossae
are
gland retracted anterio rly o r removed. Division of the
hearing be sacrificed on that side and there is a high risk
digastric tendon then allows excellent exp osure with
of facial nerve palsy. The Fisch type D approach, which
direct visualization and p roper oncological removal of 9 97 the tumour. 2 ,
uses
an infratemporal preauricular incision,
provides
more limited access but preserves hearing. Evidently,
2534 I PART
1 7 H EAD AI'J D N ECK TU M O U RS
due
to
delayed
arterial
occlusion,
presumably
from
neither approach is fully satisfactory. A recent descrip 9 tion 5 combines the Fisch type D with a transfacial
p ropagated clot, a nd o ne developed a pseudoaneurysm,
transmaxillary
necessitating postoperative balloon occlusion. In that
approach.
The
operation was
devised
p rimarily for the removal of tumo urs from the infra
series, a number of patients had vagal tumours, and
tempo ral fossa, the pterygopalatine fossa, the PPS and
permanent vocal cord palsies occurred in 1 3; however, 1 0
the o rbit. Procedures incorporating a Le Fort 1 osteotomy may
patients had facial nerve p alsy, which fortunately usually recovered. Finally, in a p ap er from North Carolina 10 3
be useful, in p articular for medial and anterior skull base
dealing with management of the carotid artery at the skull
lesions involving the clivus. Until recently the usual
base in patients undergoing tumour resection, the authors
approach for such a tumour was laterally, with accom 9 panying unacceptable morbidity. A recent description 6
was fo rtunately usually the case. They suggest that if
combines a segmented Le Fort
osteotomy with a
1
transmandibular approach. The o ncological and func
recommended that the carotid artery be p reserved, which carotid
artery
resection
should prove necessary then
vascular bypass and reconstruction be performed.
tional o utcome is said to be good but no one unit is likely to gain much experience of such a technique. Another recently described approach, this time for a massive
Ra d i oth era py
schwannoma, involved creating orbital frontal ethmoidal combined with an extended frontal ap
Almost all data on this subject concern PPS extension of
tumour would be transfacially, combined with osteo
radiotherapy is the treatment of choice, as not only is the
to mies designed to allow the maxilla to be swung laterally.
prim a ry tumour but also the regional nodal metastases
osteotomies
p roach. 1 00 , 1 0 1 The more usual method of excising such a
nasopharyngeal carcinoma . 1 04 , 1 05 , 1 06, 1 0 7 In that disease
In our experience this provides excellent access to this
exquisitely
difficult area.
carcinoma is also highly radiocurable, with the disease
sensitive
to
radiotherapy.
Nasopharyngeal
free survival at three years varying between 60 and R O UT I N E P RACT I C E IN D EALI N G WITH T H E SKULL BASE
intensity
With the advent of high-resolution scanning techniques with
or
without
angiography,
if necessary,
86
percent. Techniques such as hyperfractionated regimens,
accurate
localization of tumours is almost invariably p ossible. Although a minority of tumours of the PPS are massive,
modulated
surgery have offered
regimens
and
stereotactic
exciting advances
radio
in this field.
Certainly, these newer techniques will, in the future, have a role in treating PPS neoplasms. It is perhaps not well appreciated that convent ional
are
radiotherapy can control vagal p aragangliomas including
relatively small. Meticulous planning, based o n the results
the glomus j ugulare tumour, with very few side effects.
requiring very
extensive
surgical
exposure,
most
of imaging techniques, usually allows for less extensive
Radiotherapy is also effective in controlling the growth of
procedures than those described above, to be adequate in
the carotid body p araganglioma. For deep lobe parotid
the majority of PPS lesions. l02 Regarding the excision of
tumours that have recurred, all patients seen in our unit
skull
preauricular
have received radiotherapy. We also now use this adjuvant
infratemporal approach was the most commonly used
modality in new cases of deep lobe parotid tumours, even
what were described as extensive craniofacial neoplasms,
anatomical
some benign and some malignant. Of the 27 patients
adenoma in the deep lobe of the parotid usually involves
base
lesions,
a
subtemporal
and
in one series of 29 p atients. 1 0 2 Of the 29 p atients, 27 had
though the recurrence rate is small, mainly because of considerations.
A
recurrent
p leomo rphic
who had surgery a total resection was obtained in 23.
quite extensive and difficult surgery for its excision. In
A practical note, both from that study and fro m our
addition, it is o ur view that almost all patients with
own experience, is that the balloon occlusion test so
extensive malignant tumo urs
commonly used, is not infallible. Over the years, our
requiring surgery should also be offered postoperative
department
irradiation.
has witnessed two deaths
from
cerebral
of the head
and neck
insuffi ciency when the ballo on occlusion test was normal. Further, we have experience that occluding the internal carotid artery on a long-term basis using a balloon
C h e m othera py
technique in therapeutic angiography can cause death from a p ropagated clot, developing over a period of days, causing cerebrovascular insufficiency. Our policy now is
to preserve the internal carotid artery if at all feasible. If the artery must be sacrificed, where p ossible it is repaired
by grafting. Other units have had s imilar experiences. Of 27
p atients
operated
on
for
extensive
skull
base
neopiasms, l 02 one patient died fro m cerebral vascular
accident, one patient suffered a cerebrovascular accident
Chemo radiation p rotocols
are
used primarily in the
treatment of rhabdomyosarcomas and other sarcomas of the PPS. In nasopharyngeal carcinoma extending into the PPS, chemoradiation p rotocols are also frequently used, and almost always include cisplatin and 5 - fluorouracil. For
p rimary
PPS
malignancy,
chemotherapy
should
include doxo'rubicin for glandular neoplasms and for squamous cell carcinomas, cisplatin and 5 - fluo rouracil . 1 0 8
I 2535
Cha pter 1 9 1 Tu m o u rs of the p a ra p h a ry n g e a l space
�
Treatm e n t of the n eck
interpretin
ertainly, it is our policy to give i age . ? � � postoperatIve IrradIatIOn for pleomorphic adenomas in
Usually, tumours of the PPS spread locally and invade
the PPS, in which case one may a rgue that if malianant
locally. Rarely, neck node metastases will occur from a variety of malignant legions. As long as local control has been achieved, the neck should be treated as appropriate fo r the histological type, and according to the protocols given in
Chapter
1 99 , Metastatic neck disease.
Our
practice is to reduce the risk of neck node metastasis happening by employing postoperative irradiation to the primary
site
and
the
regional
nodes.
Apart
from
squamous cell carcinomas arising from the o ral cavity, o ropharynx and post- nasal space, elective neck dissection is not usually considered. A final difficulty is in dealing with patients with bilateral
vagal p aragangliomas or neurofibromas.
For
successful removal of these tumours the vagus nerve will, almost certainly, have to be sacrificed. Therefo re, it is best to operate on the side with the most advanced lesion and to administer radiotherapy to the opposite side.
There is essentially n o literature on this subject; however, in our experience, failure becomes manifest in a s imilar fashion to the primary tumour ( Table
1 9 1 . 1 ) . Thus,
benign lesions tend to present with a new mass. In the poststyloid compartment, further cranial nerve palsies may develop, and fo r lesions compressing the internal carotid artery, cerebrovascular insufficiency may become manifest. The only way of detecting early recurrences of benign tumours would be by serial scanning, which we consider unnecessary, as the only reason fo r revision surgery would be fo r the treatment of symptoms. A specific problem, very rarely, arises when a benign tumour undergoes malignant transfo rmation. Almost all parapharyngeal salivary tumours arise in the deep lobe of p arotid
glan d
and
occurs
Paragangliomas
it
is
at
unlikely
highly
all sites
within
to
�
be
cu able.
the PPS
may be
malignant, probably involving between 5 and 10 percent 3 of tum ours.2 It is likely that any, so-called, benign tumours thought to undergo malignant transfo rmation are, in fact, malignant from the start. Involvement of the PPS by other cancers, in p articular nasopharyngeal carcinoma and some oropharyngeal and oral cancers ( including the s uperior gingivolabial fold) does happen. In the case of oral and o ropharyngeal cancers invading this region the cure rate, at best, is 1 0 percent a t five years, therapeutically
and thus it i s unlikely t o be 1 to treat a recurrence. 09
rewarding
Although the outlook for patients with nasopharyngeal carcinoma is somewhat better, it is still a sign of extremely poor
p rognosis
and,
again,
salvage
almost no chance of cure. 1 1 0
treatment
offers
Prog n o s i s a n d s u rviva l
PATTE R N S OF FAI LU RE
the
change
nearly
all
are
pleomo rphic
adeno mas. There is no consensus as to the risk of
The Liverpool series of primary PPS tumours is given in Table
1 9 1 .2; 84 percent of the tumours were benign and
the remainder malignant. Of the malignant tumours, 67 percent were malignant salivary cancers. As the vast majority of tumours are benign, the tumour-specific five year survival was excellent at 97 percent ( 9 5-96 percent confidence
intervals
percent)
8 2- 1 00
(Figure 1 9 1 . 7 ) .
Survival calculations for malignant tumours must not be
overinterpreted
as
the
numbers
( p articularly
of
malignant tumours) were small. Nevertheless, the five year survival fo r malignant salivary tumours was surpris ingly good at approximately 8 5 percent; however, nearly half of these had adenoid cystic carcinomas and the survival fell to 5 5 percent at 10 years
(Figure 1 9 1 . 7 ) .
There were two lymphomas; o n e patient was cured but the other died at six years after recurrence. There
malignant change in a pleomorphic adenoma, but a figure of app roximately 10 percent over a lifetime is p robably
1 .00 -
reasonable. For a full discussion on this topic the reader is referred Chapter 1 90, Malignant tumours of the salivary glands. The risk of malignancy in a deep lobe p arotid tumour and, indeed , risk of recurrence is probably lower than
for
superficial
parotid
pleomorphic
adenomas.
However, I am personally convinced with regards to the above discussion that there is no scientific literature to support
one
line
of management
or
another.
The
Liverpool head and neck database of some 7000 patients includes only 34 deep lobe pleomorphic adenomas. Serial, yearly MRI
may be considered app ropriate
CJ) .� >
'2
::J if) c 0
L-e-�� � Benign
0 . 75 -
Malignant
0.50 -
t
0 0..
e
Log rank test p
0 . 25 -
D....
0 . 00 -
I
I
0
1 000
if such
facilities are readily available, as a scan carried out only
I
2000
=
0 . 0285
I
I
3000
4000
5000
Survival (days) o 0 0 Censored observations
when a patient has symptoms is of little help because
F i g u re 1 9 1 . 7
scarring and residual oedema will create difficulties in
with tu m o u rs of t h e PPS (Ka p l a n - M e i r) .
Act u a ria l tu m o u r-specific s u rviva l of pati e n ts
2536
I
PART 1 7
H EAD AN D I\J ECK TU M O U RS
was o ne malignant carotid body paraganglioma. The
associated with a T4 classification. 1 l 3 The risk of local
has
chest
recurrence in these cases is 36 percent and the mortality
malignant
vagal
high . Sp read of o ral or oropharyngeal cancer to this
paraganglioma which was treated by surgery and irradia
region is again associated with a T4 stage and frequently
tion o n the side of the largest tumour and radical
renders the tumour inoperable.
patient
has
metastases.
survived There was
six
years
o ne
but
bilateral
now
radiotherapy o n the side of the small tumour. That patient is alive and disease free at seven years. Of the two sarcomas, o ne died at 6 months and the other at 18
months . The data fo r
The co m p l i cati o n s of treatm ent
Table 1 9 1 .2 were accrued
from 1 970 to 1 997, a period of nearly 33 years, with a
Surgery for P P S lesions i s difficult , prima rily because
median
Of those
of poor access, extensive access procedures and complex
with malignant tumours, three had regional neck node
anatomy. It is largely because of this that complications
potential
metastases
and
follow-up
these
all
of 1 5 . 2
occurred
years. in
patients
with
associated with surgery are high (vide infra ) . According to Carrau et
malignant salivary gland neoplasms. There is very little written about the prognosis and
al.,70 permanent complications from surgery
include cerebrovascular accident (4 percent) and palsies
survival of patients with PPS tumours. This is partly
of the Xth (4 percent) , XIth (4 percent)
because all series are relatively small, the overwhelming
nerves
majority of tumours are benign and individual series
effects of surgery, nerve palsies were the most common,
(9
percent ) .
As
regards
and XIIth
temporary unwanted
contain relatively small numbers of malignant tumours. If
affecting over 60 percent of patients. The commonest
malignant paragangliomas are considered, they account
was injury to the marginal mandibular nerve and the
fo r only approximately 10 percent of all pa ragangliomas of the pPS. 2 3 For example, the literature contains less than
next in frequency was injury to the hypoglossal nerve. Vascular morbidity happened in 13 percent and tempor
20 cases of metastatic vagal paraganglioma. While these
ary cerebrovascular accident in 4 percent. There were
patients succumb to their disease, the majority of those
haematomas in almost
with malignant paragangliomas do not, but have a locally
same number had p roblems, usually respiratory infection
10 p ercent of patients and the
progressive behaviour which can be cured, or at least
or heart failure. Nearly all surgical morbidity associated
controlled,
III
with PPS surgery appears to happen during the surgical
by
radical
surgery
and
radiotherapy.
Malignant salivary cancer, in our experience, does not
treatment of paragangliomas?O The above figu res are
behave any differently in the PPS than elsewhere in the
in line with other surgical series of similar tumour
head and neck, but the surgical exposure is considerably
resections.
16
more difficult . Owing to the small numbers of malignant
As regards unwanted effects o f radiotherapy, there is
salivary cancers of this region, the reader is referred to
almost nothing written regarding primary PPS tumours.
Chapter 1 90, Malignant tumours of the salivary glands.
Ext rapolation can be made from irradiation of cancers of
Since the natural history is unlikely to be much affected
the adjacent post-nasal space. The greatest problem is the
by the anatomical site of the tumour, extrapolation of
significant risk of tempo ral lobe necrosis, in particular
data of the relevant malignant tumours can be made to
with hyperfractionated schedules in which the incidence
give an idea of how a similar tumour is likely to behave in
may be as high as 14 percent after 7 1 Gy in 40 fractions
the PPS.
over 35 days. O n the other hand, the five-year actuarial
The overall p rognosis of PPS tumours is excellent, with
incidence of temporal lobe necrosis fo r those receiving 66
the survival greater than 95 percent at five years. The
Gy in 3 3 fractions over 44 days was nil . l 14 The latter dose
prognosis o f the tumour then depends on two factors: the
schedule is equivalent to that used in the UK and thus
fi rst is death from treatment o r its complications and
tempo ral lobe necrosis should be a very rare occurrence.
the second is death from the tumour itself, dependent on
O ne of the maj o r problems in delivering radiotherapy
its histology. Deaths from treatment will be dealt with
to the area is xerostomia. This is essentially related to
under complications ( see later under The complications
the radiation dose delivered to the parotid gland, and
of treatment) and deaths from type of tumour in our
fo r each gland independently, salivary flow is reduced
series ap ply almost entirely to malignant tumours, with
exponentially at a rate of app roximately 4 percent per
the outcome described above. Other very rare causes of
gray of mean parotid dose.
death include intracranial spread of a benign tumour,
radiotherapy available to most units, it is exceedingly
and fatal syncopal attacks, usually ascribed to pressure
difficult not to irradiate the parotid gland. Techniques to
algorithm fo r evaluation of PPS tumours and perhaps, more impo rtantly, fo r their management. 1 1 2
ment of the patient presenting with neck lymphadeno
on the glossopharyngeal nerve. Others have described an
Sp read of tumours to the PPS from elsewhere in the
head and neck has been discussed elsewhere in this chapter. The most common and best-documented group is nasopharyngeal carcinoma where spread into the PPS is
1 IS
With the techniques of
spare the parotid are discussed in Chapter 1 9 8 , Manage pathy and an unknown primary carcinoma. The drug amifostine reduces parotid damage but expensive.
is
extremely
It should be remembered that xerostomia
is permanent �nd, significantly, adversely affects quality of life scores.
Cha pter 1 9 1 Tu m o u rs of t h e p a ra p h a ryng e a l space I
2537
S U M M ARY
the PPS where malignancy has only been diagnosed
Parapharyngeal space tumours are rare, fo rming less than
in the lungs and alth ough it is very rare it is a salutary
5 percent of hea d and neck neoplasms . In the Liverpool series they form less than 2 percent. More than 8 0 percent
lesson. Assum ing there is a cytological diagnosis and imaging,
once a distant metastasis has developed; this is usually
of PPS tumours are b enign. Over half of PPS tumours
together with clinical assessment, leading to a reasonably
present as a lump, usually in the neck and occasionally in
certain
the orop harynx or oral cavity. Owing to the deep location
irradiation is effective at inhibiting further growth of a
of the PPS, tumours do not present until they are quite
number of benign les ions and , on occasion, causing
large. Not infrequently, cranial nerve palsy will b e noted
shrinkage of the tumour. This is true for all paraganglio
diagnosis,
it
sho uld
not
be
fo rgotten
that
on exam ination or may be the presenting feature. One
mas
m ust not forget the PPS when considering the cause for
paragangl iomas of the jugular fo ramen and j ugular bulb.
unexplained syncopal attacks, which in o ur experience
It is probably also the treatment of choice in an elderly
and
is,
perhaps,
the
treatment
of choice
for
be
patient with symptoms fro m a carotid para ganglioma, in
remembered that high PPS lesions can gain access to
who m surgery is likely to carry a h igh risk, particularly of
the cranial cavity via the skull base foramina and this can
cerebrovascular accident.
have
occasionally
proved
fatal.
It
should
also
happen even in benign tumours, in particular, vagal
Considering malignant tumours, combined treatment protocols are usually indicated with surgery followed by
p aragangliomas. The PPS contains the h igher cranial nerves, also the
chemoradiation. Owing to problems with access and
mandibular branch of the Vth nerve and, of co urse, the
associated
VIIth nerve is at risk d uring access procedures. The PPS is
tumours may not, in practice, prove amenable to total
quite
devastating
aesthetic
sequela,
these
a very d ifficult area fo r the surgeon as not only are there
surgical excision. In the rare patient with unilateral or
cranial nerves to consider but also the internal carotid
bilateral malignant paragangliomas, o ur experience is that
artery is not infrequently involved by various tumours,
they are only diagnosed at operation, where obvious
most notably with the
b ody paraganglioma.
malignant behaviour is seen, most notably as invasion
Procedures involving the internal carotid artery can be
of surrounding tissues. In these cases a radical excision
carotid
the cause of a disastrous cerebrovascular accident, albeit
on the side of the largest lesion should be carried out,
infrequently.
almost always with the sacrifice of the vagus nerve, and
Crucial of this spi ral
to
the
region
CT.
successful
are
FNAC,
Cytological
and
management MRI
and,
imaging
of lesions
if
indicated ,
techniques
have
irradiation offered for the other side. Finally, although tumours form the vast maj o rity of lesions of the PPS, this site can be affected by abscesses
revolutionized diagnosis and management in this dif
and . also
by
ficult area.
branchial
cleft.
As most of the tumo urs of the PPS are b enign, surgical management is usually necessary.
'congenital'
abnormalities
There may
also
of the
third
be second branchial
cleft abnorm alities. The embryology is a little irrelevant
One m ust
as these lesions form cysts, usually requiring surgical
not fo rget however that j udicious follow-up rather than
excision. The PPS is immensely complicated anatomi
surgery, perhaps with serial yearly MRI,
is perfectly
cally and the oncologist needs to have an intimate
acceptable, pa rticularly if there is a tissue diagnosis, or
knowledge of the region. Base of the skull invasion
at least a reasonably certain radiological diagnosis, as in
and spread means that skills in lateral skull base surgery
the case of a
carotid body paraganglioma. Tumours
such as this are very m uch an area where the treatment
m ust
be
available.
Also,
anterior
spread
may
affect
the mandible, requiring b one excision. The head and
decision must be reached between the doctor and the
neck
patient.
We have a number of young patients with
of reconstructive techniques and, in particular, micro
carotid p araganglio mas who did not wish to have surgery
vascular composite graft reconstruction. It should not
once the risks were explained to them
be fo rgotten that spread into the PPS by other tumours
and
this is
surgeon
must
have
a
full
working
knowledge
obviously entirely reasonable. As in oncology, in general,
is at least as common as pri mary PPS tumours. Spread
the
pain,
to the PPS most com m only involves post- nasal space
involvement of other structures (such as cranial nerves
cancers but tumours of the p osterior, superior oral cavity
or
simple muscles
invasion,
rules
of
increasing
of mastication)
suggest
that
or
prompt
tumour imaging
size,
evidence
investigation
of
and superior oropharynx infrequently also involve this
followed
area. The stage of such tumo urs is always very advanced
by approp riate treatment is required. Finally, one must
( T4 ) . While skull base spread to the PPS may usually
not forget those in which a tissue diagnosis
be dealt with by radiation, oropharyngeal and oral cavity
is not
certain. This, of co urse, would suggest that excision
spread is p rimarily a
and histological assessment should be advised. It s hould
such lesions should be deemed inop erable is open to
also
be
noted
that
even
not always possible to malign ant
or
not.
with
assess
it
is
question. At least PPS involvement by malignant cancer
tumour
IS
spread should make one aware that inoperability is, in
histop athology whether
a
surgical p roblem and whether
We have seen p araganglio mas
of
practice, likely.
2538
I
PART
1 7 H EAD A N D N ECK TU M O U R S
KEY PO I NTS •
Early diagnosis is difficult.
•
Anatomical diagnosis relies almost completely
2. 3.
conditions with emph asis on n eurogenous tumours, 2 n d ed n . Was h i n gto n , D C : Am e ri c a n Aca d e my of
The tissue diagnosis can almost always be
Otolary ng o l o g y - H e a d a nd N eck S u rg e ry Fo u n d a t i o n .
obtained by FNAC - image guided if necessary. •
More than 8 0 percent of tumours are benign and if treatment is required it is almost
1 987. 4.
access followed by problems related to
•
Most malignant tumours involving the PPS arise from adjacent structures close to the
spaces: Pa rt I. Anato my. Radiology. 1 9 8 4 ; 1 50 : 7 2 3 - 8 . 5.
C u rti n H D . S e p a ration of the m a sti cato r s p a ce f r o m the
6.
Al l ison RS, Va n der Waa l I, S n o w G B. Pa ra p h a ry n g e a l
pa ra p h a ry n g e a l s pace. Radiology. 1 9 8 7 ; 1 6 3 : 1 9 5-204. t u m o u rs : a rev i e w o f 23 ca ses. Clinical Otolaryngology a n d
space: the post-nasal space, tonsil, parotid •
S i lver AJ , M a wad M E , H i l a l SK, Sa n e P, G a n ti SR. Co m p u ted to m o g ra phy of t h e ca rotid s pa ce a nd re l ated cervica l
always surgical. The main problem is one of adjacent structures.
H e e n e m a n H , J o h n so n JT, Cu rt i n H D, et a l . The parapharyngeal space: Anatomy and path ologic
on imaging techniques.
•
B a s m aj i a n JV. Grant's method of anatomy, 9th e d n . B a l t i m o re : W i l l i a m s a n d W i l ki ns, 1 97 5 : 564-5.
Allied Sciences. 1 9 8 9 ; 1 4 : 1 99-203.
and oral cavity.
7.
Sta n l ey RE. Pa ra p h a ry n g e a l s p a ce t u m o u rs. Annals of th e
survival is greater than 90 percent. Some
8.
Ti n ca n i AJ , M a rt i n s AS, Alte m a n i A, Sca navi n i J r. RC,
As most tumours are benign, the five-year benign tumours, notably paragangliomas,
Academy of Medicine, Singapore. 1 99 1 ; 20 : 589-96. Ba rreto G , Lag e HT et 01. Pa ra p ha ry n g e a l space t u m o u rs :
may in fact be malignant but can only be
con s i d e ra t i o n s i n 2 6 ca ses. Revista Paulista d e Medicina.
diagnosed surgically not histologically. Survival for malignant lesions in the PPS is relatively good but the survival of those
1 99 9 ; 1 1 7 : 34- 7 . 9.
a n 1 8 -ye a r revi e w. Journal o f Laryngology and Otology.
patients in whom malignancy has spread to the PPS is less than 1 0 percent over five years, suggesting that PPS involvement (other than
200 2 ; 1 1 6 : 1 70-5. 1 0.
Som PM, B i l l e r H F, La wson W, Sacher M , La n z i e ri CF. Para p h a ry n g ea l s p a ce m asse s : an u pdated p rotoco l based
post-nasal space) of adjacent tumours should be considered a sign of relative incurability.
Pa ng KP, G o h CH, Ta n HM. Pa ra p h a ry l1 g e a l s p a ce t u m o u rs :
u po n 1 04 cases. Radiology. 1 9 84; 1 5 3 : 1 49 - 5 6. 11.
Kasse l EE. Pa ra p h a ry n g ea l a nd d ee p l ob e pa rotid t u m o u rs. Journal of Otolaryngology. Supplement. 1 9 8 2 ; 1 2 : 25-3 5.
1 2.
J o h n so n AT, M a ra n AG. Extra -cra n i a l tu m o u rs of t h e i nfra te m po ra l fossa . Journal o f Laryngology a n d Otology.
Best c l i n ica l p ra ctice
1 98 2 ; 9 6 : 1 0 1 7 - 2 6 . 1 3.
on clinical pathologic diagnosis. Rochester, M I'J : A m e ri c a n
./ I n it i a l a ssess m e n t s h o u l d c on sist of a th oro u g h cl i n i ca l exa m i n a ti o n t h a t d ocu m e n ts a l l cra n i a l n e rve d efi cits, fo l l owed by a scan a n d fi n e n e e d l e a s p i rati on
Aca d e m y of O p hth a l m o l ogy a n d Oto l a ry n g o l ogy, 1 97 7 . 1 4.
those pati e n ts w h ose i n t e r n a l carotid a rt e r i es a re at
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Bozzetti A. B i g l io l i F, G ia n n i A B , B ru s a t i R. M a n d i b u l otomy
ca rc i n o m a w ith accel erated fract i o n a tion (6 fra ctio n s p e r
for access to b e n i g n deep l o be p a rotid tu m o u rs w i t h
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Att i a EL, B e n t ley KC, H ea d T, M u l d e r D. A new exte r n a l
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E n h a n ce m e n t of l oca l control i n l o ca l ly a d v a n ced n o d e positive n a so p h a ry n g e a l ca rci n o m a b y a dj u n ctive
B i l l e r H F, S h u g a r J MA, Kres p i YP. A new tec h n i q u e fo r
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Otolaryngology. 1 9 8 1 ; 1 07 : 698-702.
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M a l o n e J P, Ag rawa l T, Sch u l l e r D E. Safety a n d effi cacy of
g i n g ivo l a b i a l s u l cus. Oral Oncology. 2000 ; 3 6 : 461 -5. 1 1 0.
p a ra p h a ry n g e a l s pa ce i n vo l ve m e n t in n a so p ha ry n g e a l
As i a n G , Ka rg i E, G o r g u M , Erd o g a n B, Ki l i n c H . Mod ifi ed
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Biology, Physics. 2 002 ; 5 2 : 957-63. 111.
La ck EE, Cu b i l l a AL, Woo d r u ff .1 M . Pa ra g a n g l i o m a s of
D i a z-Go n za l ez FJ , Pa d ron A. Fo n ce a AM, G a rc i a d e Sola R,
the h e a d a n d neck reg i o n . A path o l o g ica l study of
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the c l ivus a n d pa ra p h a ry n g e a l s p a ce : the p a rt i a l se g m ented L e Fort I osteoto my. Plastic and Reconstructive
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Surgery. 1 999 ; 1 0 3 : 9 55-9. 1 00.
X i a o G L, Gao L, Xu GZ. Pro g n osti c i nfl u e nce of
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t ra nscervi c a l resection of p a ra p h a ry n g e a l s pa ce n e o p l a sms. Annals of Otology, Rhin ology, and Laryngology. 98.
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Physics. 2 0 0 1 ; 50 : 1 1 8 1 -9.
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spa ce tu m o u rs : an a l g o ri t h m fo r eva l u a t i o n a n d
Sc h w a rtz Th, B ru ce J I\J . Exte n d e d fro n ta l a p p ro a c h w ith b i l atera l o rb i tofro nteot h m o i d a l osteoto m i e s fo r re mova l of
Pe nsa k M L, G l u ck m a n .I L, S h u m ri c k KA. Pa ra p h a ry n g e a l m a n a g e m e nt. Laryngoscope. 1 994; 1 0 4 : 1 1 70-3.
1 1 3.
C h e n g S H , Ye n KL, J i a n JJ, Tsa i SY, C h u N M , Leu SY et 01.
a g i a n t extra c ra n i a l sch w a n n o m a i n t h e n a so p h a rynx ,
Exa m i n i n g p ro g n ostic fa ctors a n d p a tterns of fa i l u re i n
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Neurology. 2001 ; 5 5 : 2 70-4.
ra d i o t h e ra py a n d c h e m ot h e ra py : i m p a ct o n fu tu re cl i n i ca l
2542 III PART
1 7 H EAD AN D N EC K TU M O U RS
tri a l s. In ternational Journal of Radiation Oncology,
1 1 4.
1 1 5.
Chao K S , Deasy J O, M a rk m a n J , H ay n i e J , Pe rez CA,
Biology, Physics. 2001 ; 50 : 7 1 7 - 2 6.
Pu rdy J A et 01. A p rospect ive stu dy of sa l iva ry
Lee AW, Kw ong D L, Le u n g S F, Tu n g SY, Sze W M , S h a m J S
fu n ct i o n spa r i n g in pat i e n ts w it h h ead a n d n eck c a n c e rs
e t 01. Factors affect i n g r i s k o f sym ptomatic t e m p o ra l l o be
receivi ng i n te n sity- m od u l ated or t h re e d i m e n s i on a l
n ecros i s : s i g n ifica nce of fracti ona l dose a n d t reatm e n t
ra d iati on t h e ra py : i n itia l res u l ts. In tern ational Journal
t i m e . International Journal of Radiation Oncology, Biology,
of Radiation Oncology, Biology, Physics. 2001 ; 49 :
Physics. 2002 ; 53 : 7 5 - 8 5 .
907- 1 6.
192 Oral cavity tumours including the lip
KEITH WEBSTER
Lip cancer
2543
Key points
2562
Key points
2549
Carcinoma of the hard p alate
2562
Best clinical practice
2549
Key points
2563
Oral cavity ca n cer
2549
B est cl i n i cal practice
2564 2564
Key poi nts
2551
Neck dissection in oral cavity ca n cer
Carcinoma of the tong u e a n d fl oor of mouth
2552
Key points
2565
Key points
2554
Best cl i nical pract ice
2566
Best cl inical pra ct i ce
2554
S urg ical approa ches to the oral cavity
2566
Carcinoma of base of tong ue
2554
Key points
2568
Floor of mouth tumour s
2557
Reconstru ct i on of the oral cavity
2568
Mandibular tumours
2558
Key poi n ts
2572
Key p o i nts
2559
Best cl inical pra cti ce
2572
Best cl i nical practice
2560
Deficiencies i n current knowledge a n d a reas for future
Maxillary alveolectomy
2560
B uccal ca rcinoma
2560
research Re ferences
2573 2573
SEARCH STRATEGY The
d a t a in this ch a pt er are su pp o rted by a Medline search using the key words l i p cancer, oral c ance r, lip reconstruction, cancer) buccaJ cancer, jaw reco nstruct i on and focussing on th e diagnosis) surgery and management.
ton g u e
LIP CAN CER
90% in lower lip 7% in upper lip 4% in commissure
E p i d e mio l ogy c ommon mal ignant tu m our neck and its clinical behaviour is s imi lar to that of skin ca ncer. Incidence rates vary and example s are 13.5 per 100)000 in Oceania, 12 p er lOO,OOO in E u r ope and 12.7 per 100)000 in North America.l The factors co mmo nly cited as important in lip cancer are: solar ra d iat i on, tobacco smoking a nd viruses.l The ra te of lip cancer appear s to be d i rectly related to the amount of sun exposure and its incid en ce increases towards the equat o r. It is much more common in men th an women, wit h a 14:1 ra t io . The main aet i o l o gi ca l factor of solar radiation means tha t the lower lip is m uch more commonly affected than the uppe r l ip. Ninety percent Cancer of the lip is the most
affe c t i ng the head and
of tumo u rs arise in the lower l i p with 7 pe rcen t occur ri ng oral comm i ssu re. Squ a mo us cel l carci noma is the commonest hi sto lo gical tumour type, followed by basal cel l carcinoma. Th e commonest nonsquamous form of lip cancer arises fr om tumours of the minor s al iv a ry gl a nds , with the upper lip be ing more commonly involved t h a n the l ower lip. The distrlbution of lip cancer is shown in Figure 192.1. in the upper lip and 4 percent at t he
C l i n ica l c h a ra cteri stics The clinical presenta ti o n of ca nce r of the lip is us u ally that of an exop hytic crusted lesion with variable i nv a s ion into underlying muscle (related to the size of the p r ima r y tumou r ) . Th e a dj ace nt lip often shows features of actinic sun d a mage such as crusti n g ) c ol o u r c ha n g e, thinning of
2544 I
PART 1 7 HEAD AND NECK TUMOURS ..-.�""""""
...
-.t "" -_
/ ' ,t("{f"'
-�
S tage
4% 6%
.
..�
90%
Figure 1 92.1
TN M definition of lip cancer.
Table 1 92.1
'\��">-.,.......----�,
Distribution of lip cancer.
Description
TX
P rima ry tumour cannot be assessed
TO
No evidence of primary tumour
T is
Carcinoma in situ
T1
Tumour 2 cm or l ess in greatest dimension
T2
Tu mou r mo re than 2 cm but not more t ha n 4 em in
T3
Tumour more t han 4 em in greatest dimension
T4
Tumou r invades th roug h cor tica I bone, inferior alveo la r
g reatest dimension
nerve, floo r of mouth, o r skin of face, i.e. chin o r nose
Primary tumour
(T).
FACTORS AFFECTING CHOICE OF TREATMENT
FIgure 1 92.2
Expohvtic l ip cance r.
the lip and various associated areas ofleukoplakia (Figure 192.2). The staging of primary cancer of the lip is similar to that of the oral cavity and is sho wn in Table 192.l. Tumo ur s less than 2 cm are sta ged as Tl, 2-4 cm as T2, greater than 4 cm as T3 and tum o urs with invasion of deep soft tissues, adjacent bone or skin are staged as T4.
Treatment is guid e d by the anatomical po si tio n of the tum our and also by associated pat ient factors. Small lesio ns are managed by simpl e surgical excision and prim ary clo sure. E qual ly good resul ts are achieved with external beam radiotherapy ( which may be mor e a ccept abl e in elderly pa tie n ts) . [Grade C] Larger l esio ns of the lip require more consideration with regard to reco nstructio n techniques.3 The amount and type of reco nstructio n necessary will relate to the extent of l ip resection and whether adjacent tissue can be used with a good aesthetic outcome.4, 5 The fu ncti o nal outcome of the repair with regard to lip sens itivity and muscle fu nct i o n also needs to be taken into consideration. The gener al physical and medical and psycholo gical condition of the patient is impo rt ant in deciding between primary surgery and primar y radiot her a py. [H]
REPAIR OF UP DEFECTS
Investigations I magin g of
early stage tumours of t he lip is us ually not indicated. However, advanced tumours of the lip (particularly if t h ey are adherent to the adj acent mand ible) requi re CT or MR imaging to allow complete sta gin g and treatment planning with regard to res ectio n ma r gi ns which may incl u de adj a cen t jaw bone. [HI""]
Ablation and reconst ruct io n should i d eally be perfo rm ed at the same time. It is impo rtan t to remember that the lip should have se n sat io n, mo ti on, preven t droo ling, permi t speech and have a reasonable cosmetic appearance. Whenever p o ssibl e, full thickness skin flaps (skin, muscle, and mucosa) should be use d . The repair should provide sufficient mucosa co n tiguou s to the commissure to avo id co n tracture .
LIP SHAVE AND MUCOSAL ADVANCEMENT
Treatment
Early stage lip cancer can be treate d equally well by surgery or radiation therapy. The five-year crude survival rates for surgical treatment are arou nd 75-80 percent for Tl to T2 tumo urs, d r o ppi n g to 40-50 percent fo r T3 and T4 t umo urs. 2 The presence of cervical nodes at presenta tion is a poor pro gno st ic i ndicato r. Approx ima tely 15 percent of pat ien ts fail initial therapy and this usually presents as local or regi on al failure.
Superficial field change les ions affecting the exte r n al vermilion of t he lip, such as leuko plakia or actinic keratosis, are best manage d by a lip shave and mucosal a d va ncem en t . With extensive premalignant changes, the entire vermilion surface of the lip may r equi re excision. Following adequa te excision of the vermi li on border, the mucosa of the residual labial sulcus aspect of the lower lip is mo bilized down to the gingival buccal sulcus. The blood supply t o t hi s tissue is maintained via its lateral margins. A ho riz o ntal relieving incision in the buccal
Chapter 192
sulcus is often required to allow sufficient mucosal advancement. The undermined mucosa is now advanced
O ral
cavity tumours including the lip I 2545
Lower lip defect
advanced mucosa is sutured to the remaining lip with
il
il
interrupted resorbable monofilament sutures. An appli
<1/2
112-2/3
to the edge of the previous vermilion excision and accurate alignment restores the vermilion border. The
cation of chloramphenicol ointment prevents scaling of the lip during healing and irritation from the sutures. The
Wedge excision
patient is warned that an initial loss of sensation will
Karapandzic Abbe-Estlander
return over the course of a few months. Following treatment) advice on the use of sun block to the lip to
il >2/3 Bernard Burrow Gillies fan flap Webster flap
prevent recurrence of the original problem is given. [**/*]
Free flap
Figure 192.3
Lower lip reconstruction.
Figure 192.4
Lower lip cancer W excision.
LOWER LIP
The techniques for treating defects of the lower lip are summarized in below.
Figure 192.3 and described in detail
Infiltrating lesions of the lower lip affecting less than one-third Small lesions invading into the adjacent muscle are amenable to a wedge excision. A through and through surgical defect is thus created. Tn closing the defect, the vermilion is temporarily approximated with a resorbable suture. This allows the underlying muscle to be closed in two layers. The external skin is closed with an interrupted monofilament and the labial and intraoral wound is closed with a resorbable suture. The excision can also be completed using a W plasty or half W plasty to avoid the bottom of the excision encroaching on the crease line of the chin
(Figure 192.4). [**/*]
Lower lip defects one-third to two-thirds Defects of the lower lip over one-third require a different surgical approach. The dimensions of the lip resection require the introduction of tissue from the other lip by means of an Abbe or an Abbe-Estlander flap or rota tion of tissue from the adjacent lip via a Karapandzic flap.6. 7.8,9
Abbe-Est/ander flap The Abbe-Estlander staged reconstruction requires the development of a triangular full thickness flap from the upper lip. The width of the flap is one-half to two-thirds the horizontal length of the lower lip defect, with the vertical dimension of the flap being the same as the surgical defect. The flap is pedicled on the labial artery with the full thickness incision extending within 2-3 mm
Estlander flap is a laterally based Abbe flap that is used
of the vermilion border. With the flap mobilized, initial
when defects affect the commissure.) The commissure is
inset into the defect is completed in a layered fashion
thus rotated when the tissue is transferred to the defect in
(Figure 192.5). Two to three weeks after the harvest of the
the lower lip. The patient needs to be placed on a soft diet
flap, the pedicle is divided and the final insetting of the
whilst the transposed flap takes. Venous com promise of
flap'is completed. Care is taken accurately to reconstruct
the flap is usually due to leaving too thin a bridging
the white line. T he Estlander modification of the cross-lip
pedicle or too tight a closure. A few sutures should be
flap is used to reconstruct the oral commissure.
removed in the early stages to see if this reverses the
(An
2546 I
PART 17 HEAD AND NECK TUMOURS
Figure' 92.5
Abbe flap
(a)
T1 squamous cell carcinoma, right lower lip; (b) outline of excision mar ked on lower lip and rotation flap
on upper lip; (c) the tumour has been excised;
(d) the
upper lip rotation flap has been raised. Note the anterior limit of the incision at
(f)
the verm i l lion border; (e) the upper l ip rotation has been inserted into the lower l ip a n d the don o r site repai red; just prior to incising the ped icle.
three weeks later,
venous compromise, or consideration to the use of
remalDlDg
superficial to the orbicularis oris
medicinal leeches to deal with the venous stasis needs to
Sufficient
length
be undertaken. The bridging pedicle is divided under
performed to permit medial mobilization of both flaps
local anaesthetic after two to three weeks.
for a midline closure. The repair of the defect begins with
(**/*J
the
Karapandzic flap
vertical
in
midline
the
mucosal
closure
of
incisions
the
lower
muscle. must
lip
be
with
approximation of the vermilion border by a temporary
The Karapandzic flap is useful for defects involving more
nylon suture. The advanced muscle in the orbicularis oris
than two-thirds of the lower lip where the defect is in the
is closed in the midline followed by external skin closure.
midline.lo The main advantage of the Karapandzic flap is
Following
that the nerve and blood supply to the underlying
between the advanced cutaneous margin of the flap and
this,
reapproximation
of
the
suture
line
orbicularis oris muscle is retained and the underlying
the residual cutaneous margin of the chin and nasolabial
orbicularis muscle is rotated so that a sensate functional
region is undertaken
lip reconstruction occurs. The tissue is rotated from the
the tighter the reconstructed lip will be, and thus a certain
(Figure 192.6). The larger the defect,
nasolabial region and this tissue is shifted medially and
amount
rotated into the lower lip. The lateral incisions of the
Karapandzic flap reconstruction. This is more easily
Karapandzic
accommodated in the elderly edentulous patient where
flap
follow
the
nasolabial
skin
creases.
of
microstomia
can
be
present
following
Resection of the tumour on the lower lip is performed
there is a certain amount of skin laxity. The restricted oral
in the usual manner and then the skin incisions for
aperture will stretch gradually over the course of a few
elevation
of
the
Karapandzic
flap
are
made.
It
is
important to avoid division of the muscle fibres contain ing the neuromuscular control of the orbicularis under the skin. To aid mobilization,
mucosal incisions are
placed in the gingival labial and gingival buccal sulcus on each side. The flap is elevated in a subcutaneous plane
months
and
physiotherapy.
the
stretching
[**1*]
can
be
augmented
by
Lower I ip defects greater than two-thirds With
' larger defects of the lower lip, reco nstruction
requires either large cheek flaps to be advanced to repair
Chapter 192 Oral cavity tumou rs incl u d i ng the lip I
(0)
Figure 192.6
Unilate ra l Karapandzic flap.
(bl
Figure 192.7
Gil l ies fa n flap.
Figu re 192.8
Webs ter- Berna rd reco nstruction.
two flaps are advanced medially, the triangles closed and the flaps are approximated in layers
the defect or the use of free tissue transfer. The common forms of cheek flap include the bilateral Gillies fan flaps or the Bernard-Webster cheek flap reconstruction.4 [Grade D) In the Gillies fan flap, a full thickness incision is made around the commissure, extending onto the upper lip at the nasolabial fold. The incision is cut and advanced almost to the vermilion border of the upper lip.
The flap
is now pedicled on labial vessels and can be advanced unilaterally or bilaterally and
closed in layers.
The
modified fan flap differs from a classical fan flap in that the flap rotates around the angle of the mouth to fill in the defect. The vermilion is reconstructed by mucosal advancement of a tongue mucosal flap which is divided at ten to fourteen days advancement
flap,
(Figure 192.7). In the Webster cheek horizontal incisions
2547
are
extended
laterally from the base of the defect and the commissure.
(Figure 192.8).
Free tissue transfer is required for lip reconstruction when the total remaining lip or adjacent rotated
tissue
is
insufficient to create a reasonable circular and symme trical mouth. Often these defects include cheek, skin and
underlying mandible. In this case, a radial artery
free
forearm flap using the palmaris longus tendon to suspend the lower lip is used. This reconstruction technique,
however, is insensa te and immobile and merely provides a static platform for the mobile upper lip to close against. The flap is used as a double paddled flap rotated on the underlying palmaris longus tendon. The skin and contour match is not as accurate as when using adj acent rotated tissue. The excisions
lip can remain ptotic and may require wedge
a
few
months following
reconstruction to
improve the lip tone, allowing the formation of an adequa te seal with the upper lip. Similarly, fascial slings
may be required to maintain lip closure.
[**1*]
The resulting four Burrows triangles are excised above and below the lateral aspect
of the flaps. The flaps are
advanced bilaterally and closed in layers, and the resulting
triangles are closed. The vermilion is reconstructed by mucosal advancement or
a
tongue flap.
In the Bernard-Webster flap, Burrows triangles are
UPPER LIP
In the upper lip, defects again can be divided into less
than one-third, one-third to two-thirds and greater than
two-thirds
to
complete
defects.
The
techniques
formed at the edge of the lower lip excision. Incisions are
treating them are summarized in
extended laterally from the base of the defect. The buccal mucosa from the base of the excised Burrows triangles are
Figure 192.9.
Defect involving up to
of upper lip
one-third
lower lip defects,
for
rota ted 'inferiorly over the free margin of the triangle and
Similar
used to reconstruct the lateral vermilion of the lip. The
advancement flaps can address upper lip defects which
to
wedge
excisions
and
2548 I
PART 17 HEAD AND NECK TUM O U RS
Upper Ii p defect
D
D
<1/2
1/2-2/3
Wedge excision
PeriAlar Crescentic
>2/3
D
Burrow Diffenbach
that obtained surgically. 12, 13 However, the cosmetic results of radiation therapy to the lip may not be as satisfactory as surgical excision and repair. Surgical excision of small lip tumours involves relatively minor surgery, often under local anaesthetic and may be therefore less burdensome for the patient than a course of radiotherapy.
Reverse Karapandzic free flap Abbe-Estlander
Figure 192.9
Upper l ip reconstruction.
involve up to one-half of the width of the upper lip. Care is taken to respect the relevant aesthetic subunits. Defects of less than one-third in the midline can be closed primarily. [**/*] Defects between one-third and two-thirds
These can be reconstructed with cross lip flaps from the lower lip. Perialar crescentic advancement flaps can be used to disguise the advancement of the upper lip when the advancement encroaches on the medial part of the nose. [**/*]
EXTERNAL BEAM THERAPY
The lower lip is one of the few ideal sites for orthovoltage x-ray therapy. Using a single anterior field, a fractionated course of 50 Gy in 15 fractions over three weeks is given.
BRACHYTHERAPY
192-Iridium brachytherapy can be used in the treatment of lip cancer. Patients can be treated twice a day for four to five days with a total radiation dose between 40 and 45 Gy in eight to ten fractions. [Grade B] The Paris system is often used, where needles are placed horizon tally and parallel to the mucosa of the lip with 9 mm spacing between them.12 [**/*]
Defects greater than two-thirds of the upper lip
A Burrow-Diffenbach reconstruction can be performed. The Burrow-Diffenbach flap replaces upper lip defects by utilization of laterally based advancement flaps. Bilateral perialar crescentic excisions are required to provide adequate advancement. [**/*]
NECK DISSECTION IN LIP CANCER
Squamous cell carcinoma of the lip does not appear to be as lethal as squamous cell carcinoma at other sites in the oral cavity. The favourable survival rate of lip cancer is often due to the early stage of presentation of tumoursll and most large series in the literature show that the majority of patients have small lesions without palpable cervical metastases. The local recurrence rate is low due to the relative ease of surgical excision and even re-excision because of local failure leads to salvage in 75-80 percent of patients.s The incidence of synchronous cervical metastases increases as the size of the primary tumour increases. The primary lymphatic drainage of the lower lip is to the submental and submandibular level 1a and 1b cervical lymph nodes. Neck dissection is generally not performed in the absence of clinically suspicious cervical lymph nodes as less than 5 percent of patients are likely to develop recurrence in the neck following treatment of the primary lesion.ll [*** 1
PHOTODYNAMIC THERAPY
Photodynamic therapy can also be used to treat primary cancer of the lip.14 A light sensitizing drug such as photofrin is given intravenously followed four days later by a single nonthermal illumination of the tumour using a light dose of 20 J/cm with an irradiance of 100 mW/cm2 (Figure 192.10). This form of treatment yields complete response rates comparable to those published for surgery or radio therapy.ls (Grade D] As this treatment works by a cold photochemical process producing apoptosis and vascular shutdown, less scarring should occur compared to radiotherapy and surgery. However, clinical experience suggests that some scarring does occur with larger lesions and the problems of light sensitivity and pain following
RADIOTHERAPY TECHNIQUES
Various studies have shown that for small tumours, radiation therapy can achieve a cure rate equivalent to
Figure 192.10
Photodynamic the ra py fo r lip cance r.
Chapter 192
Table 192.2
Tu m o u r thickness a n d s u rviva l rate i n l i p ca n ce r.
Tumour size (em)
Five year survival
(%)
Table 192.3
O ra l cavity t u m o u rs incl u d ing the l ip I 2549
Ca n ce r of the o ra l cavity.
Site
G rad e
94
Tongue
COl-C02
<2
84
Mouth
C03 -C06
<3
58
O ro pharynx
C09-ClO
<4
67
Othe r a n d i l l -defined sites
C14
>4
62
Reproduced from Ref. 17, with permission.
Presence of nodal disease and five year survival: N+ 61%; NO 89%.
oral cancer diagnosed in the UK in 2001. thus
lack of tissue memory for photodynamic therapy means
(outnumbering
that, unlike radiotherapy, this treatment can be given on a
Although oral cancer is not common, the disease is
number
Laser
increasing in younger adults, particularly men in their
[***]
forties and fifties.
occasions.
See
also
Chapter
58,
principles in otolaryngology, head and neck surgery.
for
1.6
cervical
percent cancer)
of
all
Oral cancer
treatment may limit its general application. However, the
of
accounts
18
new
(Table
cancers
192.4).19
All oral cancers have similar risk factors, the most important of which are tobacco and alcohol consump 2o tion. Around one-third of oral cancers are diagnosed in
Surviva l rates fo r l i p cancer
the mouth cavity and just over one-quarter in the tongue. The survival rates for lip cancer are shown
192.2.
16
III
Table
In the UK, oral cancer is more common in men than women, however, the sex ratio in the UK has decreased rapidly from 5: 1 50 years ago, to less that 2: 1 today. Rates of oral cancer in Scotland are significantly higher than in other parts of the UK,21 which correlates with a higher rate of tobacco and alcohol consumption in Scotland.
KEY PO I NTS
Studies of the disease in ethnic populations have shown a •
Lip cancer arises mainly as a result of solar
high rate in South Asian and Chinese populations in
radiation.
which the habit of areca nut or betel quid chewing is 22 prevalent.
•
Surgical reconstruction usually involves local
•
Neck metastases are unusual.
•
Radiotherapy is reserved for elderly and
cancer in men and may account for up to 30 percent of all
medically unfit patients.
new cases of cancer compared to 2 percent in the UK and
In high risk countries such as Sri Lanka, India,
rotation flaps.
Pakistan and Bangladesh, oral cancer is the most common
8 percent in France. In Europe, the highest male incidence
rates are found in France and Hungary, with the lowest rates in Greece and Cyprus. Oral cancer is strongly related
Best c l i n ica l p ractice A l i p shave is used for dys p l astic l i p m u cosa.
Loca l fla ps a re adequ a te reco nstructi o n s fo r s m a l l t u m o u rs. Recon stru ctive tech ni qu es sho u l d aim to m a i nta i n form a n d fu n ctio n .
to social and economic deprivation, with the highest rates occurring in the most disadvantaged sections of the in inner cities.17 The age standardized
population incidences
of
oral
cancer in
British
men
stood
at
7: 100,000 between 1975 and 1989 but since then the rate
has increased to reach 9.3:100,000 in 2001 (an average increase of 2.5 percent each year since 198 9).18
White female rates have also increased at a rate of 2.8 percent each year since 1989. For men over 80 years of age, the incidence rate of oral cancer has halved since 1975, whilst rates for men in their sixties and seventies has
O RAL CAVITY CANCE R
remained stable. The rate of oral cancer diagnosed in men in their forties and fifties has doubled from 3.6 to 8.4 per
18 100,000.
E p i d e m i o l og y
[***]
In 2003 there were 1592 deaths from oral cancer in the UK. Mortality rates are highest for Scottish men reflecting
The International Classification o f Diseases Version 10 defines the sites shown in
Table 192.3 as cancer of the oral
cavity. Using this definition, there were 4400 new cases of
their higher incidence rates. The overall age standardized mortality rate has remained stable at around 3.5 per 100,000 for men. Oral cavity cancer has an overall survival
2550 I
PART 17 HEAD AND NECK TUMOURS
Table 192.4
Occurrence of lip and oropharyngeal cancer in UK, 2003.
Grade
Site
Female
Male
Total
M:F ratio
Lip
IC010 COO
245
114
359
Tongue
IC010 C01-02
784
455
1239
1.7:1
Mouth
IC010 C03-06
843
561
1404
1.5:1
Oropharynx
IC010 C09-1O
532
185
717
2.9:1
Piriform sinus
IC010 C 12
207
44
251
4.7:1
Hypopharynx
IC010 C13
112
88
200
1.3:1
Other and ill-defined
ICOlO C14
145
85
230
'.7:'1
2868
1 532
4400
1.9:1
Oral cancer
2:1
Reproduced from Ref. 19, with permission.
rate of 45 percent with tongue cancer having an overall survival rate of
42 percent. Happily, there has been an
increase in survival for all sites over the past ten years.
lS
C: Nonsmoker
Ex-smoker
• 20-39/day for 20+ years
• 40+/day for 20+ years
1-19/day lor 20+ years
As for most cancers, survival is better for younger than older patients. There are significant differences between
40 35
the most affluent and most deprived groups for cancer of the tongue and oral cavity. Most of the improvement
30
in survival has therefore occurred in the affluent group.
� 25
The five year survival rate has increased from percent between
1971-1975
and
1986-1990
43 to 55
for affluent
patients, compared with a very small increase over the same period of 42 to patients.
44 percent for the most deprived
·co
� �
�
20 15 10 5
40+/day for 20+ years
o
30+
Risk factors
Figure 192.11
As has been stated) the most important risk factors are tobacco usage and excess consumption of alcohol and the two
factors
act
synergistically
(Figure
192.11).
In
developed countries, the risk of oral cancer attributable to these factors is estimated to be more than
80
percent?3
Synergistic effects of alcohol and tobacco on
cancer risk.
as a cost-effective screening test. These differences may be related to different patient populations.
A deficient diet also predisposes towards the development
ALCOHOL
of oral cancer and may be responsible for
percent
Alcohol is the second major risk factor with 75 percent of
percent of patients with oral cancer use
alcohol per day, the risk increases linearly with amounts
10
to
15
of cases in Europe. Over
90
tobacco in some form. Smoking cigarettes is the main
form of tobacco use in the UK. The risk of oral cancer associated with smoking is both dose and duration 2 dependent 0 and the excess risk of oral cancer from smoking almost disappears within ten years of giving up. Due to the effect of carcinogens, patients are at risk of developing
second
primary
tumours
aerodigestive tract and there is a
in
the
upper
4 percent risk per year
of developing a new primary in the aerodigestive tract. Although some early studies have suggested there is a
10
percent risk of having a synchronous primary elsewhere in the aerodigestive tract at the time of presentation of the index primary) clinical experience suggests that this rate is
patients frequently consuming alcohol. 25 Above
30 g
of
of alcohol consumed. Those consuming more than thirty drinks a week and smoking more than forty a day for twenty years have a 40 times relative risk of developing cancer compared to nonsmokers and nondrinkers. The total amount of alcohol ingested is more important than the type of product. In the UK, consumption of alcohol has more than doubled since the middle of the last century_ The pooling effect of alcohol in the floor of mouth is one factor suggesting the predilection of oral cancer for the floor of mouth and lateral tongue.
DIET AND NUTRITION
too high?4 Hence the pick up rate of triple endoscopy is
Dietary deficiencies of vitamin A, vitamin C) vitamin E,
lower than that previously thought and the use of
iron, selenium, folate and other trace elements have been linked to increased risk of oral cancer.26•27
surveillance endoscopy in at risk patients is questioned
Chapter 192 Oral cavity tumours including th e lip I 2551
Table 192.5
VIR U SES
role of viruses remains unclear. Evidence is s trongest for infection with high risk human pa pilloma viruses (HPV). Studi es show an increased risk of oral cancer in women with cervical cancer, suggesting that common risk factors other than smoking such as HPV infec tions may be involved. The role of infection with Epstein-Barr and 28,29 . h erpes simp I ex v}fuses ' rema l. OS unc I ear.
Stage
The
ORAL HYGIENE
PREMALIGNANT CONDITIONS
There are several premalignant conditions that precede oral carcinoma and the commonest of these are leukoplakia 30 a nd erythrop laki a (Figure 192.12). Estimates of leuko p laki a prevalence range from 0.2 to 11 percent of the population. The annual transformation rate of oral leukoplakia to oral squamous cell carcinoma may be up to 5. 7 percent per year. T he most predictive factors of cancer risk are histology, cancer history and three biomarkers ( chromosomal polysomy, p53 protein expres sion and loss of heterozygosity at chromosome 3p or 9p.30
stag i n g
of oral cancer.
T
N
M
0
Tis
NO
MO
I
T1
NO
MO
II
T2
NO
MO
III
T3
NO
MO
T1
Nl
MO
T2
Nl
MO
T3
Nl
MO
T4
NO, N1
MO
Any T
N2, N3
MO
Any T
Any I\J
Ml
IVB
Any T
N3
MO
IVC
Any T
Any N
Ml
IVA
Poor oral hy giene and ill-fitting dentures may also play a role in loc alizing a s ite where tumours may develop. However, both of these factors are unlikely to cause oral cancer in the absence of other risk factors.
TNM
rate of clinical resolution but there is a high rate of relapse therapy is disc ontin u ed and the side effects of the treatment mean it is not ap p lic a ble as a preventive treatment in t he population groups at risk. Guidelines to general practitioners from the National Institute for He a lth and Clinical Excellence (NICE) on the possible symptoms of ora l cancer include a mouth sore or ulcer that fails to heal or bleeds easily and all red and white patches in the mouth that witl not go away or a l ump or thickening in the mouth tongue or throat. when
Path o l ogy
--����----�--.
Cl i n ica l presentati o n
=-c===
Symptoms vary according to the site of the twnour. White or red patches on the oral mucosa may indicate a precancerous condition and a biopsy is essential. Up to 6 p ercent of leuko plaki a s may become malignant over a ten-yea r peno . d. 30 A recent Cochrane review concluded there is no effective treatment preventing malignant transformation of leukoplakia.31 Treatment using chemoprevention with vitamin Alretinoid analogues is associated with a high
Over 90 percent of primary malignant tumours of the oral c avit y are squ am ous cell carcinomas. A p prox ima tely 5 percent of tumours are those arising from the minor salivary glands, with less than 1 to 2 percent of tumours being melanoma, lymphoma or sarcomas. Thirty-seven percent of tumours pr es ent as stage I disease, 36 percent of tumours present as st a g e II dis ease with 18 percent presenting as stage III and 9 percent presenting at stage IV disease (Table 192.5).
KEY POI NTS •
• •
1.6 percent of c ancer worldwide. 30 percent found in mouth, 25 per cent on tongue. Rates increasing in young men and women. Tongue cancer thickness d efines risk of metastasis.
•
•
• •
Figure 192.12
Leukoplakia in the floor of mouth.
Tongue base cancer treated by chemoradiothera py. Jaw resection usu ally requires mi crov ascula r reco nstru cti on. Surgical approaches improve access to tumours. Reconstruction im por tant to function.
25 52
I PART 17 HEAD AND NECK TUMO U RS
CARCI N O M A OF THE TONGUE AND FLO O R OF M O UTH
survival of
85.7
percent) significantly greater
than the rates of
58.3
tumour thickness of
Cli nical p resentation
further
(p < 0.05)
percent for patients with
4-7 mm and
.
1
> 7 mm) respective y_
33
[***J These survival figures relate predominantly to the
35 percent of
squamous cell carcinoma of the oral cavity and the floor of mouth accounts for a
57
presence or absence of nodal metastases.
====,-----
Carcinoma of the tongue accounts for
and
30 percent. These
50
Patients with tumours greater than 1 cm thick have a percent risk of nodal metastases and an associated
lower five-year actuarial disease-free survival.
tumours may present as ulcerative, exophytic or endo phytic tumours and may be associated with pre-existing or
adjacent
areas
of
leukoplakia
or
erythroplakia.
Tumours often present with a raised hard indurated edge (although the exophytic forms may show a verrucous or cauliflower-like appearance)
(Figure 192.13). They are
also associated with bleeding) although pain is an unusuaL feature. Carcinomas that appear to have an endophytic growth pattern may present merely as a hard fixed lump
within the body of the tongue with very little surface change to
indicate the underlying carcinoma, except
perhaps a colour change at the mucosal surface. The most common site for presentation of carcinoma of the tongue is the lateral or ventral surface. These lesions may be in continuity with the floor of mouth. It is unusual for squamous cell carcinoma to present on the dorsum or the tip of the tongue. Carcinoma of the floor of mouth normally presents in the anterior floor of mouth or in the lateral floor of mouth between the tongue and the alveolar process. It is thought that the pooling of saliva and carcinogens in the floor of mouth and lateral border of the tongue explain these sites being the commonest sites of oral carcinoma. Carcinoma of the tongue appears to have a higher risk of metastases to the regional lymph nodes and subclinical nodal metastases may be found in up to carcinomas.32
30 percent of
Tl and
T2 oral tongue
Tumour thickness has been shown to be the most 33 useful feature in predicting subclinical nodal metastases. Patients with tumour thickness of � 3 mm have a five-year
I nve sti 9 ati 0 n All ulcerated lesions of the tongue and floor of mouth that last for longer than two to three weeks require an incisional biopsy to confirm the underlying diagnosis. Suspicious lesions require an incisional biopsy as an attempted excisional biopsy of all but the smallest lesions increases the risk of leaving positive margins at the deep margin (as the depth of invasion can be difficult to assess clinically). Similarly, all areas of leukoplakia and erythroplakia require a biopsy) although the degree of dysplasia in these specimens may not give an adequate indication of likelihood of progression of these lesions. Recent studies suggest it may be the ploidy of cells rather
than the degree of dysplasia that may be the important factor in malignant transformation.34 The ability
to
intervene prior to this advanced stage may improve treatment results_ This requires the early identification of
molecular events that represent early phases of malignant
transition, which is possible through measurement of DNA ploidy in the epithelial cells of oral leukoplakia. A
study
looking
at
ploidy showed
that
aneuploid dysplastic oral lesions had a
patients
96
with
percent rate
of oral cancer with a
70 percent rate within three years) (22 of 27), and a 74 percent rate of death from cancer (21 of 27).34
an
81
percent rate of subsequent cancer
However, we do know that there can be clinical and
pathological regression of these lesions if the risk factors of smoking, and alcohol are withdrawn. Definitive oral squamous cell carcinomas may not develop in the area of pre-existing leukoplakia. The presence of leukoplakia
and erythroplakia on the tongue and floor of mouth
indicate that there may be field change cancerization within the mucosa of the whole oral cavity. It is for this reason that subsequent squamous cell carcinoma may not develop in the areas of leukoplakia that are being clinically observed.
IMAGING In
the
mobile
anterior
tongue
B-wave
ultrasound
sonography has been shown to be helpful in assessing the depth of invasion of suspicious lesions which will help with the subsequent management of these lesions.35 MR scanning (with Tl and T2 scanning with fat suppression Figure 1 92.13
T2 tongue tumO'Jr in a 32-ye a r-old man.
and stir sequences) is the imaging mode of choice for soft
Chapter 1 92 Oral cavity tumours including the lip I
tissue lesions of the oral cavity. Extension of the scan to involve the cervical nodes and chest helps with identifica tion and staging of metastases. The presence of dental amalgam causes significant degradation with CT scanning of the oral cavity, however, in the edentulous patient new spiral CT scanners have reduced the overall radiation dose and time required for scans. This may be more appropriate in elderly patients who have trouble lying flat for the period of time required to obtain a high definition MR scan of the area. The use of vital dye staining and electrofluorescence are experimental and controversial methods of looking for altered dysplastic mucosa. Tl-weighted scans display anatomy, with fluid containing structures such as cerebrospinal fluid (CSF) appearing of low signal intensity (i.e. black) and fat appearing of high signal intensity (i.e. white). The T2-weighted sequence displays fluid-containing struc tures as high signal intensity. As many tumours have higher water content than normal and surrounding peritumoural oedema, this is easily displayed on the short time inversion recovery (STIR) sequence. Intrave nous gadolinium is administered to look for the pathological enhancement of involved nodes and is useful for assessing perineural spread of the primary tumour (Figure 192.14).
Selective fat suppression should be used on these sequences following intravenous contrast since both fat and gadolinium are of high signal. MRI is better than CT for the assessment of perineural and intracranial tumour spread. Positron emission tomography (PET) is useful in improving the detection of head and neck cancer, especially recurrent disease, but lacks anatomical detaiL Its main use in the head and neck is for separating residual scarring from recurrent disease and also poten tially showing the anatomical site of a clinically undetectable unknown primary in a patient presenting with metastatic neck disease. Co-registration of the PET
2553
scans with CT or MRI may improve anatomical detaiL An orthopantonogram (OPG) is used to assess the state of dentition and potential gross mandibular invasion. The use of technetium bone scans will show up areas of tumour but will also show up associated areas of inflammation due to periodontal disease and recent dental extractions. It may be necessary to perform both a CT and MR scan for their different diagnostic criteria if a tongue or floor of mouth tumour spreads to the adjacent mandible.
Management of cancer of the oral tongue STAGE I-II ORAL TONGUE CARCINOMAS
The depth of invasion appears to correlate to the risk of nodal metastasis. Thus management plans based on tongue cancer are based on tumour thickness, measured by ultrasound or MR scanning. Recommendations based on tumour thickness are given in Table 192.6. Some authors have suggested that tongue cancer has a propensity to fast track to level IV nodes and thus an extended supraomohyoid neck dissection rather than a level I-III neck dissection should be performed.32 B rachyth era py
Brachytherapy in the oral cavity12 is limited to the anterior two-thirds of the mouth, as the insertion of the radioactive wires elsewhere is difficult due to access. This essentially limits treatment to the anterior two-thirds of the tongue and floor of mouth. The use of brachytherapy in the UK is limited by the availability of expertise and afterloading equipment. [Grade C] The technique works best on the lateral aspect of the mid tongue. The high dose of local radiotherapy can increase the risk of osteoradionecrosis in the adjacent mandible, especially the dentate mandible, and this is a major factor in patient selection?6 However, preservation of function and form is an important advantage of brachytherapy compared to surgical procedures that produce defects that are not amenable to primary c1osure.37 Brachytherapy should be combined with elective neck irradiation when the
Table 192.6
Management of cancer of the oral tongue
according to tumour thickness.
Tumour
Recommended management
thickness (mm)
< >3
4-9
Partial glossectomy alone Partial glossectomy +
J
-
elective, ipsilateral
level I-IV, selective neck dissection
>10
Partial glossectomy, neck dissection and postoperative radiotherapy to primary site
Figure 192.1 4
M R scan o f tongue cancer.
and neck
2554
I PART 1 7 H EAD AN D N ECK TUMO U RS
thickness of the primary tumour exceeds 3 mm, due to the increased prevalence of neck node micrometastases (Figure 1 92.15). 33
STAG E I l l - IV O RAL TO N G U E CAR C I N O MA
Larger primary tumours have a higher risk of nodal metastases.38 The extent of surgical resection is defined by the clinical and radiological dimensions of the tumour tempered by the quality of life issues that are associated with subtotal glossectomy.39 Patient factors often override tumour factors in deciding whether radical resection of
tumour produces a poor functional outcome in the presence of disease that may only give a 20-30 percent five-year survival. The risk of aspiration increases as the tumour extends into the tongue base and a combined glossectomy and laryngectomy may thus be required. The functional outcome of reconstruction after subtotal glossectomy often relates to the amount of functioning base of tongue muscle that remains after reconstruction. •
Partial to subtotal glossectomy : - modified radical neck dissection type III of N positive neck; - ipsilateral selective level I-IV for NO neck; - postoperative radiotherapy of oral cavity and neck.
Postoperative radiotherapy for stage I and II tongue carcinoma is also required in the presence of positive surgical margins, e:A."tracapsular spread of nodal metastases at neck dissection and the presence of multiple nodal metastases. [*]
K EY PO I NTS •
•
• •
Tongue cancer prognosis depends on thickness of tumour. Tongue base tumours treated by chemoradiation. Microvascular reconstruction aids function. Labiomandibulotomy improves access.
Best c l i nica l p r a ctice /
I n ton g u e ca n cer, a n ec k dissection is i n dicated i f tumour thickness exceeds 3 m m .
,-' S m a l l to n g u e t u m o urs can be treated b y wedge excision a n d pri m a ry c l osure.
,/ M i crovascu l a r fl a ps h e l p m a i nta i n m obi l i ty a n d fu n ction.
CARC I N O M A OF BAS E O F TO N G U E
Fi g u re 192. 1 5
I ri d i u m h a i r p i n s p l a ced into to n g u e ca ncer.
The base of tongue appears to be more sensttlve to chemoradiotherapy than oral carcinoma.40 Access to these tumours often requires a labiomandibulotomy, causing a potential cosmetic deformity. The importance of the mobility of the base of tongue in speech and swallowing is often interfered with in surgical resection and reconstruc tion. There has been a recent tendency to adopt an organ ' preservation schedule of synchronous chemoradiotherapy for base of tongue tumours where the volume and site is
Ch a pter 192 O ral cavi ty tu m o u rs i n c l u d i ng the l i p I 2 5 5 5
suitable
fo r
inducti on
curative
intent
chemotherapy
by
then
responders, a survival o f up
radioth erapy.
Using
chemoradiotherapy to
in
64 percent may be
achievable with a three-year progressi on-free survival with
o rgan
preservation
of
52
percent,
allowi ng
a
co nclusion in this carefully selected group that p atients
a second layer o f closure is used for t h e adjacent m ucosa . A wedge style of excision of tumours allows for a linear clo sure of the defect in the anterior mobile tongue . Superficial lesions can be left to granulate and epithelia lize by secondary intentio n, especially if the surgery of superficial lesions is carried o u t by
CO2 laser therapy.
with base of tongue or hypopharyngeal cancer treated wi th this regimen of indu ction chemotherapy fo llowed by definitive chemoradiotherapy have a good rate of o rgan
R ECONSTR U CT I O N TECH N I QU ES
Thus, regimes for the management of tongue cancer
to half of the tongue when there is no resulting tension on
preservation with o ut compromise o f survival. 40 [ Gr ade B 1
base
include: •
stage
the wound or decreased mobili ty of th e tongue .
When more than half of t h e tongue is excised, o r the
I-II: radio therapy or wide local excision i f
exophytic a n d well-localized via la teral p haryngotomy o r labio mandibulotomy;
•
stage
Primary closure is adequate fo r p ar tial glossectomy of up
tumour extends into the adjacent floor o f mouth or a djacent anatomical areas, then primary closu re will compromise tongue functi o n
III-IV: synchrono us chemol radiotherapy.
resu rfacing and
replacement
(Figure 192. 16). Mucosal
of tongue volume then
becomes the metho d of choice. Historica lly, pectoralis
Adva n ced i n opera b l e ca rci n o m a of t h e to ng u e Palliative sh ort course radiotherapy may b e useful for the management of symptoms such as pain and fungating extraoral tum o u r.
major myocutaneous
flaps were used
to reconstruct
extensive tongue defects, but the p o or tongue mob ility and
bulk
of these
flaps
has
led
to
their
gradual
replacement with microvascular fasciocuta neo us or myo cutaneous flaps as these have been shown to have better fu nctio nal o u tcome,
cosmetic
ou tcome and
mobility.
Similarly, the u se o f local muscle fl aps, such as masseter
Su rg i ca l tech n i q u e of to ng u e ca n ce r resect i o n Transo ral resection and primary closure i s the treatme n t o f cho ice fo r small tumo urs o f t h e mob ile tongue, mainly of the lateral bo rder and floor of mouth. When tumours spread from the tongue to the adjacent floor of mouth ( o r fr o m flo or of mouth to the adjacent tongue or mandible) , the surgical defect o ften requires free flap reconstruction to maintain to ngue m ob ility. D uring transo ral resect ion the tongue is fixed in position by the use of a tongue suture and a 1 . 5 cm margin is marked around the clinical tumour site. The mucosa is cut open with a monopolar d iathermy or harmonic scalpel and dissection of the underlying tongue muscle and salivary glands is p er
and cutaneous flaps, have been superseded d ue to the better functional outcome of microvascular free tissue transfer in large defects that may co mpromise function and mobility. The free radial forearm fasciocu taneo us flap (Figure 192.17) is a suitable ch oice o f thin flap fo r resurfacing o f the tongue a n d h a s a 96 percent survival rate. However, when
a
mo derate
soft
tissue vo lume replacement is
required to imp rove swallowing function then the deficit may be best reconstructed with an anterolateral thigh flap where a greater soft tissu e vo lume can be o btained . If one looks at the quality of speech following significant tongue reconstruction, then it is significa ntly worse six and twelve mon ths after treatment than before treatment. This
fo rmed. D uring the dissec tion th e border of the tumour should be palp ated, especially with regard to the deep m argin, to ensure correct surgical excisio n. A clear histological resec tion margin can be achieved at a
95 percent confidence interval with a
1 . 5-2 em su rgical
margin of resection from the border of the tumo ur.
41
A
resecti on margin of 1 . 5 em is recommended fo r tumo u rs less than
4 em in largest diameter and less than
1 cm thick
lesions, although the margin should be increased to
2 em
fo r larger or thicker tumours. The use of frozen sections
to confirm adequate surgical excision margins is con troversial. A negative frozen sectio n does not exclude the presence
o f disease
(as
a
frozen section is
a
two
d imensional image of a three - dimensional t umo ur) . After haemostasis is achieved, repair of the surgi cal defect
is
performed.
The
deep
m uscu lature
can
be
approximated using interrupted resorbable sutu res and
Fi g u re 192. 1 6
La tera l to n g u e cancer.
2556
I PART 1 7 H EAD AN D N EC K TUMOURS
Fig u re 1 9 2 . 1 7
R a d i a l forearm fl a p reconstru ctio n .
effect after treatment i s caused by the inevitable anato mical and functional alteratio ns caused by surgery and radio therapy. Currently, op timal functional results are observed with the use of free flaps and, in the oral cavity
and o ropharynx, the best o utcome is obtained by the use of thin pliable fascio cutaneo us flaps, such as the radial fo rearm free flap and anterolateral thigh flap. There is better speech function after reconstruction with a free flap rather than with the more bulky pecto ralis major flap . Intelligibility is also fo und to b e improved fo r patients
who undergo reconstru ction by a radial forearm free flap than those who undergo a somewhat thicker lateral upper
arm flap. The use of the radial fo rearm free flap is presently the best reconstructive option, especially when the created defect takes up m ultiple anatomical sites.42 The reconstructio n of subtotal glossectomy defects is co ntroversial.
Some authors wou ld co nsi der that the
quality of life ou tcome following total glossectomy and free flap reconstruction is so poor that this treatment option should not be offered when the patient's main
co ncern of ou tcome are speech and functio n rather than cure and survival. However, others have shown that
swall owing aspiration
and
speech
fo llowing
can
be
maintained
microvascular
without
reconstruction
of
sub-total glossectomy defects.43 I n appropriate patients, an organ preservatio n regime using synchronous chemo radio therapy may be appropriate but overall cure is o ften reduced as the target volume of tissue to be treated is very large.44 If reconstruction of total glossectomy defects is
undertaken, there are two schools of thought about the
reconstruction. One gro up suggests that the bulk of the tumour should be replaced with similar mu scle, even
though this may not be fun ctioning m uscle. In these
Fi g u re 1 9 2 . 1 8
To n g u e reco n st ructed w ith antero l ate ra l th i g h
fl a p .
Other authors feel that a b ulky immobile reconstruc tion p ro duces a worse outcome and therefore a thin pliable radial fo rearm flap to replace the floor of mou th is all that is indicated.42
[* ]
As the overall survival rate of patients with stage In
cases, even a small amo unt of resid ual base' of tongu e can
and stage IV to ngue cancer is often of the order of 30-40
general principle of restoring the m uscle bulk of the
sho uld be gu ided towards quality of life rather than the
allow sufficient to ngue movement to allow a swallow. The
removed tongue is to enable the patient to perfo rm a
bolus swallow by compressing the fo od against the hard
and soft palate to ini tiate the oral phase of swallowi n g
(Figure 192. 1 8 ) .
percent, then it may be that the choices of treatment
complexity of recons tructio n that is available.43
A tempo rary tracheostomy is necessary for patients
with flap reconstructio n and nasogastric or gastrostomy
tube feed ing fo r up to a week is necessary fo r a patient
Ch a pter 1 9 2 Oral cavity t u m o u rs incl u d i n g t h e l i p I
w i t h a flap reco n struction to reduce the risk of oro cervical fistulas. Speech a nd la nguage therapy are involved at an early st age in t ra i ning t he patient to develop the recovery to an o ral diet. B rachyt herapy
using
irid i u m wire
implants
is
an
effective altern a t ive t reatment fo r T l I small T2 lesi o ns of the la tera l a n teri o r to ngue . 1 2 The spaced i r id i u m wires a re placed d i rectly or by after lo ading i n to hollow plastic t ubes placed i n the to ngue. [ G rade
C] Th e t reatment gives
a very h igh dose o f local radio therapy. Th e tech n iq u e cannot be u s e d adjacent t o t h e den tate mandib l e a s significant rates o f os teoradio necrosis m a y occur. T h e results a r e co mparable w ith s u rgical excision b u t some p ro p o nents of the tech nique a rgue tha t the fu nctional outcome is bet ter as no surgical resection and reconstruc tio n occurs.
12
[ **]
2557
M a n a g e m en t Peroral eXCISIOn o f sup erficial lesio n s o f the floor o f m o u th a n d the lateral flo or o f mouth can b e p erfo rmed
with the surgical defect left open to granul ate and heal by seco n d ary intention. However, when such an area is
likely to cause fibrosis and contra cture d u e to secondary heali ng, then reconstru ction of the s u rgical defect with a skin
graft
consi dered
or
fascio cutaneous
free
1- 1 .5 em
of mouth can be excised w ith a often
flap
should
be
(Figure 192.20) . Lesions of the anterior floor margi n . It is
necessary to include the u nderlying s ublingual
gla nds i n the resection as tumour i n the anterior floo r of mouth can invade along the small saliva ry d ucts lea d ing from the sublingual gl ands. Where p o ssible, Wharto n's d uc ts are p reserved a n d dissected free a n d rero uted to the posterio r aspect of the de fect where they are sutured to the mucosal margi n . S uperficial defects above the
F LO O R OF M O UTH TU M O U RS
s u b l i ngual gl ands a nd mylohyoid ca n be left to heal by seco n da ry intentio n but la rger defects ca n be reco n
Presentati o n
s t r ucted with
The floor o f mouth and lingual gutter is one o f the most co mmon s ites of oral ca rcinoma
(Figure 192. 19). The
pooling of saliva in t his area, where the carc i nogenic products of tobacco a n d alcohol a re concentrated, p redis poses these sites to t umo ur. Precancerous l es ions such as leukopl akia and erythroplakia are co mmo n . The t umours are often exophytic and are often fo und in the region of the opening of the submandibular d ucts.
In
the dentate
p atient, an endo phytic t umour presents as u l cerat ion with craggy
borders,
often
infiltrating
i nto
the
adjacent
mandible. Late presentation o f such t u m o urs show vario us degrees of fixation and swelling of the anterior to ngue as the t umour infiltrates into i ntrinsic tongue m uscles.
a split s k i n gra ft .
However, when the
s u rgical defect involves th e m uscles of the floor of the m o u t h a nd extends i n to the neck then microvascular free flap reco n struct i o n wi th a ra dial fasciocuta neo us flap is indica ted to red u ce the risk of an orocervical saliva r y fist u l a . S i milarly, lateral fl oor of mo uth defects can be left to hea l by seco n d a ry i n tention. Whe n the lesion moves into a seco nd t issue plane, s uch as the adjacent ventral s u rface o f the tongue or the m an d ibular alveo l u s, mic rovasc ul a r reconstr uction aids three-dimen sio nal
reconst ructions
a nd
maintains
mo bility
and
fu nctio n . I n the elderly, b ilate ral nasolabial flaps may b e used to repair small
o r moderate defects
i n the
a nter io r floor o f mo u th .45 However, this t issue is th i ck a n d not as p l i a ble as t he radial fo rea rm flap a nd in the yo u nger patient the scar i n the naso l abial fo l d is m o re p rominent .
I m ag i n g
Ped icled fl aps, s uc h as the subm ental island or the
The relationship of these t umours to the o u ter cortex o f the man dible i s critical a n d thus
CT scannin g lo oking fo r
cortical erosi o n is important in the p reo perative planning.
F i g u re 1 9 2 . 1 9
F l oo r of mou th tu mo u r.
facial ar tery musculo m u cosal fla p,46 m ay also be useful i n s m a ll d e fects o f the anterio r o r lateral fl oo r o f m o u t h . By comb i n i ng
F i g u re 1 9 2 .2 0
the
p ri nci ples
of
nasolabi al
and
buccal
Followi ng ra d ia l fo re a rm fl a p reco n struction.
2558
I PART 17 H EAD AN D N ECK TU M O U RS
Ta b l e 1 9 2.7
T u m o u r thickness a nd surviva l rate in to n g u e a n d
M a n agement
------
floor of mou th cancer. Tu m o u r th i ckn ess
(m m)
Five year s u rviva l
0-3
86
4-7
58
>7
52
(0/0)
Small tumo urs of dentoalveolar o rigin can be considered fo r a transo ral alveolectomy. Mandibu lar invasion in oral carcinomas ranges fro m 1 2 to 56 p ercent according to various studies , and involvement of the mandible occ urs by direct invasio n rather than by lymp hatic spread . Panoral
radiographs
play
an
important
role
in
the
detection of bone invasion, especially determining the
Reprod u ced from Ref. 33, w ith pe rm ission.
s uperior mucosal flaps, the facial artery musculomucosal flap has proven to be reliable, either superi orly based ( retro grade flow) or in ferio rly based ( antegrade flow) . It has been used successfully to reconstruct a wide variety of difficult oro nasal mucosal defects, including defects of the palate, alveolus, nasal septum, a ntrum, upper and lower lips, floor o f the mou th and so ft palate.
extent
of the
tumour
in the
bone.48
The
sensitivity of orthopantomograms may be 92 percent.
Routine radiographs are u nable to detect initial bone invasion until 30 percent o f the mineral has been lost. If mandibular involvement is super ficial on the alveolar crest,
then marginal resection
rather
than segmental
resection of the mandible may be adequate. There are two basic patterns of bone involvement of the lower alveolus and gingiva. These are termed expansive and infiltrative patterns. In the infiltrative pattern the tum o ur invades the mandible through defects in the cortical bone or perio d
S u rviva l rates fo r to n g u e a n d fl oor o f m o uth ca n cer The survival rate of tongue cancer i s related t o tumour thickness and is shown in
Table 192.7. 33
ontal space. I n these cases, tumours are o ften fo und to invade the periosteum and the inferior alveolar nerve, I n the expansive pa ttern there is n o tumour invasion in relation to the periodontal space, the neurovascular canal or the periosteum. Thus the expansile pattern can be excised successfully by marginal mandibular resection. Conventional radiography cannot accurately differentiate these two types of bone involvement.
M A N D I B U LAR TU M O U RS
Maintaining the lower border of the lnandible in resection
P rese ntat i o n In
the
dentate
patient,
t hese
tumours
may present
insidio usly by loosening of teeth and be misdiagnosed as pe rio dontal disease, Gra nulomatous swelling of the gingival margin should be co nsidered suspicio us. Alve olar tumours o ften present as discrete cauliflower-like lesions on the attached gingiva. In the edentulous patient, the alveolar pro cess is often reso rbed a nd tumo urs arising from the alveolar crest o ften invade into the adjacent cortical bone by direct extension. Clinically,
it
of alveolar
carcino ma is important
the
is
o ften
free flap reconstruction
(Figures 192.21 and 192.22) have
a high degree of mo rbidity and increased free flap failure compared to so ft tissue replacement alone. [Grade D] When all teeth are lost a nd bone is resorbe d in the edentulous
mandible,
the
option
to
assess
whether
bone invasio n. The underlying periosteum is , however, a useful barrier to ingress of tum o ur into the alveolar pro cess of the mandible or maxilla.
I maging to be
the
most
senSItIve
investigation and tomography, the most specific regarding mandibular invasion.47 There is a trend fo r the sensitivity and specifiCity of the o rthopantomogram and MRI to improve in eden tulous patients , bu t this is not so clear fo r bone scintigraphy.
the
on rim or segmental resection with regard to the presence
dentate or e den tulo us mandible show any underlying
scintigraphy appears
co nserve
achieved. Some a uthors have devised a clinical algorithm
edentulous = without teeth
difficult
to
mandible decreases if a safe margin of resection is to be
tumo urs arising o n the attached or free mucosa of the
Bo ne
to
functio n. Segmental resections requiring osseocutaneous
Fig u re 1 92.2 1
Co m posi te fi bula fla p.
Cha pte r 1 9 2 O ra l cavity t u m o u rs i n c l u d i n g the l i p I
Ta b l e 1 9 2 . 8
2559
Su rv iva l r a t e s i n m and i b u l a r cancer treatm ent.
Factor
Five year s u rvi va l (0/0)
R i m rese cti o n
84
Segme n t a I resection
92
B o n e i nvasion
83
No i nvasion
88
Positive m a rg i n
4{)
N e g a t ive m a rg i n
72
overall > 70%
Reproduced from Ref. 5 1 . with pe rm i ssion.
R I M RESECTI O N OF M A N D I BLE
F i g u re 1 9 2 . 22
Seg me ntal resection w i t h com posite fi bu l ar fl ap.
o f i nvasion monito red by ort h opanto mog r a m , MR o r CT scann ing using the Cawood and Howell cl ass i fi ca ti on of alveolar b one resorpt i o n . 48 It has also b een s ugg ested that i t is the soft tiss ue resection that is the m ain determinant o f comp ro m ised m argi ns and compro m is ed bone mar gins in segmental or rim r esec t io n are less l i kely. In gener al, for tumours e n cro ach ing or s u perfic i ally invad ing the mandib ular cortex, a m a rgi nal resection can be plan ne d regardless of the dentition, as l o ng as a 1 - 1 . 5 cm resid ual bone at the lower border ca n be maintained to allow st r uctu ral integr it y from the forces of m astication. Segmental jaw resec tion is c l ea rly ind ica ted when tumour invades the medullary ca v i ty or i n a n atroph ic mandible where dear marg i ns will not a llow an adequate r i m o f bone. Various stud ies have shown that bone invasion itself cont ri b utes l i t tle to overall p rognosis.47 Therefore, if bone invasion is p resent b u t l i m ited a nd an a deq u ate margin of mandible rema ins, t b en rim resection o f the mandible should be co n s id ered . Every attempt should be made to achieve negative soft tissue margins as this is the only facto r i dentified w h i ch si g n ificantly acco unts for control rate and survival du ring resection of m andibular bone. Based on the current literat ure, gross bone involvement in previo usly i r r a d i a te d p a ti e n t s or in nonirradiated patients in who m there is obvio us involve ment of the me d ullary space is best managed wi th a segmental resect i on . 49 The ab i l i t y to resto re th e co n tinui ty of the mandible using a recons t r u ct io n p late andlor free fl ap p r ovi d es surgeons wit h a me t h o d of mandib ular reconstruction and therefo re l im i ts t he posto pe rative cos metic and fun c tional defo rmi ty. Irrespecti ve o f this reconstruction, it is impo rtan t to limit the nature of the resection unless there has been a demo nst r ate d benefit to perfo r m ing a segmen tal resectio n. While the use of panoramic radi og r ap h s , CT and MRI studies can be extremely helpful in a cc urately p re dict in g b o n e erosion preopera tively, i ntra ope r a tive c lini cal eva l ua tion wi th periosteal strip pi ng raises t he se nsitivity of detection of bone erosion and possibly represents t he mos t accurate method for determining the extent of su rgery . 49, so
The soft tissue margins of the tu mo u r to be excised are m a rk ed u s i ng m o no pola r d iathermy. This is an incision taken direc t ly down to the u n d e r ly ing bone. It is often possible to raise the adjacent per i oste u m of the bone in this a rea to exclude a ny transperiosteal spread of the tumour that may s uggest a s egmental ra ther tha n a rim resection is required. Fo ll ow i n g delineation o f the soft ti ss u e m arg in , the periosteu m is l i fted off the adjacent bone to expose the bone for r esec tion . The resec tion mar gi n w i ll u s ua l ly be s u pe rio r to the inferior alveolar nerve unless the preopera tive imaging investigations suggest tha t the inferior a lveolar nerve needs to be sacrificed to achieve adequate b ony s u r gica l m a r g i ns . A reciprocating saw is the n u s e d to produce a saucerized r im resection of the mandible . The sharp ed ges of the bone are smoothed with a de n ta l b u r and soft tissue reconstruction of the defect us ua l ly necessitates a fasciocu tane o us free flap. As most of these patients will require post opera tive rad i othera py, si m p l e spli t skin grafts or ped icle fl a ps in t h is area le a d to a high incidence of bone exposure a n d osteoradionecrosis followin g the subsequent ra d i oth era py. [ * ] O utco m e of m a n d i b u l a r ca n ce r tre a t m e n t The survival rate for the va r i o u s types of ma ndibular cancer treatment is shown in Table 1 92.8. 5 1 Thus, the presence of posit i ve bo ny m a rgins appears to be the most s i gnifican t prognostic factor.
KEY POI NTS • •
•
•
Tumour invades bo ne v ia most d irect ro ute. Examination of p eri o s t e um is b e s t indicator of invasion . Rim, rather than segmental , resecti o n in s u i ta b le dentate mandib l es . Implants aid o b t u rato r retention in maxi l lecto my.
2560
I PART 1 7 HEAD AN D NECK TU M OURS
carcinoma in this site
Be s t cl i n i c a l practice
1 9 2. 2 3 ) . A multivariate
depth of invasion, showed that patients with tum ours less
-/ A rim resection is in d ica ted in limited a lveo l a r
than 6 mm in thickness had a signi ficantly better survival
invasio n . J
(Figure
analysis looking at sex, clinical stage, tum our thickness and
'
rate co mp ared with those with tumours greater than 6 mm
A se g men ta l ma ndibu l a r resection i s required where
in thickness,
m a rrow is i nvolved or l ess than 2 cm of m a n d ible
regardless of the tumour stage
192.24) . Thus, the
persis ts after rim resection.
(Figure
measurement of tumour thickness
should be included in estima ting prognosis and plann i ng therapy for these patients.52
[ **]
The buccal mucosa includes all the intraoral mucosal lining of the inner surface of the cheeks and lips . Tum o urs
MAX I L LARY ALVEO LECTO MY Small
tumours
of dentoalveolar
that o ccur on the bu ccal mucosa can easily gain access to ongm,
or
primary
tumo urs of the mu cosa of the upper alveolus, can be excised via alveolectomy. A 1 . 5 cm margin of incision in the mucosa around the palpable tumo u r is made down to the underlying bone. The underlying bone can be resected with the soft tissue tumour via a segmental resection of the alveolus. I f i t does not comp romise excision margins, then limiting the alveolectomy to just below the maxillary antrum prevents an oro antral co mmunication or fenes tration. However, the avoidance of fenestration into the adjacent maxillary antrum or floor of nose sho uld not be
adjacent structures, such as the alveolar ridges, retromolar
Survival Stage I: 100% Stage IV:50%
trigo ne, lips and buccal spaces .
The overall stage-specific survival fo r buccal carcin o ma ranges fro m
1 00,
5 0 , 65 and
52 percent for stages I
through IV, respectively.
The most common signs and symptoms of buccal carcinoma are p ain and mucosal ulceration. Patients with submucous fibrosis may also
develop
squamous
As the buccal mucosa is often left in co ntact wi th carcinogens p resent as a result of betel nut chewing and
u ndertaken if it comp ro mises surgical resection margins.
With a small fenestration or alveolectomy proced ure p osterio rly in t he maxilla, the defect can be closed by the use of an advancement flap utilizing the buccal fa t pad. If a buccal fat pad is used, a temporary acrylic dressing plate is secured to the upper maxilla to protect the buccal fat
p ad
during
epithelialization.
subsequent
If a more
extensive defect is created, then a tempo ralis flap can be rotated to
close
over the
oroantral co mmunication,
although in the elderly this is co mp romised by the p o o r cosmetic result due t o hollowing o f the temporalis donor site.
In
small
defects
o f the posterior
maxilla)
no
reconstruction is required if adequ ate prosthetic rehabi litation with obturato rs using osseointegrated implants in the
edentulous
maxilla
is
performed.
The
use
of
zygo maticus osseo integrated implants is necessary where a
more
extensive
limited
posterior
required to establish tumo ur clearance.
maxillectomy
is
Fi g u re 192.23
Buccal carcin oma in betel nut chewer.
Fi g u re 192 .24
Ful l thickness buccal ca rci noma.
[*]
B U CCAL CARCI N O M A C l i n ica l pres e n ta ti o n a n d ep i d e m i o l ogy Buccal carcinoma seems to occur m o r e commonly in men than women and in the elderly co mpared to the middle aged. There also appears to be a higher incidence of buccal carcinoma in Asians and those of African
origin. 52 The
chewing of betel nut and pan supari co ntaining slaked lime and alkalo ids which are carcinogenic) predispose this site to squamous cell carcinoma. Similarly, the use of chewing tobacco, which is
often
retained alo ngside the cheek
mucosa, also potentiates the development of squamous cell
cell
carcinoma in the affected buccal mucosa.
Cha pter 1 9 2 Ora l c a v i ty tu mou rs i n c l u d i n g t h e l i p
to bacco chewing, associated
widesp read
leuko p l akia
I 256 1
precancerous lesions such as
and
erythropl akia
are
often
present. As in most oral ca ncers, the p resence o r absence of
nodal
enl argement
at
p rese n tati on
impo rtant, significa n t p rognostic fa ctor.
is
the
most
In p a tients where
the t umou r invades into adjacen t maxillary or m a n dib ul a r bone, aggressive co mposite resec tion is req uired . The
addition of postoperative ra d i ot h e ra p y in s tage III and IV tumours has been shown to p ro d u ce an i nc rease in overa ll survival from 40 p e r ce n t (with s u rgery a l o n e ) to 68 p e r cen t after combined t herapy. So me a uthors have shown t hat the p rese nce o f resi dua l rec urrent
buccal
carcinoma
therapy as a
a ft e r
primary
radiatio n
primary t reat men t m oda l ity h as an extrem ely poor p r o gn os i s . [ * * J I nvesti g ati o n s
Fig ure
1 92.2 5
Dou ble padd led ra d i a l free fl a p.
The buccal mucosa is somet imes a ffected by verrucous
Although a n estim a t ion
o f clin ical
thickness
o f the
possible by bim a n u al p a lp a t io n of the cheek, thickness and extension is best assessed by MR scanning. This help s determine those lesions that h ave escaped ou tside the buccal space and extended o n t o t h e m a n d ible or maxilla or i nto the infra t e m poral fossa o r para p h aryn geal space. tumour is
carcino m a , which is a slow growing, well-differentiated carcinoma that is chiefl y
exophytic b u t i nvad es lo cally. It of the b u ccal mucosa . Although t he t umour is exo p hyt ic some of th ese
p resents as a n exten sive white warty lesio n ,
verruco us carcinomas can s h ow aggressive local infiltra tion and t h ei r t reatment sh o u l d no t be underestimated. When b ucca l ca rcin o m a s i nvolve a large surface area
of
tiss u e, b ut do not show extensive t h ickness o f involve ment, then s urgical excision of s u ch
Treatm ent T I carci nomas of t h e b ucca l m ucosa c a n be excised with a s uit able m argin via
a
pero ral excis io n . Reco nst ruc tio n of
the s urgical defect depends on loca t io n but s m a U defects can be left to gran ulate , wh i l st more mod erate defects can be reconstructed
by a dvancing the b u ccal fa t pad of t issue
i n to the d efect, which allows seco ndary epi thelialization. S pli t
skin grafts can be used to cover the resected a re a o ve r bolster to maintain the graft i n positio n . Local fla p s such as the facial artery m usculomyo cuta using a tie
a large area c reates a surface area o f m ucosa req uiring replacement often requires free tissue trans fe r or a p ed icled t em p o r o p a ri etal fascial flap to difficu l t reco nstructive problem . T h e large
-
,
neo us fl ap , can be u sed to reco nstruct l a rger defects. Larger a reas of mucosal loss wi l l
resul t in fib rosis a nd left t o epithel ial ize o r reco nstructed with split skin grafts, and in s uc h cases, free tiss u e transfer using thin fascial or fasciocutaneous flaps, s u ch a s the
reconstruct t h e defec t . However, th is has the d is advantage of i nc reased mo rbid ity fro m a second operative site. Sup erfi cial b u t widespread lesions may be suit able for photodyna m i c therapy as i t s mode of act i o n is tho ught to
reduce i n t r i n si c sca r r ing. Second gene ratio n ph otosensi mm thickness of actio n which may be suitable fo r most su p er fi c i al widespread buccal carci nomas. 1 4 However, this trea t ment is exp e ri
tizers can p rod uce up to an 8
mental
and
long-te rm
s u rvival
results
therapy techniq ues.
rad ial fo rearm flap, may b e req uired. I f there i s a ny
O utco m e after s u rg e ry a n d RT
the
overlying external
cheek
ski n is i nvol ved and fixed by the b u ccal carc i n o m a , then a throu gh and t h ro u gh d e fect needs to be created and reco nstruction with a bipaddled radial fo rearm fl ap using s kin fo r extern al cheek a nd internal chee k reconstruction should b e considered
(Figure 192.25 ) . Recons tru ction wi th a r a d i a l fo rea r m fre e fl a p for b uccal m ucosal defects is more effective to p reserve the
original mouth-open width than with a p ed icled buccal fa t pad
fl ap or spli t - thickness skin gra ft among the selected p a tients who undergo t u mo u r resec t i o n fo r T2 or T3 b u ccal cancer. [ * J
still
not
trea tment op tio n in place of stand ard surgical or radio
contract ure if
su ggestion that
are
avail able . Cautio n sho u ld be used wh e n consi dering th is
---====
The survival rate fo r b uccal carci n o m a is
192.9. 53
Ta b l e 1 92 . 9
shown in Table
S u rviva l ra tes fo r b u cc a l ca rci n om a .
Sta g e
Stage I Sta g e I I
F i ve year survival (0J0)
95
64
Stage I I I
55
Sta g e I V
62
Reproduced from Ref. 53 , w i th permission.
2562 I
PART 1 7 H EAD AN D N ECK TU M O U RS
requ ired. Flexible nasendoscopy and antral sinoscopy will
KEY PO I NTS • • •
also give an indication as to the extent of spread of these
Low rate of metastatic disease.
tumo urs into the a djacent paranasal sinuses.
More common in the Asian population.
Local flap reconstruction.
Treatment PARTIAL LATERAL MAX1 LLECTOMY
CARCI N O MA OF TH E HARD PA LATE
This surgical approach i s tailored fo r small tumo urs of the
C l i n i ca l p rese ntat i o n
incisions sho uld allow for margins of at least 1 cm to
Unlike other regions i n the head and neck, only two
creating an artificially close margin. Gingivo buccal and
lateral maxillary alveolar ridge and hard p alate. Mucosal allow for post-excision shrinkage by
30 percent or more,
thirds of malignant neoplasms of the hard palate are
palatal incisions may be made with scalpel or cautery and
gland t umours make up the bulle of the rest of the
walls o f the maxillary sinus are then exposed with a heavy
squamous cell carcinomas
( Figure 192.26 ), and salivary
carried to the bone o f the maxilla. The anterior and lateral
In the Indian subco ntinent, reverse cigarette
periosteal elevator. Providing that the maxillary sinus is
cell carcinoma of the hard palate in elderly men . 55 The
anterior osteotomy, inferior to the infraorbital rim. Care
tumo urs.54
smoking or pipe smoking increases t he risk of squamo us
not invaded, the maxillary sin us is entered with an
most frequently occurring symptoms are painful ulcer
mu st be taken not to disrupt the tooth roots with a low
lump is the more common presentation with tumo urs of
equally well in creating the anterior maxillotomy. The
ation or a slow growing lump in the palate. A submucosal
osteotomy. An osteotome or sagittal saw will perform
salivary gland origin. Problems with dentures or altered
osteotomy is carried through the lateral wall of the
palate and ulceration are often misdiagnosed as being
recip rocating or sagittal saw. The hard palate is transected
speech can o cc ur less frequ ently, and swellings of the hard
dental in origin. Over 50 percent of lesions extend beyond
the anatomical confines of the palate at the time of
p resen tati 0 n.
maxilla past
the area of cancer involvement with a
lateral to the midline and in to the maxillary sinus, thus
avoiding the lateral nasal wall and nasal cavity. This is most accur ately performed with powered instr umentation
using the reciprocating or sagittal blades. The soft palate is transected, if necessary, with electroca utery, freeing the
I nvesti g ati o ns Both CT and
posterior and inferio r po rtions of the specimen, which
"= = = - '="I.:.':"::::a:::". � :-=""' � == ="'=====
MRI are useful in defining the extent o f
infiltration of sq uamo us cell carcinoma into the under
lying nasal cavity fo r anterior lesions and maxillary
antrum for more posterior lesions. This imaging will guide the surgeon as to whether a peroral excision is
adequate or a mo re extensive approach via a cheek flap is
inclu de
mucosa,
p alate musculature and the medial
pterygoid muscle. The posterior osteotomy is perfo rmed
with an osteotome, if possible preserving the posterior
wall of the maxillary antrum and avoiding significant
blood loss. The posterior osteotomy is reserved for the
final step to avoid unnecessary blood
loss,
because
bleeding fro m the pterygo maxillary space can be co m pletely controlled only after removal o f the specimen.54 Stage
I tumou rs affecting the hard palate can be
excised via a peroral app roach. If preo perative imaging suggests destruction of the underlying palatal bone, then
the fenestration procedure should be performed as part of the
surgical
excision.
However,
if no
obvious
bone
involvement is shown on the preoperative scanning, then examination
of
the
presence
of
infiltration
of
the
periosteum overlying the palatal vault at the time o f
s urgery will indicate whether a n en b l o c resection o f underlying bone i s required. I f t h e tu mo ur extends onto
the gingivae, then an en bloc resection of the adjacent
alveo l us containing teeth sho uld be undertaken.
If the
preoperative investigations show extension of the tu mour
into the maxillary antrum or floor of no se, then a formal maxillectomy approach via a Weber-Ferguson cheek flap
sho uld be undertaken Figure 1 9 2 . 2 6
Carci n o ma o f h a rd palate.
(Figures 192.27 an d 192.28), so as
not to compromise s urgical margins by a peroral excisio n .
Chapter 1 9 2 O ral cavi ty tu m o u rs i n cl u d ing the l i p I 2 5 63
Tab l e 1 9 2 . 1 0
S u rvi val
ra tes for h a rd pa l a te ca n cer. Five yea r su rvival (0/0)
Stage
Stage I
92
Stage
43
II
Sta g e III
37
Stage
17
IV
Reproduced from Ref. 56, with pe rmission.
ln the absence of p o sto pe r a t iv e r a d io t he r a py o steo dis tech niques can be utilize d to close sma ller bony defects, especially those i nvo l v i ng the a lve o l u s . In the immediate p os to pe r a t i ve p h a s e tem p orary ob turation of ,
tr a ction
,
Webe r-Ferg uson i n cision.
Figure 1 9 2 . 2 7
the fenest ration o r a l i m ited lower level m ax illectomy cavity
is o ft e n r e q u i re d . At the end o f the s u rgi cal
resectio n, a den ta l i m p r ess i o n of the s u r gi cal defect is
to help the dental p r ost h et is t p repare the inter p reexi sti ng d e n t u re, or a dental cover p la te ( prepared prio r to o p e r a t i o n ) , can be secured in place u sing 2 mm titanium screws screwed into the unaffected alveo lus o r the u n a ffected h a r d p alate. The cavity is t e m p o r a rily occl uded w ith either expansible fo am po ured int rao pe ra t ive ly o r by t he use of a r ibb o n gauze pack co ate d i n b i s m u th io dofo r m p a raffi n paste ( B IPP) o r Vaseline i mp regnat e d ribbon gauze . Filli ng of the cavi ty prevents haematoma fo rmation. The pack is norma l ly removed seven to ten d a ys fo Uowi n g initial su rgery and a t e m p o ra r y obtu rator is i nserted a t this s tage or the cavity left o p en i f a retentive dent ure or cover p l a t e is available. A per ma n en t dent a l o b t u ra t o r is even t u a l ly fabrica ted three to fo u r mo n t hs fo llow i ng initial surge ry, when most of t he contracture and h e a l i ng o f the wound is co m p l e te Osseo integra ted i mpl a nts p laced at the t i me o f surgery can a lso b e s u rgica l ly exposed a t this stage t o he lp retai n the ultimate o b tu rat o r. The result of treatment of s ta g e 1 l esio n s shows a 7 5 percent five-year s urvival . P at ie n ts with stage I n and IV squamous cell carcinoma of t he palate s h o u ld be treated by a d eq u a t e surgical resection fol lowed by pos t o pera ti ve radiothera py to the primary site a nd the en tire neck. [** 1 taken
mediate o b t u rato r. A
Fig u re 1 9 2.2 8
C h e e k fl a p elevated.
Assessment
i n to a dj a cent soft p al a t e t o be given careful consi dera tion durj ng preoperat ive pl a n n i n g as a resect i o n of the soft palate has a significant c o m p ro m i s e on p osto p e r ative sw a llowi n g and speech . P reope ra tive /vfR s c a n n i ng can h el p deci de wh ether the pal a t a l muscles can be left in co ntinuity wj t h o u t c o m p ro mi sin g resection margins. Reconstructio n of the surgical defect depends on the size of the d e fe c t . S m a l l fe nestratio n cavities can be closed d i re c tl y by a t r an sp ose d muscle flap, such as a temp o ra hs fla p Larger d e fects can be closed usin g a radial forearm fa sci o c u t a n e ous flap suspended ac ro ss t he p a l a t e usi ng t h e p a l m a ris lo n gu s tend o n . I n the edentulous elde rly, a sim p l e addition to the den t u re ( to act as an obturator) is s a tis fact o r y. The u se o f osseo integrated imp l a nts i nto the uninvolved a lveolus or the use of a zygo m a ti cus implant into the u n i nvolved zygoma wi l l he l p retai n the dentu re a nd obt urator. [ G r a d e DJ When a formal low level h emi maxi l lect o m y is performed , co nsidera tion of bony reco nst ruction o f the p a l a t e with a h o rizo n tally placed deep ci rcu mflex i l iac a r te r y flap i s u n d e r t a k e n . Defects i nvo lving the anterior ma x i l la and alveol u s can be reconstru cted similarly by the use of rad ial co m p os i t e fla p s altho u gh these fl a p s have signi fica nt morbi d i ty d ue to wrist fra c t u r e and decreased wrist fu nctio n. [* J muscu l a t u re
o f extension
needs
,
.
,
.
O utco m e S urvival rates for 1 9 2. 1 0 .56
h ard p ala te cancer are shown i n Table
KEY PO I NTS •
• •
Sa l iva r y gland neo pla s ms account for 3 3 pe rce nt o f tu mo urs. Soft p al at e p re s e rvatio n m aintains functio n. Ob t ura t o rs retai ned by osseointegrated i mp l a nts .
2564
I PART 1 7 H EAD A N D N ECK TU M O U RS
Best cl inica l p ra ct i ce ,I
Sma l l maxi l l a ry d efects ca n be treated w ith a n obtu rator. La rger d efects may requ i re co m posite m icrovascu l a r reconstruction. Denta l i m p l a nts a i d reconstruction a n d d e n ta l reh a b i l itatio n .
NEC K DISSECT I O N IN O RAL CAVITY CANC ER Stag i ng Nodal staging for oral carcinoma is shown in
Figure 1 92 . 2 9
S u p raomo hyoid n eck d i ssection.
Fi gure 1 92 . 3 0
Mod ifi ed rad ica l n eck d issection (type IV) . Red
Table
1 9 2. 1 1 . In the management of lip and oral cavity cancer,
the standard neck dissection for NO or limited N+ disease is a level I-III or supraomohyoid neck dissection 1 92.29 ) .
(Figure
57 58 59 60 , , , Anatomical studies have shown that
the nodes at risk of metastasis with a primary tumour of the oral cavity or l ip hardly ever involve level V if level 2 is negative.61 (There may be some fast tracking to level IV in some tongue cancers.32 , 62) There are few randomized trials of the role of neck dissection in head and neck cancer and those trials that exist are poorly planned and subject to bias.63 , 64 Thus, in oral cavity cancer, even in the presence of positive nodes, it is unusual for a radical neck dissection
(Figure
1 92.30)
to be performed, except in the presence of N 3 disease, or where invasion into the sternomastoid muscle or internal jugular vein or adjacent structures has occurred. Treatment of the clinically NO neck appears to show some
survival
advantage.
Wei
et
al.
in
discussing
d otted l i n e shows t h e cou rse of t h e accesso ry n e rve.
management of the NO neck in oral cancer,65 note that patients undergoing elective treatment of the NO neck
when elective neck dissection was carried out together
appear to have a survival advantage over patients who are
with
simply observed. A review of 156 patients with Tl and T2
compared with
carcinoma of the tongue staged N O, demonstrated that
served.66 In another study of 63 similar patients, the
Table 1 92 . 1 1 Stage
glossectomy, the survival 33
percent
rate
was
55
percent
when the neck was ob
N o d a l stagi ng fo r o ra l ca rci noma.
Description
NX
Regiona l lym p h n o d es ca n not be assessed
NO
No regio n a l lym ph node m etastasis
N1
M etastasis i n a si ngle i psi latera l lym ph n o d e, not m o re t h a n 3 c m i n greatest d i mension
N2a
M etastasis in a s i ngle ipsi lateral lym p h n o d e m o re t h a n 3 cm but not m o re t h a n 6 cm i n greatest d i m ension
N2
M etastasis i n a s i ng l e ipsi latera l l y m p h n o d e, m o re t h a n 3 cm but n o t m o re t h a n 6 c m i n greatest d i me n si o n ; or i n m u l ti p l e i psi latera l lym p h nod es, n o n e m o re t h a n 6 cm i n greatest d i m ension ; o r i n b i l atera l o r co ntra latera l lym p h n o d es, n o n e m o re t h a n 6 cm i n greatest d i mension
N2b
M etastasis in m u lti p le i ps i latera l lym p h n o d es, n o n e m o re t h a n 6 cm i n greatest d i m ension
N2c N3
M etastasis in b i latera l or co ntra late ra l lym p h n o d es, none m o re t h a n 6 cm i n � reatest d i mension lV1 etastasis in a lym p h n o d e m o re t h a n 6 cm i n grea test d i m e n s i o n
C h a pter 1 9 2
regional failure rate was 9 percent in the elective neck dissection group compared to 47 percent in the observa tion group. The five-year actuarial disease-free su rvival rate was also higher; 86 percent in the elective neck dissection group and 55 pe rcent in the patients under going observation alone.67 A prospective randomized study involving 67 patients staged NO with T 1 or T2 ca rcinoma of the oral cavity also showed that following
O ra l cavity tu mou rs i ncl u d i ng the lip I 2565
However, various authors have questioned the role of comprehensive neck dissections in the managem ent of , , 1 1m1 · ' te d N + d'1sease.57 , 5 8 73 76 I n a stu dy 1 0 0 k'mg at neck dissection in elective and therap eutic treatment of the neck, the three-year regional recurrence
selective
rates were: pNO, 4.7 percent; pN 1 , 4.9 percent; pN2 , 1 2 . 1 percent. A comparison of recurrence rates with respect to the extent of neck disease and postoperative radio
elective supraomohyoid neck dissection, the three-and-a
therapy demonstrated a tendency to an improved regional
half-year survival was 7 2 percent for the surgery group, compared with 49 percent in the observation group. 59
control in irradiated patients with one metastasis and a
Similar prospective randomized studies with a larger
distinctly improved regional control in patients with multiple
number of patients would be valuable, especially for
spread.
patients with T1 or T2 lesions of the anterior two-thirds
the
of the tongue.
compare
metastases or [ Grade
results
metastases
with extracapsular
D] This led to the conclusion that
achieved
favourably
with with
selective the
neck
results
dissection
reported
for
The decision to observe or treat the NO neck is
modified radical neck dissection. The application of
frequently left to the joint decision of the patient and the
selective neck dissection might be extended to more
head and neck oncologist. It is recommended that when
advanced neck disease.73
the probability of occult cervical lymph node metastasis is more than 20 percent, the neck should be electively treated.68 This would therefore include all stage T3 and
Senti n e l n o d es
many T2 oral cavity carcinomas and carcinomas of the tongue thicker than 3 mm. 69 When ultrasound-guided
Lymphoscintigraphy
fine-needle aspiration technology is employed, patients
identified first echelon nodes at clinically unpredictable
with early stage oral cavity cancers might be spared
sites in breast cancer and melanoma. The nodes detected
elective treatment of the neck.70 In
various
studies
sentinel
node
biopsy
have
are first echelon nodes, but also represent the varied direct
Lymph node groups in the neck a re described by levels ( I-V ) .71
and
of
the
distribution
of
lymphatic drainage of tumours. In oral cancer, the nodes most likely to be involved a re those located in levels I-III.
metastases from oral cavity tumours, a predominance of
Level IV nodes are involved in approximately 5 percent of
certain levels is seen for each primary site. Levels I, II and
clinically node negative necks and level V involvement in
III are at highest risk for metastasis from cancer of the
the clinically NO
oral cavity. A supraomohyoid neck dissection (clearing
supraomohyoid neck dissection is often used for staging
levels
purposes.
I,
II
and
III)
for
patients with
NO
primary
neck is exceedingly rare . 6 1 Thus, a
Regional failure
following
a
pathologically
squamous cell carcinomas of the oral cavity is normally 1 recommen ded. 6
approximately 5 percent of cases, and these can be either
In the recent modification of the standardization of
within or outside the operated field. If the recurrence is
negative
supraomohyoid
neck
dissection
occurs
in
neck dissection, the Committee on Head and Neck
outside the operated field, the node dissection failed to
Oncology divided levels I, II and V into A and B groupS.72
include the first echelon nodes for the tumour. Sentinel
This division
node biopsy is emerging as an alternative technique for
appears to
be
anatomically
sound in
relation to metastatic disease to the neck. For example,
staging the neck and, although still in its infancy, several
level IA is rarely involved in metastatic disease. At the
case series have been reported and the technique seems to
same
be an accurate means of determining nodal status.77, 78, 79
time,
level
lIB
nodes
are
rarely
involved
in
metastatic tumour unless there is a bulky metastatic
[ Grade
D]
disease at level II. On this basis one may consider super selective neck dissections. There appears to be a trend in deleting specific names for the modification of neck dissection and use selective neck dissections with the
KEY PO I NTS
structures and group of lymph nodes removed as specific types.
•
It is now widely accepted that in the clinically NO neck, a selective neck dissection will sample the node levels at
•
risk.
been reinforced by anatomical and pathological studies. 58, 73, 74 In NO necks, it is thought
•
that neck dissections have a therapeutic as well as staging
•
This
has
l ast five years.74, 75
Improved survival if NO neck treated. Level I-III neck dissection for oral cavity primaries.
role and have thus contributed to the increase in five-year survival figures for oral squamous cell carcinoma over the
Elective treatment of NO neck is necessary if likely metastasis >20 percent.
Increasing role of selective neck dissection in limited N + disease .
•
Sentinel node staging has a role.
2566
I PART 1 7 H EAD AN D N ECK TU M O U RS
Best cl i n i ca l p ractice N+
n e c ks a re trea ted by a modifi ed ra d ica I neck
dissection
(M R N D).
Pro p hyla cti c se l ective n e c k d issectio n s a re performed
v
when the risk of occ u l t metastasis exce e d s 20 pe rce n t.
/ Leve l V nodes a re rarely p osi tive in o ral ca n c e r.
S U R G I CAL A P P ROACH ES TO TH E O RAL CAVITY Oral
cavity
t u m o u rs
can
be
a ccessed
via
pero ral ,
ma nd ib u l oto my lower cheek flap, visor flap and upper ,
c he ek flap app roa ch es . The cho ice of access depend s on
the a nato mical site of t he tumour, th e size of the tumour, the need to pe r fo r m a n in-co ntinuity resection and the p rox i m i t y of the tumo u r to t he mandible and maxilla. Fi g u re 1 92.3 1
I nc i sion fo r l a b io m and i b u loto my.
Fi g u re 1 9 2.32
Pa ra me d i a n m a n d i b u l o to my.
Pe ro ra I s u rg i ca I a p p ro a c h As l o n g as the tumour is smal l and easily accessib le, s m a l l
p rim a ry tumours of t h e tongue, floor of mouth , buccal mucosa a nd h a rd o r soft palate are suitable fo r pero r a l excisions. Th is is es pecia l ly s o
in edentulous patients.
However, patie nts with limi ted mouth op enin g co nstric ,
tion of the oral co mmiss ure a n d p revio u s rad io t herap y ca u s i n g fibrosis, may not be sui table fo r pero ra l e xci sio n . Pe ro r a l excisio n c a n b e assisted b y t h e use of su i t a b le gags sll c h as t he Dingman cleft lip and p al a te gag. This allows retraction of the l ips a nd to ngue to allow gre a ter s u rgi ca l a ccess.
La b i o m a nd i b u l otomy A
parame d i a n
m an dib ul oto my
osteotomy t ech nique to gain
utilizes
a
mandib ula r
access to the oral c a vi t y or
oroph a rynx fo r tumours tha t are not accessible th rough
the pe ror a l or lower cheek flap appro a ch. The m a n d i b u n or ma lly p erformed i n the p ara med ian site. A
l o t o m y is
m idline i ncisio n s p li ts the lower lip a nd extensio n of this i nc i sio n meets the an terior part of th e n eck di ssect i o n
1 9 2.31 and 1 9 2.32) . The skin incision divides t h e chin a n d lower l ip to its full t h i ckness up to the reflection of the mucosa in th e buccal sulcus. An extension o f the in c ision is m ad e in the buccal su lcus to a l l o w a sh ort cheek fl a p to be
i n cisi o n a lo n g a n uppe r n e ck skin crease ( Figure
s tra ig ht c u t or i n a step l adder fash ion which increases the su rface a rea fo r bony he al i n g .
p erfo rm ed in a vertical
elevated . T he soft tissue att achments are elevated by
A re c iprocat ing saw is used to mark the o u t er co rtex of
s ubpe r ios teal dissection off th e u n derly i n g m a n d i b l e . The
t h e bone . At this point, two 2 m m ti ta n iu m p l ates are
cheek flap is r e fle c te d up to the exit p o i n t o f the ment a l
p re con t our ed over the pl a n ned osteoto my c u t. The p lates
nerve, which is always found between the ro o ts of the
a r e pla ce d at right angl es to the o s t eoto my c u t , above and
lower first and secon d p remo lar te eth . In the e d e ntulous
below the me ntal nerve. In the den tate m a n d i bl e
mandible,
the
p a ra media n
osteo to my can be either
,
t he
ma n dib uloto my is o ften p l a ced between the l ower se co n d
Ch a pter 1 92 O ra l cavity tu mou rs i n c l u d i n g t h e l i p I
incisor and the canine teeth. However, when there is not enough space between the roots of the teeth to place the mandibulotomy, the first premolar tooth is normally extracted and the mandibulotomy performed through this tooth socket. The tissues on the lingual aspect of the mandible are protected by a suitable retractor an d the mandible is divided with a reciprocating saw. The cut segment is retracted laterally and a mucosal incision is made in the floor of the mouth, leaving a small cuff of mucosa attached to the ma ndible to allow approximation of the wound at closure. The mucosal incision continues in the lateral floor of the mouth to the retromolar area or 1 cm anterior to any adjacent tu m o u r. The soft tissue muscular attachments in the floor of mouth are divided and thjs allows the mandible to be retracted l aterally. The mylohyoid muscle attached to the mandible has to be divjded to permit the mandibular swjng. Access to the oral cavjty provided by these mandibular access osteotomies means that a commando operation resecting part of the mandible purely to gain access to oral tumours should never now be performed . Similarly, a lateral mandibul otomy cutting through the inferior alveolar nerve is also contraindicated.
Visor fl a p a p p roa ch fo r resecti o n of tu m o u rs of th e o r a l cavity
2567
the reflection of the buccal sulcus is made from angle to angle of the ma ndible. This involves section of b o th mental nerves, which is the main disadvanta ge of this procedure. This then allows the mandible and the floor o f mouth t o b e dropped down through into the neck, allowing satisfactory exposure of the oral cavity and mandible. However, exp osure of the retromolar and tonsillar area is not as effective as in a labiomandibu lotomy approach and, therefore, posterior tongue and palatal tumours are better excised through a labiomandi bulotomy approach, even if a bilateral neck dissection is being perfo rmed. Segmental or marginal resections of the mandible can be performed through this i ncis i o n in continuity with selective or radical neck dissections. One of the main disadvantages of this appro ach is that the division of the soft tissues on the lingual aspect of the mandible to drop the floor of mouth into the neck can compromise swallowing and lingual function postopera tively. Some quality of life studies have shown that this is o f more significant effect on postoperative function than the perceived cosmetic drawbacks of the labiomandibu lotomy skin incision. Clinical examination showed no differences in function between the two access procedures. [ Grade D 1 Although there was a small number, the lip split mandibulotomy group reported significant ly better speech, swallowing and chewing. Previous concerns about a possible detrimental effect on appearance following lip split) are not borne out.so [**]
A visor flap (Figure 192.33), rather than a labiomandi bulotomy, should be considered when a bil ateral neck dissection is being performed or a subtotal glossectomy is necessary. In this approach, the cosmetic defect created by the labiomandibulotomy is avoided by utilizing a single transverse skin incision extending from one mastoid process to the other along an upper neck skin crease. The skin flap is raised in a subplatysmal plane up to the lower border of the mandible. At this p oint, a peroral incision in
U p pe r c h e e k fl a p Although anterior maxillary and low level posterior maxillary and palatal lesions can be accessed via a peroral approach) more extensive tumours involving the maxilla and maxillary antrum will require an upper cheek flap to enable adequate access. This requires a Weber-Ferguson
�,-----+- Apron flap ,-:--\-�---..,-+---- Lower edge of mandible
Soft palate
+--�---r+---- Anterior belly of digastric
----F--{--+--- Tongue
Fi g u re 1 92 . 3 3 tec h n i q u e .
Viso r a p p roach o r d rop down
2568
I PART 1 7
inClSlOn
H EAD AN D NECK TUMO U RS
(Figure
192. 34)
with
ei ther
a
Lynch
or
establishing s o ft tissue coverage of any bony resection
Diffenbach extensio n . The ph iltrum o f the up per l i p is
margins should be considered. Therefore, a small cuff of
divided in the midline from the vermilion border to the
p alatal and buccal mucosa should be left overlying the
columella, where
underlying bony osteotomy to allow some soft tissue
the incision turns along the nasal
A reciprocating saw
vestibule and fo llows the alar of the nose and the lateral
coverage of resected bone m argins.
aspect of the nose. The o rbicularis oris and musculature
divides the alveolar process and hard palate. In a limited
around the alar of the nostril are divi ded with electro
low level maxillectomy for palatal or alveolus squamous
cau tery up to the anterior surface of the m axilla . Following
cell carcinoma, it is important to maintain
completion of the skin incision, a mucosal incision is made
soft tissue muscula ture of the soft palate as possible. The
as
much of the
in the gingivolabial and gingivobuccal sulcus leaving a
soft tissue containing the muscles of the soft palate should
small cuff of mucosa attached to the palate around the
b e elevated off the posterior aspect of the hard palate and,
periphery of any tumour. The thickness of the cheek flap
where possible, the posterior aspect of the hard palate and
d ep ends on any extension of the underlying tu mour
pterygoid plates should be left in situ ( if this does not
If there is no extension
compromise tumour removal) as the origin and insertion
of tumour through the anterior maxilla, then a thick cheek
of many of the palatal muscles occur in this area. Following
flap is elevated containing full thickness of muscle and fat
tumour excision, the surgical defect should be temporarily
from the u nderlying maxilla . If there is penetration of
obturated with ribbon gauze, i mp regnated with a suitable
thro ugh the anterior maxillary wall.
tumour through the anterior maxilla, then a thinner skin
haemostatic and bactetiostatic agent and temporary d ental
in the fatty layer between the underlying
o bturators or dressing plate anchored used per-alveolar or
facial muscles attached to the maxilla and the overlying
per-palatal titanium 2 mm screws. Altho ugh, historically,
facial skin. D epend ing on the location of tumour, it is
the inner aspect o f the cheek flap was reconstructed with a
flap is elevated
so metimes p ossible to osteo to mize the infraorbital nerve,
split skin graft, the p lacement of an adequate intraopera
where it runs from the floor of orbit through the anterior
tive obturator or dressing reduces the contracture and
maxillary wall, into
scarring previously associated with a n upper cheek flap. [ * ]
the soft tissues of the cheek to
maintain sensation in the cheek flap. However, this should not co mpromise access to the underlying tumour. When considering placing the
osteotomy cut
to
divide the
u nderlying palate or maxillary bones, co nsideration to
KEY PO I NTS •
Access procedures improve clear resection margins.
•
P re-p lating mandibulotomy aids stability.
•
Drop down p rocedures in bilateral neck
•
Up per cheek flap gives good cosmes is.
dissection.
RECO N STR U CTI O N OF TH E O RAL CAVITY In reconstruction, o ne should always replace ' like with
like' where possible. S m all defects can be either left to
granulate, p rimary clo sure can be co nsidered or the defect covered wi th split skin grafts. Reco nstructive o ptions depend on the balance between the so ft tissue and bone requirement of reconstruction and whether the resected tissue is mo bile or immobile.
Pri m a ry clos u re P rimary closure c a n b e used in small defects of the buccal cavity or tongue, where such action does not compromise function. When surgical defects involve more than two planes, such as in the floor of the mouth or a defect Figure 1 9 2 . 3 4
Weber- Fe rg uson i n cis i o n .
extending on to the lateral aspect of the tongue or the
C h a pte r 1 9 2
alveolus, then fixation of any tissue here impairs speech and swallowing. When mobility is of prime importance in maintaining speech and function, the use of thin, pliable, mobile mucosa or skin available via free vascular tissue transfer should be considered.
O ra l cavity tu m o u rs i n c l u d i n g the l i p I 2569
intraoral reconstruction and can be used as a pedicle flap, but is more dependable as a free flap.
[*]
M i crova scu l a r free t i ss u e tra n sfe r The majority o f soft tissue reconstructions within the oral cavity require soft, pliable, mobile skin with a variable
S p l it s k i n g rafts
degree of underlying bulk to reconstruct tissues such as
These are not commonly used in the oral cavity anymore, but may be suitable for small anterior floor of mouth defects and for b uccal defects where any contracture of the split skin graft, or failure of take, is unlikely to be a problem.
the tongue. The most commonly used soft tissue free flaps for intraoral reconstruction are the radial forearm flap, the anterolateral thigh flap, the latissimus dorsi flap and the rectus abdominus flap. When mucosal lining alone is required,
then
the
radial
forearm
free
flap
in
its
fasciocutaneous or fascial only form is the workhorse of intraoral reconstruction. When a little bit more bulk is
Loca l fl a ps
required,
Small and moderately sized defects which require replace ment of lining plus the bulk of underlying tissue may be reconstructed using a local flap. Defects involving the buccal mucosa can be reconstructed using the vascularized buccal fat pad. Defects of the anterior maxillary alveolus or the posterior maxillary alveolus can be reconstructed using transposition flaps of the hard palate based on the greater palatine vessels. In the elderly, small defects of the anterior mandible and floor of mouth can be reconstructed using bilateral nasolabial flaps when the overlying skin is lax and scars can be hidden in the nasolabial fold.
then
the
anterolateral
thigh
flap
has
the
advantage of being a large skin area with variable levels of underlying muscle that can be harvested to alter the thickness
of
the
flap.
The
rectus
abdominus
and
latissimus dorsi flap are used to provide bulk in subtotal glossectomy
reconstruction,
although
the
functional
benefit of an immobile muscle flap is questioned by many.
Very
elderly
patients,
particularly
with
poor
functional status and medical co-morbidities, such as diabetes, are poor candidates for microvascular surgery. The problem of second donor site morbidity needs to be considered when choosing the donor site for free tissue transfer. The radial forearm flap is considered to be the best flap for reconstruction of mucosal and soft tissue
D i sta nt pe d i cled fl a ps
defects in the oral cavity. The flap is highly reliable with a
Historically, myocutaneous flaps from a distant site have
dimensions of the flap can be altered to match the
97 percent success rate in most series. The shape and
been used for reconstructing those defects of the oral cavity
requiring
mucosal
coverage
and
bulk.
The
myocutaneous flaps most commonly used for intraoral reconstruction are the pectoralis major flap, the latissimus dorsi flap, the trapezius myocutaneous
flap and the
platysma flap. These flaps provide a one-stage reconstruction with lining and bulk. The pectoralis major flap was historically the workhorse of orofacial reconstruction, but at present it is unusual for this flap to be used in oral cavity reconstruction, except as a salvage procedure. The large bulk of immobile muscle prevented any dental rehabilita
surgical defect. Although there has been a vogue for using sensate flaps, most radial forearm free flaps pick up some degree
of sensory
input
from
the
adjacent
tissue.
Significant problems with causalgia can occur in these flaps. The radial forearm free flap comes into its own in surgical defects affecting the retromolar trigone, the soft palate and oropharynx, where the complex three dimensional anatomy means that nonvascularized recon structions are not pliable or anatomically adaptable to reconstruct the surgical defect successfully.
[*]
M a n d i b u l a r reco n str u ct i o n
tion of patients and up to 25 percent of pectoralis major flaps suffer some form of partial necrosis due to the skin
As most patients with stage III and stage IV oral cavity
component being reliant on perforators from the under
cancer will require postoperative radiotherapy, the use of
lying muscle. Postoperatively, the muscle atrophies and
nonvascularized bone grafts has little role in mandibular
tends to sag and pull back towards the site of origin. The
reconstruction. Current options for mandibular recon
arc of rotation of the pectoralis major flap makes its use
struction
difficult above the level of the mandible. However, this
bridging reconstruction plates and composite microvas
flap is a useful salvage procedure when a radical neck
cular free flaps. In the elderly, segmental defects of the
involve
pedicled
composite
flaps,
metallic
dissection is performed in continuity with external skin
posterior mandible may not require reconstruction in the
over the mandible or where a sectional mandibulectomy
edentulous or high risk patient. This is due to the fact that
The
the soft tissue envelopes around these defects mask the
latissimus dorsi similarly provides bulk and lining for
is performed without plans
for
reconstruction.
cosmetic defect and therefore it is unusual for a functional
2570 I
PART 1 7 H EAD AN D N E CK TU M O U RS
swi ng of the mandible to co m p rom ise function. The use
, ,
. .
o f margi n al mandibulectomy or rim r esect ion i n selected p a t i e n ts to maintain the co n tinu i ty of the mandible will reduce the m o r b id ity a sso cia ted with compo si t e resec tions and reco nstructions. The use o f me tall ic b r id gi n g p la t es covered by p e dicl ed flaps) such as the p ec to r ali s major) may be suitable in elderly pat ien ts but m os t bridging plates tend to fail or p ro tr ud e t h r o ugh th e ove rlyi ng ski n a fter two to th ree years) es p ecia lly in t h ose patients t rea ted wit h postoperative radiother ap y. The
success of the use of va scu larize d bo ne- free fl aps i n
re s t o ri n g co n t inu i ty t o t h e mandible i s clearly demon
strated. There is an acceptable incidence of donor- and reci p ien t-si te com p lic at io ns that result in m i ni m a l long t e r m morbidity. The careful selection of a don or site (s) for orom a n dibular recons truction allows for a n o p t i ma l restoration of bony a n d s oft tissue defec ts . [ Grad e C] D ental i mp l a n t s can be s a fely used in orom andibular reco nstructio n with a high level of success. Placing these implants during the initial surgery sho rtens the du ra t i o n fo r ach ieving dental rehabilitation and enhances the success o f t he implants when po sto perative r a di o t her ap y is administered . An over all success rate of 96 p e r ce n t for co m posite flaps is now usu a1 . 8 1 The overa l l success rate fo r endosteal de ntal implants is aro und 90 percent.82 The implant success rate falls to 86 percent when the bone i n which the fixt u re i s placed i s irradi at ed po s t o p e ra t ively. However, the success rat e falls to less than 64 pe rcen t in fixt u res t h at are p la ce d i nto p revi ous ly irradiated b o ne.8 1 In t his way) the use of com p osite microvascular fl aps has re vo lu t i o n ized t he treatment of s egm en t a l defects of t he mandible. The h a rvested b o ny tissue can be co n t o u re d and osteo to mized to rep ro duce the co nto u r o f t h e excised b o ne . Free fl ap opt io ns for m a nd i bula r reco n s t r u ctio n i n c l u de t he ra dius s cap ul a ilium and fibula. Normally) reconstruction o f the mandible is perfo rmed at t he time of resection, as delayed recons t ru c ti o n is a m ore diffi c ul t pr o cedure es p eci a ll y fo llow i ng radiotherapy due to the fibros is and reduced vascularity i n the i rr ad ia te d t issue ,
,
,
.
Rad i a l fo rea r m osteocuta n eo u s free fl a p a dva n ta ge o f th is flap s tems from the excellent the r ad ial fo rearm skin (Figure 192.3 5 ) . However, the length a nd circumference of t he bone available is limited, and t he blood sup ply is n o nsegme nt al and there fore p rec a ri ou s. There is s i gn i fica n t d onor s ite m orb id i ty at the wrist, with app roxim a tely 20 percent o f p at ie n ts suffer in g radial fractures) even when the rad i al donor s it e is p re-p l a te d . There is also significant functio nal m o rb i d ity of the wrist j oint and hand and a r m s t re ngt h . The donor site needs i mm ob iliza t i on in p l a s ter which may also compro m is e rehabilitation in the el de r ly patient. It is for t h i s reason that the co m p os ite radi al fo rea r m flap is ra rely used for bony reconstruction, s a ve fo r
The m a i n
soft t issue co mpo nent o f
,
Fig u re 1 9 2 . 3 5
Com posite ra dia l fl a p u sed i n ma nd ibu l a r
reeon st ructio n .
alveolar
or
t h e nose or
an teri o r maxillary reconstru ctio n t o close off antrum from t he o ra l cavity.
Sca p u l a r free fl a p The
main role of the sca p ul ar flap (Figure 192.36) is
when th rough a n d through defects of the mandible exist .
and ext r a ora l skin i s lost and the an external and a n internal skin p a d d le. The natu re of the p a rasc apul ar flap blood s upply means t hat two separate skin pa d dles can be harvested Here
i n t ra ora l
reco nstruc t i o n req u i res
wi t h t h e u nderlyi ng b one. These harvested skin p a d dles are more freely mobi le o ver the u n de rlyi ng bone than the comparable fibu la o r ra di a l free fla p s. However, the skin co m p onen t s rely on perforating vessels p assing t h ro ug h a bulk of subdermal fat . This means that these bulky skin fl ap s are less tha n ideal flaps to use as intraoral lini n g . These flaps a re t herefore best used fo r composi te m andibular d e fect s wi th l arge extr a oral and intraoral skin and m u cos al defect s . As previously m ent ioned t he versat il i ty o f t h e p a rasca p ul a axis of b lo o d vessels me ans that a latissimus dorsi flap can also be harvested along with t he bone o f the sc ap ul a and the two i ndepende n t skin paddles all ra ised on one vascula r pedule . The d isadva n ta ge o f this flap is tha t th is often has to be raised as a two -stage p rocedure) as h arvest of the flap requires the pa ti en t to he pl a ced in a la teral po sition and therefore fla p h a r ve s t ca nnot be p erform e d at the same time as resectio n . However, d o nor site morb idity is minim a l an d ,
Ch a pter 1 9 2 Oral cavity tu mou rs incl u d ing
F i g u re 1 9 2.36
the
lip I 257 1
M axil l a ry reconstruct i o n u sing sca pula fl a p.
full shoulder function returns three to fo ur weeks following surgery with m inimal donor site scars.
Deep ci rcu mfl ex i l i a c a rtery fl a p A composite flap o f ilium and overlying skin can be harvested, altho ugh this flap is best used as a myo-osseous flap in reconstruction o f post-maxillectomy defects (Figure 1 92.37). This is especially true for radical maxillectomy where orbital rim reconstruction is attained by placing the ilium in a vertical plane. When palatal reconstruction is required, the bone can be placed horizontally and the internal oblique muscle draped over the bony defect, which then heals by secondalY epithe lialization . The iliac crest myocutaneous flap is also the flap of choice in defects of the mandible of yo unger dentate patients, especially lateral segmental defects o r anterior mandibular defects. The cutaneous co mponent has a variable blood supply and the large bulk of bone harvested makes the failure rate of this flap one of the highest of all the osseous flaps. F i b u l a free fl a p
====�--�===-��-- �=
This flap is normally the flap of choice for mandibular reconstruction since the bone is appropriately long and it is possible to produce an angle to angle re construction of the mandible with segmental osteotomies
Fi 9 ure 1 92. 3 7
Deep ci rcu mflex il i a c a rtery fla p used
to
reco n s t ru ct rad ica I m ax il lectomy.
(Figure 1 92.38). The circumferential cortical bone makes this bone flap suitable for o sseo integration and the segmental style of bloo d supply makes multiple osteo tomies safe and dependable. The flap can be prefabrica ted in situ on the leg, allowing a simultaneous resection and harvest of free flap to occur. Altho ugh it was originally thought that the skin component was variable in its survival, as long as consideration to the position of the perfo rators in the lower third o f the leg is undertaken, and that regard to the musculoseptal perfo rators is taken during harvest, then the skin co mponent is reliable for intraoral reconstruction. H owever, the skin component cannot be mobilized outside the long access of the fibula and therefore with large intraoral defects, a second radial forearm free flap may be required for mucosal recon struction. The fibula bone can be osteotomized to produce an ascending ramus and a mandibular condyle where a true hemi-mandibulectomy has been undertaken. The main disadvantage of the fibula bone is that it provides very little vertical depth of bone when reconstructing a dentate mandible. However, it is possible to undertake vertical distraction o f the fibula bone at a later date to allow successful osseointegratio n of mandi bulectomy defects. [ * ]
2572 I
PART 1 7 HEAD A ND NECK T U M OURS
Figu re 1 9 2 . 3 9
Osteoradionecrosis with path o l ogical fracture.
shown that insertion of osseo integrated implants at the time of resective surgery allows t hree to four weeks of osseointegration to occur before radio therapy impairs the s blo o d supply to the healing free flap. 2
O steorad i o n ecros i s Osseous free flaps are also used a s reconstructions i n the presence of extensive osteoradionecrosis ( Marx type
(Figure 192.39) . When
3)
extensive dead bone is open to the
oral cavity or extraoral skin, hyperbaric oxygen therapy has little place. It is important when resecting osteoradio necrotic bone that dead bone is cut back to vital bone. If not, a nonunion
will occur at the junction with the vascular
ized free flap leading to further infection and dehiscence.
Figure 1 9 2 . 3 8
M and ibular reconstru ction with co m posite
fi bula fl a p .
KEY PO I NTS •
O sseo i nteg rati o n a n d vascu l a r i zed bone g rafts As a general principle, osseointegrated implants should be placed at the same time as vascularized reconstruction occurs. Careful p reoperative planning with a p rostho
•
Replace like with like if po ssible. Head and neck local flaps have good blood supply.
•
Radial fo rearm free flap has
97 percent
success rate. •
Microvascular bone flaps have donor site morbi dity.
dontist using surgical j igs and cover plates a llows the correct o rientatio n of osseo integrated imp lants into the bony reconstruction at the time o f ab lative surgery. In general terms, for implantation the ilium appears better than the fibula, which is better than the scap ula, which is better than the radial bone. Osseo integrated implants also require immobile thin skin where they penetrate through
Best cl i n i c a l p r a ct i ce ,/ When considering reconstruction re place l i ke with
into the oral cavity. It is o ften necessary to resect some of
l i ke .
the overlying vascularized skin component of free flaps
Rad ial forearm fla ps have a 95-9 7 perce n t success
and replace this with split skin grafts to provide the perfect skin to implant interface, to prevent implant loss and peri-implantitis. The osseointegrati on success rate falls fo llowing radio therapy, but various studies have
rate. · J
The co III monest fl ap used in m a n d i bu l a r re constructi o n is the fibu l a .
Cha pter
6.
Defi c i e n c i es i n cu rre n t know l e d g e a n d a reas fo r fu tu re resea rch
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193 Oropharyngeal tumours
PATRICK J BRADLEY
I n trod u ction Anatomy Cl inical presentation Pathol ogy Cl assifi cation and staging of mal ignancy of the oropharynx Evaluation of the pati ent Treatment pol i cy
,'---"7"-----
-
2577 2577 2579 2579 2581 2583
Treatment opt ions Site-specific treatment and results Sequ e lae of treatment Fol low-up Key po ints Best clinical practice References
2585 2589 2591 2592 2592 2593 2593
2584
-��� ----�.�..__ .
. SEARCH STRATEGY
The data in this chapter are supported by a PubMed search using the key words head and neck cancer, oropharynx tumours, oropharynx cancer, aetiology, diagnosis, radiotherapy, surgery, complications of treatment, results and outcomes. Also used was literature published in the journals Current Opinion in Otolaryngology Head and Neck Surgery and Current Opinion in Oncology, which are current literature review sources on topics related to the diagnosis and management of clinical scenarios relevant to oropharyngeal tumours.
INTRO DUCTION
purposes of tumour classification, four main anatomical subdivisions are described. the
The anterior wall of the oropharynx is formed by
oropharynx, is at the crossroads between the respiratory
the base or posterior tongue bounded anteriorly by the
The
location
of
this
portion
of
the
pharynx,
and digestive tracts, and neoplasms, when present, are
v-shape line of circumvallate papillae. There are numer
prone to alter swallowing, speech and breathing. Treat
ous lymphatic aggregates giving this portion of the
ment planning for patients with these tumours must
tongue its characteristic nodularity, a normal feature that
therefore be guided not only by disease-free survival
may cause difficulties in the diagnosis of early neoplastic
statistics
lesions. Lymphatics from the tongue base course down
but
also
by
the
expected
or
anticipated
functional outcome of each therapeutic modality avail
wards towards the hyoid bone where they pierce the
able and each treatment approach used. I
pharyngeal wall to drain into the upper deep cervical
Tumours or neoplasms of the oropharyngeal region are uncommon but, unfortunately, the majority encountered in clinical practice are malignant.
chain or level
II nodes. Crossover patterns of lymphatic
drainage have been demonstrated, and tumours involving or growing close to the midline often exhibit bilateral nodal involvement. The lateral wall of the oropharynx includes the tonsil,
ANATO MY
the tonsillar fossae, the faucial pillars and, more poster
The oropharynx extends from the level of the hard palate
posterior wall. Immediately lateral to the lateral phar
(Figure 193.1). For the
yngeal wall lies the parapharyngeal space. Lymphatics
iorly, the lateral pharyngeal wall that blends into the above to the hyoid bone below
2578
I PART 17 HEAD AND NECK TUMOURS
Nasopharynx
Oropharynx
Oral cavity
Hypopharynx
Larynx
Figure 193 . 1
The
oropharynx.
from the upper part of the lateral wall drain to the
in the midline. Tumours of the soft palate drain lymph to
retropharyngeal nodes, of which the only constant one is
the upper jugulodigastric and the retropharyngeal nodes.
the node of Rouviere situated close to the skull base between the internal carotid artery and the lateral wall of the pharynx. The posterior pharyngeal wall extends from the level of
Nerve s u p ply
the hard palate and Passavant's ridge superiorly to the level of the hyoid bone inferiorly where it becomes
The oropharynx is supplied with sensory and motor
continuous with the hypopharynx. In contrast to the
innervation mainly through the glossopharyngeal and
other areas of the oropharynx, the mucosa is smooth and
vagus
contains only occasional small aggregates of lymphoid
innervation to the base of tongue and the trigeminal
nerves. The hypoglossal nerve supplies motor
(V2, V3)
tissue. The primary echelons of drainage from posterior
nerve
pharyngeal wall tumours are the retropharyngeal nodes
tion of the soft palate. The vagus and glossopharyngeal
and the nodes at levels II and III.
nerves have tympanic and auricular branches, which
The roof of the oropharynx is formed by the curved arch of the inferior surface of the soft palate and the uvula
provides the motor and sensory innerva
make otalgia a frequent complaint in patients with tumours in this area
(Figure 193.2).
Jugular foramen
Jugular ganglion
Superior laryngeal n. (CN X)
Petrosal ganglion
{--- External branch
Glossopharyngeal n.
(CN IX) Internal branch
Figure 193.2
Referred o talgia .
Chapter B l ood su p p ly a nd lym phatic dra i n age
through
the
193 O ro p h aryn g e a l t u m o u rs I
glossopharyngeal
and
vagus
2579
nerves.
As
tumours grow and infiltrate into the tongue muscles, The blood supply to the o ropharynx is from branches of
movement
the external carotid artery. Levels II and III of the neck
swallowing. Further tumour growth leads to local necrosis
can
be
impaired
and
affect
speech
and
provide most of the lymphatic drainage. Central struc
and secondary infection, resulting in fetor, foul breath or
tures such as the tongue base, soft palate and the posterior
even spontaneous haemorrhage.
pharyngeal wall drain bilaterally. The posterior pharyn geal wall and the tonsillar reglOn also drain to the
Occasionally,
the first presenting symptom is the
presence of a lump in the neck, usually high up. Many such patients are young and have no symptoms referable
retropharyngeal nodes.
to the throat. Not infrequently, these lumps are removed or, after investigation, are considered branchial cysts.
Fascial s p a ces
These patients must, after confirmation of metastatic
The o ropharynx is surrounded by two potential fascial
excision biopsy of the ipsilateral tonsil. Ideally, such
carcinoma in a cystic neck node, have endoscopy and an spaces. The retropharyngeal space is an area of loose
patients presenting with a lump in the neck should have
connective tissue that lies between the buccopharyngeal
fine needle aspiration cytology (FNAC), imaging and
fascia of the pharynx and the alar layer of the prevertebral
endoscopy including unilateral tonsillectomy and blind
fascia. It extends from the skull base to the superior
biopsies before excision of the gland.
mediastinum. It communicates with the parapharyngeal space laterally. The parapharyngeal space is defined by the space from the skull base to the hyoid bone lying lateral to the pharyngeal walls. The parapharyngeal space can be further divided into prestyloid and poststyloid compart ments. The prestyloid compartment contains fat, the deep
PATHOLOGY Benign tu m ours
lobe of the parotid gland and a small branch of the The
Benign tumours occur more frequently in the oral cavity
poststyloid compartment contains the carotid artery,
than in the oropharynx. Most tumo urs that occur in the
trigeminal
nerve
to
the
tensor
veli
palatini.
jugular vein, cranial nerves IX to XII, sympathetic chain
oral cavity have also been reported in the o ropharynx and
and lymph nodes.
include squamous papilloma, adenoma, fibroma, hae mangioma, leiomyoma, lipo ma, lymphangioma, schwan 3 noma, neurofibroma and others. All such abnormalities
C LI N ICA L PRESENTATION
should be co mpletely excised, if possible, o r at least subjected to biopsy after computed tomography (CT)
Small tumours at certain sites, such as the tonsils, the
imaging to confirm their true nature and predict their
glossotonsillar sulcus and the tongue base, rarely produce
natural histo ry.
symptoms and are not always easy to detect. When
The lingual thyroid is the term applied to a mass of
o ropharyngeal
ectopic thyroid tissue located in the base of the tongue in
malignancy are often vague and nonspecific, leading to
the midline. The incidence is estimated to be one in
present,
the
initial
symptoms
of
an
a delay in diagnosis. Consequently, the overwhelming majority of such patients have locally advanced tumours
when they present. 2
Presenting symptoms may thus vary from the finding
100,000 people, and affected individuals have no other 70-100 percent of cases . There is a
thyroid tissue in marked
female
p redominance.
Most
lingual
thyroid
glands contain histologically normal tissue, but there are
of a coincidental swelling or sensation in the throat that
rare
causes the patient to seek specialist advice. Alternatively,
thyroid.
reports 4
of carcinoma
arising
within the lingual
[**] Careful workup is recommended and
some patients develop the daily habit of looking into their
removal is rarely necessary. The swelling can be treated
oral and o ropharyngeal cavity and inspect and palpate the
with suppressive doses of thyroxine, with surgery reserved
areas, and thus p resent with a 'clinical abnormality' which
fo r large symptomatic masses or when the diagnosis is in
they have seen or felt - the majority have seen 'normal
doubt.
anatomy' and can be reassured. However, some may see
Desmoid
tumours
are
rare,
nonmalignant,
slow
cysts on their tonsils or, more rarely, a swelling in the
growing neoplasms with the potential for locally aggres
posterior tongue, which may be a lingual tonsil or even a
sive growth invading surrounding structures. Desmoids
lymphoma. These 'throat gazers' should be taken seriously
are sometimes misclassified as low-grade fibrosarcomas
and reassured, in the main, that what they see or have
because of their invasive growth patterns. Histologically,
palpated is no rmal. Other more serious symptoms that require investiga tion include sore throat, foreign-body sensation in the throat, altered voice or referred pain to the ear, mediated
they are of low cellularity, have a benign appearance lacking the nuclear and cytoplasmic features of malig nancy and, clinically, they do not display any metastatic s [**] Function-preserving surgery is the
potential.
2580
I PART 17 HEAD AND NECK TUMOURS
treatment to minimize morbidity. The benefits of radiat ion therapy in patients with positive margins has not clearly demonstrated any tumour regression and should be balanced against radiation-related m orbidit y.6 primary
Mal ignant tu m ours
decades of life.9 It appears that the number of cases being is increasing as cases are be ing recorded in the fourth and fifth decades of life and in women. Patients aged less than 45 years are also susceptible to this disease, and the prevention of tobacco and alcohol abuse among younger patients is imperative.10 (**1 diagnosed
Aetiology
Malignant tumours of the oropharynx may arise from any constituent tissues but the vast majority of epithelial tumours are squamous cell c arcinomas (70 pe r cent) (Figure 193.3). There is a higher concentration of lymphoid tissue in the oropharynx and the incidence of lym phomas (25 percent) is, therefore, considerably higher compared with other sites in the upper aerodigestive tract. There are also concentrations of minor salivary glands in the soft palate, uvula and base of tongue, which may present as a salivary malignan cy « 5 percent). There is the possibility of more uncommon tumours such as soft tissue sarcomas and metastases from distant sites presenting in the oropharyngeal region. of its
SQUAMOUS CELL CARCINOMA
Epi dem i 0 logy
Oropharyngeal squamous carcinoma is said to rep resent 10-15 percent of all head and neck t umo u rs 0.3-0.5 percent of all registered malignancies and has an annual incidence in the UK population of approximately ten per million per year.7 This incidence may be as high as 100 per million in other countries. There is an increasing prevalence of oral cavity and oropharyngeal cancers in the last decade, particularly in men aged 35-64 years.s The frequency distribution of the primary site carcinoma in the oropharynx is tonsil or faucial pillar 45 percent, posterior tongue 40 percent soft palate 15 percent and posterior pharyngeal wall 5 percent. The incidence of oropharyngeal cancer varies considerably in different coun trie s, and for many countries there are no data. The condition is more common in men, with a sex ratio of 4:1, and is usually associated with the sixth and seventh ,
,
The main associated aetiological factors are smoking and alcohol consumption, the effects of which are cumulative.ll Dietary deficiencies of vit am i n A, chronic irritants, poor dental hygiene, syphilis and ma rijuana smoking have also been identified as predisposing factors in upper aerodiges tive tract cancers.12 En hanced expression of the human papilloma virus types 2, 11, and 16 has been observed, specifically in patients with ca rc i noma of the t onsil, perhaps 4, implicating it in the aetiology. 13, 1 15 Human immunode ficiency virus (HIV) may be implicated in the development or acceleration of squamous cell carcinoma.16 Patients who are HIV p ositive are prone to developing Kaposi's sarcoma, lymphoma or squamous cell carcinoma.]7.18 It has been reported that vascular tumours may affect the orophar yngeal area and may present a diagnostic challenge. It is important to differentiate between an isolated Kaposi's sarcoma and a spindle cell haemangioepithelioma. The importance of a diagnostic tool such as the human herpesvirus 8 marker may represent the only reliable test 9 for clearly establishing the diagnosis.1 [***]
LYM PH O EPITH ELIOMA
This type of malignant tumour is also know as an undifferentiated carcinoma of nasopharyngeal type and is a variant of squamous cell carcinoma. It may be found in the tonsil and the base of tongue. It is associated with a high incidence of nodal metastases and its clinical behaviour is similar to nasopharyngeal carcinoma.
LYMPHOMA
lymphoma accounts for approximately 8 percent of oropharyngeal cancers (Figure 193.4).20 The tonsil and the base of tongue are the most frequent sites, with an annual incidence estimated to be between 4.4 and 3.6 per million population in a study performed in Nottingham ? 1 The vast m aj o ri ty are of the high grade B cell type (mostly large B cell type). Men predom i nate 2:1 with the mean age at presentation being the mid-sixties. These lesions present with similar symptoms to the more common squamous cell c a rcinoma but, predominantly, are usually not associated with f eto r. Non-Hodgkin's
SALIVARY
Figure 193.3
Palatal tumour.
GLAND TUMOURS
Minor salivary gland tissue is located in the oropharynx and is co ncentra ted in the soft palate, tonsil and the
Chapter 193 Oropharyngeal tumours I
Table 193.1
Tumour sites in the oropharynx, TNM classification.
Site
Description
C01.9
Figure 193.4
Non-Hodgkin's lymphoma of the tonsil.
Base of tongue, NOS
C02.4
Lingual tonsil
C05.1
Soft palate, NOS
C05.2
Uvula
C09.0
Tonsillar fossa
C09.1
Tonsillar pillar
C09.8
Overlapping lesion
C09.9
Tonsi l, NOS
Cl0.0
Vallecula
Cl0.2
Lateral wall of oropharynx
Cl0.4
Branchia I
Cl0.8
Overlapping lesion
gland tumours as the total of oropharyngeal tumours is
Cl0.9
Oropharynx , NOS
probably not possible. Benign salivary tumours are not
NOS, not otherwise specified. Reproduced from Ref. 30, by permission.
posterior tongue. An exact true incidence of salivary
registered and seldom present to the larger specialized
2581
cleft
institutions that report on the incidence of maligna nt salivary tumours. Jones et
aI.22 reported on a series of
patients with minor salivary gland tumours of the head and neck seen in LiverpooL Of these pa t ients, malignant lesions and 42 benign. salivary tumours, more than
103 had
Of the malignant
50 percent are adenoid
Class i fica tion of primary tumours in the
Table 193.2
oropharynx , TNM classification. Descr i pt i on
Classificatio n
TX
Primary tumour cannot be assessed
epidermoid carcinoma, adenocarcinoma and malignant
TO
No evidence of primary tumour
Tis
Carcinoma in situ
minor salivary glan d malignancies is the same as the
T1
Tumour 2 cm or l ess in greatest dimension
T2
Tumour more than 2 cm but not more than
T3
Tumour more than 4 cm in great e s t dimension
T4a
Tumour invades the larynx, de ep/ex trinsic
cystic carcinoma but other malignancies include muco mixed sali vary tumours?3 ,
24,25,26 The staging of these
staging criteria used for head and neck squamous cell carcinoma?7
[**]
4 cm in greatest dimension
muscle of tongue, medial pterygoid, hard
METASTATIC DISEASE PRESENTING IN THE OROPHARYNX Seldom quantify,
reported as a series and thus difficult to 28 metastatic disease presenting in the orophar
palate or mandible T4b
Tumour invades lateral pterygoid muscle, pterygoid plates, lateral nasopharynx, sk u ll
ynx are most likely to be primaries outside the head and neck area
-
breast, lung , stomach, prostate and kidney.
Malignant melanoma should always be suspected if such a disease has been previously region.
[**]
treated in the head and neck
base or carotid a rtery
T, tumour. Reproduced from Ref. 30, by permission.
H is t opathological grades, TNM classification.
Table 193.3 Classification
CLASSIFICATION AND STAGING OF MALIGNANCY OF THE OROPHARYNX The TNM classification system describes the anatomical extent of a carcinoma of the oropharynx before
(Tables
193.1, 193.2, 193.3, 193.4
and
treatment
193.5).30
staging is a critical determinant of prognosis
193.6)?9
TNM
(Table
Description
GX
Grade cannot be assessed
Gl
Well differentia ted
G2
Modera tely differentiated
G3
Poorly differentiated
G, grade. Reproduced from Ref. 30, by permission.
There is no doubt that, for carcinoma of the
head and neck, anatomical extent is one of the most
disease. In head and neck cancer, especially when the
i mpor tant factors guiding treatment, decision making
cancer presents in an advanced stage, other factors widely
and est imating prognosis. However, it is known that the
recognized
prognosis of a pa tient with cancer is influenced by a
related factors
variety of factors other than the anatomical extent of
symp t oms,
as
prognostically significant (e.g. age,
comorbidity) ;
are:
performance status,
p atient clinical
tumour-related factors (e.g.
2582
III PART 17 H EAD At'lI D I\J ECK TUM O U RS
Table 193.4
Reg i o n a l lym p h nodes, T N M c l assifi cation. Description
Classification 1'1 X NO N 1 UL 1\J 2UL
Reg iona l lym ph nodes ca n n ot be assesse d No reg iona l lym p h node metastasis Metastasis in a sin g l e i ps i l ateral lym p h node, 3 c m or l ess i n g reatest d i mension M etastasis i n a si n g l e i psilatera l lym ph node, more tha n 3 cm b u t not more t h a n 6 cm i n g reatest dimension ; in m u ltip l e i psil atera l lym ph nodes, none more than 6 cm i n g reatest d i m e nsion; in bi lateral o r contra l atera l lym p h nodes, n o n e more t h a n 6 cm i n g reatest d i me n sio n
1\J 2a N2b N2c N 3 UL
M etastasis Metastasis M etastasis M etastasis
in in in in
sing le ips i l ateral lym p h node more t h a n 3 cm b u t not more than 6 cm in g reatest d i mension m u ltip l e ipsi latera l lym p h nod es, n o n e more t h a n 6 cm i n g reatest d ime nsion bilatera l or contra latera l lym p h nodes, none more than 6 cm i n g reatest d i mension a lym p h node more th a n 6 cm i n g reatest d i m e nsion
L , lower neck. Metastasis located below the level o f the cricoid cartilage; N , node; U , upper neck. Metastasis located above the level o f the cricoid cartilage. For pN, a selective neck dissection will ordinarily include six or more lymph nodes and a radical or modified radical neck dissection will ordinarily include ten or more lymph nodes. Negative pathological examination of a lesser number of nodes still mandates a pNO designation. Reproduced from Ref.
Table 193.5
30, with permission.
site of origin, thickness, maximum depth of invasion of
Metastatic sites, TN M classification.
Classification
the p rimary tumour site, location and extracapsular
Description
MX MO M1
spread of lymph nodes metastases); treatment-related
Dista nt metastasis ca n n ot be assessed No d ista nt m etastasis D ista nt m etastasis
factors
(e.g.
status
of resections
margins,
prolonged
treatment time for radiotherapy). Regarding other vari ables (e.g. gender, histological grading, ploidy, prolifera
M , m etastasis
tion index and other genetic abnormalities) conflicting 31 data on prognostic significance have been published.
The lungs are the commonest sites of distant metastases; skeletal or
Improvements
hepatic metastases occur less often. Mediastinal lymph node metastases are considered distant metastases. Reproduced from Ref.
estimates
in
the
of prognosis
classification will
lead
of patients to
assessment of treatment effectiveness, 32 33 improved patient care. , [***]
30, with permission.
more and
and
accurate hence
to
Following a nationwide study of oropharyngeal 34 carcinoma in the Netherlands, 640 patients who had
Table 193.6 Stage
Primary tumour classification
0 I
II III
IVA
IVB IVC
been referred for primary treatment were analyzed for
Stag e g ro u p i ng, TN M classification.
Tis T1 T2 T3 T1 T2 T3 T4a T4a T1 T2 T3 T4a T4b Any T Any T
Reproduced from Ref.
Regional lymph node classification NO NO NO NO N1 N1 N1 NO N1 N2 N2 N2 N2 Any N N3 Any 1'1
30, with permission.
Distant metastasis classification MO MO MO MO MO MO MO MO MO MO MO MO MO MO MO M1
epidemiology, treatment and survival rates. Staging was first evaluated in a proportional hazard regression analysis controlled for these data. Next, all possible combinations of T, N and M were tested in a stepwise backward elimination model until the remaining indicator variables had a
p value of less than 0.05. New stages were defined
based on the coefficients of the remaining indicator variables. These revised stages revealed a more balanced distribution of p atients and an improved prognostic discrimination for the disease-specific survival rates. 31 Ambrosch et al. applied this Hart system to their series of
224 p atients and concluded that the groupings
improved the International Union Against Cancer/Amer ican Joint Committee on Cancer (UICC/AJCC) system with respect to prognostic discrimination In
a
review
of head
and
neck stage 34 oropharynx and
(Figure 193.5). groupings
in
carcinoma of the the tonsillar 35 region it was demonstrated that the current TNM staging system could be enhanced by optimizing the 36 design of stage groupings through empirical investiga m tion and be i proved by adding defined patient variables to the staging system.
[***]
Chapter 193 O ropharyngea l tumou rs I 2583
NO
T1
N3
N2
1\J1
NO
N1
N2
T1
I
I T2
N3
II
III
T2
II MO
T3
I II
T3
MO
I II
II
IV
IV T4
T4
III
Any N
AnYT
I
IV
AnYT
L_____________________________�
(0)
Figure 193.5
I
Any N
IV
I
_ _ '---_ __
M1
_ _
(b) (a) U I CC!AJCC 1 992 stage g rou pi ng; (b) Hart sta g e grou p i n g . Redrawn from Am b rosch, P
o ro p h a ryng e a l ca rci noma.
Cancer
et al.
C l i n ica l stag i n g of
1 998 ; 82:1 61 3-20, by k i n d permissio n of J o h n W i l ey Et Sons, I n c. presenting synchronously.39 This needs to be sought for
EVALUATI ON OF THE PATI ENT
deliberately at the initial assessment. Assessment of motor and sensory deficits of the oral
Sym pto m s The
majority
cavity and pharynx may forewarn the clinician of a more of
oropharyngeal
tumours,
especially
the malignant ones, are advanced on presentation. The initial symptoms are vague, with soreness or descriptions of discomfort that has been present for months. More than
70 percent are staged Ill/IV with more than two
thirds
presenting
presentation.37,38
with
a
palpable
lymph
node
at
[**]
extensive tumour than is clinically apparent. Examination of the neck for the presence of nodal metastases is also mandatory as part of the physical examination. Each level of the neck must be palpated systemically. It must be remembered that the majority of lymph node metastases will be located in levels II, III and IV.40,41 [**] The results of palpation alone will differ among different clinicians depending on their experience. The
Phys i cal exa m i n ation
specificity and sensitivity of cervical staging by palpation has been reported as between
60 and 70 percent.42 The
deep cervical chain of nodes may be particularly difficult I t i s important that a full examination o f the upper
to assess if the patient has a thick short neck or is
aerodigestive tract and the neck is conducted, and it must
experiencing pain in putting the neck muscles into spasm.
include the use of a fibreoptic endoscopic evaluation.
Occasionally, neck metastases associated with orophar
Inspection may reveal a suspicious ulcerative lesion but
yngeal
not infrequently the lesion may need to be palpated
degeneration or necrosis,
squamous
cell
carcinoma
may
bimanually to appreciate its full extent. Often the patient
increase in size and no other associated symptoms, may
and thus,
cause
cystic
due to a rapid
will not tolerate such an examination in the clinical
erroneously be considered to be a branchial cyst. It is
setting and an examination under a general anaesthetic
therefore recommended that all patients who present over
will be required. The association of trismus or involve
the age of
ment of the maxilla or mandible by tumour makes such
assessed by CT/magnetic resonance imaging (MRI) prior
40 years with a suspected branchial cyst must be
an examination without anaesthetic very uncomfortable.
to surgery to exclude a mucosal primary, most often
Some lesions may only present as a smooth nonulcerative
located
lesion, in particular, lymphoma or an adenocarcinoma.
advancing T stage, the greater the risk of cervical nodal
As such, then a representative biopsy can only be obtained
metastases. Primary tumours of the tonsil and posterior
in
the
oropharynx.38
[**]
In
general,
with
by having the patient anaesthetized. It should also be
tongue are the most likely to metastasize to the cervical
noted that there could be a second primary lesion
nodes, with positive nodes in
70 percent of patients.43
2584
I PART 17 H EAD AN D I\J EeK TU M O U RS
diagnosis as to the options of care to be provided and to
Radiologi cal i m ag i ng
look after patients' physical and psychological needs. There are many techniques available for radiological evaluation of the primary disease and the neck. For patient convenience, speed and cost -effectiveness it would seem better to use one method rather than several; however, there are advantages and disadvantages for each method.
The
use
of
CTIMRI
is
almost
universally
available. There are advocates for the use of ultrasound to evaluate the NO neck and the use of FNAC has increased the accuracy of all methods of evaluating the NO neck.44 It is important to assess the size, site and extent of the primary tumour and its potential spread into neighbour ing anatomical areas: parapharyngeal space, tongue base and supraglottis, posterior pharyngeal wall up to the nasopharynx or downwards to the hypopharynx, as well as both sides of the neck. It is also important to assess the presence of maxillary or mandibular invasion and this is probably best illustrated by a combination of imaging rather than by one method alone.45 Should the head and neck area be imaged by CT, then it is practical and useful to extend the imaging to include the chest at the same time. The incidence of distant metastases is correlated with advanced T stage and even more strongly related with an advanced N stage, and the oropharynx has the highest incidence of distant metas
tases of all head and neck squamous carcinomas.29
Treatment is expected to be with curative intent in approximately and up to
60-70 percent of patients when first seen, 30 percent are treated with palliative intent and
require a significant amount of support from the team members. The general treatment of tumours of the oropharynx is dependent on the histological diagnosis. Treatment of benign disease is generally surgical whereas the treatment of malignant disease will vary, depending on whether the diagnosis is the commoner squamous cell or salivary gland carcinoma. Early tumours can be treated by a single modality alone or with combination surgery and postoperative radiotherapy. Where expertise is available, the use of the carbon dioxide transoral laser has been used to good effect and with impressive results.46, 47, 48 The treatment of a patient with advanced malignant disease is fraught with a multitude of problems.49,50 Patients are, in general,
in a very poor nutritional state and may already have experienced significant weight loss. They require nutri tional
support
and,
currently,
the
placement
of
a
percutaneous gastrostomy is necessary in the majority of patients, whichever treatment plan is being consid ered.51,52 Other co-morbidities that may also be present are associated with chronic alcohol and smoking addic tion,
as well as chronic obstructive airways disease,
diabetes mellitus and chronic cardiovascular insufficiency.
[***] B i o psy All patients with an oropharyngeal tumour or mass should be examined with the use of a general anaesthetic, sometimes even when they are seemingly high risk. This procedure will allow a thorough examination of the whole of the head and neck region and allow for representative biopsies to be taken. If there is a smooth swelling of the
The finding of clinical metastatic disease in the neck, even in tumours that seemingly have a small burden of primary tumour disease, is the norm, with N2c and N3 disease not infrequent. The management of the neck disease should follow the general principles advocated for N + disease elsewhere. There is also a high association of second
primary
malignancies
with
oropharyngeal
carcinoma.
tonsil then a tonsillectomy is preferred. The biopsy of a posterior tongue lesion can sometimes be difficult or next to impossible, and the use of a Tru-cut or core needle
Factors affecti ng cho i ce of treatm e nt
biopsy under bimanual guidance can be very rewarding rather than risk a second anaesthetic. In the presence of metastases in the neck without an obvious primary tumour the tonsil will frequently look and feel normal even to bimanual palpation. Therefore the tonsil must be excised completely, pinned out and sent fresh to the pathologist for serial sectioning for the
It remains true that a variety of interrelated factors must be considered when choosing the appropriate treatment for a patient who presents with a tumour located in the oropharynx. Ultimately, the treatment must be suited to each patient.53
detection of a possible occult primary carcinoma.
TUMOUR FACTORS Small, superficial lesions in accessible sites, such as the
TREATMENT POLICY
anterior faucial pillar and soft palate, are easily treated by
At present, the management of head and neck tumours is
or by laser m�thod, with good effective tumour control
best carried out in a multidisciplinary treatment environ ment. The team will be involved in counselling after
peroral excision using the conventional method of scalpel rates and preservation of function. In contrast, advanced
tumours of the posterior or base of tongue may require a
J
Chapter 193 O ro p h a ryngeal tumou rs I 2585 total glossectomy with or without a total laryngectomy and the patients may be better advised to consider nonsurgical treatment, reserving surgery for salvage.54
[***] Not infrequently, the margins of oropharyngeal
results of treatment have been an improvement of five year
survival,
relapse
free
survival
contro1 rates.58 " 59 60 The advan tages
and 0f
locoregional . · usmg · mtenslty-
modulated radiation therapy (IMRT) in the treatment of
tumours are not discrete and there are often areas of
oropharyngeal carcinomas are still being evaluated but
erythroplakia or 'unstable mucosa' which would require a
early results appear encouraging.61,62,63, 64
large 'safe margin' to ensure complete surgical resection.
occurrence of second tumours is relatively common in
Sadly,
the
In this case radiotherapy may be a better option. In
such patients and may contribute substantially to causes
general, exophytic tumours fare well with radiotherapy
of death.58
whereas endophytic and deeply ulcerative tumours are
Over the years many workers have established which
radiation
tumours respond well to radical irradiation and which do
therapy, as these tumours respond poorly to primary
not.65 There is agreement that T1, T2 and some T3
best
treated
surgically
with
postoperative
radiation and the results of salvage surgery are dismal.
tumours of the oropharynx respond well
to radio
therapy.66 The combination of surgery and postoperative radiotherapy is becoming more popular, and there is an
PATIENT FACTORS
appreciable improvement in control of the locoregional important
disease.67 Alternative methods for delivering radiotherapy
factors that affect the outcome of treatment.55 The use
have been advocated, with the use of interstitial or
Performance status
and
co-morbidity
are
of aggressive treatment may technically be feasible but
intercavity implantation of radioactive sources into the
poor performance status or significant co-morbidity may
tumour.68,69 Many complications arising from the use of
require modification of treatment to ensure compliance
radiotherapy for the treatment of oropharyngeal tumours
and/or safety. The patient's preference, ability and will
have been reported and these must be considered for each
ingness to cope with the treatment and its functional
patient being treated?O It must also be remembered that
consequences
The
the patients who smoke during radiotherapy appear to
presence of advanced dental or alveolar disease has the
have lower response rates and shorter survival durations
will
also
influence
the
decision.
potential to delay and complicate radiotherapy whether it
than those who do not.7! The total dose as well as the
is given primarily or as an adjuvant to surgery.56
overall treatment duration is important to the treatment
[**]
outcome of oropharyngeal cancers.72
[***]
FUNCTIONAL OUTCOME AND LONG-TERM SEQUELAE The functional deficit that is expected to result from surgery or radiotherapy is a useful factor to help make the choice when one or more options are known to produce equivalent locoregional control. The effect of xerostomia following radiotherapy and the possible risk of a second carcinoma, especially in the young patient, may support a surgical policy. However, when surgery will involve the likely loss of tongue or larynx, due consideration must be given to organ-sparing nonsurgical approaches.57
[**]
Surgery Most oropharyngeal tumours are operable but whether they are curable by surgery alone is debatable. Extension into the poststyloid space, involvement of the prevertebral fascia or the carotid system decreases the chances of curing the cancer to nearly zero. The surgical principles which continue to be advocated are that resection must include a margin of 1-2 cm of grossly normal tissue. Frozen section may be used to ensure complete excision when there is doubt or debate about completeness at the time of surgery.73 Oropharyngeal cancers can be resected
TREATMENT OPTIONS
through three main surgical approaches: the transoral, transpharyngeal and the transmandibular approaches.
Rad i othera py
The choice of approach depends on the size and location of the tumour, whether a concomitant neck dissection is
It must be emphasized that oropharyngeal tumours, other
being planned and the method of reconstruction.74
[**]
than those in the tonsillar fossae, have bilateral lymphatic
In the last few decades there have been major advances
drainage and are associated with a high incidence of
in the quality of reconstruction of major surgical defects,
lymph node metastases. The treatment techniques depend
no more so than in the oropharyngeal area. There are
on the site
Radiotherapy
many different methods of reconstruction, which range
and
the stage of disease.
techniques are similar whichever site is being treated,
from primary closure and healing by secondary intention
with the exception of small tonsillar carcinomas, and
for the smaller defects to the use of local, myocutaneous
bilateral radiation fields are used to treat the whole
and free microvascular tissue transfer flaps. The choice of
oropharynx including prophylactic nodal irradiation. More recently, since the introduction of concomitant
reconstruction varies among surgical groups and is based on experience and comfort levels?5,76 The effect of
radiotherapy and chemotherapy, in suitable patients the
radiotherapy on reconstructive flaps has been studied. It
2586
I PART 17 HEAD AND NECK TUMOURS
was found that there were fewer complications in the postoperative group than the preoperative group, sug gesting that radiotherapy is better administered after
surge ry.77 [***]
Steiner and colleagues for the excision of tonsil and base of tongue tumours , with excellent results and minimal functional disabi lit y . 3 1 . 46 However, these results need to
be repro d u ced b y o thers treatment
to prove the effectiveness of this modality. [***]
TRANSORAL APPROACHES
These include the ora l
approach and the lip-splitting approach without mandibulotomy. The oral approach removes the tumour through the mouth with no external incisions. Owing to its limited exposure, it is good for small tumours (T 1), superficial or exophytic cancers of the upper or anterior orop har ynx. In dec i ding to use this
TRANSORAL/TRANSCERVICAL COMBINED APPROACH
Lingual-mandibular release is indicated mostly for tongue base
lesions.
This
is the concept of the 'pull-thro'
technique, which releases the tongue and floor of the mouth
in order to
mandible
into
the
pull neck.
these structures below the 78 Sometime the use of a
approach, the presence of trismus, obstructing dentition,
mandibular s pl i t will
excessive soft tissue and the height of th e mandible need
the tumour and important structures, and allow for better
increase th e access, visualization of
to be considered. The use of a B oyl e -D avi s gag can assist
flap positioning and suturing into place. Structures at risk
in exposure to many of these tumours. Many of these
with t his approach include the lingual arteries and the
defects can be closed primarily or, if considered ' bigger', may be left to granulate secondarily
hypoglossal nerves. [**]
(Figure 193.6). The
use of the carbon dioxide laser has been advocated by TRANSPHARYNGEAL APPROACHES Transph a ryngeal
phar yngotomy
approaches
include
the
su prahyoi d
lateral pharyngotomy. The 9 supr ahyoid pharyngotom/ is used for small tumours
and
the
of the tongue base and the pharyngeal wall. Entrance is through the vallecula. This allows preservation of the lingual arteries and hypoglossal nerves. Extension of the phar yngotomy late r ally and inferiorly along the thyroi d
ala allows for wider exposure
if required. The major
difficul ty with this approach is the poor visualization of the superior margin of large tumours; however, it results in excellent
fu nctional
and cosmetic out co me s.
l ** J
The lateral pharyngotomy is also useful for small tumours of the base of tongue and lateral pharyngeal wall and tonsil. The pharynx is entered posterior to the thyroid ala on the diseased side . Care is necessary in order to avoid damage or undue stretching of the hypoglossal
and superior laryngeal nerves. Once the pharynx has been
op ened , the larynx is retracted to the opposite side and surgery
commenced.
Should
expos u re
additional
be
required, the ph a ryngotom y can be extended acro ss the vallecula or can be combined with a mandibulotomy.
TRANSMAN D I BU tAR APPROACH Transmandibular app roaches include 8o and mandibulectomy procedures. , 81.
m andibulo t omy 82
If the patient
has a full set of tee th , limited mouth opening or a poste rio r located tumour, a mandibular splitting ap
proa ch should be considered. Using this approach the tumou r can be removed in contin u ity with the neck dissection. [****] Mandibulotomy should be avoided when the tumour has invaded the bone or the periosteum of the mandible, in Figure 193.6
(a)
So ft
which case a �andibulectomy is required
palate
tumour;
(b) radial forearm flap.
Mandibulotomy
procedures
incl ude
(Figure 193.7).
the
lip-split ting
Chapter 193 Oropharyngeal tumours I
Figure 193.7 showing T3
and
2587
Tons il
(a) squamous cell carcinoma; (b) CT scan neck; (c) CT scan showing T3 with ( d ) approach via mandibulotomy (continued
no d e in
extension into neck; over) .
approach, midline labiomandibular glossotomy and man
bone the pI ates should be selected and adapted to the
dibular swing approach. The site of the mandibulotomy is
mandible, with screw holes placed and the screws initially
based on the presence of dentition and the fact that it
positioned. This allows for rapid and accurate closure at
should be made between the two mental foramina. Lateral
the end of a long procedure. The mandibulotomy may be
mandibulotomy, performed
vertical, stair-step or deep V (arrow head) configuration.
through the body of the
mandible, is not carried out routinely because of the high
Should the lip be split, there are several possible
complication rate should the patient require postoperative
approaches. Most simply, a vertical incision can be carried
radiotherapy. This is due to division of the artery in the
through the full thickness of the lip, the mentum and into
mental canal, which can result in ischaemi� necrosis when
the neck. The
lip is split in the midline jf the marginal
radiation is used. Therefore, the mandibulotomy is made
mandibular nerve is sacrificed to prevent eversion of the
anterior to the mental foramen, through a tooth socket to
paralyzed lip with scarring.
support the reconstructive plates. Prior to splitting the
zigzag-stepped technique, which minimizes the risk of
Another approach is the
2588
I PART 1 7 H EAD AN D N ECK TU M O U R S
t h e chin , t he incis i o n i s made through this natura l concavity. T he m a n dibul a r swing a ppro ach p rovides exposure o f
[**** ] I t is the procedure o f bloc resec tion o f t h e tumo ur a n d neck
th e en tire oropharynx.so c hoice for a n
en
d issection. I t is useful for tumou rs that do not involve t he m a n d i b le, fo r tumo u rs tha t involve multiple sites a nd fo r tumours tha t involve the p a rapharyngea l space. M a n di bulecto my is requ ired if there is bony i nvolvemen t either d iagn osed radiologica lly or at t he time of su rgery. In a segmenta l resec t ion, the co n dyle-to -co ndyle co ntinu ity is dis rupted by removing a l l or a p o rtion of the r a mus, a n gle, body a nd parasymp hysis. I f the tumour is fixed to and only involving the perio stium, a m a r g i n a l m a nd i b u lecto my sh ould be co nsid ered . Once the cancer has spre a d i n t o the m a rrow space a wide m argin o f a t least 2 c m sh o u ld b e
taken
beyo n d t h e visible extent o f b o ny
invo lvemen t . Rep lacement of the bony defect is to be reco m mended a n d there a re many free tissue co mposite flaps ava ilable to rep l ace bone and soft t iss ue. An alternati ve to the lip -spli tt i ng approach t o the oral cavity is the visor flap. An in traoral incision is m a d e in the
buccogingival
sulcus
without
lip
split
to
allow
eleva tion of the cheek flap as a visor. A suture can be placed at the tip of the t ongue or on its lateral margin to stretch the mu cos a prior to m aking the i ncision. The incisio n can b e extended into the co n t rala tera l gingivo l a bi a l
sulcus
bu t
care
must b e
taken to
avo i d
the
co n tral a teral mental nerve. Visor flaps h ave the fo l lowi n g disa dvantages: they c a n result in division o f both mental nerves and they so metimes provide inadequate p osterior exp osure in the case of l a r ge tumo urs. Determi n ation o f the mandibu lar bony involvem ent may be d i fficult p reoperat ively. I maging stud ies may help , a n d i n clude CT a n d MRI. The most accurate method o f determining bony involvem e nt i s b y d i rect intraoperative
[***]
i nspec tio n.s3
M a n age m e n t o f the neck N eck d issection needs to be consid e red preo pera tively a n d Fig u re ' 93.7
forearm
To n s i l
(conti nued) (e)
m a n d ibu l o tomy;
(f) ra d i a l
fl a p to re p a i r tonsil/ p a l a te ; (9) m a n d i b u l o to my.
es peci a l ly when the diagnosis i s squamous cell ca rcino ma . In the cases of n eck d isease or suspected d isease, the neck should be treated wi t h surgery o r irradi ation. In the case of su rgery, the levels that should b e included remain
vermilion contracture. T his tec h n ique d o es not d isturb the contour o f the ch in skin o r d a m age fac i a l o r m e n ta l nerves. The incision begins with a n o ff- mid l i n e i ncisio n th rough t h e vermilion with
a
ho rizontal t ria n gu l a r flap a t
t h e b o rd er. This inci s i o n i s extended vertica l ly to t h e m e n t a l crease. The in cision i s c a rried a ro u n d t h e c h i n p a d in a b roken geo met ric line which fo rms
a
h a l f h exago n
fl a p. Then the incision is co n nected w i t h a h igh cervical in cision with a m o d e r ately s ized tri a ngular flap through the submentu m. In those pa tients with a vert i ca l cleft i n
co n tro versial.
In
the
clinically
NO
neck,
the
author
performs levels I , l I a and I lb , I I I and u p p e r Va . In t h e presence of N +
neck disease either a modified r a d i ca l
neck dissectio n , with preservation o f X l a n d t h e int e r n a l jugular vein n ecessa ry.
O f,
occasion ally, a radical neck d issect io n , is
For p a t ients who p resent wi th
T3 staged
ton sill ar c arcino m a or above, the risk of co n t ra.l ateral occu lt n o d al disease is
estimated
to
be 2 1
percen t ,
t h erefore i t is reco m mended tha t a n elect ive co ntral ateral neck trea t ment be a dvoca ted in p a tients who present w i t h i psilate ral no d a l metastases . 84
Chapter 193 Oro p h a ryngea l tumours I 2589
193.8J�
(Figure
S ITE-S PECI FIC TREATIVIENT AND R ES U LTS
recommended.
Postop rative radiotherapy is always � IS debate as to whether total
There
glossectomy as a curative procedure should be offered as
Ca rci n o m a of the to n s il o r l ate ral wa l l
a primary treatment with postoperative radiotherapy or as
In stages I-II and some stage III (T l -2, N1) squamous cell carcinoma, external beam irradiation is given to the local and regional site to good effect. In the Liverpool series,38, 85 it was concluded that tonsillar carcinoma with lymph nodes can be treated by radiotherapy to the tonsillar region and with radical neck dissection if the disease is more than N 1. In Birmingham,86 a similar policy was adopted, namely of local radical surgery or laser surgery,31 with appropriate neck dissection followed by external beam radiotherapy to the primary site and the neck. In Birmingham, this resulted in a two-year 100 percent and five-year 92 percent survival, with minimal functional deficit. It appeared to have little significant impact on the patient's quality of life as assessed by the European Organization for Research and Treatment of Cancer questionnaire. The expected five-year survival in early tonsil cancer is in the region of 50-90 percent.
[*H J
In more advanced disease, stage III and IV combined resections,87,88 which currently necessitate reconstruc tions by myocutaneous flaps or by free tissue transfer, are performed and followed by postoperative radio therapy to the primary site and the neck. It is considered by most that advanced disease of the tonsillar fossa
a salvage procedure.54 In one series, postoperative course and functional outcome were similar in the two groups, and overall survival was 32 percent at three years and 2 1 percent a t five years.92 Local tumour control was the main
factor influencing the patients' survival. In a retrospective analysis of 262 patients treated by five different modalities with long-term follow-up, the authors concluded that no single treatment produced a significantly improved survival advantage, and that focussing on improving locoregional control might improve overall survival.92
[H*J
An alternative approach in advanced (stage III or IV) tongue base tumours is the use of chemoradiotherapy,93, 94 with some encouraging results long term and minimal functional deficit. A trial has shown that chemotherapy (carboplatin plus fluorouracil) with radiotherapy provides better local control and improved three-year actuarial overall and disease-free survival than radiation therapy alone.95
[*H J
Irradiation and surgery remain the standard treatment. Other possibilities to promote improvement are currently under evaluation and include acceleration of irradiation and concomitant chemotherapy combinations,
which
appear to be the most promising approaches.96
remains a challenge and requires combined surgery and radiation.89, 90 If the tumour is not considered resectable then radiotherapy with or without chemotherapy is given as the only treatment.
[HJ
The expected five-year survival of advanced tonsillar carcinoma is in the region of 20-55 percent.
Soft p a l ate tu m ours Early stage cancer of the soft palate I-II may be treated by surgical excision with the use of a dental obturator, external beam radiotherapy or the use of brachytherapy, with equal expectation of cure. The functional outcome may be critically different, with significant hyponasality
Poster i o r to ngue or to ngue base tu m ours
of speech and nasal regurgitation which may be intoler able to many patients. In advanced stage disease III-IV
The
management
of
cancer
of the base
of tongue
the use of radiotherapy or combined treatment is advised.
generates considerable controversy and different philoso
In general, advanced disease of the soft palate involves
phies of management in individual institutions, depend
both tonsillar fossa and these areas require treatment as
ing
upon the
primary
surgical
or
radiation
bias.4 9
well as the palate. The use of the radial forearm flap free
Laterally located stage I-II tumours, which generally do
tissue transfer has become the choice of repair world
not cross the midline, are treated by single modality:
wide.97,98
[HJ
combined resection of the primary and the lymph nodes or radiotherapy to the local and regional sites. Infre quently, there may be a small primary tumour with
Poste r i o r pha ryngeal wall
extensive neck disease which may be treated by pre operative neck dissection and radiotherapy to the neck
Little has been written about oropharyngeal posterior
and primary site. The five-year survival expected in early
pharyngeal wall carcinomas, and studies have tended to
stage disease is 45-70 percent.
combine the oropharyngeal and hypopharyngeal poster
This early presentation is unusual as the maj ority of
ior wall as the tumours may present in the same fashion
these tumours are staged III-IV at presentation. Should
and are therefore treated similarly.99 Most of the tumours
surgery be considered then a wide resection with a maj or
are advanced when diagnosed. Treatment options include
reconstructive procedure is necessary. Access may be by
radiotherapy alone or surgical resection with or without
using a mandibulotomy or a suprahyoid approach and
neck dissection. The decision to preserve the larynx has a
may require replacement of bone as well as soft tissue
significant bearing on the method of repair should
2590
I PART 1 7 HEA D AND N EC K TU M O U RS
(d)
Poster i o r tongue. (a) Sq u a mous ce l l ca rcinoma ; (b) CT sho w i n g right-sided tu mour; (c) posterior tongue; (d) m a nd ibu l otomy ; (e) pectora l is major flap. F i g u re 1 9 3 . 8
surgery be co n side red. Cu rren tly, the use of
3
radial
forearm flap, a j ejunal graft or a free o m e ntal graft will
neck dissection co nsi dered.
[***]
needs t o b e perfo r me d n e e d s t o
be
preserve pha ryngeal fu nction and most p robably may reviewing
a
series o f
1 00, 1 0 1 , 1 02
Julieron et al., 103 77 p a t i e n tc; trea ted by ra d ioth era py
allow laryngeal p rese rva t i o n .
and by su rgery, d iscuss t h e i r fu n ct i o n a l a nd o ncological
M a n ag e m e n t of the n e ck
results. The b igger the tu m o ur the worse is the o u tcome.
The treatmen t of cervical lym p h n ode m et astases is an
The debate co ncerning whet her a u n ilatera l o r b ilateral
imp ortan t part o f the ma nage m e n t o f o ro p h a rynge a l
Chapter 1 93 O ro p h a ryn g e a l tumou rs I 259 1 squamous cell carcinoma. Metastases are already clinically present
in
as
many
presentation. 1 0 4
as
64 percent of patients at
[**] Metastases occur most frequently
rates
of
organ
surviva1. 1 07
preservation
and
possibly
improved
[**]
in levels II, III and IV, and less frequently in levels I and V. It is therefore a suggestion that all patients who undergo
SEQUELAE OF TREATMENT
curative treatment should have treatment directed to the likelihood of disease in the neck by the application of
There are three main issues that result from curative
radiotherapy or by
treatment of oropharyngeal cancers: sequelae or compli
performing
some
form
of neck
cations of the treatment; functional deficits or inter
dissection, depending on the N stage.
ference
Presen ce of d i sta nt m etastases Distant metastases are a significant problem in patients with carcinoma
of the oropharynx,
of
physical
or
physiological
functions;
the
management of recurrent/persistent disease.
Co m pl i ca t i o n s of treat m e nt
and happen in
15-20 percent of all patients over the
Radiotherapy is associated with several sequelae such as
course of their disease. However, it is unlikely to be the
mucositis, xerostomia, fibrosis of the local tissue treated
first site of failure, as compared with local and regional
and, possibly, the development of osteoradionecrosis.70 , 108
recurrence. Distant spread is most commonly to the
[**]
approximately
lungs, in patients who present with advanced disease, and
The combination of chemotherapy with radiotherapy
especially in those with histologically proven lymph nodes
to treat locally advanced tumours can result in severe
at multiple levels of the neck or in the lower neck.29
toxicity and a higher than usual rate of treatment-related morbidity and even mortality. When surgery is used as part, or the only treatment, of
Chem othera py/orga n - p reserv i ng a p p roaches
oropharyngeal tumours, the correction of preoperative
The concept of combined modalit y treatment is that
gastrostomy for maintaining nutrition has significantly
nutritional deficits and the placement of a percutaneous surgery best addresses gross disease, whereas radiotherapy
reduced the postsurgical complications.51 These can be
eradicates microscopic disease, for which surgery is less
classified into local ( bleeding, wound breakdown, flap
effective.1 05 Recent studies using molecular techniques
failure and fistula formation) and general complications.
have provided further evidence that surgical margins are frequently
involved
involvement
is
not
by
tumour,
always
even
obvious
on
though
such
microscopic
Fun ct i o n a l outco m e
examination. Thus, the addition of postoperative radio therapy for advanced tumours would reduce the like
Functional outcome after the use o f radiotherapy, either
lihood
alone
of
local recurrences.
The
suggestion,
though
difficult to prove, is that if locoregional recurrences are
or
with
chemotherapy,
acceptable preservation
of
in general,
results
in
function when
related
to
reduced this will improve overall surviva1. 1 05 In head and
eating,
neck cancer, and particularly in oropharyngeal cancers,
assessment
poor survival is currently associated with the additional
carcinoma treated by operative and nonoperative meth
drinking of
and
speech.
patients
who
However, had
a
in
base
a of
recent tongue
mortality from metastases, second primary cancers and
ods, the results suggested that the tongue remained
intercurrent illness. The use of chemotherapy alone or for
dysfunctional in both groups.1 0 9, 1 1 0 ,
recurrent disease is disappointing, but there is a modest
lyzing speech function following surgery, it was concluded
improvement in overall survival when the chemotherapy
that the combination of the method used to close the
targeted chemoradiation protocol, referred to as RAD
percentage of soft palate resected had the strongest
PLAT, has been introduced which infuses cisplatin directly
relationship with overall speech function at three months 1 after treatment. 1 2 A consecutive series of 54 patients who
is given simultaneously with the definitive therapy.1 06 A
into the tumour bed, while minimizing the effects of the
defect,
the
percentage
of
tongue
III
Specifically ana-
resected
and
the
drug systemically. This technique allows an increased dose
underwent a total glossectomy with or without total
of cisplatin five times higher than standard chemotherapy
laryngectomy were analyzed for function and quality of
protocols, thereby enabling the delivery of an enormous
life. It was concluded that the outcome, from the patient's
amount of drug over a relatively short period. Results
perspective, can result in meaningful survival and an
have shown complete regression of tumour at the primary
adequate
site in
patients. 113
80 percent of patients and regional sites in 6 1
percent of patients. It has, therefore, been concluded that
quality of life can be achieved in selected The
selection
of
the
most
appropriate
reconstruction following primary ablation is of profound
this type of regimen is an effective method of manage
importance.
ment in patients with advanced disease resulting in high
primary compared with secondary reconstruction because
The
functional
outcome
is
better
after
2592
I PART 17 H EAD AN D N ECK TU M O U RS
primary
and
advantages have been achieved with cisplatin and 5 -
contracture. Irrespective of the surgical management,
reconstruction
results
in
less
fibrosis
fluorouracil i n combination.1 2 s A French study reviewed a
surgical rehabilitation can be enhanced by nonsurgical
group of patients with advanced stage IV oropharyngeal!
measures.11 4 In most patients, many of the global and
hypopharyngeal cancers, treated by concomitant twice a
disease-specific quality of life subclasses initially worsened
day continuous radiotherapy with no acceleration and
due to extensive surgery and radiotherapy, but most
chemotherapy with cisplatin and 5 -fluorouracil. One
returned to baseline by
6 months post-treatment and had
third of patients are alive more than three years later.
116 The
They reported that at 1 2 months, taste, smell, dry mouth
surpassed pretreatment values by 1 2 months.
l I S,
consensus conclusion is that the use of large resections
and sticky saliva are worse than at baseline, but the side
and reconstructions is justifi ed despite predictable initial
effects between 1 2 and 24 months improved markedly.
worsening
resection
They also commented that there is a large individual
controls the local disease and microvascular reconstruc tion restores reasonable functional status.11 7 , 118 [***]
sequelae of radiotherapy, and the time it takes for these to
of
measured
criteria:
extensive
variability concerning the acute side effects and late disappear.126
[**]
Tu m o u r rec u r r e n ce FOLLOW-UP Recurrence of tumour is frequent in patients with treated oropharyngeal cancer.11 9 It has been recommended that if negative margins cannot be achieved, a postoperative irradiation dose of
66 Gy be recommended, with every
effort made to avoid treatment interruption.1 20 In a review of 221 patients treated by irradiation alone in . L·Iverpoo1 , 1 21 the pnmary recurrence at fi ve years was 27 percent, with a five-year survival after recurrence of 3 1 percent. The metastatic rate in the cervical lymph nodes was
44 percent at five years, with a survival at five years
after
node recurrence of
19
percent.
Two-thirds
of
patients had advanced disease (N2 and N3) when node recurrence was diagnosed and approximately 1 5 percent were
unsuitable
for
surgery.
Survival
after
tumour
recurrence has not been systematically studied despite its prevalence, morbidity and cost. A suggested practical staging system for clinicians who manage patients with recurrence has been formulated based on the TNM status, muscle invasion and weight 10SS.1 22, 1 23
[**]
The options of further management of recurrent disease depend on the stage of disease at presentation, the mode and method of treatment initially (whether for cure or palliation) , the timing of the recurrence from primary
treatment,
the
location
of
the
recurrence
(whether at the primary site, the neck or both) or the detection of distant metastases. The following are the standard options. •
Surgical resection if radiation therapy fails and it is
Follow- up of patients treated for head and neck cancer aims at early detection of locoregional relapse and the detection of
second primary cancers,
based
on the
assumption that early detection of both recurrences and second tumours are more likely to be cured. Second malignancies develop in this population at a rate of approximately
3-6 percent per year. Salvage surgery can
be proposed in a significant number of patients with local recurrence, and along the neck node distribution. In general, two-thirds of patients will have recurrence during the first two years and approximately 1 0 percent during the third year of observation. In approximately
60 percent
of patients with recurrence, relapse is diagnosed because of symptoms and for the remainder it is by clinical examination. A suggested protocol for follow-up would include an examination two to three months after completion of curative treatment. Subsequent examinations should be scheduled every two to three months in the first two years, then every four to five months for the third year and on an annual basis after the third year. The role of radiological imaging
CT/MRI
and positron emission
tomography for the early detection of a recurrence is under investigation. It is suggested that a chest radiograph should be performed annually, even though there is no clear benefit from performing it. Other investigations should be performed only as clinically indicated.1 27
technically feasible. •
�adiation therapy when surgery fails if not previously
gIven. •
•
Surgical salvage when surgery fails if it is technically feasible. Other treatments include the use of chemotherapy,
KEY POINTS •
oropharyngeal tumour are commonly
hyperthermia with further radiotherapy, 4 electroporation, etc. 1 2
overlooked by patients and as a result most patients present with advanced disease.
Patients with recurrent or metastatic disease have a median survival of approximately six months. There has been
evidence
from
randomized
trials
The symptoms and signs suggesting an
that
survival
•
The majority of tumours are malignant and are deserving of a biopsy under general anaesthetic.
Chapter 1 93 O roph aryngeal t u m o u rs I 2593 •
Most malignant tumours are squamous cell
H a rker LA (eds). Otolaryngology - h ead and neck St Lou i s : M osby Yea r Book, 1 98 6 ; Cha pter 71 :
carcinoma but others include lymphoma,
surgery.
salivary cancer, sarcoma, as well as distant metastasis. •
4.
Early tumours are best treated by surgery with o r without radiotherapy.
•
Late tumours are frequently inoperable and p robably best treated by chemoradiotherapy,
5.
with surgery reserved for operable recurrences. •
Tumours located in the base of tongue have a worse prognosis than other sites in the oropharynx.
•
Death frequently results from local and regional recurrence, in spite of aggressive treatment.
•
8 1 4-21 . Abd e l ka d e r M, Riad M, W i l l i a m s A. Agg ressive fi b romatosis of the head a n d neck (desmoid t u m o u rs). Journal of Laryngology and Otology. 200 1 ; 1 1 5 : 7 72-6. 7. B rad l ey PJ . Ma n a gement of squamous ce l l ca rci noma of t h e orop harynx. Current Opinion i n Otolaryngology and 8.
and quality o f life.
9.
Best cl i n i ca l practice c/
Pa i n i n the th roat, if i nvestig ated by rad iolog ica l i m a g i n g , CT a nd/or M R I , may increase early d i a g n osis
1 0.
of m a l i g n a n t oro p h a ryngea l tum o urs. �I The majority of patients have adva n ced d isease at
.'
,I
p rese ntation a n d many a re treated with p a l l i ative i ntent. Both s u rgery a n d ra d i oth e ra py, when used as modal ities for treatment, resu lt i n s i g n ifica n t morbidity, speech, swa l l owing, b reath i n g , as we l l a s xerosto mi a, w i t h o u t n ecessa ri ly a d d i n g a n y extra l o n g evity to l ife. Preve n ti o n , by e l i m i nating smoking a n d excessive a l cohol d ri n ki n g , is best p ractice to red uce the l i kely i n ci dence of the com m o n est m a l i g n a n t o ro p h a ryn gea l t u m ou r.
11. 1 2.
1 3.
1 4.
1 5.
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2.
Pate l SG, Shah J P. Tu m o u rs of the orop ha rynx. I n : Shah J P (ed.). Cancer o f the h ead and neck. American Cancer Society. H a m i lton , Lon d o n : BC Decker I n c., 200 1 ; C h a pter 6 : 1 27-45.
1 6.
Pitchers M, M a rt i n C. Delay i n referra l of orop haryngeal sq u a m ous cel l ca rci noma to seco n dary ca re corre lates
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3 1 2-6. H oos A, Lewis J L, U rist MJ, Shaha AR, H a w k ins WG, Sh a h J P e t 01. D esmoid t u m o u rs of t h e head a n d n eck - a c l i n ica l study of a ra re e ntity. Head and Neck. 2000; 22 :
6.
Early diagnosis and treatment may lead to a better outcome with improved local function
1 255-67. Wi l l iams JD, Sclafa n i AP, S i u pc h i nski 0, Douge C. Eva l uation a n d ma n a g ement of the l i n g u a l thyroid g l a nd . Annals o f Otology, Rhinology, and Laryngology. 1 996; 1 0 5 :
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Oncology, Biology, Physics. 1 99 8 ; 4 1 : 371 -7. Sessions DG, Le nox J , Spector GJ , Chao C, Cha u d ry O-A. Ana lysis of treatment resu lts fo r base of ton g u e ca n ce r. Laryngoscope. 200 3 ; 1 1 3 : 1 252-61 . Robbins KT, K u m a r P, Reg i ne W F, W o n g FS, Wei r A B , F l i c k P et 01. Efficacy o f ta rg eted s u p ra dose cisp lati n a n d conco m ita nt rad iation thera py for a dva n ced head a n d neck cancer: The M e m p h i s experie nce. International Journal of Radiation Oncology Biology Physics. 1 99 7 ; 3 8 : 2 63-71 . Ca l a i s G, Alfonsi M, B a rd et E, S i re R, G e rma i n T, B e rgerot P et 01. Rando m ised trial of rad iation thera py conco m ita nt che mot h e ra py and rad iation thera py fo r a dva nced sta ge o ro p h a rynx carci noma. Journal of the National Cancer Institute. 1 999 ; 9 1 : 208 1 -6. B row m a n G P, H odson D I , Macke nzi e RJ , Bestic N , Zu raw L. Choosi n g a conco m itant chemothera py and rad ioth e ra py reg i m e n for sq u a m o u s ce l l h e a d a n d n e c k cancer: A systematic revi ew of the p u b l ished l i te rature with su bgro u p a n a lysis. Head and Neck. 2001 ; 2 3 : 579-89. B ru n i n F, M osseri V, J a u l e rry C, Poi nt D, Cosset J IVl , Rod rig u ez R. Can cer o f the base o f ton g u e : past a n d futu reo Head and Neck. 1 999 ; 2 1 : 7 5 1 -9. B rown J S, Zuyd a m AC, J o n es DC, Rogers S N , Va u g h a n ED. Fu ncti o n a l outcome in soft p a l ate reconstruction usi n g a rad i a l forearm free fla p in conj u n ction with a su perio rly based p h a ry n g e a l fl ap. Head and Neck. 1 997 ; 1 9 : 524-34. Kim ata Y, Uchiyama K, Sakura ba M , Ebi h a ra S, H ayashi R, H a neda T e t 01. Ve l o p ha ry n g e a l fu n ction after m icros u rg ica l reco nstruction of latera l and superior oro p h a ryng e a l defects. Laryngoscope. 2002 ; 1 1 2 : 1 037-42. J o n es AS, Ste l l P M . Sq ua mous carcinoma of t h e poste rior p h a ryngeal wa l l . Clinical Otolaryngology and Allied Sciences. 1 99 1 ; 1 6 : 462-5. Jol J K, Qua k JJ , d e Bree R, Lee m a n s CR. La rynx prese rvation s u rgery for a dva n ced poste rior wa l l carci noma with free fla p reco nstruct io n : critica l a p p ra isa l. Oral Oncology. 2003 ; 3 9 : 552-8. Na kats u ka T, H a ri i K, Ebi h a ra S, Asa i M , H ayash i H, Yos h i zu m i T. Laryng e a l prese rvation su rg ery u s i n g a free fl a p pat � h fo l lowing resection of a carci noma of the poste rior wa l l of t h e oro p h a rynx. Annals of Plastic Surgery.
1 99 8 ; 4 1 : 2 89-94.
Chapter 1 93 O ro p h a ry n g e a l tumou rs I 2597 1 02.
Lyd iatt W M , Kra use D H , Co rd e i ro PG, Hidalgo DA, S h a h J P. Poste rior p h a ry n g eal carci noma resection with l a rynx p reservation a n d ra d i a l fo rea rm free fl a p reco nstru cti o n : a
pre l i m i n a ry repo rt. Head and Neck. 1 99 6 ; 1 8 : 50 1 -5. 1 03 . J u l i eron M , Kol b F, Schwaab G, M a ra n das P, B i l l a rd V, Lu sinchi A et 01. Su rg i ca l m a n ag em ent of posterior p h a ry n g eal wa l l carci no mas : fu ncti o nal and o n co l og i c 1 04.
1 05.
1 06.
1 07 .
1 08.
1 09.
res u l ts. Head and Neck. 200 1 ; 23 : 80-8. J ose J, Coatsworth AP, Joh nston C, MacLe n n a n K. Cervica l node m etastases in o ro p h a ry n g ea l sq u a mous ce l l carci noma : Prospective a n a lysis o f preva l ence a n d d istri bution. Journal of Laryngology and Otology. 2002 ; 1 1 6 : 925-8. Robbi ns KT. The evo lvi ng ro l e of co m bi n ed mod a l ity thera py in head a n d neck ca ncer. Archives of Otolaryngology - Head and Neck Surgery. 2000 ; 1 2 6 : 265-9. EI -Sayed S, N e l so n N . Adjuva nt a nd a dju nctive chemothera py in the ma nagement of sq uam o u s ce l l carci noma o f t h e head a n d n eck reg io n : A m eta-ana lysis of p rospective and ra n d o m ised tri a ls. Journal of Clinical Oncology. 1 99 6 ; 1 4 : 83 8-47. Robbins KT, K u m a r P, Wong FS, H a rtse l l W F, F l i c k P, Pa l m e r R et 01. Ta rgeted chemorad iation for adva n ced h ea d a n d n e c k ca nce r : a n ana lysis of 2 1 3 patie n ts. Head and Neck. 2000 ; 22 : 687-93. H u nter S E, Scher R L. C l i n ica l i m p l i cations of rad i o n ecrosis to the head and neck s u rgeon. Current Opinion in Otolaryngology and Head and Neck Surgery. 2003 ; 1 1 : 1 03 -6. Perl m utter MA, Joh nson JT, Snyd erma n C H , Ca no ER, Myers E N . Fu n cti o n al outco m es after treatment of squa mous cel l carci noma of the base of the tong u e . Archives of Otolaryngology - Head and Neck Surgery.
2002 ; 1 2 8 : 8 8 7-9 1 . Robertson M L, G l eich LL, Ba rrett W L, G l uckman J L. Base of-to n g u e ca ncer: su rviva l , fu nction, and q u a l ity of l i fe after exte rn a l - beam i rra d i ation a n d brachythe ra py. Laryngoscope. 2001 ; 111 : 1 3 62-5. 1 1 1 . Borg g reven PA, Leeuw Vaedo nc k-de I , La ngen d ij k JA. Doorn a e rt P, Koster M I\J , de B ree R et 01. Speech outco me after s u rg ica l treatment for o ra l a n d o ro p h a ryn g e a l c a n c e r: a longitu d i n a l assessment of patients reconstru cted by a m icrovascu l a r fl a p. Head and Neck. 2005; 2 7 : 7 85-93. 1 1 2. Pa u l oski B R, Log e rm a n n JA, Co l a n g e l o LA, Rademaker AW, 1 1 0.
McCon n e l l FM, H eiser MA et 01. Su rg ical va ria b l es affe cting speech in treated patie n ts with ora l a n d oro p h a ryngeal ca nce r. Laryngoscope. 1 99 8 ; 1 08 : 908- 1 6. 1 1 3.
*1 1 4.
1 1 5.
* 1 1 6.
*1 1 7 .
1 1 8.
1 1 9.
1 20.
800-4. S ko n e r J M , Andersen PE, Co h e n J I , H o l l a n d JJ, Ha nsen E, Wax M K. Swa l l owi n g fu nction a n d tracheostomy depen dence after com bi n e d - moda l ity trea tment i n c l u d i n g free tissu e tra nsfe r f o r adva n ced -sta g e o ro p ha ry n g ea l ca n cer. Laryngoscope. 2003 ; 1 1 3 : 1 294-8. Kissu n D, M a g e n n i s P, Lowe D, B rown JS, Va u g h a n ED, Rogers SN . Ti rn i n g and presentation of recu rre nt ora l a n d o rop h a ry n g e a l sq ua mous ce l l carci noma a n d aware n ess i n outpatients cl i n ic. British Journal of Oral and Maxillofacial Surgery. 200 6 ; 44 : 3 71 -6. Machtay M , Pe rch S, M a rkiewicz D, Th a l e r E, Cha l i a n A, Gold berg A et 01. Co m bi ned su rg e ry and posto perative ra d iothera py for ca rci noma of the base of ton g u e : a n a lysis of treatment outcom e and p rog nostic va l u e of m a rg i n status. Head and Neck. 1 99 7 ; 1 9 : 494-9.
1 2 1 . Via n i L, Da m m e ijer P, J o n es AS, Da l by J E, Ste l l PM. Recu rre nce of oro p h a ry n g e a l ca rci noma a fter radiot h e ra py. Journal of Laryngology and Otology. 1 99 1 ; 1 0 5 : 24-8. 1 22. Yu e h B, Fei nste i n AR, Weaver EM, Sasa ki CT, Con cato J. Prog n ostic stag i n g system for recu rren t, persistent, a n d secon d pri m a ry ca n cers o f t h e ora l cavity a n d orop h a rynx. Archives of Otolaryngology - Head and Neck Surgery.
1 23.
1 24.
1 99 8 ; 1 2 4 : 9 75-8 1 . Lacy PD, Sp itzn a g e l EL, Picci ri l l o J F. Deve l o pme n t of a new stq g ing system for recu rre nt o ra l and orop h a ry n g e a l squamous ce l l carci noma. Cancer. 1 999 ; 8 6 : 1 397-5. I n g ra m s DR, Rhys- Eva ns P. Strateg i es for the m a n a g e m e n t of recu rrent h ead a n d neck sq u a m o u s cel l ca rci noma. Current Opinion i n Otolaryngology and Head and Neck
2001 ; 9 : 1 09- 1 3 Kim ES, Kies M , H erbst RS. N ovel the ra peu tics for head
Surgery.
1 25.
1 26.
R u h l CM, G l eich LL, G l uckman J L. S u rviva l , fu n ction, a n d q u a l ity of l i fe after tota l g lossecto my. Laryngoscope. 1 99 7 ; 1 07 : 1 3 1 6-2 1 . Rog ers SN. S urgica l p rinciples a n d techniques for fu n ctiona l reh a b i l itation after o ra l cavity a n d o ropharyngea l o ncolog ic su rgery. Current Opinion in Otolaryngology and Head and Neck Surgery. 2001 ; 9 : 1 1 4-9.
N etsc h e r DT, Meade RA. Good ma n CM, A l ford EL, Stewa rt M G. Qua l ity of l i fe a n d d isease-specific fu ncti on a l status fo l l ow i n g m icrovascu l a r reco nstruction for a dva nced (T3 a n d T4) o rop h a ryng e a l ca nce rs. Plastic and Reconstructive Surgery. 2000 ; 1 05 : 1 628-34. Mowry SE, Ho A, Lotem pio M M , Sad eg h i A. B lackwe l l KE, Wang M B . Qu a l ity of l i fe i n adva n ced oro p ha ryng ea l ca rci noma a fter c h e m o rad ioth e ra py versus su rg e ry a n d rad iation. Laryngoscope. 2006 ; 1 1 6 : 1 589-93. S m e e l e LE, I rish J C, G u l l a n e PJ , N e l ig a n P, Brown DH, Rotstei n LE. A ret rospective com pa rison of the morbid ity a n d cost of d iffe re n t reco nstru ctive strategies in ora l a n d o ro p h a ry n g ea l ca rci noma. Laryngoscope. 1 999 ; 1 09 :
*1 2 7.
.
and neck cancer. Current Opinion in Oncology. 2002 ; 1 4 : 334-42. M a g n e N, Ma rcy P-Y, C h a m o rey E, G u a rd iola E, Pivot X, Sch n e i d e r M et 01. Co ncomitant twice-a-day rad iothera py a n d chemothera py in u n resecta b l e head a n d neck ca n cer patients: a long-term q u a l ity of l ife a n a lysis. Head and Neck. 2001 ; 2 3 : 678 - 82. Licitra M, Bernier J, G ra n d i C, M e rlano I\J , B ruzzi P, Lefebvre J L. Ca n ce r of t h e o ro p h a rynx. Critical Reviews Oncology/Hematology. 2002 ; 4 1 : 1 07-22.
in
194 Tu mou rs of the larynx
MARTIN A BIRCHALL AND LAYSAN POPE
2619
I ntrod uction
2598
Best clinical practice
Pathology
2599
Deficiencies in current knowledge and areas for future
2619
Risk factors for squamous malignancy
2603
Diagnosis
2603
Acknowledgements
2619
Management of laryngeal squamous cancer
2609
References
2619
Key points
2618
research
SEARCH STRATEGY The Cochrane database was sea rched for relevant systemat i c reviews and further ' Cochrane ' ev i dence gleaned from the proceedings of National Otorhinolaryngology Trials hypopha rynx) and 1999
Office study days held
in
Newcastle in
1997
(Larynx and
( Managemen t of the neck). Review papers in the key areas of pathology, d iagnos is , management
of T3 and T4 squamous cell cancers and rehabilitation were sought , reference lists examined and best level of evidence extracted. Expert opinion was sought by telephone and
e-mail consultation in the areas of pathology, radiology and
radiotherapy. Consensus views on best pract ice were derived from a variety of UK and US documents.
INTRODUCTION
regular education, mechanisms for early detection and systems for continuing care after treatment,. especially
T he starting point, therefore, is to give
Laryngeal carcinoma is the most common head and neck
laryngectomy.
cancer worldwide. As previously undeveloped countries
otolaryn gologists a sound training in the management of
acquire more economic strength, so access to cigarettes and
lar yngeal cancer.
alcohol has increased . Hence, countries such as C hina are now facing incidences of this disease at least as high as those in co untries with long-standing strong economies. Within
Without a
functionin g larynx, quality of li fe is hu gely
affected . Fortu nately, the ava ilabi h ty of
a
large number of
treatment options in the twenty- first century mi nimizes rep lace )
developed countries, the mean age of the population is
(but
increasing due to improvements in health and the standard
However, the im pact on voice , swallowing and psychol
does
not
the
need
for
laryngectomy.
of living, this ag a i n will lead to a rise in the incidence of
ogy,
laryngea l cancer. Nonetheless, for the average physician ,
estimated. All of these areas requi re detailed preoperative
including general pract it i oners in the UK, laryngeal cancer remains a rare disease an d understanding of its presentation
or impl ications for their patients is generally low.
The onus on otolaryngologists is to ensure effective networks to assist local services, no matter how far from the tertiary ' head and neck
centre '.
These should include
amongst other domains, should
not be
under
assessment, counselling, peri trea tment care and post treatment rehabilitation.
Unlike some other areas of
surger y, rehabilitation often continues for the lifetime of the patient, r � quiring not only the effective networks advocated here, but also the resources and skilled staf f.
provision of
necessary
Chapter 194 Tumours of the l arynx
This chapter attempts to cover the main areas of diagnosis, treatment and rehabilitation of laryngeal cancer in its various guises. However, as with the other chapters in this edition of Scott-Brown's otolaryngology, head and neck surgery, a high emphasis has been placed on real evidence-based medicine.
PATHOLOGY Requirements for pathology P R E PA R I N G SPECIM ENS FOR T H E PATHOLOG I STS
Guidelines for the preparation, analysis and reporting of head and neck cancer were published in 2005 by the Royal College of Pathologists and are available at www.rcpath. org/resources/pdf/HeadNeckDatasetJun05.pdf. Partial or total laryngectomy specimens and asso ciated neck dissections should be orientated by the surgeon and pinned to cork or polystyrene blocks. The surgeon should indicate surgically critical margins and identify the general territories of nodal groups in neck dissection specimens (e.g. metal tags/sutures). Digital photographs are a useful adjunct to show the resection bed. Request forms should include demo graphic data, duration of symptoms, treatment intent, reference to previous pathology reports and an annotated diagram. There are no guidelines as yet for dealing with the small, sometimes piecemeal specimens resulting from laser excision of low bulk tumours. Nevertheless, it is vital that the histological assessment of the excised specimen is accurate, as clear margins are usually only a few millimetres in thickness. This requires a close liaison between surgeon and pathologist, with correct orientation and minimal distortion of the specimen. One method that avoids pins, excessive shrinkage and curling, is to glue the specimen to a dehydrated vegetable template. [H/*] A study from Glasgow has shown that system atically dehydrated cucumber slices offer the best base in this context. However, good results have also been obtained with gluing or pinning specimens directly on to card or cork templates.
PATHOLOGICAL M A N AG E M ENT OF SPEC I M EI\J
Surgical margins of larger specimens should be painted with Indian ink or other appropriate dye. Horizontal slices,S mm thick, provide optimal demonstration of the relationship between the tumour and the laryngeal cartilages. Sagittal sections are recommended for supra glottic carcinomas to demonstrate the relationship to the base of the tongue. A standard reporting sheet is provided by the Royal College of Pathologists, and copies are sent to Cancer Registries. [*]
I 2599
Benign tumours PAP I LLOM AS
Papilloma (recurrent respiratory papillomatosis (RRP)) is the most common benign neoplasm of the larynx (adult prevalence is approximately one in 120 cases in the UK). Juvenile papillomas are covered in Chapter 91, Juvenile onset recurrent respiratory papillomatosis. The adult form presents most commonly in young adults (18-39 years old) with hoarseness or following biopsy of an incidentally discovered laryngeal 'polyp'. Although papillomatosis may occur throughout the airway, it is more commonly seen at the junction of the respiratory epithelium with the squamous epithelium, generally at the glottis.1 Papilloma disease within the aerodigestive tract is caused by the human papilloma virus (HPV), which can be detected in macroscopically normal mucosa both from papilloma patients and normal controls. The virus infects the epithelial cells of the larynx and triggers cell proliferation resulting in a warty growth. The mechan isms responsible for the variability in the clinical course and the persistence of latent HPV infection remain unknown. The most common subtypes of HPV detected are 6c-f and 11, which share 85 percent of their genome. These subtypes are probably nonmutagenic, as they do not integrate their DNA into the human genome, unlike for example types 16 and 18. Experiments with laryngeal cells infected with HPV in culture suggest that the highly unpredictable behaviour of HPV-infected laryngeal epithelium may be the result of defective antigen presentation to cytotoxic T cells. This might be a fruitful route for therapy in the future. Furthermore, the recent advent of a promising vaccine for 'high-risk' HPV infection of the uterine cervix2 raises the possibility of a similar approach to benign respiratory papillomatosis. Surgical management aims to debulk tumours, origin ally by microforceps, but in recent decades with lasers. Unfortunately, the growths recur regularly, requiring repeat operations. Papilloma recurrence can occur up to 30 years after remission.3 Adjunct medical treatments, aimed at containing the virus and growth of tumours, include indole-3-carbinol or its dimer diindolylmethane, interferon, podophyllum, cidofivir or photodynamic therapy. Photodynamic therapy has been reported to limit the recurrence rate (see Chapter 58, Laser principles in otolaryngology, head and neck surgery).4 Preventive and therapeutic vaccines hold promise for eliminating the virus, but previous attempts using attenuated HPV have met with little success. [H*IH1*]
U N COM MON BENIGN TUM OURS
Detailed analysis of all uncommon tumours of the larynx is beyond the scope of the present chapter. However, a list of such tumours with summary information and useful references is given in Table 194.1. [H/*]
2600 I
PART 1 7
Table 194.1
H EAD A N D N ECK T U M O U RS
R a re b e ni g n neo p l asias affecting the l arynx.
Type of tumour
Rep orted
cases
Aetiology
Clinical features
Reference
Affects the you n g. Prese nts as hoarseness or a i rway d ifficulty. C l i n ica l cou rse h i g h ly va riable. P l ethora of treatments, i n c l uding s u rgery, laser, i nte rfe ron, m u m ps vacci nes, p h otothera py and radiation Cricoid ca rt i l a g e m ost com mo n ly affected.
5
La ry n g ea l p a pil loma
M ost co m mo n
H u m a n papi l l o m a virus (type 6, 1 1 ). Poss i b l e in utero tra nsm ission.
Chondroma
1 00 + cases
6-7th decade. More freq uent in m en 4:1
Pa rag a n g l i o m a
80 cases
4-6th decade. M o re fre q u e nt i n women 4:1
Benign sch w a n noma
1 00 cases
R are ly associated with n e u rofi b ro matosis I
N e u rofi bro ma
30 cases
Associated with neu rofi b romatosis I
O n cocytoma
R a re
Leiomyoma
35 cases
Arise from smooth m uscle
R h a bdomyoma
30 cases
Arise from striated m uscle. Divided i n to foeta l o r adu l t type
Lipoma
1 00 cases
Sal iva ry g l a nd neoplasm G ra n u lar cel l tu mours
20 cases
Pleomorp h ic adenoma
2 0 cases
Derived from schw a n n ce l ls
H a e m a n g iomas
J uve n i l e and adu lt fo rms
Present com mo n ly w ith hoarse n ess. Differentiation w ith m a l i g n a n t l esion is difficu lt. Excision is cu rative Arise from o n e o f t h e two-pai red normal p a rag a n g l i a in the lary n x. Usua l ly p rese n t with hoarsen ess. Functiona l paraga n g l ioma, although repo rted, a re exceedi n g ly ra re. H i g h ly vascu l a r l esions, w h ich p rese nt s u b m ucosa l ly. Treatment is with conservative su rg ical excision Com m o n ly i nvolve the s u p rq g l ottic l a rynx a nd can l ead to u p p e r a i rway obstruction. Cure is achieved by co m p lete s u rg ica l excision A sma l l percentage m ay undergo m a l i g nant tra nsformation Predom i n antly fou nd in the su p rag l ottis. Endoscopic excision i s g e n e ra l ly cu ra tive Predisposition fo r the su p ra g l ottis. Treatm ent i s local excision, often by e ndoscopic resection Foeta l type usua l ly prese nt in chi ldhood
S u p rag lottic distri b ution. M a n ifests w ith dysphagia, dyspnoea a nd hoarsen ess Present i n s u p ra g l ottic o r s u b g l ottic struct u res S u b m u cosa l i n orig i n . Present with h o a rseness .. Up to 15% may be m u ltifoca l . Rare ly m ay u nde rgo m a lig n a n t tra nsfo rmation (2%) Juve n i l e fo rm g e n e ra l ly associated w ith
6
7
8
9 10
11
12
13 14 15
cutaneous l esion. Large tumours m ay req u i re a tracheosto my u nt i l t h e i r n atu ral reso l ution
Malignant SQUAMOUS C E L L CAR CI NOMA
Laryngeal cancer is the eleventh most common cancer in men worldwide, but is relatively uncommon in women.
However, there is now a trend towards a proportional increase in female numbers compared to males in the UK, probably secondary to increased tobacco consumption. Squamous cell.carcinoma is by far the most common type of tumour, comprising 90 percent or more of all laryngeal malignancies in large series.
Chapter 1 94 Tumours of the larynx I
as was shown as long ago as 1969 by Kirchner's laborious
Pathology Macroscopically, larynx
may
attempts
be
squamous cell cancer exophytic
or
(SeC) of the
endophytic.
However)
to correlate such appearance to behaviour
have been unconvincing.16 Microscopically, it is char acterized by the presence of 'prickle' cells and keratin whorls. Where tumours are poorly differentiated, their squamous origin may be confirmed
by immunohisto
chemistry, using monoclonal antibodies to one of a number
(Figure
of squamous
markers,
such
as
cytokeratin
194.1 ).17 The molecular biology of laryngeal
cancer, as with all other cancers, is the subject of much Current research.
whole organ dissections.
h
inevitable. This was perceived to be due to the lack of an inner perichondrium in that area. However, recent work
has shown that the ligament is in fact an effective barrier, but it is extension superiorly and inferiorly (via subglottic wedge and thence cricothyroid membrane) that worsens prognosis. Direct spread may continue via the anterior commissure to the opposite cord, or may extend poster iorly to invade the arytenoid cartilage. Glottic tumours be
confined
embryological
Laryngeal squamous cell cancer has characteristic patterns of spread depending on the site of origin. Local spread is along tissue planes, while lymphatic spread is guided initially by the boundaries between embryological anlagen
III-VI), notably at the free edge of the glottis. Yet,
despite long-held beliefs, there is no true anatomical barrier to check spread between the supra- and subglottis,
18
Historically, glottic cancer spreading to the anterior commissure was feared, because early invasion throuO'h Broyle's ligament directly into cartilage was thoug t
may
Spread
(arches
2601
to
Reinke's
boundary
space
superiorly
by and
the
above
the
conus
elasticus inferiorly. In order to reach the paraglottic space and thence gain an easy passage cranially and caudally, tumours need to transgress both the vocal ligament and vocalis
muscle.
The
laryngeal
skeleton
is
relatively
resistant to invasion, though ossified areas appear less so. Nonetheless, external extension directly through the cartilages is regularly seen. Lymphatic spread of glottic cancer is less common than at other subs! tes. It has been suggested that the lack of submucosal lymphatics in this area is responsible. However, detailed studies of mucosal
cell trafficking have
not yet been performed to confirm this. Spread, when it occurs, is to levels II, III, I V and VI. Estimates for the incidence of macroscopic lymph node metastasis by disease stage are: percent
(T3)
<5 percent (Tl), 7 percent (T2),
and
33
percent
(T4).
The
14
so-called
'Delphian' node (also known as the midline anterior metastatic node or Poirier's prelaryngeal ganglia node) is very rare, but is thought to be associated with T3 or T4 tumours with significant subglottic extension. Supraglottic cancers tend to remain locally confined (even with pre-epiglottic or nodal spread) to their subsite until relatively late. As a result, supraglottic laryngectomy
is often a viable option even for bulky tumours. However,
as noted above, there is no real anatomical barrier to inferior
spread. Indeed, the routine use of angled
Hopkin's rods during staging procedures to examine the cavity
of
the laryngeal ventricle reveals a steady
transmucosal progression of tumours just like anywhere else and permits the precise selection of patients suitable for supraglottic partial laryngectomy.
Overall, several
studies have shown that approximately
50 percent of
supraglottic cancers spread to the glottic region. The presence of foramina within the epiglottic cartilage makes this less of a barrier to spread than that presented by the other cartilages. However, invasion of the hyoid is rare (2-4 percent), meaning that it can often be retained during
operative
clearance.
'Suprahyoid
supraglottic'
carcinomas tend to invade the paraglottic spaces and Figure 1 94.1
(a,b)
the deep muscles of the tongue and spread mucosally H8:E stained sections showi ng the
architecture of invasive squamous ce l l carcinoma .
into the piriform fossae rather than anteriorly into the pre-epiglottic space. Supraglottic tumours also have a
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-
------------
2602 I
PART 1 7
H EAD AN D N ECK TU M O U RS
propensity for bilateral nodal metastasis. In reports of advanced disease, supraglottic carcinoma has a positive nodal rate of over 60 percent, compared with much lower rates of 20 percent in advanced glottic cases, and this has a major influence on the decision to perform elective neck dissections for these patients (see Management of the neck) . [****] Subglottic carcinoma tends to extend caudally and circumferentially. Fifty percent invade the cricoid and 75 percent have already extended outside the larynx by the time of diagnosis. Despite this, clinically detectable nodal metastasis is surprisingly uncommon, although a micro scopic incidence of one in three puts this disease into the category of requiring elective nodal dissection. Due to the propensity for inferior extension, nodal dissection for subglottic cancer should include the paratracheal/med iastinal nodes. Laryngectomy for subglottic carcinoma should always include removal of the isthmus and probably extend to total thyroidectomy to be completely sure of clearance. This is because one reported series has shown a thyroid invasion rate of 20 percent, although others have not replicated this. Transglottic cancer is defined by spread, both super ficially and into the p araglottic space to span all three laryngeal subsites. True primary transglottic cancer is said to originate in the laryngeal ventricle, though in practice it is impossible to be precise about the original epicentre. It is, by definition, at least T3 at presentation and subsequent consideration will therefore be alongside advanced cancers. Tracheal squamous cell carcinoma is exceedingly rare, with approximately eight cases per annum in the UK and one in Holland, despite being theoretically exposed to the same carcinogens as the larynx. Interestingly, the trachea has the highest density of immunologically active cells suggesting that mucosal immunosurveillance may be a crucial factor in defence against airway mutagenesis. A rule of thumb for spread in each site is given in Table 194.2. Table 194.2
The incidence and preferential sub site, although not the histological type, of laryngeal cancer varies with geogra phy. The incidence is highest in reports from South America and the countries surrounding the Mediterra nean, while the lowest reported is in Finland. A racial demography exists with the Afro-Caribbean population in the United States having higher rates than the white population. Interesting variations in the distribution of SCC within the larynx also occur: glottic tumours predominate in the Anglo-Saxons, while the Afro Caribbean, Indian subcontinent and French populations have approximately equal cases of glottic and supraglottic growths. These differences suggest areas of study for aetiological factors such as diet, alcohol, gastrolaryngeal reflux and viral infection. [***] LYM PHOMA
The second most common malignancy of the larynx, lymphoma, is treated differently depending on stage and histology. However, laryngeal surgery, apart from biopsy or tracheostomy, is very rarely indicated. Its importance for otolaryngologists lies in: •
•
avoiding laryngectomy for any presumed cancer until the surgeon has seen a written histology report excluding lymphoma. Examples of litigation are recorded where this rule was overlooked; ensuring that the patient with laryngeal lymphoma is referred promptly to the regional multidisciplinary lymphoma service.
For descriptions of lymphoma classification and treat ment see Tan and Bartlett, 2000.19 UN COM M ON MALIG N A N CIES
Detailed analysis of all uncommon tumours of the larynx is beyond the scop e of the present chapter. However, a list
Spread of la ryngeal ca rci no ma. Look for involvement of
Primary site
S up raglottis
Epig l ottis Epig lottic peti o l e I ntrala ryngea l m u cosa, false cord s All
G lottis
Ante rior cord Posterior cord All
S u bg l ottis
Epidemiology
Pre-e p i g l ottic space Anteri or com m issu re Pa raglottic space Voca l fold La ryngeal carti l a g e Anterior com m issu re/contra l a teral cord Thyroid carti l a g e ( Fig ure 194. 7c) a n d cricothyroid m e m b ra n e Aryten o i d carti lage/cricoa ryten o i d joi n t/poste rior com m issu re Pa raglottic space Su prag l ottic/subg lottic spread Trachea Thyroid gla n d Cervical oesopha g u s
Chapter 194 Tu m o urs of
of such tumours with summary information and useful references is given in Table 194.3. [*J One uncommon tumour worthy of special mention is the chondrosarcoma. These low-grade malignancies are difficult to diagnose as they grow slowly with smooth contours and require deep biopsies with strong biting forceps to obtain adequate tissue for diagnosis. Total laryngectomy is usually required, but partial laryngec tomies including endoscopic resection have been de scribed. Prognosis for survival is excellent.
RISK FACTORS FOR SQUAMOUS MALIGNANCY Most patients with laryngeal cancer are male (UK, 78 percent) and the most common age at presentation is the seventh decade. Some reports suggest that supraglottic cancer is proportionally more common in women than men. Laryngeal cancer is more common in areas with higher levels of social deprivation. Over 70 large case-control studies, covering most of the world populations, have examined the aetiology of squamous cell laryngeal cancer. Tobacco (relative risk (RR), 6-60) and alcohol (RR 2-6) are so dominant in these studies that the quantification of risk due to other possible factors is difficult. Good case-control studies have repeatedly shown that these factors have a multi plicative effect. Alcohol is thought to promote carcino genesis through acetaldehyde exposure, malnutrition and desiccation of mucosa. Tobacco acts via polycyclic aromatic hydrocarbons, like benzopyrene, whose pro ducts bind directly to DNA and RNA. Molecular changes include upregulation of myeloid cells. However, family history (RR 4) and 'high-risk' subtypes of HPV infection (e.g. 16: RR 3) stand out as other possible agents. A host of dietary (e.g. regional hot drinks) and occupational (e.g. asbestos exposure) risk factors have been examined in this . ·· detec ted.44 [***J way, With even weaker assoClatlOns Patients who have no exposure to alcohol and tobacco may still develop laryngeal cancers, but this is usually a decade later and there are a higher proportion of glottic tumours.
the larynx I 2603
by an expert, making it both costly and time-ineHi cient. No trials have been published at the time of writing. [*J
Glottic cancer tends to present early with voice change. In the UK, general practitioner referrals of patients with hoarseness for three weeks or more are required to be seen by a specialist within two weeks. Although this has increased referrals for benign laryngeal problems, up to 6 percent have laryngeal cancer. For supraglottic tumours, long delays in presentation to primary care are common due to the vagueness of symptoms such as 'globus' and otalgia, and therefore many are advanced and have nodal disease at the time of presentation. In the south of England, 'delays' of more than two weeks between general practitioner referral and first specialist clinic were associated with longer, rather than shorter, two-year survival (a result also seen for colorectal cancer). The reason for this is that larger tumours are easier to diaanose and are therefore sent for specialist attention /::) more promptly. A retrospective study of 581 patients with early glottic cancer showed that longer waiting times between diagnosis and the start of radiotherapy were not a significant predictor of local control, although longer treatment times increased local recurrence rates. Other endpoints, such as quality of life, were not examined. A recent systematic review45 performed metanalysis on 12 studies of delays in radiotherapy for head and neck cancer. Combined analysis also showed that the loco regional recurrence rate (and by proxy 'organ-preserva tion rate') was significantly higher among patients who received postoperative radiotherapy for head and neck cancer (including larynx) more than six weeks after surgery compared to those treated within six weeks of surgery (OR 2.89; 95% CI, 1.60-5.21). There was little evidence about the impact of delay in radiotherapy on the risk of metastases or the probability of long-term survival in any situation. Retrospective evidence also shows large potential gains from reducing breaks (planned or unplanned) in radiotherapy rather than reducing times for other parts of the pathway. [***I****J =
DIAGNOSIS Screening Attempts to screen for laryngeal cancer have met with little success as the populations who would benefit most from screening are those least likely to seek it (elderly, male, with low socioeconomic status). A recent large exercise based on improved education in Detroit yielded only the worried well. Furthermore, screening would either require nasendoscopy by an experienced endo scopist or subsequent review of endoscopic images
Clinical guidelines STAGING
Although this is covered in Chapter 181, Staging of head and neck cancer, it should be emphasized that the fifth edition of International Union Against Cancer (UICC) staging makes no mention of tumour size and there are also problems with staging a T3 tumour. For exa�ple, the staging of supraglottic cancer is presently unsatlsfactory; T3 can mean pre-epiglottic space or pyriform fossa
Table 194.3
R a re m a l i g n a nt n eop lasms of the l arynx. Incidence
Type of tumour
Epidemiology
Clinical features
Treat neck in
Reference
NO stage
Epithe l i a l
Verrucous ca rci noma
1%
Smoki n g re lated, possi ble h u m a n pa p i l loma virus a etiology
Lym phoepithel ia I ca rci noma
8 cases
Occu rs in 5-6th decade
M a l ig n a n t m e l a noma
53 cases
May be associated with skin primary, but most a re isolated l esions
Sa l iva ry g l a n d type (i nc l u d i n g a d e n oca rci noma, a d e nocyst ic, a n d aci n ic ce l l )
Less tha n 1 %
M ost patie nts a re m e n a n d over 6 0 . (The a d e n o i d cystic g ro u p has a slight pred o m i n a nce t o wo m e n )
M ucoepi dermoid
80 cases
Stri k i n g m a l e p red o m i n a n ce
Ad en osq ua mous
2 6 cases
Alcohol a n d tobacco abuse. M a l e p re d o m i n a n ce
Fo rm of we l l d i ffe rentiated SCc. Relative n o n a g g ressive w ith low m etastatic rate (n o positive n eck nodes re ported). H o a rse n ess is the pri ma ry p rese nti n g co m p la i nt. Often has pa p i l l omatous a p pea ra nce. Most fou n d i n the g lottis. Treatment pri m a rily is s u rgical excision as it is re la tive ly ra dioresista n t Lym p h oe p it h e l i a l ca rcinoma may a rise at the l a ryngeal ventricle ( l a ryngeal tonsIl ) . D e rived from both lym p h atic a n d epithe l i a l tissu e. Early t u m o u rs treated w ith rad i othera py, but in adva nced cases req u i re su rg ica l excision M a l ig n a n t m e l a n omas a re usua l ly su p ra g l ottic, p i g m e nted a n d polypo i d a l . They a re ra p i d l y p rog ressive a n d d isse m i nate w i d e ly. Treatm e nt o f choice i s co m p l ete excision. Altho�g h regio n a l lym ph n o d e m etastasis is ra re, the ove ra l l five-ye a r su rviva l i s b l e a k. Dista nt m etastatic l esions i n 80% at p resentation Often su p ra g l ottic d u e t o h i g h e r g l a n d u l a r co nce ntrati on. Su rgery is the m a i nstay of treatment. I ncide nce of cervical node spread depends on h istolog ical type, from n e a rly a l l in adenoca rci noma to 4% i n a d e noid cystic va ri a nts. Dista nt metastases a re p ri m a ri l y to l u n g a n d bone (spi ne ) Often su p ra g l ottic. G rou ped d e p e n d i n g on d i ffe re ntiation. Lower metastatic rate than co rrespo n d i n g s i m i l a r staged SCC S i m i l a r to h ig h - g ra d e m ucoe p idermoid. Te n d e n cy for e a rl y lym p h node m etastases (65%) . Agg ressive nature means the m a i nstay of treatment is su rgery with
l I..Jo
20, 21
No
22
No
23
No
24
Yes i n h i g h g ra d e form
25
Yes
26, 27
(Continued over)
Table 194.3
Rare m a l i g n a n t n eoplasms of the la rynx (conti n u ed). Incide nce
Ty pe o f tumour
Epidemiology
Clinical features
Treat neck in
Reference
NO stage
l\J e u roe n d ocri ne (incl u d i n g ca rci n o ids)
Mese nchy m a l
500 cases
Sarcomatoid ca rci noma (spi n d l e ce l l, pseu dosa rcoma, and ca rc i nosa rcoma) Leiomyosa rcoma
40 cases
Chon d rosa rco ma
600 cases
7 6 cases
M a l e pre d o m i na nce, occur i n 5-6th d eca d e
U ncerta i n ty over pathog e nesis. H i story o f smoking a n d m a l e pre d o m i nance i n the 7th d ecade
Prior irra d i ation. Neu rofi bromatosis, G a rd e n e r's, Werner's and Tu rcot syn d ro m es M a l e pred o m i n a nce, occur i n the 4-6th d ecade
rad iation. Five-ye a r su rviva l is a d ismal 1 3% M ost common symptom is hoa rsen ess fo l l owed b y n eck d iscomfort. Suprag l ottic i n most cases Low rate of ca rc i n o id syn d ro me (2-3%). M etastases occur in 1 /3 of typica l ca rci noid cases, but have a high rate i n atypica l forms The atypica l forms a re g e n e ra l l y more a g g ressive w ith poo re r outcom e Treatment is fu n d a m e nta l ly the sa me as eq u a l ly staged sq u a mous ce l l ca rci noma. S u rviva l rates s i mi l a r to SCC
Low m etastatic potentia l . Poor respo nse to ra d iothe rapy therefore pri ma ry treatment is s u rg e ry. H istol ogy can be confused with spi n d l e ce l l n eopl asia Most common i n crico i d carti l a g e. H igh i n cidence of voca l cord pa l sy, which may be bi l atera l . M etastases a re ra re but prese nt in the l u n gs or cervica l lymph nod es. Treated usua l ly with l a ryng ecto my.
Osteosa rcoma
1 3 cases
Nearly a l l cases in m e n . Has been reported fol l owing rad iotherapy fo r SCC
M a l ig n a n t histiocyto ma
30 cases
Fibrosa rcoma
R are
Su bglottic tu mou rs occu r i n the you n g e r age g roup (30-50s) I rrad iation of l a rynx
S u rviva l rates a re a ro u n d 80% Arisi n g i n the ca rti lage. Often high-g rad e sa rco mas w ith ea rly haematogen ous spread. Treatment is with wide l oca l excision a n d rad iotherapy Fast g row i n g t u m o u r g e n e ra l ly affecti n g the subg l ottis. Treatment of choice is wide loca l excision ± ra d iotherapy Pri m a ry treatment by su rg e ry. H a e matologous spread occurs but regional n o d a l m etastasis ra re
No
28
Atypica l
Yes Yes
29
No
30
No (on ly 2% have positive n eck nod es)
31
No
32
No
33, 34
No
35
(Continued over)
Table 194.3
Rare m a l i g n a n t n eopl asms of the l arynx [conti n u ed). Incidence
Type o f tumour
Epidemiology
Clinical features
Treat neck in
Reference
1\10 stage
Hae mopo ietic
liposarcoma
29 cases
? Smoking re l ated
Angiosarcoma
1 3 cases
Pri or i rrad i ation in 3 cases
Kaposi sa rco ma
Rare
H IV associated
Synovia l sa rco m a
1 0 cases
Ove r 65% of cases a re u n d e r 40
Rha bdomyosa rco m a
9 cases
I\lo n - H o d g ki n 's lymphoma
less than 1 %
Most o rig i n ate fro m B ce l l s and a re low g ra d e
Often supra g l ottic dysphonia and dysphagia a re the m a i n presenting comp l a i nts. No cases have shown cervi ca l m etastases a n d t h e treatment is s u rg e ry (ofte n l i m ited to resectio n of the lesion) Symptoms re l ated to tumou r l ocatio n , pri m a rily hoarseness. Mo s t d eve lop i n the supra g l ottis. S u rgica l excision i s the treatment of choice. Poor prog nosis with ove r 50% m o rta l i ty Occu rs i n t h e late stag es of AI DS. Most if not a l l cases have synchronous ski n lesions Present w i t h hoarsen ess, d ifFicu lty breath i ng o r dysphag i a. Ra rely a rise from the syn ovial m e m bra n e. Su rg ica l excision is treatment of choice, with n eck d i ssection i n positive lymphadenopathy. Five-yea r s u rviva l 50% Presentation is often m o re a dva nced t h a n SCC, probably d u e to th e fast rate of m i toses. H a l f of a l l prese ntations a re a i rway compromise re lated Predo minately supra g lottic w ith l oca l ization to one side. The treatment i n cl u d es
1\10
36
No
37
1\10
38
1\10
39
1\10
40
No
41
1\10
42
1\10
43
rad iotherapy ± su rgery. Chemotherapy is u sed in d i ss e m i n ated cases Acute or chronic lymphocytic
Very ra re Acu te o r ch ronic mye logenous M u ltiple myel o m a
Very ra re 3 cases
Ciga rette smoki ng
Cll i ncrease t h e risk of a seco n dary so l i d t u m o u r i n depe n d ent of treatment O rig i n ate fro m wit h i n the ca rti l a g e. Treatment is by chemotherapy. The prog nosis depends o n tumour exte nt but th e five-ye a r s u rviva l is repo rted at 1 8%
Chapter
194
Tumours of the larynx I
2607
invasion (viewed by some as more amenable to partial surgery)
or
vocal
cord
fixation,
which
is
generally
managed with total laryngectomy or radiotherapy. Like wise, early T4 tumours can actually be smaller than Tl tumours. It is recommended that the new European Laryngo logical Society classification of glottic cancer should now be used routinely.46 For all subsites, the UICC classifica tion can be ordered directly from Chapter
www.uicc.org
(see also
193, Oropharyngeal tumours). [*]
Radiology
Figure 194.2
CT scan showing an extensive laryngeal tumour.
MRI scan of a larynx, (a) coronal; (b) axial;
It lS not presently thought that all laryngeal tumours require imaging, although present and future studies of the routine use of computed tomography (CT) and/or magnetic resonance imaging (MRI) in prospective trials of all stages of laryngeal disease will test this hypothesis. Stage I and some small stage II glottic tumours can be managed safely without the need for further imaging of the primary tumour. However, some centres still prefer to image all patients as part of registration protocols or trials of new treatments. Tumour volume has been shown by some authors in retrospective series to be predictive of local
control,
and
CT or
MRI
data
using
various
algorithms can be used to generate such a volume.47,48 This may be a more important component of staging in the future. Laryngeal tumours on CT are typically of soft-tissue attenuation and enhance with intravenous contrast media
(Figure 194.2). With MRI, tumour tissue generally has high-unbound water content and hence has high intrinsic contrast on T2-weighted MRI, particularly if sequences are chosen which suppress the signal from fat
(Figure 194.3). As with CT, enhancement is usually seen following
intravenous contrast media. Peritumoural oedema, how ever, may also display contrast enhancement, which may make it difficult to define accurately tumour margins and size. For this reason, it is important that imaging is performed prior to multiple biopsies. Both CT and MRI perform well in imaging the larynx and
hypopharynx.
Magnetic
resonance
is
generally
preferred, but may be poor in restless/breathless patients, and is contraindicated in some individuals, such as those with
metallic
implants.
MRI
tends
to
overestimate
cartilage invasion, resulting in high sensitivity and lower specificity. It follows, however, that cartilage that returns a
Figure 194.3
normal signal on MRl is highly likely to be normal and
showing a large glottic carcinoma partially occluding the
this may be of particular value when selecting and
laryngeal airway.
planning
partial surgery.
underestimate
cartilage
CT,
by contrast, tends
invasion
resulting
in
to
higher
specificity . With CT, small foci of mucosal tumour may be difficult to detect. With both modalities inflammatory
and improved Z-axis r esolution and better multiplanar, three-dimensional
(3D) and 'virtual endoscopic' views.
Positron emission tomography (PET) using 2-(FI8)
and oedematous change may cause overestimation of
tluoro-2-deoxy-D-glocose
tumour extent. Helical CT has clear advantages over
used to evaluate laryngeal tumours49 even though spatial
single-slice methods, including reduced motion artefact,
resolution is relatively low. Alone or colocalized with
(FDG-PET)
is
increasingly
2608 I
PART 17 HEAD AI\JD NECK TUMOURS
CT/MRJ, it has shown some p romise in distinguishing 5o tumour recurrence from post-irradiation change.
symptoms. Paraneoplast ic phenomen a , such as peripheral
[**I*J
neuropathy and rashes are very ra re. As a result, it is
It is hoped tha t the increased a vailability of PET sca n ning
possible to provide primary care workers (and indeed the
wl11 further delineate the role of this form of imaging in
general
p lanning laryngeal cancer treatment.
'warning' sympto ms that require urgent referral to an
population)
with
a
fairly
a ccurate
idea
of
otolaryngo logis t.
Endoscopy and biopsy Outpatient
endoscopy,
GLOTI I C CAN C ER
stroboscopy
and
preoperative
It is fortunate that even the earliest glottic cancer a l ters
163,
the voice b y affecting wave pattern forms over the voca l
Assessment and examination of the upper respiratory
cord. Since normal voice production depends on the
voice assessment a re covered elsewhere in Chapters
tract; a nd 181, Staging of head and neck cancer. Once a clini ca l diagnosis of laryngeal cancer is suspected, direct exa m i nation and biopsy under general anaesthesia is ma ndatory. The evolution of dire ct laryngoscopy has been 5! chronicled by Zeitels. Suspension (whether 'true' or 'levered') microlaryngoscopy with modern endoscopic equipment is required. The examination should be fully documented, ideally with
0° and 90° photographs taken 194.4). This defines
with Hopkin's rod telescopes (Figure
a nd records the 3D status of the tumour. Adequate, multiple
biopsies
sho u ld
be
taken
with
fine
( e.g .
Bouchayel') dedicated biopsy forceps under high micro scopic magnification. This should be accomplished in such a manner as to preserve the superficial lamina propria
(SLP) of any uninvolved cord, which
for m aximal preservation of voice quality.
is essential
[H*/**/*]
i ntegrity of a six cell thick epithelium and a delicate, je lly like superfici a l lamina propria, even carcinoma in situ may produce significa nt voice change. Thus, any person with hoarseness persisting for three weeks or more (some wo uld say even less time than this) should be referred urgently to an o to laryngo logist
for exa minat i o n. The
National Health Service in the UK has implemented a fast track protocol to aid this. With increasing lesio n size, maximum phonation time decreases and with the o nset of cord fixation, breathiness may be superimposed, with va riable degrees of aspiration. Advanced lesions may lead to a irway obstruction ca using progressive dyspnoea a nd stridor. Haemoptysis is usually associated with larger t u mours. Refe rred ota lgia (via the vagal co mplex) is a sinister sign suggesting deep invasion. Dysphagia a nd odynophagia are rare in uncomplicated g l ottic cancer. Neck nodes are rarely the presenting co mpl a i nt; if present, they signify deep invasio n .
Clinical presentations SUPRAGLOTI I C CA N C ER G E N ERAL
As with other cancers, laryngeal cancer m a y present with
Voice alteration is different i n quality from tha t seen with glottic and subglottic cancer. Sm a l l supraglottic lesions
local symptoms or those due to metastatic spread to
not extending to the glottis may present with globus or
nodes or beyond. Occasionally, p atients present with general systemic signs, such as weight loss or anaemia, but
may
in laryngeal ca ncer these are rare in the absence of lo cal
foreign body sensation and parasthesia. cause
ha e moptysis.
As
tumour
If exophytic, they bulk
increases,
phonation is altered, with a 'hot potato' voice . If tum o urs extend to the co rds, then hoarseness ensues as for glott ic disease. Further extension latera lly m ay cause referred otalgia,
odynophagia
and
true
dysphagia.
However,
lesions may be asympto matic until quite large and, as
a
result, first presentation with a neck l u m p due to cervical nodal metastasis is common.
SUBGLOTI I C CAN C ER
Again, early symptoms can be vague, with a feeling of 'globus' or foreign body sensation in the thro at. Any involvement of the glottis o r recurrent laryngea l ne rves results in hoarseness. With paralysis, diplophonia may occur
with
a
shortened
maximum
phonation
time.
Therefore, this diagnosis should a lways be co nsidered in the Figure 194.4 cord.
Early squamous cell carcinoma of the left vocal
possible differential causes of 'idiopathic' cord paralysis, espe cia lly in high risk cases. Circumferent i a l
progression leads t o progressive dyspnoea and stridor,
Chapter 194 Tumours of the larynx I
2609
with markedly shortened maximum phonation times and rapid vocal fatigue. Direct extension into the thyroid may mimic a thyroid isthmus lesion.
MANAGEMENT OF LARYNGEAL SQUAMOUS CANCER Multidisciplinary teams
All recent guidelines and standards require that laryngeal cancer patients be treated in dedicated multidisciplinary teams. The minimum team as defined by the British Association of Otolaryngologists - Head and Neck Surgeons is an otolaryngologist, a radiotherapist/oncolo gist, a dedicated specialist liaison nurse, speech and swallowing therapist (at least 50 percent of time dedicated) and a dietician.52 [***1*] Figure 194.5
Carcinoma in situ
Biopsy of this lesion showed carcinoma in situ.
However, clinical suspicion of invasive disease was high, and the resection specimen following endoscopic excision showed
Carcinoma in situ (Tis, TNM, VICC) is the replacement of the full depth of the epithelium by malignant cells, without those cells transgressing the basement membrane. However, since this is usually a pathological judgement based on sampling of a small area, it is technically impossible to say whether the area biopsied represents the true limits of disease, or whether, in areas by chance not sampled, tongues of tumour invade the lamina propria. Thus, Steiner et ai.S3 have found that wide resection of areas labelled as Tis in fact demonstrated invasive cancer in over two-thirds of cases. Indeed, resected specimens of carcinoma often exhibit carcinoma in situ around the margins of frankly invasive disease, blending to varying degrees of dysplasia more distantly. The second problem facing clinicians is the existence of field change. Although the diagnosis and management of this condition in the oral cavity is well described, its management in the larynx is less clear, especially given the high incidence of occult invasive disease. Usually occurring in heavy consumers of alcohol and tobacco, field change, with areas of varying grades of dysplasia and carcinoma in situ, can predispose to multifocal and recurrent disease. 54 Combined, these two facts suggest two paradigms for the management of patients with this pathological diagnosis:
1. Tis should be regarded as part of the continuum of 'early' laryngeal cancer and managed in the same way as TI carcinoma (Figure 194.5). 2. The high possibility of recurrent disease suggests holding back the use of radiotherapy for those lesions where resection would lead to significant functional deficits, and the use of surgical techniques wherever possible.
multifocal invasive carcinoma (here, T1 b).
Nonetheless, endoscopic eXClSlOn, with or without laser, and radiotherapy appear to produce equivalent excellent results in published case series).55.56 There have been no reports of chemotherapy or novel agent (e.g. HER inhibitor) use for this condition to date. A recent large trialS? of low dose isoretinoin did not show significant reduction in the prevention of multiple primary tumours of the head and neck (intuitively most likely for those with field change and carcinoma in situ), There are reports that dysplasia and even Tis may reverse with the removal of alcohol and tobacco. Serial microflap excision of tumours resulted in progressive reduction in stage of dysplasia, although the possibility that gradual removal of irritants was responsibll: remains. 58 Thus, following treatment of a defined lesioll, as much assistance as possible should be given to he patient to withdraw these addictions. The emergence of extra-oesophageal reflux as a possible causative agent suggests that reduction of exposure to pepsin and acid by lifestyle changes and use of Gaviscon@ or proton-pump inhibitors would be reasonable also. Clearly, given all the above, careful nasendoscopic follow-up of patients with carcinoma in situ is essential, with the possibility of multifocal change kept in mind. However, how often and for how long such patients should be followed up has not been demonstrated. A rational approach would be to introduce the interventions above and adopt more rigorous follow-up in those patients who are unable, despite the best possibk support, to stop smoking and drinking.
26 1 0 I
PART 1 7 H EAD AN D N EC K TU M OURS
E a rly glotti c ca n cer : Choice of tre atm ent Dey
et ai.59 has p ublished a systematic review comparing
ra dio therapy, open surgery and endolaryngeal excision (with or without laser ) for early (Tl, T2 a) glottic laryngeal cancer. All are presently accepted mod alities of treatment and the published large case series of each treatment suggest that they confer similar s urvival advantages. Thus, at present, a state of clinical equipoise exists. Only one 60 rand omized controlled clinical tria1 was identified, which compared
open
surgery
and
radiotherapy
a mong
a
substantial number of p atients with early glottic laryngeal cancer
(Table 1 94.4), although it was limited by concerns
about the adequacy of treatment regimens with deficien cies in the reporting of the study design and analysis. The reviewers concluded that, despite much being written by enthusiastic exponents of one treatment or another, there is currently insufficient evidence to guide management decisions on the most effective treatment. Endolaryngeal resection of early glottic tumo urs is becoming more common and a well - designed, multicentre, randomized controlled trial is warranted. Mahieu et ai. 6 1 described 46 patients with complete
Figure 1 9 4.6
Endoscopic a ppea rance of the larynx three
months following laser resection of left Tl a mid-cord squamous cell carcinoma (trans-ligament resection) .
laser vaporization of the cancer of which three recurred
( Figure 1 94. 6 ) . With vapo rization, assessment of residual disease is impossible. Based on t hese limited data, this method cannot be recommended.
laryngectomy ( HP L ) , 44 by primary radio therapy and
Where tumours involve the anterior co mmissu re 62 o r 6 arytenoids, 3 consensus seems t o be that prognosis is
locoregional control fo r the N +
worse. Some advocate open p artial surgery p referentially in su ch cases, although Desloge and Zeitels64 suggest that
reserved fo r patients with p ositive neck nodes.
fear of the anteri or commissure is sim p ly related to lack of a dequate exposure at endoscopy. Various radiotherapy regimens have been used, but typically involve the use of small field external bea ms to a total dose of between 40 and 60 Gy over fo ur to six weeks dep ending on the centre.
[ ****1***]
Early s u praglottic cancer : C hoice of tre atm ent Of a to tal of
lent fo r the NO p atients, but HPL s h owed better results in p atients
(p < 0 .0024) .
They co nclude d that operative management should be Unfortunately, only abo u t 30-40 percent of patients who might benefit from p artial laryngectomy ( o f what ever
sort)
are
medically
( respiratory
function)
and
anatomically (shape of neck) suitable. These patients must be able to tolerate various degrees o f postopera tive 66
asp iration.
[ ***]
HPL horizontal partial laryngectomy
T3 and T4 ( i ncluding transglotti c) cancer : Cho ice of tre atm e n t
89 p atients described retrospectively by
Gregor et al. , 6 5 26 were treated by horizontal par tial Ta b l e 1 9 4.4
19
by total laryngectomy. Locoregio nal co ntrol was equiva
Results of randomized controlled trial of surgery
versus radiot h era py for early glottic laryngeal cancer.
Five-year su rv iva l
T1 T2
Five-year d isease-free survival
Tl T2a
S u rg ery
Ra d i oth era p y
(0J0)
(0J0)
1 00 97 .4 1 00 78.7
9 1 .7
O P E RATIVE T R EATM ENT
Detailed descriptions of endoscopic surgery can be fo und 6 Steiner and Ambrosch, 7 an d of partial laryngeal 6 surgery in Weinstein et al. 8 However, broad outlines are
in
presented below. There are no
rand omized controlled trials
( RCT)
co mparing different surgical treatments for advanced laryngeal cancer, but the Veteran's Administration Trial69
88.8
and text books such as Weinstein et a i. 6 8 recommend total
71 . 1
laryngectomy with voice rehabilitation for T4 tumours
60. 1
" Si g n i fi ca nce is o n ly obtai ned for d isea se-free survival (ch i 1 .8 p = 0.036],
and are in clinical equip oise between laryngectomy and radiotherapy fo,! T3 tu mours. The latter are clearly an
w h i ch would n o t h ave been sign ificant with a two-ta i l ed test Reproduced
impo rtant subject fo r Cochrane review and subsequent
from Ref. 60, with permission.
multicentre trials.
Ch apter
Studies of partial surgerl5 rarely describe complica tion rates, especially voice effects and postoperative aspiration. Where high rates of aspiration after partial surgery are reported, most patients have had adjuvant radiotherapy. All future prospective randomized trials should include voice, aspiration, performance status and quality of life measures. [ ***J RAD I OTH E RA PY
One RCT,70 which included all head and neck squamous cancers, showed 'evidence of a trend towards increasing benefit with more advanced T stage' (p 0.002) with the use of continuous, hyperfractionated, accelerated radio therapy ( CHART) for laryngeal cancer by comparison with conventional radiotherapy regimens. However, very few T l laryngeal cancers were actually included in the trial and this finding therefore requires further study. Most retrospective reports comparing regimens suggest that more than 2 Gy per day and a total course of less than 35 days improves survival. Robertson et al.'s 1993 stud/ I of 303 patients with T 1 cancer is recommended for further reading and includes a good discussion on radiobiology. After radiotherapy, tumour recurrence tends to present in a 'tentacular' invasion front, such that even in centres performing a high volume of partial laryngeal surgery, only about 20 percent of patients who are salvageable post-irradiation receive conservation surgery rather than a total laryngectomy.72 Thus, most patients who fail the first treatment protocol finish up with a total laryngect omy. [ ****I***J =
C H E MOTH E RA PY
Early metanalyses of the use of chemotherapy in head and neck cancer gave this treatment a bad reputation. Stell and Rawson73 found a survival advantage of 6 percent, but a death rate from complications of chemotherapy of 7 percent. However, this and other studies did not segregate tumours by staging and included studies of adjuvant, synchronous and neoadjuvant settings, also individual patient data analysis was not undertaken. More recently, Pignon et az.74 used individual patient data metanalysis of high quality trials and found an 8 percent survival advantage in the synchronous setting, whilst neoadjuvant and adjuvant chemotherapy conferred small, nonsignifi cant advantages. These advantages appeared to decrease for patients aged over 60 years. Again, however, there was no separate consideration of laryngeal cancer. In 1984, the Department of Veterans Affairs Coopera tive Studies Program began a trial in which 332 patients with resectable squamous cell carcinoma of the larynx were randomized to receive either standard surgery followed by radiation therapy or neoadjuvant therapy (three cycles of cisplatinum and 5-FU) followed by 70 Gy radiation therapy for those achieving a greater than 50
1 94 Tu m o u rs of the larynx I 261 1
percent tumour response to the chemothera py (J·udaed b after the first two cycles).69 Although there were fewer local recurrences (p < 0.0005) and distant metastases (p 0.016) in the chemotherapy arm, estimated two-ye ar survival was very similar (68 percent) for both treatment groups (p 0.98). Importantly, only 36 percent of patients in the chemotherapy arm required total laryngectomy (primary or salvage) within two years. These results were interpreted as suggesting that chemotherapy could be effective in avoiding laryngectomy in a large proportion of patients with advanced laryngeal cancer. However, follow-up time was relatively short and there was no arm for radiotherapy only, which effects may have been responsible for the laryngeal preservation. Longer term, they found that neoadjuvant chemotherapy was well tolerated and did not compromise either the treatment that followed or the survival of nonresponding patients who underwent salvage surgery. Quality of life studies suggested slightly better results with the chemotherapy arm, but the proportion of patients surviving and contactable by the time this secondary analysis was performed was small ( 25 and 21 in each group, respectively).75 In 2001, a phase III randomized trial from Italy compared alternating chemoradiotherapy ( ALT) with partly accelerated radiotherapy ( PA-RT) in locally ad vanced ( 'unfavourable stage II', stage III, IV) squamous cell carcinoma of the head and neck. Actuarial three-year overall survival and progression-free survival were 37 and 35 percent, respectively, in the ALT group and 29 and 27 percent, respectively, in the PA-RT group (nonsignifi cant). However, there were significantly fewer mucosal and skin side effects in the alternating chemoradiotherapy group? 6 [ ****J In 2003, the Radiation Oncology Group and Head and Neck Intergroup published the results of a trial to compare radiation alone with induction and synchronous chemotherapy in the treatment of stage III and IV laryngeal cancer?7 A total of 518 patients were enrolled and evaluable (number of eligible patients approached was unreported). The inclusion criteria were that 'the patient would have merited laryngectomy', but specifically excluded patients with tumours extending through the thyroid cartilage or into the base of tongue ( assessed by CT scan and clinically). Since these were stage III and IV, rather than T3 and T4, some tumours were actually restricted to local disease, albeit with nodes. The primary endpoint was preservation of the larynx. Median follow up was 3.8 years, so five-year survival data are incomplete, although no obvious differences were seen at this stage, there were significantly better locoregional control and laryngeal preservation with synchronous chemoradiation ( 5-FU plus cisplatinum). The results appear very clear, but the significant increase in toxic side effects seen with combined chemoradiation and the absence of validated voice and quality of life data, make it difficult to assess the functionality of the preserved larynx. It is unclear why the =
=
26 1 2 I
PART 1 7 H EAD AN D N ECK TU M O U RS
authors reported at a median follow-up time of
3.8 years,
as co mp lete five-year follow up would not have been far away and
would have increased
the strength
of the
observations. Hence,
in
this
group
o f rando mized
trials
and
metanalyses, synchronous chemo therapy and radiother apy seem to have significant advantages for advanced laryngeal cancer in comp arison with o ther treatments. On the o ther hand, the toxicity of this combined treatment means that it can only be o ffe red to relatively healthy p a l ienls.
Imp o r tan lly,
keeping
the
larynx
after
lhis
regimen may not correlate with future quality of life
F i g u re 1 9 4.7
and voice strength. F uture trials must include ro bust
tu mour.
Pathology speci m e n s h o w i n g exten sive l a ryngeal
measu res of these two outcomes, as well as measures of loco regional control and survival.
[****]
Operative p roced ures EN D O SCO P I C R ES ECT I O N
End oscopic treatment should
only b e undertaken by
clinicians fo rmally trained in the p roced ure who treat sufficient numbers per annu m to be able to au di t their results ( a minimum of ten new cases per annum has been suggested) . The highest possible specification equipment should be used. If cold steel excision is to be employed ( as with small free margin tumo urs) , then ded icated micro la ryngeal instruments are necessa ry.
If a carbo n dioxide
laser is used, it should have very fine focussing and power co ntrol. Charring and damage to the
SLP should be
strenuously avo ided. The use of submucosal vocal fold infusion with saline helps delineate the extent and depth of penetration of such lesions and increases the ' heat sink' for l aser excision. Specimens should be ca refully o rientated for p athological examination as ab ove
(Figure 194.7) .
For glottic lesions, endoscopes should have a sharply right-angled anterior pole to gain the best possible access to the anterior commissure. In p art, the poor reputation of anterior commissure tumo urs may simply have been d ue to the difficulty in visualizing this region. The supraglottis, on the o ther hand, is oval in cross-section and so oval laryngoscopes should be used here. For larger sup raglottic lesions, a distending scope is extremely useful and a device for applying vascular l igatio n clips should be available in case the in ternal branches of the laryngeal vessels are enco untered
(Figure 194. 8) . Given the variability in
tumours and normal anatomy of the upper respiratory tract, a wide range of endoscopes is required a nd, since familiarity with these is necessary, these techniques a re not recommended for small volume p ractices. An i mpo rtant concern has been the s upp osed safety of
F i g u re 1 9 4 . 8
Large T4 subg l ottic s q u a m o u s ce l l ca rci n o m a .
even b ulky gl ottic tumo urs can be safely removed via an endoscopic manner
a nterolateral
in an en bloc bloc resection wherever
laryngectomy
(Figure 194.9). Such
en
possible sho uld be enco uraged for the time being, until the safety of dividing specimens still attached to the patient is confirmed.
If the laser is employed it is imperative that the
risk of airway fire is min imized, by using specialized resistant tracheal intub atio n tubes, a ir ventila ti on, and wet swabs in the pha rynx and larynx.
[**]
removing tumou rs piecemeal. For large tumours , as well as some small ones, this is certainly the easiest way. However, the scientific basis fo r this belief, which challenges known oncolo gical principles, is weak, and more research is 1 required here. Meanwhile, ZeitelsS has demonstrated that
PART I A L LARYN G ECTO MY
At least
40 d iffe rent types of partial laryngectomy have
been described . With this number of varieties and strict
Chapter 1 94 Tu mou rs of th e l a rynx '
261 3
Pa rti a l vertica l proced u res
Cordectomy, with resection of the entire cord up to the vocal process of the arytenoid, may be achieved by an open approach via a laryngofissure. A tracheostomy is not required. Frontolateral laryngectomy extends cordectomy to take in that part of the thyroid cartilage into which the anterior commissure inserts, whilst anterior frontal laryngectomy removes this region together with part of both cords. Hemilaryngectomy removes a vertical block of larynx to include one cord (occasionally including arytenoid) and the anterior two-thirds of the ipsilateral thyroid cartilage. Requirement for a temporary tracheost omy varies. Although these operations have been superseded by endoscopic approaches in many countries, they still retain a place for patients with glottic lesions where radio therapy is not preferred and where it is not possible to insert suspension laryngoscopes for any reason. Suprag lott i c l a ry n gectomy
Fig ure 1 94.9
End oscopic a nte ro late ra l l a ryng ecto my in a n
e n bloc m a n n e r.
selection criteria, it IS not surpnsmg that there is no randomized trial evidence of their efficacy, either by comparison with radiotherapy or with one another. Case series tend to be small and from single institutions, if not single operators. This makes evaluation and comparison of results difficult. Operations vary in ambition from cordectomy to near-total laryngectomy. The general aim of these procedures is to perform oncological clearance of tumour with as much preservation of normal voicing and swallowing as possible. However, it must be emphasized that: •
•
•
•
survival is more important than voice, and if in doubt a more radical procedure is better than one with positive margins; partial laryngectomy requires experience and training, as well as adequate numbers of operations passing through the department to maintain operative and rehabilitative expertise; with all partial laryngeal surgery, patients must have good pulmonary reserve and, crucially, a positive mental approach to their ( sometimes prolonged) rehabilitation, both in terms of speech and swallowing; the more radical partial laryngectomies should be avoided in patients who have been previously irradiated.
? requsition for SL
As with much surgery, success depends on knowing which patients to select for which operation. Nowhere is this more the case than in supraglottic laryngectomy. The recent advent of routine CT IMRI and 90° Hopkins rod endoscopy in the staging process before treatment, has made it possible to select with increased accuracy those patients in whom the tumour does not transgress the corner of the laryngeal ventricle, nor extend excessively into the paraglottic space in either direction. Staging endoscopy must also assess the mobility of the arytenoids, fixation of which contraindicates the operation. Nor must tumour extend into the suprahyoid part of the epiglottis, as this affects the ability to achieve good clearance and diminishes the chances of normal swallowing postoperatively. Following tracheostomy and raising of flaps, the supraglottis is excised en bloc with cuts through both valleculae, aryepiglottic folds and ventricles (with at least a 3 mm margin inferiorly) and removal of the upper half of the thyroid cartilage and all the epiglottis. As discussed below under Management of the neck, the operation is usually carried out with a bilateral selective neck dis section (NO clinically) or more radical neck dissections if positive nodes are present (N +) . It is perfectly possible to carry out supraglottic laryngectomy by endoscopic means, especially with the aid of a distending laryngoscope (Figure 194. 10) . This is a time-consuming, but satisfactory procedure, which re quires clipping of the internal branches of the superior laryngeal vessels ( and consequently dedicated equipment to do this) . Although this method of resection has been criticized for removing the tumour piecemeal, published series so far demonstrate comparable local control and survival as with the open method. A further advantage is avoidance of a tracheostomy in 90 percent of patients. Neck dissection can be carried out simultaneously or delayed.
2614
I PART 1 7 H EAD AN D N ECK TU M O U RS
radiotherapy. He reports 70-80 percent five-year survival and the vast majority of patients do not have a long- term tracheostomy. Nea r-tota l l a ryngecto my
Described by Pearson et al. in 1 9 80, 7 9 this is a technically complex procedure to create a physiological voice shunt based aro und one m obile arytenoid. It necessitates the creation of a permanent stoma and may still result in aspira tion. As a resu lt, the initial optimism surro unding the operation has s ubsided, though in specialist hands it m ay still have a place in selected cases. A recent quality of life study revealed no significant gains over total laryngectomy with tracheooesophageal puncture and maximal voice rehabil i tation. New. 'voice preserv i n g ' opera tions for adva n ced d i sea se F i g u re 1 94. 1 0
Su prag l o t t i e l a ry n g e cto my.
S u btota l l a ryngectom y
This operation, popularized by Biller and Lawson in the 78 1 9 80s, is in effect a three-quarter l aryngectomy, combini ng supraglottic laryngectomy with vertical hemi laryngecto my on t he side of the tumour. The operatio n is used for supraglo ttic ca ncers, which involve an arytenoid a nd/o r vocal cord on one side only and do not extend significan tly into the subglottis. Tumours sho uld be no larger than 2 cm maximum diameter. Resection proceeds as above, but preserves a posterior flap of cartilage attached to the inferior constrictor muscle and removes the ipsilateral glottis/arytenoid . The cartilage flap is swung in to reconstruct the hemilarynx. S u pra cri coid l a ry n gectomy with cricohyoidopexy
This is a common operation in southern Europe, but rarely perfo rmed i n northern Europe or America. This may be as m uch d ue to the different epidemiology of laryngeal cancer in those cou ntries as the perspectives and traini ng of the surgeons concerned. According to Laccourreye e t al. ,63 ind ications inclu de T l ,2 supraglottic cancer extending to ventricle, infrahyoid epiglottis, posterior false cord , anterior commissure or glo ttis; T3 tra nsglottics; and 'selected' T4 transglottics. He also recommends avoiding the operation when there is extens ion o utside the la rynx, fixation of either aryteno id for any reason or cricoid invo lvement. The operation is designed to avoid long-term tracheostomy. Preoperative percu taneous endoscopic gastrostomy is recommended . Followi ng tracheostomy, the entire ante rior infrahyo id larynx is resected including all thyroid cartilage, but retaining at least one arytenoid intact. Care is taken to preserve both recurrent laryngeal nerves. The thyro id isthm us is included in the resection. Clos ure is by direct apposition of the cricoid and the hyoid. Laccourreye e t a l.63 combines the proced ure in nearly every case with neck dissectio ns and postoperative
The drive for an operation which provides radical onco logical clearance of advanced cancer at the same time as preserving a near-normal voice has led to m any, often co mplex, p roposals for new operations, o f which the near total la ryngectomy is but one. Recently, Delaere et aI.so have developed a procedure using tracheal au totransplantation, with vascularity provided by a ra dial forearm free- flap. Thirty-six patients have been treated with reportedly excellent results (Figure 194. 1 1 ) . I n 1 969, Kluyskens and Ringoir8 1 attempted a 'laryngeal transplant', using a nonrevascularized free m ucosal graft i nto the framework of a diseased larynx. The t u m o u r recurred rapidly. However, in 1 9 9 8 , Strome et al, s2 performed the first true laryngeal transplant in Cleveland, USA. At the time of writing the patient is eight years on and is working full- time with a normal voice, both speaking and singing. He also swallows normally, altho ugh he retains an end-stoma. This success h as stimulated further research into how this technique might eventually be brought into ro utine clinical practice.
Fig u re 1 94. 1 1
•
I n tra ope ra tive tra nshyo i d approach for a l a rg e
T 4 l a ry n g e a l t u mou r. Rep roduced w i th pe r m i ssi on from R e f. 80.
C h apter
Compl i cations of parti a l l a ryngectomy
These operations rarely result in airway obstruction, though this is possible when postoperative radiotherapy causes oedema. However, marked problems with aspira tion may occur with the larger and less competent laryngeal lumens, removal of superior laryngeal nerve supply and the effects of radiation. Where this persists, completion laryngectomy becomes necessary to prevent life-threatening pneumonia ( reports suggest about 6 percent of cases, though this may be conservative) . After subtotal or supracricoid laryngectomy, it is possible to decannulate patients fairly quickly (e.g. one week) . However, swallowing outcomes are more questionable, with only half swallowing well at one month and long term gastrostomy feeding not uncommon, especially where one arytenoid is lost. Results are better with standard supraglottic laryngectomy. As more centres gain experience with larger endoscopic resections, the true complication rates of these procedures will become clearer, although Iro et al.'s reports show relatively few problems so far. 83 TOTAL LARYN G ECTOMY
This remains the mainstay of treatment for advanced laryngeal cancer and has 1 50 years of proven oncological safety. It is largely the same operation as that first performed by Billroth in the 1 870s, but has more recently been coupled with modern rehabilitative techniques to give an improved quality of life, including voicing. 84 Preparation of the patient should include a full nutritional assessment with supplementary feeding as necessary, speech and language review and a visit by a previous laryngectomee. A week or so preoperatively, a percutaneous gastrostomy is placed, unless primary tracheooesophageal puncture is planned. As with all major cancer procedures, before anaesthesia, the surgeon checks both the pathology report and the multidisciplin ary team ( MDT) decision again, and must not proceed if either of these is uncertain. After general anaesthesia with endotracheal intubation ( or preliminary tracheostomy if the tumour is obstruct ing), direct laryngoscopy is performed to confirm the extent of the tumour. Exposure may be achieved either through a large U-shaped flap ( Gluck Sorensen) or through a midline horizontal incision ( Figure 1 94. 1 2a) . The choice of incision is determined in part on personal preference and in part on whether a neck dissection is to be added. The skin flaps are raised to above the level of the hyoid superiorly and to the level of the sternum and clavicular heads inferiorly ( Figure 1 94. 12b). If neck dissection is to be performed, it is undertaken at this point. Strap muscles are divided and the larynx isolated by ligation of vascular pedicles on both sides. By convention, the lobe of the thyroid gland contralateral to the tumour is preserved on its inferior vascular supply, although occasionally removal of a bulky tumour penetrating thyroid cartilage will necessitate total thyroidectomy. If a
1 94 Tu m o u rs of the l a rynx I 26 1 5
preliminary tracheostomy has not been performed, it is undertaken at this point and anaesthesia switched to a cuffed flexible tube placed in the stoma and passed under the drapes. Further dissection may take place from the bottom up or top down. Assuming the latter, the tongue muscles are cut from the hyoid ( Figure 1 94. 1 2d) and the epiglottis grasped through the vallecular mucosa. The mucosa is opened on the side opposite the tumour and mucosal cuts made in such a way as to preserve as much mucosa as possible whilst allowing a margin around the tumour of at least 1 cm ( Figure 1 94. 12e). Laryngectomy is completed by dissecting in the plane between trachea and oesopha gus to the level of the superior aspect of the stoma. The best stoma results are achieved if the trachea is cut directly transversely, rather than obliquely, as the latter leaves ends of cartilage exposed on which granulations may form and results in an overacutely angled trachea. The specimen is removed and sent for histology ( Figure 1 94. 1 2f) . Frozen sections may be sent if margins are thought to be closer than 1 cm at any point. The pharynx is sutured in layers without tension. Lack of tension is more important than the exact shape of the closure, which may be straight horizontal, T-shaped or straight vertical. However, there is a suggestion that straight horizontal will give the best voicing and swallowing results in the long term (Figure 1 94. 1 2g). Crucially, it is now necessary to divide the fibres of the cricopharyngeus over a 2 cm length right down to mucosa ( the use of loupes or a microscope may help ensure completeness of this) . This procedure allows the correct tension for voice rehabilitation later on. Skin closure is in layers, with drains, and a cuffed tracheostomy tube placed overnight ( Figure 1 94. 1 2h). Depending on local practice, laryngectomy may be combined with primary tracheo oesophageal puncture and passage of a Foley catheter for feeding until swallowing is resumed, usually at one week ( and following a test feed or check contrast swallow) . Subsequently, the catheter is replaced by a voice valve and speech therapy started.
Management of the neck
Consistently, the main predictor of survival in squamous cell carcinoma of the head and neck is the presence, number and extracapsular spread of lymph node metastases rather than the size of the the primary tumour. 1\10
Although contrary opinions exist, elective neck dissection is commonly performed for the management of node negative, T2-4 supraglottic cancer. Shah et a1. 85 have set an arbitrary threshold for performing neck dissection in clinically negative necks of 20 percent and this was supported by an earlier decision-analysis report. 8 6 For the
26 1 6
I PART 1 7 H EAD A N D N ECK TU M O U RS
Fig ure 1 9 4. 1 2
T h e ste ps in a tota l laryngectomy (con t i n ue d over).
la.ryrLx, therefore, this would i nclude supraglotti c ( r i sk 1 6--4 3
p ercent) t ransglottic ( 1 1-52 percent) a nd subglottic ( 1 9-65 percent) tum ou rs Some have also argued t h a t the likelihood of patient follow up after surgery should i nfluence whether ,
.
the neck is operated on.
Only retrosp ective
analyses
with
li m i ted numbers have looked at whether to perform elective neck necks
irrad.iatio� rather than neck and these are i nconclusive.
dissection in 'high r isk'
Chapter 1 94 Tu mou rs o f the l a ry nx •
26 1 7
Brazilian H ead and Neck Cancer Study Group rando. . . 1s 88 ' 89 0 f nee k d Issectl ' mIze d tna O n fo r NO disease a re the o n ly s u ch s tudies fo r head a n d neck cancer p ublished to d a t e. On this evid ence , it wo u l d seem that
a selective neck dissectio n would be the correct o p era tio n fo r l aryngea l cancer. This s t ra tegy h a s b e e n s u p p o rted recently b y
studies in
2003 by Spriano
et
al.90 showi ng a posi tive level
V n o d a l rate of 1 . 6 percent in a total o f 602 neck
dissections . However, in supraglot tic cance rs with the
prevalence fo r bilate ral nodal spread , i t i s u n clear whether one s h ould perform uni la teral o r bilateral neck d i ssec
t i ons. In a ret rospect ive st udy, Fo ote et p atients w i t h n o neck d issect i o n ,
al.9 1 co mpared
22
1 8 8 w i t h u n i lateral
dissec tion a n d 34 wi t h bilateral d i ssect ion. Cox's regres sion analysis sho wed no signi ficant d i fference in five-year actuali a l s u rvival. There are n o and
no g o o d retrospect i ve
p rospective st u d ies o f t h i s d a ta
s u pporting
bilatera l
o pera t ion, whi ch is o fte n overlo oked . Fu t u re prospec tive tr ials of neck d issection for t h e node-negative neck in laryngeal cancer sho uld fo cus on the role of senti nel node biopsy, comparing selective neck d i ssect i o n wi t h elective neck irra diat ion operation cancer.
in 'at risk' groups and whet her bilateral
co nfers
survival
advant age
in
supragl o t t i c
[**** /***]
THE N+ N EC K IN LA RY N G EA L C A N C E R
This top i c is covered in Chapter 1 9 9 , Metast a t i c n eck d i sease.
Figure 1 9 4. 1 2
The ste ps i n a to t a l la ryng ecto m y (co n t i n u ed ) .
Th e operation o f ch oice h as often been t h e mo dified r ad i ca l neck d i ssecti o n ' type fu nct ional
neck
I l l ', o ften refered to
di ssect i o n.
lym p h n od a l gro ups
Th i s
proced ure
as
the
removes
I-V, but p reserves the sterno cleido
m a sto i d muscle, accessory n e rve, internal j ugu l a r vei n and the subma ndibu l a r gland. Recen t ly, t here has been debate a s to whet her t h e nodal gro ups r and removed
in
nodal- nega t ive
V need t o be
supragl ottic
d i sease.
All
operations a re a bala n ce between risks and b enefits. The m a in risk of opera t i ng o n
a
node- negative neck is possi ble
damage to the accessory n erve a nd trials to co mpare neck dissecti on strateg i es s h o u l d j ncl ude m easu res o f fu nctio n and long-term shoulder pa i n
( 1 0 percent wi t h either
selective or m odi fied radical dissect io ns) 87 An exa mple of this is given i n a prospect ive ra ndom i zed co n t rolled t rial o f neck dissectio n fo r tongue cancer, where m o dified rad i cal
neck
dissection
prod u ced
complications than sel ect ive (levels vers us 4 1 percent, However, dissection
p = 0.04 ) . 88
when
levels
si milar
II-IV,
61
si gnificantly
more
II-I I I ) d i ssecti on (25
o p e rations
p a t i ents
(lat eral
allo cated,
PRETREATM ENT PLAN N I N G
Loss of a functio ning larytL'< causes problems wit h speech, swallowing, coughing, altered appea rance, lifting, laugh ing, crying, smelling, tas ting and even kissi ng. Loss of t hese very 'hu m anizing' functions can so m e times lead to severe psychological problems in a p atient population t h a t already car ries a sign ificantly higher preoperative
psychological m o rbidity than
the general pop ulation.
F i n ally, loss of the larynx can m e an the end o f employ ment
fo r m any pati ents
and
its associated
fina ncial
difficu lties ( in one study, 43 p ercent of patients left work or
changed
jobs
post-surgical
excision
of laryngeal
carci n o m a ) . 92 These factors need to be taken into acco unt when m a king the decision to p erfo rm laryngeal surgery a nd d iscussed in a pretreatment case confere n ce . The
impor tance of the i mm ediate and extended ( e.g. so cial worker) m ul tidisciplinary team is never higher than at t his part of the patien t p athway.
[*J
neck versus
m odified radi cal, 71 p a tients a ll o cated ) were co mpared fo r sup raglottic a nd transglotti c can cer, no d i ffe rence i n complication rate n o r a ct u a rial s urvival
Re h a b i litation
was fo und .89 Two
POST-TR EAT M ENT O F EA R LY STA G E D I S EAS E
Alt h o u g h early stage patien ts a re general l y left with a fu nctioning larynx, there are still aspects of rehabi l itation
26 1 8 I
PART 1 7 HEAD AN D NECK TU M O U RS
to be emphasized. The patient should be helped to stop s moking and a t tenda nce a t ded ica ted antismoking clinics s hould be strongly enco u raged . The same a pplies to assistance with alcohol ad diction, where spec ialist agen cies can be called upo n . Even mino r altera tions to voice can a ffect e m p loyme n t a n d social circumstances and the services o f a dedicated adult voice therapist experienced in the rehab ilitat ion o f la ryngeal cancer cases is funda mental.
For
endo sco pic
selected excision
patie n t s of
who
cord
have
tumours ,
undergone
l OJection
or
l aryngeal framewo rk op era t i o n s may help give optimal voice quality in the long term.
[*]
POST- LA RY N G ECTOMY
Focus group studies
have shown that laryngecto m ees
val ue the input o f the head and n eck clin ical n u rse speci alist above all o ther members of the tea m . They may faci l itate early rehabil itation and ass ist the local co m mu n i t y ca re tea m . Studies to co n fi r m such o utcomes o f n u rse i n tervention are requ ired , although all qualita tive and a necdo tal evidence is st rongly in favour o f such roles. Reh abilitation of the voice req u i res the services o f an
Figure 1 94. 1 3
T racheo-oesophagea I voice re h ab i l itati o n va Ive
h e a v i ly c o l o n i zed by ca ndida after being in situ for fo u r months.
adult speech and language therapist w ith tra i n ing i n the
Can di d a-resistant valves a re now ava i l a b l e wh i ch may prolong
care o f larynge ctomees. This is covered further i n Chap ter
th e usefu l l i fe of t h ese d evices.
195, Rehab ilitation a fte r la ryngectomy, as is s u rgical voice rehab i l i ta tio n with valves and other devices. However, in t h is sectio n i t is wor t h n o ting that the use o f stoma ' filter' devices has been shown in a p rospective rand o m i zed s tu dy
to
imp rove
laryngectomees'
periph eral oxygen
saturation levels and, fo r t h is a n d o ther reaso ns, should be rout inely prescribed. A p ro blem with this d ev ice is i ts p ropensity to ca ndida infection of the valves. H owever, t his may be overcome w i th the developm ent of cand ida res istant valves i nco rpo rating magnets to prevent ina d vertent op e n i n g o n swallowi n g
recurrences occur i n t he first two years and that early detectio n of t h ese may lead to survival bene fit . Whether or not this is the case, patients themselves welcome th is degree o f monito ri ng which provides a contact point with seco n da ry care and psychological suppo rt .93 It is im port a nt to recognize that a significant minority of p atients w ith recurrence 'self-diagnose' after becoming sympto matic between appointments. Patient follow up should ideally be in a mult idisciplinary setting.
[*]
( Figure 1 94. 1 3 ) . Early
reports h ave suggested an i ncreased firs t valve l i fetime from a median o f between o ne and two months, to a med i a n of ten mo n t hs to a year.
KEY PO I NTS
[H,,"]
Psych oso cia l support i n clu des info rming the patient
•
The ma in risk facto rs fo r laryngeal cancer a re
•
Treatment requires a multidisciplinary team,
a n d carers about p a tient suppo r t o rgan izatio ns , such as the National Association of Laryngectomee Clubs in t he
tobacco a nd alcohol co nsump tio n .
United Kingd o m and similar o rganizations wo rldwide. In many
co untries,
d i sability and
l a ryngec t o my
opens
the
door
is
now
a
to
financial aid . The
i ncluding surgeons, radiotherapists, clinical
registered
nurse spec ialists, p allia tive care physicians, dietici ans and dedicated sp eech and
ass ista nce of a socia l worker, preferably before d i scharge from hospital,
can
help
al lay some
concerns o f the new la ryngecto mee.
of the
financial
swallowing therap ists. •
Early-stage disease may be treated endoscopically or with radiotherapy.
[UlI-J"' ]
Advanced disease may be treate d with l aryngecto my o r chemoradiotherapy.
Follow - u p
•
Definitive randomized con t rolled trials of a dequa te power are urgently needed to
There have been no t rials on how o ften one s hould fo l low
differentiate between the alternative
up post - la ryngeal cancer p atients. The axi o m is that o ne should see patients mo nthly
fo r the first yea r,
two
monthly for t h e seco nd year a n d then fo u r t o s i x mo nthly t hereafter to five yea rs, o n t he basis that
85 percent of
treatments in these two clinical scenario s . •
Rehabilitation o f the laryngectomee must s ta rt with preopera tive p l anning.
Chapter 1 94
Best c l i n i ca l practice A l l patie nts with hoa rseness for t h ree weeks or m o re s ho u l d be refe rred u rg ently for an oto l a ryngolog ical o p i n ion. A l l p reviously u n d iag nosed l a ryngeal lesions i n persons ove r 30 years o l d shou l d be s ubject to u rgent bio psy. Bio psy is perfo rmed usi ng suspension m icro l a ryngoscopy and Hopkins' rod photodocu m entation. Not all l a ryngeal tu mou rs req u i re imaging. Sta ge I a n d some sma l l sta ge I I g l ottic tu m o u rs can be safely ma naged without the need fo r fu rther imaging of the primary tu mou r. Howeve r, some centres sti l l p refe r to i mage all cases as part of reg i stratio n p rotoco ls o r tri a l s o f new treatme nts.
Defi c i e n ci es i n cu r re n t k n o w l ed g e a n d a re a s fo r fu tu re resea rch La ryn g e a l cancer is a h eterog e n eous d i sease with m a ny com b i n ations of sta g e a n d su bsite. I n a d d itio n, there a re few cou ntries where the cu ltu re of c l i n icians a n d patie n ts w i l l s u pport ra ndo m ized tri a l s o f t h e size a n d d u ration req u i red fo r u n co m m on d iseases l i ke l a ryn g ea l cancer. Noneth e l ess, the B razi l i a n Head and Neck G ro u p, in pa rticu l a r, have shown that such tri al s a re poss i b l e a n d a n a logous stu d i es o f s u rg e ry fo r prostate c a n c e r a re su ccessfu l ly recru iti n g in the U n ited Kingdom. I n early g l ottic l a ryngeal ca ncer, there is a need for a tri a l of e n d oscopic excision ve rsus ra d ioth e ra py. Tri a l s of neck treatment shou l d i nc l ude senti n e l node biopsy a n d com p a rison o f sel ective n e c k d i ssectio n with ra d iothe ra py for hi g h-risk d isease. Fo r adva nced d isease, tri a l s of chemora d i othera py ('o rgan p reservation stu d ies') shou l d conti n ue, pa rticu l a rly in the syn c h ronous setti n g . Adj u nct thera py n e e d s t o be assessed . There a re n e w e r age nts such as taxa nes and o t h e r agents d esi g n ed to red u ce the d ose [a n d therefo re toxicity) of chemothera py, such as e p i d e rm a l g rowth facto r b l ocke rs a n d a n g iogenesis i n h i bitors. These q g ents n e e d t o b e tri a l l ed with conve ntio n a l treatment modal ities. Ph ase I a n d I I tri a l s of gene thera py [e.g. rep l aci ng mutant with w i l d type p 53) a re i n p rogress and shou l d soo n re port wheth e r p h ase I I I tri a l s a re wa rra nted. Ove r the next te n yea rs, genom ics a n d p roteom ics may w e l l p rovi d e a more re l i able a l te rn ative syste m of p redi ction a n d d ecision making than is p rese ntly offe red by the Tf\I M sta g i ng syste m .94 H oweve r, governme nts n eed to be rem in d e d that no tri a l of treatment cou l d eve r p rod u ce red uctions i n deaths fro m l a ryngeal cancer com p a ra b l e t o th ose
Tu m o u rs of the l a rynx I 261 9
ach i eva b l e b y sto p p i n g peo p l e smoking to bacco. I t has been est i m ated that cessation of smoki n g wou l d d ecrease the cases o f l a ryngeal carcinoma b y 9 0 percent. Recent p ress u re fro m m e d ical age ncies is beari n g fru it, w ith tobacco adve rtising bans and i n some cou ntries the p ro h i bition of smoki n g in p u b l i c p l a ces.
ACKNOWLE DGEMENTS
This chapter is dedicated to the memory of Graham Buckley, one of the UK's finest laryngologists, who surely would have been writing this chapter himself were he with us today. The authors would like to thank the following for their invaluable contributions: Mrs Eva Hicks ( administration ) , M r Paul Tierney (ENT) , Dr Eric Loveday (Radiology), Susan Armstrong ( Radiology) , at North Bristol NHS Trust. Dr Justin Weir ( Pathology) and Dr Steve Falk ( Radiotherapy and Oncology) , at United Bristol Hospitals NHS Trust.
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* 60.
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Sigston E, d e Mones E, Ba b i n E, H a ns S, H a rtl OM, Clement P et 01. Ea rly-stage g l ottic ca ncer: oncolog ica l res u l ts and m a rg i ns i n laser cordectomy. Archives of Otolaryngology Head and Neck Surgery. 2006; 1 3 2 : 1 47-52. Ga rcia-Serra A, H i n e rm a n RW, Amd u r RJ , Morris CG, M e n d e n h a l l W M . Rad iot hera py for ca rcinoma i n situ of the true voca l cords. Head Neck. 200 2 ; 24: 390-4.
Kh u ri FR, Lee JJ , Lippman S M , Ki m ES, Cooper JS, B e n n e r S E et 01. Ra n do m ized ph ase I I I tria l of l ow-dose isot ret i n o i n for preve ntion of second primary t u mors i n stag e I a n d I I head a n d neck ca ncer pati ents. Journal of the National Cancer Institu te. 200 6 ; 9 8 : 441 -50. Schw e i n fu rth J M, Pow itzky E, Ossoff RH. Reg ression of l a ry n g e a l dys p lasia after seri a l m icrofl a p excision. Annals of Otology, Rhinology and Laryngology. 2001 ; 1 1 0 : 8 1 1 -4. Dey P, Arn o l d 0 , W i g ht R, MacKenzie K, Ke l ly C. W i lson J. Rad iothera py ve rsu s open s u rgery versus e n do laryngeal s u rg e ry (with o r without laser) for early l ary n g e a l sq u a mous ce l l ca nce r. Cochrane Database of Systematic Reviews 2002 ; CD00202 7. Ogoltsova ES, Pasches AI, M atya kin EG, Dvoirin W, Fedoten ko SP, Alfe rov VS et 01. Compa rative eva l u ation of
the efficacy of ra d i othera py, su rgery a n d com bi n ed treatment of stag e I nad II l a ry n g e a l ca n ce r (T1 02 1\JOMO) on the basis of co-operative stud i es. Journal of Otorhinolaryngology (Moscow). 1 990 ; 3: 3-7. This is the only published randomized con trolled trial of surgery versus radiotherapy for early laryngeal cancer. 61 . M a h i e u H F, Kooper DP, Leem a n s CR. [C02 laser treatme n t ; a n effective a n d m i n i ma l ly d isru ptive e nd oscopic th era py for s ma l l g l ottic laryngea l carc i n o mas]. Nederlands Tijdschrift voor Geneeskunde. 1 99 6 ; 1 40 : 886-90. 62 . R u cci L, B a n i 0, Ga l l o 0, Arbi Ricca rd i R, Borg h i Ci rri M B, Fi n i -Storchi O. I nte rd i g itati r] g ce l ls in the peritu mora l i n fi ltrate o f l a ry n g e a l ca rcinomas: a n i m m u nocytoch e m i ca l a n d u ltrastructu ra l study. ORL; Journal for Otorhinolaryngology and its Related Specialties. 1 99 1 ; 53 : 349-56. 63. Laccou rreye 0, Wei nste i n G , Chabardes E et 01. T1 sq ua mous ce l l ca rcin o m a o f the aryte n o i d . Laryngoscope. 1 99 2 ; 1 02 : 896-900. 64. Desloge RB, Ze ite l s SM. Endolaryngeal m icros u rgery at the a nterior g l otta l com m issu re : controve rsies and observations. Annals of Otology, Rhinology, and Laryngology. 2000; 1 09 : 3 85-92. 65. G regor RT, Oei SS, Bari s G, Keu s RB, Ba l m AJ , H i l g e rs FJ . S u pra g l ottic l a ry n g ectomy with postoperative rad iation versus primary rad iation i n the m a nag e m e nt of s u p rag l ottic l a ryngeal ca ncer. American Journal of Otolaryngology. 1 99 6 ; 1 7 : 3 1 6-21 . 66. Bocca E, Pig n ata ro 0, O l d i n i C. S u p ra g l otti c l a ry ng ectomy: 30 yea rs of expe rie nce. Annals of Otology, Rhinology, and Laryngology. 1 983 ; 9 2 : 1 4-8. 67.
T 2 g lottic ca rcinomas treated b y ca rbon d ioxi d e laser. Annals of Otology, Rhinology and Laryngology. 2004; 1 1 3 : 853-8. 55.
1 94 Tu m o u rs of the l a rynx I 2621
68. 69.
Ste i n e r W, Am brosch P. Endoscopic laser surgery of the upper aerodigestive tract: With special emphasis on cancer surgery. New York : Th i e m e Medical P u b l i sh e rs, 2000. Weinste i n GS, B rasnu 0, Laccou rreye H . Organ preservation surgery of the larynx. Cal iforni a : Sing u la r Press. The Department of Vete ra ns Affa i rs La ry n g ea l Ca n ce r Stu dy G ro u p. I n d uctio n che mothera py p l u s rad iation com pa red with s u rgery plus rad iation i n pat ients w ith a dva nced laryngea l ca ncer. New England Journal of Medicine. 1 99 1 ; 3 2 4 : 1 685-90.
2622
I PART 1 7 H EAD At\I D N ECK TU M O U RS
* 70.
D ische S, Sa u n d ers M , Ba rrett A, H arvey A. G i bson D, Pa rm a r A. A ra ndom ised mu lticentre tri a l of CHART versus conventional ra diothera py in head and neck ca n ce r. Radiotherapy and Oncology. 1 99 7 ; 44: 1 23-36. High quality randomized trial failed to show significant benefit of CHART over conventional regimens. Robertso n AG, Robertson C, Boyle P, Symonds R P, W h e l d o n T E . The effect o f diffe ri ng ra diothera peutic schedu les o n the response o f g l ottic ca rci noma o f the l arynx. European Journal of Cancer. 1 99 3 ; 29A: 50 1 - 1 0. H owe l l-Bu rke D, Peters U , Goe pfert H , Osw al d MJ. T2 g l ottic ca ncer. Recu rre nce, sa lvage, and surviva l afte r d efi n itive rad i othe ra py. Archives of Otolaryngology - Head and Neck Surgery. 1 990 ; 1 1 6 : 830-5. Ste l l PM, Rawso n NS. Adj uva nt che moth e rapy in head a n d n e c k ca ncer. British Journal of Cancer. 1 990 ; 6 1 : 7 79-87. Pig non J P, Bourhis J , Domenge C. Desi g n e L. Che motherapy a d d ed to l oco re g i o n a l treatment for head a n d n eck sq ua mous-ce l l ca rci noma : t h ree meta-ana lyses of u pdated i n d ivi d u a l d ata. IVlAC H - N C Co l la borative G ro u p. lVl eta Ana lysis of Chemoth e ra py on Head a n d N eck Cancer. Lancet. 2000 ; 3 5 5 : 949-55. A high quality patient data metanalysis trial, which found a modest survival advantage in the neoadjuvan t setting, whilst adjuvant chemotherapy conferred only a small nonsignifican t advantage (all h ead and n eck cancers). Te rre l l J E, Fisher SG, Wolf GT. Lon g -te rm q u a l ity of life after treatment of l aryngeal ca ncer. The Vete ra ns Affa i rs La ry n g ea l Ca n ce r Stu dy G ro u p. Archives of Otolaryngology - Head and Neck Surgery. 1 99 8 ; 1 2 4 : 9 64-71 . Corvo R, Ben asso M, Sangu i neti G, Lio netto R, Baciga l u po A, M a rg a ri n o G et 01. Alte rnati ng chemorad iothe ra py ve rsus partly acce l e rated ra diotherapy in loca l ly adva n ced sq u a mous ce l l ca rci noma of the head a n d neck: Resu l ts fro m a phase I I I ra n d o m ized tri a l . Cancer. 2001 ; 9 2 : 2856-67. Fo rastiere AA, Goe pfert H , Maor M , Paja k TF, Weber R, Morrison W et 01. Concu rre nt che moth e rapy a n d rad iothe ra py for o rg a n p reservation i n a dva nced l ary ngea l ca ncer. New England Journal of Medicine. 2003 ; 3 49 : 209 1 -8. Large randomized con trolled trial of radiation versus chemoradiotherapy (either induction or concurren t). Large trial in which larynx preservation was increased in the concurren t group, at the expense of increased side effects and an uncertain voice outcome. No surgical arm.
71 .
72.
73. * 74.
7 5.
76.
* 77.
7 8.
79.
80.
B i l l e r H F, Lawson W. Pa rti a l l aryng ectomy fo r voca l cord ca ncer with ma rked l i m itation or fixation of the voca l cord . Laryngoscope. 1 98 6 ; 9 6 : 61 -64. Pea rson BW, Woods 2nd. RD, H a rt man D E. Exte nded h e m i l a ryng ectomy fo r T3 g l ottic ca rcin o ma with p rese rvation of speech a n d swa l l owing. Laryngoscope. 1 980 ; 9 0 : 1 9 50-61 . D e l a e re P, Va n d e r Poo rte n V, Vra n ckx J , H i e rner R. La ry n g e a l re p a i r afte r resection of adva n ced ca ncer: an opti ma l reco nstru ctive p rotocol. European Archives of Otorhinolaryngology. 2005 ; 2 6 2 : 9 1 0-6.
81. 82.
83.
84. 85.
86.
87. 88.
* 89.
90.
91 .
92.
93.
94.
Kl uyske ns P, R i ngoi r S . Fol low- u p of a h u m a n l a rynx tra nspla ntati o n . Laryngoscope. 1 970 ; 8 0 : 1 244-50. Strome M , Ste i n J, Escl a mado R , H i cks D , Lo renz RR, B ra u n W et 01. La ryngea l tra ns p l a ntation a n d 40-month fo l low u p. Ne w England Journal of Medicine. 200 1 ; 344: 1 67 6-9. I ro H , Wa l d fa h re r F, Alte n d orf- H ofm a n n A, Weiden becher 1Vl , Sa uer R , Ste i n e r W. Tra nsora l laser s u rgery of s u p ra g lottic ca n ce r : fol l ow- u p of 1 41 patie nts. Archives of Otolaryngology - Head and Neck Surgery. 1 99 8 ; 1 2 4 : 1 245-50. Ste l l PM. The fi rst l a ryngectomy. Journal of Laryngology and Otology. 1 97 5 ; 89 : 3 53 -8 . Sha h J P, M e d i n a J E, Shaha AR, Scha ntz S P, M a rti J R. Cervica l lymph node m etastasis. Current Problems in Surgery. 1 99 3 ; 3 0 : 1 -335. Weiss MH, H a rrison LB, I saacs RS. Use of decision a n a lysis i n p l a n n in g a m a n a g e ment strategy for the stage NO neck. Archives of Otolaryngology - Head and Neck Surgery. 1 994; 1 20 : 699-702. Kuntz AL, Weymu l l e r J r. EA. I m pact of neck d issection on q u a l ity of l i fe. Laryngoscope. 1 999 ; 1 09 : 1 334-8. B razi l ia n Head and Neck Ca n ce r Stu dy G roup. Res u l ts of a p rospective tri a l on e l ective mod ified rad i ca l classica l versus s u p raomohyo i d n eck d i ssection i n the m a n a g em e nt of ora l sq ua mous ca rcinoma. American Journal of Surgery. 1 99 8 ; 1 7 6 : 422-7. B razi l i a n Head and N eck Ca n ce r Study G ro u p. End res u l ts of a p rospective tri a l on e lective lateral n eck dissectio n vs type I I I mod ified rad ica l n eck d i ssection in the m a n a g e m e n t of s u p rag lottic a n d tra nsg l ottic carci no mas. Head and Neck. 1 999 ; 2 1 : 694- 702. Adequately powered randomized controlled trial of different neck dissection strategies for transglottic and supraglottic cancer. Found no advantage of modified radical over selective dissection in the clinically NO neck. Spria n o G, P i a nta n ida R, Pe l l i n i R, M u scate l l o L. El ective treatment of the n eck i n sq u a m ous ce l l ca rci n o m a of the l a rynx: c l i n i ca l experie nce. Head and Neck. 2003 ; 2 5 : 97- 1 02. Foote R L, Buskirk SJ , Sta n ley RJ , G ra m bsch PM, O lsen KD, DeSa n to LW et 01. Patte rns of fa i l u re after tota l l a ry n gecto my fo r g lottic ca rci noma. Cancer. 1 989 ; 6 4 : 1 43-9. Sch u l le r DE, Tru deau 1Vl , B istl i n e J , La Face K. Eva l uation of vo ice by patie n ts a n d c lose re l atives fo l l owing d i ffere nt l a ryngea l ca n ce r treatme nts. Journal of Surgical Oncology. 1 990; 44: 1 0-4. B i rch a l l M , Richardson A, Lee L . E l i citing views o f patie n ts w ith head a n d neck cancer a n d ca re rs on p rofession a l ly d e rived sta n d a rds for ca re. British Medical Journal. 200 2; 3 2 4 : 51 6. S q u i re JA, Baya n i J , Lu k C, U n w i n L, Toku naga J , M a cM i l la n C et 01. lVl o l ecu l a r cytog e netic a n a lysis o f head a n d neck sq ua mous ce l l ca rci noma : By co m p a ra tive g en o m i c hybrid iza t i o n , s pectra l ka ryotypi n g , a n d expression a rray a n a lysis. Head and Neck. 2002 ; 2 4 : 874-87.
95 Rehabilitation after laryngectomy
ANDREW J PARKER
Introduction
2623
Assessment of quality of life and rehabilitative outcome
2630
The rehabilitation process
2623
Key points
2631
Historical and technical aspects
2624
Best clinical practice
2631
Speech
2627
Deficiencies in current knowledge and areas for future
Swallowing
2627
Tracheostomal problems
2628
Psychosocial rehabilitation and adjustment
2630
2631
resea rch
2631
References
SEARCH STRATEGY The content of this chapter is supported by PubMed searches using the key words laryngectomy, rehabilitation, alaryngeal voice, tracheostomy and tracheo-oesophageal fistula.
1976 for the purposes of promoting the rehabilitation of
INTRODUCTION
laryngectomees, collecting, coordinating and disseminat This chapter deals with the rehabilitative aspects follow
ing information relevant to rehabilitation.1 This associa
ing laryngectomy. The text primarily refers to pat i ents
tion also gives guidance in respect of free prescriptions,
undergoing total laryngectomy, but may also refer to
hospital transport arrangements, social benefits, speech
those undergoing excision in its partial form. The main
aids and miscellaneous items such as stoma buttons,
problems are those of speech, swallowing, those asso
humidifiers, suction machines and stoma covers.
ciated with a tracheostomy and airway diversion, in addition to psychosocial effects. Rehabilitation
following laryngectomy is a
phase of the treatment as undertaken principally
by
crucial
the ear,
nose
and
throat
(ENT) surgeon in conjunction with a communication therapist and supported by a multidisciplinary team. It is particularly
important
that
THE REHABILITATION PROCESS
a whole and should be
patients undergoing this
rehabilitation should have the programme supervised by those appropriately trained, working within a cancer centre or cancer unit with open access for the patient The .
use of patient liaison professionals, e.g. head and neck cancer support nurses, is also important in facilitating this process and many patients derive rehabilitative
There are various aspects to rehabilitation aft er laryn gectomy and the process is divided into that prior to surgery, during the surgery/whilst the patient remains in hospital and then aftercare. There have been significant advances in all rehabilitative aspects post laryngectomy in 2 recent times, but most notably in voice production. -
Ultimately, the best form of rehabilitation following total laryngectomy will be laryngeal transplantation, but this is still in the highly experimental stage.3 The rehabilitative process is directed towards mini
assistance from self-help groups such as the National
mizing disability or adverse functional effects following
Laryngectomee Association, which was inaugurated in
treatment by maximizing residual function or finding
2624
I PART 17 HEAD AND NECK TUMOURS
compensatory strategies. The primary aims of rehabilita tion are as follows: G
G G G
G
G
assessment and treatment of disability produced by surgery; maximizing recovery of residual tissues and function; provision of appropriate aids; education of the patient and relatives/carers in respect of likely impairments and an appropriate pretreatment appraisal indicating realistic outcome goals; to facilitate development of coping strategies for patient, relatives and carers; to facilitate the education process so that the patient can understand the potential effects of the operation.
The chief problems where rehabilitation is likely to be required are: G G G G G G
speech; swallowing; tracheostoma problems; problems with loss of glottal occlusion, e.g. lifting; problems with airway diversion, e.g. loss of olfaction; body image/psychological/social problems.
Several methods of voice rehabilitation have been developed, but they are principally nonsurgical and surgical, and there are advantages and disadvantages of each. Patients who have had laryngectomy have altered anatomy and as a result alteration in deglutition. Swallowing problems are common, particularly if there has been associated pharyngeal resection because of tumour spread and/or the effects of radiotherapy.4 [**] Rehabilitation of voice and swallowing can be made easier by attention to detail with maximum preservation of pharyngeal mucosa and various surgical manoeuvres thought useful, such as cricopharyngeal myotomy and pharyngeal neurectomy. The alteration of body image following laryngectomy can present the patient with significant difficulties with a broad spectrum of disorders from full-blown psychiatric conditions such as loss of self-confidence to depression. In most types of laryngectomy where extensive surgery has been performed, and certainly after the total resection of the larynx, tracheostomy is a permanent feature. Breathing in this way causes alteration in the physiology of the lower respiratory tract leading to repeated chest infections, crusting and occasionally aspiration through a surgically created tracheo-oesophageal fistula to facilitate voice rehabilitation. Loss of sense of smell by airway diversion can also be a problem for some patients. By removing the closure effect of the glottis, patients with tracheostomy can experience great difficulty in executing manoeuvres where the intrathoracic pressure needs to be raised, e.g. in lifting heavy objects. The rehabilitative process should begin prior to surgery with engagement of the multidisciplinary team, but all patients require a post-treatment re-evaluation of
rehabilitation needs, and active speech therapy generally begins when the patient has healed. This should ideally be whilst the patient remains in hospital. Discharge from the ward should be planned and appropriate support arrangements should be in place following necessary liaison with the patient's general practitioner and support services. The patient should be aware of how to get further advice before the first follow up appointment, if required. For patients who find long term communication is poor, carers may find lip reading instruction useful and instruction in the methods of telephone communication and summoning emergency 5 aid should be advised. [*]
HISTORICAL AND TECHNICAL ASPECTS
In the early days, laryngectomy was not only performed for malignant disease but also tuberculosis and syphilis, notably for the relief of airway obstruction and pain. As loss of voice was considered to be the major problem after this operation, most effort was concentrated in this area as voice is required to communicate. Methods of voice rehabilitation included: G G G
pseudowhisper; electric larynx; vibrating pharyngo-oesophageal segment: 'oesophageal speech'; - fistula speech.
In earlier times, pseudowhisper and oesophageal speech were considered to be appropriate rehabilitative strategies. In pseudowhisper, the patient uses air in the oral cavity moved by muscles of the floor of the mouth/tongue with articulation carried out by the usual mechanisms. This is effectively, as its name suggests, a whisper and is difficult to hear in background noise. More substantial speech is achieved by the patient injecting air into the oesophagus and then by coordinated muscular action it can be expelled causing the cricopharyngeus muscle or pharyngo oesophageal segment to vibrate producing a noise which can be articulated into recognizable speech. For most patients this has to be taught by extensive speech therapy and, although it is louder than pseudowhisper, the speech is staccato and in short bursts. Some patients use it as their main method of communication, particularly if surgical measures to assist in voice production have proved unsuccessful or troublesome. Probably only about 25 percent of patients achieve functional oesophageal speech, but there is no doubt that a small number of patients can use this method to excellent effect and it does not rely on any functioning prosthesis.6 [**] Throughout the 1960s and up to the present, the 'electric larynx' has also been an option, although it is less popular now ,that rehabilitative techniques have im proved. This is sometimes known as a Servox after the company that produces one particular type and has the
Chapter 195 Rehabilitation after laryngectomy I
disadvantage that it is a mechanical device that needs batteries and maintenance. In this type, an electrical buzzing device is held against the neck. The quality of voice is very metallic and monotonous. The patient is unable to use a device such as this without using their electric hands, but it does produce a useable voice where there is supple tissue. Another example is the copper Rand device, where the vibrating sound source is transmitted intra pneumatic orally via a short pipe. Devices of this nature are often used as a temporary measure for patients who are developing or are about to use other methods, e.g. tracheo-oesophageal speech. The modern basis for voice rehabilitation post laryngectomy is to provide a vibrating segment of the remaining upper aerodigestive tract and this has almost exclusively been the pharyngo-oesophageal (PE) segment, i.e. in the region of the remaining cricopharyngeus. Improved fluency and duration of speech can be achieved by providing a source of air to maintain these vibrations other than that held in the oesophageal reservoir. Thus, the concept of fistula speech was developed. Initially there was great reservation about surgically creating a tracheo oesophageal fistula just below the PE segment for reasonable fear of aspiration. Complex multistage proce dures were developed to create a surgical fistula between the pharynx and the skin in the region of the tracheostomy with air then being diverted from the trachea into this fistula, so setting up vibrations of the PE segment. These procedures were often associated with S significant postoperative problems, including mortality?' In some cases, external prostheses were developed which also contained the vibrating source, although these were not uniformly successfu1.9 Conley et al.lO devised a shunt consisting of a tunnel of mucosal tissue from the oesophagus to the trachea with modification using a vein graft, whilst Asai's technique involved creating a phar yngotracheal fistula using a skin-lined tube and this often took two or three stages.ll Other procedures used a tracheopharyngeal anastomosis and was carried out immediately or some time after laryngectomy. In one of these procedures the proximal end of the trachea was sutured to the hypopharynx with a resulting tracheophar yngeal shunt composed of tracheal cartilage and phar 12 yngeal mucosa. , 13 [*J The concept of a simply created tracheo-oesophageal fistula by puncture of the back wall of the upper trachea into the upper oesophagus was a landmark in surgical voice rehabilitation and goes back to 1927 where there are reports of a patient who had deliberately punctured the back wall of the trachea by passing a heated ice pick through the stoma.2 Although this is often thought to be a report in respect of speech rehabilitation after laryngectomy, it was rumoured that the patient was in fact trying to commit suicide and he subsequently found that on occlusion of the stoma with a finger, exhaled air caused vibrations in the throat which could be articulated into speech. [*J It was not until the use of a valve by Blom
2625
and S·mger14 that fistula speech started to become mainstream in voice rehabilitation after laryngectomy. The first tracheo-oesophageal prosthesis was a silicone tube with a 'duck bill' valve sitting in the upper oesophagus. Voice was obtained by air being diverted through this from the upper trachea following occlusion of the stoma by the patient, again setting up vibrations in the PE segment. The valve was designed to be kept in position with occasional removal by the patient or speech therapist for cleaning. There is no doubt that this was a benchmark innovation in the annals of voice restoration following laryngectomy. IS There were obvious advantages to this device over other methods in that it was accomplished either at the time of, or as a secondary procedure after laryngectomy. There was no significant salivary leakage into the tracheobronchial tract, it was not associated with major complications unlike some of the other procedures and it did not need an external device. Voice production by this method has become the mainstay of speech restoration following total laryngect omy and other valve prostheses have followed, working along the same principle. Valve speech is associated with increased acceptability, intelligibility and with more normal phrasing when compared with that produced by other means, particularly oesophageal voice. Later devel opments included the use of indwelling devices which are put in usually at the time of laryngectomy or in a smaller number of patients as a secondary procedure, the earliest 16 of which was the Groningen valve and more recently the 17 ProvOX. In each case, modifications have taken place and the Groningen valve is now marketed in its low resistance form. The Provox and Blom-Singer valves have been modified to take into account the trend for 'front loading' indwelling prostheses. A selection of these devices is shown in Figure 195.l. Initially, there was much controversy over the physical characteristics and pressure flow parameters of these valves in respect of the anticipated ease of use and perceived voice quality and all of these valves were noted to fail because the prosthesis degrades, usually by the action of candida and other organisms. Much has been written about the in vitro aerodynamic properties of these IS, 19,20 valves, but this is now considered less important. The degradation and failure of these prostheses is a worthwhile area of study since both in outpatient and economics it causes a significant workload for the ENT/ Speech Therapy Department responsible for these patients 21 22 and is a process that is incompletely understood. , There has been much discussion and effort in producing valves with low forward resistance in the quest to produce the perfect valve and perfect alaryngeal speech by this method. The technical problems have now largely been surmounted and all the current modern range of valves have low in vitro and in vivo resistance. The problem probably only becomes significant if the resistance of a prosthesis becomes appreciable when taken in conjunction with the tracheo-oesophageal/PE segment
2626 I
PART 17 HEAD AND NECK TUMOURS
Figure 195.1
A selection of various tracheo
oesophageal voice prostheses: (a) Blom-Singer 'duck bill' prosthesis with in trodu cer ;
(b) (c)
indwelling Provox prosthesis with introducer;
G roning en low resistance prosthesis;
(d) indwelling Blom-Singer prosthesis, introducer and 'gel cap'.
as a whole, but in vivo studies of aerodynamic measure
have been set by the PEGASUS study. For example, vocal
ments have yielded some interesting results; for example,
intensity was determined as the sound pressure level in
a significant relationship between maximal vocal ampli
dB(A) under quiet conditions for phonation of the vowel
tude and maximal flow of air through the tracheo oesophageal shunt. 23
A major contribution has been made to assessment of
rehabilitation
/a:/ at a microphone to mouth distance of 30 cm, the
maximum
[****/***/** 1
after laryngectomy from the
PEGASUS
project funded by the European Union (EU).24 This was a multicentre project throughout Europe including the
vocal
intensity
and
the
softest
possible
phonation being determined three times and averages taken. Maximal phonation time in seconds is taken as the longest of three phonated vowel /a:/ sounds. Speech rate was also determined by reading aloud a standard text by
United Kingdom and was undertaken to appraise the
recording the time it takes for the laryngectomee to read
different
this in their native language. Data from this study present
rehabilitation
centres where
strategies
of
major
European
total laryngectomy was performed.
Its
ultimate aim was to achieve a coordinated and cohesive
a useful longitudinal analysis with none of the factors
significantly different between three and six months after
European approach to post-laryngectomy rehabilitation.
the operation, but with the speech rate in words per
Most
perform
minute slightly better at the later appointmen t. Voice and
primary surgical speech restoration, whilst others prefer
speech training of these patients did not lead to a more
to
centres
wait
for
throughout the
Europe
development
of
routinely
oesophageal
voice
efficient tracheo-oesophageal voice, but interestingly to a
before deciding whether or not to recommend tracheo
more forceful pulmonary drive to enable phonation to
oesophageal puncture. Interestingly, the average lifetime of
take place. Those patients doing well at three months
a voice prosthesis from insertion to replacement was
continued to do so thereafter. No significant differences
significantly longer in the southern European institutions
were found between the voice and speech measures of
(average 8 months) than in the centres in Northern Europe
male and female patients, but the maximal phonation
(average 4.7 months). There was no clear reason for this,
but it may be that the patienfs diet is implicated, although
in some countries the patients are directly charged for the
prosthesis, which could result in patients tending to wait
longer before presenting for replacement. With a limited
evidence-base, some centres went to significant lengths to assess the PE segment tonicity preoperatively using various
time tended to be longer in male patients. Younger
patients tended to do better in respect of most voice and speech parameters and these differences were significant. One of the major controversies in this field is whether or not PE segment tonicity modifying procedures, i.e.
myotomy, pharyngeal neurectomy or both, leads to better voice quality. This study has shown that these procedures
forms of manometry, fluoroscopy, electromyography and
tended to lead to a distinct reduction of intratracheal
endoscopic evaluation, but this is by no means uniform,
pressure required to phonate, i.e. that the voice is easier to
with the majority simply assessing tonicity at the time of the procedure by palpation. Northern European centres
tended to perform procedures which modified PE segment tonicity, such as cricopharyngeal myotomy and/or phar24 yngeal neurectomy.
Much has been written about the assessment of voice
and speech following laryngectomy and various standards
produce and that a
combination
of
myotomy and
neurectomy seemed more effective than myotomy alone. Better results for voice and speech factors in patients who have undergone PE segment surgery were given, but with reported increased problems in swallowing, aeructation
and flatulence. Patients who underwent valve insertion as
a primary procedure showed only slightly better results
Chapter 195 Rehabilitation after laryngectomy I
2627
than those in whom it was performed on a secondary basis. [***/**]
SPEECH
An active surgical voice restoration programme is now essential in centres where laryngectomy is performed. Primary tracheo-oesophageal puncture is now accepted as the optimal method for voice rehabilitation. It is probably desirable that a choice of tracheo-oesophageal prostheses should be offered to a patient, although professionals tend to have their own preferences and this must be taken into account, particularly as experience is usually built up using just one variety. Problems arise, however, when patients relocate and present to other departments and expertise needs to be obtained in the use of other devices. The various prostheses generally have similar advantages and disadvantages and there are few studies comparing each type.25 Speech therapy should continue until a patient's speaking/swallowing is sufficient that all agree the best expected outcome has been produced. The vast majority of patients nowadays undergo tracheo-oesophageal puncture at the time of the initial laryngectomy and this is recommended. The usual approach is to make the fistula with a curved pointed trocar, taking care to protect the upper oesophagus against further trauma by the use of a fenestrated tube to accommodate the trocar, but effectively protecting the back wall. The fistula can be maintained by inserting a feeding tube and during the postoperative phase the patient's hydration/nutrition can be maintained in this way. At around ten days after the operation, providing all has healed, this can be removed and a 'front loading' prosthesis inserted. In Sheffield where we have tended to favour the Groningen and Provox valves, the prosthesis is inserted at the time of laryngectomy by pulling it into position using a flexible steel cable with a small chuck on the end supplied by the manufacturers, which is then connected to the valve and then pulled into position from above (Figure 195.2). The patient's hydration/nutrition after the operation is then maintained by a conventional nasogastric tube or, in some situations, by a fine bore feeding tube being placed through the valve. Secondary insertion is much less frequently practised now that the residual population of patients who underwent surgery before the introduction of this speak ing method have been fitted with valves. The principle is the same except that a fenestrated hypopharyngoscope or short oesophagoscope is inserted in the conventional manner and once in position the puncture is made through the back wall of the trachea and either maintained for ten days or so with a nasogastric feeding tube or, in the case of the indwelling prostheses that can be introduced by being pulled into place through the pharynx (rather than 'front loading'), the device can be inserted at the time and the patient can start to use it after
Short fenestrated oesophagoscope
Pharynx after removal of larynx
\---- Circumference of trachea viewed end-on
Trachea
(a)
Indwelling valve ---+-----1 sitting in fistula
(b) Figure 195.2
The sequence of events in respect of creating a
tracheo-oesophqgeal fistula and insertion of a speaking valve as a primary procedure. (a) A stab incision is made in the back wall of the trachea and the guide wire and applicator are introduced. (b) The short oesophagoscope is removed, the valve is attached to the guide wire and pulled into place.
24-48 hours. The essential steps of a patient undergoing secondary puncture is as shown in Figure 195.3. Patients who have undergone prosthesis insertion need open access to a specialist clinic as problems other than valve failure can arise. Granulation tissue may need to be trimmed from the fistula or the prosthesis size alters from time to time. In some patients, the fistula diameter increases with resultant leakage around the valve. In this situation tube feeding for a few days after removal of the valve reduces the problem. Figure 195.4 shows one decision-making paradigm for obtaining optimum speech as used at Charing Cross Hospital in London. This primarily relates to the Blom-Singer valve and tracheo oesophageal insufflation and videofluroscopy are used to assess PE segment tonicity.
SWALLOWING
A significant proportion of patients who have undergone total laryngectomy report swallowing problems.4 Surgical attention to detail with preservation of the maximum amount of pharyngeal mucosa at the time of resection is
2628 I
PART 17 HEAD AND NECK TUMOURS
{ol
Figure 195.3
The sequence of events in respect of
creating a tracheo-oesophageal fistula and insertion of a speaking valve as a secondary procedure. (3) The fenestrated oesop hagoscope is inse rted, an i ncision is made into the back wall of the trachea and an applicator inserted. The guide wire is then removed through the lumen of the oesophagoscope. (b) The oesophagoscope is removed and the valve is attached to the guide wire, The valve is pulled into pOSition by the guide wire, which is then detached.
thought to reduce this. There is some evidence from the
significant swallowing problems occur following a period
PEGASUS st udy cited above that surgical modifications to
of successful rehabilitation should be regarded as having
the procedure to improve the voice may adversely affect
recurrent disease until proven otherwise. Dietetic advice
swallowing,
should be obtained in patients who find it difficult to
neurectomy.
i.e.
cricopharyngeal
Otherwise,
it
is
myotomy/pharyngeal
difficult
to
determine
preoperatively the effect the operation will have on an
swallow and may require liquid supplementation in some cases through the use of a gastrostomy.
indivjdual patient's swallowing and counselling should take place prior to the procedure in respect of this. There are currently no standardized data in respect of the
TRACHEOSTOMAL PROBLEMS
optimal laryngectomy swallow and most unjts will rely upon the conventional clinical techniques of history,
Patients who have undergone total laryngectomy will have
examination, flexible fibreopt i c rhinolaryngoscopy, direct
a
examination under anaesthesia and contrast examinations,
problems of increased chest infections,
such as video fluoroscopy, to elucidate any problem.
stenosis. Surgical attention to detail when fashioning the
Patients with postoperative pharyngeal strictures often
stoma with access to nebulization and humidification
permanent
tracheostomy
with
the usual
potential
crusting
and
find that the only benefit they can obtain is through
devices can reduce these. The current trend is to use
periodic dilatation, either with
hands�free occlusion for speech and moisture conserva
a
bou gie or a balloon, and
this procedure needs to be repeated every few weeks. For
tion devices applied directly to the stoma (Figure
195.5).
those with spasm and hypertoxic pharyngeal muscles,
Patients who have had total laryngectomy do not have
Botox can be used by direct injection. Those in whom
an air stream through the nose and mouth and are not
Chapter
Remove
�
14 Fr catheter
Open
DilateTEP
-+-
up to 18 Fr
tract
--+-
voice?
� �_
R elax
(
voice?
floppy/mobile?
S,ze and Insert 16 Fr low pressure valve
No/Effortful?
-
) -
Insert 16 Fr t-------.� --' low pressure valve
Size and insert Voice?
16 Fr low press ure valve
Q-�
2629
Voice? valve
Effo rtfu I
TEP under 10 mm
Rehabilitation after laryngectomy'
d
voice �__ -.l
t
1 95
�
____ No/ EffO
? UI
-r _ _
_�
'
Arrange videotllJoroscopy and insufflaticn
•
.
t"
KeeR._9u�'a'rr�:-ge
vi9��U��S�t��. ,
�.
" "
•�
-
j
.
: .•
Insuffl ation
...
�
-
Dilate TEP
up to 22 Fr
I,
Open tract vo ice?
.
.
f.
Replace catheter or'insert
20 Fr standard low pressure valve
'
r:l �...--, Size and insert
20 Fr sta ndard
low pressure valve
Arrange videoflucroscopy ,anei insufflation
Voice?
� iJ.lJ
Keep but arrange videofluoroscopy and Insul��tiori
Keep and review/change in 6 months or \\'hen leaks
Or insert 20 Fr Indwelhng valve Keep and review/change in 6 months Of when leaks Figure 195.4
Surgical voice decision-making flowchart.
©
P. Kromer
2001
(updated
2003).
FG, French gauge; TEP, tracheo
oesophageal pressure. This schema is printed with kind permission of P Kromer, based on lectures and notes by Y. Edels
able to perform a glottal stop. This, therefore, can make activities such as lifting
difficult and there is reduced olfaction. They can be taught to perform movements with the cheeks which can move some air up into the nose, but
Or keep and teach to serf-change
(2001).
this is clearly a major problem which has not yet been surmounted. Patients from any cause
who have an open tracheostomy in addition may have problems swim
ming, bathing and taking a shower.
2630
I PART 17 HEAD AND NECK TUMOURS
He a t moisture exchange devices.
Figure 195.5
(a) Sto m ve n t (Gilbeck); (b)
Trach e n aze Plus with shower protector (Kapitex);
(c)
Trachenaze (Kapitex); (d) Provox (Atos Medical).
PSYCHOSOCIAL REHABILITATION AND ADJUSTMENT
ASSESSMENT OF QUALITY OF LIFE AND REHABILITATIVE OUTCOME
Assessment of psychosocial adjustment is necessary to
The ability to quantitate outcome in all aspects of
improve clinical insight) obtain the best possible out
rehabilitation has improved with the passage of time
come for a particular patient and assess the results of
with
treatment better. There are several methods of assessing
although there is not yet standardization. Perception of
this. The PEGASUS study24 used the COOP-WONCA
speech is essentially subjective, but several instrumental
system
which
has
proved
by
different
authors)
outcome measures are also available?9.30 W hilst some
clinically usefu1.26 This has proved feasible for multi
standardized measurements can be made in respect of, for
centre use in clinical practice. Six months after total
example, oesophageal speech, their use is by no means
laryngectomy,
be
universal and many of the factors are largely subjective.
maximal and stable. In this study gender and age did
The evidence base associated with this area is very limited,
not seem to be a major influence on functional status,
but increasing all the time. [***/**/*] A range of outcome
whilst the presence of a partner resulted in a better
measures is summarized in
psychosocial
British Association of Otolaryngologists - Head and Neck
adjustment,
acceptable
advocated
and
psychosocial
reliable)
measurements
adjustment
especially
seems
those
to
concerning
social activities.24 This study also showed some surpris
Beyond primary treatment, the
Surgeons (BAOHNS) consensus document 2003?9
ing findings) for example, that the role of laryngectomee
Rehabilitative measures are directed to increasing or
support groups did not necessarily benefit individuals
restoring an individual's quality of life and this is a
and their effect on the rehabilitation process is variable.
multifactorial entity, which may be related to functional
Patients who had a poor psychosocial outcome often
status, symptoms due to disease) psychological aspects
experienced a high level of anxiety) seemingly associated
and ability to socialize,31 Consideration of rehabilitation
with extensive presurgical counselling and this result
following
goes against the generally accepted belief that counselling 7 improves rehabilitation.2
discussion of these concepts and the principle of health related
laryngectomy
quality
of
life
is
not
complete
measurement.32
It
without is
a
usually
Major resective surgery of this nature is associated
measured by a structured questionnaire completed by
with psychological/body image problems in head and
the patient or in conjunction with discussion with a
neck cancer treatment in general, but particularly in
health professional. Whilst this is a rapidly increasing area
respect of the post-laryngectomy patient?8 It is im
of interest, there is no standardization as yet between head
portant that the views of patients undergoing total
and neck centres and each scheme may measure slightly
laryngectomy should also be taken into account and with
the recent trend for patient empowerment in making the treatment groups
decisions,
have
concerns)
this
advised
such
as
in
the
is
essentiaL
respect
of
availability
Laryngectomee their of
principal
pretreatment
counselling, 'befriending' patient partnerships to both the
patient
appropriate
and
family
treatment)
throughou t. 29
with with
access the
to
timely
necessary
and
support
different factors. Examples include the European Orga nisation for Research and Treatment of Cancer (EORTC) and the University of Washington Head and Neck Cancer questionnaire,29 which contains items specific to head and neck cancer. Much of this work has been undertaken in patients with oral carcinoma and it is recommended that quality of
lif�
assessments to establish rehabilitative
aspects should be completed at pretreatment, six months and one year at least.33
Chapter 195 Rehabilitation after laryngectomy I
would eliminate the need for tracheo-oesophageal
KEY POINTS •
Aspects after laryngectomy requiring
speech.
»
rehabilitation include:
- problems with tracheostomy;
be directed to making prostheses last longer and maintain low resistance.
>- Further work needs to be undertaken in connection with maintaining tracheobronchial humidification and
- problems with loss of glottal occlusion;
eliminating airway irritability.
- problems with airway diversion;
As treatment with radiotherapy and chemotherapy
- body image/psychological/social problems.
•
Whilst tracheo-oesophageal speech is the current gold standard for voice rehabilitation, work needs to
- speech; - swallowing;
2631
improves, total laryngectomy may ultimately not be
The majority of patients nowadays are offered
necessary in the treatment of laryngeal cancer.
primary tracheo-oesophageal puncture and valve fistula speech which should be obtainable in the majority of patients undergoing this. •
Secondary insertion of tracheo-oesophageal valves is much less frequently practised now.
•
undergone total laryngectomy report swallowing problems. •
REFERENCES
A significant proportion of patients who have
Rehabilitation should be undertaken using a team approach, which includes a speech
1.
Anonymous. Information for laryngectomy patients. The National Association of Laryngectomee Clubs: London, 1995.
2.
Dworkin JP, Sparker AA. surgical vocal rehabilitation following total laryngectomy. A state of the art report.
therapist.
Clinical Otolaryngology. 1980; 5: 339-50. 3.
Birchall MA. Laryngeal tranplantation. British Journal of
4.
Armstrong E, Isman K, Dooley P, Brine D, Riley N, Dentice R
Surgery. 1997; 84: 739-40.
Best clinical practice
et 01. An investigation into the quality of life of individuals after laryngectomy. Head and Neck. 2001; 23: 16-24.
Almost all patients these days should be offered
5.
tracheo-oesophageal voice prosthesis fitting at time
whistle: A simple device for laryngectomees. Journal of
of primary surgery, exceptions include complex reconstruction and patients with poor manual
Laryngology and Otology. 1995; 109: 137-8. 6.
Zannoff DJ, Wald D, Montague JC, Kruegar X, Drummond
dexterity.
S. Tracheo-oesophageal speech: With or without
The management of the patient should be undertaken
tracheostome valve. Laryngoscope. 1990; 100: 498-502.
by a multidisciplinary team, including a speech
7.
Taub S, Spiro D H. Vocal rehabilitation of laryngectomees.
8.
Sisson GA, McConnel FMS, Logemann JA, Yehs. Voice
therapist.
,/ The patient should have access to ENT clinics on an
American Journal of Surgery. 1 972 ; 124: 87-90.
emergency, as-required basis, should the prosthesis
rehabilitation after laryngectomy. Archives of
start to leak or malfunction. The patient should be given appropriate information
../
Jepson R, Alderson DJ, Clegg RT, Parker AJ. The Jepson
Otolaryngology. 1975; 101: 178-81. 9.
Shedd D, Schaaf N, Weinberg B. Technical aspects of
should they need to seek advice when away from
fistula speech rehabilitation following
their usual hospital support base .
pharyngolaryngectomy. Journal of Surgical Oncology.
Prosthesis selection remains a matter of personal preference by the team, but should be one with which
1976; 8: 305-10. 10.
Conley JJ, De Amesti F, Pierce MK. A new surgical
they are familiar and for which they have adequate
technique for the vocal rehabilitation of the
supplies. The prosthesis should be low resistance and
laryngectomised patient . Annals of Otology, Rhinology and
most patients prefer front-loading devices.
Laryngology. 1972; 67: 655-64. 11.
Asai R. Laryngoplasty after total laryngectomy. Archives of
12.
Arslan M, Serafini I. Restoration of laryngeal functions
Otolaryngology. 1972; 95: 114-9.
Deficiencies in current knowledge and areas for futu re research )'7 Laryngeal transplantation would ultimately be a desirable option following laryngectomy and
after total laryngectomy. Report on the first 25 cases. Laryngoscope. 1972; 82: 1349-60. 13.
Staffieri M, Procaccini A, Steiner W, Staffieri A. Surgical rehabilitation of speech after total laryngectomy: The Staffieri techniques. Laryngologie, Rhinologie, Otologie. 1978; 57: 477-88.
2632 * 14.
15.
I PART 17 HEAD AND NECK TUMOURS
Blom ED, Singer MI. Surgical prosthetic approaches for
and rehabilitation for cancers involving the larynx. Final reports parts I and II. An EEC funded concerted
Hill Press, 1979: 251-76.
action: BIOMED BMH1CT94-1611. Brussels: EEC,
Blom ED, Singer MI, Hamaker RC. A prospective study of
2000. 25.
randomised comparative study of tracheo-oesophageal
l\Jijdam HF, Annyas AA, Schutte HK, Leever H. A new
voice prosthesis: Blom-Singer versus Provox.
Archives of Otorhinolaryngology. 1982; 237: 27-33.
Laryngoscope. 1998; 108: 1561-5. 26.
Hilgers FJM, Schouwenburg PF. A new low resistance self
WONCA charts. Disability and Rehabilitation. 1993; 15: 96-101. 27.
laryngectomy quality of life dimensions identified by
Aerodynamic properties of the low resistance Groningen
patients and healthcare professionals. American Journal of
Surgery. 1991; 117: 657-61.
Surgery. 1992; 164: 619-22. 28.
Heaton JM, Parker AJ. In vitro comparison of the Provox speaking valves. Journal of Laryngology and
Otolaryngology. 2001; 26: 351-6. 29.
Parker AJ, Stevens JC, Clegg RT. An apparatus to measure
Otolaryngologists - Head and Neck Surgeons at the Royal
pressure flow and speech parameters in patients
College of Surgeons of England, 2002.
producing speech using the Groningen valve prosthesis.
30.
Mahieu HF, Van Saene HKF, Rosingh HJ, Schutte HK.
European Archives of Otorhinolaryngology. 1998; 255:
Candida vegetation on silicone voice prostheses. Archives
371-4.
of Otolaryngology Head and Neck Surgery. 1986; 112:
31.
Aaronson NK. Quality of life - what is it? How should it be
* 32.
Ringash J, Bezjak A. A structured review of quality of life
measured? Oncology. 1988; 2: 69-76.
321-5. Ell SR, Mitchell AJ, Parker AJ. Microbial colonisation of the
instruments for head and neck cancer patients. Head and
Groningen Speaking Valve and its relation to valve failure.
Neck. 2001; 23: 201-13.
Clinical Otolaryngology. 1995; 20: 555-6. 23.
Pastore A, Yuceturk AV, Trevisi P. Evaluation of voice and speech following subtotal reconstructive laryngectomy.
Journal of Laryngology and Otology. 1992; 106: 896-9.
* 22.
Wilson J (ed.). Effective head and neck cancer management consensus document. British Association of
Otology. 1994; 108: 321-4.
* 21.
Owen C, Watkinson JC, Pracy P, Glaholm J. The psychosocial impact of head and neck cancer. Clinical
Groningen high resistance, Groningen low resistance and
20.
PMohide EA, Archibald SD, Tew M, Young JE, Haines T. Post
Zijlstra RJ, Mahieu HF, Van Lith-Bijl J, Schutte HK. button. Archives of Otolaryngology Head and Neck
* 19.
Van Weel C. Functional status in primary care: COOP
retaining prosthesis (Provox) for voice rehabilitation after total laryngectomy. Laryngoscope. 1990; 100: 1202-7. 18.
Delsupehe K, Zink I, Lejaegere ST, Delaer P. Prospective
Head and Neck Surgery. 1986; 112: 440-7. prosthesis for voice rehabilitation after laryngectomy. 17.
Mahieu HM (coordinator). The PEGASUS project: Surgery
FC (eds). Laryngectomy rehabilitation. Houston: College
tracheo-;oesophageal speech. Archives of Otolaryngology 16.
* 24.
post laryngectomy voice restoration. In: Keith RL, Darley
Heaton JM, Sanderson D, Dunsmore IR, Parker AJ. In vivo
33.
Rogers SN, Lowe D, Brown JS, Vaughan ED. Head and neck
measurements of indwelling tracheo-oesophageal
cancer measure as a predictor of outcome following
prostheses in ala ryngeaI speech. Clinical Otology. 1996;
primary surgery for oral cancer. Head and Neck. 1999; 21:
21: 292-6.
394-401.
96 Tumours of the hypopharynx and oesophagus
ANDREW S JONES
I n trodu cti on
2633
Partial pharyngeal resection in hypo pharyngeal cancer
2648
Aetiology
2634
Tota I pharyngo laryngectomy
2648
Epidemi 01 ogy
2634
To ta I pharyngolaryngooesphagectomy
2649
Benign tumours and other non-neoplastic lesions
2635
Chemothe rapy
2649
Molecular and cell biology of hypopharyngeal cancer
2635
Combined treatment protocols
2649
Histology
2637
Other treatments
2650 '
Anatomy
2638
Treatment of the neck ( irradiation)
Locoregiona I spread of hypopha ryngea I canee r
2638
Treatme nt of the neck
Sym ptomato logy
2642
Patterns of failu re
2651 2653
2651
(su rg ery)
2651
Signs, diagnosis and investigation
2643
Prognosis and survival
Staging
2645
Complications
2655
Tumours of the cervical oesophagus
2646
Summary
2656
Treatment
2647
Key points
2656
Radiotherapy
2647
Best clinical practice
2657
Surgery
2648
References
2657
Endoscopic surgery
2648
----�
._..-
SEARCH STRATEGY The initial search strategy used PubMed and Medline with
the lvleSH headin gs hypopharynx, piriform fossa, postcricoid, gast r i c transposition, free jejunal graft , radiotherapy
posterior pharyngeal wail, tumour, cancer, squamous cell carcinoma,
and che mot herapy, in various combinations. The search was refined or extended as necessary. Back searching from review
d atabas es were searched, such as a ll, 1678 relevant references were identified. Initially these were selected using t he title and then the abstracts; finally 381 o r i gin al articles were used in the pre pa ration of the present chapter. The chapter also makes use of the data from 599 p a tien t s from the University of
articles and from book cha pters revealed a n umber of additional references. Finally, other the Cochrane database, the library of the Btitish Medical Association and CHINAL. In
Liverpool head and neck database. This was started by my predecessor, Philli p Stell, and since his retirement maintained by me. The database contains details on over
7000 patien ts with head and neck tumours and this chap ter makes lise of these
data, not only in its preparation, but also for detailed calculations of recurrence and survival. All calculations have been carried out specifically for this chapter.
I NTRO D U CTION
hypopharynx and the larynx are only millimetres apart,
pharynx and is an atom i cally arbit rarily defined. Historically) tumours in this re gion have been considered as extrinsic laryngeal
hypopharyngeal cancer being assoc i at ed with less than
their natural history could not be more dissimilar with The hypopharynx means literally the low
carcinomas)
as
opposed
to
intrinsic.
Whilst
the
half the survival rate of its laryn geal neig hbour. Cancer of the hyp ophary nx:
is rare. 'vVith 2000 new cases bein g
regist ered annually in the Un i ted Kingdom, this would
2634 I
PART 1 7 HEAD AND NECK
TUM OURS
approxim ate to an incidence of 1 in 100,000. Bradlei estimates that the general otolaryngologist sees three previously untreated hypopharyngeal cancers per year in the U K and the majority of these would be (incorrectly) treated with irradiation. Sweden has an excellent national cancer database and reported just over 2000 cases of this cancer over a period of 30 years. This would approximate to an incidence of around 1 in 80,000 2 with the tumour specific five-year survival only 1 3 percent. In the Euro care 2 Project, Berrino and Gatta studied 35,000 reported cases in 17 European countries over four years and found that hypopharyngeal cancer has the p oorest prognosis of any head and neck cancer (22 percent at five years) . For some reason, cancer of the hypopharynx was common in Sweden and Iceland, it was half as common in Eastern European countries, but the prognosis there was sub stantially poorer. 3 [**1
AETIOLOGY The aetiology of hypopharyngeal cancer has not been extensively studied. There is little doubt that cancer of the piriform fossa is smoking related, but alcohol consump tion is also a factor.4, 5, 6 The IARC multicentre study confirms that important causes of hypopharyngeal cancer are cigarette smoking and alcohol consumption. 7 They were specifically interested in the effect of diet and point out that a low intake of fruit and is associated with an increased risk of these cancers. Studying a population of over 3000, they found that a diet particularly rich in vitamins C and E and high in polyunsaturated fatty acids, as opposed to saturated fatty acids, was protective. Another study demonstrated that a sufficient ( European Union defined daily intake) consumption of zinc-containing foo d increased the disease-free interval for patients with head and neck cancer in generaL This included cancer of the hypophar ynx; a decreased intake was associated with increased size of the primary tumour at presentation. These effects are likely to be immune mediated. The detrimental role of alcohol was further highlighted by work carried out on Swedish head and neck patients with a known excessive intake of alcohol. The standardized incidence ratio (SIR ) for cancer of the oral cavity and pharynx (largely hypopharynx) was 5.3. cancer was also more common with an SIR of 4.29. In a Japanese study, 6 2 patients with cancer of the hypopharynx were investigated with regard to subsite-specific risk factors. Oesophageal cancer was also studied. The most important risk factor for hypopharyngeal cancer was the excessive consumption of alcohol. The risk of combined high alcohol intake and smoking was multiplicative. In contrast, they found that daily raw vegetable consumption lowered the risks of these cancers. IO Indeed, postcricoid and oesophageal cancer may be particularly influenced by dietary factors.
[**]
Most head and neck oncologists have suspected that occupational exposure to various substances may con tribute to the risk of head and neck cancer. In another Swedish based study, asbestos was associated with an increased risk of laryngeal cancer but not hypo pharyngeal cancer. Exposure to welding fumes for over eight years was associated with an increased risk of all pharyngeal cancers, with a relative risk of 2 . 3 and a dose response was noted. Significant exposure to polycyclic aromatic hydro carbons was associated with oesophageal cancer, with a relative risk of nearly 2 . This finding may also extend to the postcricoid region. l l Radiation exposure, largely related to the old p ractice of irradiating the thyroid in Graves' disease, has long been suspected as being a cause of hypopharyngeal cancer. Two case reports from 1979 support this suspicion 12 and our department has also noted this association. Of great significance to the overall survival of patients with hypopharyngeal cancer is its well-known association with cancer of the lung. This is hardly surprising as both sites share similar aetiological factors . The relative risk of developing lung cancer in a patient who has had hypopharyngeal cancer is approxi mately 2 : 3 [***] .
EPIDEMIOLOGY The epidemiology of postcricoid cancer has been considered historically to be different to that of cancer of the piriform fossa. Certainly the former is more common in women, according to the Liverpool series of Jones and Stell ( own data) . 1 3 The male and female ratio is approximately 1:2. In our series of these cancers (in which we include cervical oesophageal tumours ), both p ost cricoid cancer and piriform fossa cancer each accounted for 43 percent of the cases, pharyngeal wall 9 percent and cervical oesophagus 5 percent. Postcricoid cancer is rare in North America, forming less than 5 percent of two series,14 , 15 but for reasons that are not apparent, postcricoid cancer is more common in Canada and in largely malnourished India. The incidence is also high in Iran. 16 It should be noted that in Europe generally, postcricoid cancer is relatively unusual. Kleinsasser I6 attributes the variation in incidence of postcricoid cancer to the Patterson-Brown Kelly syndrome. This syndrome is characterized by a small well known to trainees, stomatitis, smooth pale narrow lipped mouth, facial skin and koilonychia. Later, iron deficiency was added to the collection of symptoms and signs.17 Whilst it appears that the Patterson-Brown Kelly syndrome was risk of future development of associated with a 30 postcricoid cancer, the condition is no longer common. and anaemia due to dietary Widespread iron deficiency is now rare in western Europe, although the same may not be true for other countries, such as India. Whilst this syndrome has had a high prevalence in parts of Scandinavia, the United Kingdom and Holland, its
Chapter 1 96
incidence has dramatically declined since about 1 950. 1 9 The experience of most head and neck units in this country, including our own, is that the Patterson-Brown Kelly syndrome is not an important cause of postcricoid carcinoma and dietary considerations and alcohol con sumption may now be far more pertinent. [**J
B E N I G N TUM O U RS A N D OTH E R N O N N EOPLASTIC L ESI O N S Benign tumo urs account for less than 1 percent o f all hypopharyngeal neoplasms. The most common are leiomyomas, fibrolipomas and papillomas, and carcinoma in situ occurs very occasionally (own data) . 2o One reason for the very low incidence of all these lesions is because they tend to be asymptomatic and the relatively high, perhaps disp roportionately high, incidence of leiomyo mas and fibrolipomas may be because they are readily seen on barium swallow. Once diagnosed they are usually readily dealt with endoscopically or occasionally by lateral pharyngotomy. Sofferman et al. first described the nasogastric tube syndrome in 1 98 1 and it has been described by others since, 2 1 , 22 , 2 3, 24 so that by 200 1 , 29 cases had been described in the world literature. It usually manifests itself as a bilateral vocal cord palsy, pain and stridor. Endoscopy demonstrates ulceration of the posterior surface of the cricoid cartilage. It is thought that this damages the posterior cricoarytenoid muscle by mechanical, inflam matory and infective mechanisms including gastrooeso phageal reflux. 22 The condition is relatively common in diabetic patients with renal failure 2 1 and presumably other at risk gro ups, such as those with bone marrow depression from whatever cause. It is known that the use of large-bore nasogastric tubes increases the risk of developing this condition, a risk ameliorated by the use of small-bore tubes. 22 It is likely that less fulminant forms of this syndrome are relatively common, 2 3 but the diagnosis can only be excluded by direct visualization of the postcricoid area. Perhaps surprisingly, other non-neoplastic conditions of the hypopharynx, such as congenital stenosis, mal formation or hamartoma, have never been described. A condition that has started to cause some concern in Liverpool is acquired stenosis of the hypopharynx. This is always following radical radiotherapy for laryngeal or hypopharyngeal cancer and it may be more common still after chemoradiation protocols. At the time of writing the database contains eight patients. The condition appears several years following radiotherapy and although at first mild, the symptoms worsen quite rapidly. The main symptom is dysphagia, but laryngeal incompetence soon follows leading to overspill, coughing and chest infection. Pain is often present. Undo ubtedly some patients have chondroradionecrosis and this should be treated with long-term tetracycline and steroid therapy. It will not,
Tu m o u rs of the hypop h a rynx a n d oeso p hagus I 2635
however, cure the stenosis. Endoscopy demonstrates a rigid, nonpliant larynx and hypopharynx and typically it is very difficult, or impossible, to displace the larynx anteriorly with the hypopharyngoscope. Often the hypopharynx can only be entered by small-bore fibreoptic instruments. The mucosa is scarred and fibrous, typically white in colour and bleeds easily. It is unwise to take a biopsy because of the risk of initiating necrosis. In our series, two patients have been operated upon with a view to treating the stenosis. The hypopharynx is approached via a lateral pharyngotomy using a horizontal neck crease incision comp atible with further, more extensive surgery. The constrictor muscles are divided vertically and the larynx reflected anteriorly and to the opposite side. A free, revascularized, radial forearm flap is then used to repair the defect. In one patient the results were good, but in the second symptoms soon recurred due to restenosis between the larynx and pharynx. Following this experi ence, it is now our policy to offer a radiological percutaneous endoscopic gastrostomy (PEG) and a tracheostomy (with a speaking tube) if necessary. A final non-neoplastic condition of the hypopharynx is dilated veins on the posterior aspect of the posterior cricoid plate. These are frequently seen on barium swallow and are of no consequence.
MOL ECULAR A N D CELL B I OLOGY O F HYPOP HA RYN G EAL CA N CE R A s discussed i n Chapters 1 80, Aetiology of head and neck cancer; and 1 83, Prognostic indicators and serum markers, cell and molecular biology generally is in a state of some disarray. Considerable data are available which are frequently confusing and often contradictory due to a variety of factors, not least a lack of understanding, or a 'unification theory' that embraces the whole of this bewildering subject. The main problems are great redundancy within the genome, how genes relate to the proteome and how genes communicate within the nucleus. Consequently, one is left with a large number of factors that have at some time been described as being important. As regards head and neck cancer, these are often not obviously connected and certainly interplay between these factors is poorly understood. A reasonable place to start is with the genome. In head and neck cancer it is likely that between seven and nine genetic alterations are necessary to produce full carcino genesis (own data) and no single gene or marker is likely to be of much relevance in isolation. Indeed, personal experience of one and a half decades of research in the field of cell and molecular biology of the head and neck has revealed no factor or gene studied to be as good as standard clinicopathological staging at predicting a cure for the patient. In 200 1 , Rodrigo et al. 25 studied the variability of genetic alterations at various sites, including 37
2636 I
PART 17 HEAD AND NECK
TU M O U RS
hypopharyngeal carcinomas. They only studied gene amplification in the region llq 13, which is the site of various oncogenes. They found amplification (a numer ical increase in the number of actual genes) of the oncogenes CCND 1, FGF3 and FGF4. They also studied loss of tumour suppresser genes (genes that control cell and tumour growth; most famously the p53 gene) . In this series they found that p53 was not associated with hypopharyngeal cancer. In the Liverpool department, 32 hypopharyngeal and 35 laryngeal cancers were studied. 26 This was an immunohistochemical ( IHC) study where the object of interest was p athological stabilization of the p53 protein. Normal p 53 protein only survives for between five and twenty minutes. Stabilization of the protein can occur for a variety of reasons, but is generally considered to be pathological and represents inactivation, an oncogenic process. Overexpression was found in 66 percent of hypopharyngeal cancers and 5 1 percent of laryngeal cancers. Whilst we found that an overexpression of the p53 protein in laryngeal cancers was associated with a relatively poor prognosis (the usual finding) , the converse was true for hypopharyngeal tumours where a significant increase in survival was noted with increased stabilization of the p 53 protein. 26 This is a novel finding, which has since been confirmed by other laboratories. Regrettably, p53 mutation detected by IHC does not correlate well with gene mutations. 2 7 In addition, mutation occurs in dysplasia and is thus associated with a very early stage of malignant transformation. [**] It has been noted that the stabilization of the p53 protein is predictive of multiple primary cancers in the hypopharynx and oesophagus. Increased expression of p 53 is not only caused by stabilization, but may represent a true overexpression. This can be caused by a variety of factors including (relevant in this case) , cyclin D 1 expression. Cyclin D 1 ( as the name implies) is important in the progression of the cell cycle and cell division. Because of this it is important in carcinogenesis. Cyclin D 1 overexpression, apart from being predictive of multi ple neoplasms, 2 8 is also predictive of advanced clinical stage, tumour extension and relapse after primary radio therapy and survival. [***] Ki67 is a proliferation marker expressed in the Gl and S phase of the cell cycle. In a recent publication, 13 1 squamous cell carcinomas of the hypopharynx were studied. Cells with high proliferation had a lower five year survival than patients with low proliferation. The five-year survivals were significantly different, being 16 and 30 percent, respectively. 29 , 3 0 [**] The retinoblastoma (Rb) tumour suppresser gene (Rb) is also thought to be important in head and neck cancer. The retinoblastoma protein is complexly related to cyclin Dl. For the cell cycle to progress, the cyclin D 1-CDK4 complex must phosphorylate and thus inactivate the retinoblastoma protein during the G1 phase of the cell cycle. On the other hand, expression of cyclin D 1 in tumour cells requires the presence of a functional
retinoblastoma protein. The current concept is that inactivation of the retinoblastoma protein is essential for carcinogenesis. 3 1 Recent work in our department by Rafferty et al. 3 1 does not, however, demonstrate a significant relation between retinoblastoma protein ex pression, clinicopathological factors or survival in a cohort of T2No laryngeal cancers treated by irradiation. In addition, there was no association between loss of heterozygosity in the Rb gene and the expressed protein detected by IH C. [*] Whilst there is a general consensus among those studying the genesis of head and neck cancer that the p53 gene product inactivation occurs early in tumour formation, followed perhaps by an inactivation of retinoblastoma and amplification of the PAAD 1 ampli clon ( including CCND 1; cyclin D 1) , various studies would suggest that this is an oversimplification. Overexpression of growth factor receptors or over secretion of growth factors may be considered as oncogenic events. The epidermal growth factor receptor ( EGFR) and its ligand have been studied extensively. 3 1 Both of these seem to be overexpressed in 30 percent of 24 hypopharyngeal carcinoma specimens and represent an autocrine 100p. 3 2 Incidentally, in this study p53 mutation ( protein stabilization) occurred very early and indeed even in dysplasia. [**] Overproduction of tumour cells is not the only way a tumour may enlarge. There is a very important process, which occurs in normal cells, termed 'apoptosis', or programmed cell death. This is a normal occurrence allowing remodelling of tissues and disposal of elderly cells. It has been noted that apoptosis is reduced in hypopharyngeal cancer, thus effectively increasing the number of cells in a tumour. 33 Various factors are involved, perhaps particularly the balance between the Bcl2 gene and its heterodimer the Bax gene. The two gene products are very closely related, but Bax is proapoptotic and Bcl2 is antiapoptotic. Thus, increased expression of Bax will push a cell towards apoptosis, whereas the relative overexpression of Bcl2 may save it from apoptosis. Studies have noted that Bax expression is reduced in most head and neck tumours. 34 Needless to say, p 53 is involved in the regulation of these gene products. [**] A bewildering array of tumour markers of putative clinical relevance has been studied by various institutions throughout the world. Whilst some have their advocates, in practice none have survived the rigours of the clinical environment. Several, now out of date, prognostic systems included a number of factors such as the total lymphocyte count (which in practice is the T-lymphocyte count) and more importantly the actual tumour mor phology assessed by a variety of ways, perhaps best defined by Jakobsson. 3 5 Other cytological markers that may be of some relevance are the presence of eosinophils around or i� the tumour and the presence of tumour infiltrating lymphocytes. [**]
Chapter 196 Tumours of the hypopharynx and oesophagus I
A full review of the available (clinically unproven) markers is not appropriate here, but a few of the more promising ones are discussed. Most carcinomas express cytokeratine normally found in the basal layer of the epithelium. Which cytokeratines are expressed will depend on the site of origin and the tumour. Cytokeratine 18 particularly appears to be expressed i n nearly all cancers arising from the hypopharynx and larynx. Others suggest that cytokeratine 18 is likely to be present in cancers occurring from glandular epithelium, where cytokeratine 5 and 6 are seen in carcinomas arising from mucosa. Unfortunately, in practice the picture is much less clear.36 Cathepsin-D is a ubiquitous lysosomal enzyme. In cancer its role is in degrading the extracellular matrix allowing tumour invasion and metastasis. A recent publication suggests that cathepsin-D is a potential independent predictor of cervical node metastases, but not in all tumours.37 Similarly matrix-metalloproteases (MMP) also degrade the matrix. These proteases are controlled by natural inhibitors (TIMP) and it has been found that expression ofMMP-9, with a concomitant lack of expression of TIMP-1 indicates tumour aggressiveness 38 ['**] and an increased risk of relapse. Tumour immunity is a complex subject and has developed somewhat separately from the mainstream of cell and molecular biology. One reason why cancer cells are able to invade and progress is because they have largely escaped the major histocompatibility complex (MHC) system, which is the most highly developed mechanism for dealing with foreign cells of whatever type. Cancer cells largely fail to express relevant MHC antigens necessary for an effective host response to the tumour. There is a more primitive immune system with such effectors as natural killer cells that can often be active against cancer cells. Normally an acute phase response occurs when a foreign cell enters a host. This acute phase response is characterized by a dramatic increase in the concentration of certain plasma proteins, termed (acute phase proteins'. Of these, interleukin 6 (JL6) is particu larly important. Other important acute phase proteins include C-reactive protein, alpha-1-anti-trypsin, alpha1-acid glycoprotein, haptoglobin and fibrinogen?9 The data strongly suggest that IL6 may play a key role in acute phase protein synthesis in head and neck cancer and in regulating the complex host response to such malignan cies. ['*'*]
Table 196.1
2637
Non-squamous tumours of the hypopharynx.
Histology Carcinoma in situ
2
Lymphoma
1
Spindle cell carcinoma
3
Metastases
2
Adenoid cystic carcinoma
2
U nd ifferentiated ca rcino ma
2
T ransitiona I carcinoma
1
Small cell neuroendocrine
3
Adenoca rc i noma
2
Malignant fibrous histiocytoma
2
Benign
4
Liverpool series
n:=
24.
arise from areas of dysplastic epithelium, which merge into a malignant phenotype with invasion of the basement membrane and then adjacent tissues (Figure 196.1). The cancer then invades deeply and centrifugally. Clinically, the cancers behave aggressively with the most dismal five-year survival for any head and neck site. Whilst the biology of these cancers shows some differences from cancers at other head and neck sites (see Molecular and cell biology of hypophalyngeal cancer) none account for their aggressive phenotype. Thus this must be attributed to anatomical and clinical factors. Of the oncogenic viruses and hypopharyngeal cancer, only human papilloma virus has been studied in any detail. It is of interest that the presence of viral DNA in the tumour genome can stabilize p53 protein leading to overexpression. Types 16 and 18 have been detected in this cancer and may be the most important. However types 3 1, 33 and 45 may also be involved. Recent evidence40 suggests that the viral DNA of HPV16 and 18 were also present (using polymerase chain reaction (PCR)) in 11 percent of patients with hypopharyngeal
HISTOLOGY
Nearly all tumours of the hypopharynx and cervical oesophagus are malignant and most are squamous cell carcinomas. Nonsquamous tumours and carcinomas in situ account for only 3.5 percent of twnours in this region in the Liverpool series (Table 196.1). Of the squamous cell carcinomas, the majority (70 percent) are moderately or well differentiated. As usual, the cancers
Figure 196.1
A well-differentiated squamous cell carcinoma
of the hypopharynx arising from the mucosa and showing marked invasion.
2638 I
PART 17
H EAD A N D f\I ECK TU M O U RS
cancer. The findings were significant, although no causal relationship could be inferred. [**]
A NATOMY The hypopharynx was divided into three parts in 1997 by the International Union Against Cancer (UICC) (Table 196.2) 41 and the American Joint Committee on Cancer (AJCC) . The piriform fossa or sinuses represent paired channels for swallowing. They are formed as the pharynx extends laterally around the laryngeal structures. The piriform fossa is bounded medially by the aryepiglottic fold and laterally by the thyroid cartilage. The superior limit is the pharyngoepiglottic fold, as well as the aryepiglottic fold. The inferior limit is a little variable with the tip of the inverted cone-shaped structure extending into the cervical oesophagus. The post cricoid region is the part of the pharynx behind the cricoid cartilages and has only an anterior wall which extends from the level of the arytenoids and connecting folds, to the inferior border of the cricoid cartilage. The third part of the hypopharynx is the posterior wall extending from the level of the floor of the vallecula to the inferior border of the cricoid cartilage (UICC) and from one apex of the piriform fossa to the other. The anatomical subsites of the oesophagus are given in Table 196.3. Small postcricoid and piriform fossa cancers are shown in Figure 196.2.
Ta ble 196.2
LOCO R EG I O NAL SP R EA D O F HYPOP HA RY N G EAL CA N CE R The spread o f tumours within the hypopharynx i s less well defined than tumours within the adjacent larynx. The larynx has well-defined structures forming ligaments and potential spaces that dictate the spread of tumours. To a large extent, this is lacking in the hypopharynx. The pattern of spread is, therefore, more difficult to determine. Some studies involving serial pathological sections have been carried out, however, and from these the spread of piriform fossa cancer can be described in moderate detail. 16 , 42, 4 3 , 44 , 4 5 , 46 Typically, a patient with advanced carcinoma of the piriform fossa will have a neck node metastasis and may indeed present with this. The tumour often extends over the area of the aryepiglottic fold into the larynx or down into the cervical oesophagus (Figure 196.3). Smaller carcinomas of the piriform fossa can be usefully divided into those that arise on the medial wall and those that arise on the lateral wall. Medial wall carcinomas tend to extend into the larynx. They may grow posteriorly, invading the cricoarytenoid joint (Figure 196.4) and also spread through the aryepiglottic fold. Once inside the larynx, submucosal spread occurs with the involvement of the vocal cord, laryngeal ventricle and paraglottic space. As in laryngeal cancers, once the paraglottic space is invaded the tumour may spread outside the larynx again via the cricothyroid membrane.
UI CC c l a ssifi cation of the a n atom i ca l su bsites (hypo p h a rynx) .
UICC classification
Pharyngooeso p h a g ea l j u n ction (postcricoid a rea) (C 1 3 .0) exte nds fro m the leve l of the a ryte n o i d ca rtilages a n d connecti ng fo l d s to the i nfe rior bord e r of the cricoid ca rti lage, thus fo rm i n g the a nterior wa l l of the hypo p h a rynx 2 Pi riform sinus (C 1 2.9) exte nds from the pha ryngoe pig lottic fo l d to the u pper e n d of the oeso p h a g us. It is bou n d e d late ra l ly by the thyro id ca rti l a g e a n d m e d ia l ly by the hypo pha ryngea l s u rface of the a rye pi g l ottic fo l d (C 1 3 .'I ) and the a ryte n oids and c ricoid ca rti l ages 3 Poste rior p h a ryngea l wa l l (C 1 3 .2) exte nds fro m the su perior l evel of the hyo i d bo n e (or fl oor of the va l l ecula) to the l evel of the i nferior bord er of the cricoid ca rti l a g e a n d fro m the a pex of o ne pi rifo rm sinus to t h e oth e r Reproduced from Ref.
Ta b l e 196.3
41, with permission.
U I CC c l a ssifi cation of a n atom ic a l su bsites (oeso p h a g us).
UICC classification
Cerv i ca l oeso p h a g u s (C 1 5.0) co m m e n ces at t he lower bord e r of the cricoid ca rti l a g e a n d e n d s at the thoracic i n l et (su p rastern a l n otch), a pp roxi mately 1 8 cm fro m the u pper i n cisor teeth I ntrathoracic oeso p h a g u s
2 (i)
The u pp e r thoracic po rtion (C1 5.3) exte n d i ng fro m the thoracic i n l et to the l evel of the tra c h e a l bifu rcati o n , a pp roxi mately 24 cm fro m the u pper i n cisor teeth
(ii)
The m i d-thoracic po rtion (C 1 5.4) is the p rox im a l h a l f of the oeso p h a g u s between the tra c h e a l b ifu rcation a n d the oesophagogastric j u n ction. The l evel is a p proxi mately 3 2 cm fro m t he u pp e r i n cisor teeth
(iii) The lower thora cic po rtio n (C1 5.5) , a p p roxi mate ly 8 c m in l e n g th ( i n c l u des a bdo m i n a l oeso p h a g u s) , is the d ista l h a l f of t h e oeso p h a g u s between the trachea l bifu rcation a n d the oeso p h a g og astric j u n ction. The lower l evel is a p p roxi mately 40 cm fro m the u pp e r i nc isor teeth Reproduced from Ref.
41, with permission.
Chapter 196 Tumours of the hypopharynx and oesophagus I
2639
About half the cases of piriform foss a cancer demonstrate
vocal co rd fixation at the time of prese n tation
196.5).
Laterally
pla ced
tumours
frequently
(Figure spread
thr ough the thyr oid cartilage. The tumour commonly
jnvolves the thyrojd gland by sp reading inferiorly and
often involves the muscles of the posterior pharyngeal wall by submucosal extension. Recurrent laryngeal nerve involvement is a frequent
skeleton is i nfil tra ted
finding and the laryngeal
in about
half the cases, particularly
in apical piriform fossa tumours. Vocal cord
fixation can
be due to three causes: invasion of the cricoarytenoid
j oin t, invasion
of the posterior cricoarytenoid muscle or
involvement of the recurrent laryngeal nerve.44,47 The m ost
part
common
lS in
destroyed
the
thyroid
cartilage to be
region
of the
superior
of
the
cornu,
superi orly and posteriorly. Piriform fossa cancers, when
spreading superiorly, often involve the base of the tongue and lateral oropharyngeal wall. Not infrequently, parti Fi g ure 196.2
A small postcricoid carcinoma (arrow).
cularly with laterally based tumours, a mass is prese nt in the neck,
representing lymph
node
metastasis.
This
frequently forms a continuous tumour mass with the primary cancer and the mass is o ft e n attached to the carotid artery.
�
..
;'
." J,:
, 'c. '. }" #'--* .
,
-I� ..,
"
· ·' ·
, ::;.,
. �.J: .
; .'
. .
. '
r � .' .
.'
fit
.
��
.
"
: . �
..
:,;:
� " ',
�
�
-
� �.' . �.;�,'.'" > �,. ,"I
_..
'-' > .
.
. ---. .',
/
Pirifonn
l H]
fossa cancer as
postcricoid cancer
tends
to pre sent later than
cancer in one piIiform fossa still
allows swallowing down the uninvolved fossa , Postcricoid studied,
carcinomas
but the
data
have
not
been extensi vely
that have been published43•46
demonstrate that the cricoid c a r tilag e is often invaded
and the tumour may spread into the trachea, causing a irway obstruction
(Figure 196.6). As with p iri form
cancer, the tumour may infiltrate the posterior
ytenoid muscle and may escape thro ugh the cricothyroid
'.
.' '
::.L
Fig ur e 196.3
A large right piriform fossa carcinoma.
Fi g ure 196.4
Invasion of the cricoarytenoid joint by piriform
fossa cancer (arrows),
fossa
cricoar
Figure 196.5
A right vocal cord palsy due to a small
postcricoid carcinoma .
2640
I PART' 7 HEAD AND NECK TUMOURS
Figu re
, 96.6
Figure
Trachea I invasion by a postcricoid card noma
196.7
Thyroid gland invasion by a postcricoid
carcinoma.
(arrows).
membrane and from there into the thyroid gland
(Figure 196.7). Postcricoid lesions usually have si gn ifican t sub mucosal spread, in the region of 0.5-1 cm43,48 or more from the mucosal margin of the tumour and this extension is much more pronounced inferiorly
than
superiorly. The proximity of t hese lesions to the cervical oesophagus
and subm u cosal lymphatic plexus ensures skip lesions within the cervical oesophagus are not 49 Of great concern is that uncommon (Figure 196.8). submucosal extension in the cervi cal oesophagus has been reported for up to 8 em from the tumour edge, although it is uncertain how many of such cases represent a second tumour. Invasion of the cr icoaryteno i d muscle, crico th at
arytenoid joint or recurrent laryngeal nerve ensure that vo cal cord paralysis is not an uncommon feature of
Figure
A large postcricoid carcinoma extending into the
tumour edge (arrow).
p ostcricoid cancer occurri ng in about a third of pa tients at presentation. Posterior pharyngea l wall tumours are
196.8
cervical oesophagus with a skip lesion 4 em from the advancing
The spread of carcinoma of the hypopharynx and
and are frequently large at the time of diagnosis. In spite
oesophagus is greatly fac i litated by a rich supply. The lymph nodes along the internal jugular vein tend to be involved, particularl y the upper
of this, invasion of the prevertebral fascia occurs late. The
and mi ddl e deep cervical nodes.51 Seventy percent of
rel atively unusual and, because of this, have not been
studied extensively. The tumours tend to be exophytic
tumour
usually
l ymphatic
first
lymph node metastases from the hypopharynx occur in
always involves the posterior wall
the upper deep cervicat and 23 percent occur in the mid
involves
dia gnosed and almost
ce rv ical
adjacent
areas
when
of the oropharynx. The tumour may extend superiorly to
and lower deep cervical nodes.
the base of the tonsil and laterally to the orophar ynge a l
in
wall, or spread inferiorly in to the postcri coid region and cervical oesopha gus . As the tumour enlarges and bulges into the phar ynx it typically ulcerates in a linear fashion.
[**]
Tumours of the cervical oesophagus are rare. The
cervical oesophagus itsel f is a ver y artificial ana tomical
category, forming the top of the oesophagus within the
neck, i.e. from the inferior border of the cricoid cartilag e to the thoracic inlet. The main reason for including it
with hypopharyngeal cancer is that the treatment of
cancer of the two si tes is s imi la r. The d isease tends to be SO characterized by endomural skip metastases and such lesions may occur many ce n t i me tres from the mu cosal
edge of the tumour.
(**1
Of pa rt icular si gnific anc e hypopharyngeal ca ncer is the spread to the retro pharyngeal system of lymphatics and nodes. The frequency of such involvement is unknmvn, but it is c ertainl y i m porta n t . 52 Thus, the lymphatic drai n ag e of the hypophary nx is largely to the inferior extent of the deep jugutar chains3 and the posterior pharyngeal wall subsite probably drains mos tly to the retropharyngeal nodes. 52 Piriform fossa tumours tend to drain via lympha tic vessels which pass with the recurrent laryn geal nerve through the cricot hyroid membrane and this tends to fa vour metastases in the upper deep cervical region. Inferior hypo pharyngeal tumours metastasise via lymph vessels
along
.the tracheooesoph ageal groove, to the lymphatic drainage of the larynx and hypopharynx into an anterior and paratracheal nodes , 52 dividing the
Chapter 196 Tumours of th e hypopharynx and oesophagus I
posterior system. The anterior system drains the piriform fossa and follows the line of the superior laryngeal artery, piercing the thyrohyoid membrane, then joining vessels from
the
supraglottis,
to
drain
ultimately
into
the
subdigastric and middle jugular nodes, as well as nodes below the common facial vein. The posterior group are represented by lymphatic vessels from the pharyngeal
2641
produced a neck node metastasis. Regrettably, a propor tion of such patients will have nodes extending down the
system into the superior mediastinum. Of those patients who develop neck node metastases, 53 percent had nodes in the upper deep cervical region
paratracheal
and 27 percent had nodes in the lower or mid deep
cervical regions. Up to
wall. These pierce the inferior constrictor muscle and pass
80 percent of patients with carcinoma of the
into the retropharyngeal and deep cervical nodes. This
posterior pharyngeal wall will have neck node metastases
drainage is of particular significance as
it probably leads to ear ly involvement of nodes in the superior mediasti
. at presentatIOn.
num. The cervical oesophagus may drain superiorly and
metastases; 23 percent were NI, 17 percent were N2 and
follow
the
of
pattern
hypopharyngeal
lymph
node
metastases, or may drain inferiorly into the superior mediastinum. explain
the
This
lymphatic
finding52
that
drainage
pattern
patients with
neck
may node
metastases from cervical oesophageal carcinoma survive
43 ' 57
I n th e L'lverpoo I serIes, ' only 44
percent of patients with this cancer had neck node
4
percent
were N3. Eighty percent occurred in the upper
deep cervical region. Again, the retropharyngeal lympha tic system is almost certainly very important. Neck node
metastases
occurred in 31
percent of
patients with cervical oesophageal cancer and they all
longer than patients without. Presumably the latter group
occurred in the mid to lower deep cervical region. Again,
suffered mediastinal lymph node
the retropharyngeal lymphatic system is almost certainly
involvement. [HJ
The incidence of lymph node metastases in hypophar yngeal cancer is very high: between 70 and
80 percent of
with piriform fossa cancer will have lymph node 54 metastases at the time of diagnosis (Figure 196.9).43,44, ,55 The Liverpool series is shown in Table 196.4. Seventy-four patients
very important. As previously stated, these patients did better than those without node metastases
,
probably
because drainage to the superior mediastinal lymphatics occurred in the latter group. 56
[Hl
As in laryngea l cancer, distant metastases at presenta
percent of patients with neck nodes from the piriform fossa
tion in the absence
had nodes in the upper deep cervical region and almost all
probably relatively unusual, although this is by no means
of regional lymph node involvement is
the remainder were in t he mid or lower deep cervical
56 Less than 10 percent of piriform fossa tumours
always the case.16 Once distant metastases have been
region.
diagnosed, survival is usually less than one year.60 Most
have bilateral metastases at the time of presentation,S7 but
patients with metastases due to hypopharyngeal cancer
even small (T1 or T2) pirifonn fossa cancers are frequently
will have lung involvement and these usually become
associated with a lymph node at presentation. 44 Even
mani fest
within 18 months of presentation of t he original
patients who have no p alpable nodes at the time of
tumour. The incidence of distant metastases at presenta
presentation of their piriform
tion in
harbour
occult
neck
node
fossa cancer frequently
metastases.58, 59
important to note that 11 percent of patients
It
5019 cases was reviewed by Merino
et ai.61 and was
also
11 percent for squamous carcinoma of all head and neck
with piriform
sites. In the case of hypopharyngeal cancer, the figure is
is
fossa cancer with node metastases have disease in the
much higher in
supraclavicular fossa or posterior triangle.
metastases in the mediastinum and paraaortic region
[**]
Postcricoid cancers are less often associated with neck 49 and in the
the
region
of
24
percent.
Further
may be detected in patients 'With lung metastases. In my
node metastases than piri form fossa cancer
experience, liver metastases are found next in frequency
Liverpool series o nly
and they tend to be sma] I and multiple. Liver function
30 percent of cancers at this site
biochemistry is often not affected until late in the disease process, but even jf abnormal may merely reflect the high alcohol intake typical of patients with this cancer. Bone metastases, which are usually osteolytic, occur next in frequency and in hypopharyngeal cancer may account for up to 35 percent of all cases of distant metastases. As in the larynx, they usually occur 'Within one year and are
almost always associated with metastases to the lung and liver.16 Skin metastases occur in patients, particularly if they have had surgery, and are still more common in the
presence of locoregional recurrence. Metastases to other
organs, such as adrenals, kidneys, brain, bowel and heart, have all been described Second Figure 196.9 mass
(an
A
patient presenting with a large right neck due to an ipsilateral piriform fossa cancer.
N3 node)
primary
as
late events.
tumours
[**]
occur
in
hypopharyngeal cancer, as they do
in
patients
'With
patients 'With
cancers elsewhere in the head and neck. The incidence has been repor ted as
6 percent over a period of up to 30
2642
I PART 17 HEAD AND NECK TUMOURS
Host, tumour and treatment factors in previously untreated hypopharyngeal squamous cell carcinoma.
Table 196.4
OJb
Factors Sex and age
Host factors
Men
58
Minimum age 62.4
Women
42
Minimum age 61.9
(0)
63
Quite well (1)
21
years years Well
General condition
Moderately well (2) Unfit Tumour factors
Site
T stage
N stage
6
3
(3)
Moribund (4)
7
Pi riform fossa
45
Post cricoid
40
Posterior pharyngeal wall
8
Cervical oesophagus
7
1
25
2
27
3
35
4
13
0
55 13
Histology
Primary curative treatment
2a
10
2b
2
2c
6
2
14
Well-differentiated
26
Moderately differentiated
45
Poorly differentiated
29
No curative treatment
27
Radiotherapy
32
Surgery
41
Source. University of Liverpool database,
n ==
599. All factors are percentages.
years,62 but other studies have reported higher figures.
63
such as the globus sensation, is the source of common
In our series, the incidence of second primary tumours
referrals in otolaryngological practice. It is usually not due
was less in the hypopharynx than for other head and neck
to serious disease, but if it persjsts it must be investigated.
sites, and this may be attributed to the relatively poor
It is frequently stated that hypopharyngeal cancer presents
survival
late. Reference to the Liverpool database, however, shows
in this condition,
reducing
the number
of
patients available to develop a secondary primary tumour.
that half of the patients in fact presented with Tl or T2
(**)
lesions. This is crucially important as early disease may be successfully treated by irradiation.64 Otalgia has been well described and is due to referred pain. The vagus nerve
SYMPTOMATOLOGY
supplies the supraglottis and piriform fossa mucosa, as
Symptomatology is necessarily a subjective entity both for the patient and the oncologist. Nevertheless, certain symptoms
of hypopharyngeal
cancer
can
alert
the
physician to this condition. The cardinal symptoms and
signs are dysphagia) hoarseness of voice, sore throat, otalgia and weight loss with or without a lump in the neck
(Table 196.5).
Pain on swallowing and the presence
of a unilateral sore throat tend to occur early in the disease. True -dysphagia, hoarseness of voice and otalgia are later indicators. Altered sensation during swallowing,
well as the mucosa of the postcricoid and a little inferiorly to this. This pain is referred through a small branch of the vagus
nerve,
the
nerve
of
Arnold,
which
supplies
sensation to the external auditory canal. Branches of the glossopharyngeal nerve supply the base of the tongue mucosa, which may be involved in a high piriform fossa cancer. Pain may again be referred to the ear, in this case by Jacobson's nerve supplying sensation to the middle ear mucosa.
[**)
Cancer of the three subsites of the hypopharynx produce slight1t different symptoms. For example, true
Ch a pter 1 9 6 Tu m o u rs of the hypoph a rynx and oesophagus I
Ta b l e 1 96.5
2643
patients all that will be seen is pooling of saliva, frequently
Prese nting symptoms of hypopharyngeal ca nce r i n
unilaterally. Unilateral otalgia is common and Trotter's
o rder from early to adva nced d isease.
sign (loss of laryngeal crepitus) may be present with large
Presenting symptom
(usually postcricoid) tumours. Neck palpation will de
1
U n i la te ra l sore th roat (very rarely g lo bus sensati on)
2
Pa i n on swa l l owing (odynophag ia)
3
Oysph agia
4
Hoarseness of vo ice - u n i l atera l cord pa lsy
5
U n i l ate ra l ota l g i a
6
We ight l oss
monstrate nodes in 75 percent of patients with piriform cancer and 20 percent of patients with postcricoid cancer ( Live rpool data) . As in most cancers of the head and neck, level 2 is affected first and levels 3 and 4 later. An enlarged node should have fine needle aspiration cytology per formed by the cytologist in the clinic67 and in most cases an accurate diagnosis
will be available in
20 minutes.
[**]
Diagnostic imaging should be carried out next. A soft tissue lateral radiograph of the neck previously carried out in all patients is now redundant. Some type of
dysphagia occurs quite early in postcricoid tumours, but is a relatively late symptom in p iriform fossa cancer. In
modern imaging procedure must be carried out on the
these as well as in postcricoid cancer, hoarseness is due to
head and neck. This is crucial fo r staging and radio
various mechanisms including invasion of the po sterior
therapy planning and is indispensable to the surgeon.68
crico arytenoid muscle, invasion of the cricoarytenoid
At the primary site computed tomography ( CT) and MRI
(Figure 196. 1 0 ) . To some extent they
joint, invasion of the recurrent laryngeal nerve, or even
are
spread into the paraglottic space fixing the hemilarynx.
subserve different roles. MRI scans do not visualize bone,
A lump in the neck is a presenting feature in about one (Figure 196.9) . For piriform fossa cancer, a lump in the neck
whereas CT does. In tumours that may involve bones
adequate
such as the base of skull and oral cavity, both modalities
in five patients with hypopharyngeal cancer
should be employed. Much controversy exists between
usu ally at level 2 is present in 75 percent of patients when
the two methods regarding soft tissue tumour detaiL
first seen as confirmed by the Liverpool database. Those
MRI is more sensitive and magnetically images protons
patients without a node will almost always harbour occult
that largely reflect the water content o f the tissues.
nodal disease. In postcricoid cancer, only around 20
Peritumour oedema will show up tending t o overestimate
[*]
percent of patients have a node at presentation, but
the size of the tumour. On the other hand, CT scanning
mediastinal nodes and retropharyngeal nodes may well be 65 66 present , and are usually demonstrated on magnetic
may underestimate the size
resonance imaging (MRI) .
of the tumour.
In
our
institution, we tend to use MRI and certainly in areas where much tumour extensi on occurs, such as the base of
[**1
the tongue, we feel it is superior. The argument still rages ho wever,
regarding
the
general
superiority
of either
S IGNS. D IAG N O S I S A N D I NVESTIGAT I O N Most patients entering a clinic who have hypopharyngeal cancer will be in their early seventh decade and most will be
men,
while
women
are
twice
as
likely to
have
postcricoid cancer as men. Inspection may reveal the patient is attempting to swallow frequently and a lump may be noticeable in the neck. Most patients with this disease look unwell and will have lost weight some will have foetor. A
full head and neck examination should be
carried out, inclu ding the use of a fibreoptic endoscope. A biopsy channel in the latter is useful
for immediate
diagnosis by a cytologist who should be present in the clinic. If a tumour is evident) a photograph sho uld be taken and put with the case notes. Most tumours of the piriform fossa will be visualized by this method) although one should be wary of tumours in the apex of the fossa. Most post cricoid cancers are
large
and
will not be visualized unless they
extending
superiorly.
Most
posterior
pharyngeal wall tumours are exophytic and spread widely, and
will often be visualized at the superior extension. It is
rare for a posterior p haryngeal wall tumour not to involve
•
Fig u re 1 96. 1 0
A CT scan of a T4 postcricoid ca nce r
the oropharynx. Fixation of the ipsilateral hemilarynx will
enve l o ping the trachea a n d i nvo lving the prevertebra l fasci a . The
be seen in half the cases of piriform fossa cancer. In some
tu mo u r i s i no p e rable.
2644 I
PART 1 7 H EAD AN D N ECK TUMO U RS
metho d for imaging both the primary site and the neck.69 [*'"] There is a large amount of recent literature on positron emission tomography (PET) . The iso tope usually used is 1 8F-fluro-2-deoxy-D-glucose and the technique is essen tially a measure of tissue metabolic rate. This is variably related to proliferative index. It is a very sensitive tool for detecting primary malignant lesions, as well as metastatic spread) and is known to be superior to CT or MRI in terms of sensitivity. In a recent study from Cologne, 723 pa tients were investigated of whom 27 (3.7 percent) had an u nknown primary tumou r) following ultraso und to the neck and liver, chest radiograph and full upper aerodigestive tract endoscopy. All 27 patients underwent scanning and in just over a quarter of these a primary tumour was found; five were in the head and neck, two were nasopharyngeal, one in the parotid, one in the hypopharynx and one in the tonsil, the remaining patients had bronchogenic carcinoma ?O An important question would be whether CT or MRI would have picked these lesions up; this was no t a ddressed in this publication. [H] The possibility of the presence o f distant metastases must be entertained when considering the most appro p riate co urse of treatment. This is crucially important for patients who are likely to undergo major ablative and reco nstructive surgery. This is a massive undertaking) not only for the patient but also for the su rgeon. The median operating time for a hypopharyngeal tumo ur in our unit is eight ho urs (incl uding free flap repair) . For patients with the rare T l or small T2 cancer, where full staging including panendoscopy has been carried o ut and radio therapy is to be the recommended treatment modality, it may be reasonable to carry out a chest radiograph (Figure 196. 1 1 ) . It must be remembered that with this imaging facility only metastases or second primaries with a diameter o f greater than 1-2 cm will be detected radiologically, whereas CT scanning of the chest has a resolution down to 3 mm. 7 L The Liverpool head and neck u nit carried o ut a study o f the role of chest CT scanning in 1 998 in the management of patients presenting with head and neck cancer, 81 patients were entered into the study all ha d CT scanning o f the chest and liver, 14 of the 8 1 patients were found t o have small p ulmonary tumo urs. Patients with clinically and radiologically negative necks did not tend to get pulmonary metastases) although this was not always the case.72 No patient had liver metastases; a finding noted by other groups. [H] Prom the management point o f view, it may be useful to know if the lu ng tumo ur was a second primary or a metastasis. There are no clearcut guidelines. If the histology is similar, which is usually the case, one is left with a purely clinical decision. Patients with large volume neck disease are much more likely to have a lung metastasis, whereas patients with no neck disease a re more likely to have a second primary tumo ur, altho ugh there is no ro utine method of proving this at present,62 In
Fig u re 1 96. 1 1
A ch est rad iog raph of a p a t i e n t with advanced
p irifo rm fossa ca ncer showing l eft u p p e r zone sh adowi n g . An o bstru cti ng t u m o u r was c l ea rly seen o n bron c hoscopy.
If o ur unit, unless there is good evidence to the contrary and the lung tumour is operable, a thoracic surgeon carries out a pneumonectomy or lobectomy and the head neck cancer is dealt with some six weeks later. There is no evidence that the final o utcome is any different if the lung tumour is a primary or metastasis. Although we have only dealt with a small number of these cases) three are still alive at ten years. [ **] Obvio usly the decision regarding the treatment choice has to be one of goo d clinical j udgement. Many of the pa tients seen in a head and neck oncology clinic will have recurrent disease, which is notoriously difficult to diagnose because of fibrosis, anatomical disorganization and post-treatment oedema. Advocates of PET scanning suggest that two scans performed in sequence (with a gap of a minimum of one year) have 97 percent sensitivity. I t i s suggested that i f the scans a r e negative no biopsy is necessary.73 The Netherlands Cancer Institute have suggested using Th20 L thallium chloride single photon emission computed tomography (SPECT) , which basi cally assesses tumour cell receptor status and they also fo und this method useful for detecting recu rrence and in the investiga tion of occult head and neck tumours. Although the sensitivity of CT/MRI was considerably higher, their specificity was 10wer.74 [ H ] I t is now recognized and common practice i n most head and neck u nits that full panendoscopy must be
is
Cha pter
carried out in every case of head and neck cancer, whether it is primary or recurrent. Panendoscopy not only assesses the primary tumour but is also important 2 in the exclusion of synchronous tumours. 6 , 7 5 In postcricoid cancer, oesophagoscopy is essential because of the skip lesion phenomena. Examination should start with a full inspection and palpation of the oral cavity and oropharynx. A tonsil gag is useful for inspecting the oropharynx, but it must be remembered that it distorts the anatomy and does not allow visualization of the base of tongue. This area is best examined by palpation. If the postnasal space (PNS) appears abnormal using a trans nasal 0° Hopkins rod telescope, then multiple biopsies of the PNS must be carried out. A wide view of the laryngopharynx, lower oropharynx including the base of tongue and upper part of the hypopharynx should be obtained using a Lindholm endoscope. This device allows a p anoramic view otherwise not obtainable by other means. The laryngeal ventricles and the subglottis must be assessed using an angled Hopkins rod telescope. The laryngoscopy continues with the Negus type instrument, the hypopharynx is then examined with a pharyngoscope. It is essential to follow a systematic protocol when carrying out this examina tion (Table 1 96.6) . Next, a full oesophagoscopy is carried out. In our unit, a flexible fibreoptic instrument is used. If cancer is found, the examination should continue with a rigid oesophagoscope to assess fixation and obtain several large biopsies. Finally, with the cooperation of the anaesthetist, the endotracheal tube is replaced with a Stortz pattern ventilating bronchoscope. A full broncho scopy is undertaken using the Hopkins rod telescopes. When the anaesthetist is ready to awaken the patient, the bronchoscope may be removed. [**]
STAG I N G It is essential to carry out staging for the adequate practice of clinical oncology. Treatment is stage dependent, as is p rognosis. Staging allows audit of the department's results, publication of results, sharing of results with other units and thus is the only method of determining if one's practice and treatment is of good quality. Staging is a crucial part of the data storage and retrieval system of any institution. It is the basis of oncological research. Without it, departments cannot budget accurately and neither can health authorities or even governments. Staging is so important that no true advances in oncology can be made without it. In oesophageal cancer, the same p rotocol should be carried out but with the surgeon's main attention being focussed on the oropharyngoscopy, laryngoscopy, hypopharyngoscopy, oesophagoscopy and bronchoscopy. Staging is not only crucial for the above reasons but it focusses the oncologist's mind to assess each tumour in a systematic, scientific and clinically relevant manner.
Ta b l e
1 9 6 Tu m o u rs of the hypopharynx a n d oeso p h a g u s III 2645
1 9 6.6
Hypopharyngea l cancer e n d oscopic assessme nt.
Procedure
M a ke s u re patient is a naethetized, re laxed a n d sti l l 1 . U s i n g a Li n d h o l m scope, p l u s occasiona l ly tonsi l l ectomy g ag , a ssess the u p p e r l i rnit of tu m o u r: Th e th ree fol d s : pharyngoepig l ottic fol d a rye p i g l ottic fol d g l ossoe pi g l ottic fol d 2. U s i n g a p h a ry n g os co pe, assess the : Base of ton g u e Pi riform fossa Postcricoid Poste rior p h a ry n g e a l w a l l 3 . Assess the l ower l i m it o f tu m o u r u s i n g oesophagoscopy (crucia l for p l a n n i ng s u rg ica l treatment) 4. Assess if the tu m o u r m oves freely on p reve rte b ra l fascia 5. U s i n g a l a ry n g oscope, p e rform a l a ry n g oscopy, exa m i n i ng the s u bg l ottis and u p p e r trachea ca refu l ly with a H opkin's rod 6. Perform a fu l l oeso p h a g oscopy using a flex i b l e o r rig id oeso p h a g oscope Ta ke severa l b i o psies of the t u m o u r edge at various sites 8. Perform a fu l l bro n c h oscopy u s i n g a Storz rig i d bro n c h oscope with H opkin's rod tel escopes 9. Al l ow a n aesth estist to ta ke c h a rg e of the a i rway with the bro n c h oscope and s u bseq u ently extubate and reverse the a n a esthetic
7.
Without staging protocols there is the danger that the tumour is merely observed but not assessed. The universally accepted staging system is that of the UICC ( 1 997 ) 4 1 and its AJCC equivalent. The system is not without fault, but has the major advantage of being universally adopted. Not only does it define staging but also anatomical site (Tables 1 96.7, 1 96.8 and 1 96.9). The large head and neck cancer database in Liverpool has demonstrated that the TNM system largely stands up to univariant and multivariant statistical scrutiny, particu larly as regards survival. A sequential staging protocol is given in Table 1 96. 1 0. There are problems of course. Large T2 tumours are difficult to differentiate from T3 cancers. In addition, T3 cancers from all head and neck sites have greatly differing volumes on CT scanning and in the case of hypopharyngeal cancer the median volume is 1 7.4 mL and ranges from 8.9 to 67.8 mL. This represents more variation in tumour volume than at any other site in the head and neck.7 6 In another study, no prognostic distinction could be made between the neck stage N2 and N 3. 77 An important and misunderstood rule of staging is that in the case of difficulty in deciding a stage (e.g. T2 or T3 ) only the lower stage should be assigned. This is mainly because of the risk of centres or treatment protocols being associated with more weight than they deserve. [**J
2646 I PART 1 7 H EAD Ar\l D N EC K TU M O U RS Table 1 9 6.7 U I CC cl assifi cation of d isease at the p ri m a ry site (hypoph a rynx) .
Table 1 9 6.9
Sta g i n g of oeso phageal ca ncer.
Stage
Stage Descri ption T1
T2
T3 T4
Tumou r l i m ited to one su bsite of hypop h a rynx (see Treatment of the neck (irra d iation)) and 2 cm o r l ess i n g reatest d i m e n s i o n Tu m o u r i nvades m o re t h a n one su bsite of hypo p h a rynx o r an a djacent site or measu res mo re t h a n 2 cm, b ut not m ore than 4 cm in g reatest d i mension, without fixation of h e m i l a rynx Tu mou r measures more tha n 4 cm i n g reatest d i mension or with fixation of h e m i l a rynx T u m o u r i nva d es a djacent struct u res, e.g. thyroid/cricoi d ca rt i lage, ca rotid a rtery, soft tissues o f n ec k, preve rtebra l fascia/m usc l es, thyroid a n d/or oeso p h a g u s
Reproduced from Ref.
41 , with permission.
T1 T2 T3 T4 N1 M1
Tumour of lower thoracic oeso phagus M1a M1b
Coe l i a c n odes Oth e r d ista nt metastasis
Tu mour of u p pe r thoracic oesophagus M1 a M1b
Cervical nodes Other d ista nt metastasis
Tu mour of m i d-thoracic oeso p h agus M1b
Ta ble 1 9 6.8 N o d a l stag i n g fo r sq u a m ous ce l l ca rci no ma of the hypop h a rynx.
La m i n a p ro pria, s u b m u cosa M uscu l a ris p ro p ri a Adve ntitia Adjacent structu res Reg i o n a l Dista nt metastasis
Dista nt m etastasis, i n c l u d i n g n o n re g i o n a l lym p h n od es
Reprodu ced from Ref.
41 , with permission.
Stage Descri ption NX NO N1 N2
N2a N2b N2c N3
Reg ion a l lym p h n od es ca n n ot be assessed N o reg i o n a l lym p h node metastasis M etastasis i n a s i n g l e i ps i l atera l lym p h node, 3 c m o r l ess i n g reatest d i m ension M etastasis i n a single i ps i l atera l lym p h node, mo re than 3 c m , but n ot m o re tha n 6 cm in g reatest d i mensio n ; o r i n m u lt i p l e i ps i l a teral lym p h n od es, n o n e more tha n 6 cm in g reatest d i mensio n ; or i n b i l atera l or contra latera l lym p h nodes, n o n e m o re t h a n 6 cm i n g reatest d i m e nsion M etastasis i n a single i ps i l atera l lym p h node, m o re tha n 3 cm but n ot m o re tha n 6 cm i n g reatest d i menson M etastasis in m u l t i p l e i ps i l ateral lym p h n od es, n o n e mo re tha n 6 cm i n g reatest d i m en s i on M etastasis in b i l ate ra l or contra latera l lym p h n odes, n o n e m ore t h a n 6 cm i n g reatest d i m ension M etastasis i n a lym ph node more tha n 6 cm i n g reatest d i mension
N , reg ional lymph nodes. Repro d u ced from Ref. 41 , with permission.
TUMOU RS OF TH E CERV I CAL O ESOP HA G U S These are included with hypopharyngeal cancers because there are many similarities with postcricoid cancer and management strategies overlap. The UICC subsites and staging are given in Tables 196.3 and 196.9. Whilst cervical oesophageal malignancies tend to present earlier in terms of T-stage because dysphagia is a relatively early symptom, nodes in the neck are relatively unusual. Patients frequently have mediastinal nodes and are often
Table 1 9 6. 1 0
Seq u e n ti a l sta g i n g p rotocol.
Protocol H istory a n d exa m i n ation 2 Fi ne needle aspiration cytology o r a smear. S m a l l biopsy if fea s i b l e 3 Chest rad iogra p h 4 Routi n e base l i n e hae matology a n d bioch e m i stry ( i n c l u d i ng thyroid fu n ction a n d creati n i ne) . Others may be a p p ro p ri ate d e pe n d i n g on the d isease, e.g. thyroid or n e u ro e n d ocrine t u m o u rs 5 Pa n e n d osco py a n d b i o psy ( ± fresh froze n speci m e n s i n s pecia l i zed or resea rch u n its) 6 M R I of head a n d neck (someti mes CT in a d d ition is h e l pfu l a n d is esse nti a l if b o n e is l i ke ly to be i n volved) 7 CT of chest and l iver 8 H istopathology w ith i m m u n o h istochem istry if n e cessary Su bsequent sta g i n g H isto logy of operative s p e c i m e n - t u m o u r m a rg i n s a n d h isto l ogy o f n e c k d issection 2 H istology, etc., (as a bove) of a ny l ocoregiona l rec u rre n ce 3 S u bseq uent d ata from sca ns of l oca l or d ista nt rec u rre n ce ; post m ortem
incurable at the time of presentation. The Liverpool unit described a series of 47 patients with oesophageal cancer of whom nearly half were only suitable for palliative treatment. Nearly half of the patients had tumours smaU enough to warrant treatment with radical irradiation, but 14 had surgery in the form of total
Chapter 1 96
pharyngolaryngooesophagectomy and gastric transposi tion. The three-year survival of all cases was only 1 8 percent compared with 3 3 percent for a matched group of patients with hypopharyngeal cancer. It should be noted that the treated patients had a 30 percent three-year survival, rather better than for the rest of the oesopha guS. 1 3, 56 [ * * ]
TR EATM E NT The treatment protocol developed in Liverpool is shown in Table 1 96. 1 1 . Whilst this serves as a guide to treatment, it must be remembered that there are many exceptions and that it does not replace clinical experience. However, it has been developed from a large complex statistical analysis of data collected over 30 years and therefore has a degree of credibility (data from previously untreated patients is shown in Table 1 96.4) . Treating patients with hypopharyngeal cancer may initially appear straightforward; however, few conditions in oncology are as difficult to treat. Using an incorrect treatment modality will almost certainly be met with disaster, either in terms of under- or overtreatment leading to death or to an intolerable quality of life. In the Liverpool series, nearly a third of patients seen at presentation in a combined head and neck oncology clinic were deemed incurable. This is not an easy decision to make, as for the patient it removes any glimmer of hope.78 [ * * ] In specialist head and neck units that use organ preservation strategies, half of all the patients receiving surgery do so after radical irradiation with intent. This increases the technical difficulty of surgery and makes some type of flap repair necessary, frequently involving adjuvant procedures such as the insertion of brachyther apy tubes. Needless to say there is a corresponding increase in the complication rate but conversely the chance of cure is reasonably high, in the order of 50 'percent.79 , 80 [ * * ]
Tab l e 1 96. 1 1
Tu m o u rs o f the hypop h a rynx a n d oeso p h a g u s I 2647
RA D I OTH E RAPY One of the early well-executed and analyzed studies of the use of radical irradiation in the treatment of hypophar yngeal cancer was by Mendenhall et al. in 1 9878 l and showed very encouraging results. In Liverpool, T l through t o T 3 , N O piriform fossa cancer was studied with regard to treatment modality, 1 7 were treated by primary irradiation (with surgical salvage if necessary) and 34 underwent primary surgery, 14 were unsuitable for any curative treatment. The tumour-specific five-year survival in the primary radiotherapy group was 55 percent and for the surgery group was 44 percent; the difference was not significant. 8 2 [ * * ]
In a later study node-negative postcricoid carcinoma was studied, 67 underwent primary surgery and 50 primary irradiation, 36 were unsuitable for curative treatment. Again there was no significant difference between the two modalities of treatment, with surgery having a 43 percent tumour-specific five-year survival and radiation 48 percent, in both these studies the two gro ups were well matched.8 3 When comparing such studies, whilst both modalities of treatment may deal with retropharyngeal nodes, only irradiation routinely treats superior mediastinal nodes. [** ] In Liverpool as in the rest of the UK, the irradiation dose given to patients has varied over the past 35 years. Latterly, a median dose of 66 Gy in 33 fractions is delivered by a 6 MeV linear accelerator. Although the above survival figures sound quite acceptable for this , disease, they sho uld also be considered in the light of primary site control. In the case of p iriform fossa cancer, 35 percent of patients treated by irradiation had control at the primary site compared to 68 percent in the surgery group. The reason for the apparent success of irradiation was that most of these primary site failures were amenable to salvage surgery. With regard to the postcricoid region, a third of patients receiving primary surgery had recurrence at the primary site compared to one-half receiving primary irradiation. Again most patients with
Live rpool treatment po l i cy for hypo pha ryngea l ca rci noma.
Radical
Laryngecto my a n d partial
rad i otherapy
pharyngectomy
(±
flap)
Total
Total
pharyngolaryngectomy
pharyngolaryngooesophagectomy
(usual ly jej u nal loop
(usual ly gastric transposition)
repa i r)
Piriform fossa T, . T2 Post-cricoid < 5 cm l o n g and not b u l ky Low vol u me poste rior wall
Pi riform fossa with o p posite side c l e a r and not exte n d i ng to m i d l i n e poste riorly Poste rior wa l l not inva d i n g l a rynx
Pi riform fossa post-cricoid a rea (300f0) Sma l l post-cricoid La rg e r posterior wa l l Sma l l recu rre n ce i n p h a ryngea l re m na nt
La rg e post-cricoid Cerv i ca l oeso p h a g u s Seco n d t u m o u r i n oeso p h a g u s Tu mou r a n d pe rforation Thyroid ca n cer inva d i n g p h a rynx H eavy i rradiation d a m age Pe risto m a l recu rrence Fa i l ed p revio u s m ethods
2648 I
PART 1
7 H EAD A�I D �I ECK TU M O U RS
the recurrence at the primary site in the radiotherapy group were suitable for surgical salvage, although interestingly very few of primary site recurrences within the surgery group could be salvaged. 64 , 79 , 8 2 The rationale behind this approach is organ preservation and thus improved quality of life. [**J Because of this high risk of primary site recurrence, most oncology units have adopted some type of enhanced protocol. It has become apparent that treatment results with irradiation are improved by some type of hyper fractionated accelerated regimen (continuous, hyperfrac tionated, accelerated radiotherapy ( CHART) ) . 83 There are of course other enhancements possible. For example, the addition of mitomycin C to the CHART regimen suggests significant improvement in the combined treatment, at least as regards tumour control.8 4 [****] In the Danish Head and Neck Cancer study ( DAHAN CA) protocol,85 a consistent improvement in locoregional tumour control was achieved using nimorazole as a hypoxic cell sensitizer. The European Organisation for Research and Treatment of Cancer ( EORTC) head and neck cancer cooperative group studied laryngeal preservation in piri form sinus cancer.8 6 The protocol was complex. The control arm consisted of immediate surgery and postoperative radiotherapy (the standard) , the second arm consisted of induction cysplatin and 5-fluorouracil chemotherapy. An assessment was then made endoscopi cally. Partial and complete responders went on to receive a third cycle of chemotherapy and complete responders went on to have radical radiation; those that failed to respond had surgery following irradiation. This system preserved the larynx even in some patients with advanced primary site disease and this preservation was achieved without jeopardizing survivaL Such good results are not universally reported, whilst generally an improved local response rate is achieved,87, 88 survival benefits are often not seen. However, chemoradiation protocols do appear to have some success in the very poor prognostic groupS.89, 9 0 [****]
S U RG E RY Radiotherapy and chemotherapy have been subject to well-designed randomized control trials, often where surgery is one of the arms of the study. Surgery itself for the hypopharynx has never been subjected to a randomized controlled trial. Nevertheless, for advanced disease most head and neck oncologists are in little doubt that for curative treatment surgery must be a major modality. The types of surgery available are endoscopic, total laryngectomy and partial pharyngectomy, total pharyngolaryngectomy and repair with some type of flap (the best at the present seems to be free revascularized jejunal interposition) and finally a total pharyngolaryn gooesphagectomy, which is almost certainly best repaired by stomach transposition, although transposed colon and free revascularized jejunum have been used.
E N DOSCOP I C S U RG E RY Endoscopic laser surgery for the treatment of hypophar yngeal cancer was pioneered by Steiner et a1. 9 1 The initial results appear encouraging, although it is unclear whether this method is superior to chemoradiation. Anxieties do exist regarding the large unrepaired defects sometimes open to a carotid artery that this type of surgery may produce. Few in the UK have much experience of extensive surgery using endoscopic techniques and it should be remembered that early cancers that may well be suitable for such treatment are also likely to be radio curable. Nevertheless, the technique does have its advocates, 92 but its place in the treatment armamentar ium for hypopharyngeal cancer remains to be established. [**J
PARTIAL P HA RYN G EAL RESECTI O N I N HYPOP HA RYN G EAL CA N C E R I n a recent review, Ferlito e t al. 9 3 have reviewed this topic with regard to larynx and hypopharynx, they found that conventional conservation surgery could be used with good effect in tumours of the hypopharynx that are not too extensive. They do not recommend endoscopic surgery for hypopharyngeal cancers. Apart from the posterior pharyngeal wall, partial pharyngeal resection necessitates removal of the larynx. A number (perhaps most) of the cases suitable for this procedure may ultimately be treated by nonsurgical methods. [*J
TOTAL P HA RYNGOLA RYN G ECTOMY This procedure first performed by Czerny, 94 Bilroth's assistant, leaves a certain amount of oesophagus in the lower neck. Seidenberg et al. 9 5 described the first satisfactory repair in 1 959. Although the resection can arguably be continued into the upper mediastinum, and an oesophagojejunal anastomosis carried out with a stapling device, it should be remembered that any leakage that occurs after the anastomosis is likely to prove fatal. [**] The upper opening will be the lower part of the oropharynx. In the experience of the Liverpool unit, free revascularized jejunal interposition (Figure 1 96. 12) offers the best swallowing rehabilitation with the least number of severe postoperative problems; in particular, the perioperative death rate is low with a free revascularized jejunal 100p.8 0 We noted a 4 percent perioperative mortality with this procedure, whereas Wei et al. 96 report 9 percent hospital mortality. [**] In Liverpool, the jejunal loop series consisted of 90 patients with a median follow-up of 4.9 years. Tumour specific five-ye�r survival was 42 percent. D isappointingly, 48 percent developed primary recurrence at three years
2649
Ch a pte r 196 Tu mo u rs of the hypo p h a rynx a nd oeso p h a g u s I
patients
had hypo pharyngeal
or cervical
oesoph ageal
cancer. A hospital mor tality of 9 percent is rep o r ted, which has vastly improved from earlier publications from this group where morta lity was in the region of 30 percent. Anastomatic leakage and bleeding was reduced to only
10
p ercent.
They
carried
out
a
transthoracic
mobilization o f the oesophagus and rep o rted a five-year tum o ur-specific survival of 25 percent. Again, in previous years this was d own to 1 8 percent.
[**J
I n the Liverp ool series,98 5 0 p atients are rep o rted and they
had
to tal
ph aryngolaryngooesophagectomy
and
gastric transp osition, two-thirds of the operations were carried ou t fo r pri mary disease and one- third for salvage F i g u re 1 9 6.1 2
A
fo llowing
free revascu la rized j ej u n a l loop used to
repa i r a tota l p h a ryng ectomy d e fect. Note the s e g m e n tation
and 53 percent developed neck node recurrence a t five
pharyngeal
areas.
Postoperative
and retro
irra d iation
did
not
influence the stenosis rate. Interestingly, survival was better fo r those having salvage surgery following radical r adiation, than i t was fo r th ose having primary surgery. Scrutiny of the statistics shows why this pheno menon occurred. The salvage surgery ha d smaller tumours at the time of p rimary ra diotherapy and d ue to the time interval between p rimary irradiation and the salvage surgery a large number of p atients will have either died of their disease or d ied of distant metastasis. Thus, the salvage surgery group is a h ighly selected group cont aining many p ositive survival factors . Flaps o ther than the jej unum can be used . Nakatsuka et
al.97 reported a comp arison between jej unal loop and
radial forearm tubed free fla p . The free jej u n al flap faired better
having
fewer
problems
with
strict ures,
described
two
technical
used for pharyngea l diver ticulu m surgery, is used to
years. In most of this series, posto pera tive radiation was superior mediastinum
We
over the period o f this study. A diverticuloscope, usually
co n tra ctions i n d icating a hea l thy m i c rovascu l a r a n asta m osis.
given to the neck,
radio therapy.
modifica tions to the standard procedure we have evolved
but
significantly m o re fistulas. The question o f whether to carry o ut a total pharyngolaryngectomy o r total phar yngola ryngo oesophagecto my is a d ifficult o ne. No t all authors apply the same criteria and some , such as the
d issect in the middle mediastinum. This area presents a prob lem using the pull-through technique and obvio usly serious or fatal damage can occur, such as avulsi o n of the azygos vein. The clear view obtained using the d iverticu losc ope allows proper safe surgical dissection. Microlar yngoscopy instruments and the opera ting microsco p e assist. I n a ddition, t h e rou tine inser tion o f chest drains perioperatively
overco mes
the
risk
of
fatal
tensio n
pneumotho rax. In the described series, com plications were relatively unusual in the primary surgery group and anastomatic stenosis
does
not
tend
to
o ccur.
Three
patients had delayed gastr ic atonia, although we ro utinely perform a pylo roplasty in order to attempt to prevent this comp lication preemptively. The three-year, tumour-spe cific survival was 39 percent.98 A recent publication describes free colon transfer fo r pharyngooeso pha geal reconstructi o n . 99 Ped i cled tra nsverse colon interposition can be used and was popular ize d by Ga l lagher in the 1 950s. We do not use this technique routinely, b ut it is valuable sho uld a stomach transposition fail. A tech nical n ote
is
that
the
colo nic
marginal
artery
may
be
discontinuous and an angiogram sh o uld be carried o ut p reoperatively.
[**]
University o f Hong Ko ng, prefer a gastric transposition even fo r pharyngeal repair, which obviously requires a more extensive abdomin a l procedure and extension of the operation into the thorax. Although pharyngolaryngect omy is usually carried out fo r less advanced disease than total p haryngolaryngo oeso p hagecto my, this is not a lways the case and the TNM classification has many problems with regard to staging cancers in this area.
[**1
CH E M OTH E RA PY The role of chemotherapy is as an a djuvant to radio therapy, surgery o r both . l oO
[*]
Head and neck oncologists in the UK would not serio usly consider attempting to cure a treatable patient with
head
and
neck
cancer
using
this
thera peutic
moda lity a lone; therefore, it is appropriate to consider it with co mbined treatmen t .
TOTAL P H A RYN G O LA RYN G O O ES P H A G E CTO MY The University of H o ng Ko ng h ave been advocating this procedure
with
gastric
transposition since
the
CO M B I N E D T R EATM E N T P ROTO CO LS
mid-
1 960s.96 They rep or ted clinical results with 69 patients
The use of combined treatment is frequently necessary in
having this
hyp opharyngeal cancer. The co ncept of treating whenever
procedure
between
1 986
and
1 995 .
All
2650 I PART 1 7 H EAD AN D N ECK
TUMO U RS
possible with irradiation, followed in about half the cases by surgical salvage, is in a way a combined treatment protocol. This is in effect an organ preservation protocol as half the patients will keep their larynx with a significant improvement in the quality of life compared with surgery. 64, 7 9, 80, 8 2 , 9 8 [ H ] Surgery followed by radical irradiation to the primary site and neck is a true combined treatment and effective at least in reducing locoregional recurrence. 55 , 101, 102, 103 Preoperative radiotherapy is of no benefit as demon strated by Strong et al. 104 The various chemotherapy regimens available in some type of adjuvant setting can be bewildering, but as yet with only slight evidence of therapeutic gain. 1 0 5, 1 06 , 107 [ H ] Irradiation causes microangiopathy and a poor local blood supply to the area irradiated, flaps bring in fresh unirradiated healthy tissue for repair allowing the oncologist to increase the dose of radiation if needed. This is not to say that irradiation should be delivered to all patients, but suggests that a certain primary site recurrence rate may be acceptable, as it is still amenable to surgical salvage and flap repair. It must be emphasized that full cure in the absence of any function and a very poor quality of life is not a particularly good outcome. Quality of life following irradiation of head and neck cancer is better than quality of life after surgery and this is particularly true in the hypopharynx. 108 [ H ] The first established combination therapies were radiotherapy and surgery. Radiotherapy can be given before surgery, after surgery or more recently at the time of surgery. Although preoperative irradiation produces no survival benefit, postoperative radiotherapy does when used appropriately. A retrospective study in 1 994 lO 1 suggests there is a very large benefit in five-year survival, between surgery only ( 1 8 percent) and the surgery with postoperative radio therapy (48 percent) . The difference was significant (0.029) and obviously leads the way to a randomized controlled trial. In the Intergroup studylO9 patients including those who had complete resections of hypo pharyngeal cancer were randomized to receive either three cycles of cisplatin and 5-fluorouracil followed by postoperative radiotherapy or post-operative radio therapy alone. Patients were then categorized as having either a low-risk or high-risk treatment volume, depend ing on whether the surgical margin was greater than 5 mm, whether there was extracapsular node extension or carcinoma in situ at the surgical margin. Up to 54 Gy were given to low-risk volumes and 60 Gy to high-risk volumes. A total of 442 analyzable patients were entered into the study, which lasted for a period of 46 months. The results demonstrated that chemotherapy offered no additional benefit, in terms of overall tumour-specific survival or locoregional control. In a complex study, 1 10 biopsy-positive operable p atients with head and neck cancer, including hypopharyngeal cancer, were adminis tered paclitaxel and carboplatin with 45 Gy of radiation
and rebiopsy carried out five weeks later. Those with a positive biopsy underwent definitive surgery within five weeks, whereas those patients with a negative biopsy received three additional weeks of irradiation to a total dose of 72 Gy plus paclitaxel and carboplatin. The authors conclude that this regimen was associated with a very high complete response rate at the primary site and a high level of organ preservation. A median follow up of 1 2 months was achieved. Tumour-free and overall survivals were between 70 and 80 percent. These results are encouraging, but the follow up is by no means long enough and in addition the study lacked statistical power. It seems unlikely that they could imp rove upon the overall tumour-specific survival for treatable head and neck cancer, achieved in major centres of around 60 percent. 1 1 1
In a retrospective study from Chicago, an eight-year analysis of results in their institution was carried OUt. 1 1 2 Patients with stage 3-4 disease were included and the follow up was at least two years. A concomitant chemoradiation protocol was adopted. Chemotherapy was used for a total of seven, two-week cycles of a relatively low dose of cisplatin and 5-fluorouracil. Irradiation at 2 Gy a day for five days for seven cycles was delivered (70 Gy in total) . The overall survival was 43 percent, but hypopharyngeal cancers did rather worse than other sites and a total of 78 patients were treated. It seems likely that at least the 16 p atients with stage 3 disease may have benefited from surgery as well, but this was not carried out in this study. At the moment, it appears that cisplatin and 5-fluorouracil are the standards in chemotherapy, but paclitaxel at this relatively early stage looks extremely promising, although other agents have proved disappointing. 1 1 3 [ H H ]
OTH E R TR EATM E NTS The basic concept of tumour ablation has not changed radically since the time of Hippocrates (born 460BC). Certainly over the twentieth century, surgeons knew very well that they had to obtain clear margins to have any chance of cure, although it is now known that this is not necessarily true. 1 14, 1 1 5 A positive margin can be rendered safe by postoperative irradiation. 1 1 6 It seems improbable that surgery on its own is going to progress much further as regards ablation. Surgery has made massive advances since the 1 960s in terms of reconstruction and improve ment in quality of life. Irradiation has limitations and apart from different regimens such as CHART, there is unlikely to be much further survival benefit on its own. Multimodal treatment with the addition of chemotherapy would seem to offer some hope for the future. Other methods such as photodynamic therapy and various endoscopic laser treatments, apart from a possible role in the cure of early lesions, is probably only going to be useful in palli�tion. Toxic chemoradiation regimens are rarely used for palliation in Liverpool, but fortnightly
Cha pter 1 96
mJections of methotrexate (50 mg) have a palliative ro 1 e 1 00 ' 1 0 6 , 1 0 7 an d C I' Sp 1 atm can pro duce a very b ene fi Cia ' 1 response in selected patients. [**] The main hop e for the future lies i n a completely new range of therapies targetting either the genome or the proteome. Such modalities include gene therapy using virus vectors, the delivery of drugs and radioactive agents to specific sites using antibodies and substances them selves aimed at binding with the relevant epitopes on specific receptors and enzymes. Some discussion is given in Chapter 1 , Molecular biology.
Tu mou rs o f the hypop h a rynx a n d oesop h a g u s I 265 1
TREATrvl E NT OF TH E N ECK (S U RG E RY)
.
TREATM E NT O F TH E N ECK (I RRA D IATI O N ) For treatment of the neck i n general, the reader i s referred to Chapter 1 99, Metastatic neck disease. There are various aspects of neck disease in hypopharyngeal cancer that are appropriate to address here. Seventy-five percent of patients with piriform fossa cancer will have neck node metastases at presentation and it is highly likely that the remainder will have occult metastases. Approximately 5 percent will have bilateral metastases. Thus, the ipsilateral neck must be treated. Even in the NO neck, the risk of occult nodes in hypopharyngeal cancer is well over 50 percentl 17 and the risk of death following uncontrolled neck node disease correspondingly high. l l s Normally, if the primary tumour is being treated by irradiation, elective neck irradiation should be given as well. When the primary tumour is being treated by surgery, the neck of necessity will be violated and should be treated by some type of neck dissection. 1 1 9 For the NO neck, a selective neck dissection should be carried out, which must include areas two, three and four; often known as a lateral selective neck dissection. Failure following a selective neck dissection is usually because of extracapsular spread or tumour-containing nodes were present and the involved nodes were not removed. 1 2 0 Careful histology must be carried out on the neck dissection specimen and if multiple nodes are present, or in particular if extra capsular rupture has occurred, radical postoperative irradiation must be administered. The incidence of bilateral neck nodes for cancer of the piriform fossa is around 5 percent ( Liverpool data) . For the hypopharynx, if ipsilateral nodes are present, there are no adequate data regarding occult disease on the opposite side. It is oncologically sound to assume that it is present and irradiation to the contralateral side is recommended in the presence of ipsilateral nodal disease. [**] When a small hypopharyngeal cancer i s present and suitable for radiotherapy, then the neck can be treated in two ways. If the node is less than 2 em across, radio therapy may be given, 1 2 1 the likelihood is that the node will be sterilized, but in the event of it still being present at three months a neck dissection must be performed. If the node is larger than 2 em, a neck dissection is required with subsequent irradiation to the primary site. [**]
In the event of more extensive neck node disease and a small hypopharyngeal primary tumour, little data are available. According to data from a Liverpool series dealing with oropharyngeal cancer, 1 22 it is safe to perform an appropriate type of neck dissection, followed six weeks later by radical irradiation to the primary tumour and of course the neck. Cancer of the postcricoid region presents two problems as regards neck node metastases. These are nodes in the retropharyngeal space and particularly nodes in the superior mediastinum. With the advent of modern scanning techniques (MRI) , nodes in these areas can be visualized down to less than 0.5 em (Liverpool data) . Although enlarged nodes are likely to harbour tumour, this is not always the case as piriform fossa cancers in particular tend to be large, fungating and associated with infection. Nevertheless, an enlarged node should be treated either by irradiation, which sterilizes relatively small nodes, or by surgery. In the case of retropharyngeal nodes, these can be easily dealt with at the time of total pharyngectomy or in the case of radiotherapy by including the neck in the treatment field on occasions. Nodes adherent to the prevertebral structures may be dissected free and if disease is extensive, after-loading brachytherapy tubes can be inserted. The same technique can be used for limited invasion of the prevertebral area by primary tumour. No data exist as to whether such treatment has any effect on survival, though our experience suggests that locoregional control is improved. As regards suspicious nodes in the superior mediastinum, these may be inspected easily by mediastinoscopy at the time of total pharyngectomy, as of course is mandatory during a total pharyngolaryngooesophagectomy. Frozen section can be performed and, if positive, our practice is then to perform a manubrial resection and carry out a superior mediast inal dissection under direct vision. If the frozen section of a lymph node sample is negative, a superficial mediastinal dissection can be undertaken. Small nodes can, of course, be treated by radical irradiation and this modality should be employed in any case in this disease. Again, in the case of hypopharyngeal cancer, no robust data exist as regards treatment of the superior mediastinum. In the Liverpool experience, recurrence in this area is in any case rare, presumably because of our irradiation protocol.
PATTE R N S OF FA ILU R E This subject cannot b e discussed without reference t o the primary treatment modality. All cases in the Liverpool series that had primary irradiation to the primary site had relatively early disease ( T l IT2 ) . Primary site recurrence rates are higher in the radiotherapy group than in a similar surgical group. Most patients with primary site failure following radiotherapy are suitable for salvage
2652 I PART
17
H EAD AN D I\J ECK TU M O U RS
surgery. Final survival rates, therefore, are calculated as radiotherapy with or without salvage surgery as necessary. Similarly, patients with larger volume disease in the hypopharynx (T3-4) tended to have surgery and nearly all of these had postoperative irradiation. The actuarial primary site recurrence rates for the whole group of patients with hypopharyngeal cancer in the Liverpool database was calculated as 34 percent (95 percent confidence intervals, 28-40 percent) at five years (Figure 196. 1 3 ) . Most of these occurred within the first year and most of the rest within the second year. There was no significant difference in primary site recurrence rates as regards site. If treatment differences are ignored, recur rence in late (T3-4) disease was more likely than that in early (T l-2) disease. As regards recurrence in the neck, this is a more complex issue. In the Liverpool database from 1 965 to 1 99 1 , routine computed scanning techniques were not employed in assessing the neck. In addition, if clinically node negative at the time of presentation, the neck was not routinely treated even in cases of piriform fossa cancer, when it is now known that 25 percent of patients (who do not have obvious neck nodes at the time of presentation) almost always have occult disease. Now adays, most head and neck oncologists believe that treating the NO neck should be considered in all patients with a high risk of occult nodes. These include not only piriform fossa, but also oropharyngeal cancer, supraglot tic cancer, floor of mouth cancer, etc. In spite of this, there is no absolute statistical proof that demonstrates a survival disadvantage from the 'wait and watch' pol icy. 5 9, 1 1 7 In the Liverpool series, however, from 1 99 1 , all cancers of the head and neck apart from T 1 cancers had the head and neck assessed first by CT scan and later by IVIRI. Needless to say the incidence of 'NO' neck disease decreased with a significant decrease in recurrence in the neck; survival, however, did not improve. Nevertheless, we now treat the NO neck in high risk areas such as the piriform fossa, and this can be done at the time of operation with some type of modified neck dissection or by postoperative irradiation. Our rationale for this change in policy - not based on firm evidence - is that neck
recurrence is reduced by elective neck treatment. We accept that distant metastases are more common the larger the loco regional tumour burden and are more common if regional metastases are present. It must be emphasized, however, that this concept is by no way proven and has not been demonstrated to be associated with a survival advantage. For the whole of the Liverpool series of hypopharyngeal cancer, the neck recurrence rate was 26 percent (95 percent confidence intervals, 20-32 percent) (Figure 196. 14) . Again, most recurrences occurred within the first two years and most occurred in patients already treated for primary nodal disease. Variables predictive of a neck node recurrence included advanced neck disease at diagnosis (N stage) , the presence of more than two nodes and extracapsular spread. [**] The pathological anatomy of a primary site recurrence is a difficult and unpredictable area. The lymphatics of the head and neck were remarkably accurately mapped by Rouviere in 1 932 and Fisch 1 2 3 further detailed the lymphatic anatomy of the head and neck using lymphan giography and isotope scanning. Irradiation damages the lymphatics, but does not obliterate them at the doses used therapeutically. After radiation and surgery, new lympha tic channels develop in the head and neck within a year, but with a different distribution from normal. 1 24 The obvious practical implication of this is that the oncologist must retain a high index of suspicion and not rely on the usual patterns of spread of tumour in the untreated patient. Where the primary site has been treated surgically, a primary site recurrence p er se is obviously not possible, but recurrence near the primary site or at 1 , 6 the margins can occur. 1 4 1 1 5 , 1 1 In the case of postcricoid cancer and cervical oesophageal cancer, skip lesions in the oesophagus are a common phenomenon and recurrence can occur here. Indeed, inadequate surgery or irradiation are possible as skip lesions have been documented to , 6, , 1 occur up to 8 cm from the primary tumour. 1 3 5 9 8 2 5 In the neck, where lymphatics are p articularly profuse, the systematic spread of cancer from one lymph node area to the next does not always occur and metastases may jump to a more distant node even in the absence of previous
1 00
1 00
� 75 Q)
� 75 Q)
0 c
� �
0 Q) 0:
0 c
34% (95% Confidence 28-40%)
50
� �
0 Q) 0:
25 12
Fig u re 1 96. 1 3
a ctu a ri a l p l ot.
24 36 Time (months)
48
25 12
60
Recu rre n ce at the p ri m a ry site : Ka p l a n - M e i r
26% (95% Confidence 20-32%)
50
F ig u re 1 96. 1 4
p l ot.
24 36 Time (months)
48
60
'Recu rre n ce in the neck: Ka p l a n - lVl e i r a ct u a ri a l
C h a pte r 1 96 Tu m o u rs of t h e hypo p h a rynx a n d oeso p h a g u s I
treatment.
1 25. 1 26
This is one o f t he a nxieties rega rd ing
selective neck dissection .
however, st ill open to observer error. Figure
[**]
2653
196. 1 8
i l l ustrates this p roblem . Pa tie nts w i t h NO, N 2a and N2b disease have a 3 8 p erce n t five-year surviva l , with n o sign ificant difference between t h e gro u ps. For some reason in the Liverpool series, p a t i e n ts with N l neck disease appear to do ra ther
PROG N OSIS AN D SU RVIVAL
worse wi th a
20 perce n t five-year s u rvival rate, signifi
In the Liverpool series of hypopharyngeal cancer, t h e fi ve
cantly d i fferent from the stages p reviously mentioned
observed survival
28 p ercent and the 16 p ercent. O n t heir own , t h ese figures mean l i ttle; just over a quarter of pa ti ents (27 pe rcent )
d isease do very ba dly taken together, having a
were not su i table for any curative treatment, the five -year
acc u ra t e met hod of assessi n g p rognosis in head and neck 2 ca ncer. l 7 The two cr ucia l factors a re th e number of
(p
year, tumour-specific survival was
(95 perce n t 0-4 percent ) . O f treated patients, 3 2
percent h a d p r i ma ry radioth erapy wit h ,
0.000 1 ) . Less surp risingly, patients with N2c and N3 5 percent
fi ve-yea r s u rvival. Pa t hologica l node stage is the most
s u rv ival for these pati ents was 2 p er cent confidence i nterval,
<
involved nod es a nd t h e p resence o r absence of extra capsular rup t ure. The e ffects of t h ese fa ctors on survival
i f necessa ry,
Figure 1 96. 1 9 . I t can be seen tha t the
salvage su rgery and the five-year survival fo r this group
a re s hown i n
percent)
rup ture does no t adversely a ffect su rvival, whereas more
was
46 percent (47-55 p ercen t ) . The la rges t grou p ( 4 1 was
treated
by
surgery
and
most
p resence o f one or two nodes without extracapsular
had
than two nodes or t h e presence of extracapsular ruptu re
postoperative radiotherapy. In this group, the five-year survival was 42 percent
( 34-50 percent) . The d i ffe rence in
effectively
survival between the treated groups and tho se receiving no curative treatment was highly significant
(p
<
hal ves survival.
There a re p robl ems when
p a t hologica l ly assessing the neck as it is still subjective,
0.000 l ).
but more i m porta n tly t h e re a re t wo d i l emmas. The neck
60 nodes on ea ch side. Pathologists do
There was no significant d i fference in survival between
co n t a i ns a round
the t reated groups as regards primary treatment modality
not rou t i nely exa m i ne a nyth ing like t h is n u mber. Even a
( Figure 196. 1 5).
small node
«
5 m m ) can ha r bo u r t umour. As regards
extracapsu la r rup t u re ( ECR) , t he more ca refu l ly one looks
There was no di fference between postcricoid ca ncer and p i r i fo r m fossa cancer with regard to su rvival, but
fo r it the more it w i l l be fo und if mu l t i p l e sect ions are
pat i e nts wi th posterior pha ryngeal wall cancer d id slightly
exa m i ned (own d a ta ) . Thus, even p N stage is subj ective.
worse
(p
=
[ **1
0.04 1 0) and cervical oesophageal cancers did
pa rticula rly bad ly with an 1 1 percent five-year su rvival
(p
At p resent , the most acc u ra t e too l w e have for t he analysis of su rviva l facto rs in ca n cer is Cox's p roportional
0 .0 1 5 2 ) (Figure 196. 1 6). Increasing T stage adversely a ffected surviva l with T 1 having a 46 percent survival a n d T4 cancers havi ng a 1 5 p ercent su rviva l . TI a n d T 3 =
haza rd mod el . 1 28 I n retrospective a na l yses, la rge nu m be rs a nd complex statistica l met hods a re req u i red. The Liver
599 patients with squamous cell
ca ncers were no t signi ficantly d i ffere nt, pe rhaps under
pool database co n tains
l i n i n g the confusion i n assigning a T stage to a large T2
ca rcinoma o f the hypo p harynx . D.
t u mo u r or a sma l l T3 t u mour. The d i ffe rence between all
particular diffi culty in a nalysis i s t h e very large d i fference
(p 0.000 1 ) , but the d i ffe r T2 a n d T3 cancers was not ( Figure 1 96 . 1 7).
a re analyzed compared with only those who a re t rea t ed .
fo u r groups was signi ficant e n ce between
56. 6 4 . 79. 80, 82, 98. 1 29
between prognost i c facto rs when all patients
=
In hypopharynx, this i s
I t is well k nown that t h e most accurate p redictor of
a
in
a
One
coh o rt
part i c u la r p roblem a s a la rge
su rvi va l i n h ead a n d neck cancer is neck node stage,
p roportion of patients are no t su i ta b l e
particula rly t h e pa thol ogical neck stage. Clini cally, the
treatment. The resu l ts of an ana lysis ca r r i ed out u sing
neck
is
d i ffi c u l t
tech niques
c o
1 .00
.2
0.75
.� c c
to
stage
i mp rove acc u racy
ma nual ly
and
consi dera b ly.
scann i ng
Cox's model on all pa tients with hypop ha r yngea l cancer on the database for t his chap t e r yields the fo l low i n g
Radiothe rapy
:g 0.50
Vi :.0
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:::J
cu rative
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(j)
fo r
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0.00 o
250 o 0 0
500
750
1 000
1 250
1 500
1 750
Survival t ime (days) Censo red data
Fi g u re 196. 1 5
S u rv iva l by trea tm e n t ca teg ories.
2654
.8
I
PART
17 HEAD AN D N ECK TUMOURS
1 .00
t5 c
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:s .0 ·c
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o 0 0
c
1 . 00
.2
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POSl pharyngeal wall
0.00
o
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1 750
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g
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Survival time (days)
stage.
Censored data
,oo=i��O=-.=_________ =�� .._
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-
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-
1 500
1 250 1 000 750 Su rvival time (days)
500
-N 1
c 0
F i g ure 196.17
T2
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Tumour-specific s u rv i va l by site.
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F i g u re 196 . 1 B
Tumour-spe cific s u rv iva l by
node stage.
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Survival time (days) Key:
------------' I�o o o Ce ns ored data I
-- No nodes -- < --
2 nodes
> 3 nodes
-- <
2 nodes with extracapsular spread
-- > 3 nodes with extracapsular spread
' F i g u re 196.19
Neck node stage by neck
dissection histology.
C h a pter
results: Advanced age, poor general health (ECOG) , advanced T stage, advanced N stage, and increasing numbers of nodes and the presence of extracapsular rupture on neck dissection histology, all highly signifi cantly and adversely affect survival (all p < 0.000 1 ) 0.0006) . Interestingly, subsite and gender (except age, p had no effect on survival. [**] In the Liverpool series, 379 patients were treated with curative intent, either by surgery or radiotherapy or both. When this data subset is analyzed, there are few significant findings; women tend to do better than men (p 0.0 1 44) and there is a tendency for advanced neck disease to do poorly. A fascinating finding, which our unit has consistently reported for various sites, is that the curative primary treatment modality has no independent effect on survival when multivariant analysis using Cox's model applied to a Weibull distribution is performed. Indeed, in the present series the p value approaches unity (p 0.96 1 4 ) . Thus, it appears that whether the patient is treated by primary irradiation with salvage surgery (if necessary) or by primary surgery usually with postoperative radiotherapy, the type of treatment is not an independent risk factor as many head and neck surgeons would like to believe. Incredulous of this finding, our own department has developed complex computer models including artificial neural networks with a poly nomial algorithm and confirmed the above finding. 13 0 =
=
=
COMPL I CAT IONS
Severe
The general complications of radiotherapy include mucositis, skin damage, reduced salivary flow, etc. Mendenhall et al. 13 1, 1 3 2 found a severe complication rate of 1 1 p ercent following radiotherapy for p iriform fossa cancer. Two of these patients developed chondroradione crosis, one required a tracheostomy and the other a total laryngectomy. Three patients developed severe laryngeal oedema and one patient developed severe intractable dysphagia. Radiation-induced laryngeal oedema is fre quently quoted as a severe problem associated with the treatment of the larynx and hypopharynx. Not only does it produce severe morbidity, but it also makes diagnosis of recurrent tumour extremely difficult. In our practice in Liverpool, serious post-radiotherapy oedema is fairly uncommon and almost always resolves within six months. We have very few patients with permanent oedema. [**] A particular practical note is that extreme caution must be exercised when carrying out biopsies on irradiated tissue. An injudicious biopsy can precipate chondrone crosis. In any event, in our experience, protracted oedema suggests underlying chondronecrosis and long-term oral steroids and tetracycline treatment are recommended. In the case of irradiation for posterior pharyngeal wall cancer, Mendenhall et al. 1 3 1 , 1 3 2 reported a severe complication rate of around 10 percent, half of their patients requiring a permanent tracheostomy. Irradiation to postcricoid cancer
1 9 6 Tu mou rs of the hypo p h a rynx a n d oesop h a g u s I 2655
may lead to stricture and this can be a late finding, appearing up ten years after treatment. Indeed, radiation to any subsite in the hypopharynx or larynx may be accompanied by this problem, although its incidence is uncertain. Certainly, a nasogastric tube should not be used in these patients because of the 'nasogastric tube syndrome'. In the Liverpool series of hypopharyngeal cancers, the incidence of severe post-irradiation oedema or fibrosis is 3 percent (own data) . If primary irradiation is the treatment of choice for the primary tumour, those with neck nodes over 2 cm in diameter will require a neck dissection, sometimes bilateral. A bilateral neck dissection is usually accom panied by oedema of the whole head and neck and usually, but not always, resolves. Staging the neck dissections may help, but it is not oncologically ideal. As radiation damages the lymphatics less than surgery, irradiating the less involved side of the neck may be useful. Even if a neck node recurrence occurs it at least gives time for lymphatic regeneration. Neck dissections, particularly bilateral neck dissections, are very likely to make laryngeal oedema worse. If surgery to both sides of the neck is unavoidable, some effort should be made to preserve one internal jugular vein. In any event N 3 bilateral disease heralds a disastrous prognosis of around 5 percent at three years (own data) . Moving on to surgery, most patients who have a total laryngectomy and partial pharyngectomy have similar complications to those having laryngectomy. The fistula rate is not particularly high, being in the region of 4 percent, and stenosis is also relatively uncommon. In the very rare event of this operation being carried out after irradiation has failed, then the risk of fistula is very high, in the region of 30 percent. 133 Almost all cases that require salvage following radiotherapy will require a total pharyngolaryngectomy and a repair of the pharynx by new tissue, either a free j ejunal loop or stomach transposition. With new tissue being brought into the area, the fistula rate is not high. The Liverpool series of 90 consecutive jejunal loop procedures79 had a total complication rate of 49 percent; fortunately, most of these were minor. Once experience had been gained in the technique, the graft necrosis rate fell to 6 percent. Early on in the series, the necrosis rate was considerably higher, indicating a learning curve and suggesting that such procedures should only be carried out in units with sufficient expertise and case load. A complication rate of around 50 percent has been reported by others. 1 34 The perioperative mortality (up to one month) is only 4 percent for jejunal loop, but the main problem with the technique is stenosis. In our series, 10 percent of patients developed a stenosis severe enough to require a pharyngoscopy and dilatation at least occasionally. [**] The stomach transposition operation cannot be compared to the jejunal loop procedure in the Liverpool series, as they are used for different indications. Stomach transposition is used for cervical oesophageal and large
2656 I PART 1 7 H EAD At\I D t\I ECK TU M O U RS postcricoid cancers. From the patient's point of view, the operation itself is a large undertaking, with complex upper abdominal surgery, a mediastinal dissection, as well as a neck procedure. The upper mediastinum can be visualized by the head and neck surgeon and the lower mediastinum by the abdominal surgeon. The problem in our experience comes in the middle mediastinum and we now use a diverticuloscope and a microscope, using microlaryngoscopy instruments to dissect the oesophagus free of surrounding tissue under direct vision. A superior mediastinal node sampling and dissection may be carried out at the same time. We have had no significant problems with this technique, but severe haemorrhage and pneumothorax are the main risks. In the early years of stomach transposition procedures, the perioperative death rate was high. It is now down to 10 percent, 9 8 which is approaching the results of Wei et a1. 96 who have great experience in this operation and use this procedure for the great majority of patients requiring hypopharyngeal replacement. [**] The causes of death following gastric transposition include pneumonia, graft necrosis, ana stomatic leakage, haemorrhage, myocardial infarction, cerebrovascular accident, respiratory failure and tracheal necrosis. In carrying out the superior mediastinal dissection on a patient who has failed radiotherapy, great care must be taken not to damage the posterior wall of the trachea. In our unit, the posterior tracheal wall has been severely damaged in several cases, but this can usually be successfully repaired using a fascia lata graft, laid between the stomach and the trachea. Once the stomach is in position, the graft is held tightly in place. One advantage of the stomach transposition procedure is that stenosis is rarely a problem, affecting only 3 percent of our p atients. The median hospital stay for both free revascularized j ejunal loop and stomach transposition procedures has been reduced to about three weeks. The treatment of posterior pharyngeal wall cancer presents a particular problem; radiotherapy is recommended for low volume disease, but this is relatively unusual. This exophytic cancer frequently does not invade the prevertebral structures until late and can be approached by the lateral 1 pharyngotomy method of Ogura et al. 3 5 After excision, a free revascularized radial forearm flap can be used for repair. It must be remembered that functional recovery is poor and most of these patients never swallow, requiring p ermanent gastrostomy. Finally, it should be emphasized that any patient who has been treated for hypopharyngeal cancer by whatever method is at risk of developing 1 hypothyroidism, sometimes many years later. 3 6 [**]
dogma, half of all patients present with relatively early (T 1 -T 2 ) lesions. However, half will have a node in the neck and a third a paralyzed or fixed vocal cord. The tumour-specific survival is 27 percent, the worst for squamous head and neck cancers. One-third of patients are incurable at presentation. Such a decision must be made only after full and systematic assessment. Attempt ing to cure the incurable will lead to disaster. Treated patients may expect good cure rates (50 p ercent) and over a quarter of patients will be suitable for radical irradiation with a good chance of loco regional control. In the event of failure, salvage surgery offers a 50 percent cure rate. Neck node metastases are a problem in this cancer. Piriform fossa cancer presents with a node in 75 percent of cases and even when no node is evident, occult nodes are likely. Some node systems, such as the retropharyngeal or upper mediastinal, are relatively inaccessible. Surgery for hypopharyngeal cancer has improved dramatically with the advent of the free jejunal flap and the greatly enhanced perioperative survival for stomach transposition. With a logical approach and a systemic assessment, together with adequate experience and expertise, the head and neck oncologist can successfully manage these unfortunate patients.
KEY PO I NTS •
•
•
•
•
S U rvlMARY Hypopharyngeal cancer is rare in the United Kingdom with an incidence of ten per million. It is arguably the most difficult head and neck cancer to treat. Contrary to
•
Accurate staging is essential. Following the ethos of organ preservation and improved quality of life, irradiation therapy is recommended for T 1 and T2 lesions. If a recurrence occurs, then good results may be obtained with surgical salvage with an acceptable cure rate. The neck should be treated as appropriate for neck metastases; dogged adherence to the old and now discredited concept of en bloc resection should not be followed. If a total pharyngolaryngectomy is necessary, if at all possible a jejunal loop repair should be employed. In practical terms, this means that the lesion does not extend below the clavicles. The neck, and in particular the superior mediastinum, must be treated in all cancers of the hypopharynx. If neck nodes are above 2 em in diameter, then surgery is necessary. If at all possible, irradiation therapy should be used on the opposite side. In our experience, most nodes in the superior mediastinum are less than 2 em in diameter and can be sterilized using irradiation. It must be remembered that nearly one-third of patients with hypopharyngeal cancer are incurable at the time of presentation.
C h a pter
•
The overall five-year, tumour-specific survival is less than 30 percent, although the survival of treated patients rises to 50 percent.
1 9 6 Tu m o u rs of the hypo p h a rynx and oeso ph ag u s I 2657
R E F E R E NCES 1.
2.
Ca rci noma of the hypo p h a ry n x : Ana lysis of i n cide nce a n d s u rv iva l i n Swed e n over a 30-yea r p e riod. Head a n d Neck.
Best cl i n i ca l p ractice A l l patie nts s h o u l d be ma naged by a m u lti d i sci p l i n a ry tea m that i n c l u d es a head and neck s u rgeo n , p l astic and reco nstructive s u rg e o n , ra d io o n co l ogist, d i eticia n , pa l l iative ca re co nsu lta nt, n u rse s pecia l ist a n d m edi ca l soci a l worker. Pa tie nts m ust have a ca refu l a n d thoro u g h exa m i nation u n d e r a n a esthesia for sta g i n g pu rposes to i n c l u d e a rigid p h a ry n g osco py, fl exi b l e oeso p h a g osco py, m i cro l a ry n gosco py, b ro nch oscopy a n d pa l pation of the neck. A conscious dec isio n m ust be made by the tea m a bou t treatment i ntent a n d whether a ra d ica l a p p roach h a s a rea l istic c h a nce of cu re or w h ether t h e treatment offe red is for pa l l iation. The treatment m ust be a g reed with th e patient, their fa m i ly and co m m u n i cated to t h e i r g e n e ra l pra ctitioner. Ea rly t u m o u rs (T l 8 T2) a re better ma n a g ed by a co m b i nation of s u rg e ry a n d ra d iothera py. Su rg ery u su a l ly i m p l i es a parti a l p h a ryng ectomy a n d l a ry n g ecto my with a free fla p re pa i r o f th e operative defect. Radiothera py a lo n e may be s u i ta b l e for t h e occasi o n a l sma l l t u m o u r. La rg e t u m o u rs (T3 8 T4) a l m ost a lways req u i re a tota l l a ry n g o- p h a ry n g ectomy a n d a com p l ex reco nstructi o n . F re e j ej u n a l tra nsfer, gastric tra nsposition or co l o n i c interposition is norma l ly req u i red. Postoperative ra d iothera py is i n d icated and exte nsion of t h e fie l d to i ncl u d e t h e su perior m ed iasti n u m shou l d b e considered. Th is w i l l i m ply t h e a p p l i cation of a l a rg e fi e l d and th e conseq u en ces of th is i n terms of morbid ity m u st be considered. Elective rad i oth era py of th e NO neck to i n c l u d e both si d es a nd t h e retro p h a ryng ea l nodes is i n d icated. I psi l atera l sel ective neck d i ssection (levels 2-4) or a mod ifi ed rad i ca l neck d i ssection ( 1 -5) is i n d icated fo r t h e N 1 n eck. Level 6 nodes a re rem oved if t h e patient h a s a l a ry ngecto my. I psi latera l ra di ca l neck d issection or sel ective neck d i ssection [ l evels 2-5 ) is i n d i cated for t h e N 2/3 n eck. Level 6 n od es a re removed if the patient has a l a ryngecto my. B i latera l n eck-d issection with preservation on o n e i n tern a l j u g u l a r vei n is i n d i cated fo r exte nsive t u m o u rs that cross t h e m i d l i n e or h ave bi latera l noda l d isease. For some, a mediast i n a l d issecti o n may be a p p ro p riate.
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head, neck, nose
1 4.
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1 6.
2658 I PART 1 7.
17
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32.
33. 34.
3 5.
3 6.
37.
38.
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25.
26.
27.
28.
29.
30.
31.
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39.
40.
41 .
42.
43.
44.
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1 09.
1 1 0.
111.
1 1 2.
1 1 3.
1 1 4.
1 1 5.
1 1 6.
1 1 7.
1 989 ; 1 7 : 293-7. Bocca E, Pignata ro 0, O l d i n i C. Fu nction a l neck d i ssection : On eva l u ation a n d review of 843 cases. Laryngoscope. 1 984 ; 9 4 : 942-5. Bye rs RM. M o d i fied neck d i ssectio n : A study of 967 cases fro m 1 970 to 1 980. American Journal of Surgery. 1 98 5 ; 1 5 0 : 41 4-2 1 . M e n d e n ha l l W M , M i l l io n RR, Cassisi I\J J . S q u a m o u s ce l l ca rci n o m a o f the head a n d neck tre ated with radiation t h e ra py: The ro le of neck d issecti o n for c l i n ica l ly positive Biology and Physics.
1 1 9.
1 20.
Seminars in Radiation Oncology.
1 07 .
E l l is ER, M e n d e n h a l l W M , Rao PV, Pa rsons JT, S pa n g l e r AE, M i l l io n RR. Does node location affect the incidence of d ista nt m etastases in head and neck sq u a m ous ce l l ca rci n o m a ? International Journal o f Radiation, Oncology,
1 21 .
neck nod es.
Intern ational Journal of Radiation, Oncology,
1 98 6 ; 1 2 : 734-9. J o n es AS, Fenton J , H usba n d OJ . The treatment of squa mous ce l l ca rci n o m a of the to nsil with neck nod es. Head and Neck. 2002 ; 2 5 : 24-3 1 . Fisch U. Lym phogra p h ische u ntersu c h u n g e n u be r d a s zerri k a l e Lym p h system fortoc h i r. Fortschritte der Hals Nasen Ohrenheilkunde. 1 96 6 ; 1 4 : 1 -9 6. Sti e g l H, Wasc h e r H . D i e sqi ntig ra p h is ser zervika l e n Iym p h b h ne n . Monatsschrift far Ohrenheilkunde und Laryngo-Rhinologie. 1 96 7 ; 1 0 1 : 409- 1 7. H e i m l ich HJ. Ca rci n o m a of the cervica l oeso p hag us. J ourn al of Thoracic and Cardiovascular Surgery. 1 970 ; 5 9 : 309- 1 8. Futre l l JW, Be n n ett S H , H oye RC, Roth JA, Ketc h a m AS. Pre d icting s u rviva l in ca ncer of l a ry n x a n d hypo p h a rg nx. American Journal of Surgery. 1 97 1 ; 1 2 2 : 451 -7. S n ow G B , An nyas AA, Va n S i ooten EA, B a rte l i n k H , H a rt AA. Prog nostic facto rs of neck node metastases. Clinical Otolaryngology. 1 982 ; 7 : 1 85-92. Cox DR. Regressio n models and l i fe tables (with d iscussion). Journal of the Royal Sta tistical Society. 1 97 2 ; 3 4 : 1 87-220. Jones AS, Ste l l PM. S q u a m ous carcinoma of the poste rior p h a ryngeal w a l l . Clinical Otolaryngology. 1 99 1 ; 1 6 : 462-5. G i ri d h ava n W, Ta kta k A, Fisher T. Fe nton J E, J o n es AS. Pred iction of s u rviva l i n l a ryngeal carc i n o m a w ith a rtificial n e u ra l n etwork and mathem atical model i n com parison w i t h Cox's reg ressio n . Clinical Oncology. Biology and Physics.
1 2 2.
1 23 .
1 24.
1 2 5.
1 2 6.
1 27 .
1 28 .
1 29.
1 30.
131.
1 3 2.
1 33.
( i n press) . M e n d e n h a l l W M , Pa rso n s JT, Dev i n e JW, Cassisi NJ, M i l l io n RR. S q u a mous ce l l ca rc i n o m a of the p ri rform s i n u s treated with surgery a n d/or ra diothera py. Head and Neck Surgery. 1 98 7 ; 1 0 : 88-92. M e nd e n h a l l WM, Pa rso ns JT, Cassisi NJ, M i l l io n RR. S q u a m o u s ce l l ca rci n o m a of the pyriform s i n u s treated with ra d ical ra d i ation therapy. Radiotherapy and Oncology. 1 98 7 ; 9 : 2 0 1 -8. McCo mbe AW, Jo nes A S . Radiothera py co m p l ications o f l a ryngectomy. Journal of Laryngology a n d Otology. 1 993 ; 1 07 : 1 30-2.
2662 1 34.
1 3 5.
I
PART 1 7 H EAD Af\I D f\I ECK TU M O U RS
Hoorweg JJ , Ra uwerda JA, Cro l l GA, Macka ay AJC, R i sse EKJ, Vries 1\1 et al. Free vasc u la rised j ej u n u m i nte rposition fo r p h a ryng oesop h a g ea l reco nstru cti o n after total l a ry n g o p h a ryng ectomy. Clinical Otolaryngology. 1 994; 1 9 : 496-50 1 . Og u ra J H , Watson R K, J u re m a AA. Pa rtia l p h a ryn g ectomy a n d n eck d i ssection fo r posterior hypo p h a ry n g e a l ca n cer. Laryngoscope. 1 960; 70 : 1 523-34.
1 3 6.
Tu rner SG, Tive r KW, Soyages Sc. Thyro i d dysfu n ctio n fo l l owi n g rad ioth e ra py fo r h ea d a n d neck ca ncer. International Journal of Radiation, Oncology, Biology and Physics.
1 99 5 ; 3 1 : 279-83.
97 -rhyroid ca ncer
JAMES RAMSDEN AND JOHN C WATKINSON
2663
I ntrod uction
2663
Problems with the thyroid cancer literature
2664
Surgical anatomy
2666
Aetiology and pathogenesis of goitre
2669
Molecular genetics of thyroid cancer
2675
Clinical assessment
2678
Laboratory investigations Prognostic factors
Recurrent disease
2693
2696
2697
Long-term f ollow-up
2697
Outcome measurements
2698
Key points
2698
Best clinical pr actice Deficiencies in current knowledge and areas for future
2682
References
2693
Paediatric thyroid cancer
2693
Radiotherapy ( radioiodine and extema I beam)
2679 2679
Staging Treatment policy
The difficult thyroid
research
2698
2699
SEARCH STRATEGY AND EVIIDENCE=-BASE
'I
A Medline search was carried out supplemented by searches on the Cochrane library a n d a number of internet resources,
which included cancerlit and cancernet, using the key words di fferentia ted thyr oid cancer, thyroid neoplasm, thyroid
nodule, ca rc inoma
-
pa pilla ry, follicular, Hurthle cell and medullary thyroi d cancer. The levels of evidence are mainly
levels two/three and the clinical recommendations are predominantly grades B/C.
INTROD U CTI O N
that safe and effective surgery can be offered to those
tu mours represents a
who require it Fine needle asp ir ati on cytology is now small
the cornerstone of investigation and for the majority
but significant workload for th e mo dern - day head and
of these patients, evaluation and subsequent treatment
The management of thyroid
neck
oncologist.
approxim ately
8
In
the
UK,
it
is
estimated
pe rce nt of the p opulation
h ave
that
nodular
thy roid disease and, of these, half are solitary n odules. l
Thyroid
nodules are more common in women
and
increase in fr e q uency with age but, while thy r oi d nodules
are com m on, thyr oid cancer is uncommon, representing
0.5 percent of new mal ignanci es (1000 new cases in the
usually means assessment b y a mu lti disc iplina r y team.
This involves an endoc r i nol og ist ,
a
surgeon and a cli ni cal
oncol o g is t working tog ethe r in a combined clinic in line with newly introduced nat ion al g uidelines. In the majo ri ty
of cases, combined treatment is highly effective an d
usually results in an excellent p rognosi s for most patients.
UK per year, which is approx im ately two per 100,000/
year ) . The most common way for thyroid cancer to present is
as a solitary thyro i d nodule a nd the fundamental and
crucial quest ion facing the physi cian or surgeon is how to detect t he 10 percent of sol i tary nodules with cancer so
PRO BLEM S W ITH TH E THYRO I D CAN CER LITE RATU R E
The I i terature on thyroi d cancer
i s di ffi cult to assess for a
number o f reasons. The disease is bo t h uncommon and
2664 I
PART 17 HEAD AND NEC K TUMOURS
are
elevated. This results in anaesthesia of the anterior neck
retrospective, often with inadequate follow-up, and there
skin, which can be particularly troublesome to men when
are multip le variables and a de fi nite outcome of any
shaving.
indolent
and
results
in
few
deaths.
The
data
prospective trial is unlikely in anyone clinician's working lifetime.
Th e
reason
for
controversy centres around
The external branch of the superior laryngeal nerve lies deep to the upper pole of the gland as it passes to the
papillary thyroid cancer since the disease is multifocal
cricothyroid muscle in the sternothyrolaryngeal (Joll's)
5 percent
triangle. This triangle is formed laterally by the upper
in about 80 per cent of cases; yet there is only a
of the gland and the superior thyroid vessels,
recurrence rate following treatment with lobectomy alone.
pole
However, half of those whose disease recurs die, and the
superiorly by the attachment of the strap muscles and
questi on is how to select those high risk patients who
deep investing layer of fascia to the hyoid a nd media lly by
midline (Figure 1 97.1 and Table 197. 1 ). Its floor is
would benefit from total thyroidectomy. In addition,
the
there is a well-r e cogni zed perception that total thyroi
the cricothyroid muscle, while its contents are usually the
regard to complication rates.
roof the strap muscles. In about 15 percent of cases, the
dectomy is associated with unacceptable morbidity with The main controversies regardi ng the treatment of differentiated thyroid cancer are as follows:
external laryngeal nerve runs with the superior thyroid vessels and leaves them close to the gland.2 It is therefore important to know where the nerve is and preserve it
•
mode of investigation;
•
progression from a low- risk patient to a high-risk
patient? •
progression from a low-risk tumour to a high - risk
•
t yp es of operation;
•
external laryngeal nerve running on c ri co thy roid and its
t u mour ?
whenever possible. The superior thyroid artery and vein, which run down to the upper pole from the external carotid artery and internal jugular vein) are in close proximity to this nerve which can be damaged if these vessels are not ligated close to the gland. Sectioning the external branch of the superior laryngeal nerve may limit
extent of surgery;
the patient's vocal range with difficulty reaching high
•
staging;
•
decidi n g who should undertake the surgery;
•
use of radioactive iodine;
notes, but unless he or she is a singer, this is unlikely to be either noticed or be a significant problem. The recurrent laryngeal nerves
• mode of follow-up.
(Figure 1 9 7.2) run in
the tracheo-oesophageal groove and can be in front of,
behind or indeed between the branches of the inferior thyroid arteries. This relationship has been used in the
S U R GICAL ANATO MY
past as a method to identify the nerves, but is not usually relied on nowadays. The inferior thyroid artery arises
The morbidity created by
poorly performed thyroid
from the thyrocervical trunk which is a branch of the fi rst
gland operation can exceed the morbidity caused by
part of the subclavian. It then pierces the prevertebral
leaving some thyroid lesions alone. Therefore, it is vital to
fascia medial to the carotid sheath to enter the posterior
a
understand the important points of both thyroid surgical anatomy and pathology, as well as the natural history of thyroid disease.
The thyroid gland is made up of two lateral lobes,
which extend from the sides of the thyroid cartilage down to the sixth tracheal ring. These are
j oi n ed together in
Superior thyroid ---Y\.\.
�+---Cricothyroid
vessels
the midline by the isthmus, which overlies the second to fourth tracheal rings. In addition, there is often a pyramidal lobe which p roj ects up from the isthmus,
Upper pole --------\-
usually on the left-hand side. The gland is enclosed in the
pretracheal fascia, covered by the strap muscles and overlapped laterally by the sternomastoid muscles. The anterior jugular veins cross over the isthmus. On the deep aspect of the gland lie the larynx and the trachea with the
pharynx and oesophagus behind and the carotid sheath laterally. On either side, there are two important nerves.
These are the external branch of the superior laryngeal nerve and the recurrent laryngeal nerve, and both lie in
close proximity to the gland and its blood supply. In
addition, the cutaneous nerves C2 and C3 run superficial to the deep investing layer of the cervical fascia and can be damaged at the time of surgery when the flaps are
Figure 197.1
Relationships of the sternothyrolaryngeal (JolI's)
triangle showing the external branch of the superior laryngeal nerve (EBSLN) running on cricothyroid.
Table 197.1
Blood vessels of the thyroid gland.
Arterial supply Superior thyroid artery
Venous drainage Superior thyroid vein
Inferior thyroid artery
Middle thyroid vein
Thyroid ima artery (inconstant)
Inferior thyroid veins
Chapter 197 Th yr o i d cancer I
part of the thy roid gland. At surgery, befor e anybranch of the infe r io r thy roi d artery is d i v ide d
,
the
recurrent
2665
side, the n er ve ascends from the chest having circumna vigated the ao r t i c arch. However, o n the ri gbt side, the
laryngeal nerve must be ident ifi ed since the anatomy
nerve is m ore superficial, being 45° t o the tracheo
can be variable. The best and safest way to identify the
oesophageal groove since it only has to pass around the
nerve
artery of t h e fourth arch ( the subclavian ) . On the right
in the tr acheo
is to look for it low dovm
oes oph ageal groove where it forms the third sid e of
side, it is i m por tan t to re m e m ber that in approxi mately
other two sides of the t rian gle are for med by the common
is
carotid and inferior t h yroid arteries. The nerves lie in, or
where it runs wit h th e i nfe r i or th yroid vessels en route to
Beahrs' ( a fter OH B eah rs ) t r ia ng le (Figure 197.3). The
lateral to, the tracheo-oesophageal groov e and on th e left
2 percent of pa t ients, the nerve may be nonrecurrent and
then found mo r e su per i o rl y in the paracarot id
tunnel
the larynx. Th e re may be e xt r a l ar ynge al divisions as far as 3-4 em below the
Additional
inferior bord e r of
b lood
the cr ic o id cartilege.
s upply sometimes comes from an
incons tant vessel, the t hyro i d ima artery, which, when p rese nt, arises from either the aortic arch or innominate ar te r y.
The venous drainage of the thyroid is into the internal
Superior
jugular vein via the superio r thy roid vein which drains t he
parathyroid
upper pole. T he middle t hyroid vein drains the lateral part of the gland and t here are m ultip l e inferior thyroid
Inferior
veins which drain the lower pole of the gland into the
thyroid
brachiocephalic vein.
artery
The parathyr o i d gl a n ds lie outside the thyro i d capsule
beneath the pr e trache a l fascia (Figures 197.2 and 197.3).3
In app roximat e ly 90 percent of pati en ts , the blood supply to both superior and i n fer io r glands is from t he in feri or
Inferior parathyroid gland
in
third of these cases
Recurrent
thyroid artery and
laryngeal
a significant supply thr ou g h the thyro i d capsule . In
nerve
a
there is also
the remainder, both glands are suppl ied eit her by an
anastomotic arch from the superior and inferior th y roid
Recurrent
vessels or from the super ior t h yro id artery alone. The
laryngeal
superi or glands are more constant in their locat io n and
nerve
usua ll y
Figure 197.2
Poste r i or relations of the thyroid gland showing
the inferior thyroid arteries, the recurrent laryngeal nerves and the usual position of
near the cricothyroid j o i nt close
to the
nerve, c e ph alic to the inferior thy ro id artery (Figure 1 97.3), wh ich is p roba bly the best initial
Right
Left
lie
rec urren t laryn geal
the par athyroid glands.
marker to l ocat e them. The inferior glands are o ften more variable in their locat i on, bei ng caudal to where the
recur ren t l a r yngeal ner v e and the infe ri or thy r oid a r tery
Superior parathyroid gland
Berry's ligament
ITA ---+-_.-:::;...., -r-------;--Inferior parathyroid gland Beahrs' triangle --\---
Figure 197.3
The relationships of the re cu rrent
la ryngea I nerve. Note: The RLN may pass in front , beh i nd
or between the branches of th e ITA. Such re lationsh ips
should not be relied upon when searching for the nerve.
CCA, common carotid artery; eM, cricothyroid muscle; ITA
inferior thyroid artery; RLN, recurrent laryngeal nerve ; RTL, RLN
right thyroid
artery : TC, thyroid cartilage.
2666 I
PART 1 7 HEAD Af\ID NECK TU M O U RS
cross at the apex of Beahrs' triangle. In half of the cases, the inferior parathyroid glands are found in and around the lower pole of the thyroid gland and a quarter may be close to, or within residual thymus tissue. As a general rule, parathyroid glands are located symmetrically on either side of the neck and this is often helpful when looking for a missing gland. Most people have four parathyroids, but approximately 10 percent have more than four glands, while 3 percent have less than four. A healthy parathyroid usually measures on average just under 1 cm 3 and is usually oval, varying in colour from light yellow in older patients to a reddish brownish colour in younger ones. The fat content increases with age. It is useful to remember that in normal saline, fat floats and parathyroid tissue sinks. Parathyroid tissue can be found anywhere in the neck and can be located high in the neck, the carotid sheath, the tonsillar area, the lateral wall of the nasopharynx, the retropharyngeal and retro-oesophageal areas, as well as within the thyroid and the mediastinum where the location is often intra thymic. The primary lymphatic drainage from the thyroid can travel in a superior, lateral and inferior direction and follows the vascular pedicles of both the superior and inferior thyroid vessels, as well as the middle thyroid vein. The upper poles of the gland together with the isthmus and the pyramidal lobe drain superiorly, terminating in the lateral neck in levels II/III, while the lateral aspect of each lobe drains into levels III and IV. The lower pole of the gland drains into the peri- and paratracheal nodes in level VI, and then on to both level IV and level VII nodes. Lymphatic drainage may also pass to nodes within the parapharyngeal and retropharyngeal spaces, but this usually tends to occur when other nodes are involved and shunting occurs, or when there has been previous treatment with either surgery or irradiation. It is very uncommon for differentiated thyroid malignancy to present with an isolated metastasis in the parapharyngeal space. There are also extensive communications between the lateral cervical lymph nodes in levels II, III and IV and the superior mediastinum via level VI. The lymphatic drainage of the thyroid is shown in Table 197.2. Tumours in the upper pole tend to metastasize to levels II/III; tumours in the middle third of the gland spread to the paraglandular and paratracheal nodes, while those
Table 1 9 7.2
Lym phatic d ra i n a g e of the thyroid g l a n d .
Node
M ajor Mid d l e ju g u l a r nodes Lowe r ju g u l a r nodes Poste rior tri a ng l e n odes M i nor Pre- a n d p a ra trac h e a l n odes Su perior medi asti n a l n odes
Level
in the lower third spread predominately to the para tracheal nodes. Isthmus tumours spread most often to the pretracheal nodes. The major lymphatic drainage is to the middle and lower deep jugular nodes (levels III and IV) and to the nodes in the lower posterior triangle (level V ) . Some lymphatics drain to the pre- and paratracheal nodes in the anterior compartment (level VI) and then to the mediastinal nodes (level VII ) .
AETIOLOGY A N D PATHOG E N ES I S OF GOITRE G o itre Goitre is a relatively imprecise term, which means the clinical observation of an enlarged thyroid gland. There is no fo rmal definition of the degree of enlargement to differentiate the gland from a normal thyroid, although the most widely adopted criteria are those of the World Health Organization ( WHO) , which defined goitre as 'a thyroid whose lateral lobes have a volume greater than the terminal phalanges of the thumb of the person being examined'. However, several studies have shown that there is considerable subjectivity in the clinical grading of thyroid enlargement, and furthermore, there is geo graphical variation in thyroid size. Goitre can be broadly divided into several entItIes which include goitre in iodine-deficient areas, goitre in iodine- replete areas and thyroid cancer. The prevalence of clinical syndromes varies considerably from area to area and is mainly determined by the availability of iodine. Nonmalignant goitres have been classified in the past as simple, nodular or multinodular on pathological grounds. It is likely that all of these have the same molecular basis and represent different time points in the development of goitre, as so-called 'simple goitres' commonly develop nodules over time. This classification is not used further. Thyroid surgery is common and there are more than 8000 thyroidectomies performed each year in the UK.4 The majority of these are for benign disease, but around 1000 are for cancer. In Switzerland, where goitre is very common because of diminished iodine uptake, the mortality rate from cancer of the thyroid is approximately ten times that in England and Wales. There is a female preponderance of approximately 3:1 for thyroid cancer and, although it can occur at almost any age, the majority of patients ( especially those with follicular, medullary and anaplastic cancers) are elderly. In adolescents and young adults, thyroid cancer is predominantly of the well-differentiated type.
III IV V VI VII
I ODI NE-DEFI C I ENT G O ITRE
It has been observed for more than 3000 years that goitre is more common in some areas than others, and this is the case in most countries, leading to terms such as
Chapte r 1 9 7
'Derbyshire neck'. Pliny made reference to goitre in inhabitants of the Swiss Alps, 5 which was correctly attributed by contemporaries to drinking water from melted snow, now recognized as having a low iodide content. Goitre was also well recognized in China, an iodine-deficient area, as early as 2700BC. The prevalence of goitre ranges from nearly zero to 80 percent of the population in areas of iodine deficiency, with the WHO identifying 7 percent of the world's population as suffering from clinically apparent goitre.6 The thyroid stimulating hormone (TSH ) , T3 and T4 are usually within the normal range, although the TSH tends to be at the upper and T4 at the lower end of normal. The goitre is in response to the persisting stimulation of the thyroid by mildly elevated TSH and represents functional glandular hyperplasia. The goitre may develop as young as three years of age, tends to become nodular over time and may reach significant proportions. Goitre is not equally prevalent in areas of equal iodine deficiency and the factors that play a role in determining goitre formation in different individuals within the com munity include genetic, cultural and dietary factors. In areas of Greece with endemic goitre, considerable variation in the incidence of goitre was found in different families. It is likely that the same aetiological mechanisms that determine the development of sporadic goitre in iodine-replete areas influence the incidence of goitre formation in iodine deficient areas. Treatment with iodine can cause a goitre in children to regress, but has little efficacy in reducing goitre in adults, and carries the risk of hyperthyroidism by the Jod Basedow phenomenon. This is iodine-induced hyperthyr oidism, which was first reported following treatment of an iodine-deficient goitre with iodine, but can also rarely occur in iodine-sufficient glands. Women with multi nodular goitre are particularly at risk, because of relatively autonomous nodules within the thyroid, which do not respond to the fall in circulating TSH. Goitre is endemic when the average ingested iodine is less than 50 �g/day and at less than 25 �g/day of iodine children are at risk of cretinism. The features of cretinism are mental and growth retardation, thickened skin and tongue. Sometimes there is deaf mutism and spastic diplegia. The incidence of endemic cretinism has been reduced by iodine supplementation of food, including bread and salt, in many low iodide-consuming communities. The majority of iodine in the UK is derived from dairy products, due to supplementation of animal feeds and salt licks with iodine. 7 Changing farming practices may lead to a reduction in iodine consumption in the future. Some groups, especially vegans, living in areas without com pulsory iodination of salt or bread may exhibit iodine deficiency even in iodine-replete communities. I ODI NE-SUFFICI ENT G O IT R E
The prevalence of goitre in iodine-replete areas has been assessed in several important population studies. Goitre is
Thyroid ca nce r I 2667
most common in premenopausal women and can be physiological in pregnancy. The best known UK popula tion study of thyroid disease is the Whickham survey, in northeast England, where 2779 individuals were selected at random from the electoral register and examined. l The thyroids were assessed and broadly divided into normal, palpable goitre and visible goitre. Overall, there was a 15.5 percent incidence of palpable goitre and a 6.9 percent incidence of visible goitres in the community. The majority were in premenopausal women and after the menopause the incidence fell. Thyroid nodules were palpable in 0. 8 percent of men and 5.3 percent of women. There was no significant difference in mean serum TSH and mean thyroid hormone levels between goitrous and nongoitrous subjects. This cross-sectional study became longitudinal, when the same population was followed up 20 years later. 8 The incidence of goitres in the surviving women had fallen from 26 to 10 percent, confirming that goitres can regress with age. The factors predisposing to goitre formation in iodine replete areas are as follows: • •
•
•
genetic factors; goitrogens: thiocyanates, isothiocyanates: (c) cassava, maize, sweet potatoes; (j) cigarette smoking; goitrin, flavinoids: o brassica seeds, millet; drugs: - amidiarone, lithium and antithyroid drugs; autoimmune thyroid disease.
G e netic There has been recognition of clusters of goitre occurring in families for many years. This is a very exciting time for the determination of the genetic basis of disease. It has been known for a long time that there is a higher incidence of goitre in some families and that monozygotic twins have higher concordance for goitre than dizygotic twins. Brix et al. in Denmark looked at 5500 monozygotic and dizygotic twins and concluded that 82 percent of susceptiblity to multinodular goitre ( MNG) was inheri table. 9 There are rare defects in thyroxine synthesis which can cause goitre. An example is Pendred's syndrome which is an autosomal recessive cause of sensorineural hearing loss, associated with euthyroid goitre and mondini cochlea, and is the most common cause of congenital deafness. The gene for this has been cloned and is an iodide-chloride transporter, called pendrin, principally expressed in the thyroid. In hypothyroid goitres, several molecular defects in the thyroglobulin (TG) , thyroperox idase ( TP O ) , and Na+/I- symporter ( NIS) genes have
2668
I PART 17 HEAD AND NECK TUM O U RS
been identified. The TSH receptor has been cloned and
expression of these factors is increased in cancer and
goitrous
multinodular goitre.lo
individuals
with
activating
and
inhibiting
polymorphisms are reported, although these are rare. It has long been recognized that goitre, hyperthyroid
Angiogenic growth factors, including VEGF and the angiopoietins have been identified in the thyroid, and
ism and thyroid cancer have a tendency to occur in many
there is accumulating evidence that VEGF, the angio
members of the same family. This has been presumed to
poietins and their receptors are important in the thyroid
be polygenic in nature, but the genetic basis for this is
in Graves' disease, thyroiditis, goitre and cancer.ll, 12
starting to become more clear.
A locus on chromosome
14q is linked to familial nontoxic multinodular goitre and
this is close to a Graves' disease susceptibility locus,
suggesting that this area may yield important, as yet unidentified genes, for further study.
Thyro i d can cer Thyroid cancer is the most common endocrine tumour, with an incidence ranging from
1.2 to 3.81100,000 cases
per year in the UK, which equates to under 1 percent of
Goitro g e n s
new malignancies, and the most common way for it to
There are large numbers of goitrogens, both natural and
patient when the incidence of malignancy is between 10
present is as a solitary thyroid nodule in a euthyroid man-made, which can cause thyroid growth and lead to goitre formation. These predominantly interfere with iodide transport, organification of iodide and release of hormone. Goitrogens are present in maize, sweet potatoes and cigarette smoke, although the clinical importance of these is small.
Other potential goitrogenic pathways
and
20 percent (Figure 197.4). It has a favourable outlook
in comparison to most other solid tumours, and accounts for less than
0.5 percent of cancer deaths. It is well
established that thyroid cancer, like all thyroid diseases, is
two to four times more frequent in women than men. It is rare in children below 16 years and the incidence increases
interfere with TSH release, alter local growth factor expression or change TSH receptor function. The effects of these compounds will be increased if acting on a background of iodine deficiency or a genetic predisposi tion to goitre formation. Medical use of goitrogens, principally amidiarone, lithium and carbimazole, are the most common goitrogens encountered clinically in the UK.
brassica family
Growth facto rs Many cell activities, including differentiation, growth and function, are modified by local paracrine or autocrine factors.
Several
important growth factors have been
identified
in the thyroid.
hormone,
TSH,
which
The most
promotes
obvious is the
growth
in
human
thyroid cells, but other important cytokines include fibroblast growth factor (FGF), epidermal growth factor (EGF) and insulin-like growth factor (IGF). Angiogenic growth factors are also essential for the formation of a large
goitre.
Changes
in
growth
factor
expression,
receptor expression or thyroid hormone expression, many of which can be mediated by TSH, may all play a role in goitrogenesis. Several growth factors are increased in goitre, includ ing FGF. FGF has many functions including proliferation and chemotaxis of several cell types including fibroblasts, endothelial cells and smooth muscle cells, and it is a potent stimulator of angiogenesis. FGF-l goitrogen in rats increasing thyroid weight
is a potent
43 percent
after six days of treatment. Human follicular cells express both FGF-1 and
-2, as well as the receptor FGFR-1, and
Figure 197.4
� ight-sided sol itary thyroid nod ule in a young woman. The risk of malignancy i s approxi mately 10-20 percent.
Chapte r 197
during life. The median age of diagnosis in most series is between 40 and 50 years. Predisposing factors for thyroid malignancy include: •
•
• •
•
prolonged stimulation by elevated TSH; solitary thyroid nodule; ionizing radiation; genetic factors; chronic lymphocytic thyroiditis.
A nodule is more likely to be malignant if: •
•
•
•
•
•
•
•
there is a positive family history; there is a previous history of thyroid cancer; it is enlarging (particularly on suppressive doses of thyroxine) ; the nodule develops under 14 or over 65 years of age; the patient is male; there is a past history of ionizing radiation; TSH is elevated; thyroid antibodies are positive.
M O LECU LAR G E N ETI CS OF THYRO I D CAN CE R There has been a n explosion i n the understanding of the molecular genetics of disease which has shed light on tumour biology. Some of this new information is giving us greater insight into the molecular pathology of thyroid cancer, although the development of novel diagnostic and treatment modalities is still awaited. Most malignant thyroid tumours have a monoclonal origin, suggesting that genetic events in a single cell account for their development. These nonp rogrammed events may involve the activation of oncogenes, or the inactivation of tumour suppressor genes. The protein products of these genes have now been identified, cloned and expressed in transgenic mice. This allows in vivo identification of the mechanism of action of known oncogenic pathways. Several oncogenes are known to play an important role in thyroid carcinogenesis and development. More are likely to be identified over the next few years as researchers use new tools to identify genetic cause and effect in models of thyroid cancer.
Ret/PTC
------
Ret is a proto-oncogene located at chromosome 1 0q 1 1 .2 which encodes a transmembrane tyrosine kinase receptor. The ligand fo r Ret has recently been identified as glial cell line neutrophilic factor (GDNF) . Ret has been identified principally in papillary cancer ( PTC) and several muta tions have been identified. These have been labelled Ret/ PTCl- and are all due to specific oncogenic rearrange 5 ments of the tyrosine kinase domain of the Ret gene. Ret mutation is restricted to thyroid carcinomas of the papillary subtype and is found at high frequency in small
Thyroid ca ncer I 2669
papillary carcinomas, suggesting that the Ret mutation can be an early event in thyroid tumorigenesis. Ret/PTC can transform follicular cells in vitro and mice transgenic for the Ret/PTC mutation develop papillary thyroid cancer. The Ret/PTC mutation was found in 60 percent of Ukrainian thyroid cancers after the Chernobyl accident and Ret/PTC3 was present in 1 9/25 of the unusual solidI follicular subset of papillary cancers seen in affected children. 13 Ret mutations are also found in medullary thyroid cancer. Up to 33 percent of sporadic medullary thyroid cancers have mutations of the Ret, but Ret mutation is most strongly associated with M EN 2A, M EN 2B and familial medullary thyroid cancer. Approximately 95 percent of families with MEN 2A have a Ret mutation in exon 10 or 1 1 . Mutations of codon 634 occur in about 8 5 percent of families; mutation of cysteine residues of codons 609, 6 1 1 , 6 1 8 and 620 together account for the remainder of identifiable mutations in exons 1 0 and 1 1 . Ninety-five percent of individuals with the MEN 2B phenotype have a single point mutation in the tyrosine kinase domain of the Ret gene at codon 9 1 8 in exon 1 6, which substitutes a threonine for methionine. Eighty-five percent of families with familial medullary thyroid cancer have an identifiable Ret mutation. These mutations occur at one of the five cysteine residues (codons 609, 6 1 1 , 6 1 8, 620 and 634) , although mutations of other codons have also been identified in a small number of families. These mutations may be rapidly identified by genetic screening, allowing identification of affected family members and counselling and treatment of affected families.
RAS RAS genes encode a signalling protein involved in transduction of intracellular signalling from the cell surface to the nucleus. RAS activation stimulates mitosis and reduced differentiation. There are three separate RAS genes, Ki-RAS, N - RAS and Ha-RAS, and mutations have been identified in all three in thyroid cancers. Point mutations ( usually co dons 1 2 , 13 or 6 1 ) can produce constitutively activated RAS, which is potently oncogenic. RAS mutations are equally prevalent (around 50 percent) in thyroid adenomas, follicular carcinomas and anaplastic tumours, but are less common in papillary thyroid cancer. Activated RAS transfected into normal human follicular cells in vitro leads to an increase in cell proliferation which is a key step in tumour formation.
trk and m et trk is an oncogene, located on chromosome 1 , which codes for a transmembrane tyrosine kinase receptor, whose ligand is nerve growth factor. It is mutated in 1 0-2 5 percent of papillary carcinomas. Several mutations
2670 I
PART 1 7 H EAD Ar-..I D r-..I ECK TUM O U RS
have been described, but the biological significance of the trk mutation in thyroid cancers has not been fully evaluated. met is a transmembrane tyrosine kinase receptor for hep atocyte growth factor (HGF) . HGF is a strong mitogenic facto r for many epithelial cells and met expression is sp ecifically increased in papillary thyroid cancer. Furthermore, met overexpression is related to RAS and Ret activation in human thyroid cells, suggesting that there is some costimulus of cells by different oncogenes, which leads to increased growth due to increased HGF sensitivity.
GcxS a n d gsp TSH is the major physiological stimulus for thyroid cell activity and acts to elevate cyclic adenosine 3 ',5' monophosphate (cAMP) . This is mediated by G-proteins, of which the active protein is GcxS and is coded by the gene gsp. The elevated cAMP stimulates an increase in protein kinase A, which leads to phosphorylation of numerous target proteins, including cAM P-responsive transcription factors which in turn leads to altered gene expression. Mutations in GcxS, leading to constitu tive elevation of cAMP, have been identified in toxic adenomas as have activating mutations in the TSH receptor. Although cAMP is growth stimulatory and might be expected to be a potent oncogenic agent, both TSH-receptor and gsp mutations have a low prevalence in thyroid tumours.
Tu mou r s u p p ressor g e n es Tumour suppressor genes code for proteins that inhibit or arrest cell division. Several have been identified, including the p53 gene. p53 is widely involved in numerous tumours and is the most frequently mutated cancer gene being affected in more than 50 percent of solid tumours. In light of this, the thyroid is unusual as p53 mutation is extremely rare, except in anaplastic tumours. This suggests that p53 inactivation may be a key event in progression from differentiated to anaplastic carcinoma. Deletions in chromosome 1 1 and 3 have been reported in follicular cancer and it is possible that further tumour suppressors specific for follicular cancer remain to be identified at these loci.
Ra d i ation Low-dose ionizing radiation is a well-recognized aetio logical factor in differentiated thyroid cancer. The energy contained in ionizing radiation is able to displace electrons and thus break the bonds that hold molecules together. This process generates reactive free radicals which cause biological damage inside the cells. DNA is the
most important molecular target, because damage to a single gene may cause cell death or altered cell behaviour. In the early part of the twentieth century, many young patients were treated for a variety of conditions with radiation. These included adolescent acne, tuberculous cervical lymphadenitis and tinea capitis. Radiation was also given to cause involution of the thymus, tonsils and adenoids. These patients were subsequently noted to have a greatly increased risk of thyroid cancer over the following decades. The Rochester study followed 2650 irradiated subjects, predominantly irradiated for thymic enlargement before the age of one year. 1 4 Using untreated siblings as a control group, there was a 60-fold increase in thyroid cancer rates, and with long follow-up ( mean of 24 years) , there was a linear dose-response curve for thyroid cancer from 0.05 to 1 0 Gy. Several other studies have replicated these findings and have also revealed that the cumulative prevalence of thyroid nodules in indivi duals treated with low-dose ionizing radiation was nearly 40 percent and of these, 35 percent were malignant. Most, though not all, of the studies have shown that the oncogenic risk is greater in the youngest individuals. The radiation-induced thyroid tumours are multifocal in nearly two-thirds of cases and develop up to 40 years after exposure, although the peak incidence is about 1 5-25 years after exposure. Survivors of radiation from the atomic bombs in Japan and the inhabitants of the Marshall Islands, exposed to radioiodines after the testing of a thermonuclear device, have shown an increased incidence of papillary thyroid cancer. The Chernobyl nuclear accident released 8 x 1 0 1 8 Bq of radiation into the atmosphere in April 1 986. There were numerous isotopes of iodine released, including 1 3 1 1, 1 32 1 and 133 1. Following this, there was an increase of thyroid carcinoma ( up to 1 00-fold) in Belarus , Ukraine and western regions of Russia, where exposure was highest. This risk of developing thyroid cancer increased rapidly and peaked at ten years post-exposure. Most of the thyroid carcinomas occurred in children below ten years at the time of the accident and nearly two-thirds were under five. This is because of a relatively high dose of radioiodine to the small thyroid gland in a child, combined with the high consumption of milk in children, which was the main source of contaminated radioiodines. Over 90 percent of the cancers were papillary, but with histologically aggressive features. The post-Cherno byl thyroid cancers showed Ret gene rearrangements in 55-8 5 percent, which were mainly PTC 1 and PTC . The 3 Ret/PTC mutation was particularly strongly associated 3 with the solid-follicular variant of papillary carcinoma. p53, gsp and TSH -R mutations occurred much less frequently in the exposed population. Radiation-asso ciated thyroid cancer is usually well differentiated and the majority of lesions are papillary. The medic �l use of 1311 for the treatment of Graves' disease, thyroid isotope scanning and thyroid cancer has
Chapter 197
been studied. In all uses, the development of subsequent thyroid cancer is surprisingly rare. Diagnostic 1 3 1 1 exposes the thyroid to a small dose of radiation ( typically about 1 -2 MBq or 1 Gy thyroid dose), but no sign ificant increase in either nodularity or cancer in exposed subjects (even children) has been detected after a 24-year follow up. The absence of a carcinogenic response may be related to the physical properties of 1 3 1 1 and, in particular, its low dose rate. Treatment for Graves' disease and thyroid cancer involves much higher radiation exposure, typically 1 00-300 lVIBq and 3000-5000 MBq, respectively. These high doses predominantly cause thyroid cell death and lead to late hypothyroidism rather than cancer develop ment. There is no significant increase in thyroid cancer rates post-exposure to 1 3 11, although there remains concern about the use of radioiodine in very young children. IS
Fa m i ly h istory Several rare familial syndromes are associated with thyroid nodules and cancer. Patients with Gardner's syndrome or familial adenomatous polyposis coli have a 1 00-fold increased risk of developing papillary thyroid carcinoma, with its characteristic multifocality. Cowden's disease, a very rare syndrome of multiple hamartomas, also has a significant risk of developing papillary thyroid carcmoma. Medullary thyroid carcinoma arises from the para follicular C cells and accounts for 5 percent of thyroid cancers. The majority are sporadic, although patients should be screened for one of the multiple endocrine neoplasm (MEN) syndromes. Hereditary medullary cancers are bilateral, multicentric neoplasms, whereas the sporadic type usually presents as a single tumour confined to one lobe. MEN 2A was described by Sipple in 1961,16 and sometimes bears his name. It is inherited as an autosomal dominant condition with complete penetrance, but variable expression. In this syndrome, medullary cancer develops in association with a phaeochromocytoma and hyperparathyroidism. Medullary cancer develops in all affected family members and is usually detectable by the second decade of life, although a palpable thyroid nodule may not become evident until 40 years of age. In patients with known familial disease, the genetic mutation on the Ret oncogene should be sought. In the past, affected family members were screened by looking at calcitonin (± pentagastrin stimulation) and CEA, but now it should be by genetic screening. Point mutations of the Ret oncogene on chromosome 10 have been identified and because 98 percent of patients with Men 2A have mutations in one of six codons of the Ret gene, and 95 percent with Men 2B have a single mutation ( methionine into threonine) at codon 918 (exon 1 6 ) in Ret, then familial screening is easy and accurate. If examination of
Thyroid ca ncer I 2671
Ret is normal then there is less than a 0.5 percent chance that there is familial disease. Family members found to be affected should be considered for prophylactic total thyroidectomy after screening to exclude a phaeochromocytoma. MEN 2B is characterized by a more aggressive medullary thyroid cancer, phaeochromocytoma, a Mar fanoid appearance with multiple mucosal neuromas affecting the lips, tongue and oropharynx, and gang lioneuromas of the gastrointestinal tract. In addition, an autosomal dominant familial variety of indolent medullary thyroid cancer has been recognized (familial, non-MEN MTC ) , which is also associated in more than 85 percent of cases with a Ret mutation.
Pre-exi sti n g thyro i d d isease Several studies have shown that benign thyroid nodules are frequently diagnosed prior to cancer in thyroid cancer patients, although this may be due to the benign lesion leading to discovery of the cancer. In some series, malignant thyroid nodules are more common in patients with Graves' disease, although this is not found in all reports. Thyroid lymphoma occurs against a background of autoimmune lymphocytic thyroiditis ( Hashimoto's disease) . Although rare, anaplastic cancer is often preceded by a longstanding goitre, and may be the result of malignant change within a pre-existing hyperplastic thyroid.
D i etary iod i ne consu m pti o n I t has been suggested that there i s a higher incidence of thyroid cancer in iodine- deficient areas, but this hypoth esis has not been proven. There is a higher incidence of thyroid nodules in low iodine areas, but also a lower proportion of nodules are malignant. Iodine intake does alter the type of cancer and low iodine areas have a relatively higher incidence of follicular and anaplastic tumours, whereas high iodine areas have a higher incidence of papillary cancer.
S u rg i ca l pathology Tumours affecting the thyroid gland are either benign or malignant, and usually arise from within the thyroid gland itself ( Table 197.3 and Figure 197.5) . Much less commonly, the thyroid may be involved by direct spread of cancers from adjacent organs, such as the larynx, hypopharynx and cervical oesophagus. Very rarely haematogenous metastases from cancers arising at other sites are found and these include the kidney, lung, colon and breast.
2672
I PART
17
H EA D AN D N ECK TUMOURS
and become autonomo us. Grossly, they are distinguished from goitrous nodules by their capsule. Microscopic patterns include follicular, micro follicular, Hurthle cell and embryonal. M alignancy cannot usually be excluded by cytological or microscopic patterns, but is diagnosed by capsular or vascular invasion. Rarely, papillary adenomas have been reported, but they are all probably low-grade papillary carcinomas. Teratomas occur exclu sively in infants. They too are rare and invariably benign. Malignant tumo urs of the thyroid gland can originate fro m any of the cellular components of the gland follicular and parafollicular cells, lymphoid cells and stromal cells. The vast majority, however, arise from follicular cells and other types are rare. Follicular cell neoplasms can be classified into three major categories. These are papillary, fo llicular and anaplastic (undiffer entiated), The only known neoplasm of parafollicular cell origin is the med ullary carcinoma. Malignant lymphomas are uncommon, usually arising within a lymphocytic thyroiditis and sarcomas are very rare. There are only a few cases of squamous cell carcinoma of the thyroid that have been described. Much more common is direct spr.ead by continuity and contigu ity from carcinomas of either the larynx or post-cricoid region. The WHO classification of thyroid tumours is shown in Table 1 97 .4.
Benign enlargement of the thyroid gland is common. Colloid and adenomatous goitres, characterized by multiple nodules of varying size and consistency, are the types most often encountered. The nodules are demar cated, but not encapsulated. Many have a gelatinous consistency with areas of degeneration or calcification. Microscopically they contain no dules of vario us sizes with flattened follicular epithelium. A variant of adenomatous goitre is the adenomatous nodule which is a solitary dominant mass that mimics an a denoma and it may be difficult to distinguish it from a true adenoma on cytology. The adenoma is the most common benign thyroid neoplasm. This usually presents as a solitary thyroid nodule or as a dominant nodule in a multinodular gland. Adenomas are most common in middle-aged women, not p remalignant and rarely become toxic, but may function
Ta b l e 197.3
Classification of thyroid tu mours.
Be n i g n
M a l i g n a nt Primary
Fol l icu lar ce l l adenoma H Urthle cell adenoma Teratoma
Papillary carci noma (800/0) Pu re papillary Mixed papi l l a ry-fol l icular Fol l icular variant Foi l icu la r carcinoma ( 1 0% ) HUrt h l e ce l l carci noma
Not WHO
Pa p i l l a ry a d e noca rci nom a Papillary adenocarcinoma accounts for 8 0 percent of thyroid malignancy. It occurs in all age gro ups and is virtually the only thyroid cancer of children. Its most frequent age incidence, however, is from 40 to 49 years. Typically, papilla ry ad enocarcinoma presents as a solitary nodule in the thyroid (Figure 1 97.4). M acroscopically, it is a firm and unencapsulated tumour which is sharply circumscribed by the surro und ing normal thyroid tissue.
Med u l l a ry carcinoma (5%) Anaplastic carci noma (3%) Lymphoma (1 0/0) Sarcoma Squamous cel l carcinoma Secondary
Kid ney, l u ng, colon a n d b reast
Anaplastic 3% Medullary 5%
""
I
----
Papil lary 8 1 %
F i g u re 19 7 . 5
The incidence of thyroid cancer.
Chapte r 197 T h y r o i d ca n c e r I Tab l e 197.4
The W o r l d H e a l t h O rg a n iz at i o n rev ised h isto l og ic a l
c l a s s i fi cat i o n of t h y r o i d t u m o u rs. Cl assification Epi th e l ia l t u m o urs A.
Benign 1 . Fol l i cu l a r (a)
(b)
2.
adenoma
Arch itect u ra l patte rns (i)
N o rm ofo l l ic u l a r (s i m p l e)
( i i)
Macrofo l l i c u l a r (co l l o i d )
( i i i)
M i crofo l l i cu l a r (foeta l)
(iv)
Tra bec u l a r a n d s o l i d (e m b ryo n a l)
(v)
Atyp i ca l
Cyto l o g i c patte rns (i)
Oxyp h i l i c ce l l type
( i i)
Clea r ce l l type
( i i i)
M u ci n - p rod uci n g ce l l type
(iv)
Sig n et-ri ng ce l l type
(v)
Atyp i ca l
Others (a)
Sa l iva ry g la n d -type t u m o u rs
(b)
Ad e n o l i po mas
(c)
Hya l i n iz i n g trabecu l a r t u m o u rs
(a)
Deg ree of i nvasiveness
B. Malignant 1 . Fo l l ic u l a r
(b)
2.
5.
M i n i m a l ly i nvasive (e n ca ps u l ated)
(ii)
W i d e ly i nvasive
Va ria nts (i)
Oxyph i l i c ( H u rth l e) cel l type
(ii)
Clea r ce l l type
Va r i a n ts
(i)
Pa p i l l a ry m i croca rci n o m a
( i i)
Enca ps u l ated va ria nt
(iii)
Fo l l ic u l a r va ria nt
(iv)
D iffuse sclerosi n g va ria n t
(v)
Oxyp h i l ic (H u rt h l e) ce l l type
Med u l l a ry thyroid cancer (a)
4.
(i)
Pa p i l l a ry ca rc i n o m a (a)
3.
ca rci n o m a
Variant (i)
M ixed m ed u l l a ry-fo l l i c u l a r carci n o m a
U n d ifferenti ated (a n a p l a stic) ca rci n o m a O t h e r ca rci n o m a s (a)
M u ci n o u s ca rci n o m a
(b)
Sq u a m o u s ce l l ca rci n o m a
(c)
M u co e p i d e r m o i d carci n o m a
II
N o n e p it h e l i a l tu m o u rs
III
M a l i g n a n t lym p h o m a s
IV
M i sce l l a n e o u s t u m o u rs
1.
Pa ra g a n g l i o m a s
4.
Terato m a s
3. V
Pa rathyro id t u m o u rs
2.
Seco n d a ry t u m o u rs U n c l a ssified t u m o u rs
VII
Tu m o u r- l i ke l esio ns
2. 3.
4.
5.
6.
7.
It is multicentric in 80 percent of cases and frequently involves both lobes. Papillary thyroid cancer is referred to as minimal (or micro carcinoma) when it is less than 1 em in diameter. The occult sclerosing carcinoma appears as an irregular white scar within a normal or goitrous gland. Such lesio ns are often incidental findings at sonography, followin g surgery for benign disease and at autopsy. Minimal and occult tumours are of interest because their incidence far exceeds that of papillary cancers greater than 1 em in diameter and the prognosis fo r patients with small tumours is so good that a conservative approach may be j ustified. Intrathyroidal tumours measure greater than 1 em, but are confined to the gland while extrathyroidal tumours extend outside the capsule of the gland to involve the soft tissues of the neck or regional lymph no des. The extent of papillary thyroid cancers is shown in Table 197.5. Histologically these cancers are divided into pure papillary, mixed papillary-follicular and the follicular variant of papillary carcinoma. The mixed pattern is most common, with pure papillary the most rare. The papillary component is characterized by a fibrous stalk with a periphery of follicular epithelium. Laminated calcifications called 'psammoma bodies' are often found in the stalk region. The nuclei o ften appear clear and are described as gro und glass or Orphan Annie nuclei ( Figure 197.6) . The biological behaviour and prognosis for all three types is the same. The features of papillary carcinoma are as follows. •
Histological variants include: pap illary microcarcinoma - occult sclerosing, occult papillary: Iii < 1 em (WHO definition ) ; � 4-30 percent incidence a t autopsy; encapsulated papillary carcinoma: @ 10 percent of all papillary tumours; • not papillary adenoma; • 25 percent associated with nodal metastases. follicular variant of papillary carcinoma - typical pap illary cytology; - tall cell and columnar - older patients, bigger more aggressive tumours: • vascular and extrathyroid invasion common; (!) associated with a worse prognosis.
_
S p i n d l e ce l l t u m o u rs with m u co u s cysts
VI
1.
2673
Tab l e 197 . 5
Ext e n t of p a p i l l a ry t h y r o i d c a n c e rs. Extent
Hype r p l a stic g o itres Thyroid cysts So l id ce l l n ests Ecto p i c thyroid tissue C h ro n i c thyroi d itis R i ed e l 's thyro id itis Amyloid g o itre
M i n i m a l (or
< 1 .0 cm
m i croca rci n o m a ) I n t ra t hyroi d a I
>
Extra t hyro i d a I
Bey o n d g l a n d ca ps u l e a n d/or w i t h l y m p h
1 .0 c m n od e m etastases
2674 I
PART 1 7 H EA D AN D N EC K TU M O U R S
found in 20-30 percent, bu t lymp h no de involvement
is less com mon ( about 10 p e rcen t) than is the case with
papillary cancer. Typ ically, fo ll ic ul ar cancer has a well-defined capsule and cases can be divided into two subgroups depending on whe ther the capsule is breached or n ot . H isto l ogi call y, it is a carcinoma co mpo se d o f follicles with no papillary structu res. The nuclei are non -vesicular and psammoma bodies are not s e en Alt h ough follicular neoplasms can be identified on fi ne needle aspiration (FNA) cytology, it is ge ner a l ly not possible to distingu ish an adeno ma from a ca rc inoma. Surge ry ( most o ften lobectomy) is usually required to provide tissue for histological examination to show whet her a fo llicular neo p lasm is benign or malignant. H isto l ogi ca l features of mal ig n a n cy include capsular and vascular i nva s io n .
Fig u re 1 9 7 . 6
T h e h i stopatholog ical fe a t u res of p a pi l l a ry
.
ca rc i noma. N ote the arboresce n t p a p i l lae, n u c l ea r crow d i n g a nd Orphan An n i e n u c l e i .
•
•
•
•
e
• •
•
Yo u ng
adults affected (20-45 years) . The female to male ra tio is 3 : 1. Pap illary carcinoma i s associated with a high incidence ( 60 percent) of i nvolved cervical lymph nodes in levels III to VII . These do no t wo rsen progn osis (excep t in elderly patients) . The primary t umo ur may be i mp a l p a b le so that initi al p resentation is with nodal enlargement. Primary tumour is unencapsulated in up to 70 pe rcent of cases. One in five patients have p ulmonary metastases at p resentation. Bone metastases are much less common. I n the older age groups, the t umour tends to behave in a more aggressive fashion and may invade the larynx and trachea. The ten-year survival from m i nimal, occult or intra thyroid p ap i lla r y carc i n oma is over 90 percent, but when it is e xt r a thy roi da l , t he ten-year survival falls to 60 percent.
Fol l i cu l a r a d enoca rci nom a Follicular adenocarcinoma occurs in older age groups, being most common between 50 an d 59 years, and seldom being seen under the age of 30 years. I t i s substantially less common than pa pillary cancer, acco unt ing fo r only 1 0-20 percen t o f aU cases o f t hyroi d malignancy. The inc idence appears t o be decreasing i n endemic goitre areas, whe r e iod i ne intake has been increased. Follicular carcinoma most co m m o nly presen ts as a so l it ary t hy ro id nodule, either de novo or less frequentlyas an obviou sly malignant change in a t hyroid svvell i ng that may have been p resen t for m a n y years. Al tern a tive l y follicular cancers may p resent with symp toms or s i gns of metastases. Bone o r l u n g involvemen t is
H u rt h l e ce l l t u mou rs The HUrt hle cell, which is also known as the eosinop hilic cell, o ncocyte o r oxyp hilic c el l, was first described by the German histologist HUrthle in 1 8 94. It is a round cell with eosinophilic, finely granular cytoplasm which is indicative o f abu nda nt mitochondria. It is derived fro m follicular epithelium and possesses a limite d ability to produce thyroglobulin, but does not usually concentrate iodine. The t rue nature o f t he cell is unclear, though it may represent a degenerative o r me tapla stic phenomenon. HU rt hle ceUs are found in nodular goit res chronic lym phocytic thyro id i t is , diffuse toxic go it re , a fter radia tion and chemotherap y, as part of the agein g process, as well as in HUrthle cell adenomas and car cinomas. HU rthle cell tumours are extremely uncommon. His t ologi ca l d istinction between benign and malignant t u mours is difficult and controversial. M a l igna nt tumours disp lay capsular and vascular invasion and may invade surrounding thyroid tissue and ext r a t hyr oid structures. Lymph node metastases are common. Benign tumours disp lay none of these features. Errors in t he p ast a nd an association between increasing tumour size and malig nancy have led some authors to recommend total thyroidectomy fo r all HUr t h le cell tumours more t han 2 c m in size. ,
M ed u l l a ry thyroi d ca rci n o m a Medul la r y thyro id carcinoma (MTC) accounts for about 5 pe r ce n t o f a l l cases of thyroid malignancy. It may occur as p a rt of the MEN syndrome (see under Fa mily histo ry above), as familial non-MEN disease or it be spo radic. In sporadic cases) medullary car cino m a is l i kely to be unifocal, but in patients with MEN it is fre q uent ly b ila teral ( 90 . percent) and multifocal . Cervical node metastases occur in up to 50 p erce n t of cases. Medullary cancers arise from the pa r afolli cul a r or C cells which
Chapter 197 T h y ro i d c a n c e r I
secrete calcitonin, which is a valuable tumour marker. Medullary carcinoma of the thyroid can be of several types: • • •
•
MEN 2A; MEN 2B; familial non-MEN; sporadic.
Macroscopically, the tumour is grey or white with a gritty texture and areas of haemorrhage, necrosis, fibrosis and calcification. Histologically, it consists of uniform, spindle-shaped cells within a variable fibrous stroma which may contain amyloid.
Lym p ho m a Primary thyroid lymphomas are uncommon, accounting for fewer than 5 percent of all cases of lymphoma. They usually p resent as a rapidly increasing swelling of the neck in elderly women. This clinical presentation can be very similar to that of anaplastic thyroid carcinoma and so histological confirmation of the diagnosis is necessary. On purely morphological grounds, lymphoma can sometimes resemble anaplastic carcinoma so that appropriate immunocytochemistry is essential to distinguish the two diseases. Accurate diagnosis is important as the treatment of the two conditions is different. The response to treatment and prognosis of lymphoma is excellent and very much better than that of anaplastic cancer. Grossly, most thyroid lymphomas appear as large grey fleshy masses, often extending outside the capsule. Infiltration of the residual thyroid tissue may be seen. Lymphoma usually arises in a background of chronic autoimmune thyroiditis and the nontumour thyroid tissue may show the gross appearance of lymphocytic thyroiditis. Histologically, the majority of lymphomas are high-grade B cell non-Hodgkin's lymphomas. Very rarely low-grade mucosa-associated lymphoid tissue (MALT) lymphomas may be encountered. Most often, primary thyroid lymphomas are localized stage I or II disease. Occasionally, the thyroid may be involved in patients with widespread systemic lymphoma.
Histologically, anaplastic o r undifferentiated thyroid cancers have no characteristic architecture and bear no resemblance to normal thyroid cells. Traditionally, they have been divided into two categories depending on the predominant cell morphology: the uncommon small cell carcinoma and the spindle and giant cell carcinoma. In the more common latter category, there exists a wide variety of histological patterns. The differential diagnosis includes lymphoma, sarcoma, spindle cell medullary cancer and metastatic cancer. If metastatic neoplasms from other sites involve the thyroid, the most common sources are the kidney and breast.
CLI N I CAL ASS ESS M E NT H istory The majority of patients with thyroid tumours will present with a solitary thyroid nodule ( Figure 197.4) . The patient's age is a critical factor in determining the likelihood of a solitary nodule being malignant. The risk of malignancy is high in young patients. A truly solitary thyroid nodule in a patient under 30 years of age has a 1 0-20 percent chance of malignancy. Of the ones that are malignant, up to 80 percent may have cervical lymph node micro metastases. The risk lessens in middle age and increases again after the age of 50 when in elderly men the likelihood of a solitary thyroid mass being malignant is double (20-40 percent) . Solitary nodules that occur at the extremes of life (i.e. children and the very elderly) are more likely to be malignant. The incidence of anaplastic thyroid cancer increases after the age of 50 years. Forty percent of patients will present with palpable neck node metastases. One in five will have hoarseness or obstructive symptoms. Rapid growth, pain and unilateral vocal cord paralysis are less common and more ominous signs. It is important to establish a history of radiation in childhood and/or a family history of thyroid disease. The presenting symptoms of thyroid tumours are: • •
• •
An a p l asti c ca n cers Anaplastic tumours are more common in the elderly and in women, and many of them are superimposed on a long-standing goitre, which then increases in size rapidly and is associated with otalgia, hoarseness and stridor. They are aggressively malignant, have a high metastatic potential and rapidly invade surrounding structures, such as the larynx, pharynx and oesophagus. These tumours carry a uniformly bad prognosis and treatment is often ineffective with the majority of patients dying within a year of presentation.
2675
•
•
• •
solitary thyroid nodule; cervical lymphadenopathy; rapidly enlarging goitre; pain in the neck; stridor due to tracheal comp ression; dysphagia due to oesophageal compression; hoarseness due to vocal cord palsy; distant metastases.
Exa m i n ation The gland should be examined one side at a time and if a swelling is present, it should be determined if it is diffuse, nodular or multinodular. Checks should also be carried out to establish if the patient is clinically toxic. The mass
2676
I PART 17 H EAD AN D N ECK TU M O U RS
should be examined to determine whether it goes up and down when the patient swallows and the area below the midline should be checked at this point for tracheal shift. If there is retrosternal extension, the patient's neck should be extended to see if the mass comes up from the chest. Cysts feel hard since they are full of fluid, colloid nodules feel doughy and chronic lymphocytic thyroiditis is charactistically firm. Papillary and medullary cancers frequently feel like hard rubbery nodules. Anaplastic tumours are hard, fixed and craggy, while lymphomas are frequently diffuse. Distinguishing accurately between benign and malignant nodules can be clinically impos sible, although certain features are typical of cancer ( Table 197.6) . The neck should be palpated carefully for lymph nodes and finally, the pharynx, larynx ( and upp er trachea if indicated) sho uld be examined by direct fibreoptic endoscopy to look fo r vocal cord paralysis or invasion by tumour.
Ra d i o l ogy The chest radiograph may show tracheal deviation, mediastinal extension or lymphadenopathy, pulmonary metastases or other comorbidity. Soft tissue radiographs of the neck and thoracic inlet may also show deviation and compression of the trachea ( although flow loop studies have been shown to be more accurate than plain films) 1 8 and finely stippled areas due to calcification in psammoma bodies are seen in papillary thyroid cancer. The appearance of a rim or eggshell calcification suggests a benign lesion. Bilateral calcification at the upper lateral portion of the gland suggests medullary carcinoma, whereas heavy irregular calcification suggests a multi nodular goitre. An ultrasound is helpful in measuring tumour size, diagnosing multinodular goitres and excluding contralateral Tab l e 1 9 7 . 6
The cha racte ristics of b e n i g n a n d m a l i g n a n t thyro i d
nod u l es. Be n i g n
Mal i g nant
Soft m o b i l e nod u l e B e n i g n on FNAC
H a rd fixed nod u l e I psi l a te ra l co rd p a ra lysis
Si rn p l e cystic nod u l e l ess t h a n 4 cm i n s i z e o n u l traso u n d Hyperfu nction i n g ' hot' n od u l e
I ps i l a te ra l cervica l lym p h nodes
o n 1 1 2 3 sca n H ig h l eve ls of seru m a nt i bod ies
Su p p ressed TSH
Suspicious o r m a l i g n a nt FNAC So l ita ry so l id nod u les or com p l ex cysts >4 cm o n u l tra so u n d Hypofu nctio n i n g 'co l d ' nod u le on 1 1 2 3 sca n
Reprod u ced fro m Ref. 1 7 , with permissi o n .
1 , disease. 8, 1 9 20 Ultrasonography can also be used to evaluate complex cysts and can distinguish purely cystic nodules. Only rarely is a cystic nodule associated with thyroid cancer. The resolution of ultrasound is good and it can detect cysts as small as 1 mm and solid lesions as small as 3 mm in diameter. Calcification may be detected but occurs in both benign and malignant disease, so is often nonspecific. In the future, high resolution ultra sound techniques may be able to distinguish benign from malignant disease and this will be of value not only at the p rimary site, but also in the evaluation of neck nodes when it may be combined with fine needle aspiration cytology. Scintigraphy, which has been available for longer than both computed tomography ( CT) and magnetic reso nance imaging ( MRI) , was regarded as the gold standard for investigation of the solitary thyroid nodule. Iodine1 23 e 23 I) is probably the optimal radionuclide for thyroid imaging because of its physiological properties, but, as it is cyclotron generated, cost and availability limit its use. The radionuclide technetium-99m ( 99 mTc) , in the chemical form of pertechnetate (Tc0 4- ) , has a six-hour half-life and is now used for thyroid imaging because it is trapped ( but not organified) by the thyroid gland in a similar manner to the iodide ion, and is cheap, readily available and the radiation dose is low. Pertechnetate uptake does not always match the physiological uptake of iodide. The uptake is low (0.4-4 percent) which leads to a high background activity. Nonetheless, with careful attention to scanning technique, the majority of nodules greater than 5 mm in diameter can be visualized on scintigraphy. False-negative results are often associated with smaller lesions in the isthmus, but these are usually easy to palpate and therefore do not cause a significant problem. More than 90 percent of lesions identified will not concentrate the radionuclide ( 'cold' nodules ) . These clinically solitary nonfunctional nodules may be an adenoma, a carcinoma, a cyst, a dominant nodule in a nonpalpable multinodular goitre or one of a variety of other rare entities. The likelihood of malignancy in a 'cold' nodule is only about 20 percent. If a cyst has been excluded on ultraso und, then the likelihood of a solid 'cold' nodule being malignant rises to about 50 percent. Truly functioning nodules, which are also called 'hot' nodules , are highly unlikely to be malignant. Sometimes confusion occurs when lesions are said to be 'warm' on scintigraphy. This is usually a false-positive result because of the vascularity of the lesion or because it is overlapped by normal functioning thyroid tissue. It may be helpful in such circumstances to do a repeat scan after 12 hours. If the lesion is still 'hot' then malignancy is very unlikely. A diagnostic strategy fo r the solitary or dominant thyroid nodule is shown in Figure 197.7. Other radiopharmaceuticals can be used in the investigation and treatment of thyroid tumours. 1 23 1 -MIBG ( metaiodobenzylguanidine) is taken up by tumours of
Cha pter 1 9 7 Thyroid ca n cer I
2677
Thyroid function tests Thyroid antlbodies
1
FNAC
..
Suspicious
M a l ig n a nt
? Ultrasound Thy 4 and 5
(Hyperplasia versus low grade neoplasia)
l '/T
Or consider Scintigraphy
Surgery
Be nign
? Ultrasound Thy 2
1
Watch ? Repeat FNAC at 1 2 months
I nadeq uate sa m p le
Thy 1
1
Repeat FNAC
1
Fig u re 1 9 7 .8
1 231 Scan
Co ro n a l M R I sca n show i n g fo l l icu l a r carci noma
i nva d i n g the ri g ht trachea. The d i sease was loca l i zed a bove the su prasterna l n otch a nd treatm ent was with tota l thyroidectomy,
' Hot'
'Warm' or 'Cold'
t
faci l i tated by m a n ubri a l split and su bseq uent p ri m a ry
�
? Observe F i g u re 1 9 7 . 7
exte nded tota l l a ryngectomy a nd u pper t rachea l resection pha ryn g ea I re pair.
Surgery
A d i a g nostic strategy for the eva l uation of a
'sol ita ry' or 'do m i n a nt' thyroid nodule.
neural crest o ngm, such as a phaeochromocytoma and in some cases of medullary thyro i d cancer. I t is therefo re useful in imaging suspected cases scanning with
67 Ga
of MEN.
Galliu m
citrate can be useful in detecting
lymphoma and may be used in pa tients with lo ngstan ding Hashimoto's thyroiditis who develop a solitary no dule. 1311
radioiodine is
used following surgery fo r well
differentiated cancers of follicular cell o rigin to ablate the residual normal thyro id tissue and to search fo r and treat metastatic d isease. Computed tomography of the neck and thorax is of help in assessing the extent and relationship o f larger thyro id tumo urs) p articularly involvement of the larynx, trachea) pharynx) oesop hagus and major vessels
( Figure 197.8) . It is also used to demonstrate nodal deposits in
the neck and mediastin um) d irect retrosternal extension and pulmonary metastases. Abdominal CT is also used fo r lymphoma staging and when a phaeochromocytoma is suspected. Magnetic resonance imaging allows m ulti planar ima ging
( Figures 197.9 and 197. 10) and has goo d inherent
soft tissue contrast. It also allows possible vessel involve ment
to be assessed with MR angiography (Figure 197. 1 1 ) . Additional advantages over CT include the fact
that io dine-containing contrast is not required and there is no radiation exposure. Both MRI and CT may be difficult investigations for patients with a compromised
F i g u re 1 97 . 9
Coron a l M R I show i n g extensive papilla ry
carcinoma of the thyroid g l and. S i g n ifica n t primary d isease is seen in the left l obe o f the g l and (sma l l arrow) , as w e l l a s i n leve l V I a n d l eve l s I I I , IV a nd V ( l a rge a rrow ) , Treatment was
w i th tota l t hy roid ectomy, l e ft mod i fi ed ra dica l n eck dissection a nd the subsequent ra d i oiod i ne a b l ation.
airway fo r who m lying flat is uncomfortable. Anatom ical imaging issues include: • extracapsular extension; • contralateral lobe;
2678
I PART 1 7
H EAD AN D N ECK
TU MOU RS
F i g u re 1 9 7 . 10 Corona l M R I showing extensive medu l lary carcinoma of the thyroid g la nd. Pri mary disease is seen in the rig ht lobe of the g land w i th metastatic d i sease on the right in level I I a n d on the left i n levels I I I, IV and V, extend i n g i n to VI I (arrow). Treatment was with tota l thyroidectomy, bi latera l neck d issection w ith mediastinal exploration and postopera tive rad iotherapy. Disease was i nvolved with the l ower end of the left internal jug u lar ve i n at i ts ju nction w ith the subclavian .
•
vascular invasio n ;
•
mediastinal involvement;
•
p haryngeal and oes ophageal involvement;
•
laryngeal and tracheal involvement;
•
n o dal disease (levels
•
distant metastatic spread;
I-VII) ;
•
lymphoma staging;
•
exclusio n of phae o chromocytoma (multiple endo crine
functio n tests, the prediction of p os t operative subclinical
F i g u r e 1 9 7 . 11 Pa t i e n t w ith recu rrent papi llary ca rcinoma of the thyroid g land presentin g 1 8 yea rs later fo llowing pa rtial t hyroidectomy and l i m ited neck cleara nce. (a) A r i g h t pa ra pharyngeal mass w a s noted presenting in t h e oropharynx and (b) on magnetic reson a nce a ngiography i s seen ex tend i ng to the sku l l base and displacing the rig h t internal carotid artery latera l ly. No evidence of vessel wall involvement was noted. Treatment was w ith comple t ion t hyroidec tomy remova l of the parapharyng ea l mass and subseq uen t rad ioiod i ne ablation. The patient remains al ive a nd wel l .
hyp othyro idism and in the assessment o f the serum thyro glo bulin I 8 P reoperative measurement of thyro glo
need fo r imaging and surgery and increased the yield o f
ne op lasia syndrome ) .
LABO RATO RY I NVESTI GATI O N S The thyroid stimulating hormone) T 3 and T4, seru m calcium and thyro id antibodies should be measured. The latter may be useful in the interpreta tion of the thyro id
.
bulin is not usually helpful unless the patient has had previo us trea tment. If medullary carcinoma is suspected , t h e calcito nin should be measured.
,
cancers i n
p a t ients who d o come t o surgery. FNA is safe) (Figure 197. 1 2) . The cl assifica t io n o f thyroid cytopathology i s shown in Table 197.7. Altho ug h cheap and reliable
it is n o t p o ssible to distinguish between ben ign and
mali g nant fo llicular neoplasms on cytolo gy alone .
Cyto l ogy
FNA
should not be relied u p o n to exclude a malignancy in patients with a histo ry of radiation exp osure, because a
The
interpretation
of
fine
needle
asp irates
by
an
experienced cytopath o l o gist has had a maj o r impact in
the management o f thyroid disease. It has reduced the
cancer may be present in up to 40 p ercen t of cases) is o ften multifocal and can easily be missed by aspira t io n cytolo gy. Sometimes a needle- core biopsy i s app ro pria t e,
Cha pter Tabl e
1 97.8
1 97 Thyroid cancer I
2679
Prognostic factors associa ted with d i fferentia ted
thyroid cancer. Pa ti e nt factors
Age Sex
1 97. 1 2
Fig u re
Th e cytologica l appeara nces of pap i l l ary thyroid
Tab l e
1 9 7.7
The classification of thyroid cyto pat hology.
CI assifi cation Thy Thy Thy Thy Thy
1
3
4 5
Tu mour s i ze Tu mour h istology Nodal m etastases (in elderly patients) Loca l i n vasion Distant metastases
Delay i n therapy Extent of s u rgery Experie nce o f surgeon Thyroid h o rmone therapy Treatment w i t h postopera tive rad ioiodine Control
Patien ts under 45 ye a rs have a better p rogno sis and women in gen eral do better th an men. However, one sho uld be b ew are o f tumours that present a t the extremes of l i fe so th a t ch i ld ren and the eld erly in general fa re worse. There is a linear relationship between tumour size and prognosis2 1 (Figure 197. 1 3 ) and the gra de of t u mo u r i s also
important. The tall
cell variant
o f p ap illary
carcinoma is p art i c u larly aggressive as are those fo ll icu l a r tumo u rs which exhi bit marked invasi on. Pat ients w i t h
I nad equate for d i a g nosis B e n i g n d isease Suspicious for neoplasia Suspicious for mal ignancy Posi tive for m a l ig n a nt d ise ase
2
Management factors
No control
No control
carc i n oma. Note the preservation of cell cohesion, but d i sord e rly pol arity wi th varia bly enla rged, crowded a nd overl a p p i n g n ucl e i . The occasional intranuclear inclu s ions and foca l nuclear g rooving are chara cterist i c featu res.
Tu mour factors
but u s u a lly a t hyro id lo bectomy w i ll be performed as an biopsy to obtain m a terial fo r h i s t ol o g i c al
excision
purp oses if a preo perat ive d iagno s is cannot rel iably be
FNA. Excision biopsy of a sma l l l a t e ra lized usually entails ip s il a tera l l o be ct o my with removal of the isth m us and a small portion of the contralateral lobe. Partial lobec to my or l u mp e ct omy is u nacce pt a b le because this is associa ted with a h i gh e r recurrence rate made on
p a p illary t hyroi d
cancer
fare better t h a n th ose with
follicular tumours and medullary thyroid cancer carries a worse prognosis than differentiated thyroid cancer. Nodal metastases are associated with a worse p ro gnos is in elderly patients as is the presence of either local invasion o r distant spread. Prognostic factors asso ci ated w ith man agement are discussed under treatment po l i cy. For m ed ull a ry thy ro id cancer, imp o rt ant prognos tic factors i ncl ude
age
at
presentation,
TNM
(tu mo ur,
node,
metastases) stage, previo us s urgery, extent of s urgery and p re- and p osto p er at ive calci ton i n levels.
tumour
and poorer s urviva l . Removal o f the ist h m us prevents an
unsightly bulge deve lop i ng as a result o f co mp e nsato ry hypertro phy Fo r small nod ules o f the ist h m u s , removal o f .
the central portion o f t h e gland wi t h a t leas t a 1 cm
i s a d eq u at e . A p a t i ent u ndergo i n g su rgery to tissue for the h ist o lo gica l di a gnosis o f an u n diagnos ed no d ule, must be made aware that the p lann e d o p er a t ion i s a d i a gnost i c one and that furt her surgery may be necessary i f malignancy is confirmed. m argin
o b tain
PRO G N OSTI C FACTO RS are a nu mber of prognostic fa ctors assoc i a t ed w it h di ffe ren t i ate d thyro i d cancer and t hese can be divided
There
into those related to pa tient, t u m o u r and m a nagement facto rs.
They are listed in Table 197.8.
STAGI N G There are a number of thyroid st a gi ng syst ems currently in use) bu t the one tha t is most widely used is t he TNM classific at i o n fo r malignant tu m o urs 2 2 This classifica t i o n a p p lie s o nly t o carcino mas a n d is based o n some o f the p rognostic fa ctors listed above. There sho uld b e h istolo .gical confirmation of the disease and divis ion of cases by .
h istological type. The current TNM class ifica tion carcinoma of the thyroid
for
is s et out in Tables 197.9 and 197. 1 0 and separate stage groups are recommended for pa p ill a ry and follicular, med ullary and und i ffe re nt i at e d carcinoma. The cu rrent UK Na t i o nal Guidelines fo r the Treatment of Thyroid Cancer1 8 are based on t h e p revio u s TNM cla ssific at i on2 3 a n d these are included for co m p leteness (Tables 197. 1 1 and 197. 1 2 ) . Some groups in t h e UK have reservations abou t t h e changes in the new TNM booklet and have yet to adopt them (Professor Sir Dilwyn Williams a n d Gill Law r en ce of the Midland Cancer Reg i st ry personal communicati o n ) . ,
2680 I
1 00
PART 1 7
H EAD AN D N ECK TU M O U RS
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80
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�
0
'9-
80
(:
40
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Q OJ c '5 '
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'2
ro
------
60
0-39 (291 ) 40-49 (1 09)
p < 0 . 000 1
(A)
Chi 2 1 0 1 .4
_ _ '-------'---_ -'_ _ _ _____ -'___ ______-'________---' _ ::; 1 .0 em (2 1 1 ) _. _ _ . _ . _ . _ . _ . _ . _ . _ . _ . _ . _ . _ . _ . _ . _ . _ _ . _ _ . _ . _ _ _ _. 1 . 1 -2.4 em (255) . . 2 . 5-4.0 on (1
.
-----�--- � 4. 1 em (96)
60 Tumour size P < 0 . 000 1 Chi 2 63 . 1
20 0
0
5
(S)
10
15
20
25
Years after initial surgery
Tabl e 1 9 7 . 9
Ca use-specifi c s u rviva l from pa p i l l a ry thyro i d ca ncer plotted by patient, age g ro u p and tumour s i ze. Red rawn with permission from Ref. 2 1 . Fig u re 1 9 7. 1 3
TN M classification fo r ca rci noma of the thyro i d g l a n d .
C I assifi cati o n
TX TO T7 T2 T3
NX NO N1 N1a N1b MX MO M1
Pri m a ry tu mo u r ca n not be assessed No evidence of p ri m a ry tumou r Tumour 2 cm or less in greatest dimension, limited to the thyroid Tumour more than 2 cm, but n ot more than 4 cm in greatest dimension, limited to the thyroid Tumour more than 4 cm in greatest dimension, limited to the thyroid or any tumour with minimal extrathyroid extension (e.g. extension to sternothyroid muscle or perithyroid soft tissues) Tumour extends beyond the thyroid capsule and invades any of the following: subcu taneous soft tissues, larynx, trachea, oesophagus, recurrent laryngeal nerve Tumour invades prevertebral fascia, mediastinal vessels or encases carotid artery (Anaplastic carcinoma only). Tumour (an y size) limited to the thyroid (Anaplastic carcinoma only). Tumour (any size) extends beyond the thyroid capsule Reg i o n a l lym ph nodes ca n n ot be assessed N o reg i o n a l lym ph node m etastasis Reg i on a l lym ph node m etastasis Metastasis in level VI (pretracheal and paratracheal, including prelaryngeal and Delphian lymph nodes) Metastasis in other unilateral, bilateral or con tralateral cervical or upper/superior mediastinal lymph nodes Dista n t m etastasis ca n n ot b e assessed N o d ista n t m etastasis D i sta n t m etastasis
pTN M
Path olog i c a l c l a ssificat i o n
pNO
H istological exa m i nation of a s elective n eck d i ssection s peci m e n will o rd i n a r i ly i nc l u d e six o r more lym ph n od es. I f t he lym p h nodes a re n eg ative, b u t the n u m be r o rd i n a ri ly exa m i n e d is n ot m et, classify as p l'J O
T4a T4b T4if T4ba
M , d i sta nt metastasis; N , reg i o n a l lymph n o d e s ; T, pri m a ry t u m o u r. pT, p N , a n d p M categori es co rrespo n d to the T. N , a n d M catego ries. Cha n g es a re s h o w n i n bold a n d ita l ic fo nt. Al l a n a p l astic/u nd ifferentiated tu m o u rs a re considered T4. Repri nted from U I CC, 6th ed nY, with permissi o n .
a
The main changes in the new classification are highlighted in Tables 1 97.9 and 197. 10. For differentiated thyroid cancer, a Tl tumour is now less than 2 cm in size. The reason for this change is that there is very little difference in prognosis between T l and T2 tumours and this now brings the 'T' classification into line with squamous cell carcinoma. Also, the nodal classification has changed with N la representing metastases in level 6
and N I b representing metastases in either the unilateral! bilateral or contralateral, cervical or upper/superior mediastinal lymph nodes. This is because in the previous classification, N 1 a indicated unilateral disease and N 1 b, bilateral or contralateral disease; yet the prognosis for the two groups. was thought to be the same . In addition, the stage groupings are now the same for both differentiated and medullary thyroid cancer.
Ch a pter 1 9 7
Table 1 9 7 . 1 0
Stage g rou ping.
T a b l e 1 97 . 1 1
Cl assifi cation
NIa T1, T2, T3 NIb T1, T2, T3 NO, N I T4a Any N T4b Stage IVB Any T Any N Stage IVC Anaplastic/undifferen tiated (all cases are stage IV) Stage IVA T4a Any N Stage IVB T4b Any N Stage IVC Any T Any N Stage IVA
The TN M cl assification for ca rci noma o f the
thyroid g l a n d .
Sta g e
Pa p i l l a ry o r fo l l ic u l a r < 45 yea rs Stage I Any N Any T Stage I I Any N Any T Papillary or follicular ;::: 45 years and medullary NO Stage I T1 NO Stage II T2 NO T3 Stage III
Thyroid ca nce r I 268 1
MO M1 MO MO MO MO MO MO MO MI MO MO MI
Separate sta ge g ro u p i n gs a re reco m m ended fo r papi l la ry a n d fo l l i cu l a r, med u l l a ry and a n a p l astic/und ifferenti ated carc i n o m as. Cha nges a re shown i n ita l i c fo nt. Repri nted from U I CC, 6th edn. 22 , with permission.
H i sto l og i ca l typ es The four major histopathological types are: 1. papillary carcinoma (including those with follicular foci ) ; 2. follicular carcinoma (including so-called Hiirthle cell carcinoma) ; 3 . medullary carcinoma; 4. anaplastic/undifferentiated carcinoma. Although the current thyroid staging systems used worldwide correctly stratify mortality rates amongst various subsets of patients, some in the lowest risk groups do die of cancer particularly when risk is defined as simply either low or high. In one large study, 2 4 1 0 percent of patients dying of differentiated thyroid cancer had a TNM stage classification of one or two and those systems that use age to stratify risk are often inaccurate in predicting recurrence with regard to survival since some young patients have high recurrence rates. Most staging systems have been derived from multivariate analysis, but do not consider either recurrence or the effect of therapy and solely rely on information available only after surgery. Finally, disease-free status and survival cannot be assured by low stage. Historically, the first staging system was that suggested by the European Organisation for Research and Treat ment of Cancer (EORTC) in 1 975 which used a scoring system based on male gender, histology, 'T' stage and distant metastases ?5 Those patients in the low risk group had a five-year survival of 95 percent, whereas the high risk group had one of 5 percent. In 1 987, the Mayo
TX TO T1 T2 T3 T4 NX I\JO 1\J 1 N1a N1b MX MO M1 pTN M pNO
OLDER TNM Pri m a ry tu mou r ca n not be a ssessed N o evid e n ce of primary t u m o u r Tu m o u r 1 c m or l ess i n g reatest d i mension, l i m ited to t h e thyroid Tu m o u r more than 1 cm, b u t n ot more than 4 cm i n g reatest d i mension , l i m ited to th e thyroid Tu m o u r more t h a n 4 cm i n g reatest d i mension, l i m ited to the thyro i d Tu mou r o f a ny s i z e exte n d i n g beyo n d the thyroid ca psu l e Regio n a l lym ph nodes ca n n ot b e a ssessed N o reg iona l lym ph node metastasis Regiona l lym ph node m etastasis Metastasis i n ipsil a te ra l cervica l lym ph node (s) M etastasis i n b i l a te ra l , m i d l i n e or co n tra l ate ra l cervica l o r med iasti n a l lym p h node (s ) Dista n t metastasis ca n n ot be a ssessed No d ista n t m etastasis Dista n t metastasis Path o l o g i ca l c l a ssification
H isto l ogica l exa m i nation of a selective n eck d issection w i l l o rd i n a ri ly i n c l u d e six or more lym p h n od es
M, d ista nt metastasis; N, reg i o n a l lymph nodes; T, p ri m a ry tu m o u r. The pT, pN a n d pM catego ries corres pond to the T, N a n d M caterg ories. Th e reg i o n a l lym p h nodes a re the cervi cal and upper mediasti n a l nodes. Al l categ o ries may be subd ivided : (a) sol ita ry tu m o u r, (b) m u l tifocal t u m o u r (th e l a rg est d eterm i n es the classification). Repri nted from U I CC, 5th ed n . ( 1 997) 23 , with permission.
clinic described the AGES classification system 2 6 for papillary carcinoma which was based on age, tumour grade, extrathyroid invasion and tumour size. Although the data were retrospective, a significant number of patients were followed up for a long period of time and the results showed that age and tumour size were important prognostic factors ( Figure 1 97. 1 3 ) and that outcomes were improved by bilateral surgery. How ever, one of the problems with this system was that tumour grading was not easily reproducible for papillary carCInoma. The following year, the Lahey clinic introduced the AJVIES classification for differentiated thyroid cancer (age, distant metastases, extrathyroid invasion and tumour size) ? ? This was based on a series of 309 patients treated between 1 9 6 1 and 1980 followed up for a median of 13 years. Low-risk patients were men less than 40 years, women less than 50 years and all patients with papillary thyroid cancer. High-risk patients included men over 40 years, women over 50 years and those with follicular tumours. Eighty-nine percent of patients were low risk and of these 2 percent died, whereas 1 1 percent were high
2682 I
PART 1 7
Table 1 9 7 . 1 2
H EAD AN D N ECK TU iVl O U RS
Stage g ro u p i n g for ca rci noma of the thyroid
gland.
Under 45 yea rs
Stage T
N
Pa p i l l a ry or fol l icu l a r Any T Any l'l Stage I Any T Any N Sta ge I I Sta ge I I I Stage IV M ed u l l a ry Stage I Sta ge II
Table 1 9 7 . 1 3
OLDER TNM
T1 T2 T3 T4 Stage I I I Any T Stage IV Any T U n d i ffe re n tiated (a l l Stage IV Any T
M
MO M1
45 yea rs a nd o l d e r T
T1 T2 T3 T4 Any T Any T
N
NO NO NO NO N1 Any l'l
NO MO l'lO MO l'l O MO MO NO 1'l 1 MO Any l'l M 1 cases a re stage IV) Any N Any M
Sepa rate stag e g ro u p i n g s a re reco mmen ded for papi l l a ry a n d fo l l i c u l a r, m ed u l l a ry a n d u n d ifferenti ated carc i n o mas. Repri nted from U I CC, 5th edn. ( 1 997) 23 , w ith pe rmission.
risk and of these 46 percent died. However, the data were retrospective, incomplete with regard to tumour size and included both papillary and follicular thyroid cancer. The Memorial Sloan Kettering Hospital has introduced the GAMES classification, which is based on the size and the extent of the tumour, as well as its grade, the presence of distant metastases and gender?8 These different classifica tions are shown in Table 1 97. 13. In 1 993, the M ayo Clinic established a more elaborate staging system for papillary carcinoma called the MACIS system ( Table 197. 14) . 2 1 Patients with a MACIS score of less than 6 had a 99 percent chance of living 20 years. The problem with many of these classification systems is that they are based on retrospective data from single institutions and have no proven advantages over the universally used and widely accepted TNM system, 2 9 which can accurately predict survival based on the prognostic factors that it uses ( Table 1 97. 15) .
TREATM E NT PO LICY The treatment of thyroid malignancy is multidisciplinary and involves five distinct and complementary modalities. For differentiated and medullary thyroid cancer, the mainstay of treatment is surgery, b ut selection of any combination of modalities should be based on tumour pathology and extent of disease. It should usually be possible to have a definitive diagnosis on the basis of cytology and imaging before any major surgery is
Memori a l
M ayo C l i n i c
La hey C l i n i c
Hospital
(AGES)
(AMES)
Ka ro l i nska I nstitute (DAM ES)
(GAM ES)
M
iVlO MO iVlO iVlO MO iVl 1
Com pa rison of class ification syste ms.
Age M etastases Exte nsion Size
Ag e G ra d e Exte nsion Size
Gra d e Age M etastases Extension Size
DNA Ag e Metastases Exte nsion Size
Prog n ostic vari a b l es for pa p i l l a ry ca rci noma of the thyroid. Th e MACIS Sta g i n g System.
Ta b l e 1 9 7 . 1 4
Stage
M A C I S Score
Dista n t ' M ' etastases (3) 'A'ge (3 . 1 or 0.08 age) 'C'om p l eten ess of excision ( 1 ) Extrathyroid ' I ' nvasion ( 'I ) 'S'ize (cm) 3 . 1 + (0.3 size) + 1 + 1 + 3 . 1 (0.08 age if >40 yea rs)
Repri nted from Ref. 2 1 , with perm ission.
Table 1 9 7 . 1 5
Prognostic scori ng systems for diffe re n ti ated
thyroid ca n ce r. 1 0 yea r ca n ce r
Stage
s pecific morta l ity
(Ofo) < 45 yea rs, t u m o u r < 1 cm,
II
III
IV
n o meta stases (any T. any N , MO) > 45 yea rs, tumour < 1 cm, n o d ista n t m etastases (T1 , NO, MO) > 45 yea rs a ny t u m o u r size i ncl u d i n g d ista n t metastases (a ny T. a ny N , M 'I ) > 45 yea rs t u m o u r 1 -4 cm and n o metastases (T2, NO, MO and T3 , l'lO MO) > 45 yea rs with t u m o u r exte n d i n g beyon d t h e thyroid ca ps u l e with o r without lym p h n o d e meta stases (T4, N O , MO a n d a ny T, N 1 , iVlO) > 45 yea rs with d ista n t metastases (any T . a ny l'l , M })
BTA g u i d e l i n es, 1 8 U I CC, 23 Brierley
et
01. 29
1 .7
1 5.8
60.9
C h a pter 1 9 7
undertaken. Treatment modalities for thyroid malignancy include: •
•
•
•
•
surgery; radioactive iodine; external beam radiotherapy; thyroxine therapy; chemotherapy.
The main controversies surrounding the treatment of differentiated thyroid cancer are the types of operation, the extent of surgery and who should do the operation. The role of radioactive iodine will be discussed later. The American ten-year survival rates for papillary and follicular cancer are 94 and 85 percent, respectively. In England, the five-year survival rates for thyroid cancer are 64 percent for men and 75 percent for women and these are below the European average (72 percent for men and 80 percent for women ) . 3 0 Patients with cancer in the UK suffer more delays and have a worse survival than the rest of Europe. Recent studies from America suggest improved outcomes for differentiated thyroid cancer and this is thought to be due, in part, to an increased use of total thyroidectomy and 1 3 1 1 ablation and sequential serum thyroglobulin measurements with TSH suppression. 3 ! , 3 2 The incidence of thyroid cancer in the UK is approximately 1 000 cases per year for a population of 60 million ; yet in the USA, there are over 25 ,000 new cases per year for a population of 288 million. This increase in incidence is thought to be due to a combination of more screening of middle-aged women and a greater use of surgery resulting in the detection of clinically nonsigni ficant papillary carcinomas within multinodular goitres. This may go some way to explaining improved survival rates in the USA over the UK, since the death rates in both countries are the same. However, some have suggested that thyroid cancer could be better managed in the UK and several groups have audited their results and have
Table 1 9 7.1 6
Thyroid ca ncer I 2683
identified deficiencies in practice. In one centre, 1 2-20 percent of cases were insufficiently managed with respect to adequacy of surgery, TSH suppression and the monitoring of serum thyroglobulin.33 These clearly identifiable deficiencies emphasize the need for locally agreed protocols and for concentration of expertise and patient management within multidisciplinary clinics and this has led to the development of national UK guidelines for the treatment of thyroid cancer. 1 8 When differentiated thyroid cancer is treated surgi cally, patients either receive lobectomy and isthmusect omy and completion thyroidectomy as appropriate, or proceed straight to total thyroidectomy based on fine needle aspiration cytology. Many then receive radioiodine ablation. The problem with this treatment strategy is that outcome is principally measured by morbidity and since early recurrence is uncommon, the question is will we ever know if our decision was correct. Is it better to be conservative and avoid treatment morbidity or be more aggressive and avoid recurrent disease? There is no doubt that the extent of surgery is a widely debated issue and relates to lobectomy versus near-total or total thyroidect omy. The arguments for and against total thyroidectomy are shown in Table 1 97. 16. The main disagreement in the literature centres on the extent of surgery for tumours measuring 1-4 em in size (the PT l /PT2 lesion; fifth edition) and the problem is that age and tumour size are continuous variables and some young patients who have low mortality rates, but high recurrence rates, may be judged to be low risk on some of the prognostic scoring systems ( i.e. AMES ) . Another commonly quoted dis advantage of the aggressive approach is the quite high complication rate with total thyroidectomy, although the reported incidences for vocal cord paralysis for nerves at risk following thyroidectomy and the incidence of permanent hypoparathyroidism are extremely low in experienced hands ( Tables 197. 1 7 and 1 97. 1 8 ) .
The a rg u m e n ts for a n d a g a i nst tota l thyroidectomy.
Tota l ' thyro i d ectomy
Radioactive iod i ne ca n be used to d etect a n d treat resid u a l n o rm a l thyroid o r l oca l or d ista nt metastases Se ru m thyroblob u l i n is a more sensitive m a rker of recu rre n ce w h e n a l l norma l thyroid is re moved The m icroscopic foci of ca n ce r p rese n t in up to 30-70% of patie n ts a re e l i m i n ated as s i tes of recu rre nce Recu rre nt cancer d evel ops i n the re m a i n i ng co ntra l a tera l lobe in a p p roxi mate ly 5-1 5% of patie nts and one h a l f of these m ay die of thyroid ca ncer Recu rre nce is l ower in patie n ts who have u nd e rgone tota l thyroid ecto my Faci l i tiates accu rate fo l l ow- up a n d sta g i n g I m proved su rviva I rates Is the treat m e n t of choice for m u lti nod u l a r goitre a n d thyrotoxicosis M i n i ma l co m p l ications of tota l thyroid ectomy i n experienced ha nds Reprinted from Ref. 3 4 , with perm issi o n .
' Less tha n tota l ' thyro idecto my
Fewer co m p l ications d eve lop O n e half of loca l recu rre n ces ca n be cu red with s u rgery Less t h a n 5% of recu rre nces occ u r i n the thyroid bed Litt l e c l i n i ca l s i g n ifica n ce is g iven to m u l ti ce ntricity Prog nosis is good with l ess p rocedu res
2684
III PART 1 7 H EAD A N D N EC K TU M O U RS
Reported i ncide nces of voca l cord p a ra lysis for n e rves at risk fo l l owing thyro i dectomy.
Table 1 9 7 . 1 7
Se ries
Tem porary
Pe rmanent
para lysis
para lysi s
%
No.
H e ra n z-Go nza les et 01. ( 1 99'1 ) La ndo et 01. ( 1 990) Tovi et ol. (1 989) H a m m i n g et 01. ( 1 989) S h a h a a n d Jaffe ( 1 988) Reeve et 01. ( 1 987) M a rtensso n a n d Te ri ns ( 1 985) Va n der Sius a n d Wobbies ( 1 985) Ca l a n d ra e t 01. ( 1 985) Watkinson (2007)a R a n d o l p h e t 01. (2004) Average
%
No.
1 1 /5 1 3
2.1
1 2/51 3
2.3
1 /80 1 / 1 97 5/290 1 /278
1 .3 0.5 1 .7 0.4
0/80 0/ 1 97 4/290 0/278
2.3 0 1 .4 0
2/230 29/749
0.9 3.9
0/230 27/749
0 3.6
2/88
2.3
1 /88
1 .1
2/41 2 4/ 1 652 0/400 50/4244
0.5 0.2 0 1 .1
9/41 2 2 1 / 1 652 2/400 7 8/4244
2.2 1 .3 0.002 1 .8
The refe re n ces cited in this ta b l e a re a l l l isted in Eisle. 3 5 a U n pu b l ished d ata ; R a n d o l p h et 01., 2004.36
Reported i ncide nces o f hypo pa ra thyroidism fo l l owi n g thyroidectomy.
Table 1 9 7 . 1 8
Series
Tem porary
Per m a nent
hypopa rathyro i d i s m
hypopa rathyro i d is m
%
No.
H e ra nz-Gonza l es e t 01. ( 1 99 1 ) La n do et 01. ( 1 990) Tovi et ol. ( 1 989) H a m m i n g et 01. ( 1 989) S h a h a and Jaffe ( 1 988) Sch watz a n d Fried m a n ( 1 987) Va n he e rd e n e t 01. ( 1 987) Reeve et 01. ( 1 987) H a rness et 01. ( 1 986) Watk i n so n (2007)a Ave rage
%
No.
1 9/ 1 8 5
1 0.3
1 5/ 1 8 5
7/80
8.8
0/80
5/ 1 00 1 0/ 1 48
5 6.8
4/ 1 00 6/ 1 48
1 /7 8
1 .3
0/78
26/ 1 83
1 4.2
6/1 83
6.1 0 4 4. 1
Another point to remember relates to papillary micro carcinoma. In one series of 5 3 5 patients with a tumour size less than 1 . 5 cm ( median 8 mm) followed up for 16 years, 37 32 percent of patients had nodal metastases at presentation; the 20-year recurrence rate was 6 percent; higher recurrence rates were seen in node-positive patients or following lobectomy alone and two patients died of their disease. Because of this, the authors recommended near-total or total thyroidectomy for papillary microcarcinoma. Another more recent study confirmed the significant factors on multivariate analysis for papillary micro carcinoma included the extent of surgery and multifocal disease and recommended near total or total thyroidectomy for the latter. 38 With regards to cancer of the thyroid and the surgical anatomy of the gland, it is important to remember that it is one organ affected by tumour which is permeated throughout by lymphatics. The most common tumour (papillary) spreads by lymphatic permeation and the whole gland is easily removed with minimal complica tions in experienced hands and, since thyroxine is widely available, this creates a strong argument for total thyroidectomy. There are some groups ( i.e. Memorial Sloan Kettering) who argue very strongly for conservative surgery for differentiated thyroid cancer for tumours . . measunng . 1ess th an 4 cm III SIZe. 3 9 ' 40 B ecause some minimally invasive follicular carcinomas can safely be treated by lobectomy alone, this argument really centres on papillary thyroid cancer. Using their criteria for low-, intermediate- and high-risk patients with differentiated thyroid cancer, their results over 20 years show that although 9 1 percent of patients were alive with tumours measuring less than 4 cm in size, no mention is made of recurrence rates and for those with low-risk tumours, there was a 6 percent incidence of local recurrence and a 1 0 percent incidence of regional recurrence28 , 4 0 ( Table 1 97.19 and Figure 1 97. 1 4) . Many would regard this as unacceptable and in another study, surgery more than lobectomy was an independent variable affecting cancer recurrence. 32
0 3.3
Ta b l e 1 9 7 . 1 9
Risk g ro u ps fo r d iffe re n tiated thyroid ca nce r. R i s k g ro u ps
1 3/94
1 3.8
1 /94
1 0/ 1 1 5
8.7
0/1 1 5
0
68/404
1 6.8
1 6/404
4
99/1 242 2 1 8/ 1 708
10 1 2.8
1 .1
7/1 242
0.6
56/ 1 708
3.3
The referen ces cited i n this ta b l e a re a l l listed i n Eisle?5 a U n pu b l ished data.
Prog nostic factors
Low
I ntermed i ate
High
Age
< 45
> 45 < 45
> 45
IL
�
Fe m a l e < 4 cm I nt rqg l a n d u l a r Low Abse n t
Male > 4 cm Extra g l a n d u l a r H ig h P rese n t
Gender Size Exte n t G ra d e Dista nt metastast:!s
Reprinted from Ref. 2 8 , w i t h perm issio n .
C h a pter 1 9 7 Thy ro i d
cancer ' 2685
reasonable. The risk stratification treatment based on t he
50
TNM classification ( gender included ) is: 40
• age;
30
• gender ;
20
• tumour histology;
• tumour size;
• nodal and distant metastases.
10
Use o f su ch a p olicy assumes that p a tients have had Low
Fig ure 1 9 7 . 1 4
op timal preo p erative imaging to give an accurate estimate
H igh ri sk
Intermediate risk
risk
of tumour size, identify multicentricity and define local,
I n cidences a nd pa tte rn s of treatment i n fa i l u re
i n low-, i n te rmediate- and h i g h - risk g roups w i th d iffe re n ti ated thyro i d ca rci noma . Redra w n from Ref.
It is
28,
with perm issi o n .
much more difficult to demo nstrate that the
a ffects
disease-free
interval.
The Mayo
clinic
repo rted in their initial series that in low- risk patients
3.99) there was no improvement in
( MACIS sco re than
cytological diagnosis possible.
A
and fo llicular) thyro i d cancer based on the UK thyroid
thyro id cancer, altho ugh there is considerable evidence it
a
suggested treatment strategy fo r differentiated ( papillary cancer guidelines 1 8 is shown
extent of surgery infl uences the survival in d ifferentiated that
nodal or distant spread and that
has bee n made preoperatively wh ereve r
in Table 1 97.20.
Solitary papillary cancers measuring less t h a n 1 . 0 c m
( pT 1 ) and which a r e surrounded by an adequate cuff o f normal thyroid tissue, in t h e absence o f multifocality and
cervical o r distant metastases, can b e safely treated by unilateral lobect omy
TSH sup p ressio n with thyroxine
,
and
sequential thyroglo bulin measurements. Simila rly
survival fo r surgery greater than 1 0 bectomy 26 They later
tumo urs in the isthmus can be treated by an isthmu
rep orted o utcomes in the study designed to co mpare
sectomy with a I -cm margin. For most other patients
surgery
with t umours
.
fo r low-risk differentiated thyroid
cancer by
meas uring greater than
1 em
in
size,
AMES criteria. Although there were no differences in
treatment sh o uld be near-to tal or total thyro idectomy.
the cancer-specific mortality or distant metastases rate in
There are some low-risk patients, i.e. women under 45
the two gro ups, the 20-year rates fo r lo cal recurrence and
years of age wi th solitary, unifocal no nmetastatic t umo urs
14 and 1 9 percent after unilateral resection and 2 and 6 percent after bilateral lobar
less than
which could p robably be safely trea t ed with lobectomy,
resection
low-risk
serum thyro glo bulin. This management plan sho uld b e
differentiated thyroid cancer and altho ugh posto perative
discussed with t h e p atient a n d agreed by t h e multi
radio active io dine does obscure the issue, in one study L 3 L1 p atients treated with bilateral lobar resection and
tumo urs, the risk o f recurrence is high so they should
no dal metastases were
1 resection.4 This led them to co nclude that b il ateral lobar was
the
treatment
of cho ice
fo r
ablation had significantly less local and dista nt recur 3 rences. 3 L • 32 It would seem that surgery and 1 1 1 therapy had
independent
effects
on
recurrence
mor t alit y and after a median follow up ,
and
cancer
of 1 6.6 years,
2 em in diameter (small pT2 No Mo tumo urs)
TSH suppressi o n with thyroxine and measurement of the
disciplinary
Ta b l e 1 9 7.20
team.
In
men
and
.
Because
of
this,
many
physicians
and
surgeons
greater
S u rg i c a l tre a tm e nt of d iffere n ti a ted thyroid N a t i o n a l Thyroid Ca ncer G u i de l i n es. ' 8
Low-risk pati e nt w ith low-risk tu m o u r
Lobectomy
Low-ris k pa tient w i th hig h - risk
Lobectomy o r total
published
joint ly
by
the
British
Thyro id
H ig h - risk pa t i e nt with low-risk
lines fro m the USA) as well as the American Thyro id 32 In add i tion an analysis of 5584 patients Asso ciation. ,
undergo ing surgery for differentiated thyroid cancer in 1 50 0 US hosp itals d uring
1 996 showed that approximately
77 percen t of them underwent a total thyroidectomy. 42
Because of this, selection of a treatment p olicy by allocation into risk groups based on the TNM classifica tion to include gender, age) stage and histo logy seems
Lobectomy or total
tu mou r
thyroidectomy
H i g h - risk pati e n t with h ig h - risk
Association and t he Royal College of Physicians, 1 8 the National Comp rehensive Cancer Network ( NCCN) guide
thyroidectomy
tumour
than 1 em in size. These include the UK national
guidelines
larger
Treatment
thro ugho u t the world recommend near-total or total thyroidectomy fo r pap illary thyroid cancer measuring
with
ca ncer based on U K
surgery more exte nsive than lobectomy was an indepen
dent variable which decreased the likelihood of cancer death by 50 percent 32
women
Tota l thyroid ectomy
tu m o u r Low-risk pati e nts i n cl ude women u n d e r th e age of 45 years; h i g h - risk pati ents i n c l ude all
men,
and
women
over 45.
Based on
th e TN M
cl assification (fifth edition) .23 a ' nte rmed iate g roup. Low-risk tu mou rs i nclude papi l l a ry carci n om as l ess th an 1 cm in size and m i n i m a l ly invasive fo l l i c u l a r ca rc i n omas less than 2 cm
in size. H i g h- risk t u m o u rs i nc l u d e papillary and w idely invasive
fol l icular carcinomas.
Also
i ncl uded
is
a ny t u m o u r associated
with
s i g n i ficant m u l tifoca l i ty. l oca l or d ista nt spread. Patients under 1 6 years
with a d iag nosis of ca n ce r sho u l d be regarded as h ig h risk a nd are usua lly best treated a g g ressively.
2686 I
PART
1 7 H EAD AN D N ECK TU M O U RS
have total thyroidectomy and postoperative radioiodine ablation. Most patients with tumours greater than 2 cm, and all those greater than 4 cm, ( PT ) and for those with 3 tumours of any size in which there is significant multifocal disease, extracapsular spread, lymph-node metastases or distant metastases should have a total thyroidectomy, selective neck dissection as required and radioiodine ablation. This means that for many patients, the operation of choice is a total thyroidectomy with parathyroid pre servation. If there is concern regarding the morbidity resulting from a truly total thyroidectomy, a near-total thyroidectomy can be performed in the absence of contralateral disease. In this procedure, a sliver of the contralateral lobe ( including at least one parathyroid) is preserved. The remnant of normal thyroid tissue can then be easily ablated with radioiodine. The routine use of frozen section during surgery for differentiated thyroid cancer is not usually of value. However, it can be useful for resolving management issues when the diagnosis is in doubt either at the primary site or within the neck. The extent of nodal surgery depends on the extent of lymphatic involvement. The lymphatics of the thyroid gland drain to nodes in the tracheo-oesophageal groove, to mediastinal (particularly thymic) nodes, to the prelaryngeal nodes and to the j ugular chain; some of the lymphatic trunks also pass through the wall of the trachea. A true radical neck dissection is not usually required for thyroid cancer, since this would be a massive and mutilating procedure for a disease that can adequately and easily be treated by a more conservative approach. In the clinically No neck, level VI should be routinely dissected in high-risk patients and levels II-V and VII palpated at the time of surgery. Suspicious nodes can be subjected to frozen section and, if involved, a selective neck dissection ( at least levels III, IV and lower V below the accessory nerve) should be performed with preservation of the sternomastoid muscle, internal j ugular vein and the accessory nerve. 43 Clinically palpable disease in levels II-V indicates the need for at least a selective neck dissection ( usually levels IIa-Vb) and depending on the size and extent of the disease, a modified radical, radical or even occasionally an extended radical neck dissection may be required. The aim of the combined total thyroidectomy and limited lym phadenectomy is to remove all macroscopic malignancy. When a multinodular goitre is removed by either lobectomy or thyroidectomy and an unsuspected occult papillary thyroid carcinoma is discovered, as long as excision margins are complete, then future treatment involves TSH suppression with thyroxine and measure ment of the serum thyroglobulin. If there is any question about incomplete clearance, multifocality or a follicular element to the tumour, then completion thyroidectomy and/ or radioiodine ablation should be carried out.
If papillary thyroid cancer is discovered in a thyr oglossal duct cyst and if excision is complete (Sistrunk's operation), there are no cervical metastases and the thyroid gland is normal on palpation and imaging, treatment is with TSH suppression with thyroxine and measurement of the serum thyroglobulin. If there is any suspicion of disease in the gland itself, particularly in a young person, then a total thyroidectomy should be performed and future treatment guided by the histo pathological findings.
Fo l l i cu l a r carci n o m a The management of follicular carcinoma i s similar t o that of papillary tumours. The mainstay of treatment is surgery. In the past, some authors have argued that minimally invasive carcinomas measuring 4 cm or less can be treated with conservative surgery because the prognosis is so good. 44 , 4 5 However, recent publications suggest that all minimally invasive carcinomas measuring more than 1 cm in size (in line with papillary carcinoma) should be treated with near-total or total thyroidectomy, radioactive iodine ablation and sequential measurements I S, of the serum thyroglobulin. 46 For all tumours which are widely invasive, a total thyroidectomy is indicated followed by radioiodine ablation. The neck and media stinum are managed as described for papillary carcinoma. Subsequent ablation of any thyroid remnants is per formed, followed in six months by screening with an 1 3 1 1 whole body diagnostic scan for residual disease in the neck or elsewhere. Haematogenous spread is more common with folli cular than with papillary carcinoma. The most frequently affected sites are lung and bone. In contrast to squamous carcinoma of the head and neck and indeed most other solid tumours, distant dissemination is not a death sentence. About half of those receiving radioiodine for pulmonary deposits alone will survive for 1 0 or 1 5 years. The prognosis is, however, much worse for those with osseous disease and in patients whose tumours fail to concentrate radioactive iodine and are often aggressive, and because of this should be treated by total thyroi dectomy. With follicular tumours, adequate iodine uptake is less likely in the elderly and in those with less well differentiated tumours. Following initial treatment, sup pressive T4 replacement and regular surveillance with thyroglobulin measurement is indicated, as in the case of papillary carcinoma. Hurthle cell cancers should be managed as follicular cancers but tend to be more aggressive and uptake of radioiodine is less common.
M ed u l l a ry ca rci n o m a The principal 'treatment advised for the patient with medullary carcinoma is surgery. The preoperative
Cha pter 1 9 7
diagnosis of medullary thyroid cancer should initiate appropriate staging to exclude a phaeochromocytoma. The surgery should be radical and involve at least a total thyroidectomy and elective, selective level 6 and 7 neck dissection, from the level of the hyoid bone down to the brachiocephalic vein . The thymus is usually removed as well. In the past, there has been no role for elective lateral neck surgery, although some authors are now recom mending it routinely ( i.e. large tumours (T3/T4 ) , unilateral nodal or mediastinal disease and familial disease) . 4 7 Palpable neck disease usually requires modified radical or radical neck dissection, although in some cases, selective neck surgery may be performed in the presence of limited low neck disease so as to preserve level !. The operation of neck dissection is extended into the superior mediastinum as indicated. Sometimes a sternal split may be required to gain control of the lower part of the internal jugular vein. If an unexpected diagnosis of medullary carcinoma is made following lobectomy, lymph node biopsy or other incomplete surgery, reopera tion is required to remove all possible remaining disease. As these tumours arise from the parafollicular cells, it is not surprising that they do not accumulate radioiodine. Postoperative radiotherapy is indicated if there is any suggestion of macroscopic residual disease in the neck and/or multiple large nodal metastases with extracapsular extension. Patients with disease considered inoperable either due to the advanced nature of the primary tumour or nodal disease, or because of serious intercurrent illness, should be considered for radiotherapy. l s Although the aim of this is principally palliative, a full radical treatment course is required and some patients live long term. Although medullary carcinoma is more chemoresponsive than carcinomas of follicular cell origin and some patients have benefitted from palliative chemotherapy, there is no regimen that can be considered as routine for patients with this disease. Because of its significant toxicity and limited efficacy, cytotoxic drug treatment should only be considered for patients with distressing symptoms refractory to other treatments. A proportion of medullary thyroid cancers take up MIBG and 1 3 I I_MIBG therapy is a possible treatment for recurrent or metastatic disease untreatable by other modalities.
It is important to differentiate medullary cancer which is truly sporadic from the apparently sporadic case which in fact is an index case of a familial form of the disease . The finding of multiple foci of tumours together with definite 'C' cell hyperplasia virtually guarantees the diagnosis of familial disease, although their absence does not exclude it. A family history of any of the tumours associated with MEN 2 should raise suspicion. In likely sporadic cases, family screening should not be undertaken initially and the emphasis should be on increasing the certainty that the case is sporadic. If the clinical information is insufficient to be conclusive, a limited analysis of Ret proto-oncogene should be under taken looking for the common mutations. If this examination is normal, this will reduce the likelihood of familial MEN 2A or familial medullary cancer to less than 0.5 percent. If a genetic abnormality is found, then this should be used to screen other family members. Patients with likely MEN 2B should also have their Ret proto-oncogene analysed expecting to find an abnormality which can be used to screen offspring. Stimulated calcitonin measurements which previously were the mainstay of diagnosing the disease have been almost completely replaced by genetic testing. They should only be considered where there is very strong suspicion of familial disease and a normal genetic analysis in the affected case. It is strongly advised that family screening and genetic counselling is done by, or in close association with, a clinical genetics department so that everyone is aware of the implications of the test before it is undertaken. This should be recorded in the notes.
Thyro i d lym p h o m a Patients with thyroid lymphoma should b e fully staged prior to treatment, but this is not always possible since some present acutely with upper airway obstruction. There are a number of investigations that are essential for I staging thyroid lymphoma S and these are as follows: •
•
GENETI C STU D I ES AND SCREENI NG FOR FAM I LI A L M EDULLARY CARCI N O M A
In excess of 90 percent of patients with any form of familial medullary thyroid carcinoma have been shown to have a mutation of the Ret proto-oncogene. I S Moreover, 98 percent of cases of M EN2A have mutations in one of just six codons. These plus mutation in an additional two codons have been found in isolated fam ilial medullary cancer, while just one single different mutation has been found in 95 percent of all cases of MEN 2B. Such a restricted range of mutations means that selective analysis of the Ret gene is a very feasible and useful technique.
Thyroid ca ncer I 2687
•
• • •
•
thyroid function tests; thyroid antibodies; fine needle aspiration cytology (FNAC) and open biopsy (or tru-cut) ; whole body CT; bone marrow and trephine; lactate dehydrogenase ( LDH ) ; erythrocyte sedimentation rate ( ESR) .
The staging system is the same for extranodal lymphoma at other sites ( Table 1 97.2 1 ) . Patients with disease confined to the thyroid comprise stage I, those who have nodal disease in the neck or mediastinum are stage II and subdiaphragmatic nodal disease is stage III. Evidence of extranodal involvement in organs other than the thyroid,
2688
I PART 1 7 H EAD AN D NECK TU M O U RS
Ta b l e 1 9 7. 2 1
Thyroid lymphoma : staging. D escri pti o n
Sta ge
Stag e 1
Localized to the thyroid Nodal disease i n the neck o r med iasti n u m Subdiaphramatic noda l d isease Extra nodal i nvolve ment to include l iver, d uct gut or bone m arrow
S t ag e
2 S ta ge 3
St a g e 4
such as the liver, gut or bone marrow indicates stage
IV
d isease . 1B
(a)
(e)
Trachea
Trachea
Altho ugh no surgery o ther than biopsy is usu ally
(b]
Trachea
(d]
Trachea
considered to be necessary fo r lympho ma at any o ther site, surgical removal o f bulky disease h as been shown to improve b o th local co ntrol and survival in p atients with thyro id lymphoma. Altho ugh this means that thyroidect o my is sometimes indicated, it is not usually feasible so that rad iotherapy remains the principal treatment for this c o ndition. Sometimes a tracheosto my is requ ired to treat airway obstruction, altho ugh this should be avoided if p ossible.
While
radio therapy
may
produ ce
a
very
dramatic resolu tion of the tu mou r mass, treatment must continue until the end o f the prescribed c o u rse to ensure
Ie)
Trachea
Figu re 1 9 7 . 1 5 Various opera tions that ca n be performed on the thyroid : (a) thyroid lobectomy; (b) near-tota l thyroidectomy ; (c) su btotal thyro i d ectomy; (d) isthmusectomy; ( e ) tota l thyroidectomy.
sustained local co ntrol. Patients with high-grade tu mo urs and more advanced disease sho uld receive approp riate
O p e rative tech n i q u es o n th e thyro i d g l a n d
chemo therapy. The progno sis fo r p atients with thyroid lymphoma is usually excellent.
There are a number o f surgical operations that have been used in the treatment of thyroid tu mou rs
197.22 shows the defin itions prop osed.
A biopsy is manda tory to confirm that a patient s uspected
of
having
an
anaplastic
carcinoma
does
not
have
lymphoma which may be curable. There are a number o f investigations tha t are necessary fo r anap lastic thyroid cancer
and
these
(Figure 197. 1 5 ) Table
and their indications have already been discussed.
An a p l a st i c tu mo u rs
are listed be1ow. 1B
So metimes
the
isthmus will need to be divided and a tracheostomy performed if there is airway obstruction. Apart fro m this, s urgery and radioiodine h ave no p art to play in the management of anaplastic carcinoma. Regression may be
I n general, the minimu m o peration which should be undertaken fo r a suspected or confirme d cancer is a to tal lobectomy. S ubsequent surgery may involve a completion thyroidecto my. Usually when the diagnosis of cancer is known p reoperatively, then either a near-total o r to tal thyro idectomy will be performed as the initial p rocedu re. The o peratio n of subtotal thyro idectomy is to be avoided and is not usually performed nowad ays since it leaves residu al thyroid tissu e on both sides of the neck.
achieved by radical radiotherapy, but early recurrence is
common and usually leads to death within 6- 1 2 months.
H istorical repo rts o f cure fo llowing radio therapy were probably
due
to
lymp ho ma
being
misdiagnosed
as
anaplastic cancer in the d ays before imm uno cytochem istry was routinely avai lable. Attempts to improve the d ismal p rognosis in this disease with chemotherapy have been disap p o inting and its routine use is not reco m mended.
In
some
p atients,
the
disease
may be
so
advanced at presentation that, o nce the d iagnosis is co nfirmed, no
active treatment is the kindest p olicy.
Investigations fo r anaplastic thyroid cancer include : • thyroid function tests;
• thyroid antibod ies; •
FNAC and open biopsy (or tru-cut ) ;
•
neck a n d chest C T ( o r chest radiogra p h ) .
Thy ro i d l o b e cto my I NCISION
The p atient i s po sitioned o n t h e o perating table with the neck extended and a sandbag under the shoulders. The
neck is prepared and d raped in the usual way. A collar incision in a skin crease is marked o ut approximately 2 cm above the suprasternal notch and the level o f the
incision may be marked in the anaesthetic room with the p atient sitting up. The skin sho uld never be cut without making a mark, as this can easily lead to an asymmetrical scar. The skin and platysma sho uld be cu t through and, with traction on the flaps, they should be elevated up to the upper edge of the thyroid cartilage and down to the
Ch a pte r 1 9 7
S u rg ica l operations used i n the trea t m e n t of thyroid t u m o u rs.
Table 1 9 7.22
Tech n i q u e
Thyroid ca ncer I 2689
Vagus nerve
Defi n itio n Carotid
Lu m p ectomy
Pa rti a l thyroidectomy
Tota l l obectomy or h e m ithyroid ectomy Su btota l thyroid ectomy
N e a r-tota l thyroidectomy
Tota l thyroid ectomy Com p l etion thyroid ectomy
Remova l o f a n od u l e a l one with m i n i m a l su rrou n d i n g thyroid tiss ue Remov a l o f a n od u l e w i t h a l a rg e r m a rg i n o f su rrou n d i n g thyroid tissue Com p lete remova l of one thyroid l obe w ith t he isth m u s B i l atera l removal o f more t h a n one h a l f o f the thyroid g l a n d on e a c h side p l u s t h e ist h m u s Tota l l obectomy a n d isth m u sectomy w i t h remova l of more t h a n 90% of t h e contra l atera l l obe Remova l of both thyroid l obes and t he isth mus A su bseq u e n t proced u re t o convert a l esser operation i nto a n ea r-tota l or tota l thyroid ectomy
level of the sternal notch. The flaps should then be retracted using a Joll's thyroid retractor.
G LAI\J D M O B I LIZATI O N
With the surgeon standing on the contralateral side, the deep investing layer of fascia in the midline should be divided and possibly the anterior jugular veins ligated at this point. The gland should be mobilized from the strap muscles and at this point, some surgeons deliberately divide sternothyroid to improve access and then do not resuture it at the end of the procedure. For larger swellings and malignant tumours which invade the strap muscles, these structures may have to be divided and/or if needed resected. As their nerve supply (the ansa cervicalis) enters low down, they should be divided high up. Next, the middle thyroid vein should be identified and ligated (Figure 197. 1 6 ) . Now access the paracarotid tunnel, retract the carotid artery laterally and the thyroid medially to identify the posterior capsule of the gland and Beahrs' triangle (Figure 1 97.3 ) . The next step is to identify and preserve the recurrent laryngeal nerve together with both the parathyroid glands.
artery
Internal jugular
ve i n
t-1��
__-----
Recurrent laryngeal nerve
Division of t h e m i d d l e thyroid vei n in th e pa racarotid tu n n e l .
Fig u re 1 9 7 . 1 6
the nerve low i n the neck where i t lies i n the tracheo oesophageal groove and forms the third side of Beahrs' triangle. Remember on the left side, 1 8 the nerve hugs the groove and is angled at 45° as it exits the chest. On the right side, since the nerve does not enter the chest, it is 45° to the midline, as well as 45° laterally. This means it may be more superficial and hence encountered earlier than on the left side. Before entering the larynx, the nerve may divide into two or three branches which should be identified and preserved. Magnification with loupes may help. One of these branches is usually a sensory branch (the loop of Galen ) . If the recurrent laryngeal nerve cannot be identified, it may be nonrecurrent. This occurs in 1-2 percent of cases on the right side. The nerve is located running with the inferior thyroid vessels and is preserved in the conventional manner. It is a good idea to practise recognition of the recurrent laryngeal nerve during total laryngectomy.
LOCALI ZATI O N A N D PRESERVATI O N O F TH E PARATHYRO I D G LA N DS
Once the parathyroids have been localized, they are peeled off the thyroid together with their blood supply and pretracheal fascia ( Figure 1 97. 1 7 ) . Devascularized para thyroids should be transplanted into the sternomastoid muscle and the lower parathyroid is particularly vulner able to ischaemia, so there should be a low threshold to transplant it.
I D ENTI F I CAT I O N OF TH E R ECU R R ENT LARY N G EA L N ERVE
M O B I LIZATI O N OF TH E U P P E R AN D LOW E R PO LES
One of the crucial steps in a thyroid lobectomy is preservation of the recurrent laryngeal nerve. First, identify it and then ensure its safety ( Figure 197.3 ) . Find
Once the recurrent laryngeal nerve has been identified, the gland should be mobilized top and bottom. The upper pole is mobilized ( Figure 197. 1 8 ) , retracted
PART 1 7 H EA D AN D N ECK TUMOURS
2690 I
Inferior parathyroid
-
Superior parathyrOid Inferior
lhyroid art ery
) v
Recurrent
------
laryngeal
nerve
\1 /�
Trachea
_
. .-
Oesophagus
�� Figu re 1 9 7 . 1 7
o
Thyroidectomy technique w i th
extracapsu lar dissection for parathyroid preservatio n.
l aterally and the superior thyroi d vessels should be li gated sep arat ely close to t he gland Th e ex ternal bra n ch o f the .
superior laryngeal nerve sho uld be i d e nti fi ed a nd p re served as it runs i n Jol l 's t r ian g le med i a l to the u p p e r p o l e ,
vessels where i t lies o n crico t hyro id
( Figure 197. 1 ) . 4 8 , 49
O ccasion ally, a n upper pa ra thyro i d
is
fo u n d
in this
Carotid artery
posi tio n . T h e lower p o l e is mob ilized b y d ivid ing t h e i n ferior thyroid vei ns Remember, t h e recu rre n t l a ryngeal .
nerve can be i nadver tently d am aged d u r ing divisi o n o f eithe r t h e upper o r lower poles Because o f t his, a lways .
Internal
jugular vein
i den tify or know where it is early in the o pe rat io n . Recurrent laryngeal
R E M OVAL O F T H E G LA N D
nerve
The recurrent la ryn geal nerve is traced upwards b y l i ft i n g t he gland o ff it and peel i n g down the p ret rach eal fascia t oge ther wit h the p arat hyro id gJa nds. Attempts sho uld be
made n o t to lift up the nerve or squeeze it. Al l t iss ue
should be dissected from it, leav i n g it u n d i s t u rbed in its bed if p o ssi b le
B ipo la r d ia therm y is p erfectly accep t able
.
to use near the nerve, otherwise tie all bleed ing points usi ng s mall mosqu i to fo rcep s and fine t ies being careful ,
not to catch the nerve in a tie.
Fi gure 1 9 7. 1 8
Superior thyroid pedicle is divided and
following division of the lowe r pole vessels, the gland is rotated medially to allow the division of Berry's ligame n t by sharp dissection (as shown) , which allows rem oval of the lobe of the g land with pres e rvation of the recu rre n t la ryngeal nerv e .
Once the gland is mob i l ized, the who le lobe can be swung med i a lly The in ferio r thyroid artery is preserved ,
Next, t h e j ugula r lymphat i c ch a i n should be p al pated
to geth er with its p ara t hyroid branch es . The p ericaps ular
any susp icio us nodes removed and sent fo r frozen sect i o n .
bra n ches are liga ted a n d at this po in t the gl a n d is attached
The anaesthetist sho uld be asked to p erfo rm a mod ified
to
Valsalva manoeuvre to help ident i fy a ny po ten t i al sou rces
.
the
trachea
Berry s ligament. '
by
a
con densation
o f fascia ,
called
Th is i s d ivid ed by shar p d issect io n
(Figure 1 97, 18) to allow the lobe to be removed t ogether
of bleed i ng
)
,
p aying p a r t icular attenti o n to the infe r io r
with the ist h m u s wh ich preve n ts an u nsightly bump
thyro id veins and t h e area i n t h e apex of the tria n gle ' fo rme d by the recurre nt l aryngeal nerve where it enters
o ccurri n g a fter s u rgery due to gl and hypertrop hy in the
the larynx and the side wa l l of the t rachea ( t he t r i angl e o f
m idli n e
co ncern) , Branches o f the inferior thyro id artery that
.
Chapter 1 9 7
come from below the recurrent laryngeal nerve at this point can be particularly troublesome, particularly if a small remnant of thyroid tissue has been left behind at Berry's ligament. Finally, a suction drain may be placed in the wound ensuring that both the thyroid bed and the superficial space are drained. The wound should be closed in two layers using either clips or a subcutaneous suture.
•
TOTAL THYRO I D ECTO MY FO R CAN C E R
This operation is essentially a bilateral lobectomy. The following points are important when performing the operation for malignancy. •
•
• • •
•
•
•
•
•
Incision is the same as for a lobectomy, except it may need extending to facilitate a neck dissection or mediastinal exploration. Access can be facilitated by dividing the strap muscles, which often need resecting if involved by tumour or when a completion thyroidectomy with level VI dissection is being performed. Both recurrent laryngeal nerves should be identified and attempts made to preserve them . An attempt should be made to operate on the noninvolved side first. Ideally the tumour should be peeled off the nerve, although microscopic deposits may be left behind to be dealt with by radioactive iodine. Do not be afraid to resect one involved nerve. Try to preserve the parathyroids and it is usually possible to keep two glands, particularly when operating on a noninvolved contralateral lobe where a small sliver of thyroid can be left (near-total thyroidectomy) to maintain an intact blood supply. The operation may include a level VI neck dissection, which removes all lymph nodes and soft tissue from within the central compartment from carotid to carotid. This can make parathyroid preservation more difficult . Any further neck disease is treated on its merits . Mediastinal access may be required to identify the recurrent laryngeal nerves low down, facilitate neck dissection by allowing inferior access to the internal j ugular vein at its junction with the subclavian, and finally to allow mediastinal dissection. Neck disease requires at least a selective neck dissection (levels II-V ) . The internal jugular vein is p reserved and the area behind its lower segment ( Chaissaignac's triangle) is carefully dissected taking care on the left side not to damage the thoracic duct . The accessory nerve is identified and there is no need to dissect cephalic to the nerve (level Va) . The sternomastoid muscle is ' preserved and the dissection may be performed with it intact by dividing its lower attachments and resuturing the muscle at the end of the operation. This does not seem to cause any long term sequelae, although in children, postoperative
•
•
•
Thyroid cancer I 269 1
physiotherapy may be required to prevent a temporary iatrogenic to rticollis. Whenever possible, the sensory nerves of the cervical plexus should be preserved, b ut this is not always easy, particularly when the nodal disease is extensive. Extension of disease just on to the la rynx may be dealt with by shaving it off if clearance is judged satisfacto ry. Since the spread of disease in the larynx is often posterior in the region of the ligament of Berry, partial laryngectomy is not usually feasible so that a total laryngectomy may be required. If a small amount of pharyngeal muscle is involved, this can be locally resected. Extensive pharyngeal involvement requires pharyngolaryngectomy and free jejunal transfer or anterior thigh flap. Gastric transposition may be used if the former are unavailable. Involvement of the trachea is not uncommon . Disease on the outer surface can often be shaved off, but invasive disease requires resection. If it is localized, then simple resection leaving the mucosa intact is perfectly acceptable, otherwise a wedge resection will be required. For anterior disease, another option is simply to insert a tracheostomy tube and allow healing by decannulation a few weeks later. This is the favoured option if the airway is compromised. More extensive disease requires a sleeve resection. Up to 4 cm of trachea can be resected with primary anastomosis following a suprahyoid release and mobilization of the trachea down to the carina. The trachea is closed primarily using interrupted vicryl sutures over either an endotracheal or tracheostomy tube. Major vessel involvement is rare in patients with thyroid cancer, but is a concern in those with extensive disease. The internal juglar vein is the most common vessel involved and can be resected in the conventional way. Differentiated thyroid cancer often extends to involve major arteries in the neck and mediastinum, but rarely invades the vessel wall. The disease can usually be dissected from the artery wall, but any concern regarding involvement is an indication for assessment with imaging. Magnetic resonance angiography ( MRA) can be particularly helpful (Figure 197. 1 1 ) . In patients with medullary thyroid cancer, the disease may invade major vessels so imaging is mandatory in the presence of extensive disease.
AFTERCA R E
Apart from general care, the following points should be considered: • •
In the immediate postoperative period, watch for bleeding and airway embarrassment. Check the full blood count and serum calcium the morning after surgery.
2692 •
•
•
I PART 1 7 H EAD AN D I\J EeK TU M O U RS
After straightforward lobectomy, patients may be discharged the next day, following drain and clip removal. Following thyroid lobectomy, there is no need to commence thyroxine replacement unless the patient develops subclinical hypothyroidism. Thyroid function tests are performed approximately six weeks following surgery. Following thyroid lobectomy for malignancy, patients are commenced on suppressive doses of thyroxine. After total thyroidectomy for malignancy, commence T4 immediately unless radioiodine ablation is planned within the next four weeks when the patient can go straight on to liothyronine ( T3 ) . This is discussed later under Radiotherapy ( radioiodine and external beam) .
Co m p l i cati o n s fo l l ow i n g thyro i d s u rg ery
.
A complication is an unexpected adverse result caused by thyroidectomy and this must be differentiated from a natural sequela (either temporary or permanent) which is inevitable following the operation, e.g. permanent hypothyroidism following total thyroidectomy. Compli cations can be divided into early, intermediate and late, . local and general and those specific to the operatIOn. 3 5 Early complications following thyroidectomy include haemorrhage, voice change, airway obstruction and temporary hypoparathyroidism. The intermediate ones include a seroma, infection and temporary palsy of the recurrent laryngeal nerve and the external branch of the superior laryngeal nerve. Late complications include subclinical hypothyroidism, permanent hypoparathyroid ism, permanent nerve injury to the recurrent laryngeal nerve, the external branch of the superior laryngeal nerve, the cutaneous nerves ( II and III) and the accessory nerve, as well as a poor scar. Temporary voice change following thyroidectomy is common but permanent change is uncommon. The most common reported and most feared complication is recurrent laryngeal nerve damage and the average palsy rate in the literature is less than 2 percent. The rates vary with surgical experience and disease status and recent evidence suggests using a nerve stimulator during surgery can significantly reduce the palsy rate 5 0 in inexperienced hands and that in the future, this technique may be useful for teaching and training purposes, revision and difficult cases and may have long-term medicolegal implications. Damage to the external branch of the superior laryngeal nerve appears to be less common and nerve damage can be limited by surgical experience, together with awareness and identification with preservation of the nerve at the time of surgery. The mechanisms for intraoperative recurrent laryngeal nerve injury include: • •
division; laceration;
•
•
• • •
•
• •
stretching or traction; pressure; crush; electrical; heat; ligature entrapment; ischaemia; nerve manipulation.
Factors that increase the injury rate include the experience of the surgeon, the extent and difficulty of surgery, surgery for malignancy, revision cases and re operation for haemorrhage. There are a number of causes of hypocalcaemia associated with thyroidectomy, but the main ones are temporary and permanent hypoparathyroidism. The former is due to ischaemia and hypothermia of the parathyroid glands, together with release of endothelium and parathyroid suppression. Permanent hypoparathyr oidism is a consequence of removal or vascular necrosis of the glands. The incidence of temporary hypoparathyroid ism in the literature is approximately 1 0-20 percent and is often an inevitable consequence of total thyroidectomy. However, the incidence of permanent hypoparathyroid ism should be definitely less than 5 percent ( and more commonly less than 2 percent) and this may be reduced by sound anatomical knowledge, surgical technique and . expenence. 35 ' 4 Haemorrhage is an unusual complication following 9 thyroidectomy and usually occurs within six hours of surgery. The incidence varies relating to the extent of surgery and should not be greater than 3 percent. There is no substitute for meticulous surgical technique nor is there any evidence that drains reduce the haemorrhage rate, but they may increase the incidence of infection. The two common sites for bleeding after thyroidectomy are the inferior thyroid veins and the branches of the inferior thyroid artery in the vicinity of the recurrent lar�nge � l nerve ( triangle of concern) . The danger of bleedmg IS pressure, which causes venous obstruction and supraglot tic oedema, which then results in airway obstruction. If this happens, open the wound in the ward, intubate the patient as soon as possible if indicated and return to theatre. Look for the bleeding points carefully and if they are in the vicinity of the recurrent laryngeal nerve, clamp and tie them carefully using mosquito forceps and fine ties or alternatively use bipolar diathermy. The use of loupes in this situation can be particularly helpful. Respiratory obstruction should not occur after lobect omy, but may occur after a total thyroidectomy if there was tracheal compression before the operation, if both recurrent laryngeal nerves have been injured or if bleeding has occurred. Wound infection is uncommon after thyroidectomy and should occur in only 1-2 percent of cases. Some advocate the use of prophylactic antibiotics and rarely following surgery, haemorrhage, hypocalcae mia and infection can be fatal. 5 1
C h a pter 1 9 7
Following neck dissection for disease low in the left neck, the thoracic duct is particularly at risk and care should be taken to identify this structure and its tributaries at the time of surgery. The accessory nerve should be identified and preserved. There is evidence from other surgical specialties that experience and patient volume can lead to improved clinical outcomes and one study from America showed the surgeons who did the most work and operated on the complex cases had complication rates and length of stays that were less than the other less experienced surgeons. The study concluded that there was a significant association between increased surgical volume and improved patient outcomes after surgical procedures for benign and malignant disease and that cases of known or suspected cancer which require a near-total or total thyroidectomy should be referred to high volume surgeons. 52 The recommendations in the UK ( and it is likely the USA will follow) is that surgeons performing this type of surgery should be undertaking between 20 and 30 cases per year. 1 S , 1 9 , 2 0 Patients have a right to informed consent and the surgeon performing the operation should take the consent, inform them of the important complications of the operation (haemorrhage, nerve palsy, voice change, bleeding, hypoparathyrodism and a poor scar) and be in a position to provide them not only with their own figures, but also those in the world Ii terature .
W h o s h o u l d d o the s u rg e ry? Historically thyroid surgery has been the domain of the general surgeon. Otolaryngology became a designated specialty in 1 948 and over the last 20 years, more and more ear, nose and throat ( ENT) surgeons have been undertaking thyroid surgery. A recent study showed that general surgeons still perform the majority of thyroid surgery in the UK (83 percent) , but ENT surgeons are now performing significant numbers ( 1 7 percent; 1 500 cases per year) . 4 One hundred and two members of the British Association of Otolaryngologists - Head and Neck Surgeons ( BAOL-HNS) perform thyroid surgery with an average case load of 1 9 per year. Ten percent of these members also belonged to the British Association of Endocrine Surgeons ( BAES) and 3 5 percent of otolar yngologists saw patients in a multidisciplinary clinic. The study also showed that the clinical practice of ENT surgeons regarding the investigation of a solitary thyroid nodule was in line with other UK and European specialists. The arguments for including otolaryngologists in the practice of thyroid surgery are that they have been treating head and neck cancer in the UK over the last 50 years and are often involved in multidisciplinary head and neck team work, which usually includes a head and neck oncologist who treats thyroid malignancy. Thyroid
Thyroid ca ncer I 2693
cancer is included in the head and neck TNM classifica tion and an ENT surgeon can offer adjunctive roles in airway management, voice assessment and the treatment of cervical lymph nodes. In addition, ENT surgeons manage other head and neck endocrine diseases, includ ing pituitary and neuroendocrine tumours and they are regular contributors to thyroid research programmes in the UK. To quote Ashok Shaha ( 200 1 ) , 'It's not your background that is important, it is the way you have been trained and the environment you work in'. It is likely in the future that ENT and general surgeons will work together in multidisciplinary teams and this can only improve the way we diagnose, stage and treat thyroid cancer. 5 3
PAE D IAT R I C THYRO I D CAN C E R Thyroid cancer i n children i s rare and the most common histological type is papillary carcinoma . Nodules in children are more likely to be malignant and previous radiation exposure is a significant risk factor. Children aged ten years or less tend to have a more aggressive disease 54 and in general, the principles of management are similar to those in adults, but the multidisciplinary team should include a paediatric endocrinologist and an oncologist. A total thyroidectomy and level 6 neck dissection is usually recommended for most patients, and the presence of clinically positive neck disease indicates the need for selective neck dissection removing nodes from at least levels IIa to Vb. Decisions regarding the use of radioiodine therapy should be individually determined based on the patient's age, extent of disease and the opinions of the multidisciplinary team. Lifelong follow-up is advised.
TH E D I FFICU LT THYRO I D A thyroid may b e difficult because o f its history, assessment, examination or imaging. In addition, some thyroids have difficult histology, they are difficult to treat and some are extremely difficult to cure. It is important that complex management problems relating to cancer are discussed in a multidisciplinary environment and the minutes of the meeting recorded.
RAD I OTH E RA PY ( RAD I O I O D I N E AN D EXTER NAL B EAM) It has been estimated that a clinical trial to address the therapeutic effect of ablative 1 3 1 1 therapy would require 4000 patients in each arm to demonstrate a 10 percent reduction in mortality over 25 years. If every one in ten thyroid patients were enrolled, recruitment would take ten years and the results would be available after 35 years.
2694
I PART 1 7 H EAD AI\J D N ECK TU M O U RS
Quite clearly, such a study will not take place, but there are many retrospective studies which report lower recurrence rates (sometimes with reduced cancer mortal 131 I ablation and in one study, ity rates) following remnant ablation was an independent variable that reduced both local and distant recurrences, as well as 3 1 32 cancer deaths ( Figure 1 97. 19) . , The rationale for using postoperative radioiodine ablation is that it destroys both normal tissue, as well as microscopic foci of carcinoma cells within the thyroid remnant, which thereby reduces the risk of local recurrence and prolongs survival. In addition, it can aid the interpretation of serum thyroglobulin measurements during the follow-up period and it also facilitates detection and early treatment of persistent or metastatic disease in the absence of remaining normal tissue. Its routine use in the postoperative ablation of the thyroid remnant has been shown to reduce local recurrence and improve survival, particularly for tumours that measure more than 1 cm in size.
Ra d i o i od i n e treatm ent The protocol to be followed for both ablation of residual normal thyroid tissue and treatment of proven function ing local residual disease or distant metastases following ablation is the same, it is simply the dose that is different. The usual ablation dose is approximately 3 GBq, although some centres may use a lower dose ( 1 . 1 GBq) which has been shown by some authors to be as effective. A post ablation scan should be performed three to five days following the treatment dose. An example of the protocol is shown in Figure 1 97.20. The patient should be admitted to hospital and accommodated in a single room equipped for radiation protection purposes with either private toilet facilities or a commode. A diagnostic radioiodine scan is usually performed six months following ablation. In selected cases with aggressive disease, this may be performed sooner ( i.e. three months) and if clear, no further diagnostic scans are
required and follow-up is with serial thyroglobulin measurements and suppressive thyroxine replacement therapy. Some recent data suggest that a post-ablation diagnostic scan may not be necessary (particularly in low-risk patients) , but that the serum thyroglobulin must always be measured. 1 s Repeat chest radiographs are unnecessary since they are much less sensitive than a diagnostic radioiodine scan. Before the diagnostic scan, patients should switch from T4 to T3 replacement which is stopped two weeks before imaging. Alternatively, the scan may be carried out using recombinant TSH (see Serum thyroglobulin measurements below) . 131 The short- and long-term side effects of 1 therapy are summarized in Table 1 97.23. Early side effects from 131 1 therapy include neck discomfort with swelling immediately after treatment, but this is rare. It is more common if a large thyroid remnant is present and a short course of steroids may be necessary. In addition, abnormalities of taste have been noted together with sialadenitis and nausea. The sialadenitis and recurrent salivary gland swelling may persist for a year following treatment, but usually settle after that and active intervention is not usually required. Women should not become pregnant for a minimum period of four months after treatment and pregnancy should be deferred 131 for at least six months after high-dose 1 therapy, when there is no risk to fertility or normal pregnancy, although there does appear to be a slightly increased risk of miscarriage if pregnancy occurs within one year of therapy. In men, the four-month period is also applicable since this allows for the life span of a sperm cell and pretreatment sperm banking should be considered in men likely to have more than two doses of radioiodine therapy. Sperm banking may also be indicated in children and this is usually before treatment with one therapy dose of radioiodine. With regard to possible late effects, the incidence of leukaemia and second cancers is extremely low and in the order of 1 percent. Radiation fibrosis can occur in patients who have had diffuse pulmonary metastatic disease treated with repeated therapy doses of radioiodine.
10
� co
..r:
ill u ill >
8 6
:ffi :::J
4
0
2
E
:::J
p
=
0.01
0 0
5
10
15
20
25
30
35
N o RAI ablation
0 802
11 664
14 548
11 446
3 385
4 258
2 1 35
51
RAI ablation
0 1 38
0 1 01
79
0 0 47 27 Years after initial therapy
10
0
0
66
0
0
0 4
Ca ncer m o rta l ity i n pati e n ts Fig u re 1 9 7 . 1 9 with stag e 2 or 3 t u m o u rs treated with s u rg e ry a Q d ra d i oactive iod i n e (RAI) at RAI2 (3 50) a n d with out RAI2 (802). Red raw n from Ref. 3 1 , with perm issi o n .
C h a pter 1 9 7
Total thyroidectomy
Ta b l e 1 9 7 . 2 3
Thyroid ca nce r I 2695
The short- and lon g-term side effects of 1 31 1
t h e ra py. Liothyronine (T3) 20 /1g tds stop 2 weeks before
1 31 1
IMP
l\J eck d isco m fo rt Avoid iodine containing medicines, fish, added salt and radiographic contrast examinations
1 31
1 Ab l ati on 3 G8q day 3 check thyrog l obu l i n (Tg) and TSH
1
Thyroxine (T4) for 6 weeks only
Six weeks out-patient appointment, check Tg , TSH, T4
Change to T3 20 /1g tds for 2 weeks (stop 2 weeks before
1 31
1 3 1 1)
3-6 months
1 Diagnostic scan 200 M8q , check Tg and TSH ..----
Scan positive Thyroglobulin raised Metastases
(stop 2 weeks before
1 4 weeks
therapy dose 5 . 5 G8q Day 3 scan
-------.. Scan negative Thyroglobulin <1 5 /1g/L No metastases
Recommence T3 20 /1g tds for 2 weeks
1 31 1
Early effects
1 31 1 )
Commence T4
Follow-up check Tg, TSH , T4 (6-1 2 monthly appointments)
Ab norm a l ities of taste a n d recu rre n t sia l a d e n itis
Late effects
Low i ncidence of l e u ka e m i a a n d seco n d ca nce rs Rad iation fi brosis
Na usea Preg n a ncy Low sperm cou nt
component and about 80 percent of well-differentiated carcinomas of follicular cell origin (not just follicular carcinoma) accumulate iodine adequately for imaging 131 and therapy. Scanning with radioiodine ( 200 MBq of 1) to confirm ablation of the thyroid remnant and to demonstrate functioning residual disease or metastases is undertaken at three months, by which time the initial treatment should have abolished residual normal tissue. Earlier assessment is not possible, as the avidity of tumour for iodine is always considerably less than that of normal thyroid tissue. If any uptake is demonstrated, a therapy 1311 dose 5 . 5 GBq of is given. This is repeated every three to six months until all tumour is eradicated or the disease progresses . Postoperative external beam radiotherapy should be considered if operative clearance is in doubt or macro scopically incomplete, or if there was extensive nodal involvement. After this combined primary treatment with optimal surgery and radioiodine or external beam irradiation, the patient should be placed on a dose of thyroxine, which is adequate to suppress TSH levels ( usually 200-2 50 �g daily) . Thereafter, patients should be followed up regularly. As the disease may recur after decades of inactivity, surveillance should be for life. Thyroglobulin assay has now replaced routine radio iodine scanning, although this is indicated if thyro globulin levels rise.
Fig ure 1 9 7 . 2 0 Protoco l for the a d m i n istration of rad i oactive iod i n e fo l lowi ng tota l thyroidectomy.
Seru m thyrog l o b u l i n m e a s u rem ents
Following total thyroidectomy, radioiodine ablation of 1311 the residual normal thyroid tissue with 3 GBq of can be performed in the immediate postoperative period, before thyroid hormone replacement has been started. If there is any delay before radioiodine can be administered, liothyronine can be used as thyroid hormone replacement and stopped ten days before radioiodine administration. Radioiodine ablation of normal thyroid function is performed whether or not the tumour concentrates iodine. In fact, most pap illary carcinomas have a follicular
Serum thyroglobulin is a useful and specific tumour marker which is produced by normal and neoplastic thyroid tissue and which is, in part, dependent on TSH. The serum level should be interpreted together with a serum TSH and in patients who have been treated with 1311 total thyroidectomy and ablation, it is undetectable in 98 percent of patients in complete remission who are on thyroxine. However, in low-risk patients who have undergone a lobectomy, it is only undetectable in 66 percent of patients on thyroxine. 55 Samples should not be collected for at least four to six weeks after thyroidectomy
2696
I PART 1 7 H EAD AN D N ECK TU M O U RS
or 1 3 1 1 therapy and its diagnostic sensitivity is enhanced by an elevated serum TSH. To ensure continuity in monitoring, clinicians should use the same laboratory and thyroglobulin assay on a long-term basis and should be aware that measurements may be falsely elevated due to interference from high levels of antithyroalobulin /:) antibodies. One of the problems for patients who stop their thyroxine treatment one month before (or liothyronine two weeks before) is the inevitable hypothyroidism that this induces. Recombinant human TSH has been recently introduced and approved for use in the USA and Europe as an alternative to thyroid ho rmone withdrawal when performing diagnostic whole body 1 3 1 1 scans. Patients using this technique have described significant quality of life improvements and everyone undergoing treatment should be informed about the advantaaes and disadvantages of this diagnostic method compa �ed with conventional techniques. In those patients known to have antithyroglobulin antibodies which interfere with the thyroglobulin assay, it may be preferable to perform a diagnostic whole body radioiodine scan after thyroid hormone withdrawal rather than use recombinant TSH. I S In those patients with hypopituitarism, severe ischae mic heart disease, previous history of a psychiatric disturbance precipitated by hypothyroidism, advanced disease or frailty, and in those with functional metastases which cause suppression of the TSH, then recombinant human TSH may be the only possible or safe option for . 1311 . d lagnostIc ' scannmg purposes. The scanning protocol should comply with the manufacturer's recommenda tions and there is some evidence that its use for 1 3 1 1 therapy may not be as effective as thyroid hormone withdrawa1. 1 s Absolute indications for recombinant TSH include: • •
•
•
•
hypopituitarism; severe ischaemic heart disease; previous history of a psychiatric disturbance; advanced disease or frailty; functional metastases with suppression of the TSH.
Exter n a l bea m rad i ot h e ra py External beam radiotherapy is used infrequently. It probably does reduce local recurrence rates in those patients at high risk of recurrent disease. Its use should be approved in the multidisciplinary team setting, and s �ould be planned carefully preferably using three . d1 �enslOnal c� nformal planning techniques with appro pnate precautlOns taken for the prevention of radiation myelopathy. Indications for external beam radiotherapy include: •
•
primary treatment; local invasion;
•
•
•
•
residual micro/macroscopic disease; refusal or allergy to RAI2; solitary osseous metastasis; focus of poorly differentiated/anaplastic carcinoma in the resected specimen.
It may be used as primary treatment in those patients who are unable to undergo surgery for whatever reason and in the postoperative setting to treat local invasion or the presence of significant residual macroscopic and micro scopic disease, particularly if the residual tumour fails to concentrate radioiodine. It may also be used to treat recurrent disease in the neck which is not amenable either to further surgery or radioiodine therapy, and also as an alternative to radioiodine in those patients who do either not want it or who are allergic to it. It may also be used postoperatively following the resection of a solitary bony metastasis. Finally, it may be used to palliate inoperable metastatic disease in the long bones, mediastinum, brain, the spine or other areas. 1 S Chemotherapy has no role in the routine management of differentiated thyroid cancer. Its use is generally rest ri �te � to end-stage disease not controlled by surgery, rad l. OlOdme therapy or external beam radiotherapy and the agents that have been used are doxorubicin and cisplatinum. However, the partial response rates are only 1 0-20 percent and so it should only be used in patients with progressive and symptomatic disease. Obviously, it may have a significant role to play in the treatment of lymphoma and in anaplastic carcinoma, where concur rent chemoradiation has been tried with some short-term benefit.
R E CU R R ENT D I S EAS E In one large series, the 40-year recurrence rates for differentiated thyroid cancer were about 35 percent of which approximately two-thirds occurred within the first 3 decade following treatment ( Figure 1 97.2 1 ) . 2 Recurrent disease is associated with patient, tumour and physician factors and is more common in high-risk patients, those with aggressive tumours and those who have had inadequate surgery or a previous recurrence. There is evidence that its early detection can lead to cure or certainly improvements in long-term survival, particu larly if it is surgically resectable or takes up radioactive iodine. Distant metastases develop in approximately 5 to 20 percent of patients with differentiated thyroid carcinoma who are followed up long term and occurs mainly in the lungs and bones. For those patients who have a recurrence in the thyroid bed or cervical lymph nodes, surgical re-exploration is usually the treatment of choice followed by 1 3 1 1 ablation. When there is -tnetastatic disease that involves the lunas /:) or other soft tissue regions which is not amenable to suraery, /:) . patIents s h oul d be treated with 1 3 1 I alone. If the tumour
Cha pter 1 97 Thyroid cancer I
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El Distant recurrences
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2697
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80
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thyroid function tests me asu red together wi th the serum
60
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a
full histo ry and examin ation sho u ld be performed a nd
For patients with medullary thyroid cancer, lifelong
20
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10
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Fi g u re 1 97 . 2 1
15
20
25
30
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Years after initial therapy
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1 528
40
fo llow u p with appo intments every six m on th s i s advised
to assess the response to pr imary s u rgery and to measu re tumour m a rkers, such as calc i t o n i n . The presence of recurrent disease sho u l d i ndicate the need for repeated imaging
patients with
d i ffe rentiated th yroid cancer (medium follow-up, 1 6.6 years).
a nd
recurrences
restaging
sho u l d
be
and
any
treated
local
by
and
su rgery
regional whenever
p o ssible. Postope rative radio therapy m ay then b e given
Red ra wn from Ref. 3 2.
if resection is incomplete. The presence of an e l eva ted but stabl e calcitonin in the postope ra tive period m ay be ta kes up radio i o d i ne, then l o ng-term su rvival is p ossible
and
repea ted
doses may be p rescribed. There is no
m anaged co nservatively. P ro gressively rising l evels should trigger the need fo r further i m aging.
IS
maxi m u m l i mit to the cum ulative dose o f 1 3 1 1 that can be given to pat ients wh o have p ersistent disease. Solitary bone m etastases sh o u l d be treated with a com binatio n of o r thop aed i c i n te rven tion, 1 3 1 1 and external beam
OUTCO M E M EASU R E M E NTS
radiothera py.
There are a number of o utcome meas u rements that a re
Within the multid isciplinary team sett ing, there should be
a
protocol i n p lace fo r th e investigatio n of patients who
have
a
rising
d i agnosti c
serum
whole
thyroglo bulin
body
rad ioiod ine
and
a
scan. IS
negative
In
this
sit uation, having checked that the diagnostic whole b o dy sca n is t ruly negative rather than being falsely negative becau se of iodine contamination o r a suboptimal serum TSH level, a n atomical imaging sh o u ld be perform ed using
CT, MRI Or ul traso und ( either sin g ly or in
com b i nation) to i nvestigate the most comm o n sites o f recurrence which a r e the thyro id b e d a n d the cervical and med i asti nal lymph nodes.
If this is negative, then bo ny
seco ndaries s ho u l d be excl uded either using a conven tional techne tium 99m-MDP scan o r with other agents, s uch as Tc
99m-MIBI or pen tavalent DMSA. If all these
a re negative, then a CT/po sitron emission tom ography
(PET) scan should be carried out to exclude potent ially
operable d isease since this has the highest sensi tivity for detecting differentiated recurrent d isease. 1 8 How
important following t h e treat ment These are l isted below:
of thyroid ca n cer.
1 8, 33
• adequate pri mary su rgery;
• incidence of vo cal cord p a ralysis;
• incidence o f hypopa rat hyro idism ( te m p o ra ry and
permanent) ;
• achievement o f TSH s u p p ress i o n;
• p rovisi o n and t reatme n t with radio i o d ine
postop erat ively when i n d icated;
• regular monito ring of seru m t hyroglobul i n; • a b n o r m a l t hyrogl o b u l i n acted up o n ;
• d isease - free i n t e rva l ;
• quality o f life; • s u rviva l .
T h e i m p o r ta nce o f adequate l o w m o r b i d i ty primary su rgery
has
a l rea dy
been
d iscussed
m o n i t o ring o f the serum t hyroglo bulin.
serum
b u l i n p rom ptly and to
thyroglobulin
result
due
to
interference
from
anti thyroglobulin antibo dies and to double check the level by perfo rming a second assay p referably i n another
with
the
t reatment with l o n g- t erm TS H s u pp ression with reg u l ar
ever, current availability of this technique in the U K is
limited. It is also important to exclude a fal s e - p o s itive
alo n g
p rovision o f radioiodine a b lat i o n and/or thera py, and
I t is i m portant to invest igat e a n ab normal thyrogl o use local p ro t ocols which are
approved by t he m u l t id i sci p l in a ry tea m . Beca use o f a long n a t u ra l histo ry, the d isease - free i nterval is important and
cen tre.
altho ugh recurrences have b een rep o r t ed up to 42 years
If all these tests are negative, then a therapeu tic dose of 1 3 1 1 may be considered, but in those cases where t he
mon
ser u m thyroglobulin is only m o d es tly elevated, re ma ins
fo l l o w i ng i n i tial treatment, late recu r rences are un com fo l lowing
appropriate
i nitial
therapy.
Com m o n
psycho social issues rela t i ng to the anxiety of a cancer
stable and i s not associated with a ny s ignificant symptoms
d iagn os is, s ide effects of radio iodine treatment and the
or signs , t hen conserva t ive m a nagem ent with ca reful
m o rbidity ass o c iated w i t h maj o r exti rp at ive surgery are
observation is entirely appro p riate.
not unco m m o n , par ticu larly i n the you ng, and should be
2698 I
PART 1 7
H EAD A N D N ECK TU M O U RS
addressed by the multidisciplinary team which includes the app ropriate counselling skills of a head and neck nu rse and/or counsellor.
Best cl i n i ca l p ract i ce
Thyroi d su rgery It is i m po rta nt to m a ke a big i ncision. Th e stra p m uscles s h o u l d be d ivided ea rly. Do the easy side a n d the u pper poles fi rst. Do not be afra id to resect one recu rrent l a ryngeal n e rve. M e d iasti n a l a ccess may be req u i red. Remember to a l ways work i n a tea m.
KEY PO I NTS • •
•
• •
• • •
•
•
•
•
Thyroid disease is common, while thyroid cancer is uncommon. The most common way for thyroid cancer to present is as a solitary thyroid nodule in a euthyroid patient when the incidence of malignancy is approximately 10 percent. Essential preoperative investigations include clinical examination, thyroid function tests, thyroid antibodies and fine needle asp iration cytology. Anatomical imaging is usually required for advanced malignancy. For differentiated thyroid cancer, the mainstay of treatment is near-total or total thyroidectomy, subsequent radioiodine ablation and lifelong follow-up with TSH suppression and serum thyroglobulin measurements. Neck disease is usually treated with selective neck dissection. Major extirpative surgery may be required for advanced disease. The treatment of medullary thyroid carcinoma is with total thyroidectomy and central compartment neck dissection. Lymphoma and anaplastic carcinoma should be treated by the appropriate specialist according to protocol. Surgery has only a little part to play apart from biopsy. Thyroid cancer is rare in children and children aged ten years or less tend to have more aggressive disease. Total thyroidectomy is generally recommended for all patients. Quantitative outcome measurements are available following treatment and include adequacy of the primary surgery, incidence of complications, achievement of TSH suppression, regular monitoring of serum thyroglobulin together with quality of life, disease-free interval and survival. Working in multidisciplinary teams and being involved in further molecular biology research can only improve the way we diagnose, stage and treat thyroid cancer.
Defi c i e n ci es in cu rre nt k n ow l ed g e a n d a reas fo r futu re rese a rc h >
Ca n ce r is a d isease of genes. Genes e n cod i ng molecu l es i nvo lved in reg u lating the g rowth, d iffe re ntiation and fu nction of ce l l s a re m u tate d , l ost o r d e reg u l ated in ca nce r. The recog n ition of g e netic cha nges and the potentia l to correct them, a re l e a d i n g to exciti ng new m od a l ities for the d ia g n os is a n d treatment of thyro i d ca ncer. M a ny of these a re i n ea rly cl i n i ca l tri a l s a n d t h e i r eve ntu a l i m pa ct o n mo rta l ity from thyro i d ca ncer re m a i n s to be see n .
> F N A is a n i m porta nt d i a g nostic test i n u s e today.
M o l ecu l a r tech n i q u es, i ncl u d i ng reve rse tra nscri ptase polymerase cha i n reactio n (RT-PCR). h ave been used in a n atte m pt to i m p rove the a ccu racy of FNA. This wou l d be especia l ly usefu l to d isti n g u ish between fol l icu l a r a d e n o m a and ca rci noma, cu rre ntly i m poss i b l e o n conve ntion a l cyto logica l methods. There is cu rre ntly no m o l ecu l a r m a rker specifi c e n o u g h to d isti n g u ish these, but Ras m utation a n a lysis shows some pro m ise.56 Oth er tech n i q ues i ncl u d i ng q u a ntitative polym e rase c h a i n reactio n (PCR) a n d g e n e a rray tech n o l ogy m a y a l low accu rate d etection of ca nce r, a lthough more s pecifi c ge netic m a rke rs of thyroid m a l ig na n cy a re req u i red. Disease p rog ression is cu rre ntly mon itore d by seru m thyrog lobu l i n , as we l l as 1 3 1 1 sca ns a n d c l i n ica l exa m i nation. U p to 25 pe rcent of pati ents h ave a ntibod ies wh ich i n te rfere with the thyrog lobu l i n assays a n d m a ke i nte rpretation d ifficu lt. Detection of seru m m R NA using q u a ntitative RT-PCR may a l l ow this su bset of patie nts to be a n a lysed more a ccu rate ly, a lthough p re l i m in a ry resu l ts i n cl i n ica l tri a l s a re equ ivoca l .57 }- Angiogenesis is the g rowth of new b l ood vessels by s prouting of existing ca p i l l a ri es a n d is esse nti a l for a l l tu mou r g rowth. N u m e rous a n g i og e n i c g rowth factors a re e l evated in thyroid ca nce rs, i ncl u d i n g vascu l a r e n d othe l i a l g rowth factor (VEG F) . fi brobl ast g rowth factor (FS F) a n d the a ng io po i eti ns. " Severa l endogenous a ntia n g iog e n i c factors, i nc l u d i n g
C h a pter
endosta t i n a n d a n g i ostat i n , have been effective a t red ucing o r p reve nting t u m o u r g rowth i n a n a n i m a l model o f thyroid ca ncer a n d m a y p rove usefu l i n h u ma n thyroid ca ncer.58 Oth e r a ntiangiogenic a g e nts a re in d eve lopment a n d a re enteri ng cl i n ica l tri a l s i n other so l i d t u m o u rs a n d w i l l soo n be a p p l ied to thyro id ca ncers. Gene thera py is the treatment of d isease by the tra n sfer of g e n etic materi a l . Seve ra l vector strateg i es may be e m p loyed , either vira l such as retrov i ruses, a d enovi ruses and l entivi rus w h i ch have re l atively h i g h tra nsfer efficiency but may have u nwa nted effects d u e to the i n herent properties of the virus, o r physica l m ethods, s u c h a s l i poso m es o r i njection o f na ked DNA, w h ich a re safe r, b u t l ess potent vectors. Approaches used i nc l u d e i ntrod u ction of p53 i nto p53-d eficient a n a p l astic ca rci no m as, transfe r of suicide genes such as thym i d i ne kinase i n to ca n ce r cel ls, overexpression o f i nterl e u ki n-2 t o i ncrease i m m u n u n o log ica l a ntitu m o u r a ctivity and i n creased exp ression of the sod i u m iod i d e sym po rter i nto thyro i d ca n ce rs that have become 1 3 1 1 resista nt. 59 Despite the relatively modest resu l ts of gene thera py h itherto, it is l i ke l y that these a p p roach es w i l l p rove to be cl i n ica l ly usefu l in the m ed i u m to l o ng term a n d have the potential to tra n sform the treatment of m a ny ca ncers, i n cl u d i n g th yro i d ca ncer.
R E F E R E N CES *
1 . Tu n bridge WMG, Evered DC, H a l l R, A p p l eto n 0, B rewis M , Cla rk F et al. The spectru m of thyroid d isease i n a co m m u n ity: The W hi ckham Su rvey. Clinical Endocrinology. 1 97 7 ; 7 : 481 -93. 2. Ka rk AE, Kissi n M W, Auerbach R, M ei kl e M . Voi ce cha n g es a fter thyroid ecto my: Role of the exte rna l l a ryngeal n e rve. British Medical Journal. 1 984; 2 8 9 : 1 41 2-5. 3 . Watkinson J C, Gaze MN, Wi lson JA (eds) . Tu m o u rs of the thyro id and p a ra thyro i d g l a nds. I n : Stell and Maran 's head and neck surgery, 4th e d n . Lo nd o n : Butterworth H ei ne m a n n , 2000. 4. Ramsden J D, Joh nson AP, Cocks H C, Watki nson J C. Who pe rfo rms thyroid s u rgery : A review of cu rre nt oto l a ryngologica l practice. Clinical Otolaryngology. 2002 ; 2 7 : 304-9. 5. Pl i ny the Elder. N a t u ra l is h istoria e, to m us p ri m u s [-terti us], 60AD. 6. Gaita n E, l\J elson N C, Poo l e GV. End em i c goiter a n d e n d e m i c thyro i d d iso rders. World Journal of Surgery. 1 99 1 ; 1 5 : 205- 1 5. 7. Ph i l l i ps 01. I od i ne. M i l k and the e l i m i n ation of e n d e m i c goi tre i n B rita i n : T h e story o f a n a ccidental p u b l ic hea lth tri u m ph. Journal of Epidemiology and Community Health. 1 997 ; 5 1 : 391 -3.
1 9 7 Thyro i d ca ncer I 2699
8. Va n d e rp u m p M P, Tu n b ridge W M , French -1 M , Appl eton 0, Bates 0, C l a rk F et al. The i n ci d e n ce of thyroid d isord e rs i n t h e com m u n ity: A twe n ty-yea r fo l low- u p o f the W hi c k h a m Su rvey. Clinical Endocrinology (Oxford). 1 995 ; 9.
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45. 46. * 47.
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1
8
Management of the patient presenting with neck lymphadenopathy and an unknown primary .
carcinoma
JAWAHER ANSARI AND JOHN GLAHOLM
Introduction
2702
Management of the putative primary site
2706
Diagnosis
2703
Recent advances
2707
Genetics and molecular analys i s
2703
Key point s
2707
Positron emission tomography
2704
Best clinical pract i ce
2708
Clinical management of carcinoma of unknown primary
2704
Deficiencies in current knowledge and areas for future
Surgical management of the neck
2706
Irradiation limited to the involved neck
2706
2708
research
2708
References
SEARCH STRATEGY The d a ta in this chapter are supported by PubMed and Medline searches using key words cervical lymphadenopathy, carcinoma of unknown pri mary, unknown primary carcinoma, head and neck cancer, neck nodes, neck dissection, positron emission t omography and panmucosal radioth erapy.
CFDG-PET) and more recently positron emission tomo (PET-CT) fusion imaging ,
INTRODUCTION
gr aphy - comp u ted tomog rap hy
The definition of an unknown or occult prima ry carcinoma is the presentation of me tas ta tic neck lymph adenopat hy without the development of a primary lesion wi th i n a s u b se qu ent five -year period. The diagnosis is,
has
introduced
a
further diagnostic mod a lity to be
considered. [*] The presentation of metastatic carcinoma involving neck nodes without clinical evidence of a primary tumour
however, one of exclusion and consequen t ly depends
is an unusual, but not a rare, situation. ]t accounts
upon the diligence exercised in the search for a primary
for only 2-3 percent of patients with head and neck l malignancy. Metastases most commonly develop at
tumour. Failure to i d e n t i fy
an
occult primary has been
attributed to either spontaneous regression of the primary tumour, autoimmune destruction or possibly accelerated tumour progression. The term carcinoma of unknown primary origin of primary examination,
(CUP)
should
be
used if no evidence
tumour is found after adequate clinical fibreoptic
endoscopy
and
conventional
nodal levels II and 111 with less frequent involvement of levels 1, N, V and VI.2 Squamous carcinoma is the most common histological tumour type and poses the
gre a test
d iag nos tic dilemma because of t he large number of prim a ry
upper aerodiges tive sites from which nodal
metastases may arise. The prognosis for these patien ts is
introduction of fluorine
relatively good with five-year survival rates exceeding so
I8-labelled deoxyglucose positron emission tomography
percent, irrespective of the management s t ra tegy .3 I sola ted
radiological investigations. The
Chapter 198 Management of the patient presenting with neck lymphadenopathy and an unknown primary carcinoma I 2703
supraclavicular nodal involvement is almost invariably
Examination under anaesthesia should then be per
related to malignant disease arising below the clavicles
formed, this consists of laryngo-pharyngo-oesophago
from the breast, chest, abdomen or pelvis and is outwith
scopy and careful palpation of the tongue base. In the
the remit of this discussion. [**/*]
absence of an obvious primary on endoscopy, tonsil lectomy, tongue base biopsy and biopsies of the post nasal space and pyriform fossa should be performed. The
DIAGNOSIS
nasopharynx is of particular importance in patients whose nodal metastasis lies in level V and in those with
When a patient presents with an isolated neck mass, a
an anaplastic histology. Tonsillectomy is recommended
thorough clinical history and examination is essential,
because up to 25 percent of tumours are found at this 6 site. , 7 A previous tonsillectomy does not exclude this
including a full ear, nose and throat (ENT) assessment with nasendoscopic examination of the upper aerodiges
risk, as cancer can develop in residual tissue and is easy to
tive tract. The majority of patients presenting with a level
overlook. Traditionally, tonsillectomy ipsilateral to the
II/III mass will have a primary tumour of the tongue base
nodal
or tonsil and so particular attention must be paid to the
contralateral spread from occult tonsillar lesions may be
examination of these areas. It should be emphasized that bulky neck nodes can present in conjunction with a very
as high as 10 percent and consequently bilateral 8 tonsillectomy will offer a higher diagnostic yield. Tongue
small primary tumour of the tonsil or a submucosal
base biopsy will subsequently reveal an additional 10-15
has
been
recommended;
however,
tumour of the tongue base. Additionally, the skin in the
percent of occult primaries. As biopsy of the tongue base
head and neck region including the scalp should be
can
carefully assessed together with the external ear and
submucosal, consideration should be given to performing
be
difficult
and
many
occult
carcinomas
are
auditory canal. At this point a note of caution should be
a wedge biopsy, cutting deeply into the tongue base rather
sounded in relation to the diagnosis of a branchial cyst in
than just using cupped forceps. [**]
patients over the age of 40 years. It is not unusual to have
These conventional processes of clinical examination,
a fine needle aspiration (FNA) reported as consistent with
panendoscopy, CT and/or MRI followed by panendo
a branchial cyst only for the histology following excision
scopy with biopsy have been shown to reveal the primary
to
report
the presence of metastatic
squamous
cell
site in over 40 percent of patients initially diagnosed with
carcinoma (SCC). It is important to maintain a high index of suspicion in relation to adults with a seeming
neck node metastatic squamous carcinoma of unknown 9 primary origin. Diagnostic accuracy may be further
branchial cyst. They may present at any age; however,
enhanced using laser-induced fluorescence endoscopy in
more often than not a presumed branchial cyst in a
may
metastasis
parallel with conventional panendoscopy and biopsy. In a
patient over the age of 40 years, particularly if they are a
study of 13 patients reported by Kulapaditharom et al.10
smoker, even after cytology consistent with a branchial
the identification rate of an occult primary was increased
cyst, will prove to be a cystic metastasis from a tongue
from 15.4 to 38.5 percent. [**/*]
may
base or tonsil carcinoma. [*] Fine
needle
aspirate
cytology
(FNAC)
from
the
abnormal neck node should then be performed and
GENETICS AND MOLECULAR ANALYSIS
will often afford clear indication of the pathological nature of the lesion. In cases of uncertainty, open biopsy
Anaplastic carcinoma is a particular example in which the
is necessary. Excision biopsy is advisable and is no
diagnosis of nasopharyngeal carcinoma can be strength
longer considered to compromise outcome in metastatic
ened by the detection of Epstein-Barr virus in the lymph
squamous
node metastasis either by polymerase chain reaction
carcinoma
provided
definitive
treatment,
taken
such as neck dissection and/or radiotherapy is under 45 soon afterwards. , A chest radiograph will
sufficient
exclude primary bronchial carcinoma in the majority
Serology combining IgA with early antigen serology will
(PCR) or in situ hybridization, techniques which have sensitivity
to detect the virus in FNAC.11
of patients with squamous histology and must not
also provide a high degree of sensitivity and specificity
be
when type III nasopharyngeal carcinoma is suspected.
overlooked.
Anatomical
imaging
with
computed
tomography (CT) and/or magnetic resonance imaging
[**/*]
(MRI) of the head and neck is the next diagnostic stage
Genetic alterations in apparently normal tissue from
of the process and may assist in directing subsequent
putative primary sites should be identical to those from a
biopsy.
metastatic lymph node and can be defined by micro
It
is
also
important
to
undertake
imaging
before biopsy, because subsequent swelling and inflam mation
may
confound
interpretation.
Those
centres
satellite identification. This technique has been used
successfully by Califano et al.12 in which 10 of 18 patients
with easy access to PET/CT may choose to acquire this
demonstrated
information at this stage before biopsy. This is discussed
apparently benign mucosa from surveillance biopsies.
identical
molecular
abnormalities
in
in greater detail under Positron emission tomography
The technique may prove clinically useful in patients with
below. [**/*]
an unknown primary squamous cell carcinoma and
2704 I
PART 17 HEAD Af\ID f\IECK TUMOURS
warrants further assessment. Cytomorphological charac teristics,
such as monolayered papillary
fronds
with
intranuclear cytoplasmic inclusions in thyroid papillary
patients studied had abnormalities on PET scans in terms of locoregional disease and distant metastases in
23 and 6
percent, respectively. I? Similar conclusions were drawn by
carcinoma; large, polygonal, keratinized cells with a low
Bohuslavizki et al.1s in a study of
nuclearlcytoplasmic ratio in perioral cancers; and numer
Sixteen out of
28 patients with CUP. 28 patients showed increased tracer uptake
ous naked nuclei with marked lymphocytic infiltrates in
corresponding to potential primary tumour sites. Of
nasopharyngeal cancer could possibly be utilized for
these, nine tumours were found suggesting that approxi
presumption of primary site in cases of CUP. In this retrospective
review
of
133 cytologically
diagnosed
carcinomas, the accuracy rate of presumption of primary sites was
100 percent in thyroid papillary carcinoma (6/6), 83 percent in perioral cancer (24129) and 77 percent in nasopharyngeal cancer (26/34), but low in other malig nancies.13 [H]
mately
a
third
of
patients
may
benefit
from
the
procedure. IS Wong et al.19 reported treatment-related benefits of FDG-PET scans in
9 out of 17 patients (53 percent) with CUp.19 Of particular concern, in one
series reported by Greven et a1.20 the apparent false positive rate was as high as
46 percent which could have
significant implications should the technique be used to select treatment options. Higher false-positive rates in some studies could be attributed to the fact that the PET scans may have been performed after the biopsy.17
POSITRON EMISSION TOMOGRAPHY
[H]
FDG-PET has been summarized as having a positive P ositron emission tomography using 18-fluorodeoxyglu
predictive value of
cose is a promising disease detection modality because of
of
56 percent, a negative predictive value 86 percent and an overall accuracy of 69 percent.21
its ability to differentiate between tissue with a high rate
Therefore,
of metabolism, such as tumour, inflammation or infec
imaging, examination under anaesthesia and biopsy of
following clinical
tion, and tissue with a low metabolic rate, for example
possible
scar tissue. The technique has been cited as being more
additional detection of an occult primary carcinoma.
primary
sites,
examination,
PET may
offer
anatomical
only
limited
sensitive for detecting occult tumour than anatomical
However, the benefit of FDG-PET scans is not only
imaging with CT or MRI
limited
(Figure 198.1). However, the
data are heterogeneous and results can be misleading and
to
identifying
a
primary carcinoma,
as
the
detection of advanced locoregional disease or distant
are frequently contradictory. Detection rates for FDG
metastases can significantly alter management in terms of
PET following conventional procedures, including anato
modifying radiotherapy fields from unilateral to contra
mical imaging, are nevertheless extremely variable with
lateral neck or changing treatment intent from radical to
reports ranging from 14 to almost
50 percent.14,15 This
, palliative. I? 19 Nevertheless, the technique must not be
wide range can possibly be attributed to small sample
dismissed and further technological developments, in
sizes, varied definitions of CUP and the variable extent of
particular higher resolution scanners and the advent of
conventional radiological imaging used in the studies.
PET-CT, may prove to offer greater sensitivity, selectivity and specificity. Fakhry et al.22 reported a prospective
[H/*] Fogarty et al.16 have reported a series of
21 patients
study of
20 patients with CUP who underwent PET-CT
with CUP who underwent FDG-PET. A potential primary
scan, and concluded the sensitivity and specificity of PETI
tumour was detected by the procedure in eight patients,
CT to be
although none was considered unequivocally PET-posi
fusion imaging has also significantly reduced the number
tive. Only one case was pathologically confirmed, in five
of false-positive results
this could not be confirmed, of which three had no
At
70 percent.22 Additionally, the use of PET-CT
present
in
the
(Figure 198.1).23 [H] UK,
the
expense
and
limited
evidence of primary disease within a subsequent two-year
availability of PET scanning precludes it as a routine part
period. The authors concluded that FDG-PET did not
of the diagnostic work up for CUP. However, in an ideal
add significantly to conventional comprehensive investi
world, all patients undergoing investigation should have
gations as previously discussed.16 Conflictingly, a similar
PET-CT prior to endoscopy and biopsy. Once the biopsies
sized prospective study performed at Christie Hospital,
have been carried out, a PET scan would need to be
drew differing conclusions recommending routine use of
delayed for approximately six weeks to prevent false
FDG-PET scans in the management of patients with
positive results at the site of the previous biopsies. Such a
unknown head and neck primary carcinoma. In this
delay is not acceptable in the time course of the patient's
study, a primary site was identified in
treatment.
with CUP
9 out of 25 patients
[H1*]
on the basis of positive FDG-PET scans.
Although only
42 percent of patients had a positive PET scan, 33 percent had a true positive PET scan confirmed by
histopathology (three out of nine patients). The rate of true negative scans was very high at 88 percent
(14 out of
16 patients). Although an occult primary was detected only in a small number of patients, nearly a third of the
CLINICAL MANAGEMENT OF CARCINOMA OF UNKNOWN PRIMARY Despite exten;ive investigations, a primary tumour will nevertheless remain elusive in approximately
60 percent
Chapter 198 Management of the patient presenting with neck lymphadenopathy and an unknown primary carcinoma I
Figure 198.1
2705
The patient had presented with a mass in the left s i d e of the neck that had been present for almost 12 months. FNA
had shown it to be metastatic squamous cell carcinoma. He underwent tonsillectomy as a chi Id and no abnorma lity was visible on clinical examination.
(a)
The primary was not clearly apparent on the axial (T. (b) Axial and (c) coronal PET -CT show that the site of
the primary was in the tonsil remnant; (d) PET uptake in cervical nodes.
of cases. Management of pa t ien t s with CUP presents a clinical dilemma due
to
the lack
of evidence-based
management strategy for patients
with CUP is yet to be
defined. Therapeutic options include excision biopsy of
treatment, exclusion of most patient s from randomized
involved lymph
clinical trials and rarity of the disease. Controversies in
chemoradiotherapy or radiotherapy with salvage neck
the management of patie n ts with CUP, range from types
dissection.
of neck dissection to be performed, fields of radiotherapy
(EORTC-24001-22005) looking into the selection of the
The
nodes, neck dissection, radiotherapy, only
randomized
phase
III
study
(whether ipsilateral neck only, whole neck or additional
target volume for postoperative radiotherapy in patients
panmucosal fields), the role of chemotherapy, to sequen
with cervical lymph node metastases from
cing of ra d io t hera py and neck dissection. The optimal
July 2004 with very poor a ccrual [*J .
CUP closed in
2706 I PART 17
HEAD AND I\lEeK TUMOURS
SURGICAL MANAGEMENT OF THE NECK
Modified radical neck dissection is the most commonly used technique for the management of nodal metastatic disease. The procedure can be considered definitive if the histological specimen reveals no more than two involved nodes without evidence of extracapsular spread. Postoperative radiotherapy will then be unnecessary and an active surveillance policy for the occult primary carcinoma can be safely adopted, avoiding definitive treatment to putative mucosal sites and consequent treatment-related morbidity. [**/*] There is evidence to support the use of radiotherapy alone for management of the neck following the excision of a single metastatic node without recourse to neck dissection, with 88-100 percent control rates quoted in the literature?4,25 A Canadiari retrospective study of 61 patients with CUP compared outcomes after panmucosal radiotherapy, preceded by either biopsy (67 percent) or neck dissection (23 percent). There was no statis tically significant difference in eight-year overall survival between patients who had biopsy (FNAC or excision biopsy) or neck dissection (64.8 and 67.6 percent, respectively). They concluded that definitive radiotherapy to the neck and potential mucosal sites is effective in achieving good local control rates, whether preceded by neck dissection or not.26 A retrospective review of 106 patients with CUP demonstrated a reduction in mucosal and neck recurrences with the addition of radiotherapy, but failed to show a survival improvement.3 Coster et al.27 reviewed records of 117 patients with CUP and concluded that patients with N1 neck disease with no extracapsular extension can be managed by surgery alone. However, they recommended postoperative radiotherapy for pa tients with a pathologic stage N2 or higher or with evidence of extracapsular extension.27 [**] The authors would advise definitive modified neck dissection following excision biopsy in all cases, because recurrent disease in the irradiated neck usually presents as a diffuse tumour infiltrate for which successful salvage rates are low. An exception to this would be where the nodes are small « 2 em) and where there is no evidence of extracapsular spread. For N2 and N3 disease, the current consensus is for dual modality therapy, involving both neck dissection and radiotherapy. Both neck dissection followed by postoperative irradiation to the neck and radiotherapy followed by an interval neck dissection are acceptable. [**/*]
IRRADIATION LIMITED TO THE INVOLVED !\IECK
The most commonly used techniques employ either an anterior radiation field or anterior-posterior parallel opposed fields to encompass the clinical target volume of the lateral neck nodal compartments and to exclude the midline structures, thereby reducing mucosal toxicity.
Sinnathamby et al. 28 reported their series of 69 patients treated between 1983 and 1992. Sixty-three patients were treated with radical radiotherapy, 23 by radiotherapy alone and 40 with surgery and postoperative radio therapy, only four patients having surgery alone. The actuarial incidence of primary mucosal occurrence at ten years was 30 percent and appeared unrelated to whether or not the mucosa was irradiated. This value is equivalent to the ten-year risk of second primaries in patients with successfully treated head and neck cancer. Their five-year overall survival was 36 percent, which is consistent with most other series?8 A retrospective study of 144 patients by Wier et al.25 compared 85 patients receiving radio therapy to the neck only, with 59 patients treated with irradiation to both neck and mucosa. Primary tumours developed in only 8 percent of the former group and in 2 percent of the latter. While they reported a trend towards improved survival in those receiving neck and mucosal irradiation, the difference was no longer evident once the extent of nodal involvement was taken into account. Their overall five-year survival rate was reported as 41 percent with no significant difference between the two groups. The authors cautiously suggest that radiation to the involved nodal region alone may be adequate. These data corroborate the earlier much quoted work from the Middlesex Hospital, London reported in 1990, in which 83 unselected patients at that centre over a 30-year period were treated with radiotherapy to the neck alone, 58 with radical intent for which the overall five-year survival was 40 percent. Only 7 percent subse quently developed a primary tumour above the clavicles, supporting the argument for avoidance of routine panmucosal irradiation in this circumstance?9 [**]
MANAGEMENT OF THE PUTATIVE PRIMARY SITE
When there is a clear indication for postoperative irradiation to the neck, the choice of management strategy becomes considerably more challenging. Irradia tion of lateral neck structures will largely preclude irradiation of subsequently occurring primary sites, particularly those which lie in the midline because there will be considerable overlap with radiation fields required to treat a primary site. The management choice will be either to treat putative mucosal sites by panmucosal irradiation, or alternatively by selective mucosal irradia tion, using techniques which will also include the involved neck, or alternatively to irradiate the involved neck alone. Postoperative neck irradiation requires a dose of 60-63 Gy over 6-6.5 weeks, or the biological equiva lent/o is well tolerated with mild acute toxicity primarily short-term skin erythema and confers a low risk of associated long-term toxicity. [****/***] Panmucos'al irradiation requires doses of 50-60 Gy over five to six weeks encompassing nasopharynx,
Chapter 198 Management of the patient presenting with neck lymphadenopathy and an unknown primary carcinoma
oropharynx, hypopharynx and larynx, and in contrast causes considerable morbidity.31 Acute mucosal toxicity is usually severe and patients frequently require enteral support with nasogastric or percutaneous endoscopic gastrostomy (PEG) feeding. Symptomatic xerostomia is unavoidable with conventional two- or three-dimensional CT treatment planning and results from irradiation of both major and minor, mucosal, salivary glands. When the probability of an occult nasopharyngeal tumour is low, selective mucosal irradiation avoiding this site can be employed and reduces mucosal dryness, although xerostomia may nevertheless remain significant. [**] At present, all data are retrospective and there are no completed randomized trials. Published reports can be broadly divided into those which propose elective panmucosal irradiation and into those which suggest that avoidance of irradiation to mucosal sites is a safe alternative incurring significantly less morbidity. The Danish Society for Head and Neck Oncology reported their series of 277 patients from five oncology centres with unknown primary carcinoma treated radi cally between 1975 and 1995. The majority, 224 patients (81 percent), received panmucosal irradiation, 26 patients (10 percent) ipsilateral neck irradiation and 23 patients (9 percent) neck surgery alone. The five-year actuarial risk of emergence of the primary was significantly higher in the surgery-only group (54 percent), compared with those treated with surgery and radiotherapy (15 percent). When comparing panmucosal with 'neck-only' irradiation, the five-year actuarial control rates were 51 and 27 percent, respectively, although the number of patients was small in the latter group? A smaller study from Reddy et al.32 compared 36 patients treated with panmucosal and bilateral neck irradiation with 16 patients who received irradiation to the ipsilateral neck alone. Occurrence of a primary tumour at five years was 8 versus 44 percent, respectively, and contralateral neck node control 86 versus 56 percent, suggesting superior control rates for more comprehensive irradiation. Patient numbers are small; however, the study is noteworthy because electrons were used to treat the neck only, avoiding incidental irradiation of midline structures and to the contralateral neck, which can occur with photon (radiograph) beam techniques. Earlier reports from the University of Florida and from Institute Curie, Paris, have also alluded to the efficacy of mucosal radiotherapy for eradicating occult primary tumours, although neither included data from non irradiated patients.31, 33 [**]
RECENT ADVANCES
Intensity modulated radiotherapy (IMRT), a new techni que for delivering tumoricidal radiation doses to mucosal sites, along with permitting a reduction in dose to sensitive major salivary glands, is still in the early stages of development in the UK. Results with IMRT in patients
I 2707
with CUP have been encouraging with two-year survival exceeding 80 percent with acceptable toxicity.34 Other attempts to protect salivary glands with amifostine, a radioprotecting agent, while promising may become redundant if IMRT is effective and readily available.35 [**] Concurrent chemoradiotherapy is now a standard nonsurgical management option for patients with locally advanced head and neck cancers. The role of chemo radiotherapy for patients with CUP has not been fully established. Shehadeh et al.36 reported a benefit in locoregional disease control with postoperative radio therapy with concurrent cisplatin (100 mg per m2 given three weekly) in 37 patients with CUP. The majority of patients in this cohort had greater than N2b disease (71 percent) and extracapsular spread (68 percent). After a median follow-up of 42 months, regional and distant recurrences were noted in 5 and 11 percent of patients, respectively. Substantial acute and late morbidities were seen, particularly incidence of grade 3/4 mucositis III 46 percent and xerostomia in a third of patients. [**]
KEY POINTS •
•
•
•
•
•
•
CUP is an unusual clinical scenario and accounts for only 2-3 percent of patients with head and neck malignancy. Involvement of nodal levels I-IV is almost exclusively associated with occult upper aerodigestive tract primary squamous carcinoma, with level II being the most common site. CT, MRI or FDG-PET scans should be performed prior to biopsy in order to guide subsequent biopsy and to avoid imaging artefacts or false-positive results with PET scans. The only tumour marker of clinical value is Epstein-Barr virus (EBV) serology. Positive EBV serology should be followed on by multiple biopsies of the nasopharynx in the search for an occult primary. The usefulness of FDG-PET scans in the diagnostic pathway of patients with CUP has been reported with varying degrees of success. Careful analysis of all available data reveals that FDG-PET can alter management in up to a third of patients with CUP. There is good evidence to recommend ipsilateral tonsillectomy, but the evidence for tongue base and nasopharyngeal biopsy is less compelling. Definitive modified neck dissection should be performed in all patients with CUP after either FNAC or biopsy.
2708 •
•
•
•
•
I
PART 17
HEAD AI'JD NECK TUMOURS
Panmucosal radiotherapy has demonstrated a reduction in primary site occurrence with no improvement in overall survival. Associated morbidity is quite high, in particular grade 3/4 mucositis and xerostomia. Radiotherapy-related morbidity may be reduced if selective mucosal irradiation is undertaken, most commonly by exclusion of the post-nasal space within the clinical target volume in patients who present with nodal involvement of levels I-IV. For panmucosal radiotherapy, a dose of 50 Gy in 25 daily fractions, five fractions per week, is sufficient for control of occult primary disease. Nodal stage is the most important risk factor for local relapse. Benefit of IMRT and chemoradiotherapy in patients with CUP is still investigational.
elective mucosal irradiation (EMI) and its associated morbidity? The optimal field for elective irradiation is yet to be defined - whether selective irradiation of the ipsilateral neck is adequate, or is panmucosal or selective mucosal irradiation required for an improvement in disease-free survival and overall survival?
>- The role of IMRT and chemoradiotherapy for management of patients with CUP still needs prospective evaluation.
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*
2.
Best clinical practice
primary tumours. Results from a national survey by the Danish Society for Head and Neck Oncology. Radiotherapy
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Ellis ER, Mendehall WM, Rao PV, McCarty PJ, Parsons JT, Stringer SP et al. Incisional or excisional biopsy before
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Mack Y, Parsons H, lVIendenhall WIVI. Squamous cell carcinoma of the head and neck: management after
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Blind biopsies ( or perhaps PET-directed, if increased
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Iganej S, Kagan R, Anderson P, Rao A, Tome M, Wang R et al. Metastatic squamous cell carcinoma of the
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]:"- Is definitive neck dissection sufficient for patients with N1 and N2a disease, avoiding the need for
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Mendenhall WM, Mancuso AA, Parsons JT, Stringer SP, Cassisi NJ. Diagnostic evaluation of squamous cell carcinoma metastatic to cervical lymph nodes from an unknow n head and neck primary site. Head and Neck. 1998;
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Kulapaditharom B, Boonkitticharoen V, Kunachak K.
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Glynne-Jones RG, Anand AK, Young TE, Berry RJ. Metastatic carcinoma in the cervical lymph nodes from an
JJ et al. Should FOG-PET scanning be routinely used for
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Peters U, Goepfert H, Ang KK, Byers RM, Maor MH,
Bohuslavizki KH, Klutmann S, Sonnemann U, Thoms J,
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Bataini JP, Rodriguez J, Jaulerry C, Brugere J, Ghossein NA.
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Coster JR, Foote RL, Olsen KD, Jack SM, Schaid DJ, De
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2710 I PART 35.
TUMOURS
17 HEAD
Bennett el, Economic
0, Stinson
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Glatzel M, Buntzel J.
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19 Metastatic neck disease
JOHN C WATKINSON
Introduction
27'1
Surgical anatomy
2712
Natural history and evolution of neck disease
2712
Chemoradiation
2729
Organ-specific drainage
2713
Quality of life
2730
Tumour biology
2714
Neck dissection
2731
Radiotherapy in the management of metastatic neck
2728
disease
Clinical staging
2719
Key points
2749
Clinical examination
2720
Best clinical practice
2750
Treatment of metastatic disease
2722
Deficiencies in current knowledge and areas for future
The difficult neck
2727
Contra indications to neck dissection
2727
2750
research
2750
References
SEARCH STRATEGY AN D EVIDENCE-BASE The data in this chapter are supported by a Medline search (as well as the websites Cancerlit and CancerNet) using the keywo rds neck mass, head and neck neoplasm, imaging, fine needle aspiration cytology and focussing on diagnosis) surgery and management. The evidence in this chapter is mainly levels
3/4 with some level
2 evi dence. The clinical
recommendations are predominantly Band C.
INTRODUCTION
carcinoma in the neck in relation to when to treat) how m uch to treat and which modality to use. It reviews the
One of the most important progn ostic factors in head and
evidence in the literature) together with tumour biology,
neck cancer is the presence or absence, level and size of
the various rationales for assessment, as well as methods
metastatic neck disease. Many tumours within the head
for elective and therapeutic treatment, and particularly
and neck will at some stage metastasize to lymph nodes
focusses on quality of life issues. The management of
and there are a number of factors that control the natural
tumours other than squamous cell carcinoma (i.e. salivary
history and spread of disease.
gland and thyroid tumours) is not discussed.
Controversies surrounding the management of malig nant
neck
di sease
literature over the
have
continued
unabated
in
the
last 50 years or so but, unfortunately,
Literature assessment
due to the lack of any randomized controlled trials, evidence is sparse to confirm or refute which treatments
The majority of papers published in the li terature which
at what time and in which combination are best in any
relate to head and neck squamous cell carcinoma are
particular situation Currently, there are no standardized
retrospective and, because of this, many of the con
management protocols for metastati c neck disease.
troversies that existed
.
This chapter outlines the major c linical controversies regarding the management of metastatic squamous cell
Retrospective
50 years ago have yet to be resolved.
data
suffer
from
bias
since
in
a
nonrandomized study, treatment is controlled by factors
2712 I PART 17 HEAD AND NECK TUMOURS
relating to the pa tient, the tumour and treating physician.
head and neck cancer, but there is little evidence to
The site and extent of the tumour are important, as are
support this statement.
social and medical factors as well as informed consent.
It is possible to predict the site of a primary tumour
from institution
to institution and combination therapy is applied in
based upon the distribution of cervical metastases and 2 this was done by Lindberg in 1972 in a clinical study. It is
various ways and at various times. Data collection may
the accepted rule that patterns of subclinical microscopic
Diagnostic and treatment expertise varies
1981,
require perusal of the notes, which are often incomplete,
metastases follow a similar distribution and in
and studies that report different end points are not strictly
following Lindberg's work, the Memorial Sloan-Kettering
comparable. For example, survival is the usual end point
Hospital published a number of levels or regions within
reported by head and neck surgeons but when studying
the neck which contain groups of lymph nodes represent
e fficacy
type
of neck
treatment,
with regards to the control of neck disease, it is important
sites for metastases from head and (Figure 199.1)? These five levels have been described in Chapter 137, Surgical anatomy of the neck. Levels 1,2 and 5 can be further subdivided into (a)
that the study evaluates previously untreated necks, the
and (b).
the
of any
locoregional
control is more important.
ing t h e
first
echelon
neck primary sites
When assessing any single or combination treatment
method of treatment is standardized and the primary site
The fac tors which affect the pattern of spread of
is controlled. In addition, any positive nodes should be
malignant disease to the neck depend upon both patient
verified by rigorous histological examination. Prospective
and tumour factors. The site of the primary tumour is
randomized
importan t with some sites having a higher incidence of
therapeutic
trials
control
for
all
these
variables, but unfortunately they are notable by their absence in the current head and neck literature.
SURGICA L ANATOMY The anatomical divisions of the neck, as well as the fascial neck spaces, the head and neck lymphatics and the various lymph nodes are discussed in Chapter
137,
Surgical anatomy of the neck. Examination of the neck is discussed in Chapter
138, Examination and imaging of
the neck.
(0)
(b)
NATURA L HISTORY AND EVO LUTION OF NECK DISEASE Factors which affect the natural history of neck disease are the size and
thickness of the primary tumour, the
laterality of the tumour and whether or not there has been any previous treatment to affect patterns of spread. 1 The key factors are: •
tumour site;
•
tumour size;
•
tumour thickness;
•
previous treatment;
•
tumour recurrence;
•
tumo ur histology;
•
tumour immunology.
Perineural
and
perivascular
(e) Figure 199.1
Accessory nerve The lymph node levels of the neck. Level I,
submental and submandibular lymph nodes; level II, cervical jugular chain nodes above the level of the hyoid. Further divided into Iia and lib by their relationship to the accessory nerve;
invasion,
the
degree
of
level III cervical jugular chain nodes from the level of the hyoid
tumour differentiation and recurrence at the primary site
to the level of the cricoid; level IV, cervical jugular chain nodes
are all important. It has also been shown that those
from the level of the cricoid to the suprasternal notch; level V,
tumours with an infiltrating margin are much more likely
posterior triangle lymph nodes. Can be further divided into Va
to metastasize.
and Vb as to whether they are above or below the omohyoid
With regards to host factors, few would argue that the
muscle; level VI. central compartment nodes; and level VII,
immunological response of the host to the tumour is
su perior mediasti naI nodes. Not classified: retro pharyngeaI and
crucial in determining spread and ultimately prognosis in
pa rapharyngeaI nodes.
Chapter 199 M etastatic n ec k d isease II
metastases, both palpable and otherwise, at presentation (Table 199.1).
It is important to realize that the above patterns apply to the nontreated neck. Once the natural history of the disease is altered, lymph node metastases can occur anywhere. This explains why the operation of selective neck dissection is only suitable in the previously untreated neck. An incision in the neck for a neck node biopsy can alter patterns of lymphatic drainage for up to one year following surgery. Further shunting of lymph with opening up of abnormal channels occurs when more extensive surgery and radiotherapy is undertaken, and once a lymph node is palpable and contains tumour there Table 199.1
T h e probabi l i ty of c e rvica l m etastases
(1\1)
re l a ted t o
p r i m a ry (T) s ta g i n g i n patie n ts w it h h ea d a n d neck sq u a m o u s ca rci n o m a .
Primary site F l o o r of m o u t h
T-Stage
NO%
1\11%
N2-N3%
T1
89 71 56 46 86 70 52 24 88 62 46 32 8
9 18 20 10 10
2 10 24 43 4 11 31 66 9
T2 T3 T4 Oral to n g u e
T1 T2 T3 T4
Retro m o l a r trig o n e
T1
Ante ri or fa u ci a l pi l l a r
T2 T3 T4
N a sop h a rynx
T1 T2 T3 T4
Soft pa l ate
T1 T2 T3 T4
Base of ton g u e
T1 T2 T3 T4
Tonsi l la r fossa
T1 T2 T3 T4
S u prag l ottie l a rynx
T1 T2 T3 T4
Hypopha rynx
T1 T2 T3 T4
Source: Lindberg
2
16 12 17 92 64 35 33 30 29 26 16 30 32 30 10 61 58 36 41 37 30 21 26
4 and Sessions and Picker.
19 16 10 2 18 21 18 11 12 9 6 0 12 26 11 15 14 23 8 41 14 18 13 10 16 25 18 21 20 26 15
20 33 50 82 72 80 78 8 24 39 56 55 56 52 76 30 54 52 76 29 26 40 41 42 49 54 58
2713
may be early shunting of cells to the contralateral neck. All these factors play a part in the management of neck disease.
ORGAN-SPECIFIC DRA I NAGE The nasopharynx, nasal cavities and sinuses drain via the junctional nodes into the upper deep cervical nodes (levels II and III), having passed through retropharyngeal or submandibular lymph nodes. The oropharynx similarly drains into the upper and middle deep cervical nodes, again either directly or via the retropharyngeal or submandibular nodes. Within these areas of deep lymph node collections in the neck, certain nodes can reach quite large proportions and some have specific names. There are 500 lymph nodes in the body and 200 of these are in the head and neck. The normal range in size is from 3 mm to 3 cm, but most nodes are less than a centimetre. Within the upper deep cervical nodes in low-level II or high-level III, the node is often called the jugulodigastric node and is situated within the triangle formed by the internal jugular vein, facial vein and posterior belly of the digastric muscle. It is important because it receives lymph from a wide area which includes the submandibular region, the orophar ynx and oral cavity. The jugulo-omohyoid nodes are situated at the junction between the middle and lower cervical group (low-level III/high-level IV) where the omohyoid muscle crosses the internal jugular vein and receives lymph from a wide area which includes the anterior floor of mouth, oropharynx and larynx. The oral cavity has a wide area of drainage and this is important because there is often free communication between the two sides of the tongue. This means that the normal acts of mastication and swallowing facilitate tongue massage and can promote both early and rapid lymphatic spread directly to low in the neck. The posterior parts of the oral cavity either drain directly into the upper deep cervical nodes (level II/III), or indirectly via the submandibular nodes in level lb. More anterior parts of the oral cavity and tongue also drain to these nodes but, in addition, may drain to the submental nodes (levella) or directly to the jugulo-omohyoid nodes (levels III/IV) low in the neck. Given the previous anatomical considerations, it is important to realize that may occur early in those contralateral neck tumours situated in or near the midline. Laryngeal is separated into upper and lower systems with embryological connotations with a division which occurs at the level of the true vocal cord. The supraglottis drains through vessels which accompany the superior laryngeal via the thyroid membrane to reach the upper cervical nodes (levels II/III). The lower system drains into the deep cervical nodes (levels III/IV) through vessels which pass through or behind the membrane and drain into the
2714
I PART 17 H EAD AN D N ECK TU M O U RS
prelaryngeal, pretracheal or paratracheal nodes (level VI) before reaching the deep cervical nodes. Because the vocal cords are relatively avascular, they have an extremely sparse lymphatic drainage and, as such, lymph node metastases from small carcinomas at this site are uncommon. The hypopharynx is similar to the larynx and both may have contralateral spread, particularly in those areas that are either close to the midline or have significant communications across the midline, such as the epiglot tis, posterior pharyngeal wall and postcricoid region. Drainage is to levels IV, VI and VII. Tumours in the oral cavity and pharynx have a higher incidence of metastatic disease at presentation than those in the larynx and this is important when treating these sites. The high incidence of occult metastases in tumours of the oral cavity, pharynx and, to a lesser extent, the supraglottic larynx forms the basis for selective neck dissection and assuming that the patterns of spread from tumour sites is applicable to subclinical microscopic metastases, the following rules apply. The first echelon lymph nodes for the oral cavity lie in levels 1, II and III. The first echelon lymph node levels for the larynx and pharynx lie in levels II, III and IV. The first echelon lymph nodes for the thyroid lie in the tracheo-oesophageal groove in level VI, the superior mediastinum (level VII) and in level IV. For the parotid gland, the first echelon lymph nodes are the preauricular, periparotid and intraparotid lymph nodes, along with those in level II, III and the upper accessory chain (level IV). For the submandibular and sublingual gland, the first echelon lymph nodes lie in levels 1, II and III.
T U M O U R BIOLOGY One of the crucial questions regarding lymph node tumour biology is whether or not lymph nodes represent a favourable site for tumour growth. The literature is divided on this and some papers suggest that once squamous carcinoma is established within the lymphatic system, tumour growth is difficult to arrest, but there are other reports that suggest that the regional lymph nodes are involved in effective tumourlysis.1 One important question that needs to be answered (and resolved) is if there is any benefit treating the regional lymphatic basin early (NO), or later on in the disease process (N +). Tumours do not have primary lymphatics so cancer cells are thought to gain access to the lymphatic system from the tumour periphery through gaps between the lymphatic endothelial cells. The spread of disease from the primary tumour to the regional lymph nodes occurs by passive transport within lymph. The afferent lympha tics join the marginal sinus in the cortex of lymph nodes and, at this point, cancer cells may lodge so that cellular division occurs first peripherally and tumour migration can then occur to involve the medulla.
Tokers described four distinct growth patterns of squamous cell carcinoma within cervical lymph nodes. Following the original cancerous deposits in the subcapsular sinus, growth within the affected node proceeds to a considerable extent before extranodal spread occurs. Ultimately, extranodal extension occurs by the direct penetration and destruction of the capsule, or by the arrest of further underlying capsular or juxtacapsular lymphatics. 2. Extranodal spread occurs at an early stage in the genesis of tumour growth within the node. 3. A less common pattern involves the deposition of a malignant embolus within the subcapsular sinus, together with the simultaneous arrest of tumour within capsular or juxtacapsular lymphatics. This results in the coincident and equivalent proliferation of cancer both within and outside the node. 4. The least common growth pattern shows capsular or juxtacapsular emboli with no intranodal cancer. This is important to realize since, in some instances, extranodal spread can occur much earlier in the natural history of the disease process and, as such, may be important when undertaking conservation neck surgery. 1.
Metastatic involvement of various lymph node regions usually progresses from superior to inferior in an orderly fashion, but it has been shown that in some situations lymph node groups can be bypassed even in the normal lymphogram. 6 Once tumour cells arrive at a draining lymph node, they can proliferate, die, remain dormant or enter the circulation through nodal blood vessels. The process of metastasis is not a random phenomenon, although random events may be important. Paget's seed and soil hypothesis was an attractive one and although largely disproved, a number of important properties have recently been assigned to tumour cells or metastatic seeds and these include cell growth, chemotaxis, immunological, metabolic and hormonal factors. Similar host environ mental (soil) factors include tissue and stromal environ mental, hormonal, inflammatory and immunological responses and the presence or absence of vital nutrients. There are several stages of metastases via lymphatic pathways. Premetastatic invasion of the epithelial basal lamina of the primary tumour is followed by subsequent encroachment, penetration and translocation of cells through a lymphatic. This is followed by intranodal settling, proliferation and destruction of the lymph node. Secondary metastases to other lymph nodes soon develop, although their occurrence is not always accompanied by the destruction of the primary echelon node. Metastatic squamous cell carcinoma within a cervical lymph node can stimulate the stroma in a variety of ways, and a number of histological and immunological patterns have been described. 1
Chapter
From here, efferent channels leave the hilum to Jom the terminal collecting trunks (the right and left lymphatic ducts), and then drainage is into the venous system. However, there are other routes whereby cancer cells can access the bloodstream and these include entering directly from a node, or alternatively lymph nodes may be completely bypassed through collateral channels and this mechanism is enhanced by local obstruction due to metastases, reactive hyperplasia and sinus histiocytosis. This process may lead to fast-tracking and the phenomenon of skip metastases. This means that in some patients there may not be an orderly progression of metastases down the neck. Communications between the vascular system can therefore be defined as lymph aticovenous, venous-lymphatic and inter-lymphatic. Because of this, it is extremely difficult to discriminate between which metastases occur via the bloodborne or lymphatic routes. Vascularization of tumours usually occurs when growths are greater than 0.1-1 mm in size and following this, rapid rates of neoplastic growth and increased rates of vessel invasion can occur. Animal studies have shown that tumours in the range 2-4 g release up to 4 x 106 cells per gram of tumour tissue per day. 7 These may be released as single cells, more often as cell clumps and more often still as a thrombus fragment containing tumour cells. It is now generally accepted that considerable fragments of tumour are required to cause bloodborne metastases and the success of implantation is determined by both tumour and host factors. When tumour cells reach the lymph nodes, it appears that not all nodes act as a filter barrier and that some tumour cells pass directly through. Various experimental studies have shown that tumour cells are able to pass through lymph nodes even when they are filled with metastatic tumour, others have shown that cancer cells can transverse nodes that themselves remain free of tumour, implying that nodes can be an ineffective barrier and some authors have suggested that regional lymph nodes have a reasonable constant holding capacity and that above that threshold, all other tumour cells pass to efferent channels and then into the general circulation. 1 The exact role of the regional lymph node system in the spread of head and neck squamous carcinoma has yet to be fully defined and current evidence suggests that lymph nodes are not simple mechanical barriers but are involved in conferring anti-tumour immunity, and that some lymphocytes are cytotoxic to cancer cells. The survival of cancer cells in the regional lymph node is unlikely to be an all or none phenomenon and cell destruction probably does occur in lymph nodes but only when the tumour burden is small. The mechanism for this is probably immunological and there is some evidence that after exposure of a regional lymph node to an antigenic tumour, T lymphocytes may be specifically sensitized and activate macrophages via lymphokines. Subsequent recirculation of long lived T cells can then bring distant lymph nodes into the immune response.
1 9 9 M etasta tic n eck d isease I
2715
The response of these lymph node cells to the tumour may also change over time and vary based on their location with respect to the primary growth. Work by Schuller8 has shown that there is a dynamic interaction when tumour emboli encounter lymphocytes within the regional lymph nodes of patients with head and neck cancer. This does raise the possibility whether tumour specific cytoxic T cells could be generated from draining lymph nodes which then might prove useful in Im munotherapy. Further work is currently underway.
M o l ecu l a r methods for the d etection of m etastases Molecular assays are estimated to be over 500 more times more sensitive than histological methods for the detection of cancer calls. One of the many goals of translational research in cancer has been to refine disease prediction by detecting tumour-specific molecular alterations in histo logical normal tissues, either at resection margins or in regional lymph nodes. The feasibility of this sort of strategy was demonstrated in an elegant study by the Sidransky laboratory at Johns Hopkins University in 1995.9 This study, using a phage-clone technique, identified tumour-specific p53 mutations in six of 28 lymph nodes harvested from five patients which were histologically negative for metastatic disease, thereby upstaging the disease in four patients. Although highly specific, this technique is technically demanding and labour intensive and, to date, has not been widely adopted in clinical practice. A newer and highly sensitive oligonucleotide-mediated mismatch ligation assay has since been demonstrated in the detection of cancer cells in histologically negative regional lymph nodes in colorectal and lung cancer. 1 0, 1 1 Recently, mitochondrial DNA mutations have been shown to be present in head and neck and other tumours. 1 2 Identification of these mutations in regional lymph nodes may have potential for molecular staging in the future. The presence of regional lymph node metastases acts as an indicator of the ability of the primary tumour to metastasize both locally and to distant sites, rather than acting as an instigator of distant metastases on their own. This is because positive lymph node involvement indicates a host response which is permissive for the development of metastases, not only in the regional lymph nodes but also to distant sites. Therefore, the degree of lymph node involvement should be regarded as an indirect index of the systemic tumour burden. Having accepted this hypothesis, the removal of regional lymph nodes then serves as a biopsy staging procedure to ascertain whether or not metastatic disease is present, and therefore to identify high risk patients who might benefit from systemic adjuvant therapy. This means that, like breast cancer, tumour-free survival depends more on the biology of the tumour present at the operation rather that
2716
I PART 1 7 H EAD A N D N ECK TU M O U RS
the extent of surgery and that in the field of head and neck cancer, elective neck dissection would not be expected to be a useful therapeutic manoeuvre for decreasing metastatic potential. This explains why patients with positive lymph nodes in head and neck cancer have approximately a 50 percent decreased chance of survival when compared with those who are node negative. It has long been recognized that systemic spread can occur early in many solid tumours and this includes head and neck cancer. The question that one must ask is - 'if cancer is a systemic disease, how can cure ever be effected?' Followers of the traditional Halstead School of Head and Neck Surgery would argue that early radical surgery to the neck is justified because those patients who have a large number of occult positive nodes fare better since these nodes are discovered earlier. This philosophy is now being questioned with regard to locoregional disease being cured with local treatments (surgery and radiation) , since distant metastases are now a significant problem. Recent advances in locoregional control mean patients are now living longer only to die more frequently of second primaries or distant metastases. Overall survival has not changed. The main arguments for prophylactic elective node treatment assumes that regional lymph nodes are not the only effective barriers to tumour cells, but also represent further sources of disease dissemination with regard to distant metastases. It is now well recognized that metastatic lesions do have the ability to metastasize. I It is clear in the literature that the role of the regional lymph node in head and neck squamous carcinoma is very important but its exact role will continue to remain controversial. The arguments put forward for retaining regional lymph nodes that are free of tumour in order to maintain systemic tumour immunity may be a simple one and that the subsequent initiation of immunity by the regional lymph nodes (if present) is probably dependent upon the specific antigenicity of any one individual tumour and other, as yet to be defined, tumour-host interactions. The evidence in the literature seems to suggest that if malignant tumour cells have reached the regional lymph node and that a host defence response has been initiated, then by the time the tumour becomes clinically apparent, elective treatment of the regional lymph nodes will probably not affect overall tumour control and survival. I
Tu mour metastasis Tumour metastasis is a complex process which involves many different interactions between the tumour and its host and is influenced by a number of humoral, endocrine, cellular, metabolic and nutritional factors. Metastases involve the release of cells from the primary tumour and subsequent dissemination to distant sites, arrest in the microcirculation of organs, extravasation and
infiltration into the stroma of those organs and survival and growth into new tumour colonies. For a successful metastasis to take place, tumour cells must go through all these steps and the subsequent outcome depends upon a variety of both host and tumour factors. Historically, metastatic potential has been correlated with the primary tumour and includes size, site and differentiation. Current research suggests that the success of the metastatic process depends upon the selective emergence of a pre-existing subpopulation of cells that have special properties to allow them to survive for this length of time along with the difficult process of metastasis. Fidlerl3 observed that 24 hours after entering the circulation, fewer than 1 percent of injected cells was still viable and less than 0.1 percent of the cells subsequently survived to produce a metastasis. The mechanism for invasion of local tissues is not known, but there is a strong correlation between the ability to produce spontaneous metastases and the possession of high levels of type IV collagenase. Treatment modalities can effect tumour-host equili brium in unpredictable ways and these include the following: • •
•
• •
surgery; chemotherapy; radiotherapy; trauma; wound infection.
Surgery can undoubtedly mechanically alter the local regional tumour environment. Considerable gaps between lymphatics mean that collateral channels form, and the ability to do this relates to the consistency of connective tissue through which the lymphatics must grow. These mechanical effects can alter patterns of lymphatic metastatic spread and divert lymph flow to the contra lateral neck. Surgical scarring can trap tumour cells, although this may not always ultimately lead to established local recurrence. I It seems sensible to suggest that gentle handling of cancer tissues may decrease the amount of exposure that a surgical wound has to free cancer cells and as such minimize the potential for any growth. Chemotherapy is immunosuppressive and both it and radiotherapy have proven carcinogenic effects with regards to increasing the risk of secondary neoplasia. Radiation therapy has not only a number of well recognized local effects, but also systemic ones which include effects on the lymphatic system and tumour growth. There is evidence in the literature that the immune response is compromised following radiation to the head and neck. I, 14 Lymphoid tissue and circulating small lymphocytes are extremely radiosensitive and very small doses of radiotherapy (as low as 2.5 Gy) may produce a detectable decrease in the peripheral lympho cyte count. IS Suppresser T cells are also thought to be particularly radiosensitive. Radiation is associated with changes in the regional lymph nodes and lymphatics in •
Chapter
general, so within a few days of radiotherapy starting, there is a decrease in the numbers of lymphocytes within lymph nodes and thickening of the walls of both lymph nodes and blood vessels is noted. Some of these changes explain why previous radiotherapy can cause lymphatic obstruction and shunting of lymph both into the subdermal vessels and also to the contralateral neck. It becomes clear from the above discussion that the spread of head and neck cancer to the regional lymph nodes indicates an aggressive tumour and although this spread may occur in an orderly fashion, skip metastases do occur and that within the lymph node itself there are structural and immunobiological mechanisms that may effect tumourlysis, but that in a certain proportion of cases, systemic spread occurs early. This can take place by lymphaticovenous or haematological communication. These processes of spread and tumour arrest can be affected by previous treatment and as the systemic effects of multimodality head and neck cancer therapy are taken into consideration, both the number and the complexity of modalities that are used become ever more important.
Exa m pl e of a nother sol id tu m o u r - breast ca ncer The classical Halstedian concept of treating a solid tumour is based on the fact that cancer spreads in an orderly defined manner, that tumour cells travel the lymphatics to lymph nodes by direct extension which would support en bloc resection and that a positive lymph node indicates tumour spread which can cause distant disease. 1 This theory also holds that regional lymph nodes are barriers to the passage of tumour cells, and are therefore of anatomical importance so that spread of tumour by the bloodstream is insignificant. The final part of the concept states that the tumour is autonomous of its host, that operable breast cancer is a locoregional disease (and not a systemic one) and as such, the extent of surgery is the major factor which influences patient outcome. Alternative subsequent views opposed this hypothesis and stated (already discussed) that there was no orderly pattern of tumour cell dissemination and that cells travel lymphatics by embolization, thereby challenging the classical view of en bloc dissection. 1 In addition, the view was that regional lymph nodes are of biological importance, that they are ineffective as barriers to tumour cell spread and that a positive lymph node is an indicator of a tumour-host relationship which permits the devel opment of a metastasis rather than instigating the spread of distant disease. Finally, the bloodstream is probably of considerable importance in tumour spread and that complex tumour-host relationships affect all aspects of the disease. The final view was that operable breast cancer is . a systemic disease and, as such, any variation in locoregional therapy was unlikely to affect survival substantially.
1 9 9 M etasta t i c n eck d i sease I
2717
These views were sustained by a trial looking at patients with early breast cancer without clinical evidence of regional lymphadenopathy and who were randomized to receive radical mastectomy, total mastectomy or total mastectomy plus postoperative locoregional radiation. 1 6 After five years, the incidence of distant metastases in the three groups (i.e. those who had nodes removed, irradiated or untreated) were similar and overall survival did not differ significantly in frequency or in time from operation to death. Forty percent of the patients who had radical mastectomy were node positive and because the treatment groups were equivalent, it would be expected that approximately the same number of women subjected to total mastectomy alone would also have had positive nodes that were untreated. Based on original Halstedian concepts, such retained positive nodes could be the source of further tumour dissemination and distant metastases yet, as previously stated, the incidence of this in the three groups was similar. Further trials showed that in pathological node positive patients who had surgery and then received chemotherapy, there was a significant increase in the disease-free interval and this represented the first evidence in the literature that adjuvant systemic treatment could change the natural history of a solid tumour in humans. 1 7 At present, one should regard metastatic breast cancer as incurable, but that systemic treatment can improve disease-free interval in approximately 40 percent of patients. One could argue that in head and neck squamous carcinoma, we need to move on from the classical historical Halstedian concept to a less radical approach and that probably head and neck squamous cell carcinoma is also a systemic disease, and what is required is effective systemic adjuvant therapy which can increase the disease-free interval in those patients who develop distant spread.
Is occu lt nod a l d isease sig n ificant? One important question that needs to be answered is 'What is the natural history of occult neck disease and is it always clinically significant?' It is important to address this question because this affects whether or not the disease needs to be treated and by what method. The literature suggests that the conversion rate from the NO to the N + neck without neck treatment is approximately 25 percent and this would correlate with the incidence of pathological positive nodes in elective neck dissection specimens (around 30 percent). 1 This indicates that occult neck disease does have the potential to manifest itself subsequently as clinical disease and we know that subclinical spread does not represent early cancer. Unfortunately, the fate of tumour cells in regional lymph nodes is probably variable and at the time of node dissection and subsequent histology, some detectable cancer cells may be artificially arrested and that while a
2718 I PART 17
H EAD AN D N ECK TU M OLI RS
clinical and histologically posItIve lymph node does indicate that tumour cells did reach the node and grew there, a lymph node may be negative on examination because either cancer never arrived, or if it did, it was not retained or indeed was destroyed. Another point to consider is the more you look for tumour within neck dissection specimens, the more you find it! In summary, there is a continuing lack of knowledge of how occult cancer behaves in the lymph node system, and therefore it is impossible to comment accurately on the role of elective neck treatment. At present, clinicians can only detect occult disease when it is removed, thereby removing their ability to comment on its natural history. One of the problems that currently faces head and neck oncologists is the inability to detect and monitor subclinical disease by noninvasive methods. Another question that needs to be answered regarding occult neck disease is 'Does microscopic neck cancer carry a more favourable prognosis than macroscopic neck disease?' The evidence in the literature is that patients with micrometastases tend to be three times more curable than those with macroscopic disease. 1 As previously stated, the true incidence and significance of occult neck disease is still unclear and the more you look for it with histological sectioning and newer sophisticated immuno histochemical and molecular genetic probes, the more you find the incidence increases. However, the literature suggests that because of the unknown prognostic significance of micrometastases, or indeed implications for additional postoperative treatment, then the extra work involved in discovering it on a routine basis is not currently justified.
Extraca psu lar nodal spread There is a general consensus that the presence of extracapsular spread outside a lymph node is associated with a poor prognosis. 1 , 1 8 However, because of the problems in assessing the literature, it is difficult to ascertain how important a prognostic factor it actually is. There is no properly controlled prospective study which relates survival to extracapsular spread and before one can say how important it is, both the start and end points of neck control together with reference to the primary site and cancer-specific survival need to be assessed and correlated with its presence. Currently, it is not clear whether or not it represents an increase in tumour burden or an increase in tumour aggressiveness. Some workers have speculated that it represents the latter and may indicate the presence of a depressed host-immune I response. However, it is reasonable to assume that spread of cancer beyond the lymph node capsule would result in a high incidence of neck recurrence. Some workers have noted that invasion of the soft tissues of the neck by tumour lowers treatment success rates by 80 percent.
Others have shown that patients with extracapsular spread are at increased risk of local recurrence, distant metastases and that the time to recurrence is shorter. In addition, the presence of extracapsular spread decreases survival rates by approximately half compared with patients whose tumour was confined to the nodes. Also, statistically, patients who have occult involvement of nodes but extracapsular spread fare less well. 1 The literature abounds with statements that suggest the standard treatment for extracapsular spread is surgery and postoperative radiotherapy, even for those who have only one node involved. 1 , 19 This dogma is so ingrained that it is unlikely to be investigated scientifically, despite the fact that a number of articles have demonstrated that extracapsular spread is not a significant independent variable using either univariate or multivariate analysis when investigating prognostic factors associated with neck cancer. 20 In addition, some workers have found that postoperative radiotherapy does not appear to improve the outcome of patients with extracapsular spread and have suggested that some form of systemic adjuvant therapy (i.e. chemotherapy) is required as well, although this has not been of proven use in increasing locoregional control, decreasing the incidence of distant metastases or improving overall survival. 1 As previously discussed, Toker demonstrated that a primary spread of tumour emboli within the node capsule may lead to extranodal spread occurring quite early in the metastatic process and as such may represent a normal anatomical phenomenon rather than an aggressive tumour.5 In addition, not all nodes within a neck dissection specimen show extracapsular spread and the question has to be asked 'Is it as significant when it occurs in only one node as when it occurs in ten?' In one series21 which looked at breast cancer, extension through the axillary node capsule worsened the prognosis only for patients who had more than three involved nodes. It is quite clear that extracapsular spread needs to be evaluated more scientifically, but at the moment the mere mention of its presence dictates that many will recommend the patient for postoperative radiotherapy, even though only one positive node is found in the neck dissection specimen. On the basis of the current literature, this is probably not justified.
Retropharyngea l nodes There are a number of reports in the head and neck literature that associate the presence of retropharyngeal I, nodes with a very poor prognosis. 22 Tumours that are associated with these nodes include primary disease of the oropharynx, paranasal sinuses and piriform sinus as well as advanced primary tumours at any site together with massive unilateral or bilateral neck disease, which presumably involves these nodes due to shunting from obstructed lymphatic ducts or channels.
Chapter
It is important to be aware of the existence of retropharyngeal nodes and to evaluate them properly when assessing tumours at risk and magnetic resonance imaging (MRI) is probably more accurate than computed tomography (CT). One author suggests that they are so significant in initial treatment planning that there should be a new designation in the tumour node metastasis (TNM) staging system (N4/stage V) where N4A would represent positive retropharyngeal lymph node status without evidence of cervical lymphadenopathy anywhere else, and N4B would designate the same condition with associated cervical lymphadenopathy. 1 Unfortunately, this has not been adopted.2 3
Pred ictors for d ista nt m etastases It is difficult to evaluate from the literature how many patients actually die of their neck disease, rather than with it. The literature argues the overall five-year survival rates are reduced by at least 50 percent when cervical nodes are positive and the reason for this is an aggressive primary tumour and its ability to metastasize, not only loco regionally but to distant sites. The incidence of distant metastases is related to the size of the primary tumour, the presence of neck disease and overall stage. Another important finding is that the incidence of distant metastases increases by 50 percent when there is recurrent disease present (either at the primary site or in the neck). Although certain features of the primary tumour have been correlated with the incidence of distant metastases, the amount of disease within the neck at presentation is the most prognostically significant factor. This is supported by the finding that very few patients who have an NO neck at presentation actually go on to develop distant metastases. These data support the theory that if the presence of neck disease is an important prognostic indicator for distant spread, then elective neck surgery would play an important role in staging.
Prog nostic nod a l features There are a number of features of cervical lymph nodes which indicate a poor prognosis: •
• • • •
site, size and number; level; extracapsular extension; morphology; laterality.
The ones that are often cited include the site, size and number of positive nodes as well as the presence of nodes at multiple levels and extracapsular extension. However, many of the data used to arrive at these conclusions are retrospective. Prognostic significance is also a feature of certain morphological lymph node patterns and these include lymphocyte predominance and sinus
1 9 9 M etastatic n eck disease I
2719
histiocytosis. A poor prognosis is also associated with lower level nodes, bilateral and contralateral disease. One study24 attempted to correlate 12 characteristics in metastatic lymph nodes with survival and although involvement of low-level nodes and noncontiguous or multiple sites was associated with a worse prognosis, no one factor was accurate enough to be prognostically useful to the clinician. Unfortunately, there was no mention of whether or not the primary tumours were controlled in the survival analysis. However, the study concluded the most important information relating to lymph node status and prognosis was whether or not the primary tumour was controlled and that adding further significance to any other features of lymph node involvement was probably not necessary. In view of this, it may be prudent again to re-evaluate the need to give postoperative radiotherapy if two or more occult positive nodes are found in the neck dissection specimen.
CLINICAL STAG I N G There is a joint UICC/AJC classification for regional cervical lymphadenopathy (Table 199.2). This is based not only on the presence or absence of cervical lymphadenopathy, but also the size of the lymph node, the number of lymph nodes but as yet, not the level. It applies to all head and neck tumours apart from the nasopharynx and thyroid.
Criticisms of the cu rrent sta g i ng system Careful pathological studies now cast grave doubts upon the significance of clinical staging. The most important prognostic factors are the number of nodes involved and, in particular, the presence of extracapsular spread. Neither of these factors can be measured clinically. In addition, no account has been taken in clinical series of the level of lymph node with regard to prognosis and retropharyngeal nodes are excluded. Furthermore, clinical staging gives great weight to laterality whereas pathological studies have shown that bilateral nodes, particularly if they are N1, do not carry any worse prognosis than unilateral N1 nodes at certain sites, e.g. supraglottis. For other sites, contralateral and bilateral nodes carry a dismal prognosis and, as such, probably deserve an N3 grouping. Finally, this scheme does not allow independent classification of massive nodes on both sides of the neck, which are often fixed and almost universally fatal.
Assessment of cervica l lym p hadenopathy Any patient with a head and neck primary tumour requires assessment of the neck. This begins with a history
2720 I PART 17 H EAD AND NECK Ta ble 199.2
TU M O U RS
T M N c l ass ificati o n of reg i o n a l codes.
TM N classification Nx NO Nl N2
Reg i o n a l lym p h n od es ca n n ot be assessed l\Jo reg i o n a l lym p h node metastases Metasta s is in a s i n g l e i ps i l a te ra l lym p h node
3 cm
or l ess i n g reatest d i m e ns i o n
Metasta sis in a s i n g l e i ps i l ate ra l lym ph n od e , m o re t h a n
3 cm
b u t not m o re th a n 6 cm in g reatest d i m e n s i o n , or in m u l t i p l e
i p s i l atera l lym p h n od es n o n e m o re t h a n 6 cm i n g rea test d i m e n s i o n , o r i n bi l atera l o r con tra latera l lym p h n od es, n o n e m o re th a n 6 cm in g reatest d i m e n s i o n N2a
Metastasis i n a s i n g le i ps i l atera l Iyrn ph n od e, m o re t h a n
N2b
M etastasis i n m u l t i p l e i ps i l a te ra l lym p h n od es, n o n e m o re tha n 6 cm i n g reatest d i m e n s i o n .
3 cm
b u t n ot m o re t h a n 6 cm i n g reatest d i m e n s i o n
N 2c
Metastasis i n b i l ate ra l or con tra l atera l lym p h n od es , n o n e m o re t h a n 6 cm i n g rea test d i m e n s i o n
N3
Metasta sis in a lym ph n ode m o re t h a n 6 cm in g rea test d i m e n s i o n
Reprinted from Ref. 23, with permission.
and full clinical examination which may be supplemented by an examination under anaesthetic. Further assessment with radiological imaging may be indicated and fine needle aspiration cytology (FNAC) can help confirm or refute the diagnosis. Occasionally, an open biopsy may be required. If surgery is undertaken, a full pathological examination of the specimen will allow final staging in relation to the presence or absence, number and size of lymph nodes along with pathological grading, presence or absence of extracapsular spread and any vascular or lymphatic permeation.
CLINICAL EXAMINATION Clinical examination remains a n important initial meth od of assessing regional lymph nodes. Great care should be taken with this and this has been discussed in Chapter 138, Examination and imaging of the neck. Clinical examination of the neck has a variable reliability and with inevitable false positive and false negative rates of around 20-30 percent. 2 5 In addition, not only are some necks more difficult to examine than others, but some regions are inaccessible such as the retropharyngeal area. Nodes in these areas are impossible to palpate until they reach a considerable size.
CT There is no doubt that CT scanning can detect malignant cervical lymphadenopathy within the neck. It is more accurate than clinical examination and a meta-analysis of CT versus physical examination using a IS-year Medline review with 647 neck dissections showed CT to have a sensitivity of 84 percent with a specificity and overall accuracy of 83 percent. This compared with physical examination which had a sensitivity of 74 percent, specificity of 81 percent and an overall accuracy of 77 percent. This is particularly true in necks that are difficult to examine, i.e. for restaging or inaccessible areas such as the retropharynx. The detection of malignant disease is
based on the fact that as cancer invades the lymph node, its size, shape and characteristics change so that as it enlarges, its centre dies and appears necrotic and there is a thin rim of inflammation around the edge which shows up on scanning as rim enhancement. The range of non malignant cervical lymphadenopathy is 3 mm up to 3 cm, but most authors recognize that nodes greater than 1 cm in size on CT may contain metastatic disease. Currently, the literature suggests that approximately an 80 percent overall accuracy rate can be achieved on CT by considering all nodes greater than 1 cm in size as containing malignant disease, except those in the low-level II, high-level III region when a 1.S cm size criterion is often applied.26 It is important to realize that the two most difficult areas in imaging head and neck cancer are the detection of low-volume neck disease and residual and recurrent disease following surgery and irradiation. Based on the above imaging criteria, it is possible to miss cancer in an 8-mm cervical lymph node, which can be disastrous since such disease is not early cancer. Such a lymph node would contain 108 malignant cells and it is important not to rely on CT scans alone and base any management decisions on the natural history of the disease in question and consider elective neck treatment where indicated. At present in the UK, the majority of head and neck tumours are imaged as part of initial evaluation. This means that the majority of necks are evaluated radi ologically but an image of the neck (either CT or MRI) should definitely be considered in the following situations: • • •
•
• •
if the neck is being scanned as part of primary tumour assessment; as an alternative to elective treatment if there is a high chance of occult disease (>20 percent); in the presence of significant ipsilateral disease when the presence of deep fixation or contralateral spread may change management from surgery to no treatment at all; to assess the difficult neck; staging prior to nonsurgical treatment; for restaging.
Cha pter 199
M RI This technique can detect cervical lymphadenopathy with similar accuracy rates to CT although some authors have found CT to perform better than MRI.26 However, MRI may be better in evaluating the NO neck. Similar criteria for malignancy are used in both techniques. Various indications where MRI might be more suitable that CT are discussed in Chapter 1 38, Examination and imaging of the neck.
U ltrasound This technique can demonstrate the presence o f cervical lymph nodes, however the absolute criteria for differ entiating benign from malignant disease are notable by their absence. There has been a vogue for ultrasound guided FNAC to try and detect occult malignant disease and to play a role in the evaluation of the NO neck. Snow's group from Holland have been able to achieve excellent results with a 76 percent sensitivity and 1 00 percent specificity.l However, the technique requires an expert ultrasonographer to be present in the outpatient clinic, is operator dependent and labour intensive. Also, it may miss disease which might condemn patients to a policy of 'wait and see' rather than elective treatment. One recent studl7 evaluated the outcome of observing the clinically NO neck in high-risk patients (mainly oral carcinoma) using ultrasonographic-guided (US)-FNAC for follow-up after transoral excision. Patients were followed up for between one and four years using palpation and US-FNAC. Fourteen patients ( 18 percent) had occult lymph node metastases and subsequent neck failure. Of the 1 4 neck failures, nine were detected within seven months and, of those, six were not palpable. Ten out of 1 4 patients were successfully salvaged but four died of uncontrolled disease. The authors concluded that the high salvage rate (7 1 percent) indicated that a strict follow-up policy using US-FNAC enables early detection of recurrence in the high-risk NO neck and justifies a policy of 'wait and see'. Although the authors did not identify the T staging of the primary tumour, some neck failures (and indeed subsequent death) might have been prevented by elective treatment rather than elective investigation. Ultrasound also appears to be useful in assessing invasion of the carotid artery and jugular vein by lymph node metastases.
Rad ionucl ide sca n n ing Over the last 30 years, various workers have used a number of radionuclides including gallium-67 and, more recently, technetium-99 dimercaptosuccinic acid (pentavalent DMSA) to detect metastatic cervical
M etasta tic n eck disea se I
2721
lymphadenopathy. However, these techniques have suffered from a low sensitivity and specificity and an inability to detect low-volume disease. Currently, there is no role for radionuclide scanning of cervical lymphadenopathy. The introduction of position emission tomography (PET) now means that we can assess the metabolic activity of cervical lymph nodes using 18 fluoro deoxyglucose (FDG). However, there are still problems with poor sensitivity and specificity for low-volume disease and currently there is no evidence that PET is superior to CT in the detection of malignant cervical lymphadenopathy. Currently, the role of CT/PET (scan ning with anatomical localization) is confined to detect ing the occult primary, and for assessment of residual and recurrent disease following surgery and irradiation.26
FNAC Not every lymph node in the neck requires FNAC investigation. In the presence of palpable disease and a proven primary, treatment will usually be directed towards the assessment of the neck disease rather than confirming that a metastasis is present. However, in many cases it is beneficial to carry out an FNAC on a palpable node since a positive result is often back before the examination under anaesthesia (EUA) can be performed. Few surgeons would ignore a clinically palpable node in the presence of proven primary disease, particularly as the aspiration cytology test may not be sufficiently reliable. The technique is particularly useful in the assessment of a palpable node when searching for an unknown primary when the nature of the histology may help in the search for the primary tumour. The possibility of anaplastic carcinoma or lymphoma usually makes a tru-cut or open biopsy mandatory. The technique is easy to perform, can be reported immediately (particularly if a cytopathologist is present in the outpatient clinic) and has overall accuracy rates exceeding 90 percent. There is, however, a well-recognized learning curve associated with the technique.
Pathology The head and neck pathologist has the ultimate say in the assessment of cervical lymphadenopathy. Following neck dissection, the specimen should be pinned out on a board and presented to the pathologist. It will then be examined to assess the total number of lymph nodes in the specimen, the number that are positive, the levels that are involved along with the presence or absence of extracapsular spread, vascular and lymphatic permeation. This information is recorded on a diagram as part of the pathological report and stored in the notes. Within the current UICC classification, histological examination of a
2722
I PART 1 7 HEAD A N D NECK TU M O U RS
selective neck dissection will ordinarily include six or more lymph nodes and examination of a radical neck dissection will include ten or more lymph nodes. Standardization of pathological reporting is essential in order to compare data across centres and to facilitate comparative audit and there is currently a standardized reporting form, which has recently been produced by the Royal College of Pathologists.28
Open biopsy In general, this is to be avoided at all costs. However, in situations where FNAC is not available, equivocal or nondiagnostic, or when the results suggest either a lymphoma or an anaplastic carcinoma, it may be necessary. There is no evidence in the literature that an open biopsy alters the prognosis, as long as correct treatment is instigated within six weeks.29 Any incision should be made to facilitate the removal of the scar via a subsequent standard neck dissection incision and pre vious surgery may mean that structures such as the sternomastoid muscle may have to be sacrificed due to scar tissue. This is unavoidable.
Senti nel node bi opsy This technique has received much attention in the literature due to its use in non-head and neck melanoma and breast cancer. Within the head and neck, its use in melanoma has not been adopted routinely and recent reports have described its use in head and neck squamous cell carcinoma. The technique relies on the injection of radio nuclide at the primary site and the patient is then imaged in an attempt to identify the sentinel node. This is the first node that is involved in the drainage of a tumour within the primary lymphatic basin of an NO neck. Once this is identified, it can be removed and evaluated using conventional serial sectioning and staining with either H or E andlor immunocytochemistry to confirm or refute the presence of metastatic disease. Although the technique is considered standard for melanoma in non-head and neck sites as well as breast cancer, in the head and neck the technique suffers from a number of inherent problems. To date, the exact nature of the head and neck lymphatic drainage remains unclear, skip metastases do occur, collateral channels are often present and the technique involves the violation of an oncologically significant area. In addition, there is an inherent risk of facial nerve damage when assessing parotid nodes, the technique is operator dependent with a recognized learning curve and its role would only be in the treatment of T 1 NO disease within the oral cavity and oropharynx. Although some initial reports have been disappointing, 1, 3 0 overall the studies showed sensitivity rates over 90 percent and a statistical decision analysis
model demonstrated that locoregional control and mortality payoffs are better for sentinel node biopsy than for elective neck dissection, although the morbidity of surgery was disregarded.29 Large numbers are required for a randomized control trial to compare sentinel node biopsy with elective selective surgery and this is currently being planned by the European Organization for Research and Treatment of Cancer (EORTC) . One author recently stated that there is currently no role for the sentinel node biopsy (or indeed any minineck dissection) in head and neck squamous cell carcinoma. 1
TREATrvl ENT OF rvl ETASTATIC D I S EASE It is reported that the presence of metastatic cervical lymphadenopathy has an adverse effect on survival and that only 50 percent of patients with neck disease survive five years, although better results have been published in selected series.3 1 However, this means that careful and effective treatment can provide a cure in the rest so that a significant proportion of node-positive patients do well. The treatment of a patient with neck disease is clouded with controversies which have continued unabated and unanswered over the last 50 years or so. These include the following. • • • • • • • • • • • • •
What is the significance of occult disease in cervical lymph nodes? Can occult nodal cancer instigate distant metastases in other words do metastases metastasize? Treatment of the NO neck. Role of selective neck dissection in the management of N 1 disease. What is the role of the sentinel node biopsy? What is the role of radiotherapy in the management of neck disease? The role of modified radical, radical and extended radical neck dissection. Treatment of the neck in a patient with an occult primary. The treatment of suspected or established bilateral neck disease. The management of the difficult, inoperable or untreatable neck. What is the role of salvage surgery in the management of recurrent neck disease? What is the role of chemoradiation? What is the quality of life following single and multimodality treatment for neck disease?
It is important to remember a number of general principles when discussing the management of metastatic neck disease. In the untreated neck, patterns of spread may be predictable (as already discussed), and in the NO neck, occult pisease is usually found within the first echelon lymph node drainage basin. This permits the principle of selective neck dissection. Once the patient has
Chapter 199
had previous treatment involving either surgery or radiation, drainage patterns may be altered so usually all five levels should be either dissected or irradiated. In those patients with palpable neck disease, nonpalpable spread may be present anywhere in the neck so that the correct approach is to encompass the disease completely and dissect all levels together and remove other structures (when appropriate) in the form of modified radical, radical or extended radical neck dissection. However, there is some evidence that radiotherapy may have a place for low-volume N 1 necks (nodes less than 2 cm) and this is discussed later. Depending on the presence or absence of nodal disease, the number of nodes involved together with extracapsular spread, postoperative radiotherapy may be administered in certain situations.
Patients with no pal pable nodes (NO) Historically, evaluation and treatment for the NO neck has been one of the great dilemmas in head and neck surgery and its treatment today is still controversial. The problem that faces the head and neck oncologist is whether or not to treat the neck electively. The reason why elective treatment to the NO neck has been proposed is, that on retrospective evidence from elective radical neck dissec tion specimens, there is a high incidence of subclinical disease for squamous cell carcinomas affecting the oral cavity, pharynx and supraglottic larynx. However, the likelihood of nodes being involved depends not only on the site of the primary disease but also on tumour size and histological differentiation. The controversy extends to when and how the NO neck should be treated. There are a number of treatment options for the NO neck. These include the following: • •
•
•
elective surgery; elective radiotherapy; elective neck investigation; adopting a policy of 'wait and see'.
El ective su rgery Over the last few decades there have been a number of proponents for and against elective neck dissection 1, 32 , 33 and the arguments for and against are listed below. •
For elective neck surgery
The high incidence of occult metastatic disease. - Limited neck dissection has a low morbidity and mortality. - If the neck has to be entered to remove the primary lesion, it is better to perform an in continuity resection at that time. It is impossible to provide the clinical follow-up necessary to detect the earliest conversion of the neck from NO to N l .
M etastatic n ec k d i sease I
2723
- Allowing neck metastases to develop increases the incidence of distant metastases. The cure rate for neck dissection is decreased if gland enlargement occurs or multiple nodes appear. Elective neck surgery can be performed during primary surgery, in patients with short fat difficult necks and when follow-up may be difficult. •
Ag ainst elective neck surgery
- Cure rates are no lower if the surgeon waits for the neck to convert from NO to N l . Careful clinical follow-up will allow detection at the earliest conversion from NO to N 1 . - Radiation is as effective as neck dissection for nonpalpable disease. - Elective neck dissection results in a large number of unnecessary surgical procedures associated with inevitable morbidity. Elective neck dissection removes the barrier to the spread of disease and may have a detrimental immunological effect.
Proponents of elective neck treatment maintain it prevents some cancer-related deaths because untreated neck disease can shed tumour into the vascular or lymphatic system and produce distant metastases. Obviously if distant metastases only arose when lymph nodes are involved, then removing them early would be important but only if metastases can metastasize and the lymphatic route is the exclusive route for spread. Unfortunately, only distant metastases which are seeded from developing nodal disease can be prevented by elective neck treatment and since spread can occur by other routes, then quite clearly the argument for elective surgery is weakened. Elective neck dissection can undoubtedly serve as a biopsy and a subsequent indicator of the risk of systemic disease since local neck and distant metastases are manifestations of the same process and represent the ability of the tumour to metastasize in an individual host. Unfortunately, unlike breast disease, there is no systemic effective treatment that can significantly prolong the disease-free interval. There is no prospective evidence to suggest any decrease in survival by delaying neck treatment until nodes become clinically palpable. Until 1 980, all evidence for and against elective surgery was retrospective, but a randomized prospective trial attempted to address this issue. Between 1 966 and 1 973, 75 patients with T 1-T3 NO SCC of the oral cavity were studied. 3 4 Approximately half underwent elective radical neck dissection within two months of treatment of the primary tumour using interstitial brachytherapy while the others were treated similarly at the primary site but only underwent therapeutic radical neck dissection when nodes became palpable. However, the distribution of the different T stages of the primary tumour were different between the two groups but the percentage of patients in each group with histopathological positive or negative nodes were the same. Patients with positive nodes
2724
I PART 1 7 H EAD A N D N ECK TU M O U RS
received postoperative radiotherapy. Careful five-year follow-up detected no difference in survival between the two groups but in the delayed treatment group, primary tumour problems or the patients' general condition precluded an operation when nodes were palpable in two patients and this is the problem when adopting a policy of 'wait and see' for NO disease. These findings are corroborated in subsequent studies.35, 36 These studies seem to support the contention that elective treatment of the neck is not prophylactic in that it does not prevent cancer-related deaths or improve survival, nor does it prevent neck recurrences. Gordon Snow has suggested that 5000 patients would be needed for the definitive randomized study of the management of the NO neck and this will never happen. Recently, a number of randomized prospective studies have looked at the treatment of the NO neck in T1 and T2NO squamous cell carcinoma of the oral cavity. 1 , 19 , 36 , 3 7 In order for these studies to be valid, they should report outcomes with primary tumour control (including adequate median follow-up consistent with the natural history of the treated disease, i.e. two to three years) and establish a study format to facilitate frequent regular follow-up of the neck. All these recent studies are flawed. The general consensus in the literature for the NO neck in oral cavity tumours is that there are trends from retrospective studies which do show an improvement in survival from elective neck treatment rather than observation alone and that salvage surgery appears to produce worse survival figures than elective neck treatment. 19 If a selective neck dissection is performed, adjuvant radiotherapy should be considered if positive nodes are discovered and in the oral cavity, elective neck surgery should include levels I-IV. On the basis of retrospective evidence, observation of the neck is difficult to justify and assessment of function and quality of life outcomes need to be included in any further clinical trials. 19 For laryngeal and hypopharyngeal tumours, the incidence of NO necks is low, and there are no convincing data to support selective neck dissection (either unilateral or bilateral) in the treatment of tumours from either site. 1 9 However, i f the primary tumour is being treated surgically, the low incidence of nodal involvement in levels I and V would support the elective treatment of levels II-IV only, but the data are less convincing than those currently available for oral cavity tumours. Any weak evidence favouring elective treatment must be weighed against the morbidity of surgery, but there seems no reason why elective selective surgery (levels II-IV) should not be performed as part of a laryngectomy and/or pharyngect omy particularly when it may reduce stomal recurrence.
El ective n eck i rrad iation I t i s widely stated in the literature that external beam radiation of approximately 40-50 Gy to the clinically NO
neck will control occult metastases in up to 90-95 percent of cases.38 This is based on the observed rate of converSlOn of NO to N + necks after elective neck irradiation (3-1 5 percent) and the expected rate of appearance of nodes when the neck is observed, based on a 20-40 percent histological incidence of occult neck disease. 1 However, this assumes that all occult lymph node cancer deposits are clinically significant and evidence from other studies suggests this is not necessarily the case. Although there are no published controlled prospective trials evaluating elective neck irradiation, two retrospective studies evaluating its role in the treatment of patients with squamous cell carcinoma of the oral cavity and tongue39, 40 did show that elective neck irradiation does improve locoregional control and may prolong survival in some cases. Current data do support that the principal value of elective neck treatment, whether by surgery or irradiation, is to reduce the risk of relapse in the neck which may in some situations be translated into improved overall survival. On the basis of these retrospective and prospective studies, it seems reasonable to suggest that in those patients with a greater than 20-25 percent chance of subclinical neck disease, where vigilant follow-up is not possible, where clinical evaluation of the neck has proven difficult, where the neck is being entered for access for reconstruc tion and where imaging of the neck suggests possible occult nodal spread, then elective treatment with surgery or external beam radiotherapy should be considered. Where the primary tumour is being treated with surgery, then the neck should be treated with elective surgery as well. If the primary tumour is being treated with interstitial brachytherapy, then the neck may be treated electively with either surgery or irradiation. Good quality elective surgery has little morbidity and although it is very difficult to quantify the morbidity of elective neck irradiation and there are no prospective studies looking at the quality of life following its administration, radiation does have potentially unfavourable local and systemic effects and can mask deep recurrence. Currently, both elective neck dissection and irradiation are viewed as prophylactic treatments, but if one recognizes the significance of occult neck disease as a marker of the ability of any individual tumour to metastasize, thereby providing a significant prognostic indicator of eventual distant metastases and the possible need for systemic adjuvant chemotherapy, then only surgery can provide the histological data to give this information. When the primary tumour is being treated with radiotherapy (i.e. T lateral tongue border or floor of 1 mouth), then elective treatment should be with radio therapy to at least the first echelon lymph nodes (or the whole neck) and where midline extension occurs, treatment shquld be bilateral. When the primary tumour is treated with surgery (i.e. larger T2/T squamous cell carcinoma of the lateral 3
Chapter 199
tongue border), then elective neck surgery should be carried out since it provides further information for clinical staging, lymph nodes in the area are cleared to give access to vessels for reconstructive purposes, local recurrence rates may be reduced and survival enhanced. Which selective neck dissection to perform is based on the site of the primary tumour and this is discussed later. Another option in the NO neck is to consider elective neck investigation. Could a radiological investigation, such as CT, MRI or ultrasound, demonstrate malignant cervical lymphadenopathy and if so, could a treatment plan be adopted on the basis of these scans? It would seem that many of the arguments levelled against neck dissection could be levelled against elective neck imaging.32 For example, in one series only 5 percent of clinically NO necks were correctly upstaged by CT4 1 and, if false positive results are inevitable in the presence of inflammatory neck nodes and false negatives do occur, then surely CT (or MRI) could play no role in the routine evaluation of the NO neck. Treatment should be based upon the understanding of the natural history in question and currently it is probably cheaper and as effective to offer elective treatment to those high-risk patients who need it and 'wait and see' in the others. This will avoid large numbers of unnecessary CT scans and subsequent inevitable inappropriate surgery, since, as already explained, false positives are inevitable and the natural history of the tomographically positive node is not known. In addition, some patients in high-risk groups with negative scans may be offered a policy of 'wait and see' which could have disastrous results. Because of this, most surgeons now recommend elective treatment rather than elective neck investigation. It is perfectly reasonable to adopt a policy of 'wait and see' in low-risk necks, i.e. carcinoma of the glottis or the soft palate, but for those that are high risk there is now evidence that waiting for the neck to develop from NO to N l has a detrimental effect on the patient3S, 37 and should not be recommended in current clinical practice. In summary, in high-risk necks there is currently very little evidence to support either elective neck investigation Ta b l e 199.3
Fa i l u re ra te Salvage attem pted Sa lvage s u ccessfu l M e d i a n fo l l ow- u p (fo r salvage cases)
S i n g l e pa l pa b l e m etastasis i n one side of the neck l ess tha n 3 em i n d ia m eter (N 1 ) Generally, these nodes are treated surgically and since the survival figures are good and major extranodal spread is uncommon, conservation neck surgery is feasible. It is important to remember that in palpable neck disease, all five levels may be involved and should usually be dissected. The gold-standard operation is radical neck dissection but in the majority of cases, the accessory nerve can be preserved so that the minimum operation that is usually performed is a modified radical neck dissection (type I). Based on a current review of the literature, 19 there is no evidence that radical neck dissection achieves better survival figures than modified radical neck dissection. Although there is a pathological basis for either modified radical neck dissection or selective neck dissection in N l and indeed some cases of N2 disease, due to flawed data it is not known what is the most effective oncological procedure to treat palpable neck disease. However, there is no doubt that the morbidity of a neck dissection arises largely from level V dissection and there is a low incidence of nodal involvement at this level unless two or more levels (especially level IV) are involved.19 Unless a second-side neck dissection is being performed or the internal jugular vein is required for reconstructive purposes, the sternomastoid muscle and the internal jugular vein are usually sacrificed. This is on the basis that the spread of metastatic neck disease can be between these two structures in an orderly progressive manner down the neck and to get it right first time, it is important to encompass the whole area involved rather than violate NO
n e c k.
E l ective neck d i ssection E l ective neck ra d i ation
Su r g e ry a n d ra d i ation
O bservation
9.5% (2/21) 11 m o n th s 2/2 50% (1/2) 15 yea rs R a n g e : 1-216
14% (9/64) 11 m o n t h s 4/9 25% (1/4) 11 yea rs Ra n g e : 16-180
7% (17/244) 12 m o nt h s 16/17 63% (10/16)
months
18% (17/96) 11 m o n t h s 13/17 15% (2/13) 5 yea rs R a n g e : 6-180
months
10 months
yea rs
Range:
1-156
m o n th s Ca n ce r-free s u rviva l Ove ra l l s u rvival M e d i a n fo l l ow- u p s u bg ro u p Reprinted from Ref. 1 , with pe rmission.
71% 33% 34 m o n t h s
2725
or a policy of 'wait and see'. These necks should be treated electively and the mode of treatment dictated by a number of factors which include physician and patient choices, quality of life issues and how the primary site is managed. The results of the various treatments of the NO neck based on a literature review are shown in Table 199.3.
Co m pa ri s o n of res u l ts of the va ri o u s t reatme nts of the
M e d i a n time to recu r re n ce
M eta sta t i c n eck d isease I
53% 15% 35
months
62% 25% 33 m o n t h s
75% 41% 48 m on t h s
2726 I PART
1 7 H EAD A N D N EC K TU M O U RS
oncologically significant areas and risk the possibility of spreading malignant cells at the time of surgery which can then lead to subsequent local recurrence. Recurrence rates following neck dissection have been reported and in the few papers that comment on it 1 where the primary tumour has been controlled, overall recur rence rates range from approximately lO percent for N l disease, 20-30 percent for N 2 disease and up to 8 5 percent for N3 disease, although some small series quote better results.3 1 In many cases of N3 disease, the primary site was not controlled.l There are proponents for a 'less than five level' neck dissection for N l disease on the basis that in the untreated neck, the arguments for the distribution of metastases within first-echelon lymph nodes in nonpalpable disease can be applied to early palpable disease. However, this sort of surgery requires considerable expertise, is fraught with danger and some cases receive subsequent postoperative radiotherapy to all five levels which may affect outcomes with regards to quality of life. The Sloan Kettering Experience42 gives a guarded outlook on extending the indications for selective neck dissection (supraomohyoid neck dissection) for positive neck disease as even with the addition of postoperative radiotherapy, treatment failure was more frequent than NO disease. In that study, 80 percent of the necks dissected were clinically NO and 3 1 percent contained occult nodal disease.39 When the supraomohyoid selective neck dissection specimen was negative, contained micro- or macrometastases, the rates of recurrence increased to 5, 15 and 29 percent respectively despite the addition of postoperative radiotherapy for almost all the patients with proven occult cancer. Further studies with controlled trials are awaited but at present, caution should be adopted in performing such limited surgery for clinically evident disease. There are also proponents in the literature to perform modified radical neck dissection (type 2 and type 3, see below under Modified radical neck dissection) for palpable neck disease. Although there are no prospective trials, many surgeons have for a long time been preserving the internal jugular vein (and indeed the sternomastoid muscle) on one side when bilateral neck dissection is required and there are reports of long-term survivors. 3 1 , 43 However, many (if not all) have received postoperative radiotherapy. A recent review of the literature suggested that the sternomastoid muscle should only be removed if involved by disease. 1 9 Whilst further studies are awaited, it is unlikely that any hard data will accrue that will answer this question so current evidence would suggest that where there is doubt regarding the spread and extent of disease, it is better to be radical first time around. The role of radiotherapy in the treatment of N l disease is controversial. The current consensus is that it is less efficient than surgery and, in general, represents the less preferred option unless the primary site is being treated with radiotherapy as well, or the patient is unfit. The
classic example of this is carcinoma of the nasopharynx with unilateral or bilateral cervical lymphadenopathy when the conventional approach is radical radiotherapy and subsequent surgery for salvage.
La rg e (g reate r than 3 cm l ess than 6 cm) nodes (N 2a) or m u lti p l e u n i l atera l nodes (N2b) This group represents advanced disease and once deemed operable should be treated with radical surgery. In a few cases, the accessory nerve can be preserved so the operation of choice is either a modified radical neck dissection (type 1) or a radical neck dissection and, depending upon the pathological findings, postoperative radiotherapy is usually administered.
B i l atera l and contra l ateral nodes (N2c) Patients with bilateral neck nodes are uncommon and occur overall in approximately 5 percent of head and neck cancers. The common primary sites involved are the tongue base, supraglottic larynx and hypopharynx. Conventionally, it used to be thought that the presence of bilateral neck disease was a grave prognostic sign and this was indicated historically in its staging. However, subsequent careful pathological studies have shown that, in certain instances, this is not so. The prognosis is determined more by the size, number of nodes and by the presence or absence of extracapsular spread within the neck rather than by pure laterality. This is particularly true for the supraglottic larynx and in those patients where the bilateral nodes are either N l or N2a, treatment can be worthwhile using conventional surgery. Conservation neck surgery may be possible on the less involved side and postoperative radiotherapy will usually be adminis tered .3 1 , 43 The decision to treat will often be helped by the location and size of the primary site. Supraglottic tumours with bilateral nodes are often eminently treatable with a laryngectomy and the appropriate neck dissection, but patients with an extensive tongue base tumour and bilateral cervical lymphadenopathy will usually be inoper able at presentation. Patients with bilateral nodes when one side is fixed are usually incurable.
I nterva l contra l atera l lym ph adenopathy A proportion of patients in whom a node appears on the contralateral side of the neck some time after a dissection on the other side may be salvaged, provided there is no recurrence at the primary site. In this situation, a modified radical or radical neck dissection will produce a five-year survival figure of approximately 30 percent. 3 1 The incidenc� of such second side modified radical or radical neck dissections may have been reduced by the
Chapter 199
administration of postoperative radiotherapy to both sides of the neck in high-risk patients.
M assive nodes (g reater tha n
6
em :
N3)
The presence of massive nodes i s again a n uncommon event occurring in patients with head and neck cancer. Only 5 percent of all patients will present with N3 swellings. In previous classification systems, such nodes were referred to as fixed but because of the difficulties in both defining and assessing what this meant, fixation has been removed from current staging systems. However, it is important to realize that many nodes that do reach 6 cm in size are often fixed to the skin and/or underlying structures. In general, many of these patients will be incurable but surgery may be possible in certain instances. The decision whether or not to operate depends upon the staging of the disease, the presence or absence of fixation, what the node is fixed to, the experience of the surgeon and the needs of the patient. The incidence of true fixation of neck masses is often difficult to determine from the literature and varies from series to series with figures from 23 percent in Stell' s series44 up to 30 percent in Snow's outcomes. 4 5 Fixation to the mandible, sternomastoid muscle and prevertebral fascia or muscles in the midline may not represent as much a problem as fixation to the brachial plexus or carotid artery.
TH E D I FFICU LT N ECK The difficult neck includes those necks that are difficult to assess, such as the short stocky neck, those with recurrent disease, assessment of the retropharyngeal nodes and those necks with extensive disease which involves vital structures such as the carotid artery, prevertebral muscles and the brachial plexus. Careful clinical assessment with mandatory radiologi cal imaging will help to assess operability and some of these patients will be helped by extended radical neck dissection. Fixation to the skull base and brachial plexus is almost certainly a contraindication to surgical treatment, but fixation to the skin may be treated by wide resection and flap repair. Assessment of tumour invasion of the arterial tree requires careful consideration. In the past, replacement of the common or internal carotid arteries by a vein graft has been practised. There was a high operative morbidity (33 percent hemiplegia) and mortality ( 1 2 percent), but there are some reports of some patients living for a number of years. If the carotid artery is involved (indicated by frank invasion or by encroachment of tumour which encom passes more than 2700 of the vessel wall), the disease should be assessed as to whether or not cure may be achieved by its resection. If this is the case (which is
M etasta tic n eck d isease
I 2727
unlikely), then the best option is to resect the carotid artery. This is particularly true in patients who have nonsquamous carcinoma disease, i.e. young patients with a malignant glomus vagale tumour surrounding the internal carotid artery at the skull base. If the carotid artery is to be resected and not replaced, the patient needs to be assessed as to whether or not this can be carried out safely without significant risk of hemiplegia. This may be done preopera tively by measuring the cross-cerebral flow and pressure in the carotid stump which can be combined with psycho metric testing during digital carotid pressure. Alternatively, the carotid stump pressure may be measured at surgery. In either case, unless the carotid stump pressure exceeds 70 mmHg, resection alone carries a high risk of significant morbidity and replacement of the carotid should be performed. This requires the help of a vascular surgeon. The technique is associated with inevitable morbidity and significant mortality (particularly the elderly), the graft may become infected and a subsequent blow out can occur. However, in certain instances, particularly in young patients and in those with nonsquamous disease, it may be worthwhile but the current consensus in the literature is that in untreated patients with head and neck squamous carcinoma, the carotid artery may not often be involved even when massive disease is present in the neck and that neck dissection may be possible. In contrast, carotid resections are uniformly unreward ing in recurrent head and neck squamous carcinoma from the point of either achieving locoregional control or improving survival. This is because locoregional failure is common due to arterial involvement, recurrent disease is left behind and once there is failure above the clavicle, systemic disease often occurs afterwards so that resection of the carotid artery is unlikely to affect the natural history of the disease. There is one meta-analysis in the literature46 which reported a two-year survival rate of 22 percent following carotid artery resection. This study was criticized for failing to identify those patients who had been treated previously, for not distinguishing between the treatment of isolated neck recurrence compared with recurrent disease at the primary site as well as the neck, and also 50 percent of the patients did not have histological evidence of tumour invasion of the artery. A current review of the literature fails to identify any support for carotid artery resection in recurrent head and neck squamous cell carcinoma. 1
CONTRAI N DICATI O NS TO N ECK D ISSECTIO N There are a number of absolute and relative contra indications to neck dissection. These are highlighted below: •
those patients whose primary tumours are untreatable;
2728 I PART 17 •
•
•
H EAD Af\I D N ECK TU M O U RS
any patient who is unfit for major surgery because of a serious medical condition which would render anaesthesia and major surgery unsafe; patients with inoperable neck disease; patients with distant metastases.
In those patients who are deemed inoperable, radical radiotherapy with or without adjuvant chemotherapy is seldom curative but may provide excellent palliation. Appropriate assessment is crucial in patients with advanced disease and for some, palliative care such as appropriate pain relief and supportive nursing is the best available option.
Recu rrence a n d salvage su rgery Recurrence in the neck following neck dissection carries a gloomy prognosis. Chances of salvaging recurrent cancer are reported as being 50 percent in the untreated neck, 25 percent in an electively irradiated neck and 5 percent in a previously dissected neck. 1 This means the surgical salvagability of recurrent neck cancer is twice as high in an observed and delayed therapeutically dissected NO neck as in an electively irradiated neck. Careful evaluation and staging with imaging is essential. Many of these masses will be fixed to vital structures which will negate extensive surgery. If surgery is possible, wide resections should be undertaken and postoperative radiotherapy given. If the patient has already received postoperative irradiation, then further radiotherapy using local bra chytherapy may be given when margins are close or when complete resection was not possible.
Benign neck disease There are some benign conditions in the neck (i.e. an infected brachial cyst) which, because of their location and immediate association with surrounding structures (i.e. the internal jugular vein), are best dealt with using the technique of conservative neck dissection.
The occu lt pri m a ry This clinical situation usually occurs in a patient over 45 years (usually a smoker) who presents with a single lump in the upper lateral neck that is thought to be a metastatic malignancy from an occult primary. In 90 percent of cases, the cause of the neck lump will be in the head and neck and the investigation and management of these patients should be approached in a logical manner and a vigilant search above the clavicles will provide the primary tumour site in approximately 50 percent of cases. 33 The investigation and management of the occult primary is discussed in Chapter 1 98 , Management of the patient presenting with neck lymphadenopathy and an unknown primary carcinoma.
B ra nchogenic ca rci noma This i s a very rare condition, but a definite entity presenting as a single mass in the upper neck. It was at one time thought to be fairly common, but it is now known that the majority of these represented secondary malignancies in cervical lymph nodes. A diagnosis of branchogenic carcinoma arising with the branchial system can only be made if the following criteria are fulfilled: the carcinoma should be demonstrated as arising in the wall of a branchial cyst; • the tumour should occur in a line running from a point just anterior to the tragus along the anterior border of sternomastoid muscle to the clavicle; ., the histology should be compatible with an origin from tissue found in branchial vestiges; • no other primary should become evident within a five-year follow-up. •
Treatment is with radical neck surgery, with or without postoperative radiotherapy.
Ca rci noma of the p h a ryngeal pouch This is a rare disease and only approximately 30 cases have been reported in the English literature. The incidence of malignancy is between 0.5 and 1 percent. It affects men predominantly in a ratio of approximately 5: 1 =M:F and usually occurs in a long-standing diverticulum, the average duration of symptoms being greater than seven years. The age at diagnosis is usually over 50 years. The main predisposing factor is thought to be chronic irritation and inflammation of the diverticulum lining from food retention. Symptoms indicating carcinomatous change are increasing dysphagia, weight loss and occasionally blood in regurgitated food. A mass may be found in the neck. The usual lesion is an invasive squamous cell carcinoma, but a few cases of carcinoma in situ have been reported. Barium studies show a constant filing defect, unlike food debris which changes between films or repeat swallows. It is usually seen in the distal two-thirds of the pouch but can easily be missed. The diagnosis may be first made at operation. The unusual case with a tumour confined to the pouch should be treated by diverticu lectomy. Most cases require total pharyngolaryngectomy as for postcricoid carcinoma. The outlook is dismal.
RADIOTH ERAPY I N TH E MANAG EM ENT OF M ETASTATI C N ECK DISEASE Radiotherapy may be used to treat the neck following clinical situations: the clinically negative neck (NO neck); " the clinically positive neck (N + neck);
•
m
the
Chapter •
•
electively after surgery (pathologically N + neck); neck disease developing or recurring after initial treatment: - nodal metastases developing in the untreated neck after initial treatment of the primary tumour alone; - recurrence after previous surgery to the neck; - nodal recurrence after combined treatment.
The cl i n ica l ly N O neck No survival advantage from elective treatment of the NO neck in squamous cell carcinoma has so far been demonstrated by controlled trials, although there is some evidence of multivariate analysis of retrospective data of a significant benefit in locoregional control. There is now a consensus view that the neck should be treated in cases with a high probability ( >25 percent) of cervical micrometastases. The choice between elective neck dissection and radiotherapy will depend upon the method of treatment of the primary tumour. This has already been discussed.
The cl i n ica l ly positive neck Generally speaking, involved nodes are best managed with surgery and postoperative radiotherapy (when applic able), although there is no prospective trial to confirm this. This is especially true for large lymph node masses. This is not just because these are resistant to radiotherapy, but because of the greater difficulty in diagnosing and surgically salvaging recurrences in the neck compared with those of the primary site. Obviously this does not apply to radiosensitive tumours such as a lymphoma or undifferentiated nasopharyngeal carcinoma which can usually be controlled with radiotherapy. Another exception appears to be tonsillar carcinoma where radical radiotherapy to the N 1 neck gives long term results that are as good as surgery. 1 9 Also, radical irradiation may be used as an alternative to surgery in patients unfit for an operation or with unresectable disease. Cure rates depend on both the size of the nodes and the dose of radiotherapy. Two-year local control rates as high as 8 1 percent for nodes measuring 3 cm or less have been published, but such figures are probably higher than expected due to exclusion of those patients from data analysis who had recurrence at the primary site. The results of irradiating large unresectable neck masses are usually disappointing.
El ective ly after surgery Radiotherapy has usually been indicated postoperatively in those cases with risk factors for local recurrence. These have included two or more histological positive nodes,
1 9 9 M etastatic n eck disease I
2729
one node with extracapsular spread or multiple nodes at multiple levels. There are few valid controlled studies that look at efficacy for combination treatment in either the NO or the N + neck so this topic remains highly debated. However, there is retrospective evidence and also two randomized prospective studies which do support the concept that combined treatment can reduce the incidence of regional recurrence but has no effect on the incidence of either distant metastases or overall survival. This is because both these treatment modalities are locoregional and, as such, would not be expected to affect the incidence of systemic disease. 1 , 1 9 , 47, 48 The timing of postoperative radiotherapy is also important and this should be delivered six weeks or less after surgery. 49, 50
Neck d i sease deve l oping or recu rring after i n iti a l treatment N O DA L M ETASTASES D EVELO PI N G I N TH E U I\J TR EATED N ECK A FTER I N ITIAL TR EATM ENT OF TH E P R I MARY TU M O U R ALO N E
In this situation, neck dissection is usually the preferred treatment, with or without postoperative radiotherapy. Alternatively, initial radical irradiation may be used.
R ECU R R E I\J C E AFTER P R EVI O U S SU R G E RY TO TH E N ECK
Radical radiotherapy can be used if there is recurrent disease in the neck developing after an earlier elective or therapeutic neck dissection which was not followed by elective postoperative irradiation.
N O DAL R ECU R R E N C E AFTER CO M B I NATI O N TR EATM ENT
The prognosis is extremely poor in those patients who suffer a neck recurrence following previous surgery and radiotherapy. This clinical situation is often associated with distant metastases. However, the presence of such disease in the neck causes distressing symptoms, such as pain or bleeding together with fungation, and in selected cases further treatment may be appropriate. This includes wide excision of the tumour and the overlaying skin, flap reconstruction and concomitant brachytherapy.
CHEMORADIATIO N The combination of chemotherapy and radiotherapy has been extensively investigated in head and neck cancer over the last three decades and this is discussed in Chapter 200, Developments in radiotherapy for head and neck cancer. Initial studies showed high response rates of squamous head and neck cancer to a
2730 I PART
17
H EAD AN D �I ECK
TU M O U RS
variety of chemotherapeutic agents and there were subsequently a number of trials that evaluated neo adjuvant (induction) chemotherapy or synchronous (either simultaneous, concurrent or concomitant) treatment. A large number of randomized trials have now been reported and the results of three metaanalyses5 1 , 52 , 53 have confirmed reductions in locoregional recurrence but no evidence of change in the incidence of either distant metastases or overall survival. Preliminary results from the U KHAN 1 Trial suggests that synchronous chemoradiation with methotrexate or a combination schedule using vincristine, bleomycin, methotrexate plus 5FU improves locoregional control for patients with squamous cell carcinoma of the head and neck.54
QUALITY OF LI FE There are a number of issues that relate to quality o f life and the treatment of metastatic neck disease. These are discussed below.
El ective su rgery versus i rrad i ation of the NO n eck There are no studies comparing quality of life between these two treatments and there is very little morbidity associated with a neck dissection. This is because vital structures are preserved and level V is not usually dissected. In contrast, a strategy of irradiating both sides of the neck to try and decrease the likelihood of occult cancer growth may be associated with numerous problems since radiation does not always control occult neck cancer, recurrent cancer in an electively irradiated neck is much more difficult to salvage and isolated recurrence in the contralateral neck is extremely unlikely. 1 In addition, treatment options for second primary tumours are diminished when wide field radiotherapy has been applied to both sides of the neck and there are no prospective randomized studies which demonstrate a survival disadvantage when the NO neck is observed. In summary, the quality of life issues relating to elective irradiation appear less transparent than those for elective surgery and should not be underestimated when prescribing its use. Further studies are awaited.
The exte nt of neck s u rg e ry for node-positive d i sease Neck surgery for node-positive disease usually involves a five-level dissection and there are quality of life issues that relate both to the extent of the dissection and which tissues are sacrificed (i.e. accessory nerve, sternomastoid
muscle and the internal jugular vein). There is little evidence in the literature that the sternomastoid muscle, its investing fascia, the internal jugular vein or indeed the accessory nerve have to be removed if uninvolved by tumour. Whilst current practice dictates that many surgeons remove these structures for node-positive disease, there is some evidence in the literature that preserving them in selected cases has very little detri mental effect on survival.3 1 , 43 In addition, some authors have recommended not dissecting all five levels (particu larly level IV), for node-positive disease. 1 Quite clearly, if level V is not dissected, this may improve quality of life. However, in many cases, most patients then receive post operative radiotherapy which probably then does have a significant effect on quality of life. The trade-off for not dissecting all five levels may not justify the subsequent morbidity of postoperative radiotherapy.
The use and extent of postope rative rad iothera py The justification for postoperative therapy has already been discussed. There are very few studies looking at the impact of postoperative radiotherapy on quality of life, but there appears little doubt that sparing one parotid gland would improve the quality of life of patients with head and neck cancer.1 In addition, the evidence that both sides of the neck need to be irradiated postoperatively is flimsy since the incidence of contralateral neck disease is relatively uncommon.1 Unfortunately, many oncologists continue to prescribe bilateral postoperative radiotherapy to the neck routinely.
Chemorad i ation Acute toxicity is enhanced by most regimes of simulta neous chemoradiation. This will usually be self-limiting with appropriate patient support. However, few trials collect late effects data and in the future, adjuvant chemotherapy for head and neck cancer should not be used routinely outside the context of appropriate clinical trials which focus not only on both the acute and late toxicity effects but also assess quality of life.
Psychosocia l i ssues There are a number of psychosocial issues related to the treatment of patients with metastatic neck disease,55 most of whom have primary tumours in the upper aerodiges tive tract. Recent developments in reconstructive techni ques, together with more sophisticated radiotherapy regimes that are administered by centralized specialist multidisciplinary teams, have shown significant improve ments in functional outcomes, cosmetic reconstruction
Cha pter
and tumour control. These improvements were hoped to reduce the reported psychosocial burden that followed treatment in the past. However, recent concerns over quality of life (QOL) and psychosocial support in patients have been raised again following the realization that, in the past decade, five-year survival for advanced disease has remained at approximately 50 percent. Therefore, one must ask the question - 'if we cannot presently improve survival figures, what additional quality of life psycho social support can we offer our patients?'. A recent study highlighted the fact that survivors of head and neck cancer (five-years post-treatment) had a worse quality of life than those with cancers in the lung and colon.55 The often late presentation of the disease notoriously complicates attempts to reduce the patient' s physical and psychosocial toll, as treatment traditionally requires aggressive surgery, often followed by radio therapy (and occasionally chemotherapy). Unfortunately, such forms of treatment can be traumatic and may leave patients with difficult residual 'QOL trade-offs' in the hope of a cure. What we do know from the recent surge of completing QOL assessment studies is that breathing, speech, eating, mouth/throat comfort, digestion, hope of a long life, facial-body image, fatigue, sleep disturbance, secretion, being free from pain, full shoulder movement and social functioning remained the key recorded problem areas following treatment. It has also been reported that even minor disturbances following treat ment can lead to significant dysfunction and disfigure ment which increases the psychosocial impact. It is not surprising therefore that patients following treatment have been reported to have some of the highest rates of anxiety, depression and suicide rates compared with other groups of patients with cancer. Feelings of loss, worry, mood disorders, fatigue and anger, mutilation, isolation, denial, bargaining (with God), guilt, acceptance and feeling of immense sadness have all been observed. There is a higher incidence of chronic alcohol- and tobacco related problems in patients pre- and post-treatment which can increase the demand on psychosocial support and enhance the risk of recurrent disease. In our efforts to improve QOL and reduce the traumatic psychosocial impact, a number of specialist centres are now in the process of balancing science with ethics and the human experience with a surge of QOL research and, hopefully, an evidence-based rationale to guide us in the future. Until a major therapeutic breakthrough takes place, reducing physical treatment morbidity, improving patients overall QOL and mini mizing the psychosocial impact of therapy will continue to present our greatest challenge.
N ECK DISSECTI O N The operation of neck dissection dates back over a century to 1906 when Crile described the classic radical
1 9 9 M etasta tic n eck disease I
2731
neck dissection. This was subsequently popularized by Hayes Martin and today still remains the gold standard by which other operations are judged. This operation removes the lymph node bearing areas of the neck along with the sternomastoid muscle, the internal jugular vein and the accessory nerve. The inevitable morbidity that this led to fuelled an interest in more conservative approaches and, over the last 20 years, a number of less radical procedures have been popularized based on the staging of the disease at presentation. The following neck dissections can be performed: •
•
•
•
classic radical neck dissection; extended radical neck dissection; modified radical neck dissection (types 1-3); selective neck dissection.
Preoperative prepa rati on ========c=
The patient is advised preoperatively about the risks and possible complications of neck dissection. A patient undergoing a unilateral neck dissection does not usually require a tracheostomy unless the operation is combined with the in-continuity removal of the primary tumour. It may be advisable to do an elective tracheostomy for a patient who is undergoing a bilateral or a second neck dissection following previous radiotherapy.
Position The patient is intubated and laid supine on the operating table with the head extended on a head ring, a sandbag is placed under the shoulders and the head turned to the opposite side. By placing the sandbag more on the ipsilateral side, the dissection of the posterior triangle is made easier.
I n cision There are a number of incisions available to perform a neck dissection and these are shown in Figure 199.2. The decision to use a certain incision will be based on factors which include personal preference, previous radiotherapy, the number of levels required for access purposes, any previous surgical incisions and the site of the primary tumour. If the patient has not been irradiated, probably the commonest used incision is the Y type (or Crile) or the Schobinger incision with a lazy S on the vertical limb to reduce scar tissue contracture (Figure 1 99.2) . If the patient had been irradiated, it has been popular in the past to use two separate incisions as described by McFee (Figure 1 99.2) , but the rationale for this was based upon the radiotherapy of the 1 970s and nowadays there is little evidence to suggest that wound breakdown rates are any greater in irradiated than nonirradiated patients, and
2732 I PART
1 7 H EAD AN D N ECK TU M O U R S
I
t:
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.IP-_____
(b)
(0)
(e)
c:- !
r
/
.
�
(e )
(9)
(h)
Figure 1 9 9 . 2 Various i n cisions for neck d issection. (a) Sc h o b i n g e r; (b) horizonta l -T ( Hette r) ; (c) McFee ; (d) la te ra l uti l i ty: (e) u t i l i ty : (f) visor; (9) exte nded thyroid ; (h) H -incision.
Cha pte r 1 9 9 M etasta tic n eck d i sease
there are problems with the McFee incision. It makes the dissection more difficult through limited access, there may be troublesome bleeding from the undersurface of the bridge flap and consequently many surgeons have abandoned its use. Other popular incisions are the horizontal-T (Hetter) and the utility incision. The vertical limb of any incision should not cross the clavicle since this may compromise any future chest flaps. The McFee incision consists of two horizontal limbs and is the one incision in the head and neck where anatomical landmarks are given, although they are rarely used nowadays. The first limb begins over the mastoid process, goes down to the hyoid bone and then up again to the point of the chin. The second limb lies approximately 2 em above the clavicle. It starts laterally at the anterior border of the trapezius and ends medially at the midline.
Rad ica l neck d i ssection This operation removes the lymph node containing levels in the neck (I-V), and all three nonlymphatic structures (spinal accessory nerve, sternomastoid muscle and the internal jugular vein).
I N D I CATI O N S
The indications and contraindications for performing a radical and modified radical neck dissection are con troversial, but the following view represents a majority opinion: •
•
significant operable neck disease (N2a; N2b; N3); access prior to pedicled flap reconstruction.
Firstly, for significant operable palpable neck disease in the presence of a primary tumour in the upper aerodigestive tract where an incontinuity resection with the primary site represents the best chance of a cure. Secondly, when significant operable palpable disease is present in the neck and the primary tumour has been previously well controlled and a neck dissection is indicated for salvage. In the past, the indications for a radical neck dissection rested on the size and site of the disease in relation to the accessory nerve, but it is now usually possible to perform less than radical procedures for the above indications. Other more controversial indications include a patient with an extensive primary lesion which is being treated surgically and who has an NO neck but where a flap is required, i.e. pectoralis major or latissmus dorsi and a modified radical or radical neck resection is appropriate both for access and staging purposes as well as electively treating the NO neck. Also, in the presence of a large primary tumour which by its size, site and nature carries a high risk of occult metastases, elective neck surgery may
I 2733
be indicated but usually more conservative approaches are possible and this has been discussed previously. Lastly, a radical or modified radical neck dissection is indicated in the presence of an occult primary. The blood supply to the cervical neck skin is shown in Figure 1 99.3. Blood enters from above, below and either side with a resultant watershed in the middle of the neck. Incisions can be planned to utilize this (Figure 199.2) so as to maximize blood supply to each of the neck flaps. The contraindications for radical and modified radical neck resection include those patients whose primary tumours are untreatable, those who are unfit for major surgery and those with distant metastases, apart from those with thyroid cancer where radical surgery is sometimes carried out prior to systemic treatment with radioiodine therapy and external beam radiotherapy, although this is rarely a traditional radical neck dissec tion. Finally, it is generally accepted that a patient with significant bilateral neck disease is usually incurable and, in this situation, extensive surgery offers little or no chance of cure and indeed may make the patient's plight worse. Obviously, there are times when it may be worth operating on bilateral neck disease (i.e. supraglottic laryngeal tumours) so that the final decision regarding the bilaterality of disease must rest with both the surgeon and the patient.3 1 A modified radical or radical neck dissection i s also contraindicated for what is regarded as inoperable, i.e. unresectable disease in the neck. Again, this is contro versial but most would agree that, as a general rule, involvement of the common carotid or internal carotid arterial tree, invasion of the prevertebral fascia and muscles along with the brachial plexus and extension onto and into the skull base all makes surgery rather futile, but again any final decision should rest with the surgeon and the patient.
RAI S I N G TH E FLAPS
The skin is prepared in the standard manner and the incision is marked out using a marking pen. The incision, as previously described, is based on personal preference but should provide suitable access to the four major corners of consternation which define the limits of the dissection and can make all the difference between success and failure. 3 1 •
•
Major corners o f consternation Lower end of internal jugular vein. Junction of lateral border of clavicle with the lower edge of trapezius. Upper end of internal jugular vein. Submandibular triangle. M inor corners of consternation Retropharyngeal nodes. Parapharyngeal nodes. - Chaissaignac' s triangle.
2734
PART 1 7 H EAD AN D I'J ECK TU M O U RS
(b)
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(d)
This is because the surgery involves removing not only all palpable disease but also understanding where any occult disease may occur. Any three-point junctions should be placed away from the carotid artery. Once the incision is made, the tip of an intramuscular green needle (2 1 FG) can be dipped in the appropriate ink, and dots made on the skin in three or four places to facilitate placement of critical sutures when closing. Appropriate access will usually mean that the ear is left uncovered and a suture may be placed in the earlobe to retract it upwards to facilitate access to the parotid and skull base. With traction and countertraction, the skin is incised in one movement with a No. 1 0 blade through the platysma muscle, the fibres of which spring apart if strong tension is applied. In the posterior part of the neck, the fibres of the sternomastoid muscle are inserted directly into the skin which makes the dissection and identifica tion of the appropriate plane more difficult and can result in more bleeding. It is important to keep the platysma on the skin flaps since it provides an important blood supply and increases the strength of the wound in the postoperative period. In certain instances, the platysma
Fi g u re 1 9 9 .3
B l o od s u p p l y to t h e ce rvica l n e ck
ski n .
may have to be removed because disease extends onto, into or even through it. In this situation, the overlying skin may have to be removed as well. In the past it has been said that the platysma should be removed as part of the routine operation because there are lymphatics within it, but if these lymphatics are invaded by cancer then the patient is probably incurable. The assistant places double skin hooks or a rake retractor under the platysma and applies traction in an upward direction and similar countertraction to the specimen identifies the subplatysmal plane and the dissection continues using a knife so that the flaps are quickly raised. Dissection here causes very little bleeding, provided the branches of the external and anterior jugular veins are tied so that any significant bleeding usually means that the operator is in the wrong plane. When using a double horizontal incision (McFee), raise the lower flap and the lower half of the middle flap from below, and the upper flap from the upper half of the middle flap from above. Then gain access by retracting the middle-bridging flap with tapes. Bleeding from the inner surface of the bridge flap can be troublesome and this should be controlled at this point.
Ch a pter 1 9 9 M e t a st a t i c
During the dissectio n in t h e upper neck when the upper flap is being raised, there are two branch es of the facial nerve which should be preserved whenever possible. The most i mportant of these is the marginal mandibular nerve and, of somewhat less i mportance, its cervical branch (Figure 1 99.4) . The first supplies the muscles around the mouth and the seco nd supplies the part of the pla tysma that crosses the mandib le a nd is inserted into the corner of the mouth so that divisio n of ei ther nerve can lead to a weakness of the lower lip. Both nerves ClUve d ownwards below and in front of the angle of the mandible across the facial vessels abo llt one fi nger'S breadth below the mandible . The m arginal mandib ular nerve then runs i mmediately superior to the submandib ular gland wh i le the cervical branch runs lateral and inferior to this gland . Both of the nerves then curve upwards again to reach their destinatio n (Figure 199.4) . There are a number o f ways t o p rotect these two nerves. The easiest method is to cut t h rough the deep investing layer of fascia at the level of the hyoid bone and expose the capsule of the lower part of the submandibular gland . The fascia ca n then be eleva ted as a flap over the ma ndible taking the nerve with it and the flap is then sutured superiody. Care should be taken no t to transfix the nerve and bipolar diathermy should be used on the upper flap. A less reliable method of protecting them is to ligate and divide the facial vessels on the submandibular gland and lift them over the mandible, but this technique fails when the nerve's course is lower than usual and it can also com promise the removal of pre- and post-facial nodes which m ay be involved in tum o u rs of the oral cavity. At ti mes it is difficult to p reserve the nerve when disease extends t h ro ugh the deep fascia and approaches platys ma but t h is is an oncological opera tion and for the sake of cancer cure, sometimes the nerve must be sacrificed. If there are metastatic glands in close relatio n ship to the nerve, do no t compromise the cancer operation. The flaps are elevated, t he neck is exposed with access to the corners o f consternation and the resulti ng skin flaps are su tured back to the towels using strong silk sutures (Figure 1 99.5 ) .
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neck disease I
2735
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LOWER E N D O F TH E I NTE R N A L J U G U LA R VEI N
There is generally a predefi ned order in the opera tion o f ra dical a nd mod ified radical neck dissection. I t is, by co nvention, usua l to begin at the lower end in the first co rner of consterna tion ( lower end of internal jugular vein ) or corner two (junction o f lateral border o f clavicl e with lower edge of trapezius) , but occasionally some su rgeons like to fi n d the accessory nerve early on and then p roceed to the lower end. It is a basic principle of cancer surgery that the main vein d raining the pri mary tumour being removed sho uld be d ivided first. Th is step may reduce the nu mber of systemic m etastases because small tum o u r emboli released by manipulating the tumour are unable to find th eir way
Figure 1 9 9 . 5
Flaps ra i sed s h ow i n g th e fou r corners o f
co ns tern a tion.
into the general circulation. Whether this is important in head and neck cancer surgery is uncertain, and some h ave argued that ligation of the internal jugular vein sho uld be left as late as possible since this can reduce bleeding. However, the lower end of the internal jugular vein is usuaUy a pproached early in the operation and this is done by dividin g the sternomastoid muscle (Figure 199.6). The assistant applies traction in an upwards direction while the surgeon applies countertraction to the lower end of the muscle and cuts it with a No. 10 blade. Th e m uscle
2736 I PART 1 7
H EAD A N D N EC K TU M O U RS
fi b res sepa rate e a s ily which a llows the blueness of the
The carotid sheath is opened to exp ose the i nte rnal
i nte r n a l j ug u l ar vein to be identified . O ne or two smaller
ju g ula r vei n and it is impo rta nt to i d enti fy a l e ng t h o f
a r te ries usu ally
nee d
to
be
diathermized
wit hin
the
s tern omastoid m u scle d u ri ng this p roce d ure .
at least 2 em t o fac i litate li g atio n with a de qu a te co ntrol and l i gatures of either silk or vi c ryl a r e p l ace d aro u n d the vein, ma king s ure to check th at the vagus nerve is no t included. Three l igatu res are used, two at the lower end and one at the upper e n d and, in add ition , both ends o f the ve i n a re tra nsfixed
( Figure 1 99.7 ) . The
transfix ion stitch o n the lower end i s known as the ' ho useman's suture' since, if it fai ls in t he early hours of the morn i n g fo l l owin g surge ry, it is the houseman who knows ab out it first. This is o n e area of the operation where it is worth spending some time ensuring proper suture placement. The in ternal ju g ul a r vein can be easily torn when mobil izing i t pri or to d ivis ion, either by inj u dicious passage
o f artery
fo rce ps
ben eath
the s terno mast o i d
muscle o r b y ope ni n g sc iss ors lon g it u d i n a lly n ext to t he vein: this is a manoeuvre wh ich ca n tear small tributaries
a nd con tribu te to ala rmin g b l ee d i n g
.
If bleeding does
occur, do not allow an assistan t to g rab a la rge bleeding vessel with artery fo rceps or a tt emp t d i a the rmy as this will only convert a sma ll hole in to a l a rge one. Th e b l ee d i ng injured vessel sh o u l d be i d e nt i fi e d and occluded tem
po r arily with pressure or arterial clamps and the d efect repa i red using 6 . 0 Ethil o n . The d a nger of tea rin g the
lower e n d of t he vein is n o t blood loss, b u t air embolism.
If the vein i s t or n before it i s divided, p u t a fin ge r o n t h e hole an d a s k the a n aesthetist to tilt the patien t's h ead downwards. Tie the area o f the vein a bove a n d below the hole a n d pass ligatures above a n d below the tear. When F i g ure
1 99.6
D i v i s i o n o f th e l o w e r end o f
the ste rnomastoid.
these are tied, the finger may be l i fted o ff the vei n .
F i g u re 1 9 9 . 7 vei n .
Ligation o f t h e i n te rn a l
jugular
Chapte r 1 9 9 M etasta t i c n eck d isease I 2737
If sutu res sli p off the lower end of the vein after its
laterally to approach Cha issaignac's t r iangle. This is the s ca len u s
division, again put a fi nger on the hole, tilt the p atien t
triangle between longus colli a nd
head down a n d when the sucker is turned up to full
attachm ents t o the t ubercle o f C6 ( Cha issaig nac's o r
power g r a d ually slide your finger o ff the hole, apply
a n ter ior, their
caro tid tubercle ) and the s u bclavian ar t e r y is t h e
base
On the left side, t h e main j u gu la r l ym p h
arterial clamps and stitch the ho le with a no nabsorbable
( Figure 1 99.8 ) .
s u t u re. When dealing with extensive disease low in the
d uct terminates with t h e t h o racic duct which is at risk
neck, it m ay be necessary to gain access to th e j unction o f
and, if seen, should be tied o ff and any chyl ous leak
t h e i n ternal vei n with the s u bclavian vein. I f this is
( recognized as m ilky fl u id ) sho uld be dealt with t here a nd
an t ic ip a t ed , it m ay be p ruden t fo r both oncological and
then. The d uct sho uld be iso lated , oversewn with fine silk
safe t y reasons to gain ap p ro p ria t e con trol in the upper
an d at the e n d o f the operation it is im p o r t an t to com e
m ed ia s t i n u m , a n d the upper p a rt of the sternu m m ay be
b a c k an d check t h a t t h e re a re n o fu rther leaks. A Va lsalva
d ivided or t he m e d ial end of th e clavicle may be removed
manoeuvre will faci litate this . Ever y now and aga i n o n e
to fa cilitate t h is . On the left side, the thoracic duct passes
will fi n d a whole leash o f lym ph at ic vessels t er m ina t i ng i n
med ial to the j u gular vein, then pos terior to i t and finally
this a rea and no o n e la rge d uct ca n be iden t i fi ed . I n this
cu rves a round to en t e r t he j unc t ion of the internal jugular
sit ua tion, the w h o l e a rea should be oversewn tak ing big
vei n and the s u bclavian vein
( Figure 1 99.8 ) . Once the
i n te rn al j ugular vein has been tied , the dissection extends
bites with a nonabso rbable silk su t u re which incit es a vigoro u s infl a m m a to r y react i o n . The critical s teps i n rad i cal n eck dissect i on o f t h e lower neck are as follows.
2
1 . Divide the lower end o f sternomastoid in corner 1 . 2 . Iso l a t e a n d l igate t h e internal j u gul a r vei n .
3.
Look for a n d avoid t h e thoracic d u c t and/or branches of t h e j ugu l a r lymph duct i n Chaissaign a c's triangle.
4 . D iv i d e and retract t h e omohyo i d m usc l e u pwards . 5.
Mobilize the fat pa d o verlying the p reve r tebral fascia.
6 . Id entify and p r eserve the b rach ial p lexus and
p h re nic nerve. 7. D eal wi t h corner 2.
SU PRACLA VICU LAR DI SSECTI 0 N O nce the fi rst co rner of cons ternation has been dealt with
( Figure 1 99.9 ) ,
the
d issection then p ro ceeds towa rds
corner 2 a t t h e lateral end o f t h e clav i c l e and this is d o ne by sup raclavic ular d i ssect ion
( Figure 1 99 . 1 0) . Th is part of
the operation may be a p p roached by d issect ing a rea two and then area one or, as p revi o usly d es c ribed , by d eal in g with a rea one fi rs t and then approac h ing a rea t wo . O n e t rick is to tie off the i nternal jugula r vein and then go
st raigh t to the bottom end of t h e t rapezius m u scle a n d begin the dissection th ere, beh ind the omo hyoid m uscle and then app roach the l igated internal j u gular vei n from lateral to medial. Either way, the om o hyo id m uscle is
divided wi th out any cla m p ing a nd is ret racted in a n u pwards directio n . It should n o t b leed if c u t t h ro ugh the
15 Fig u re 1 9 9 . 8
14
13
A n a tomy o f t h e root o f t h e n e c k . 1 , C o m m o n
tendon and a t this p o i nt the tra nsverse cervical a r tery and vein may be enco u ntered an d sho uld be liga t ed . Med ial t o the omohyoid m uscle, t he fascia over the fa t p ad la teral t o
caro tid a rtery; 2 , i n te rn a l j u g u l a r ve i n ; 3 , vag u s n e rve ; 4,
the internal j ug Ula r vein s hould b e i n c ised a n d t hen t h e
asce n d i n g ce rvica l a rtery; 5 , sca l e n u s m e d i u s m u scl e ; 6, p h re n i c
prevertebral fascia may b e exp o se d b y sharp o r bl u n t
n e rv e ; 7, i n terior t h yro i d artery ; 8, C 5 n e rve ; 9 , th yroce rvical
d issection with a swab i n a n upwa rd d i rectio n . Here, t h e
tru nk; 1 0, b ra c h i a I p l exu s ; 1 1 , s u bc l avian a rte ry; 1 2 , sca lenus
p hrenic nerve i s id enti fi ed a s it runs ove r scalen u s a n terior
a n t e r i o r m u s cl e ; 1 3 , s u b c l avian v e i n : 1 4, i n te r n a l th o ra c i c a rtery;
from lateral to medial. It lies behind the p revertebral
1 5 , t h o racic d u c t.
fascia and is safe as lo ng as this layer is n o t brea ched. The
2738 I PART
1 7 H EAD AN D N EC K TU M O U RS
c rucial at this point to c lear Chaissaignac's triangle which lies between scalenus anterior and the vagus nerve and common carotid artery overlying longus colli and which occupies territory which has, in part, been vacated by the internal jugular vein. This triangle contains branches o f t h e thyrocervical
trunk,
the
vertebral
vein
and the
thor acic duct and it is here that the cervical lymphatics terminate (scalene nodes) and occult disease may occur. This area should be cleared as part of the dissection in the first co rner of consternation. Once the supraclavicular d issection has been com pleted towards the anterior bo rder of trapezius, the operation continues in an upwards direction to dissect the
posterior triangle. The completion of the supraclavi cular dissection means the transverse cervical artery and vein can be encountered anywhere in the lateral half of this manoeuvre and again caudally as the dissection of the p o sterior triangle begins. The external j ugular vein also needs to be ligated and the fat in the supr aclavicular fossa c an be divided with minimal bleeding, but one should avo i d excessive traction since the subclavian vein can be pulled out of the upper chest.
D I S S ECT I O N OF T H E POST E R I O R TRIAN G L E
This dissection continues u p the anterior bo rder o f trapezius to the m astoid t i p
(Figure 199. 1 1 ), It should b e
remembered that everything that i s impOliant i n the F i g u re 1 9 9 . 9
Liga ti o n and division of t h e lower end of the
i n ternal j u g l a r vein a n d d i s sec ti o n
from
the carotid sheath.
posterior
triangle lies below,
that
is
cau dal
to,
the
accessory nerve and that this nerve runs in the ro o f and no t the floor of the posterior triangle and can therefore be damaged
early in
the
dissectio n ,
either
during flap
elevation or during this part of the dissection. It is impo rtant before dissecting the posterior triangle that the accessory nerve is identified. This sho uld be done as a matter of ro utine and, in some cases, it is possible to p reserve the nerve based on the o p erative findings. The technique of preserving the nerve is discussed later (see under Modified rad ical neck dissection below) . There are a number of ways to identify the nerve. It exits the lateral border of the sternomastoid muscle at the j unction of its upper third with the lower two-thirds, and then has a sinuo us course before arriving at the lower anterior b o rder o f trapezius to supply this muscle. In view of its u np redictable position within the posterior triangle, one of the best ways to identify the nerve is where it exits from sternomastoid. This is known as Erb's po int and can be identified 1 cm above the point where the great auricular - -
--
-----
nerve winds a round the muscle on its way to supply the p arotid
fascia.
Once
identified,
the
nerve
may
be
mobilized and preserved. Other ways of identifying it F i g u re 1 9 9. 1 0
S u praclavicu lar dissection.
are either to dissect up the anterior border of trapezius in the posterior triangle until the nerve is encountered ( and
fascia pro tects not only this nerve bu t also the brachial
co nfirmed by stimulati on) , but this is a more difficult
plexus, which is the next stru cture to be encountered in
technique
the dissection. Only use bipolar diathermy in this region
br anches of the cervical plexus which can be quite large
since conventional diathermy can damage nerves. It is
although the use
qecause
the
nerve
may be
of the stimulator
confused with
obviously helps.
Ch a pter
Another way of finding the nerve is to draw a line laterally from the laryngeal prominence through the posterior triangle and the nerve will usually cross that line as it runs from Erb's point to the lower posterior corner of the posterior triangle. During the dissection, which is carried out using both scissors and th e knife, ascending branches of the transverse cervical artery and vein run up the anterior border of the trapezius and make a bloodless dissectio n along this part of the muscle difficult. This is to be
1 9 9 M e tastatic neck d i se ase I
2739
expected and there is no substitute at this point for careful dissection, appropriate diathermy and vessel ligation. This is the only way to prevent damage to the accessory nerve. At this point, every attempt should be made to preserve shoulder function and even if the accessory nerve has to be divided, it is wise to preserve the branches to trapezius from the third and fourth cervical nerves. These lateral branches arise from the cervical plexus, being ultimately derived from C3 and C4 (Figure 199. 1 2 ) . They arise deep to the sternomastoid muscle and pass laterally beneath
F i g u re 1 9 9 . 1 1
t ria ng l e
Dissection of th e poste rior
.
Cervical plexus
Levator scapulae muscle Accessory nerve Anterior cutaneous
Supraclavicular nerve Transverse cervical artery
�
I
j
•
, \'
'
Fi g u re 1 9 9. 1 2
An a t o m y of t h e cervi ca l plexus
a n d its cutaneous b ra n ch es.
2740 I PART
1 7 H EAD AND N ECK TUM O U RS
the fascia covering the floor of the po sterior triangle to
supply the trapezius muscle and also to give off a communicating branch
to
the
accessory nerve.
It is
essential tha t the fascia is preserved on the flo o r of the posterior triangle if these nerves are to be preserved. The dissection continues, dividing the fascia from the anterior bo rder of trapezi us up to the mastoid ti p where the sterno mastoid joins with the trapezius. If there are nodes involved in the upper spinal accessory chain, then it is wise not to preserve the nerve. Otherwise, the nerve
may b e followed through the sternomastoid and this is
one way to identify the upper end of the internal j ugular vein. Clips are placed on the sternomastoid muscle and a t unnel is fo rmed so that the nerve can be followed and dissected free o f the muscle up to level II to the point where it lies on top of the internal j ugu l a r vein. At this p o int it is prudent to divide the upper end of the sternomastoid m uscle to facilitate further identification o f the upper end of the internal jugu lar vein prior t o its ligation. Firm traction is applied to the upper end of sternomastoid and , with the surgeo n p ulling down o n the body of the muscle, the up per end is cut under tension and haemostasis secured. The level of transection is at the angle of the jaw and wo uld no rmally include the lower
Fi gure 1 9 9 . 1 3
Division of th e u pper end of t h e i n ternal
jugU l a r vein.
pole of the parotid gland. With an assistant now placing a Langenbeck retractor under the digastric muscle,
the
upper end of the internal j ugular vein is identified, the accessory nerve may be transposed lateral ly, the upper end of the transected sternomastoid muscle is passed under the nerve and its d ivision completed to facilitate ligation o f the upper end of the internal j ugular vein.
D IVI S I O N OF T H E U P PER E N D OF TH E I NTE RNAL J U G U LA R VEIN
This is the third co rner o f consterna tion. Access is crucial in a cep ha lic direction to get above the disease and to obtain control on the upper end of the vein, which is identified by the divisio n of the sterno masto id muscle as previo usly described
(Figure 199. 1 3 ) . Its position may b e
l ocated b y palpating t h e transverse pro cess of C 2 over which
it
lies,
but
with
the
neck
extended
to
the
contralateral side, this landm ark is u su ally j ust in front of the vein. The vein is mobilized, and using right-angled Lahey forceps,
no nabsorbable
sutures
are
placed
to
facilitate i ts ligation and two sutu res above and one below the p o int of division along with transfixing sutures will usually suffice. It is not usu ally necessary to remove the posterior belly
of the d igastric muscle unless wider access into level II is
Figu re 1 9 9 . 1 4 Retraction o f t h e posterior b e l ly o f t h e d igastric to show the u pper end of the i nte rnal j ug u la r vein i n level I I ( t h i rd corner o f conste rnation). they can cause troublesome bleeding
(Figure 199.15 ) . The
hyp oglossal nerve runs across the external caro tid, lingual and o ccipital arteries and may fo rm , like the digastric, a convenient tunnel which can be fo llowed anterio rly. The hypoglossal tunnel is a particula rly u seful landmark when tu mour is stu ck near the carotid b ifurcation.
(Figure 199.14). This muscle may be retracted
The occipital artery crosses the p osterior part of the
upwards but if there is any problem with regards to
internal j ugular vein and this should also be ligated now
requ ired
disease extension, the muscle may be removed with the
to prevent further troublesome bleeding. If a tie does
specimen.
come
Before tying any l igatures, the vagus and
off the jugular
stump,
the
pressure inside is
hypoglo ssal nerves sho uld be identified and preserved. If
app roximately 4 cm of water so the bleeding can easily
any veno u s trib utaries of the venae nervi hypoglossi
be controlled by packing, and then l igation and over
comintantes are seen, these should be ligated carefully
sewing is performed as required. If control cannot be
as
Ch a pter
1 9 9 M e t ast a t ic
neck d isease I 2741
achieved , then t h e a rea may be packed off and the pack
3. Identify and l iga t e
removed a cou ple of weeks l a ter. The specimen is now
4 . I de nt i fy a n d preserve t h e hypoglossal nerve.
mob i l ized b o th top a n d bottom and the top section is
5.
com pleted
by fi n ding the po ste r i o r bra nch of the posterior fac i a l vein h alf an inch anterior to the interior j u gular vei n . This is l i ga te d and divided. The divisio n of t h e l o wer por t i o n of t h e p a ro t id gl a n d is c o m p l ete d and the hypo gl oss al nerve p res erve d as it turns sh a rp ly to cross the branches of t h e external caro tid artery o n its way to t he subma n d ibula r t ri a n gl e .
The critical steps in radic al neck d issection of the u pper neck a re.
1.
Divide the
upper end of the sternom astoid in
corner three.
2.
Retract t he p o s terior bel ly of d i gas t ri c u pwa rd s .
the i ntern a l j u gu l a r vein .
Deal with the ret roph a r yn geal a n d p a r a ph a r yngeal no d es .
The d iss ec t io n of the post erior tria ngle
m ay
now be
co m plet ed by lifting the specimen upwards a n d taking a
s calpel to dissect between the co ntents o f the post e ri o r t riang l e and the preve rte b ra l fascia. The b ra n ches o f the cervical p le xus can be c l ea r l y identified ru n ni n g upwa rds and t hes e are divided and the acco mpanying a rteries and veins d i athermized. The common carotid a rtery and the va gus nerve ca n clearly be identified along w i t h the stum p of the i nternal j u gul a r vein and the operation c o n t i n u e s with s h a r p dissection going between the i n ternal j ugular vein above the comm o n c a ro t i d a rtery and vagus nerve below (Figure 1 99. 1 6 ) . This fa c i l i t a t e s removal o f t he
carotid sheath an d lympha tics that a re con ta ined within it .
A nt er io rly
low d own , the d i ss e ct i o n is co m p l e te d
t a ki n g t h e s pec i me n with omohyo i d up to the j u nction
with the hyo i d bone ( o m ohyoid t u n n el ) so t h at t he s u b m a n d ib ul ar t ri a ngl e can now be d issected.
D ISSECTIO N O F TH E S U B MA N D I B U LA R TRIANGLE
This d iss ect io n represen ts the fo u rt h corner o f co nsterna tion (Figure 1 99 . 1 7 ) . The fa t is d ivided i n t h e sub mental area and t his d isp l a ys the an terior belly o f the d i ga st r i c m uscle. The anterior part of the submandibular gl a n d is th en iden tified and is d issected to the p o s t er io r bord er o f
Fig u re nerve.
1 99 . 1 5
Divisio n of the veins re la ted to the hypog loss a l
the mylohyo i d m uscle. The u p p e r bo rder of the submandibular gland is freed by d iv i d i n g an d t y i n g the vessels, including t he facial artery, that cross t h e lower bord er of the m a n d i b l e .
F i g u re 1 9 9 . 1 6 Dissection of levels I I -V is comp leted by removing the speci men and dissecting the jugu l a r vein free from the carotid a rtery and vag us nerve.
2742 I PART
1 7 H EA D AND N ECK TU M O U RS
I n ferior dental nerve
Submandibular salivary g land
Medial ptery g oid muscle
Dig astric muscle (posterior belly)
Hypog lossal nerve
Facial artery
Figure 1 99 . 1 7
Anatomy o f t h e subma n d i b u l a r
tri a n g l e. fo rward
u ndersu r face of the middle flap if a McFee incisio n has
d i rection to reveal the sub m andibular duct a n d , a t this
been used. The wound is clo sed in two layers with an
The
mylohyoid
m u scle
is
retra cted
a
in
point, the lingual ne rve i s p ulled down i n
a
curve. The
absorbable Vicryl stitch to the platysmal layer and the
the
ski n then closed using eit her interrupted or co ntinuous
submandibular gangl io n with a kn ife. The lingual nerve
s u tures of Ethilon or st aples . If the latter are used, the
latter
is
freed
by
d iv id ing
the
fascia
around
gives off a small b ut co nstant branch to the s u b m a ndib
three - po in t j unction sho uld be closed accu rately with
ular gangl io n . This bra nch is usually accomp anied by a
Eth ilo n.
vessel that can cause troublesome bl eed ing i f it is not
The wo und may be left uncovered or a gauze d ressing
properly l igated . The l i ngual nerve is identified, and two
may be applied to the suture line prior to release of the
artery forceps a re placed below it to d ivide the branch to
d ra i ns. It is important at this stage to check fo r an air leak
the subma n d ibular ganglio n . T his a l lows the nerve to
si nce drain fai l u re can have d isastro us results.
sp r ing back upwards b e h i n d the body of the man dible. The subm a n d ibular duct i s tied and d iv ided and d u r ing both of th ese m a no euvres, the hypoglossal nerve is kept u nder co nstant d irect v isio n to avo i d a ny d a m age . The specimen
is
then
removed
fo llowing tra nsfixion
and
d ivisio n o f t h e facial artery as it winds over the poste rio r bo rder o f the
digas tric muscle at t h e postero i nferior
border o f the subman di bu lar gla n d . O nce the d issection i s com p le ted, a w a r m p ack i s placed
into
the
wo u nd
and
fo l lowing
a
Rad ical neck dissection as part of a com b i n ed proced u re
Valsalva
When a primary tumour is removed in continuity with a neck disse ction,
a band
of co ntinuity
may
be
kept
between the neck dissection and the primary growth. This is currently not tho ught to be o ncologically essential.
manoeuvre, haemo stasis is completed. The wound is then ir rigated firstly with saline a nd then sterile water and any fu rther bleed ing poi n ts secured.
La ryngeal can cer I n a total laryngecto my, the neck dissection sho uld b e le ft
C LOS U R E
a ttached alo ng the whole length of t he larynx to i nclude
Following wound irriga ti o n, used i nstruments sho uld b e d iscarded a n d new gloves c a n be worn t o clo se t he wo un d . Two large drains
( 1 2 FG) are placed th ro ugh t he posterior
flap and securely tied. Drains sho uld never cross the
t he superior and inferior lymphatic pedicles.
A
neck
dissection is never carr ied out with a he m ilaryngectomy but for a supraglottic l aryngectomy, it is pe dicled on t he thyrohyoid membrane.
caro t id s heath, be cut to the correct length a n d kept well away from any m i crovascular anastomo sis . F inal ly,
m ake
a
check
for
any chylous
leak,
a ny
Pharyngeal ca n cer
bleed ing fro m t he vei ns accompanying the hyp o glo ssal nerve ( the venae nervi hyp oglossal comintantes) . This
When a pharyngectomy i s performed, the pedicle should
is fa cilitated by asking the anaesthetist to perfo rm a
be as broad as possible and is best left along the who l e
Valsalva manoe uvre. Also check fo r any bleeding on the
length o f the pharynx.
Chapter
Ora l ca ncer Oral cancers drain to the submandibular, submental and upper deep cervical lymph nodes in levels I, II and III. The specimen should be left attached along the lower border of the mandible and include the inner layer of periosteum to preserve continuity if possible when neck dissection is combined with radical resections.
Oropharyngea l ca ncer Tumours of the oropharynx drain by a pedicle to the upper deep cervical nodes in levels II, III and IV. Therefore, leave a specimen attached near the tail of the parotid gland if possible.
Complications following neck surgery are inevitable. They can be divided up as follows and are listed in more detail below: 56, 57 •
•
•
•
major and minor; early, intermediate and late; local and systemic; general and specific.
Up to 20 percent of patients will have a major complication following a radical neck dissection, and the mortality rate has been estimated at approximately 1 percent.
Genera l com p l i cati ons Anaesthetic complications, postoperative atelectasis with basal collapse, as well as pneumonia are the most important ones but others include urinary retention and deep vein thrombosis.
Loca l com p l i cations HAEM O R RHAG E
This may be perioperative or postoperative. Severe perioperative haemorrhage usually results from damage to the internal jugular vein at its upper or lower end before it has been ligated. Often the cause is tearing of a tributary and if severe haemorrhage occurs, pressure with a finger on the bleeding point, dissection of the vessel above and below the source of bleeding and then ligation of the vein is the solution. Damage to the carotid arterial system usually only occurs when the artery is invaded by tumour and when attempts are being made to dissect the cancer off a vessel. This should be a situation which has been anticipated and is discussed later under Carotid artery rupture below.
I 2743
Postoperative haemorrhage is usually reactionary and avoided by meticulous attention to haemostasis at the end of the procedure. Secondary haemorrhage may occur as a result of carotid artery rupture. WOU N D I N FECT I O N
The four most important factors in the deVelopment of a wound infection after radical neck dissection are as follows. 1.
2.
3.
Com p l i cations
1 9 9 M etastatic neck d isease
4.
Contamination of the surgical field at the time of surgery. Contamination of the surgical field because the operation involves an in-continuity radical neck dissection and primary excision (composite resection, pharyngeal and laryngeal resection) . Postoperative haematoma which then becomes infected. Flap necrosis and wound breakdown.
These factors vary in their importance and can be avoided most of the time by careful surgical technique. Prophy lactic antibiotics may not necessary in a neck dissection alone, but should always be used if the operation is part of a surgical procedure in which mucosal surfaces are opened into the neck. CAROT I D ARTERY R U PTU R E
Spontaneous rupture of the carotid artery results follow ing necrosis of the arterial wall which is usually due to infection in and around the artery. A number of factors combine to produce this situation but it usually occurs in patients who have been treated by radiotherapy followed by surgery. It can occur after surgery alone but preoperative radiotherapy is implicated in most series. 58 The situation which leads to rupture in most patients is following a major surgical procedure with excision of the primary tumour together with a neck dissection,I when a postoperative salivary fistula develops adjacent to the carotid artery. Removal of the adventitia of the artery during surgery devascularizes the vessel and predisposes to rupture. Although carotid artery rupture may be totally unexpected, it is usually predictable (i.e. in an irradiated patient who has developed a postoperative fistula with loss of neck skin) . Surgical debridement and toilet with local and systemic antibiotics should be instituted. In many patients, a warning or herald bleed occurs and when there is any significant bleeding the wound should be explored and the bleeding point located. If the bleeding is from the carotid artery this should be ligated. In the situation where a carotid bleed seems likely, blood is cross-matched and the patient should have a cuffed tracheostomy tube to protect the airway. When rupture occurs and emergency ligation of the artery is performed the complication rate is very high (mortality of 38 percent and a hemiplegia rate of 50 percent) .46 Complications are reduced if the ligation is
2744
III PART 1 7 H EAD A N D N ECK TU M O U RS
elective and when the blood pressure is normal. Local pressure is applied to the bleeding vessel until volume replacement can be instituted. CHYLO U S FISTU LA
In dissections on the left side of the neck, if the thoracic duct is seen and damaged it must be ligated. More usually, a leak of fluid occurs when the lower end of the jugular vein is being dissected and the duct must then be found and ligated. At the end of a neck dissection, this area should be inspected for any fluid leak. The loss at this stage is not severe because the patient is starved but once postoperative feeding is instituted, milky fluid pours out of the drain. Opinion is divided as to the correct management in this situation. The options are surgical exploration or conservative management. If the leak is mild, i.e. less than 1 00 mL a day, conservative management will almost always succeed. However, if the leak is major, most surgeons will re-explore the wound, attempt to identify the source of the leak and oversew it. This is far from easy but probably an attempt should be made if the fistula is producing large volumes of chyle (i.e. 300 mL a day or more). Conservative management involves pressure dressings and parenteral feeding. The problem with a chylous leak is loss of protein and electrolytes. If conservative measures and exploration of the neck do not control the leak, a lateral thoracotomy and a suture placed between the oesophagus and descending aorta in the inferior and posterior mediastinum will usually succeed. Alternatively, more and more an endoscopic approach may be utilized. P N EU M OTHORAX
If there is disease low in the neck, the apical pleura may be damaged when the disease is being dissected free. This will usually be obvious because there will be an air leak at the time if the patient is being ventilated and the tear should then be repaired. N ERVE I NJ U RI ES
In a standard radical neck dissection the nerves which are deliberately divided are: • •
•
the accessory nerve; branches of the cervical plexus. These are the lesser occipital, greater auricular, transverse cutaneous nerve of the neck, supraclavicular nerves and probably some motor branches to the trapezius (see below) ; the descendens hypoglossi.
A number of other nerves may be damaged by accident. They include: • • •
the facial nerve or its mandibular or cervical division; the hypoglossal and lingual nerves; the vagus, symphathetic trunk, phrenic nerve or brachial plexus.
The effect of damage to these nerves is obvious, but some discussion of division of the accessory nerve and its effects is worthwhile. Division of the accessory nerve during radical neck dissection gives rise to the shoulder syndrome: pain in the joint, limitation of abduction and drooping of the affected shoulder. It has been reported that this complication occurs (in varying degrees) in approximately 60 percent of patients following a standard radical neck dissection.59 This had led to the introduction of accessory nerve saving procedures, 60 or operations in which the cervical nerve supply to the trapezius is preserved. 61 , 62 It must be said at the present time that most head and neck surgeons will attempt to preserve the accessory nerve when performing a neck dissection. The main effects of this syndrome are long-standing pain in the shoulder and the inability to perform certain manoeuvres, such as putting on a jacket. Two important movements at the shoulder joint must be considered: abduction and flexion. Denervation of the trapezius muscle allows the shoulder girdle to rotate through 3 0 ° anteriorly. Abduction in these patients then becomes the equivalent of extension in the normal subject. The normal subject is unable to extend the arm beyond 4 5 ° because of locking of the glenohumeral joint. Abduction of the shoulder beyond 4 5 ° is therefore physically impossible in the patient with a denervated trapezius muscle. Flexion at the shoulder joint in the patient with a denervated trapezius is the equivalent of abduction in the normal subject. Abduction of the arm is a combination of two movements: firstly, elevation and rotation of the scapula on the trunk achieved by the trapezius muscle, and secondly, abduction of the humerus on the scapula mainly achieved by the deltoid muscle, assisted by the supraspinatus muscle, which helps to prevent displace ment of the head of the humerus during strong deltoid action. The first 90° of the movement takes place at the shoulder joint under the control of the deltoid muscle and remains possible in the patient with a denervated trapezius. However, this 90° of movement only brings the arm to approximately 7 5 ° from the trunk because the shoulder girdle is tilted downwards. Furthermore, the remaining 90° of movement due to movement of the shoulder girdle on the trunk by the trapezius muscle is no longer possible. In summary, a patient with a denervated trapezius muscle can only abduct the arm from the trunk to an angle of 7 5 ° , and abduction beyond that point is prevented by locking of the glenohumeral joint. The patient can flex the arm from the trunk to an angle of approximately 45° by the action of the deltoid muscle, but further flexion is prevented by a downward tilt of the shoulder girdle and the loss of the rotation of the shoulder girdle on the trunk by trapezius. The best way to prevent this syndrome is to preserve both the accessory nerve and the separate branches from the cervical plexus (C3 and C4) to the trapezius muscle. If the spinal acc;ssory nerve cannot be preserved, then the branch from the cervical plexus should be saved if
Cha pter 199
possible and, if both nerves are divided, then it is important to refer the patient postoperatively to a physiotherapist for early mobilization and treatment. CER EBRAL OEDEMA
A certain amount of cerebral oedema occurs after radical neck dissection, the intracranial pressure probably increasing approximately three-fold. 6 3 The dangers are much greater after bilateral neck dissection when the increase in pressure may be five-fold or more. These risks are still present, but less so, after staged neck dissection in which both internal jugular veins are ligated but at different times. The vertebral venous system together with the occipital veins and superficial veins constitute the main venous drainage system when both jugular veins have been ligated. A patient with cerebral oedema will have a congested face, the blood pressure will rise and the pulse rate will fall. The patient should be nursed in a sIttmg pOSItIon and given mannitol intravenously together with dexamethasone. These patients often have pharyngeal and laryngeal oedema and any patient having bilateral neck dissection (whether simultaneous or staged) should have an elective tracheostomy.
Extended rad ica l neck d issecti on This operation consists of removal of all the structures resected in a radical neck dissection along with one or more additional lymph node groups or nonlymphatic structures or both. The additional lymph node groups include the retropharyngeal and parapharyngeal lymph nodes, the parotid nodes, or lymph nodes in levels VI or VII. The nonlymphatic structures that may be removed include part of the mandible, the parotid gland, part of the mastoid tip, prevertebral fascia and musculature, the digastric muscle, the hypoglossal nerve, the external carotid artery as well as skin. Table 199.4
2745
This operation is indicated when neck disease invades any of the previously described nonlymphatic structures which then have to be excised in continuity with the neck dissection to facilitate clearance. It is also indicated when the primary tumour arises in the parotid gland or pharynx when a retropharyngeal node dissection is required. Finally, it is indicated for transglottic and subglottic carcinomas along with carcinomas of the cervical oesophagus and thyroid when it is necessary to remove the paratracheal, pretracheal and anterior com partment nodes with an associated neck dissection. The operation is carried out as previously described to include the whole of the parotid as required or extension into the retropharyngeal area to remove involved nodes. A level 6 dissection may be carried out as described later. The appropriate nonlymphatic structures are excised in the conventional manner.
Mod ified rad i ca l n eck d i ssecti on This operation consists of removal of all lymph nodes groups (levels I-V) with preservation of one or more nonlymphatic structures ( Table 1 99.4) . A type 1 modified radical neck dissection preserves the spinal accessory nerve, a type 2 preserves not only the spinal accessory nerve but also the internal jugular vein and a type 3 dissection is when the spinal accessory nerve, the internal jugular vein and the sternomastoid muscle are all preserved (Figure 1 99. 1 8 ) . This latter operation (type 3 modified radical neck dissection) is also known as a comprehensive or functional neck dissection. I N D I CATI O N S •
Modified radical neck dissection (type 1 ) . This operation is indicated for patients with cervical metastases where the spinal accessory nerve is not involved by tumour and its preservation will not involve encountering tumour, thereby compromising
M o d ified ra d ica l neck d issectio n .
Type Description R e m ova l of a l l lym p h n o d e g ro u p s ( l ev e l s
I n dications I -V)
w i th
O p e ra b l e p a l p a b l e n ec k d i sea se (usu a l ly N 1, N 2 a, N 2 b) not i n vo lvi n g t h e a ccessory n e rve
p reserva t i o n of the s p i n a l a ccessory n e rve
Ca n occas i o n a l ly be done fo r t h e 2
Metastatic n eck d i sease I
R e m ova l of a l l lym p h node g ro u ps (leve l s
I -V)
with
I\j O
n eck
Occas i o n a l ly perfo rm ed for t h e same i n d icatio n s as for a type
1
p reserva t i o n of t h e s p i n a l accessory n e rve a n d t h e
p roce d u re pa rticu l a rly for a seco n d s i d e o pe ra t i o n , w h e n t h e re is a
i n te rn a l j u g u l a r ve i n
n eed for m i c rovascu l a r a n astomosis or w h e n h i sto l ogy d i ctates t h e i n te r n a l j u g u l a r ve i n n eed not be resecte d , i.e. d i ffe re n tiated thyro i d ca n ce r
3
R e m ova l of a l l lym p h n o d e g ro u ps (leve l s
I -V)
with
Tre a t m e n t o f t h e
I\j O
n eck
p reserv a t i o n of t h e s p i n a l a ccesso ry n e rve, i n t e rn a l
Treat m e n t of d i ffe re n ti a ted thyroid cancer
j u g u l a r ve i n a n d t h e ste r n o m astoid m u scle
Skin t u m o u rs s u c h as m e l a n o m a , s q u a m o u s ce l l carci n o m a and M e rkel ce l l ca rci n o m a
2746
I PART 1 7 H EAD AN D NECK TU M O U RS
•
•
Lymph node levels dissected
type 2 d issec tion may be carried out where
I-V
preservation of th e internal j ugular vein is imp o r tant
Also excised:
e ither wh en performing a second side o peration, fo r
Sternomastoid muscle
microvascular anasto mosis or when histology dictates
Internal jugular vein
that the vein need not be resected, i.e. differentiated
Submandibular gland •
Accessory nerve is preserved
•
thyroid cancer.
Modified radical neck dissection (type 3 ) . This operation, otherwise known as a comprehensive or fu nctional neck dissectio n, has been used for elective trea tment fo r the NO neck in patients with squamo us cel] carcinoma of the upper aerod igestive tract. This is appropriate treatment if the p a tient has had previous ra d io therapy but if not, it is ques tio nable whether all five levels need to b e dissected and
(al •
whether a selective neck dissection (see u nder
Lymph node levels dissected
Selective neck dissectio n ) will s uffice. Some surgeons
I-V •
advo ca te i ts use for the trea tmen t o f carcinoma of the
Also excised:
thyroid gla n d with palpable lymph nodes in the
Sternomastoid muscle
l a teral co mpartment of the neck but) as previously
Sub mandib ular gland •
sta ted , level I does not us ually have to be dissected in
Accessory nerve and internal
the treatment of previo u sly untreated differentiated
jugular vein are preserved
thyroid cancer. I t is also ind icated for patients with s kin tumo urs such as melanoma, squamous ce]] carcinoma and Merkel cell carcinoma that originate in the na rrow band of the scalp within the confines of the anteri o r and p os terior aspects of the auricle.
OPERATIVE TECH N I QU E
(bl
The i ncisions and expos ure for a m o dified rad ical neck •
Lymph node levels dissected
I-V •
Also excised: Submandibular gland
•
Sternomastoid muscle, internal jugular vein and accessory nerve are p reserved
dissection a re the same as for radical neck d issectio n . The nerve is iden t i fied as p reviously describ ed. It is isolated
using a nerve hook or loop and followed to Erb's point. Cl ips a re the n placed on the sternomas toid mu scle on either side o f the nerve and lifted up, a tunnel is then made
following the nerve and the overlying m uscle
d ivided.
At
this
po int,
the branch o f the nerve to
s terno mastoid is cut . The accessory nerve
can
then be
fo l l o wed u p t o the skull base where i t runs on the anterior s u rface of the internal j ugu lar vein and forms o ne metho d of
iden tifying
the
vein.
Its
preservation
does
not
guara ntee funct io n postoperat ively since saving the nerve i nvo lves i ts devasculariza tion and unpredictable lo ss o f fu n c t i o n i n s o m e cases. Preservation o f t h e sternomastoid
(e)
muscl e makes the o perat i o n more difficult and if surgery
F i g ure 1 9 9 . 1 8
(a)
Typ e 1 ;
(b)
Typ es Type 2 ;
o
f
(c)
m o d i fi ed ra d i c a l neck d i ssecti o n .
Ty pe 3 .
very little to the proced u re, particularly in the eld erly pat ient
t h e resu lts o f the resection. It may be used fo r elective treat ment of the NO neck but, as previo u sly described, there are mo re conservat ive p roced u res •
is fo r p alp able disease, preserving the muscle may add when
the
l ength
of
time
and
the
difficult
d issection may compro mise the ultimate o u tco me. T he deep inves ting layer of fascia may be mobilized from the anterior part of the stern omastoid muscle and
currently available to t reat t his co n d i t i o n .
then dissect i o n of the muscle fro m the fascia below allows
Modified radical neck di sse ctio n (type 2) .
the muscle to be retracted up using sloops, and the neck
Preservation of the internal j ugular vein in squamous
d issect i o n then proceeds under the muscle in the same
cell carcino ma is o ften not carried out when
manner as d�scribed p revio usly for radical neck dissec
operating for p alpab l e disease bu t, in addi t i o n to the
tio n. Ano ther technique is t o divide the muscle at the
indications described above fo r
a
type 1 dissection, a
lower end, fold it upwards, comp lete the dissection and
Cha pter 1 9 9
then return the muscle after the operation and resuture it. This is particularly useful in young patients with thyroid carcinoma where preservation of the muscle is oncolo gically possible and its removal causes significant cosmetic deformity. Preservation of the internal jugular vein involves dissection of the carotid sheath along with the deep investing layer of fascia and the contents of the posterior triangle and proceeds in the plane above, not below, the internal jugular vein leaving the latter structure behind. The relevant branches of the vein are encountered in their usual position and ligated as appropriate.
•
•
Sel ective neck d i ssection A selective neck dissection consists of preservation of one or more lymph node groups and all three nonlymphatic structures. They are named accordingly depending upon the lymph node groups removed and are shown in Table 1 99.5 and diagramatically in Figure 1 99. 1 9 .
•
•
I N D I CATI ONS F O R SELECTIVE N ECK D I SSECTION
Selective neck dissections are only indicated in the NO neck when the natural history of the disease in question is predictable. They should not be carried out following previous surgery or radiotherapy. •
Supraomohyoid or extended supraomohyoid.
Squamous cell carcinoma of the oral cavity (T -T 4, 1 with no palpable lymph nodes). A controversial indication is a single palpable mobile node in level I or II associated with squamous cell carcinoma of the oral cavity, lip or skin of the middle third of the face. It may also be used in conjunction with an elective superficial parotidectomy in patients who have intermediate thickness melanoma and T4 squamous cell carcinoma in the facial region in a line anterior to the tragus.
Table 1 9 9 . 5
Se l ective n e c k d i ssect i o n (for the p rev i o u s l y u n treated
Type
I\JO
Levels d issected
Main i n d ications
I-III I- IV
T, -T4
TrT4:
Postero l ate ra l
I I - IV I I -V ( p l u s
Ante r i o r or cen tra l
VI
S u pe ri o r m e d i asti n u m
VI I
S u p ra o m o hyo id Exte n d e d s u p ra o m ohyoid (a nterol ate ra I) Late ra l
NO
Metastatic n eck d isease I
Lateral. This operation is indicated in carcinomas of
the larynx, oropharynx and hypopharynx that are staged T2-T4NO where the primary tumour is being treated surgically. Some proponents suggest that it may be indicated for carcinoma of the larynx, oropharynx and hypopharynx staged Tl -2 > N I , when palpable lymphadenopathy is confined to levels II-IV. In both of the above indications, these operations are usually carried out bilaterally due to the natural history of disease and a high incidence of bilateral metastases. Posterolateral. This operation is indicated for skin tumours such as melanoma, squamous cell carcinoma and Merkel cell carcinoma that originate in a line behind the posterior margin of the ear and arise in the posterior and posterolateral aspect of the neck and the occipital part of the scalp. Anterior compartment (level VI) . This operation is indicated for differentiated and medullary thyroid cancer and is carried out in conjunction with a total thyroidectomy. It is also performed in conjunction with a selective lateral neck dissection for tumours of the hypopharynx and subglottis. Level VII . During a level VI anterior compartment neck dissection for differentiated and medullary thyroid cancer, level VII can be palpated and lymphatic tissue cleared as part of the procedure. A cervical thymectomy can also be performed in cases of medullary thyroid cancer. True lymph node involvement demonstrated on CT or MRI often requires an upper sternotomy and subsequent access to the area which then clears lymphatic tissue together with the thymus on the medial aspect of both common carotid arteries overlying the trachea down to the brachiocephalic vein. It is indicated for suspected disease in differentiated thyroid cancer and medullary thyroid cancer as well as subglottic laryngeal cancer, hypopharyngeal and cervical oesophageal cancer. In the latter case, the dissection should only take place if the disease is completely resectable.
neck).
sec o ra l cavity
S k i n ca ncer (SeC a n d m e l a n o ma) a nteri o r to the l i n e of the trag us. Performed i n conj u n ction w ith a s u perfici a l pa rot i d e ctomy.
posta u ricu l a r n od es)
NO
2747
sec l a rynx, o ro p h a rynx a n d hypo p h a ry n x
S k i n ca ncer ( S e C a n d m e l a n o m a) poste rior to t h e l i n e of t h e tra g u s Differe n tiated thyro i d carci n o m a S u b g l ottic a n d hypo p h a ry n g e a l sec Diffe ren ti ated and m ed u l l a ry thyro i d ca rci n o m a S u b g l otti c l a ry n gea l a n d hypo p h a ry n g e a l sec Cervical oeso p h a g e a l ca rci n o m a
2748 I PART 1 7 H EAD A N D N ECK
•
•
TU M O U RS
Lymph node levels dissected: I - I I I •
Also excised:
Lymph n ode levels dissected: I -IV
Submandibular gland •
Also excised: Submandibular gland
[b)
[0)
•
Lymph node levels dissected:
•
II A
Level
II 8 (including occipital t riangle)
Level
III
Level
IV
Level
V
Lymph node levels dissected: I I - IV
Level
(d)
(e) •
Lymph node levels dissected : VI
•
Includes nodes in t h e perithyroid, delphian, tracheo-oesophageal and anteriosuperior mediastinum
Fig u re 1 99 . 1 9
Types of selective neck dissection.
(a) su pra o mohyo id : (b) exte n d e d su p raomohyoid (a n t e r ol ate ra I) ; (c) paste rol atera l ; (d) latera I; (e) ante r i o r o r ce
OPERATIVE TECH N IQU E for selective neck dissection will be governed by the preference
of
the
surge on,
the
n u m bers
and locat io n of levels to be dissected as we l l as the site of any p rimary tumour resection and the mode o f reconstructio n,
Figure •
.
s upraom ohyo i d ) , the fascia overlying the
Access to the appropri ate lymph node a reas required p e rso nal
n t ra l
Examples
o f inc is ions
are
shown
1 99 . 2 .
Supraomohyoid (levels I-III ) . Fo r a selective sup raomohyoi d neck d issection ( and extended
10
sternomastoid m uscle is mobilized anteriorly and the muscle ret racted laterally. The fa scia is d issected d o wn to the posterior tri angle. The opera tion co mmences inferio rly and proceeds superiorly d ivid ing bra nches of the cervical plexus and is taken up to the level of the digastric muscle when the d issection then proceeds in a fo rward d irection b o t h superiorly a.n d inferiorly t o identify wh ere the fascia appro aches the internal jugular vein. This tissue, wh ich in cludes the appropriate lymph n o des, is then
Cha pter 1 9 9
•
•
•
•
folded over and dissected off the internal jugular vein, the appropriate tributaries are tied and the dissection continues anteriorly leaving the omohyoid muscle behind and, as the dissection approaches the submandibular triangle, the hypoglossal nerve is identified and preserved and the submandibular gland excised in the same manner as described previously. In this dissection, care must be taken to identify and preserve the accessory nerve in the upper posterior limit of the dissection where it enters the undersurface of the sternomastoid muscle. Lateral. This operation is carried out in conjunction with excision of the primary tumour as described above except level I is not dissected. Posterolateral. In this operation, access is obtained to the posterior triangle. The flaps are elevated, the fascia is mobilized off the sternomastoid from medial to lateral, the muscle is then retracted medially in the opposite direction as described for the previous selective neck dissections and levels II, III and IV cleared from medial to lateral in the manner described above. The dissection extends laterally preserving the accessory nerve and clearance is completed by dissecting the post auricular nodes and the suboccipital triangle (if required). Level VI. This operation is carried out in conjunction with a total thyroidectomy. The lymph node bearing areas in the prelaryngeal and pretracheal areas are dissected down to the level of the suprasternal notch and laterally, level VI nodes in the pretracheal area are removed and, in particular, those nodes that lie medial and lateral to the recurrent laryngeal nerve in the paratracheal space. It is important when this dissection is carried out that levels II, III, IV and VII are palpated and any disease suspected in these areas should be confirmed on frozen section and then treated with an appropriate extended selective neck dissection or comprehensive neck dissection. Level VII. This is usually carried out in conjunction with an anterior central compartment neck dissection (level VI) and total thyroidectomy. An upper median sternotomy (with a lateral extension at the angle of Louis if required) is made to facilitate access to the upper mediastinum but if the operation is being carried out with more radical surgery to the trachea, larynx and pharynx which involves the fashioning of a low end-tracheostome, the upper sternum should be removed to facilitate exteriorization. Lymphatic tissue is cleared to the level of the clavicle medial to both carotid arteries and the area dissected, including the thymus gland, down to the level of the brachiocephalic vein. Care must be taken to preserve the recurrent laryngeal nerves (when indicated) and the operation sometimes facilitates their identification
M etastat i c n ec k d isease I
2749
in the upper mediastinum well away from disease in the lower neck. POSTOPERATIVE MAI\JAG E M E I\J T A N D CO M PLICATI O N S
Postoperatively, all these neck dissections are managed in the same way as for radical neck dissection. Prophylactic antibiotics are not indicated unless the length of the operation so dictates or the pharynx, oral cavity or upper airway are entered. Drains are used in conventional manner and closure of the skin is as per radical neck dissection.
KEY POI NTS • •
•
• • • •
•
•
•
• • •
• •
Head and neck cancer is probably a systemic disease. There is very little prospective evidence in the literature to support current treatment strategies. Metastatic cervical lymphadenopathy is the most important prognostic factor in head and neck squamous cell carcinoma. Most squamous carcinomas spread in a particular pattern. Patterns of spread are altered by previous treatment. Subclinical disease is not early cancer. Accurate staging is essential. There is very little evidence to support a policy of 'wait and see' in the NO neck. Elective surgery is probably better than elective irradiation in the NO neck and may improve survival. The morbidity of neck dissection comes from dissecting level V. Conservation surgery is feasible in selected cases. Modified radical neck dissection is as good as radical neck dissection. Surgical salvage after failed radiotherapy has a poor prognosis. Adjuvant radiotherapy is indicated for N2 + disease and Nl disease with poor prognostic features. In neck dissection, pay attention to the 'corners of consternation'. In elective neck treatment: - there is a 20-25 percent chance of subclinical neck disease; - vigilant follow-up is not possible; clinical evaluation of the neck is difficult; - access to the neck for reconstruction; imaging suggests occult nodal disease. When discussing outcomes of treatment, quality of life issues are important. _
•
2750 I PART
1 7 H EAD A t\I D t\I ECK TU M O U RS
Best cl i nica l p ractice
2.
res p i ra tory and d ig estive tra cts. Cancer. 1 9 7 2 ; 2 9 :
../ H istol ogy re p o rt i n g : - p re p a re speci m e n on b o a rd ; - re p o rt n u m be r of n od e s ;
1 446-9 . 3.
- d ra w a d iag ra m o f res u l ts.
S h a h -'P, S t r o n g E, S p i ro R H , Vi k ra m B. l\l eck d issecti o n : cu rre n t stat u s a n d futu re resp o n s i b i l i ties. Clinical Bulle tin.
re p o rt n od a l l eve l s ; - i s t h e re a n y extraca ps u l a r s p rea d ?
Li n d be rg R . D istri b u t i o n of cervica l lym ph n od es m etastases fro m s q u a m o u s ce l l ca rci n om a of t h e u p per
1 9 8 1 ; 1 1 : 2 5- 3 3 . 4.
Sess i o n s R B , Picker C A . M a l ig n a n t ce rvical a d e n o pathy. I n : Cu m m i n gs CW, Fre d e r i ckson .1 M , H a rker LA, Kra u se CJ, R icha rdso n MA, Sc h u l l e r DE (eds). Otolaryngology - h ead and neck surgery, Vol 3. St Lou is, 1Vl 0 : CV M osby Co., 1 9 8 6 :
1 737-57. 5.
Defi c i e n c i es i n cu r r e n t know l e d g e a n d a reas fo r fu tu r e resea rch ,/
metasta t i c carci n o m a w i t h i n ce rvica l lym p h n odes. Cancer. 1 9 63 ; 1 6 : 3 64-74. 6.
and Laryngology. 1 9 64; 7 3 : 870-82.
s u rg i cal tech n i q u es fo r m eta sta t i c neck d i sease i s 7.
Research. 1 9 7 5 ; 3 5 : 3084-8.
8.
1 9 84; 9 4 : 1 -3 5.
low vo l u m e d isease.
r'
;-
B re n n a n JA, Mao L, H ru b a n BH, B oyle JO, Eby YJ , Koch W M e t 01. M o l ecu l a r assess m e n t of h i stopa t h o l og i ca l
The sig n ifi ca n ce of extraca psu l a r s p read w i t h occ u l t
sta g i n g i n sq u a m ou s ce l l ca rci n o m a o f t h e h e a d a nd
o r N 1 d isease i n t h e n eck s h o u l d be i nvest i g a ted.
neck. Ne w England Journal of Medicine. 1 99 5 ; 3 3 2 :
W ha t is t h e role of observati o n/si n g l e m od a l ity
429-35. 1 0.
Ah re n d t SA, Ya n g SC, W u L, Roig CM, R usse l l P, West ra
A t ri a l of m o d i fied ra d i c a l neck d issect i o n ve rs u s
WH et 01. M o l e cu l a r assess m e nt of lym p h n o des i n
s e l ective neck d issect i o n for pa l pa b l e d i sease s h o u l d
p a t i e n ts w i t h resected sta g e I n on -s m a l l ce l l l u ng cance r:
be cond u cted.
p re l i m i n a ry resu l ts of a p rospective study. Journal of
S e n t i n e l n ode b i o psy s h ou l d be eva l u a ted w i t h a
Th oracic and Cardiovascular Surgery. 2 002 ; 1 2 3 : 466-7 3 ;
ra n d o m ized contro l l e d t ri a l .
d iscussi o n 473 -4.
!-- T h e m o l ecu l a r detect i o n o f occu l t d isease w it h i n
»
9.
s h ou l d be a d d resse d.
su rg e ry fo r occu l t/ N 1 ca n ce r in the neck?
»
Sch u l l e r D E. An a ssessm e n t of n eck n ode i m m u n o reactivity i n h ea d and neck ca n ce r. Laryngoscope.
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200 Developments In radiotherapy for head and neck cancer
JOHN GLAHOLM
Introducti on
2753
Modified radiation fractionation
2754
Accelerated radiotherapy fractionation
2754
Recent advances
2759
Hyperfractionated radiotherapy
2755
Key points
2761
Accelerated hyperfractionation
2755
Best clinical practice
2761
Meta-analysis of modified radiation fractionation
2755
Deficiencies in current knowledge and areas for future
Hypoxic cell sensitization
2756
Combined chemoradiotherapy
2757
Meta-analyses of chemoradiotherapy
2757
Combined modified radiation fractionation and concurrent
2758
chemotherapy
2762
research
2762
References
SEARCH STRATEGY The data in this chapter are supported by Medline and PubMed searches using key words modified and altered radiotherapy
and
radiation
simultaneous, neoadjuvant,
therapy
fractionation,
adjuvant,
meta-analysis
chemoradiotherapy, for modified
concomitant,
fractionation
concurrent,
and chemotherapy,
synchronous, hypoxic cell
sensitizers, cetuximab, taxotere, taxol and taxane chemotherapy, conformal radiotherapy and intensity-modulated radiotherapy.
INTRODUCTION
and structures defined by the clinician using sophisticated soft tissue imaging technology.
The last 20 years have seen dramatic developments in the
Chemotherapy has become a standard of care for
field of non-surgical treatment for squamous carcinoma
patients with advanced disease and the timing of its
of the head and neck. Whilst megavoltage irradiation has
delivery relative to radical radiotherapy has been more
been used exclusively for radiotherapy to these anatomi
clearly defined. The long-term toxicity of these more
cal sites, the science of radiation
intensive approaches has also become more apparent with
delivery
has been
transformed from simple radiation fields using cobalt 60 through the era of relatively simplistic linear accelerators
resultant effects upon quality of life. Other agents, such as hypoxic cell sensitizers and
EGFR
with treatment planning using plain radiographic films to
receptor antagonists, have also shown their worth in the
determine the clinical target for radiation treatment
enhancement of tumour control even though the afford
based solely upon bony landmarks, through to complex
ability of the latter may challenge healthcare systems.
computer-driven machines with the ability to deliver
These innovations, unless otherwise specified, have
radiation with extreme accuracy and precision to tumours
been supported by high quality level I data from multiple
2754
iii PART' 7 HEAD AND I\JECK TU M O U RS
large randomized controlled trials and individual patient
occurs within a period of four to six weeks following
data meta-analyses, which form the basis of the following
treatment completion, unless excessively high doses of
discussion.
radiation
The future is particularly exciting for the non-surgical
following which consequential damage may occur as a
head and neck oncologist, a time of change and progress,
result of excessive normal epithelial stem cell depletion.
have
been
given over
short
time
periods
but with a need for vigilance and an awareness of the
Late tissue reactions, which occur beyond three months
potential
following treatment and which may progress over many
long-term
impact
of
our endeavour
upon
years, are manifest by tissue fibrosis or, in the extreme,
patients with this group of diseases.
radionecrosis. Late reactions are relatively more sensitive than early reactions to large radiation doses per fraction and
MODIFIED RADIATION FRACTIONATION
to
high
LET radiation,
such
as
fast
neutrons.
Consequently, small doses per fraction of conventional Historically, radiotherapy dose fractionation schedules
megavoltage x-irradiation reduce the probability of late
were empirically derived, the overall length of treatment,
effects. Conventional fractionation delivers each dose
usually five days per week for three to almost seven weeks
with a minimum 24-hour interval. However, multiple
in the UK, being largely determined by local resource.
fractions per day by definition will demand shorter
Subsequent dose fractionation schedules have ranged
interfraction intervals, in which case sufficient time must
from 50 Gy in 1 5 fractions over three weeks, through 55
be allowed for normal tissue repair and is usually accepted
Gy in 20 fractions over four weeks to 66 Gy in 33 fractions
as a minimum of six hours, although tissue such as the
over six-and-a-half weeks; all of which have offered
central nervous system may require a longer period for
similar control rates in head and neck cancer.
repair.
.
4
A more scientific approach to radiation fractionation based upon known biological principles is a relatively recent innovation. A number of radiobiological factors, which may inHuence the response of both normal tissue and
tumours to ionizing
radiation,
ACCELERATED RADIOTHERAPY FRACTIONATION
have now been
investigated by randomized clinical trials of modified
This is achieved by reducing the overall treatment time,
radiation fractionation. The intention of these approaches
whilst maintaining the same or a similar number of
has been to increase the narrow therapeutic ratio of
treatment fractions as for conventional radiotherapy with
tumour versus normal tissue damage. A basic under
the objective of counteracting repopulation and thereby
standing of the biological principles of radiotherapy is
improving tumour control. The most extreme examples
necessary
have used multiple fractions per day throughout treat
for
a
clearer
understanding
of
these
new
developments.
ment. Jackson et
Repopulation of normal and tumour cell clonogens
al.5 reported excessive grade 4 acute
mucosal toxicity with 66 Gy
delivered in 3.5 weeks
occurs during the multiple weeks of conventional five day
compared to the conventional arm of 6.5 weeks. As a
per
consequence, the trial was closed after entering only 82
week
therapeutic
radiotherapy, ionizing
because
radiation
is
cell a
damage
from
phenomenon
probability. During each treatment exposure,
of
patients. An anticipated improvement in local control at
only a
three years could not be demonstrated, most probably
proportion of tumour clonogenic cells will sustain lethal
because of the small number of patients. Dose reduction
cells continue to divide and
in the accelerated arm reduces acute toxicity; however, a
multiply. Tumour eradication will only be successful once
recently reported trial of 350 patients failed to demon
all have been eliminated,
strate significant improvement in disease-free survival,
damage and surviving
until which time tumour
repopulation will continue. Furthermore, evidence has
disease-specific survival or locoregional control.6
emerged that tumour repopulation during a period of
Less extreme compression of overall treatment time
fractionated radiotherapy may actually accelerate after the
has been achieved by delivering six fractions per week,
first four weeks of treatment. 1 Tumour control may therefore be compromised when fractionation schedules are
protracted
or
when
gaps
are
inadvertently
or
deliberately introduced into a course of radiotherapy. Loss of locoregional control may range from 1 .6 to 6
percent for each day of delay.2, 3
Normal tissue reactions to ionizing radiation can be
broadly divided into early and late.
Early reactions
typically occur within the first few weeks of fractionated radiotherapy and are manifest by mucositis, taste loss, skin erythema and skin desquamation resulting from mitotic arrest of rapidly dividing cells. Healing usually
either treating on a Saturday or a twice per day treatment on one day of the standard working week. Thereby the overall 6.5-week schedule is reduced by one to two weeks. Two
large
randomized
approach. The Danish
trials
have
DAHANCA
addressed
7/8 trials,
this
which
recruited over 500 patients, have together demonstrated a 1 5 percent improvement in local control for the accelerated arm compared to conventional five-fraction per week radiotherapy, although to date overall survival is not significal1tly
different.
A result
which
has
been
repeated in a large IAEA study using the DAHANCA accelerated schedule.7 Conversely, Hliniak et
al.8 have
Chapter 200 Deve l o p m e n ts in ra d i oth e ra py for h e a d a n d n eck c a n c e r
reported
a
trial of similar
design randomizing
350
patients, which has failed to show a significant improve ment in local control for the accelerated arm despite more severe early toxicity, albeit of short duration. The smaller number of patients might explain the negative result compared to DAHANCA. However, when the next logical step was taken to avoid all weekend breaks by using a
I 2755
have now been evaluated in a number of large trials. The RTOG have recently published results of a four-arm trial
investigating hyperfractionation, accelerated fractionation
with concomitant boost (twice daily for last 1 2 treatment
days)
and
acceleration
with
two-week
rest
during
treatment compared to conventional fractionation. Both hyperfractionation, 81 .6 Gy in 68 fractions over seven
seven day per week treatment schedule, the result was an
weeks, and concomitant boost, 72 Gy in 42 fractions over
unacceptable 22 percent rate of consequential damage,
six weeks, have demonstrated improved local control
although with positive tumour control endpoints. Three
compared to the control arm, although overall survival is
year local tumour control was improved from 37 to 82
similar in all arms. Acute effects were enhanced although
percent and overall survival from 32 to 78 percent,
to date there has been no significant increase in late
respectively, for the control and accelerated arms of the
effects.13 The EORTC trial 22851 randomized 51 2 patients
study. The authors state that reducing the dose per
with advanced head and neck cancer to an accelerated
treatment fraction from 2.0 to 1 .8 Gy eliminated the
hyperfractionated schedule of 72 Gy in 45 fractions over
phenomenon of consequential damage.9 Perhaps one of
five weeks or to the conventional schedule of 70 Gy in 35
the most important messages from this trial is the
fractions over seven weeks. Locoregional control was
demonstration
of
the
criticality of
seemingly
small
changes in radiation dose fractionation.
improved by 1 3 percent, but at the expense of a 1 4 percent risk of severe late tissue damage including two cases of radiation myelitis; this is another example of unacceptable damage resulting from relatively small changes in dose
HYPERFRACTIONATED RADIOTHERAPY
and fractionation.14 Perhaps the most radical approach is
This approach employs a larger number of fractions
the largest head and neck radiotherapy fractionation
exemplified by the CHART trial which to date is one of
compared to a conventional schedule given over the same
trials. Nine hundred and eighteen patients were rando
period of time and is also achieved by giving multiple
mized between conventional fractionation 66 Gy in 33
fractions per day. For a given overall dose the reduced
fractions over 6.5 weeks and a highly accelerated and
radiation dose per fraction results in a lesser risk of late
hyperfractionated schedule of 54 Gy in 36 fractions over
tissue damage. The extrapolation of this approach there
12 days. Unfortunately, there was no significant difference
fore allows a higher overall dose to be given without
in control or survival parameters between the control and
incurring excessive late damage with the objective of
experimental arms of the trial; however, late effects appear
improving tumour control. An unqualified example of this
to be less for CHART, suggesting that the overall radiation
approach is exemplified by the EORTC 22791 trial, which
dose reduction was perhaps greater than necessary.
compared a hyperfractionated schedule of 80.5 Gy given in
similar accelerated and hyperfractionated schedule has
70 fractions
(twice
per day)
over seven
weeks to a
A
been applied in the postoperative setting. Seventy patients
conventional dose of 70 Gy using 35-40 daily fractions in
with
356 patients with oropharyngeal cancer. Five-year local
randomized
control was increased by almost 20 percent from 40 to 59
IS
locally
advanced to
receive
head
and
46.2 Gy
neck
over
12
cancer
were
days;
three
fractions per day of 1 .4 Gy with a six-hour interfraction
percent with a trend towards increased survival, but
interval for six days per week or a conventional dose of 60
without incurring a higher risk of late tissue damage.10
Gy for five days per week over six weeks. Improved three
Such an early and imposing result has not lead to
year locoregional control rates of 88 versus 57 percent
widespread adoption of this approach because of the
were achieved, although overall survival rates of 60 versus
considerable demand upon resources and upon patients'
46 percent were not statistically significant. Both early and
psychological and physical tolerance for undergoing 70
late reactions were enhanced in the experimental arm, the
radiation
later
latter considered to have resulted from a higher incidence
corroborated by an overview of several other trials showing
treatment
of consequential damage. The study also indicated that
improvement
optimal results were achieved if the interval between
in
sessions.
long-term
The
results
loco regional
were control
and
reduction in odds of death,11 although the largest trial by
surgery and radiotherapy did not exceed six weeks and
Sanchiz et al.12 analysed in this overview has been criticized
when the overall treatment time was within ten weeks.16
for the low dose of 60 Gy used in the conventional arm.
META-ANALYSIS OF MODIFIED RADIATION FRACTIONATION
ACCELERATED HYPERFRACTIONATION The
objective
of
combining
both
approaches
is
to
overcome the effect of tumour clonogen repopulation and to reduce late tissue damage. Variations on this theme
Fifteen
randomized
controlled
trials
including
651 5
patients have now been meta-analysed using individual patient data by Jean Bourhis in the MARCH study.
2756
II PART 17 H EAD A I 'l D N EC K TU M O U RS
Minimum follow-up is six years. Larynx and oropharynx
to demonstrate overall benefit, although in the RTOG
were the most commonly studied tumour sites, of which
study a subgroup of patients with early nodal disease
74 percent were stage III and IV.
appeared to show a positive result.24 Both of these
Altered fractionation is shown to convey a significant
nitroimidazole
drugs
were
dose
limited
in
humans
overall survival benefit of 3-4 percent at five years. The
because of problems with neurotoxicity, which may be a
greatest benefit is seen with hyperfractionated radio
reason why the results of preliminary animal studies have
therapy with increased total dose of 8 percent at five years.
not been realized in the clinical setting. However, the
Accelerated radiotherapy offers a 2 percent gain, but less if
Danish Nimorazole trial, DAHANCA 5, has reported a
the total dose is reduced. The main benefit appears to
significantly improved local control rate of 46 percent
result from enhanced local tumour control with a smaller I? effect upon nodal disease.
compared
to
32
percent
for drug
placebo controls
undergoing radical radiotherapy for supraglottic laryn geal and pharyngeal carcinoma in 288 patients, with an apparent additive effect of haemoglobin concentration. The rationale for selecting this drug was its reduced
HYPOXIC CELL SENSITIZATION
neurotoxicity and hence patient tolerance of higher doses Cellular hypoxia significantly increases radioresistance and is considered to be an important factor in the control of head and neck cancer. Two principal avenues of research
have
been
pursued
in radiotherapy
in
an
despite
having
a
lower
sensitizing
effect
(sensitizer
enhancement ratio) than misonidazole or etanidazole25 and these exciting results undoubtedly justify further investigation. More recently, a new bioreductive agent,
endeavour to increase the therapeutic ratio and improve
tirapazamine
control rates and survival, using methods to increase
selective electron reduction in hypoxic conditions, form
has
been
developed,
which
undergoes
tumour oxygenation either by hyperbaric oxygen or
ing free radicals resulting in cell death. The agent has been
by
shown to potentiate the cytotoxicity of ionizing radiation
oxygen
mimetic
hypoxic
cell
sensitizers.
Several
large randomized trials have been undertaken and it is
and of several chemotherapeutic drugs, in particular, the
now possible to begin to draw conclusions from the
platinum compounds and taxanes. Phase I studies have
results. The medical research trial of hyperbaric oxygen
now been completed with results from further trials
therapy for head and neck cancers reported by Henk
awaited.26 Another approach in an attempt to modify
and Smith in 1 977, randomized 49 patients to hyperbaric
tissue hypoxia has used nicotinamide, which causes
oxygen or conventional radiotherapy in air, with respec
vasodilatation with the objective of reducing transient
tive two-year local control rates of 45 and 27 percent
or acute hypoxia caused by intermittent vasoconstriction
and five-year survival rates of 38 and 27 percent. These
of tumour-feeding vessels, and the breathing of carbogen
results were statistically significant and included patients
in order to overcome chronic hypoxia, which occurs in
with oral and oropharyngeal cancers, although patients I with very large tumours, >5 cm, failed to benefit. S
cells more distant from feeding arterioles than the oxygen
However, at least half of the patients considered for
These agents are well tolerated, although nicotinamide
perfusion distance in air at 1 atmosphere of pressure.
hyperbaric oxygen are medically unfit for the proce
can cause impairment of renal function and should not
dure, which is also complex, time-consuming and costly,
be given concomitantly with nephrotoxic drugs. Pre
hence there has been little subsequent interest in the
liminary results have been promising,27 although the
technique.
approach requires confirmation by large randomized
As an alternative, a group of bioreductive nitro imidazole drugs, which mimic oxygen but have greater
trials. Anaemia has been closely correlated with reduced
tissue perfusion characteristics, have now been investi
radiotherapy control rates and survival.2 S
gated in prospective randomized trials in head and neck
appears to be independent of disease stage. A secondary
The effect
cancer. The first drug misonidazole, designed specifically
analysis of the aforementioned trial RTOG 85-27 for
for this purpose, has been assessed in two large trials; the I RTOG study with 306 patients 9 and the Danish study
advanced cancer indicated five-year survival of 35.7
with 626 patients.2o Both failed to demonstrate overall benefit compared to
their control groups,
although
subgroup analysis of the larger trial suggested benefit in 304 patients with oropharyngeal cancer. Similarly dis
appointing results were demonstrated by the EORTC
randomized trial of three fractions per day radiotherapy with misonidazole.21
A successor agent, etanidazole, has also been investi
gated in the RTOG ETA trial (RTOG 85-27), which randomized 521 patients22 and in a multicentre European trial with 374 patients.23 Once again, neither trial was able
percent for patients with 'normal' haemoglobin levels compared to 21 .7 percent for those with anaemia defined as
< 1 4.5 g/dL for men and
< 1 3 g/dL for women.29
Similarly, reduction in local control of approximately 30 percent has been shown for patients with T1 and T2 glottic cancer, although the threshold in this study was haemoglobin of 1 2 g/dL.30 However, the mechanism of action of anaemia is uncertain and may not be simply related to tissue hypoxia as the same effect has been shown for surgically treated ' patients3I and may be an epiphenomenon related to patient performance status. Nonetheless, in the absence of
Chapter 200 Deve l o p m e nts in rad ioth e ra py fo r h e a d a n d n ec k ca n c e r
a clear explanation for this phenomenon it would be wise to correct anaemia in patients undergoing radiotherapy for head and neck cancer.
induction
chemotherapy
offers
no
I 2757
advantage.
Both
chemotherapy arms appear to reduce the incidence of distant metastases. These results must be regarded as preliminary and further follow-up is necessary.35 Similar
criticism as for the Veterans Affairs trial can be levelled at the EORTC trial reported by Lefebvre et al.,36 which
COMBINED CHEMORADIOTHERAPY
investigated pyriform sinus cancer using a similar strategy The combination of chemotherapy and radiotherapy has
and resulting in a comparable conclusion albeit with a
been extensively investigated in head and neck cancer over
lower, 35 percent, rate of laryngeal preservation. These
the last three decades. The rationale was founded upon high response rates of squamous head and neck cancer to
a variety of chemotherapy agents including methotrexate, vinblastine,
bleomycin,
5-fluorouracil,
trials are frequently quoted as offering standards of care,
but their conclusions should now be reconsidered in the context of high quality meta-analyses.
cisplatinum,
carboplatin and the taxanes, either alone or in combina tion.32 The combination of cisplatin and 5-fluorouracil demonstrated complete response rates of up to 50 percent in previously untreated patients.33 Such response rates
META-ANALYSES OF CHEMORADIOTHERAPY A
large
number
of
randomized
trials
designed
to
equal those reported for other solid tumours, such as
investigate chemotherapy given as neoadjuvant (induc
breast carcinoma, and therefore there has been consider
tion), concomitant (concurrent, synchronous, simulta
able interest and enthusiasm for adjuvant chemotherapy
neous) and less frequently adjuvant (following definitive
in the treatment of advanced head and neck cancer.
treatment) have now been reported with many of the
In early studies, chemotherapy was mostly used in an
earlier studies drawing conflicting conclusions, possibly
attempt to downstage disease prior to definitive local
because of small sample sizes and because of the use of
therapies
and
to
reduce
the
incidence
of
distant
earlier less effective chemotherapy agents. Meta-analyses
metastases. These induction (neoadjuvant) chemotherapy
have greatly improved our understanding of the benefit
schedules were initially investigated in non-randomized
and limitations of these techniques.
trials using historical or case matched controls, which
The first to be published was by Stell and Rawson in
suggested a major advance in overall survival. However,
1 990,37 based upon a published data analysis of 23
such encouraging results were not subsequently born out
randomized trials of adjuvant chemotherapy in squamous
by randomized controlled trials, at least not until very
carcinoma of the head and neck, none of which were
recently.
individually large enough to detect the anticipated survival for
improvement of the order of 5 percent. The average
example, concomitant (concurrent, synchronous, simul
Alternatively
chemotherapy
has
been
given,
response rate in four induction studies was 47 percent; yet
taneous) with radiotherapy for which much data have
overall there was no significant reduction in cancer
now been accumulated and subsequently (maintenance)
mortality with this approach. Only synchronous and/or
as an adjuvant or indeed a combination of these.
maintenance trials appeared to confer benefit. Perhaps
All of these issues have now been subject to large meta
unexpectedly, cisplatinum-containing regimens offered no
analyses, but before embarking upon discussion, the issue
benefit and patients treated with the commonly used
for
vinblastine, bleomycin and methotrexate combination
'organ preservation' is worthy of note, an approach which
fared worse. Whilst the incidence of locoregional recur
of
using
neoadjuvant
(induction)
chemotherapy
was driven by the objective of avoiding ablative surgery in
rence was reduced in the chemotherapy arms, the distant
advanced disease. The Veterans Affairs study randomized
metastasis
patients between induction chemotherapy followed by
reported in these trials; however, the average mortality
radiotherapy versus surgery, followed by postoperative
rate in nine series was an alarming 6.5 percent, an
radiotherapy. Those receiving chemotherapy underwent
unacceptable figure by current standards. A meta-analysis
rate
was
unchanged.
Toxicity
was
poorly
surgery and radiotherapy if a partial response was not
of 54 randomized trials published by Munro in 1 99538
achieved. Two-thirds
reiterated Stell's findings with neoadjuvant chemotherapy
of
the
patients
treated in
the
conservation arm retained their larynx, although overall
conferring a small rate difference of 3.7 percent, with 95
survival was the same.34 The trial was heavily criticized for
percent confidence intervals of 0.9-6.5 percent. However,
the absence of a radiotherapy alone arm. Consequently
single agent simultaneous chemotherapy increased survi
Intergroup trial R91 -1 1 was initiated comparing induc
val by 12.1
tion chemotherapy and radiotherapy versus concurrent
interval of 5-1 9 percent. Once more, cisplatinum-contain
chemotherapy
ing schedules failed to confer a survival advantage.
and
radiotherapy
versus
radiotherapy
alone. An interim report has failed to indicate an overall survival benefit from chemotherapy, however laryngect
percent with a corresponding confidence
Reasons for the failure of the neoadjuvant approach to increase survival were unclear and several hypotheses have
omy-free survival is significantly longer with concomitant
been suggested. The concept that tumours treated with
chemotherapy compared to radiotherapy alone, although
chemotherapy
may
become
more
aggressive
despite
2758 I
PART 17 HEAD A N D NECK TU M O U RS
apparent downstaging was supported by a study of
that concomitant chemotherapy offers the most signifi
tumour cell kinetics using flow cytometry in 97 patients
cant overall survival gain.42
with oropharyngeal cancer which demonstrated signifi cantly
increased
mean
labelling indices
and
shorter
potential doubling times following induction chemother apy compared to pretreatment measurements, particu
Postoperative chemoradiotherapy with concomitant cisplatinum has also been compared to postoperative radiotherapy alone. Two landmark trials were published simultaneously in 2004. The EORTC trial by Bernier et
larly in poorly responding tumours.39 Alternatively, the
al.43 demonstrated improvement in overall survival and
possible
the
benefits
of
neoadjuvant
chemotherapy
for
responding patients may be offset by the adverse effect of delaying surgery or radiotherapy in non-responding patients. A potential survival advantage may also be
North
American RTOG,
Cooper et al.,44 which
reported similar results albeit in terms of locoregional control, but not overall survival. An 'entente cordial' pooling of their results was reported in 2005 where it was
eroded by excess mortality associated with the high
shown that those patients with positive resection margins
incidence of intercurrent disease, mainly second tumours
or nodal extracapsular spread showed significant bene
and vascular disease, in this group of patients which may
fit.45
be further offset by toxicity-related deaths resulting from
reported excessive late effects.
chemotherapy which were all too common in the 1 980s. Finally,
the
chemotherapy
schedules
used
in
earlier
Over the last 15 years, many more trials have reached In
2000,
almost
1 1 ,000
patients
effects were enhanced,
but
neither
trial
The MACH-NC group has shown that late toxicity is enhanced by concomitant chemoradiotherapy, but con cedes that reporting has been poor in most trials. It is
studies were often devoid of a platinum agent. maturity.
Acute
from 63
interesting to note that the 8 percent improvement in overall survival is remarkably similar to that achieved by
randomized trials had become available and formed the
dose-escalated hyperfractionated radiotherapy schedules,
basis for a large meta-analysis based upon individual
an observation made by Henk several years previously.46
patient data - MACH-NC study group. Pignon et al.40 reported a 4 percent survival benefit at five years for chemotherapy overall. Neoadjuvant and adjuvant che motherapy failed to confer a significant survival advan tage, whereas a gain of 8 percent was achieved using 'concurrent'
combinations.
However,
the
COMBINED MODIFIED RADIATION FRACTIONATION AND CONCURRENT CHEMOTHERAPY
authors
affirmed that clear conclusions could not be drawn
The most recent generation of randomized clinical trials
because of heterogeneity of the results. Most of the effect
have been designed to investigate the potential for further
appeared to relate to improved local and regional disease
improvement by combining modified fractionation with
control with less conclusive evidence for a reduction in
simultaneous chemotherapy. Enhanced acute and late
the incidence of distant metastases. By 2004, the group
toxicities
had analysed 87
treatment and have been carefully documented in most
randomized
trials including 1 6,665
are
a
major
concern
with
such
intensive
patients with a median follow-up of 5.5 years and
of these studies. Pure hyperfractionation with or without
comprising 50 concomitant, 32 induction and 9 adjuvant.
cisplatinum and 5-fluorouracil in a trial of 122 patients
The absolute benefit for chemotherapy overall is 4.4
reported by Brizel et al.47 has been shown to improve
percent at five years. As previously reported, the best
loco regional control from 44 to 70 percent, albeit with a
results are with concomitant schedules offering an 8
high risk of confluent mucositis in both arms of the trial.
percent gain; however, these later results are free from
Jeremic et al.48 using a similar approach with 77 Gy given
significant heterogeneity and therefore the data can be
in 35 fractions over seven weeks with or without low-dose
taken as conclusive. The least benefit was noted for
daily cisplatinum achieved an overall survival improve
adjuvant chemotherapy. Similar results were seen for
ment from 49 to 68 percent without incurring increased
conventional and for modified radiotherapy fractiona
early or late toxicity. Distant metastasis-free survival was
tion. The main analysis compared all patients receiving
also improved by the combined modalities.
Direct comparison of concomitant and induction che
neous chemotherapy with hyperfractionation and accel
chemotherapy to those treated with radiotherapy alone.
motherapy trials confirmed superiority of the former. Of interest, the group analysed the larynx-sparing studies,
which compared a control arm of immediate surgery followed by postoperative radiotherapy
to induction
chemotherapy, followed by definitive radiotherapy. Whilst there was no significant difference in overall survival or
disease-free survival, there was a non-significant trend in favour of the
control
arm.41 The same
group have
analysed the data from eight randomized controlled trials for nasopharyngeal cancer, drawing the same conclusion
The most intensive approach of combining simulta eration Naude49
has
also
been
compared
hyperfractionated
investigated.
conventional
and
accelerated
Do brovski
fractionation radiotherapy
and to
a
with
mitomycin C. Locoregional control was increased without an increase in mucosal toxicity, although haematological toxicity
was
significantly
greater
in
those
receiving
chemotherapy. The inclusion of two variables in the experimental . arm,
namely
altered
fractionation
and
chemotherapy, make it impossible to determine which of these agents was responsible for improving disease
Chapter 200 Developments in radiotherapy for head and neck cancer
I 2759
control and such trial design should be avoided. How
tumour. Resultant volumes are therefore relatively crudely
ever,
derived from 2D
et
the
most
recently
reported
trial
by
Staar
al.50 comparing hyperfractionated acceleration and
chemotherapy using 5-fluorouracil and carboplatin in
x-ray
films with at best assumed
lmowledge of the position of critical soft tissue structures, tumour and organs at risk.
263 patients has failed to show significant improvement
Fast computers introduced in the 1990s permitted the
in locoregional control despite the 'intensity' of the
use of computed tomography (CT) and other axial slice
combined arm.
imaging modalities to allow the radiotherapist to define
Of
stimulating factor
significance,
(G-CSF) was
granulocyte added
as
colony
a second
tumour and normal tissues. Software reconstructs a three
randomization with the intention of reducing mucositis
dimensional (3D) image of these volumes. The radiation
and resulted in decreased tumour control, possibly a
beams should 'conform' as closely as possible to the shape
result of tumour clonogen stimulation by the growth
of the tumour, which a�� by no means simple cuboidal,
factor. These results have been somewhat conflicting, perhaps reflecting the heterogeneity of approach and the need for longer-term follow-up.
cylindrical or even spheroidal structures. This is further
exemplified when associated tumour masses coexist in close proximity, for example a primary tumour with
Two more recent trials have investigated modified
locally involved nodes surrounded by normal tissues. The
radiation fractionation with concurrent chemotherapy.
3D software allows the radiation beams to be shaped by
Budach et
the linear accelerator to achieve this objective, hence the
aI.51 have compared hyperfractionated, acceler
ated chemoradiotherapy with concurrent 5-fluorouracil
term 'conformal radiotherapy'. The software also calcu
and mitomycin C to dose-escalated hyperfractionated acce
lates the dose of radiation delivered to specific volumes of
leration without chemotherapy and found chemoradiation
both the tumour-bearing target and normal tissue 'organs
to be more effective in their study. Perhaps most impres
at risk' and displays these by dose-volume histograms,
sively, the French FNCLCC-GORTEC combined group
thus
have achieved an impressive 37.8 percent two-year overall
determining precise dosimetric information for accuracy
providing
the
radiotherapist
with
a
tool
for
survival in patients with inoperable pharyngeal carcinoma
of treatment and of risk of damage to normal tissues.
using intensive hyperfractionated dose-escalated radio
Whilst long established in North America and northern
therapy with concurrent cisplatin 5FU compared with 20.1
Europe, 3D conformal radiotherapy has only recently
percent for patients treated with the same radiotherapy
become available in many UK centres
(Figure 200.1).
T hree-dimensional conformal radiotherapy has un
schedule, but without concurrent chemotherapy. Side 52 effects at two years were similar in both arms of the tria1.
doubtedly been a major step forward. Nevertheless the
Nevertheless although we know from the MACH-NC
radiation beam arrangements are relatively simple and do
meta-analysis that the benefit from concomitant che
not permit complex coverage of convex shapes; for
motherapy applies both to conventional and modified frac
example, when a high radiation dose curves around an
tionation. The question as to whether modified fractionated
organ at risk such as the spinal cord, brain stem or major
radiotherapy or conventional radiotherapy should be used
salivary
when combined with concomitant chemotherapy remains
pharyngeal irradiation.
glands,
as
is
frequently
required
in
naso
largely unanswered. This key issue is being addressed
The development of intensity-modified radiotherapy
in two large randomized controlled trials in Europe
(IMRT) is the potential leap ahead. Multiple beams of
(GORTEC 99-02) and North America (RTOG H029).
varying intensities are used to create irregular shapes if necessary
with
concave
contours
(Figure
200.2).
RECENT ADVANCES From two-dimensional planning through conformal radiotherapy to intensity modulated radiotherapy The discussion so far has focused on biological and biochemical methods
for modifying and modulating
radiotherapy delivered by conventional, 'crudely' shaped radiation beams directed at the tumour target. For more than two decades, conventional two-dimensional planning has used standard x-ray film
(2D)
(2D) taken by a
simulator, a machine that is geometrically identical to the linear
accelerator
or
cobalt-60
treatment
unit.
The
radiotherapist then defines the area to be treated on film defined by bony landmarks, together with clinical and radiological Imowledge of the position and extent of the
Figure
200.1
Three-dimensional conformal radiotherapy.
2760
I PART 17 HEAD AND NECK TUMOURS
squamous carcinoma.
6D
High EGFR receptor levels in 61 Over
tumours are associated with adverse outcome.
expression of the epidermal growth factor receptor is 62 associated with increased resistance to radiation and exposure of tumour cells to ionizing radiation increases the level of EGFR expression, the blockade of which 63 increases cell sensitivity to radiation. Cetuximab is a monoclonal
antibody
the EGF receptor.
against
the
ligand
domain
of
Phase I and II studies indicated
safety and efficacy in head and neck squamous carcinoma 64 and was shown to reverse platinum resistance. As a 65 result, Bonner et al. undertook a multicentre, rando mized controlled trial published in 2006, in which 424 patients Figure 200.2
Intensity-modulated radiotherapy.
53 54 and the Preliminary results were most encouraging • technology is rapidly gaining a prime position in the treatment of head and neck cancer in the western world, although disappointingly with the UK once more lagging behind North America and northern Europe. The ability to reduce toxicity by avoidance of critical organs at risk, specifically the parotid glands without compromising tumour coverage and control has been clearly demon S5 56 and most specifically in the nasopharynx.
strated
Quality of life has been shown to be improved when comparing IMRT to 3D conformal radiotherapy by a S7 recent French matched pair analysis and is the subject of the ongoing
UK PARSPORT trial.
Accurate definition of the position and extent of the gross tumour volume is essential and requires both clinical knowledge of tumour extent through examination and imaging. Since no single imaging modality is entirely accurate, image fusion technology has been introduced and has shown benefit, particularly with the use of 58 Never
positron emission tomography (PET) with CT.
theless, there is a potential downside to IMRT. Since multiple
beams
are
used,
often
seven
with
advanced
head
and
neck
squamous
carcinoma were randomized to radiotherapy alone versus
or
more
as
compared to two or three with 2D or 3D conformal radiotherapy, a larger volume of normal tissue receives low-dose radiation. This is potentially mutagenic and concern has been raised, albeit by calculation, about the 59 possible increased risk of second malignancies. IlVIRT is unquestionably a new gold standard, although we must proceed with vigilance. It will undoubtedly be included in future fractionation and combined modality
radiotherapy with concomitant cetuximab. Cetuximab 2 was given initially as a loading dose of 400 mg/m a week prior to commencing radiotherapy then weekly 2 throughout at a dose of 250 mg/m . Radiotherapy was defined as high dose, although
the schedules varied
according to the trial centre. Daily fractionation to the North American standard of 70 Gy in 35 fractions over seven weeks was commonly employed and also hyper fractionated and concomitant boost accelerated irradia tion, as used in the aforementioned RTOG 9003 trial.
The median duration of locoregional control, the pri mary endpoint, was 24.4 months for cetuximab plus 14.9 months with
radiotherapy compared to
radio
therapy alone. At a median follow-up of 54 months, the median overall survival, the secondary endpoint, was 49 months with the combination compared to 29.3 months with radiotherapy alone. An acneiform rash and infusion reactions were the only additional acute toxicity with cetuximab. In particular, the grade and frequency of acute mucositis was the same in both arms of the trial, in sharp contrast to the enhanced acute 6s effects when using concomitant chemotherapy. Despite clear with
benefits,
the
radiotherapy
use
of
cetuximab
concomitant
has not been accepted as a new
standard of care because concomitant chemoradiotherapy is now considered as standard and not single modality radiotherapy,
which
was
the
control
arm
in
this
study. Furthermore, this agent is costly in comparison to drugs such as cisplatinum. Therefore, proof of con cept awaits the results of a further large clinical trial, RTOG 0522.
studies, with the ultimate aim of achieving even greater enhancement of the therapeutic ratio between tumour destruction and normal tissue tolerance.
Taxanes As previously discussed, induction chemotherapy has,
EGFR inhibition The EGFR receptor is a member of the receptor tyrosine
Erb B group of
kinases which is abnormally expressed
in many epithelial tumours including head and neck
historically, proven to
be at best marginally effective. The
reasons
have
somewhat
theories
postulated
been
for
the
unclear
lack
of
with
success.
various Whilst
cisplatinum yvith or without 5-fluorouracil have been the mainstay of chemotherapy in head and neck cancer for two decades, the development of new agents,
m
Chapter 200 Deve l o p m e n ts in ra d i oth e ra py fo r h e a d a n d n eck ca n c e r
particular the taxanes, taxotere and taxol has offered new
scope in the treatment of head and neck squamous carcinoma. Extrapolation from phase II studies demon strated greater activity in advanced disease than cisplati num plus 5-fluorouraci1.66 Taxotere
(docetaxel)
has
been
most
extensively
KEY POINTS •
5-fluorouracil (TPF). Patients with stable or responsive disease then underwent radical radiotherapy. At a median of 51 months follow-up, the overall survival in the TPF arm was 18.6 percent compared to 1 4.2 percent in the PF arm. Quality of life was better in the TPF arm and
head and neck cancer is of high quality,
•
•
with advanced head and neck squamous cancer were randomized to receive neoadjuvant TPF versus PF for three cycles, followed by chemoradiotherapy with syn
chronous carboplatin. At a median follow-up of 42 months the overall survival is 70.6 months for the TPF arm compared to 30.1 months in the PF arm correspond
Multidisciplinary team working is essential Treatment should be started as soon as
possible after diagnosis and staging. •
Interruption of treatment should be avoided.
•
Alimentation support should be used, i.e. percutaneous endoscopic gastrostomy (PEG) feeding, when large areas of mucosa are being
neutropoenia, thrombocytopenia was less frequent com In the TAX 324 study by Posner et al.,68 539 patients
primarily level 1.
for ensuring optimum care.
although there was a higher incidence of grade 3 and 4 pared to PE67
The evidence base for most recent developments in non-surgical management of
trial randomized 358 patients with unresectable disease to four cycles of 'standard' cisplatinum/5-fluorouracil (PF)
Squamous cell carcinoma of the head and neck is a heterogeneous group of diseases.
•
investigated in randomized controlled trials. The EORTC
or to the same number of cycles of docetaxel/cisplatinuml
I 2761
irradiated. •
Three-dimensional conformal radiotherapy should be a UK standard.
•
Modified radiation fractionation confers local
control and survival advantage. •
•
Synchronous chemoradiotherapy confers local control and survival advantage. Consider use of cetuximab synchronous with radiotherapy in those patients unsuitable for
ing to an impressive two-year overall survival advantage
platinum agents.
of 14 percent for TPF. Grade 3 and 4 neutropenia was more common in the TPF arm. Taxotere used in the TPF combination has also been used in a larynx-sparing study reported by the GORTEC group in which 220 patients with locoregionally advanced larynx and hypopharyngeal cancer were investigated. After three cycles, non-responders underwent surgery followed by postoperative radiotherapy, while the re sponders
underwent
radiotherapy
alone.
The
overall
response rates were higher for those treated with TPF 82.8 versus 60.8 percent for PE Corresponding laryngeal preservation rates were 63.2 and 41.4 percent, respec tively.69 Taxol (paclitaxel) has been similarly investigated. Hitt
Best clinical practice It is now c l e a r t h a t o n ce d a i ly ra d i o t h e ra py doses of 2 Gy g i ven five times p e r w e e k fo r six to seven w eeks for patie nts w ith l o ca l ly a dva nced squa m ous ca rc i n o m a is substa n d a rd . Th e re a re s evera l i m po rta n t poi n ts t o be n oted fo r d e l iveri n g o pti m a l treat m e n t. "
m u l tidisci p l i n a ry tea m meet i n g , i n o rd e r that th e
et aCo have reported a randomized trial of 382 patients
o p ti m a l ca re p l a n ca n be fo rm u lated to m e et t h e
with locoregionally advanced squamous cancer of the head and neck. Following three induction cycles, patients responding to chemotherapy were treated with chemo radiotherapy with concomitant cisplatinum. The com plete response rate was 33 percent for the TPF (paclitaxel) compared to 14 percent in the PF arm, although the median follow-up time is short for this trial. These results indicate that both neoadjuvant taxotere
and
taxol
survival
improve
results.
locoregional
Nevertheless,
control
and
unanswered
overall
questions
remain; how does induction TPF followed by concomi tant chemoradiotherapy compare to concomitant che moradiotherapy alone? Can taxanes be used safely and effectively concomitant with radiotherapy? Is there an additional role for EGFR inhibition in addition to the use of these new highly active taxane agents?
A l l patie nts must be d iscussed at a n d m a n a g ed by a
n eeds of t h e i n d ivi dua l patie nt. "
Avo id gars in d e l iveri n g ra d i ot h e ra py treat m e nt. Mainta i n patient's h a e m og l o b i n at 1 2 g I L or a bove. Ma i ntain a l i m e n tat i o n th roug h out treat m e n t and afte rwards u nti l n o rm a l o ra l i nta ke has been re esta b l is h ed. The m ost co m m o n trea t m e n t a p p roa ch for a d va n ced d isease is t h e use of c o n c o m i ta nt c h e m o ra d i ot h e ra py with a p l ati n u m ag ent, eith e r ci s p l a ti n um o r ca rbo p l ati n . I m prove m e n t i n overa l l s u rviva l is of t h e o rd e r of 8 percent at five yea rs for a l l ag e n ts a n d poss i b ly h i g h e r for such p l a ti n u m co m po u n d s. En h a n ced a c u te radi atio n reacti o n s a re to b e exp ected a n d require i n tens ive pati e n t m a n a g e m e nt. Late effects a re beco m i n g i n creas i n g l y a p pa re n t a n d
2762
I PART 1 7 HEAD AI'lD l'lECK TU M O U RS
m a n y patie nts w i l l n e e d l o n g -te rm s u p po rt,
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Quality of life In head and neck cancer RANDALL P MORTON AND HISHAM MEHANNA
Introduction
2766
Key points
2778
The QL concept: definition and measurement
2767
Best clinical practice
2778
Historical developments of QL in HNC
2771
Deficiencies in current knowledge and areas for future
Current QL instruments for HNC
2772
QL in HNC: current status
2774
Demographic characteristics
2776
research References
2778 2779
The data in this chapter are supported by Medline, Embase and Cochrane searches using the key words quality of life, benefit, satisfation, outcome measures, head and neck cancer, larynx carcinoma, glottic carcinoma, supraglottic carcinoma, pharynx carcinoma and radiotherapy. Cited references from papers identified were also manually searched, as well as recent review articles and standard and specialist textbooks on head and neck cancer trials.
INTRODUCTION Just what constitutes ... quality of life for a particular patient and the therapeutic pathway to it often is extremely difficult to judge ... JR Elkington, 1966
1
In the latter half of the twentieth century, quality of life (QL) emerged as an important outcome measure of medical treatment, especially for patients with chronic or incurable disorders. It is now common practice to include QL outcomes when considering the results of treatment, especially in clinical trials where alternative treatments are being compared. For patients with cancer, the quantity of survival is naturally the outcome of primary importance, but when deciding on the desirability of a recommended treatment for any particular patient, the quality of that survival is also a major consideration. 2 Such QL will also normally be weighed against the chances of survival and the likely QL outcomes that other available treatment
options might offer. There is some evidence, however, to suggest that optimizing QL leads to more treatmentcompliant patients, resulting in an increase in surviva1. 3 [*** 1**] It can also aid in the identification of patients and families with psychosocial problems or risk factors, such as alcoholism or depression, needing active intervention. QL has special relevance for head and neck cancer (HNC) patients because of the particular difficulties that they may encounter with everyday functioning. Whilst traditional outcome measures of HNC do not correlate with patient benefit, QL correlates strongly with satisfaction. Moreover, when different treatment modalities give comparable survival, QL after treatment becomes a major factor for deciding the treatment modality. Formal QL assessments in the treatment of HNC should help to determine the balance between an optimal therapeutic effect on patient survival on the one hand, and an acceptable QL outcome on the other. QL measurement also helps the physician understand the patient's perspective. The paradox is that the patient's
Chapter 201 Quality of life in head and neck cancer
functional status, or the doctor's perceptions of a 'good result', are not necessarily reflected in the patient's own ratings of their QL. 2 The complex and the counterintuitive nature of the QL outcomes serve to make the study of QL in HNC patients most intriguing. For example, patients generally do not want to trade survival for function, while doctors consistently misjudge the patients' perception of what comprises mutilating treatment and incorrectly prioritize the patients' aims. 2 However, there are difficulties relating to the definition and measurement of QL in cancer patients. There is also a problem of the patient's premorbid characteristics, such as culture, and how these may influence QL outcomes. Furthermore, the category of HNC is a rather heterogeneous group of tumours and the associated QL measures are probably also dependent on the nature of the specific tumour types and head and neck subsites.
THE QL CONCEPT: DEFINITION AND MEASUREMENT General perspectives
'" we should recognise that the effects of therapeutic strategies and of therapy itself on quality of life are not certain until they have been measured. D Osoba, 1991 4
Most people probably have an intuitive understanding of the meaning of QL, as the term is frequently referred to and used in relation to health in general and cancer in particular. However, QL is often not measured and usually not specifically defined so that although it is well accepted as a concept, as a clinical outcome measure it represents a relatively new scientific paradigm. Social science research has led to the conclusion that QL has four particular operational characteristics that are incontestable: that is, QL is a self-reported, subjective, multidimensional phenomenon that changes over time (see Table 201.1). These characteristics provide a perspective of QL and a basis for understanding the concept but, as they stand, they do not provide a working definition. To conduct QL Table 201.1
Features of the QL phenomenon in cancer patients.
Operational characteristics
QL assessments must be selfadministered QL is subjective, but quantifiable QL is multifactorial, or multidimensional Overall QL (and each dimension's value) varies over time
Essential com ponents/doma i ns Physical function Psychological state Social interaction Somatic sensation
I 2767
research, a general, working definition for QL is needed. It should incorporate the philosophy of patient-based measures and provide a basis for comparing patients' general well-being within and between studies.
Definition
Quality of life measures the difference between present experience and expectations and between perceived and actua I goa Is. KC Caiman, 1987 5
The World Health Organization (WHO) definition of health-related quality of life (HRQL) is as follows: an individuals's perception of their positioning in life in the context of the culture and value systems in which they live and in relation to their goals, standards and concerns. It is a broad ranging concept affected in a complex way by the person's physical health, psychosocial state, level of independence, social relationships, and their relationships to salient features of their environment 6
King et aC observed that the lack of even a consensus definition of QL may be related to the nature of the concept itself. They identified ten descriptors or definitions of health-related QL from the literature to 1995. A summary statement from these offerings is that QL is a concept relating to the level of one's well-being and satisfaction and encompassing a range of physical and psychological characteristics and limitations that describe one's ability to function and derive satisfaction in doing so. In other words, QL represents one's personal, subjective assessment of general well-being which can be regarded as a composite scale involving many contributing domains. A key process in the personal integration of the various aspects of one's life is the perceived discrepancy between the reality of what one has, and what one wants, or expects, or has had. 8 The concept embodied in this process has been called the 'gap' theory and refers to the gap between reality on the one hand and expectations and desires on the other. This gap needs to be self-reported, because observers (e.g. doctors) cannot rate it accurately.2, 8 Another key factor in the QL construct is the individual's ability to adopt and employ various coping strategies. 9 A patient-rated global QL measure will necessarily take account of the gaps between expectations and reality, the relative importance of those 'gaps' to that individual, and how they cope with them. HRQL has a disease as the focus. From King et al.'s review,? it is apparent that QL in adults is related to, but distinct from, health status. Terrel et al. 10 refer to an 'overall bother' score as a global QL measure as a result of
2768 I PART
17 HEAD AND NECK TUMOURS
symptoms related to the HNC condition. They also employ a similar scale for a patient's assessment of their response to treatment. Cohen et aI.ll see HRQL as a compromise which reflects preoccupation with the disease rather than the patients' experience of illness. Their preferred approach is to focus on 'existential wellbeing' rather than HRQL, especially in cancer patients, and this is consistent with the definition, and the approach to measurement, of QL that is used here.
Characteristics of QL FIRST OPERATIONAL CHARACTERISTIC: SELFADMINISTERED QUESTIONNAIRE ... the patient's viewpoint of what constitutes a good quality of life is at least as valid as what a researcher or clinician might suggest. AJ MacSweeney and KT Labuhn, 1990 12
An important issue in QL research is the perspective from which it is defined. It is recognized that the patient's own perspective is the preferred source for QL data?' 13 An observer is effectively an onlooker of another's life situation and as such will have a limited, or at least different, perspective. Clinical observers have a perspective that usually relates to the on-going clinical management of the patient: a wealth of evidence now shows that clinical impressions by observers can be misleading, and that the patient's priorities differ from the health care worker's. 2 Some observations may be quite well correlated between physicians and patients - such as degree of disfigurement - but the personal (QL) impact of the observed variations cannot be anticipated. 14 [***] Partners and other family members are observers who usually have specific and direct concerns about their relative's disability and deformity but who do not necessarily rate the patient's perception QL accurately. IS Family members' concerns are likely to influence assessment of the patient's QL, and this perspective may determine the quality and amount of support that the patient receives. IS Society's view of QL for HNC patients may very well also approximate to a family's initial response. The net result may be a significant impact on the patient's own QL assessment.
Of course, objective measures can be used to monitor progress reliably and to validate subjective assessments. List et aI.16 have produced a reliable performance scale which can discriminate among different levels of functioning across a broad spectrum of HNC. List et al.'s more recent studl 7 of patients with laryngeal cancer shows 'virtually no relationship between [postoperative] performance outcome and emotional, social, functional or overall QL'. They found that patients cope 'rather effectively with both acute and residual disease and treatment effects ... to the extent that these residuals do not globally interfere with life satisfaction'. Ware4 also points out that regression models of objective measures of function generally explain less than half of the variance in the patients' rating of that function. Objective measures of function, such as swallowing, speech, shoulder movement and muscle strength measures, are quantifiable and reliable. However, the effect that any specific dysfunction may have on a patient will vary according to many factors, so that objective measures are not necessarily valid QL scores. The use of objective measures is said to stem from a 'beneficence model' of healthcare which assumes that health professionals know what promotes or protects the best interests of patients. It is more likely in fact that patients are in a better position than clinicians to define good and harm as it relates to them. Clinicians have traditionally regarded subjective measures as unreliable. Despite some problems with inconsistency and difficulties with interpretation and measurement, guidelines 18 have emerged from research in several different fields of oncology. These guidelines are generally accepted and can be applied for the study of QL in HNC (see Table 201.2).19 It is now understood that subjective ratings of QL can be both reliable and valid, and that patients should score their own QL, rather than have it assessed for them by an observer. [***] Several QL
Guidelines for the development and implementation of OL questionnaires in cancer patients.
Table 201.2
Guidelines
2
3
4
SECOND OPERATIONAL CHARACTERISTIC: SUBJECTIVE, BUT QUANTIFIABLE DATA
... biologic indicators are not adequate proxies for measures of functional status, well-being or other quality-of-life concepts or to changes in these variables over time. JE Ware Jr, 1991 4
5
6 7
8
Decide the hypothesis to be tested Decide on definition of quality of life to be used Disease-specific questionnaire to include: diseaseand treatment-related symptom scores; health and disease status Patient data to be self-reported Enquiry on domains of functional status to include: psychological functioning; socio-sexual functioning; physical functioning; global OL measure (patient-generated) Field testing and fine-tuning of questionnaire Instruments should have proven, or be checked for: 'reliability; validity; responsiveness/sensitivity Design longitudinal study
\
Chapter 201 Quality of life in head and neck cancer II 2769
instruments have been described for use in HNC. Rogers et al. 20 and Ringash and Bezjak13 summarize these extremely well. The most commonly used instruments are discussed below under Current QL instruments for HNC. From a practical standpoint, researchers and clinicians should attempt to obtain information from as many perspectives as reasonably possible, but the patient's subjective assessment should form the most important data nucleus, while data from clinicians (e.g. the disfigurement scale), 'significant others' and objective measures (e.g. measures of swallowing) will provide useful supplementary information. THIRD OPERATIONAL CHARACTERISTIC: MULTIDIMENSIONAL NATURE
Ultimately, the combination of quality-of-life domains assessed in a given study is a function of the patient population under consideration, the nature of the applied treatments and the specific research questions at hand. NK Aaronson, 199021
The general principle that QL is a multidimensional construct, with contributions from several different aspects, or 'domains', of life has widespread agreement among QL researchers? Certainly single-perspective, unidimensional or single-instrument evaluations of QL are now recognized as inadequate. The specific domains contributing to global QL, or general well-being, will vary according to clinical and sociocultural circumstances. 9 There are several advantages associated with the multidimensional approach in the measurement of QL. These have been identified by Aaronson22 as follows. • The positive and negative effects of a given treatment can be disentangled. • Different effects at different stages may be identified, even in the presence of a constant global QL score which would be insensitive to such changes. • Both anticipated and unexpected effects can be documented by monitoring the different components of QL. While specific terminology may differ, the essential components of QL can be divided broadly into four domains: physical function, psychological state, social interaction and somatic sensation/symptoms (Table 201.1). Other domains are also accepted as contributory, but these are not normally included in routine QL assessments. King et aI.7 suggest that any comprehensive QL measure should have a spiritual component. Only one of 18 studies in Gotay and Moore's review9 of QL in HNC included a spiritual dimension. Cella and Tulskl 3 also cite two other domains - sexuality/intimacy and
occupational functioning - which have received rather more attention. Fraser24 considers that QL should incorporate not only physical, psychological and social well-being, but also economic, occupational and domesticlfamily domains. Others regard the inclusion of the financial component as an 'inappropriate and possible distorting addition'. Although the financial consequences of an illness are clearly important, their effect upon a patient, and the community as a whole, is dependent on the structure of community social support programmes rather than the biology of the disease. Which dimensions should be included in any study would depend on the aim of the study and the profile of the population under review. Regardless of the number of domain items, the overall effect on a patient's QL will be expressed by way of a global measure. FOURTH OPERATIONAL CHARACTERISTIC: VARIATION OVER TIME
Idea lIy the data shou Id describe the QL of patients before, during and after treatment, giving a continuous picture of any changes. PM Fayers and DR Jones, 1983 25
One of the major basic principles of research into QL of HNC patients (see Table 201.2) is to design a longitudinal study. deGraeff et aI.26 discuss the difficulties of interpretation of data relating to long-term QL outcomes effects from cross-sectional studies of HNC, and King et aI. 7 state unequivocally that 'there is no substitute for longitudinal assessment in QL research' as there is an ebb and flow in global QL in patients with cancer. It is also well recognized that QL and health status may not be congruent. This apparent paradox - where patients can be severely disabled by treatment and recurrent tumour yet exhibit a relatively good QL, while other patients who are free of disease and who have minor treatment-related symptoms may be very distressed with a poor QL - is not unusual. Therefore, longitudinal studies are important so that patients may be used as their own internal controls. The baseline study is essential if future assessments are to be weighed against the initial status. The premorbid characteristics that a patient brings to the initial consultation are clearly very important in relation to later events. The ideal first assessment should probably therefore be after the time of diagnosis but before the beginning of treatment (it is interesting to note that noncancer patients presenting for diagnostic biopsy are more distressed pre-diagnosis than patients who turn out to have HNC 27 ). The critical QL value is often not any particular score a patient provides at a specific time, but rather the change over time. This can be extrapolated to comparisons of groups of patients where the central issue is not necessarily whether the overall score is better in one group, but rather whether the change in scores observed
2770 II PART 17 HEAD AND NECK TUMOURS
over time is different in each group. In that way, the dynamics controlling QL outcomes for individual patients and groups of patients can be adequately understood. Longitudinal studies of traditional HNC research differ from longitudinal QL outcomes research in that studies that select survival and disease-free curves as primary outcomes derive a single data point from each patient entered in the study. That data point is only acquired when the patient either dies or fails therapy. Thus a patient can be lost for many years and yet all the survival data can be retrieved if he appears in the clinic one day for follow-up. QL data, because of its fluctuating nature, is not recoverable once lost. QL studies require consistent and careful follow-up in order to promote meaningful comparisons and to avoid important loss of information. Given adequate data relating to each of the contributing domains, and sufficient time for follow-up, it is likely that the principle determinants of poor QL in HNC patients will emerge. Only then may one purposefully pursue Aaronson's suggestion22 that interventions to improve QL status be introduced.
Methodological issues surrounding QL assessment
Choosing an instrument is an exercise in trade offs. CM Moinpour
et 01., 1989 28
QL measurement in cancer patients should use an instrument that not only accounts for likely disease and treatment-related symptoms, but also incorporates several other domains and an overall (global) QL rating and follows them over time. These principles are central to any QL enquiry and they lead to the major methodological issues that surround QL assessment. First, there is no 'gold standard' measure against which any overall QL score can be tested. 13 This is not unusual in social science. In fact, when one considers the central role that coping strategies may play in determining QL outcomes, it is no surprise that there is also no gold standard for coping ability, even though scales such as the 'locus of control' and the 'sense of coherence'2 have been extensively investigated and developed, and applied in HNC. Nevertheless, the absence of a gold standard should not dissuade one from seeking benchmark measures against which to compare any proposed new assessment tools. The second issue relates to the need for both global and component measures. The principles regarding the component-versus-global QL measurement issue have been discussed and developed by Cella and Tulskj3 and Gotay and Moore9 and reviewed more recently by others. 29 While a 'global' score provides a ready means of comparison between treatments and between patient groups, it is also rather nonspecific and difficult to
interpret. Therefore, QL should also be assessed at the multidimensional, or component, level so that clinicians obtain the kind of information they require for understanding and interpretation. Ideally, the functional measures most important in determining general well-being for any patient or group of patients will be determined, thus enabling healthcare workers to act upon the results. In order to obtain an overall QL score, some researchers have summed the assigned scores from several different QL items. 13 This approach presupposes that the method of scoring each item actually represents the weighting, or importance, that patients generally ascribe to that item, and that there is no confounding between items. It also assumes that the selected items represent virtually all the important factors that contribute significantly to a patient's overall QL. A question on global QL in which the patient rates his or her own overall QL is more appropriate, as QL is more than the sum of its parts. 13 Each or any of the contributing domain items can then be examined for a correlation with the global QL. Fries and Spitz30 use the term 'hierarchy of patient outcome' to describe the relationship between global QL, its contributing domains, and the component measures, and to emphasize the importance of recording both global and component scores. For example, while the European Organization for Research and Treatment of Cancer (EORTC) questionnaire produces an aggregate score, it also contains a single-item, overall global QL measure. This has recently also been recognized by the University of Washington group who developed one of the first head and neck cancer-specific questionnaires, and who have now added a global single-item question to their instrument. 13 A third problem for QL instruments is that a comprehensive enquiry of all the likely contributing domains would result in a very arduous, time-consuming and unwieldy questionnaire. A short enquiry is likely to miss important contributory components, and indeed there is a functional dependence of reliability on the length of a test that serves to emphasize the importance of ensuring that a questionnaire is not too short. The notional ideal length of a questionnaire is probably best described as one in which as much relevant information as possible is obtained without tiring or alienating the patient or interfering with the efficient delivery of clinical care. This is likely to differ for every clinical department and may take some time to determine for any specific situation. Hassan and Weymuller31 regard the ideal QL HNC questionnaire to be short, concise, easy to understand, minimize opportunity for health-worker bias and be sensitive to changes in health status. As a general principle, one should probably attempt to gain a little information about as many different domains as possible, rather than to obtain a great deal of information and data from a small pumber of domains. The fourth major methodological issue relates to generic versus diagnosis-specific QL instruments. Generic
Chapter 201 Quality of life in head and neck cancer II 2771
questionnaires cover a broad range of items in different domains, but tend to lack important questions specific to any cancer site or type so that sensitivity and responsiveness to important clinical change may be lacking. Generic scales assess concepts that are relevant to everyone, but are not specific to any age, disease or treatment group. They contribute unique information about QL that is not captured in disease-specific measures. Many, including Gliklich et al.,29 believe that it is essential to use both generic and disease-specific measures and to analyze them together. In any event, to ensure content validity, questionnaires for patients with cancer need to be, at least to some degree, site-specific to accommodate the widely varying nature of disease- and treatment-related symptoms. These requirements should not discourage the clinician-researcher unduly: as Aaronson 22 states, 'we cannot ... afford to wait for the "ideal" measure or the "state of the art" infrastructure. Incremental improvement in the quality of our research can be expected only as we develop hands-on experience with the methods that are currently available to us'. It is disappointing to see that, despite a plethora of publications, no consensus has yet emerged as to which specific factors should be measured, or which methods should be used in HNC. One generic instrument that has attained widespread popularity and use is the SF-36. This has been applied to many different diseases as varied as sinusitis, hypertension, arthritis and gastro-intestinal disorders. It records data on six domains: physical functioning, role functioning, social functioning, mental health, health perceptions and bodily pain. This allows comparison between very different conditions providing data on health status across groups of patients. Although the result is rather nonspecific however, because of its generic nature, it has been used for QL assessment in HNC by several authors.
HISTORICAL DEVELOPMENTS OF QL IN HNC
since no-one has yet reported a cure by radical operation, there must be no basis for argument. It cannot increase comfort to add postoperative anemia to cancerous cachexia. C Jackson, 1901
QL assessment as part of clinical practice in oncology had its beginnings approximately 50 years ago. Early QL studies in HNC patients were narrative and crosssectional; these were followed at first by simple quantitative measures of various factors and later by longitudinal studies of greater complexity. Relatively few HNC studies have reported global QL and only recently have prospective studies and the incorporation of QL assessment in randomized HNC clinical trials emerged. As yet,
no studies have compared QL measures from widely different sociocultural groups.
Changing attitudes
in deciding the method of treatment we should not, in our eagerness to achieve cure, lightly disregard the crippling that may result from our surgical endeavors MR Ewing and H Martin, 1952 32
Although recognition of the importance of the patient's personal life-satisfaction or psychological well-being in the management of an illness goes back to Hippocrates' (c460-377 Be) time, the traditional focus of medical care has been on the treatment and control of disease, on the assumption that patient benefit will follow. So it is that in 1886 Jessett spoke of maxillary cancer' ... the only hope we have of permanently benefiting the patient suffering from this disease is by free and extensive operations, i.e. thoroughly removing the whole of the cancerous tissues and getting to healthy structures'. Open concern from doctors treating HNC for patients' psychological well-being became increasingly evident in the latter half of the twentieth century.21 In 1954, Ormerod 33 described the standard practice of taking care before laryngectomy to explain to a patient what is entailed in the operation, including counselling by a speech therapist and interviews with previous patients. In 1983, Natvig confirmed the importance of this in his studies. 34 Even so, those concerns were not universal: indeed, it was common for the diagnosis to be withheld from patients - a situation hardly conducive to systematic psychosocial enquiry. On occasions, psychological enquiry of patients with cancer was even vigorously opposed. 21 Concern for the psychosocial aspects of patients facing death gathered momentum in the 1960s with the emergence of the hospice movement pioneered by Cecily Saunders in the UK and Elizabeth Kubler-Ross in the USA. This phenomenon gave considerable impetus to the development of QL assessment in oncology in general. Despite the interest in QL outcomes after curative therapy, the study of effectiveness of palliation for patients with end-stage recurrent disease is likely to be one of the most important and useful applications of QL research in head and neck cancer.
Terminology
'What kind of a device would you call this?' asked one of his scientific friends present. 'I call it an X ray,' said Roentgen. 35 DT Atkinson, 1958
2772 I PART 17 HEAD AND NECK TUMOURS The term 'quality of life', was first used in an essay submitted to the Dwight Eisenhower's Presidential Commission on National Goals by AL Heckscher. 21 In 1977, 'quality of life' became a 'key word' by which journal articles could be retrieved by the United States National Library of Medicine Medline Computer Search program. Since then, there has been a steadily increasing body of QL-related clinical research, including work related to HNC, as evidenced in recent reviews. A Medline search for articles published in 2002 containing the words 'quality of life' reveals 7297 citations.
QL measurements and measurers
Opinions vary as to the usefulness and interpretation of various quality of life instruments (but) the need to consider the possible impact of treatment on QOL is widely recognized A Trotti et al., 1998
36
The history of QL measurement follows the history of the development of the QL concept, and the evolution of the science of psychometric analysis. Quantitative assessment of QL in patients with cancer had its beginnings in the latter half of the 1940s,21 although the psychosocial impact of treatment was regarded at that time as not generally quantifiable. Before 1980, the validity and range of QL measurement devices was such that few useful studies emerged. The patient interviews that formed the basis of many reports were usually not defined, and those psychometric instruments that were described were directed at only one or two QL aspects, such as emotional state. Only very limited information could be derived with these study designs. In 1981, McNeil et al. 37 provided some insight to society's values in their analysis of trade-offs that the different groups within the community were prepared to consider in respect of treatment alternatives for advanced laryngeal cancer. They concluded that (healthy) people were prepared to trade two or three years of life in return for preservation of the larynx when considering treatment options for a theoretical advanced laryngeal cancer. In the 1980s, the psychometric properties of QL instruments became able to be tested. Several crosssectional studies developed and tested the reliability and validity of modern QL instruments devised using Guyatt's principles.13 The most comprehensive cross-sectional study of HNC patients from the early studies was reported by Natvig. 34 The research was confined to patients in Norway who had had a total laryngectomy between six months and 18 years previously, and represented a valiant effort to cover all aspects of the impact of the surgery, including physical, social, psychological and occupational aspects of life. In general, the
early cross-sectional studies were concerned with laryngeal cancer and laryngectomy. Those reports relating to oral and pharyngeal cancers indicated that rehabilitative concerns were often greater than those generallyencountered after laryngectomy. Social scientists (e.g. Gotay and Moore9 ) see that HNC is ideally suited to QL measurement and that 'the development and application of vigorous scientific research in this field holds enormous promise'. Although the potential importance of QL outcomes in HNC research is probably still not fully appreciated by many clinical otolaryngologists, there is considerable interest in the QL paradigm from both disciplines. A 1983 paper from Sweden was the first collaborative effort between the otolaryngologist and social scientist, and the first to provide a quantified QL index in HNC. Since then there have been many examples. The most recent step in the evolution of QL measurement has been the longitudinal studies - where patients act as their own 'controls' - and data from clinical trials where like groups can be legitimately compared. These provide a much more reliable basis upon which to determine those factors which influence QL outcomes. Pruyn et aI.15 searched the literature for studies of psychosocial aspects of HNC and found 117 studies to 1984, of which only 13 'chose a longitudinal approach'. Most of those studies were limited in scope - such as voice rehabilitation following total laryngectomy - and not very sophisticated from a psychometric perspective. Pruyn's review for the period 1984 to 1995 38 showed a clear increase in the proportion of prospective studies (16 out of 50 selected studies). Several of the longitudinal studies used instruments with good psychometric properties and somewhat broader parameters than earlier reports. Most of the studies are of rather limited duration (three to six months), although studies of two and three years duration are now appearing. The longitudinal studies of less than 12 months duration have probably been too short to draw conclusions regarding overall QL outcomes. Nowadays, it is standard practice to include QL considerations in clinical research, to the extent that QL has become a recommended end-point in clinical trials, and the National Cancer Institute of Canada Clinical trials Group now incorporate QL data in all their clinical trials.
CURRENT QL INSTRUMENTS FOR HNC
It is hard properly to evaluate human suffering: the blind say they would rather be blind than deaf; whilst the patient without a voice considers himself fortunate that he is neither blind nor deaf. 39
LA Schall, 1954
Chapter 201 Quality of life in head and neck cancer I
Guidelines for development of QL questionnaires
Researchers should undertake comprehensive literature searches to ascertain whether a suitable measure is available before they decide to develop a new [measure] A Garratt et 01., 2002 40
The science of psychometric and clinimetric measures has developed to the stage where a considerable degree of confidence in reliability and validity can be generated in the data from self-administered questionnaires. Kirshner and Guyatt 18 have developed a framework for evaluating health indices such as QL assessment, in which they describe the basic steps for the development of an instrument (Table 201.2). Kirschner and Guyatt'sl8 requirements for development of QL questionnaire items are: selection of item pool, item scaling, item reduction, reliability, validity and responsiveness. The issue of questionnaire validity is a notion that is not traditionally familiar to clinicians. Bombardier and Tugwe1l41 provide guidelines for assessing questionnaire validity, in terms that can be readily understood by medical readers (Table 201.3). The principles embodied in those steps have been incorporated and developed into a guideline for the study of QL by the EORTC. 19 The EORTC QLQ-30 core questionnaire has been through this development process. It represents a generic QL instrument and a 'head and neck' site-specific module designed for HNC patients has been added. An instrument subjected to this kind of rigour will be robust and able to provide meaningful data for analysis.
Summary of commonly used QL instruments Choosing which instrument to use poses a challenge for investigators of QOL in head and neck cancer... , No one instrument is ideal for all purposes. J Ringash and A Bezjak, 2001 13
Table 201.3
There are now many instruments in use for assessing QL in cancer patients and several (71 were identified in a . 13) h ave b een developed or adapted recent reVIew specifically for head and neck cancer. Many studies have conducted cross-validation of HNC-specific instruments with various generic instruments, and between HNCspecific questionnaires, so that the validity and reliability of many instruments has now been determined. 9,13 The most commonly used measures of QL have been summarized in Tables 201.4 and 201.5. The information presented has been adapted mainly from the review of commonly used QL instruments in HNC by Ringash and Bezjak.13 All the instruments included have their particular strengths and weaknesses, and it is acknowledged that no one measure exists for all purposes. The informed selection of a measure appropriate for a specific requirement is essential, and may be guided by structured reviews, consensus and expert opinion. To take the situational examples mentioned by Ringash and Bezjak in their review,13 the EORTC or Functional Assessment of Cancer Therapy (FACT) may be useful for studies comparing HNC patients to those with other cancers, as these tools have general as well as specific modules, and have been used extensively to assess different cancers. If, on the other hand, the aim was to study very specific patient groups, then a very specific tool, for example Head and Neck Radiotherapy Questionnaire (HNRQ) for radiotherapy patients or University of Washington Quality of Life Questionnaire (UWQOL) for surgical patients, may be more sensitive. For international or multicultural studies, the EORTC or FACT may be most appropriate as they have been translated into several languages, and the EORTC has been assessed crossculturally. Garratt et al. 40 suggest that 'researchers should undertake comprehensive literature searches to ascertain whether a suitable measure is available before they decide to develop a new [measure],. Aaronson 21 advocates that energy be spent searching for existing instruments to suit (perhaps with some modification) rather than expended on generating new instruments. This is a view
Terms used to describe the various forms of validation that a QL questionnaire must exhibit.
Psychometric criterion
2773
Biomedical terminology
Meaning
Content validity Face validity Criterion validity Discri mi na nt validity Construct validity
Comprehensiveness Credibility Accuracy Responsiveness
Questions cover relevant issues Questions are clear Performance of instrument in comparison to a 'gold standard' Ability and sensitivity to detect change
Biological sense
Reliability
Reproducibility
Ability of instrument to behave in a fashion consistent with a theoretical framework Ability to produce similar results on retesting
2774 II PART 17 HEAD AND NECK TUMOURS Table 201.4
Characteristics of commonly used Ol instruments.
General (G) or specific (S) Validated No of items No of domains Self-administer Global measure Summary score Cross-cu Itu ra I validation/ tra nslation Scoring Time to complete
EORTC OlO C30/HaN35
FACT-G/HaN
HNRO
Ol-HaN
QlO
Ol-RTI/HN
HNQOl
UW OOl
Both
Both
S
Both
S
Both
S
S
+
+
+/-
+/-
+/-
+/-
+/-
+
65 6
27
22 6
29 3
19
39 5
21
12 9
4
+ +
+
+ +
+ +/-
+ Several
+
4
+ ?
+
+ + +
B 11
B Short
Japanese, German, Spanish
Ongoing
languages C30- BHN35-W B 18 5
4
+ + + +/-
B 10
B 15
? ?
? ?
+
criterion present or proven; - not present or not yet proven; +/- limited or partial proof available; ? not assessable. B means the higher the score, the better the QL; W means the higher the score, the worse the QL or symptom. EORTC QLQ C30/HEtN35, European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire for Head and Neck Cancer C30/HEtN35; FACT - G/HEtN, Functional Assessment of Cancer Therapy-General/Head and Neck; HNRQ, Head and Neck Radiotherapy Questionnaire; QL-HEtN, Quality of Life Instrument for Head and Neck Cancer; QLQ, Quality of Life Questionnaire for Advanced Head and Neck Cancer; QOL-RTI/HEtN, Quality of Life-Radiation Therapy Instrument Head Et Neck Module; HNQOL, University of Michigan Head and Neck Quality of Life; UWQOL, University of Washington Quality of Life Questionnaire. Adapted from Ref. 13.
Table 201.5
Purpose and uses for which instrument was developed.
Instrument
Stated purpose
Uses
EORTC OlO C30/ HaN35 FACT-G/HaN HNRO Ol-HB:N OlO
D, E
For use in HNC patients in all stages, acute or chronic, treated or untreated
D, E E D, E E
Ol-RTI/HN HNOOl UW OOl
E D, E D
For descriptive, discriminative and evaluative use To measure radiation-induced acute morbidity and Ol in HNC patients To be a short sensitive, disease-specific questionnaire with emphasis on psychological factors To discriminate between patients with advanced HNC undergoing radiotherapy alone or surgery and radiotherapy Very specific for measuring Ol in patients undergoing radiotherapy Overall assessment of disease-specific Ol in HNC patients Intended primarily for patients undergoing surgery
D means discriminative purpose, E means evaluative purpose. EORTC QLQ C30/HEtN35, European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire for Head and Neck Cancer C30/HEtN35; FACT - G/HEtN, Functional Assessment of Cancer Therapy-General/Head and Neck; HNRQ, Head and Neck Radiotherapy Questionnaire; QL-HEtN, Quality of Life Instrument for Head and Neck Cancer; QLQ, Quality of Life Questionnaire for Advanced Head and Neck Cancer; QOL-RTI/HEtN, Quality of Life -Radiation Therapy instrument Head Et Neck Module; HNQOL, University of Michigan Head and Neck Quality of Life; UWQOL, University of Washington Quality of Life Questionnaire. Adapted from Ref. 13.
supported by many. Future efforts should be directed at completing the assessment of reliability, responsiveness and validity of current measures, concentrating on direct comparisons between measures, and on determining the most appropriate tools for particular situations. [Grade B]
QL IN HNC: CURRENT STATUS There are many apparent inconsistencies in QL research in HNC pati~nts that are probably related to many different factors, such as patient case mix, local treatment, method of voice rehabilitation after laryngectomy
Chapter 201 Quality of life in head and neck cancer I 2775
(oesophageal voice versus tracheo-oesophageal puncture), available social support, and cultural and ethnic issues. Measuring QL outcomes using clinical trial methodology can control some of these factors.
Impact of time on QL
There was a significant improvement between diagnosis and the 3 year assessment for global QL E Hammerlid et al., 2001 42
The longitudinal studies of QL in HNC reported to date have generally used different instruments to measure QL. In those studies where different instruments are compared, it has been shown consistently that the different QL measures correlate strongly with each other, which suggests that the different questionnaires are measuring the same phenomenon, but in slightly different ways. In general, studies show that QL at diagnosis is lower for HNC patients than for the population in genera1. 43 This worsens during and immediately after treatment. In Hammerlid et al.'s study,44 QL reached its worst level one month after radiotherapy treatment, and three months after total laryngectomy. Schliepake et al. 45 found that the same was true for patients having oral cancer resections. QL then starts improving, so that by one year after treatment QL returns to pretreatment levels. 42 ,43 There appears to be a slight further improvement between the first and third years, as reported by Hammerlid et al. 42 Morton 8 showed no significant drop in general well-being (global QL) at three months after treatment but a significant improvement, compared with pretreatment levels, after 12 and 24 months. By three years, although patients still suffer significant functional deficits, their global QL shows no significant differences to the general population. 42 [***]
Impact of site and stage of disease on QL
Patients with large tumours were more affected by their disease than patients with small tumours E Hammerlid et al., 1998 44
QL is positively correlated with the stage and site of the disease. 46 ,47 The effect of stage of the primary tumour on QL may seem as a surrogate for the effects of treatment, as one determines the other. However, even at diagnosis, stage III and IV laryngeal tumours have lower global QL scores than stage I and II.44 Furthermore, QL improved after treatment for all stages, but still remained lower for the more advanced tumours. deGraeff et al. 46 found that the same was true for oral cancers and Rogers et al. 48 found that tumour size for oral cancer was a significant
predictor of post-treatment QL at one year. Therefore, it would appear that the stage of the disease independently affects QL. Interestingly, Hammerlid et al. 42 found that the difference in QL due to stage appears to increase with time after treatment, so that it was greater at three years than at diagnosis. [***] The site of the primary tumour not only affects functions specific to that site, but also appear to affect global QL. Weymuller et al.,47 in their prospective study of 210 patients, found that hypopharyngeal tumours have the worst global scores and laryngeal tumour patients have the best. Other studies have found the same. Moreover, subsites differ in their effect on QL within one site, for example, patients with tongue base tumours have the worst QL amongst patients with oral cancers. 48 [***/**]
Impact of treatment on QL
Results suggest that total laryngectomy is not necessarily a disastrous event for most patients 49 RP Morton, 1997
HNC patients do not want to trade off survival for function. 2 Therefore, survival is the consideration that should be of primary importance whenever cancer treatments are compared and the QL aspects of care need to be reviewed in the light of the eventual survivorship. There appears to be a perception amongst some clinicians that because radiotherapy does not result in tissue loss, it must lead to a better QL. This is not supported by the published data. It is important when counselling patients and deciding on treatment options to bear in mind that any treatment modality in HNC, whether it be surgery, radiotherapy or a combination of both, results in significant morbidity and a negative impact on QL. It is also important to remember that current evidence suggests that QL is primarily not determined by treatment modality. Furthermore, functional limitations caused by treatment do not necessarily translate into worse QL. In other words, QL does not correlate with physiological measures of function. List et al. 17 found no difference in global QL between total laryngectomy, hemi-Iaryngectomy and radiotherapy treatment groups in their study of 21 laryngeal cancer patients. However, they demonstrated quite marked differences between these treatment groups in respect of symptoms and physical functioning scores related to speech and deglutition. They stated that their findings 'contradicted expectations that functional restrictions ... would have a negative impact on overall QL'. Another report, comparing QL outcomes of laryngeal cancer patients treated either by radiotherapy or total laryngectomy, showed similar apparently counter-intuitive results in which patients treated surgically had greater
2776 II PART 17 HEAD AND NECK TUMOURS dysfunction than patients treated by radiotherapy, and yet had similar global QL scores. 49 In their prospective study of 210 patients, Weymuller et al. 47 also found that there was no difference in QL between the chemoradiotherapy and laryngectomy treatment groups. Furthermore, Stoeckli et al. 50 compared patients with early laryngeal disease treated by laser with those treated by radiotherapy and found no significant differences in global QL. This seems to suggest that at least some groups of patients can learn to cope with and adapt to dysfunction, given time and appropriate support measures. It should be remembered that longitudinal studies of two years or more have less than 50 percent of the initial patient group surviving to contribute to the two-year assessment. However, those that do survive seem to have adapted remarkably well to their disability or handicap. [***] Survivors from the widely reported 'VA study' of laryngeal cancer, where patients were randomly assigned to combined surgery and radiotherapy or induction chemotherapy prior to radiotherapy or surgery, have recently been reviewed for QL outcomes. 51 While the study was not designed to monitor QL, the prominence of this particular study means that the results are viewed with great interest. Only 46 of 93 'known survivors' were assessed, and speech function was found to be similar irrespective of laryngectomy status. Pain was greater and emotion/ depression scores were better in the patients in whom the larynx was preserved. The results indicated that pain and psychosocial function were more important to patients' QL than speech. Unfortunately the crosssectional nature of the QL data and the incomplete follow-up raises many questions. Another important aspect of the effect of treatment on QL is the impact that the mode of reconstruction (mainly in oral cancers) has on QL. Because of the considerably greater effort and cost involved in revascularized tissue reconstruction, it is important to establish its efficacy and superiority over less complex reconstruction techniques to justify its routine use. Schliepacke et al. 45 have recently shown that revascularized fasciocutaneous flaps produced the greatest improvement in QL, when compared to local flaps and myocutaneous revascularized flaps. Moreover, at 12 months, revascularized forearm flaps resulted in a higher QL than at diagnosis. Myocutaneous revascularized flaps for large volume defects produced the lowest QL scores, with QL being significantly lower at one year than at diagnosis. [***]
Impact of premorbid patient characteristics on QL
Psychological interventions in patients with head and neck cancer that fail to take pre-existing problems into account may incorrectly focus on adjustment to illness. W Baile et 01., 1993 52
It is likely that, if survivorship and QL outcomes are similar between treatments, economic factors will become major determining factors in the treatment decisionmaking process. One variable that may moderate that process, however, is the premorbid QL profile of any particular patient. Very little information is available in relation to the premorbid characteristics of HNC patients.
DEMOGRAPHIC CHARACTERISTICS Studies do not show a consistent difference between men and women [in QL] ... With. regard to age, it is often assumed that elderly patients fare worse ... but few data support this view A deGraeff et 01., 2000 46
Demographic information, such as age, gender, vocation, work profiles, level of education and marital status, is often reported but it is not clear what importance to place on these factors from the QL point of view. At this stage, there is no consistent evidence for any inter-group differences in QL at diagnosis or as an outcome, based on the aforementioned demographic patient variables. 42 ,43 [**]
Alcohol and tobacco
... alcohol consumption ... may not be perceived by the patients as having as much of an effect on health status as does medication ... EM McDonough et 01., 1996 53
The life-time alcohol and tobacco consumption of HNC patients has been widely reported, but these life-style features of social functioning do not necessarily reflect QL or general well-being, and they often change (by choice) after treatment for HNC. This suggests that patients' priorities alter after they discover that they have developed a malignancy. However, if patients are instructed to alter dietary habits (including reduction of alcohol consumption) after treatment for head and neck cancer, their compliance is not predictable. 53 Some research suggests that the individuals who have less disruption to their lives - for example those who have less advanced disease or who undergo less invasive treatment - are the ones more likely to continue smoking 53 despite an increased risk of recurrence and death. Importantly, there is evidence that alcohol intake 'can provide important prognostic information' in HNC, and that abstinence amongst alcoholic patients can lead to prolonged surviva1. 54 [***/**]
Chapter 201 Quality of life in head and neck cancer
Sexual functioning
2777
Some authors have investigated pretreatment sexual functioning in HNC patients. De Santo et aI.55 found that approximately two-thirds of laryngeal cancer patients treated surgically cited no change or only a slight decrease in sexual interest after surgery, but that approximately 20 percent of all patients reported serious sexual performance problems postoperatively. Presumably, not all of the patients reporting 'no-change' were sexually active pre-operatively. Hen'anz and Gavilan,56 using the same instrument as DeSanto et aI., reported 55-60 percent of patients and their spouses had no change in their interest in sex and approximately 40 percent had no change in sexual activity. It is uncertain from these reports how sexual functioning - or a change in functioning correlates with overall QL or whether it should be recorded at the time of diagnosis. [**]
Davies et aI.27 examined the psychosocial aspects of patients prior to endoscopy for diagnostic biopsy and found that patients with cancer had a significantly higher rate of depression (29 percent) before biopsy than the group of patients whose biopsies were negative. Baile 52 et aI. also found a high rate (approximately 40 percent) of pathological anxiety and depression among HNC patients prior to biopsy, but found that patients with benign lesions were slightly more emotionally disturbed and significantly more stressed. Baile et al. suggested that cancer patients may minimize the seriousness of their problems, and that there is 'a need to assess psychological status of these patients before treatment'. The very few prospective studies in this field show that depressive symptoms were one of the significant pretreatment predictors of QL. 46 [***] Moreover, there is evidence now emerging that psychosocial intervention (in the form of long-term psychological therapy) results in marked improvements in QL of HNC patients compared to controls. 44 These findings have led several authors to suggest that the identification of patients with depression should be routinely carried out, and interventions instituted as part of the rehabilitation programme. [Grade B]
Coping skills
Cultural. religious and spiritual factors
As for sex, I didn't think of my cancer of the larynx patients in terms of their sexuality. LW DeSanto, 1995 55
'" (the first area to) be considered in determining patient risk for psychological disturbance includes patient variables such as '" coping resources. RP McQuellon and GJ Hurt, 1997 57
There is a gathering body of evidence to suggest that preexisting abilities in relation to coping skills and stress management may well be important. 2 The retrospective nature of most of the studies of coping means that only survivors are assessed and that the evidence is potentially biased or nonrepresentative of the total population being studied. Baile et a1. 52 noted that HNC patients showed a more 'repressive' coping style than noncancer patients, with high scores on dependency and social conformity among the HNC group. This would explain the observation that married patients fare better than unmarried patients, and that over 80 percent of laryngectomy patients who retain their circle of friends develop oesophageal speech, whereas only 10 percent of those who lose all their friends regain speech. [**]
Psychological factors Heightened attention to the psycho-social concerns of patients treated for head and neck cancer will serve to '" increase levels of compliance and maximize patient outcomes. EM McDonough et al., 1996 53
75% of patients surveyed thought that their physicians should address spiritual issues as part of their medical care 58 DA Matthews et al., 1998
For many years, QL in HNC has been reported from different centres by authors who each used their own particular measure to record QL. In recent years, there has been wider utilization of some of the QL instruments by different centres which allows comparison between populations. Even so, there has been little or no attempt by authors, to examine or explain differences between populations according to cultural differences. Some studies have reported multicentre studies of QL in HNC patients, but still there is a degree of cultural homogeneity in the study groups. The impact of religion and spirituality has recently been studied more closely. Studies show that they have a positive role in maintaining physical and mental health in times of stress and grief and that 75 percent of HNC patients want doctors to address spiritual issues. 58 [**] Doctors are not trained in routine questioning about the role of religion in the patient's coping mechanism, but this should be encouraged. 2 [Grade B]
Social support Social support ... is thought to be a good predictor of subsequent well being SL Collins, 2000 2
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Starn et al. 59 found that satisfaction with social support and preoperative counselling by a laryngectomee predicted later satisfaction and higher QL. Natvig34 also identified three areas that were important QL determinants. These were: individual patient coping skills, family support and preoperative counselling of the patient and his family. Other studies have found similar findings. [**]
Performance status
[Preoperative] functional status ... has been shown to be positively correlated with QL 46 A deGraeff, 2000
In the study by de Graeff et al.,46 the baseline pretreatment performance status (as measured by the Karnofsky performance status) was one of the significant predictors of QL after treatment. Similar findings were reported by Hammerlid et al. 60 in their study which found that physical functioning at diagnosis was an independent predictor of global QL at three years post-treatment. [***]
KEY POINTS • Patients' perceptions differ significantly from doctors. • QL is an integral part of assessment of outcomes in HNC. • QL measurement should be routine, prospective and long term; using brief, patient-reported, validated tools, with both general and disease-specific modules. • QL should be incorporated into the management pathway of the patient to help improve patient care. • QL is the same after chemoradiotherapy or surgery for HNC, despite differences in functional deficits. • QL usually decreases immediately after treatment, then gradually increases to pretreatment levels, usually by 12 months. • Further research is required.
It is important to have a clear definition for OL. OL studies should use patient self-reported data, which account for at least the four main domains, and which provide a patient-rated global OL score, as well as disease-specific measures.
Studies should use existing validated instruments, and should follow patients longitudinally from the time of diagnosis. Preoperative counselling by a laryngectomee is important. Additional information may be gathered from the patient's family - objective assessments of function, such as swallowing and speech, may be useful. Identification of patients with depression and alcoholism should be routinely carried out, and interventions instituted as part of the rehabilitation program. Routine questioning about the role of religion in the patient's coping mechanism, and how to support that, is to be encouraged. Empower patients - give patients a sense of control by involving them in decision-making. Set realistic expectations and avoid over-optimistic outlooks. Offer patients the opportunity to talk to other patients who have had treatment - this is found to be one of the most effective interventions to increase OL. Use the most oncologically effective treatment first, then make modifications that can optimize OL, for example parotid sparing postoperative radiotherapy. Get involved in patient groups and post-treatment educational and support groups.
Deficiencies in current knowledge and areas for future research Clear consensus on which OL measures are important. Large, randomized prospective studies with same site primaries to compare different treatment regimens (e.g. is OL enhanced by the following: selective neck dissections, organ preservation surgery, organ preservation chemoradiotherapy?). More data on the impact of ethnicity, culture and spirituality on OL. Evaluation of best OL tools for particular subsets of HNC. Clearer understanding and more regular assessment (e.g. by a specialist counsellor) of contributing factors to well-being and determination of effects of intervention in these on OL. Long-term (10 + years) longitudinal data. Interventional studies (randomized controlled trials) to judge the effect of counselling, social support, etc. on OL outcomes. Future research to concentrate on validation of current measures and determination of the most appropriate tools for particular situations.
Chapter 201 Quality of life in head and neck cancer
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Palliative care for head and neck cancer CHARLES DIAMOND AND CLAUD REGNARD
Introduction Palliative care Breaking difficult news Pain in advanced cancer Oral problems Dysphagia Constipation Malignant ulcers and fistulae
2781 2782 2782 2783 2788 2789 2791 2791
Hypercalcaemia Superior vena caval obstruction Stridor Psychological problems The terminal phase (the last days and hours) Acknowledgements References
2794 2794 2795 2795 2798 2800 2800
The data in this chapter are based on evidence presented in the Cochrane database of systematic reviews and the results of a Medline search using the key word palliative care and focussing on pain, analgesics, dysphagia, wound care, mucositis, depression, radiotherapy and chemotherapy.
INTRODUCTION Palliative care comes to the fore when the effects on patients with advanced head and neck cancer become complex and severe. Primary treatment with surgery, radiotherapy and/or chemotherapy if indicated, will already have been carried out, but the disease will have progressed to a stage where a cure is no longer possible. Patients may come to feel that they inhabit a parallel world. Everyday life goes on around them but they no longer fully belong to that world. They are partly detached from it and simultaneously they live in a land where there are no long-term plans, no long-term ambitions and no long-term future. There is a sense of isolation and loneliness because everyone they know lives in the normal world and they are alone in this twilight world. They come to realize that their physical health will deteriorate and they will probably be unable to perform everyday activities that they previously took for granted. They fear that they will lose their independence and may have to
rely on others to help them with dressing and feeding. They fear they may suffer severe pain which will affect their mind and alter their personality and, as a result, treasured relationships may be lost. Inevitably, patients wonder why this has happened to them, what is going to happen next and how they will be able to manage. The diagnosis of incurable disease also has a profound effect on the patient's family and close friends. They realize that they will only have the patient for a limited period of time and they experience anticipatory bereavement and grief. A gulf develops between the patient and themselves because the patient has become partly detached from the everyday life they shared. At times, the patient's mind and thoughts seem to be in a lonely place that they cannot reach. Family and friends begin to edit what they say lest some thoughtless remark about the future might cause the patient distress. Some of the spontaneity of their relationship is lost. Families have to undertake a new role as carers for which they may feel extremely inadequate. Knowing that the patient's health
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will decline and that they will be unable to prevent it adds to their sorrow. Along with feelings of grief come (usually unfounded) feelings of guilt (,If only I had noticed sooner.' 'If only I had not been away'). The diagnosis triggers a harrowing period of anguish for the family and close friends. The diagnosis of incurable disease can also produce a feeling of powerlessness in the doctors and nurses who are the professional carers for the patient. Trained to heal and cure, they are sometimes overwhelmed by feelings of inadequacy. In addition to attempting to deal with the physical effects of the disease, they have to grapple with emotional, spiritual and social problems of which they may have little experience and for which they may have had little training. The sense of being at a loss can disturb their judgement and, as a result, their treatment of the patient's distress may be inadequate. Sadly, surveys have shown that severe pain remains unrelieved in over half of patients with cancer. 1 Many professionals and teams are able to help patients and their families effectively. This supportive care is the duty of every professional and the right of every patient. On many occasions however, problems are severe or complex and specialist help is needed. The role of palliative care is to support existing teams by providing a means of managing the distress of incurable illness for the family and the professional carers as well as for the patient.
PALLIATIVE CARE Palliative care is the total care of patients and their families by a multiprofessional team when the patient's disease is no longer responsive to curative treatment. 2 In addition, the World Health Organization (WHO) states that palliative care: • affirms life and regards dying as a natural process; • neither hastens nor postpones death; • provides relief from pain and other distressing symptoms; • integrates the psychological, physical, social and spiritual aspects of the patients care; • offers a support system to help patients live as actively as possible until death; • offers a support system to help the family cope during the patient's illness and in their own bereavement.
BREAKING DIFFICULT NEWS It is a regrettable fact that many patients express shock
and anger when they recall the way the news was broken to them that their disease had reached an incurable stage. This results in a disparity between what patients were told
and what patients perceive they were told. It is the perception of what they were told that stays with them and leads them to recount remarks like: 'The doctor said that there was nothing that could be done so there was no point in coming back to the clinic' and 'You've got cancer and it has spread, so it would be a waste of time treating you.' In their highly charged emotional state, patients and their families can experience feelings of being abandoned, rejected and devalued. In advanced disease, professionals often have the difficult responsibility of breaking bad news and need to be acutely aware of the dynamics of the situation and of the natural emotional reactions of the person receiving that news. Breaking bad news is distressing and expression of this distress by the patients and family eases the distress and helps acceptance and adjustment. It is important to allow feelings like anger to be expressed and acknowledged (e.g. 'In view of all you have gone through I'm not surprised you feel angry'). Unfortunately, doctors sometimes try to block or inhibit the expression of emotional distress in order to avoid an uncomfortable and embarrassing emotional scene. Instead, they should try to facilitate the expression of this normal and natural emotional reaction to bad news. The doctor should plan the breaking of the bad news as soon as it is known and should select a quiet room, free from interruptions, where the conversation cannot be overheard. It is helpful if another professional is present, for example a nurse who knows the patient and has been involved in the patient's care. It is also helpful for the patient to have a friend or relative present for support. Breaking bad news in the middle of a busy corridor is unacceptable and can be avoided by thoughtful planning. Bad news should be given in increments for two reasons. Firstly, it allows the patient to break the flow of bad news at any time and it ensures that the news is given at a pace the patient can control. Secondly, it helps with the understanding of the news for there is a limit to how much an individual can take in and remember at anyone time and this limit is reduced in times of severe emotional distress. Before breaking bad news it is important to determine what the patient or relative already knows. It is sometimes surprising how much, and sometimes how little, the patient knows so it is unwise to make assumptions. The WARN, PAUSE, CHECK (WPC) approach is often utilized: 3 • WARN that the news is not going to be good news (for example, 'Unfortunately there are some worrying changes in the biopsies'). • PAUSE to ensure that the warning shot has been recognized and to allow the patient to reply so that a two-way conversation can develop instead of a monologue .. Aim for dialogue, not a monologue. The patient might reply, for example, 'What's wrong with the biopsy?'
Chapter 202 Palliative care for head and neck cancer III 2783
• CHECK that the patient has taken the warning shot on board and then give the first part of the news, for example 'Do you want me to explain the changes?' • WARN 'I'm afraid the biopsy showed some abnormal cells.' • PAUSE to allow the patient to respond. They might say 'I thought I was doing all right' or 'I knew there must be something wrong.' • CHECK that the person wants to receive more information, for example, 'Would you like me to explain the biopsy results to you?' • WARN if the patient wants to continue, give an explanation, for example 'I'm afraid the biopsy shows that you have cancer in your throat.' • PAUSE to allow the patient to respond. The patient might reply 'Does this mean the cancer has come back?' Reply: 'Yes. That's what the biopsy shows.' • CHECK that the patient wants to continue. For example, 'Would you like me to tell you more about it just now?' • CHECK their feelings, for example, 'Does that surprise you?' or 'How are you feeling right now?' The WPC approach is repeated until the person has all the information they want at that time. It is important to check that the person has understood the news. It is equally important that the person knows that the door is open to return for further information or clarification. It is good practice to offer a follow-up interview. Sometimes the news is met with denial, for example 'I'm sure that can't be right. I feel so well.' It is unhelpful to force the truth on the patient at this stage. It is wiser to simply reaffirm the truth and leave it at that, for example, 'I wish it weren't true but I'm afraid that it is.' Denial can sometimes help patients to come to terms with the situation in their own time and in their own way. Less commonly, the patient will ask that the diagnosis should not be disclosed to the family and of course the patient has a legal right to this confidentiality. Occasionally, the situation is reversed and the family ask that the patient should not be informed of the diagnosis. Although these attempts at collusion are kind efforts to shield the loved ones from fear and distress, the doctor should explain the legal situation and the problems of distrust caused by collusion and attempt to negotiate a satisfactory solution. In tandem with giving bad news, one should also give hope. It is wrong to lie to a patient or to give unrealistic expectations. Hope can be generated by emphasizing what can be done to relieve symptoms and especially to relieve pain. Hope can also be fostered by switching the patient's focus from achieving a cure to achieving the best quality of life for the time that remains. This is helped by encouraging the setting of realistic goals and targets that the patient can achieve. Most of all, patients need to be reassured that they matter and are worthwhile, and that their professional carers will continue to work hard to
Checklist 202.1
D D D D D
Bad news cannot be made less bad, but it can be broken badly. Breaking bad news clumsily causes increased emotional distress. Breaking bad news constructively is a skill which can be learned. Bad news should be given in increments. Refusal to accept bad news (denial) can sometimes be helpful.
support them and to provide for their medical and nursing needs (see Checklist 202.1).
PAIN IN ADVANCED CANCER Pain is both a physical and an emotional experience. Physiologically, it is well recognized that a noxious stimulus will produce an unpleasant sensation. However, pain also causes an emotional response which aggravates the unpleasant sensation. Pain can cause fear and anxiety and fear and anxiety can increase the pain. The pain threshold can be lowered by depression, fatigue and loneliness and raised by sleep, sympathy and companionship. Dame Cicely Saunders,4 the founder of the modern hospice movement in the UK, promoted the concept of 'total pain' to include the physical, psychological, emotional and spiritual aspects of pain which results in the patient's distress. Unrelieved pain can cause misery and generate feelings of resentment and anger which may lead to a questioning of previously held beliefs and relationships. It is important to set realistic goals for both the patient and clinician. Initially, a pain-free full night's sleep should be the aim, followed by relief during the day. Freedom from pain at rest during the day should be the next step, followed by reduced pain on movement. Being free from pain on movement, and indeed at all times, is the final aim, but it may not be possible to achieve this in all patients. Analgesics are more effective in preventing pain than in the relief of established pain so it is important that they are given regularly and prophylactically. Analgesics given solely on an as-required basis will not relieve persistent pain. It is estimated that three-quarters of patients with advanced cancer have pain. Of these, approximately one-fifth have a single pain, and the rest have two or more pains, while approximately one-third have four or more pains. 5 Different pains require different therapeutic approaches and it is helpful to assess the likely cause of pain before starting treatment. It is important to distinguish between pain caused by stimulation of nerve endings (nocioceptive pain) and pain caused by nerve dysfunction (neuropathic pain), for example trigeminal neuralgia, because they respond differently to analgesic drugs.
2784 I PART
17 HEAD AND NECK TUMOURS
Common types of pain in advanced cancer
palpable band or roll of muscle beneath the trigger point. Use of transcutaneous electrical nerve stimulation (TENS), or injection of the trigger spots with a local anaesthetic or acupuncture needle are often effective. Infection can cause pain, especially in the tight tissue compartments of the head and neck. In head and neck infection, pain develops rapidly with no systemic signs such as pyrexia or neutrophilia. The reduction in pain with antibiotics is usually rapid.
Diagnosing the likely type of pain is the key to successful treatment (see Checklist 202.2). BONE PAIN
This is a well-localized pain precipitated by movement or weight bearing. Severe pain on the slightest movement suggests a fracture. The pain of bony metastases responds fairly well to opioids. Radiotherapy can effectively relieve pain and also can prevent cord compression by spinal metastases, but can take up to three weeks to be effective. The pain of multiple bony metastases requires systemic treatment in addition to analgesics and radiotherapy. An intravenous infusion of a bisphosphonate is often effective and can be used safely if the patient is normocalcaemic. Pathological fractures can cause severe pain and require strong opioids and orthopaedic intervention.
VISCERAL PAIN
This is produced by disorders of the internal organs caused by tumour, ischaemia or inflammation. 6 Liver capsule stretching pain and bowel distension pain are two examples. Commonly, the pain is a poorly localized deep aching sensation in the abdomen but it may be referred to distant sites. It may respond poorly to opioids and the treatment depends on the cause. Pain due to liver capsule distension by tumour can be eased with 6 mg of dexamethasone once in the morning. Some visceral pains respond to antineuropathic pain treatment (see under Neuropathic pain below).
SOFT TISSUE PAIN
Characteristically, this is a localized aching, throbbing or gnawing pain, which responds well to opioid analgesics. Myofascial pain occurs in voluntary muscle on active movement and is common in advanced disease. It is associated with highly localized 'trigger spots' which reproduce the pain when pressed. It is common to find a
Checklist 202.2
o
Is this breakthrough pain?
Is the pain: Present at rest o On inspiration o On eating o On elimination With unpleasant sensory changes Supplied by a peripheral nerve Periodic
Is the pain persisting? o Is there unresolved fear, anger or depression? o Is the compliance poor? o Is this a new pain? o Is the analgesic inappropriate or incorrectly administered?
o
Smooth muscle spasm causes regular episodes of pain lasting for a few minutes. This periodic feature is
Pain in advanced cancer: clinical decision checklist.
Is the pain related to: Movement o By the slightest passive movement o By bone strain on examination o By active movement only o Joints, infiltration or distension o A procedure
o o o
PERIODIC PAIN
Is infection the cause?
Fracture Bone metastases Muscle strain or spasm
Pleurisy or rib metastases Oral, pharyngeal, gastric or duodenal problem Urinary or rectal problems Neuropathic pain (e.g. neuralgia) Nerve compression Colic from bowel, bladder or ureter
Chapter 202
characteristic of colic. The bowel is the commonest source followed by the bladder and ureter. Opioids are ineffective and may even worsen the pain. If bowel colic is due to constipation, opioids will make the constipation worse and increase the colic. A smooth muscle relaxant (antispasmodic) is the treatment of choice. Hyoscine butylbromide (Buscopan) is preferred since it has fewer central effects than hyoscine hydrobromide, but it is only effective parenterally.
INCIDENT PAIN
This occurs episodically on change of dressings and other procedures, on weight bearing and on movement. Incident pain may respond to opioid analgesics, but often needs additional treatment. Procedures that are painful produce increasing pain and fear each time the procedure is repeated. Adequate analgesia and/or sedation before the painful procedure can prevent this build-up of fear and anxiety. The value of physiotherapists in restoring and improving the mobility of patients with pain on movement cannot be overemphasized.
NEUROPATHIC PAIN
This is common in head and neck cancer due to damage by treatment or perineural spread of tumour? It is due to nerve damage and does not involve pain receptors. The term includes painful peripheral neuropathies and the neuralgias. Patients describe the pain as burning, shooting, pins and needles, scalding, freezing and sometimes as a deep aching. Altered sensation is an important sign. It is often possible to elicit decreased sensation (numbness), increased sensation (hyperaesthesia) and allodynia (pain that is provoked by a nonpainful stimulus such as gentle stroking). Neuropathic pain responds to opioid analgesics but may also need an antidepressant or anticonvulsant. Low dose tricyclic antidepressants (e.g. amitriptyline 10-50 mg at bedtime) may act by enhancing central inhibition resulting in increased synaptic serotonin. Anticonvulsants, for example carbamazepine and gabapentin, reduce neuronal activity and are sometimes helpful. Since the treatment of neuropathic pain can be complex, the advice of a pain or palliative care specialist should be sought.
MUCOSAL PAIN
In patients with head and neck cancer this may be due to radiotherapy, chemotherapy, infection or local tumour. Treating infection such as candida or herpes (simplex or zoster) is essential. For other causes, topical agents have been tried. Some, such as sucralfate, benzydamine or chlorhexidine, are ineffective in the presence of severe mucosal pain. 8 , 9 Choline salicylate gel can help small
Palliative care for head and neck cancer. 2785
lesions such as apthous ulcers, but severe mucosal pain often needs topical local anaesthetics such as benzocaine pastilles or lidocaine as a cream, spray or gel, but toxicity can occur with frequent use. Topical morphine may have · some patIents. . 10 11 12 a ro Ie to p Iay III ' ,
Is the pain persisting? Persisting pain may be due to a number of reasons (see Checklist 202.2) and indicates the need for advice from a pain or palliative care specialist.
Analgesics in advanced cancer Primary analgesics have a direct blocking action on pain pathways and include nonopioids (e.g. paracetamol, nonsteroid antiinflammatory drugs (NSAIDs)), weak opioids (e.g. codeine) and strong opioids (e.g. morphine). Secondary analgesics (also known as adjuvant analgesics or co-analgesics) relieve pain through a secondary mechanism such as reducing peri-tumour oedema (e.g. dexamethasone), reducing inflammation (e.g. NSAIDs), blocking neuropathic pain (e.g. amitriptyline, gabapentin), eliminating infection (antimicrobials), reducing smooth muscle colic (e.g. hyoscine butylbromide) or reducing the pain of bone metastases (e.g. bisphosphonates). The WHO recommends the joint use of both primary and secondary analgesics in the treatment of pain due to cancer. The WHO analgesic ladder is a useful guide to the prescription of an appropriate level of analgesia. 2 If pain remains uncontrolled after the maximum dose of the step 1 drug (a nonopioid) has been achieved, move up to step 2 (a weak opioid) medication. After the maximum dose of step 2 drugs has been reached, move up to step 3 drugs (a strong opioid) if the pain is not controlled. At any stage, secondary analgesics should be used if indicated.
Nonopioids in common use PARACETAMOL
This is a relatively safe effective analgesic but has no effect on inflammation. It is well tolerated and its main adverse effects are hepatotoxicity (usually only at doses greater than 6 g/24 hours) or bronchospasm. It has no effect on platelet function, does not injure the gastric mucosa and is well tolerated by patients with peptic ulcers. NSAIDs
These drugs have the dual benefit of relieving pain and reducing inflammation. In general, they impair platelet function which is a major contraindication in head and neck cancer patients with the risk of bleeding. They also
2786 I PART
17 HEAD AND NECK TUMOURS
cause peptic ulceration and renal failure. They cause salt and water retention and thus antagonize the action of diuretics. Many NSAIDs can cause bronchospasm in aspirin-sensitive patients. NSAIDs vary in their individual toxicity and response. Two of the safest are ibuprofen and diclofenac. The COX2-specific NSAIDs have half the rate of gastrointestinal irritation compared with nonspecific NSAIDs, but other adverse effects are as common and they may be less effective. Gastric and duodenal irritation can be reduced by the concurrent use of proton pump inhibitors (e.g. lansoprazole), but H2 blockers (e.g. ranitidine) are less effective.
rapidly, allowing a steadily increasing dose to be given safely. No tolerance to constipation occurs and tolerance to the analgesic effects of opioids is not seen. In the past, a misinformed fear of respiratory depression and addiction led clinicians to prescribe inadequate doses of opioids. The key to the safe and effective use of opioids in cancer patients with pain is to give carefully titrated doses on a regular basis using additional 'as-needed' doses between the regular doses if pain returns. If additional doses are required several times throughout the day, it indicates that the regular dosage is inadequate and needs to be increased.
Weak opioids in common use
Other strong opioids
Codeine, dihydrocodeine and tramadol are weak opioids but they have the same adverse effects as strong opioids. Codeine is the weak opioid of choice with a potency of approximately one-tenth of morphine. Approximately 7 percent of individuals cannot convert codeine to morphine.
Opioids differ from each other in intrinsic activity and in receptor site affinity. There are several different opioid receptor subtypes in the brain and spinal cord. The susceptibility of patients to the side effects of different opioids can also vary and therefore there may be benefit to be gained by changing a patient from morphine to some other strong opioid if morphine proves unsuitable.
Strong opioids in common use DIAMORPHINE
Morphine by mouth is the strong opioid of first choice for pain due to cancer. Both tablet and liquid morphine can be given as immediate release or as sustained release preparations. Two-thirds of patients need less than 200 mg morphine per day, but a third may need higher doses. The usual starting dose in patients previously on a weak opioid is 10 mg every four hours (or 30 mg modified release 12-hourly). A lower starting dose of 2.5 mg every four hours (or 10 mg modified release 12-hourly) is advisable for elderly patients or those not previously on a weak opioid. If breakthrough pain occurs between the regular doses of morphine, a 'rescue dose' of one-sixth the daily dose of morphine should be given. The dose of morphine should be titrated in increments of 25-50 percent every two or three days or sooner until good pain control is achieved. If swallowing is difficult or if vomiting is present, diamorphine can be given by subcutaneous injection or continuous infusion. The common side effects of morphine and of all strong and weak opioids are constipation (90 percent), dry mouth (50 percent) and nausea (30 percent).13 Vomiting (10 percent), drowsiness (10 percent) and confusion « 1 percent) are much less common. 13 It is standard practice to prescribe a laxative alongside an opioid from the onset of treatment to ameliorate the almost inevitable constipation. Respiratory depression is rare in patients with pain who are treated with titrated doses of opioids. Addiction is not seen in patients given opioids for pain relief. Tolerance to the respiratory depressant and euphoric effects of opioids develops
This drug is much more soluble than morphine and large amounts can be given by injection in small volumes. By subcutaneous injection, diamorphine is three times as potent as oral morphine. Since it is converted to morphine (i.e. it is a prodrug for morphine), it is the preferred alternative to oral morphine when the parenteral route is needed. HYDROMORPHONE
Until recently this has been the main alternative strong opioid to morphine. It does have fewer renally excreted metabolites than morphine and is useful in patients with mild to moderate renal failure and in those with adverse reactions to morphine. Only oral preparations are available in the UK. OXYCODONE
This strong opioid is now available as instant release capsules, modified release tablets and a parenteral formulation. It is the second alternative to morphine and is approximately 1.5 times more potent than oral morphine. FENTANYL
This drug is a strong opioid available as a transdermal patch. Patches .come in different strengths and can deliver 12.5, 25, 50, 75 and 100 Ilg per hour for 72 hours. When the first patch is applied there is a delay of up to 14 hours
Chapter 202 Palliative care for head and neck cancer
before peak plasma concentration is achieved, and this period must be covered by the use of another strong opioid. When removing the patch because of opioid toxicity, it can take up to 30 hours for serious adverse effects to settle. Transdermal fentanyl is approximately 150 times more powerful than oral morphine. A useful check is to divide the amount of oral morphine in milligrams per 24 hours by three to obtain the amount of transdermal fentanyl in micrograms per hour, e.g. 75 mg/ 24 hours oral morphine is approximately equivalent to a 25 Jlg/hour TD fentanyl patch. Transdermal fentanyl is deceptively simple to use but has complex and poorly understood pharmacokinetics and deaths have been reported. 14 It should never be used for postoperative pain and caution should be exercised when using it in debilitated, elderly or cachectic patients. Its use should be restricted to relatively well patients with stable pain.
OTHER OPIOIDS
Tramadol is a weak opioid with few advantages of combinations over codeine and a secondary analgesic. Methadone is a synthetic strong opioid which is sometimes used by pain or palliative care specialists in patients with adverse effects or poor pain relief with morphine (see Table 202.1).
Nausea and vomiting Nausea and vomiting are common problems that occur in 50 percent of patients with cancer. Where possible, the cause should be identified before starting treatment with anti-emetic drugs and it is worth first considering any causes that can be treated specifically, such as constipation, gastritis, hypercalcaemia and emetogenic drugs such as opioids, NSAIDs and metronidazole. It is also important to exclude regurgitation due to oesophageal or pharyngeal obstruction. Vomiting with little or no nausea can be caused by gastric stasis (large volume vomiting, heartburn, epigastric fullness, early satiation, nausea relieved by vomiting), compressed stomach (as for gastric stasis but with small volume vomiting), regurgitation (unaltered food or drink negative for acid on testing) and raised intracranial
pressure (vomiting with little warning, especially in the mornings). Most other causes of nausea vomiting have no specific pattern of symptoms, see Checklist 202.3. Immediate, practical measures required include the provision of a large bowl to avoid the distress to patients of soiling the bed and their clothes. A small kidney dish is hopelessly inadequate and seemingly designed to spread the most vomit over the widest possible area! Tissues to wipe the mouth and water or juice to rinse the mouth are also needed. The anti-emetic drugs most commonly used in palliative care are cyclizine, haloperidol, metoclopramide, dexamethasone and levomepromazine. In choosing an anti-emetic it is helpful to consider which receptors are being stimulated and then choose appropriate blocking agents. • Metoclopramide and domperidone act on peripheral dopamine receptors in the stomach and upper bowel enhancing normal motility. They are useful in vomiting due to gastric stasis caused by opioids, antimuscarinic drugs or autonomic failure. Metoclopramide can cause extrapyramidal side effects but domperidone does not readily cross the blood-brain barrier and is therefore unlikely to cause central side effects. Initially, both are best given through a non-oral route. Metoclopramide can be given as 30-90 mg/24 hours subcutaneous (s.c.) in divided doses or as a continuous S.c. infusion. Domperidone has to be given rectally as it is not available by injection. • The vomiting centres in the brain stem and medulla have a large number of histamine receptors and these centres are stimulated directly by radiotherapy to the head and by raised intracranial pressure. They are also stimulated via vestibular pathways and via cholinergic vagal and sympathetic afferents from the pharynx, liver capsule, bowel wall and urinary tract. This makes an anticholinergic antihistamine such as Checklist 202.3
D D D D D
Table 202.1
Equivalent single doses of strong opioids.
Analgesic Morphine (oral) Oxycodone (oral) Diamorphine (subcutaneous) Oxycodone (subcutaneous) Hydromorphone Reprinted from Ref. 15, with permission.
2787
Managing nausea and vomiting.
Is the patient mainly vomiting? Is this regurgitation? Is there reduced gastric emptying which would respond to a prokinetic agent? Is there raised intracranial pressure? Is there a drug or chemical cause that would respond to low-
10
D
6
D
3 3
D D D
dose haloperidol? Could there be vagal stimulation that would respond to cyclizine? Is this bowel obstruction? Is the nausea and vomiting persisting? Is fear or anxiety present? Is gastritis present? Would low-dose levomepromazine be helpful?
D
Is specialist help needed?
Dose (mg)
2
D
2788
•
•
•
•
PART 17 HEAD AND NECK TUMOURS
cyclizine a logical choice for nausea and vomiting arising from disorders in these areas. The chemoreceptor trigger zone (CTZ) has a rich supply of dopamine receptors, which makes haloperidol, a potent dopamine antagonist, the drug of choice in the treatment of nausea and vomiting due to chemical causes such as hypercalcaemia, uraemia, drugs and toxins from infections. Haloperidol is effective in low doses (1.5-3 mg at bedtime) and its long half-life of approximately 16 hours makes once daily administration possible. Levomepromazine has a wide range of receptor site affinities which makes it a useful second line antiemetic. Dexamethasone is effective in nausea and vomiting due to increased intracranial pressure, cerebral metastases and where peritumour oedema contributes to gastrointestinal obstruction. By decreasing the oedema around hepatic metastases, dexamethasone relieves the pain and nausea caused by liver capsule distension. Ondansetron, a 5HT3 antagonist, is often very effective in vomiting caused by chemotherapy and this experience has made many clinicians try it in other situations. However, its use is disappointing in palliative care where it is not routinely used.
ORAL PROBLEMS There is a high incidence of oral problems in patients with head and neck cancer because many have had radiotherapy to the head and neck region and a number have ulcerated tumours in the mouth and oropharynx. As a result, they are at risk of developing a dry, infected and sore mouth. This considerably reduces the quality of life by limiting the ability to speak, to smile or to laugh and reducing the sensation of taste and the ability to swallow and to enjoy food, see Checklist 202.4.
Checklist 202.4
Dry mouth Xerostomia is encountered in patients with debility, reduced oral intake and dehydration. Reduced salivary gland output may be caused by surgical removal of salivary tissue, radiotherapy and by drugs with an antimuscarinic action such as hyoscine. Dry mouths are more likely to develop candidal overgrowth. 16 A number of local measures can be used to obtain symptomatic relief. Neutral pH artificial saliva preparations can be helpful if used frequently, but methylcellulose solutions taste 'oily', although this is less with a spray (e.g. Saliva Orthana). Frequent sips or sprays of water are probably as effective, more convenient and much cheaper. Low pH solutions, such as Glandosane, should be avoided for use any longer than a few days. Sucking ice cubes or frozen fruit juice can also help. Glycerine dehydrates the mucosa and should be avoided, while the previously popular glycerine and thymol mouthwashes are no longer used by palliative care specialists. Chewing gum may be as effective as artificial saliva. Systemic treatment with pilocarpine tablets 5 mg three times daily can increase salivary flow in patients who have some residual salivary gland function. If there is no response within six weeks, pilocarpine should be stopped. If there is a response after four weeks but the response is inadequate, the dose can be increased. Pilocarpine 4 percent eye drops taken orally are one-tenth the cost of pilocarpine tablets. Applying petroleum jelly to the lips helps to prevent the development of cracks and fissures.
Salivary leakage If the patient cannot swallow saliva adequately, drooling is likely to be an embarrassing and troublesome problem. Antimuscarinic drugs are a helpful treatment and can be titrated to the individual's preferences. Hyoscine
Oral problems.
D D D
Is oral health at risk? Is an ulcer present? Is the mouth dirty?
D
Is the mouth painful?
D
Is the mouth dry?
D
Is there too much saliva?
Carry out preventative oral hygiene Exclude infection (herpes zoster, herpes simplex, aphthous ulcer) Exclude: Food debris Oral candida Debris from local tumour For local pain use topical protection (e.g. Orabase paste) or analgesia (e.g. choline salicylate gel) For widespread pain use topical protection (e.g. sucralfate) or analgesia (e.g. local anaesthetic pastilles, spray or gel) Exclude dehydration, drugs, infection or anxiety. Use local measures (e.g. frequent water sips and sprays) Consider pilocarpine Try hyoscine hydrobromide transdermal patch
Chapter 202
hydrobromide (scopolamine) is available as a convenient transdermal patch, each lasting for three days.
Candidiasis The best known form of candidiasis is that associated with white plaques in the mouth (acute or chronic pseudomembraneous type). However, candidiasis may present as a red tongue or stomatitis (acute or chronic atrophic candidiasis), leucoplakia (chronic hyperplastic candidiasis), simple inflammation (Newton's type 1 and 2), papillary hyperplasia (Newton's type 3), angular chelitis, or a denture-associated stomatitis. 17 The type of candidiasis depends on the candida species and local immunity. IS Hyperplastic candidiasis (synonym 'candidal leucoplakia') presents with adherent white, nodular or speckled plaques on the oral mucosa which are not easily removed, is strongly associated with smoking and is a premalignant condition. The presence of candida does not correlate with oral symptoms and most oral candida seems to be due to an overgrowth of existing candida. 19 Cross infection is uncommon and does not easily occur by way of cups and cutlery, although it can occur by way of carers' hands. 20
Palliative care for head and neck cancer
2789
is a paste designed to adhere to the surface of the ulcer and to allow the steroid to be absorbed locally. It is generally applied two to four times daily for five days. MUCOSITIS
The term 'mucositis' could be applied to any form of mucosal inflammation. In practice, the term is restricted specifically to the acute inflammation and ulceration of the oral and oropharyngeal mucosa caused by chemotherapy and radiotherapy. Strict attention to dental hygiene, the regular use of chlorhexidine mouth washes and avoidance of irritants such as tobacco, alcohol and spicy foods will reduce the severity of the mucositis. Pain can be severe (see Mucosal pain below). MALIGNANT ULCERS
Oral pain from inflammation and ulceration can be severe. Odour can be reduced with systemic or topical metronidazole (see Malignant ulcers and fistulae below) and bleeding with sucralfate suspension as a mouthwash (see Bleeding below). Pain can have multiple causes (see Common types of pain in advanced cancer above).
DYSPHAGIA ANTIFUNGALS
To be effective, nystatin must be given at least six-hourly after food, used over at least five days and continued for 48 hours after the lesions have resolved. Ketoconazole 200 mg once daily for five days clears 90 percent of pseudomembranous candida,21 and serious adverse effects are rare. Fluconazole is effective in a single dose of 150 mg, making it useful in patients with a short prognosis, but it is more expensive than other antifungal agents. Since resistance to nystatin is very rare while resistance to ketoconazole and fluconazole are well recognized, nystatin is the first-line treatment of choice.
Oral ulcers INFECTED ULCERS
Herpes simplex and herpes zoster infections can cause painful ulceration in the mouth and should be treated with systemic acyclovir 200 mg four hourly (five times per day) usually for five days. Acyclovir cream is useful for herpes labialis but should not be applied to the oral mucosa. Aphthous ulceration is no more common in patients with head and neck cancer than in the population as a whole and is treated by the topical application of steroids. Corlan pellets (hydrocortisone 2.5 mg) are allowed to dissolve in the mouth in contact with the ulcer. The usual dose is one pellet four times daily. Triamcinolone in carmellose (Adcortyl in Orobase)
Any impediment to the free flow of solids or liquids from the mouth to the stomach can be regarded as dysphagia. It is estimated that, on average, 40 percent of patients with head and neck cancer suffer from dysphagia, the incidence being low in anterior mouth lesions and being virtually 100 percent in post -cricoid tumours. It is well recognized that swallowing becomes slower with age. 22 Consequently, older patients with head and neck cancer are more susceptible to disturbances of swallowing than younger patients. The anatomy and physiology of the swallowing mechanism is described in Chapter 150, Physiology of swallowing. Any disruption of the normal anatomy and physiology may result in dysphagia and sometimes more than one cause is active in an individual patient. The main causes of dysphagia in patients with head and neck cancer are: • mechanical obstruction due to local tumour or strictures following surgery or radiotherapy; • functional obstruction due to impaired neural control. Perineural spread of cancer can be demonstrated in nearly 90 percent of post-mortem examinations of patients with head and neck cancer? Impaired neural function may cause poor mouth and lip closure, inadequate tongue movement, palatal incompetence and laryngeal aspiration. Functional obstruction can also occur if the tongue cannot be raised because of tumour infiltration or fibrosis; • drug-induced dysphagia sometimes develops. Prochlorperazine and other phenothiazines can cause
2790 I PART 17 HEAD AND NECK TUMOURS quite marked oropharyngeal dyskinesia with functional dysphagia; • painful dysphagia (odynophagia) is seen in patients with mucosal inflammation and ulceration due to infection, radiotherapy or chemotherapy. It is worth noting that there may be no sign of oral candidiasis in half of patients who have oesophageal candidiasis?3 The 'moth eaten' appearances on the barium swallow are characteristic of oesophageal candidiasis; • fistula formation, e.g. oro-antral, pharyngo-cutaneous and tracheo-oesophageal fistulae.
past the vocal cords. If oxygen saturation (Sa02) is monitored using pulse oximetry during swallowing, a reduction of Sa02 after a swallow is a good indicator that fluid or food has been aspirated past the vocal cords into the airway. In many patients it is essential to ask the advice of a speech and language therapist (SaLT) specializing in swallowing disorders. Away from the bedside, videofluroscopy and nasal endoscopy under the direction of a SaLT are the most helpful investigations. For oesophageal causes, endoscopy and manometry under the advice of a gastroenterologist will be needed.
Examination
Management of dysphagia
A basic examination can be carried out at the bedside. Examination includes inspection of the mouth, pharynx and larynx with a head mirror or nasendoscope looking for signs of infection, pooling of mucus and retention of food debris and for reduced tongue, palatal and laryngeal movements. Rapid repetition of the syllable cpa', assesses lip closure, the inability to say eta' indicates defective movement of the anterior tongue, and difficulty in repeating the syllable 'ka' suggests poor movement of the posterior tongue. Asking the patient to push the tongue against the examiner's gloved finger gives an indication of the tongue's tone and strength. A further useful bedside examination is a test swallow using food consistencies the patient finds easiest to swallow. The oropharyngeal transit time is measured from the first tongue movement to the last laryngeal movement and times of more than one second are abnormal. Coughing and/or a 'gargle' quality to the voice suggests that food or fluid have penetrated the larynx, with a risk of aspiration
A key first step (see Checklist 202.5) is whether feeding or hydration are necessary. Patients who are deteriorating daily because of their illness will gain nothing from full hydration and feeding and they only need amounts and types of drinks and food that give them comfort and pleasure. In other patients, it is axiomatic that any of the treatable causes of dysphagia, for example infection, adverse drug effects should be remedied as a first step. Thereafter, the management has to be tailored to the swallowing problems of each individual in consultation with the patient, the relatives and the nursing staff in view of the ethical issues which may be involved. If the prognosis is weeks or months, and the dysphagia is due to malignant oesophageal obstruction, endoscopic dilatation with stenting, intraluminal radiation or laser therapy can give relief of dysphagia for a few months. In contrast, complete obstruction in a patient with a shorter prognosis may respond to high-dose dexamethasone while being hydrated intravenously or subcutaneously,
Checklist 202.5
D D
Dysphagia.
Is there doubt about the need for hydration or feeding? Is a complete obstruction present?
D
Is aspiration occurring? (i.e. penetration of food or fluid beyond the vocal cords)
D
Are drugs the cause? Is pain present? Does the patient feel the problem is at the level of the chest or abdomen? Does the patient feel the problem is at the level of the mouth or throat?
D D D D
Is the problem persisting?
Feed and hydrate for comfort and pleasure only. If the prognosis is short (day by day deterioration) consider high dose dexamethasone If the prognosis is longer start i.v. or s.c. hydration and consider treatment of obstruction or a gastrostomy If no symptoms: no action is needed If a tracheo-oesophageal fistula is present refer to gastroenterologist for a covered wallstent If symptoms are troublesome (chest infections, choking, coughing, secretions) consider a gastrostomy Reduce or stop drugs See Checklist 202.4 Refer to the gastroenterologists Refer to a specialist speech and language therapist Consider problems such as dyspepsia, fear, stroke, dental problems or problems with food presentation
Chapter 202 Palliative care for head and neck cancer
but a patient deteriorating rapidly hourly who obstructs may not need any hydration. Patients are very accurate in localizing the level of their obstruction and can therefore indicate whether the problem is oropharyngeal or oesophageal. 24 In general, nonoral feeding is usually the best option for patients whose oropharyngeal transit time is more than ten seconds or for those in whom more than 10 percent of swallowed food or fluid is aspirated. The airways can cope with small amounts of aspirated material and it has been shown that in patients who aspirate, approximately 40 percent do so silently without any clinical signs or symptoms, their aspiration only being visible with videofluroscopy or nasal endoscopy.25 When nonoral feeding is required, the choice often lies between a nasogastric (NG) tube and gastrostomy. Standard NG tubes are unsightly and are uncomfortable for more than a few days, whereas fine bore tubes are well tolerated for a week or longer, but are more difficult to replace if displaced. Nasogastric tubes do not protect patients from aspiration and may even worsen aspiration by markedly increasing oropharyngeal secretions in some patients. 26 Gastrostomies are usually inserted percutaneously with a simple endoscopic day case percutaneous endoscopic gastrostomy (PEG) procedure, but for those patients with extensive oropharyngeal tumour preventing endoscopy, the gastrostomy can be inserted under percutaneous fluoroscopic gastrostomy (PFG) control. Gastrostomies are usually comfortable and well tolerated and much preferred by patients compared with an NG tube. Feeding and hydration through a gastrostomy improves nutrition more effectively than through a nasogastric tube, is much simpler than parenteral feeding and drug administration is easier. Complications are usually limited to skin infection, tube blockage or tube displacement. Serious adverse events are less than 3 percent, but can include peritonitis. Patients with a gastrostomy are easily managed at home. The support of a gastrostomy team is invaluable in ensuring success and providing follow-up.
CONSTIPATION Constipation is the passage of a hard stool which is uncomfortable or difficult to pass. Decreased frequency is unhelpful in deciding on the presence of constipation since in advanced disease, reduced intake commonly results in reduced frequency in the absence of constipation. Constipation develops in half of patients who are terminally ill with cancer admitted to British hospices. 27 In patients with head and neck cancer, the main causes of constipation are reduced intake of food and fluids, reduced physical activity and constipating drugs. Opioids increase bowel tone but reduce peristalsis in the large and small intestines. However, most of the constipating effect of opioids is due to their antisecretory action which reduces intraluminal fluid. In addition, bowel tone and peristalsis,
2791
as well as bowel secretions, are reduced by antimuscarinic drugs such as hyoscine, tricyclic antidepressants and cyclizine. Altered biochemical states due to hypothyroidism or hypercalcaemia are causes of constipation which are sometimes overlooked (see Checklist 202.6).
Symptoms of constipation Many patients with constipation complain of a sense of incomplete emptying after defaecation, colicky abdominal pain, abdominal distension, nausea, vomiting and halitosis. There is a risk that these symptoms may be attributed mistakenly to the effects of advancing disease if the possibility of constipation is not considered. Overflow diarrhoea, urinary incontinence and confusion, especially in the elderly, are also associated with constipation. The diagnosis is usually straightforward with rectal examination revealing impacted faeces and with palpable faecal masses on abdominal examination or on plain abdominal radiograph.
Treatment of constipation Constipation can be prevented in many patients with cancer by prescribing laxatives at the commencement of treatment with constipating drugs instead of waiting until constipation becomes established. There are two main types of laxatives, those that primarily stimulate peristalsis and those that primarily soften the stool. Commonly used stimulant laxatives are senna, dantron and bisacodyl. Lactulose and docusate are effective stool softeners. In practice, a stimulant and softener are often prescribed at the same time to achieve a dual mode of action. Combinations of senna and docusate or senna and lactulose are frequently used. Dantron is a problem laxative since it colours the urine red (giving the patient the impression they are bleeding), can cause perianal burns and is only available in expensive combinations (e.g. co-danthramer or co-danthrusate) preventing individual adjustment of stimulant and softener. If laxatives fail, then suppositories, enemas and manual evacuation of faeces under sedation are employed. Some patients with impaction will respond to polyethylene glycol (Movicol) which, given with 125 mL water per sachet, acts as a safe bowel 'flusher,.28 However, for maintenance therapy, most patients dislike the large volumes needed. Unrelieved constipation imposes an extra burden of symptoms on patients with cancer and the successful management of constipation significantly improves their quality of life.
MALIGNANT ULCERS AND FISTULAE In patients with head and neck cancer, malignant ulcers involving the oral and pharyngeal mucosa and underlying
2792 II PART 17 HEAD AND NECK TUMOURS
Checklist 202.6
o
Managing constipation.
Is this bowel obstruction?
If faeces have been easy and comfortable to pass: o Ensure good hydration and diet with fibre o If constipating drugs are started, start laxatives o If diarrhoea is present, ensure this is not overflow caused by constipation N.B. Reduced frequency of a comfortable stool is not constipation.
o o
Ensure privacy at toilet Is there a treatable cause (e.g. hypercalcaemia)?
If the rectum or stoma is full: o Are the faeces hard? Give a bisacodyl suppository o Are the faeces soft? Start an oral stimulant laxative, e.g. senna If no success, consider a manual evacuation under sedative cover. If the colon is full: o Is colic present? Start docusate and consider a high arachis oil enema o Is colic absent? Start a stimulant/softener laxative combination Is the constipation persisting? o Consider using polyethylene glycol
structures can produce severe disability and pain. Malignant ulcers of the skin and fistulae cause highly visible disfigurement and they frequently exude an offensive malodorous discharge. The psychosocial effects of ulcers and fistulae are profound and cause the patient to experience feelings of shame and embarrassment, isolation, anxiety, altered body image and depression. In addition, the patient's family and friends will be distressed by the disfigurement and the foul odour these lesions produce. Good palliative care involves treatment of the distress of the patient and relatives, as' well as treatment of the wound. Treatment of the wound by radiotherapy may be possible if the area has not previously received a maximum radiation dose. In theory, cryotherapy and laser treatment might control or retard tumour growth but they are seldom employed in practice, and the role of surgery is limited to localized lesions. When these forms of medical treatment are no longer appropriate, treatment is aimed at controlling pain, infection, bleeding, exudate and odour. The target is comfort rather than cure (see Checklist 202.7).
Infection and odour Anaerobic bacteria proliferate in hypoxic and necrotic tissue and, as a consequence of their metabolism, malodorous volatile fatty acids are produced which are responsible for the unpleasant smell. The characteristic
smell is attributed to two impact odours, putrescine (1,4-diaminopeptane) and cadaverine (1,5 diaminopeptane) which can trigger the gag reflex or the vomit reflex in some individuals. 29 Habituation to these odours does not happen and the patient, family and caring staff are continuously aware of their presence. Metronidazole 400 or 500 mg eight hourly can be an effective treatment option but some patients cannot tolerate it because of nausea. Metronidazole can be administered rectally (1 g every eight hours for three days then 1 g every 12 hours) when oral administration is not possible. Contrary to popular belief, interaction of metronidazole with alcohol is rare. 30 Other systemic antibiotics can sometimes be helpful in malignant skin ulcers but are seldom of benefit in malignant fistulae. Topical metronidazole 0.5 percent gel (Metrotop) can help but it is expensive and of little benefit when large quantities of exudate are present.
Bleeding Malignant ulcers and fistulae are often vascular and have raw surfaces which can bleed easily. It is wise to check the platelet count since coagulation disorders are more common in patients with advanced disease. NSAIDs should be stopped to reduce the risk of bleeding, while patients on warfarin should be reassessed as to whether the warfarin can be stopped. Tranexamic acid (500 mg four times daily) inhibits the breakdown of fibrin clots
Chapter 202 Palliative care for head and neck cancer II
Checklist 202.7
Managing fungating ulcers.
D Can a local malignancy be treated? D Is the wound bleeding? D
Is the wound causing psychosocial effects?
D Is the odour troublesome?
D
Is the wound painful?
Checklist 202.8
2793
e.g. by radiotherapy See Checklist 202.8 Elicit problems (adjustments, relationships, isolation, sexual issues) If patient is coping poorly: refer for specialist help Start oral metronidazole Use hydrogels or polyurethane dressings to help clear debris Cover dressings with semipermeable adhesive dressing or cling film (food wrap) Avoid using hydrocolloid dressings or dressings with an adhesive Consider using non-adherent, soft silicone net dressings (e.g. Mepitel) Review the systemic analgesia Consider using ketamine at dressing changes
Bleeding.
D D D
Is the patient hypotensive? If treatment is appropriate: If treatment is not appropriate:
D D
Is a coagulation disorder present? Is the bleeding source visible?
D
Is the source of bleeding internal?
Obtain i.v. access, give fluids and crossmatch Give diazepam 5-30 mg titrated i.v. (or midazolam 5-15 mg into deltoid muscle) Use dark blue or green towels to absorb blood Place warm blankets over the patient Do not leave the patient alone Apply pressu re Apply sucralfate suspension to promote clotting If anterior nose: pack with gauze soaked in sucralphate suspension If posterior nose: pack under direct vision, consider diathermy
and can sometimes be helpful. It is commonly used to reduce bleeding after dental extraction and prostatectomy. Etamsylate (500 mg four times daily) can also be helpful and has fewer side effects than tranexamic acid. Tranexamic acid can be applied topically on the surface of malignant ulcers and fistulae using tranexamic injection solution. Sucralphate suspension, which is used primarily in gastritis and peptic ulceration to protect the mucosa, is an effective topical haemostatic agent that controls bleeding from fungating wounds in palliative care practice. Vasoconstrictors such as adrenaline are sometimes used topically, but are effective for only 10-15 minutes since rebleeding tends to recur as the adrenaline is absorbed. In theory, lasers can palliate bleeding from tumours that are accessible externally and embolization can be useful in controlling bleeding, but in practice they are seldom considered in malignant wounds in the head and neck region, see Checklist 202.8. Small repeated bleeds from fungating lesions in the head and neck region can herald a major bleed from the carotid vessels. Patients who have had combined treatment
with neck surgery and radiotherapy are more at risk. It is a myth that modern treatments have eliminated this risk, and a busy head and neck cancer unit will still see several deaths each year from a massive bleed. Nethertheless, this remains an uncommon cause of death. A powerful suction machine ready for use should be kept in the room to clear blood from the patient's mouth, tracheostomy or fistula. A good supply of dark green or blue towels should be kept in the room since these will make the appearance of the blood less frightening to the patient and relatives. A supply of midazolam or other sedative should be kept immediately available and it would seem reasonable to have an intravenous cannula in position if a major bleed is thought to be imminent. When severe haemorrhage occurs, midazolam should be given intravenously, slowly titrating the amount until the patient becomes drowsy. The aim is to reduce fear and to reduce the level of awareness of the patient. If intravenous access is not possible, 5-15 mg of midazolam can be given buccally or injected into the deltoid muscle (i.m. injections are absorbed fastest from this muscle). In this
2794 I PART 17 HEAD AND NECK TUMOURS situation, the patient's main symptoms are extreme distress, anxiety and fear rather than pain and therefore a benzodiazepine is more appropriate than opioid analgesics. Since severe haemorrhage from malignant disease in the neck is usually a terminal event, cardiopulmonary resuscitation is not indicated. Death often takes place within minutes and it is of overriding importance to stay with the patient. The urge to get some drugs or equipment to help should be resisted if this requires leaving the patient alone. These events are frightening and distressing for everyone - patients, doctors, relatives and nurses. Relatives, medical and nursing staff who witness these events will need considerable support.
Dressings for fungating wounds Wound cleansing and removal of debris is best achieved by irrigation with normal saline since antiseptic solutions can cause tissue damage. The principle of using moistureretaining dressings for acute wounds that will heal does not apply to fungating wounds. 31 Most malignant ulcers have a persistent exudate and dressings are chosen that remove or absorb this fluid. Alginates (e.g. Kaltostat, Sorbsan, Algisite) can absorb exudate and have some haemostatic action. However, they soon reach capacity and this may necessitate frequent dressing changes. Polyurethane foam dressings (e.g. Allevyn, Lyofoam, Tielle) absorb fluid and allow some evaporation which facilitates the removal of more fluid. Hydrogel dressings (e.g. Intrasite) can take up the shape of the wound and absorb a limited amount of fluid. A secondary covering is needed. Silicone foam dressings (e.g. Cavicare) can reduce the fluid exudate and form a close fitting dressing. Latex moulds and self-polymerizing silicone materials are less easily available alternatives which are quite versatile. Odour-absorbent dressings make use of activated charcoal, but their ability to control odour is limited. Semipermeable film dressings (e.g. Opsite) or cling film (food wrap) can be used over other dressings and form a more effective odour barrier. The odour of fungating wounds is at its maximum during dressing changes. Vaporization of aromatherapy oils by adding boiling water to a bowl containing some of these oils is much more effective than a deodorant spray. The use of aromatherapy oils before dressing changes is a simple and effective way of diminishing the noxious odour for the patient and nursing staff. However, the continuous use of perfumes or oils should be avoided as the new smell soon becomes unpleasant.
HYPERCALCAEMIA It is claimed that hypercalcaemia develops in only 5 percent of patients with head and neck cancer,32 but this
is a common problem in a hospital ENT unit and the incidence may be much higher. It can present insidiously with symptoms of drowsiness alone in half of patients, but other symptoms include confusion, thirst, nausea and vomiting, dehydration, polyuria and constipation. Since these symptoms can be mistakenly attributed to advancing disease, it is important to have a high index of suspicion and to measure the corrected serum calcium level, especially when drowsiness or confusion are of recent origin. Hypercalcaemia is not dependent on the presence of bony metastases and their absence should never prevent checking the serum calcium. The most important mechanism is due to a parathyroid hormone fragment produced by the primary tumour. In addition, renal clearance of calcium is reduced. A common mistake is failure to correct an apparently normal serum calcium in the presence of a low albumin. The usual correction is: Corrected serum calcium = [(40 - serum albumin) x 0.02]
+ serum calcium In contrast to chronic hypo- or hypercalcaemic states, the ionized calcium is less helpful in acute hypercalcaemia in patients with cancer. 33 Treatment with a single infusion of bisphosphonate is effective and most patients return to their prehypercalcaemic state with a good quality of life within a few days. Bisphosphonates act by inhibiting osteoclastic resorption and the bisphosphonate pamidronate 60-90 mg given as a four hour intravenous infusion in 500 mL 0.9 percent saline is commonly employed. Rehydration is helpful if the patient is dehydrated, but rehydration should never delay the use of a bisphosphonate. Treatment with pamidronate can be repeated in three to four weeks' time if hypercalcaemia recurs.
SUPERIOR VENA CAVAL OBSTRUCTION In advanced cancer, superior vena caval obstruction (SVCO) is caused by tumour or enlarged lymph nodes in the mediastinum, impeding venous drainage from the head, arms and upper trunk. Usually this develops over weeks or months allowing collateral drainage to take place. Swelling of the skin and soft tissues of the face, neck, upper trunk and arms results due to the increased venous pressure above the obstruction. The skin develops a flushed, plethoric, dusky colour and the conjunctival mucosa may become oedematous. Headache can develop as a result of cerebral congestion and some degree of dyspnoea is usually present. Dilated collateral veins across the upper arm and chest make the diagnosis clinically obvious. Occasionally, the obstruction develops rapidly over days and needs urgent treatment. Initial treatment with dexamethasone 16 mg i.v. as a slow injection over two minutes followed by high-dose oral dexamethasone
Chapter 202 Palliative care for head and neck cancer
12 mg once daily in the morning is often effective. Standard treatment with radiotherapy relieves symptoms in 50-95 percent within the first two weeks of treatment. 34, 35 If radiotherapy is ineffective or cannot be used, a stent can be inserted into the superior vena cava as an interventional radiology technique.
STRIDOR The characteristic rasping breathing of progressive upper airway obstruction due to tumour can develop rapidly over hours or days. Occasionally, the airway obstructs completely in an intermittent fashion producing repeated episodes of hypoxic confusion and agitation. To avoid continuous and complete obstruction such patients should receive dexamethasone 16 mg i.v. as a slow injection over two minutes. Most clinicians would then arrange for a tracheostomy in theatre to avoid the need for an emergency bedside procedure.
PSYCHOLOGICAL PROBLEMS Patients with advanced cancer experience feelings of fear, depression and anxiety as they struggle to come to terms with the diagnosis and prognosis. Patients need help when their anxiety, anger or withdrawal prevent them from coping with everyday life.
Anxiety Patients with anxiety complain of tension or restlessness, irritability, poor concentration and rumination, fear and insomnia. The physical symptoms are characteristically associated with autonomic hyperactivity, for example dry mouth, lump in the throat, tachycardia, diarrhoea. These somatic symptoms can also be caused by the illness itself or by the side effects of drugs used to treat the illness. Anxiety levels can be markedly reduced by encouraging the patient to discuss their fears about pain and suffering, Checklist 202.9
about the dying process, about what will happen to those left behind and about the various spiritual and practical issues that cause them concern. The opportunity to express these concerns and to receive accurate information and honest reassurance is highly therapeutic. However, discussing these issues can never be forced, and can only take place if the patient feels ready to discuss these issues. Teaching patients techniques of relaxation and distraction are helpful elements of anxiety management strategy. Many patients find that massage and aromatherapy, where available, are enjoyable and relieve tension. If in spite of this nondrug form of management a moderate degree of anxiety persists, a trial of treatment with an anxiolytic drug is a reasonable approach. The benzodiazepines lorazepam and temazepam can be helpful and are usually prescribed for a limited period of around two weeks. Lorazepam (0.5-1 mg eight-hourly) is less sedating, but temazepam (10-20 mg at bedtime) is useful if sedation is required. Alternatively, citalopram 10-20 mg once daily can be helpful. Patients with severe anxiety undergo a profound change of mood and experience feelings of fear apprehension, tension or edginess for the greater part of the day. They are so distracted by these feelings they are unable to concentrate on anything else and have difficulty making everyday decisions like what to eat, what to wear, where to go and what to do. They are so tormented by anxiety symptoms that they can no longer function effectively. In these circumstances an antipsychotic drug such as haloperidol (5-10 mg at night) or levomepromazine (25-50 mg eight-hourly) should be started, but it is good practice to ask for advice from a palliative care specialist, psychologist or a psychiatrist. Further drug treatment may help, but patients also can be greatly helped with cognitive behavioural therapl6 (see Checklist 202.9).
Anger There are many reasons why patients with life-threatening disease experience feelings of anger. They may feel robbed
Helping the anxious person.
D Is this a drug-induced dyskinesia mimicking anxiety? Acknowledge the anxiety, e.g. 'You seem to be worried.' D D
Would simple supportive measures, for example relaxation, company or distraction help? Is specialist help needed? The patient is in an anxiety state: i.e. persistent apprehension for more than two weeks and more than half the time with four or more anxiety features present. The person is functioning poorly Panics or phobias are a feature An underlying depression may be present
N.B. Anxiety and depression commonly coexist.
I 2795
2796
PART 17 HEAD AND NECK TUMOURS
of their future life and relationships, deprived of the chance to achieve their unfulfilled ambitions and compelled to give up control of their daily lives. They may be haunted by the unanswerable question 'Why me?' The key to dealing with anger is first of all to acknowledge it and legitimize its discussion (e.g. 'I can see you're angry, how can I help?') and then negotiate to discuss its cause ('What are the main things that have made you angry?'). Giving the person the opportunity to express their anger and the reasons for it usually results in the anger becoming defused. It is important to recognize pathological anger, which is escalating anger out of all proportion to the reasons being claimed. This anger is not amenable to rational discussion. Usually the individual is visibly angry and agitated. Instead of being defused, the anger continues to escalate as soon as the reasons begin to be explored. In this situation the professional should go to the nearest exit and acknowledge how this escalating anger is making things difficult, for example, 'I can see this has made you very angry. I want to help, but your anger is beginning to make me feel uncomfortable. If you don't feel you can control your anger, I wouldn't feel comfortable continuing.' If the anger is allowed to escalate, the individual is likely to lose control and become violent and abusive within a short space of time. Sometimes the anger of the patient or relatives is misplaced or transferred to the staff who understandably experience strong feelings of resentment. They may feel that the patient is being deliberately difficult, awkward and uncooperative. The professional should not react to the feeling of resentment but should regard the anger as a symptom which needs to be explored and helped. If the anger is misdirected it is reasonable to ask for an explanation (e.g. 'I can see that you are angry but can you tell me why your anger is directed to this particular person?'). Dealing with misdirected anger is very stressful for the professional who should not shrink from recognizing the stress and the need to accept the emotional support of colleagues, see Checklist 202.10.
Checklist 202.10
D
Withdrawal Patients can appear withdrawn because of distraction (pain, fear), confusion, drowsiness (drugs, infection, hypercalcaemia), exhaustion, reduced facial expression (drugs, Parkinson's), or because this is their usual behaviour. Identifying depression in patients is a matter of practical importance because treatment is effective. It is estimated that between 10 and 25 percent of patients with cancer suffer from depression and the incidence increases with higher levels of disability, advanced illness and pain. 37 The diagnosis is easily overlooked for several reasons. • Sadness is a common and appropriate response in terminally ill patients facing death. • Anxiety can mask the underlying depression. • Many of the physical or somatic symptoms of depression can be caused by the terminal illness, e.g. loss of appetite, insomnia, loss of energy and fatigue. As a result, the diagnosis is based more on the psychological symptoms of depression such as persistent low mood, feelings of hopelessness, loss of interest, despair, loss of self worth, feelings of guilt and shame, loss of enjoyment, feeling a burden to others, impaired concentration and ideas of suicide. There is no simple test for depression but simply asking, 'Have you had a depressed mood most of the day nearly every day?' may be a useful screening tool. 38 Treatment by psychological and social measures is always helpful but treatment with antidepressant drugs is usually required as well. The choice of antidepressant depends on each situation. The tricyclic antidepressant lofepramine is safe and effective with antimuscarinic effects which reduce oral secretions. It can be given at night in a dose of 70 mg which can be titrated up to 210 mg over the first two weeks. Citalopram is less sedating with useful anxiolytic properties. Improvement with antidepressants can be rapid (within two weeks) when the depression started recently, while improved sleep and reduced anxiety
Helping the angry person.
Do you know how anger affects you? If you get angry, be less assertive If you become withdrawn, be more assertive
Acknowledge the anger, for example 'I can see you're angry, how can I help?' D Is the anger correctly directed? D Is the anger escalating? Can the person contain their anger? If not, leave the room. D Is the person depressed? See Checklist 202.11 D Is their anger causing isolation?
D
Is the anger persisting
Is this normal behaviour? Is specialist help needed?
N.B. If you acknowledge the anger and are clear in your willingness to help, anger should start to defuse in the first few minutes.
Chapter 202 Palliative care for head and neck cancer I 2797
occurs earlier, so treatment is still worthwhile in someone with a short prognosis. Relatives and staff often observe an improvement before the patient does. If the depression persists, it is essential to ask for advice from psychiatric colleagues. Cognitive behavioural therapy is as effective as antidepressants and although it takes longer to be effective, relapse rates are 10wer39 (see Checklist 202.11).
Acute confusional states This term is used to cover a wide variety of symptoms due to a large number of different disorders. The shared feature they all have is a change in alertness. As a result of this, the patient's interpretation of everyday events is disturbed and their responses appear illogical and inappropriate. Confusion can be seen in patients with advanced disease particularly in the elderly and during the last days of life. Cerebral metastases are commonly suspected, but are an uncommon cause of confusion. The principal features of an acute confusional state in patients without preexisting organic brain disease are: • acute onset and fluctuating severity; • poor short-term memory (due to inability to take in information); • poor concentration; • altered alertness (either increased or decreased alertness) ; • altered behaviour (may be noisy, aggressive, disinhibited); • disorientation (sometimes with rambling incoherent speech); • abnormal experiences: delusions (often paranoid); misperceptions (where an external stimulus is misinterpreted as a result of poor concentration and reduced alertness. The misinterpretation can be corrected by refocussing attention and concentration); Checklist 202.11 D D D D
hallucinations (a false auditory or visual experience internally generated without an external stimulus. Cannot be voluntarily corrected). These features contrast with patients who have chronic confusional states, such as Alzheimer's dementia where the confusion is long standing, alertness is unchanged, it fluctuates less and the poor memory is due to the inability to retain information. In patients with advanced disease, acute confusion may exacerbate the chronic confusion of an organic brain disease. CAUSES OF AN ACUTE CONFUSIONAL STATE
A large number of the causes of confusion are reversible. Successful treatment produces a major improvement in the quality of life for the patient and the relatives. Identifying the cause or causes in an individual patient is challenging and rewarding: • biochemical causes: hypercalcaemia, uraemia/ dehydration, hyponatraemia, hypo- and hyperglycaemia; • cardiac and respiratory disease: e.g. ventricular failure, pleural effusion; • drug causes: benzodiazepines, antimuscarinics, antidepressants, anticonvulsants, cimetidine and steroids. Opioids are often blamed but they are an uncommon cause; • infections: chest and urinary infections may cause few symptoms in the elderly and need to be excluded or confirmed by examination and investigation; • miscellaneous: change of environment (e.g. a move from home to hospital), urinary retention, constipation, alcohol withdrawal, hypoxia from any cause; • recent trauma: e.g. subdural haematoma or limb fracture due to a fall; • organic brain disease, e.g. stroke. Cerebral metastases are an uncommon cause of an acute confusional state; • chemical withdrawal: this may be due to drugs such as benzodiazepines, or chemicals such as alcohol or nicotine.
Helping the withdrawn patient.
Is this the patient's usual behaviour? Acknowledge the behaviour, for example 'You seem much quieter than usual' Exclude a confusional state or organic cause Is specialist help needed?
Clinical depression, i.e. persistent low mood for more than two weeks and more than half the time with three or more depressive features present Suicidal planning or thoughts of self harm Undue guilt or shame
N.B. Depression is common in advanced disease, but is only one of several causes of withdrawal. It can respond rapidly to treatment.
2798 I PART
17 HEAD AND NECK TUMOURS
TREATMENT The patient should be closely supervised in a suitable quiet place. The probable causes of the confusion should be explained to the patient and relatives and reassurance should be given that confusion in ill people is not a sign of impending madness. In view of the patient's poor concentration, the explanation and reassurance will need to be repeated frequently. The suspected causes of confusion should be dealt with appropriately with the minimum of intrusive investigations. Drug therapy should be a last resort, since it often masks the cause and makes it more difficult to assess whether a patient is recovering. In patients who are at a risk of injuring themselves or others, then some medication may be needed. Because the features and the use of drugs can be complex, the advice of a psychiatrist or palliative care physician is often necessary. When fear or anxiety is the only feature, then a low dose of a benzodiazepine can help. Lorazepam (0.5-1 mg p.o.) causes minimal sedation while midazolam is a shortacting benzodiazepine which can be given as 2-5 mg s.c. or bucally, or as a 20-30 mg/24 hours s.c. infusion. Aggression can respond to haloperidol 2.5-10 mg once at night or risperidone p.o. 0.5-2 mg at bedtime. 40, 41 If the patient has abnormal experiences (e.g. hallucinations) or altered behaviour (e.g. paranoia) then an antipsychotic is needed. The choices are the same as those for aggression, but if sedation is needed then options are olanzepine
Checklist 202.12
Checklist 202.12).
THE TERMINAL PHASE (THE LAST DAYS AND HOURS) When a patient's condition deteriorates day by day it is reasonable to assume there are only days left before death takes place. It is important to ensure that religious and spiritual care is offered if wanted. Ask the patient, partner or family if they would like to talk to a chaplain or other professional. Resuscitation issues may need to be discussed and the question of feeding and hydration may have to be negotiated with the patient, the family and the nursing and medical staff if this has not been done previously. There is often considerable confusion about the 43 implementation of resuscitation guidelines. There are 44 several principles that should underlie such decisions. CD
CD
Decisions about cardiopulmonary resuscitation (CPR) are separate from comfort and health measures such as antibiotics, hydration and feeding. Decisions about CPR made without knowing the likely circumstances of the arrest are of little help to
Helping the patient in an acute confusional state.
D
Is memory failure present?
D
Has alertness changed?
D D
Is concentration impaired? Is the patient experiencing unusual sights or sounds? For example, ha Iluci nations Has the behaviour altered? For example, paranoia
D
p.o. 5-10 mg daily or levomepromazine 12.5-50 mg eight42 hourly p.o. or S.C. Confusional states are seldom static and the pattern of confused behaviour can alter repeatedly. As a result, the patient needs to be reviewed frequently (see
Orientate frequently Ensure a constant environment Exclude: dementia and cerebral metastases. Consider: drugs, drug withdrawal, chemical withdrawal, infection, biochemical cause, hypoxia, recent trauma, renal failure. Exclude: anxiety, persistent pain, depression Ensure a light, quiet environment Exclude: causes of altered alertness above Consider the presence of a psychotic illness (rare). Exclude: causes of altered alertness above Exclude: dementia and cerebral metastases.
Explain the cause of the confusion and treatment to the patient, family and staff D Is urgent control of disturbance N.B. Advice from a psychiatrist or palliative care specialist is necessary? often needed Ensure a light, quiet environment If anxiety is the main problem: consider a benzodiazepine (eg. lorazepam or midazolam) If aggression is the problem: consider haloperidol or risperidone If abnormal experiences or altered behaviour are the problem: consider an antipsychotic (e.g. haloperidol, olanzepine or levomepromazine
Chapter 202 Palliative care for head and neck cancer
Checklist 202.13
o
I 2799
Making decisions about CPR.
Is it impossible to anticipate the arrest? Since the circumstances of an arrest
cannot be anticipated, then it is not possible to
make a decision that would help a clinical team decide whether to attempt CPR treatment in an unexpected arrest Do not burden the patient (adult or child), partner or family with a CPR treatment decision The patient (adult or child) should be given opportunities to receive information or an explanation about any aspect of their treatment. If the individual wishes, this may include information about CPR treatment and its likely success in different circumstances Continue to communicate progress to the patient (and to the partner/family if the patient agrees or to the parents if the patient is a child) Continue to elicit the concerns of the patient (adult or child), partner or family Review regularly to check if circumstances have changed In the event of an unexpected arrest, carry out CPR treatment if there is a reasonable possibility of success.
o
Is the patient (adult or child) dying because of an irreversible condition? Allow a natural death (AND). Good palliative care should be in place to ensure a comfortable and peaceful time for the patient, with support for the family and partner Do not burden the patient, partner or family with a CPR treatment decision Document the fact that CPR treatment will not benefit the patient, e.g. 'The clinical team is as certain as it can be that CPR treatment cannot benefit the patient in the event of a cardiorespiratory arrest, so do not attempt resuscitation (DNAR).' Continue to communicate progress to the patient (and to the partner/family if the patient agrees or if the patient lacks capacity). This explanation may include information as to why CPR treatment is not an option Continue to elicit the concerns of the patient, partner and family Review regularly to check if circumstances have changed
o
Is it likely that the arrest
can be anticipated and is likely to occur because of a
reversible condition? In this situation an advance statement on CPR treatment is possible. If the patient (adult or child) has capacity for this decision:
Discuss the options of CPR treatment versus DNAR with the patient Continue to communicate progress to the patient (and to the partner or family if the patient agrees)
If the patient (adult or child) does not have capacity for this decision:
If capacity was present previously, enquire about their previous wishes from the partner or family to help the clinical team make the best decision If this is a child, discuss the risks and benefit of CPR treatment with the parents The clinical team should then make a decision in the patient's best interests Continue to communicate progress to the partner or family
Document the decision Continue to elicit the concerns of the patient, partner or family Review regularly to check if circumstances have changed In the event of the expected arrest, act according to the patient's wishes (or if the patient was not competent follow the decision made by the clinical team)
2800 II PART 17 HEAD AND NECK TUMOURS
•
•
•
•
the clinical team attending the arrest. This does not prevent discussion about end of life issues. At the end of an irreversible terminal disease, CPR treatment will not succeed and is not a treatment option since it is unethical to offer a treatment that cannot benefit the patient. If a patient is dying naturally of their cancer or its consequences, since CPR is not an option, the patient and family need not be burdened with the decision. Decisions based on estimates of quality of life are questionable since professionals are often inaccurate in making such estimates. 45 Whatever the circumstances, a continuous dialogue with the patient and family should continue to elicit their concerns and questions. This process invariably provides all the answers needed about choices (see Checklist 202.13).
In the terminal phase, the focus of medical treatment changes and concentrates more on keeping the patient comfortable rather than on treating any concurrent medical disorder. Death is a natural event and doctors should strive as much as possible to avoid making it a medicalized process. All nonessential drugs should be withdrawn. Antihypertensives, antibiotics and laxatives can usually be stopped without detriment to the dying patient. Active management of the patient's symptoms continues as before with relief of pain, relief of nausea and vomiting and of agitation and restlessness taking priority. Noisy moist breathing due to excess secretions can be helped with hyoscine. As the patient becomes semiconscious and unable to swallow, essential drugs such as diamorphine, cyclizine, hyoscine and midazolam can be given subcutaneously. At the end of life, feeding and hydration may become unnecessary. Hunger is not usually a problem in the terminal stages and unwanted feeding by any route may cause distress. As the patient's renal function diminishes, the need for fluids is reduced. At the end of life some dehydration is not uncomfortable and may have the benefit of reducing bronchial secretions and reducing or stopping vomiting. Thirst may only need sips of water or it may need parenteral hydration. Hydration, if required, is most conveniently carried out subcutaneously (hypodermoclysis). 46 The suprascapular area is safe and convenient and up to 100 mLihour can be infused without hyaluronidase. Nasogastric tubes are unpleasant and often uncomfortable and should be avoided. Sometimes the partner or family will express a strong wish for hydration to be given even though the patient is comfortable and the situation has been explained to them. In these circumstances it is reasonable to hydrate at low rates since modest hydration (1 Ll24 hours) subcutaneously is unlikely to cause discomfort, whilst refusing their request might complicate their bereavement. The relatives can be helped by explaining the changes that are happening to the patient and by telling them about the natural course of a death. It can be
helpful to explain to relatives that even comatose patients may be aware of the family's presence and may still hear although they cannot respond. The family should be encouraged to undertake as much or as little of the patient's personal care as they want, for example assisting with feeding and drinking, washing the face, sponging the forehead, assisting in the mouth care, adjusting the pillows, etc. The ability to do things for the patient can have a consoling effect on the family. Relatives should not be made to feel like intruders in the care of their loved ones. A key issue for a head and neck team is managing the transition from aggressive or curative treatment to the intensive care of caring for a dying patient and their partner and family. This transition needs to be carried out in stages. It is distressing to a patient and their family to have intravenous lines, frequent bedside monitoring and regular investigations one day, to find the next day that everything has been stopped. Patients describe feeling isolated and abandoned when this transition is abrupt. A gradual change in treatments with explanation at every stage at the patients pace allows patients and families time to adjust, while maintaining relationships and confidence between the patient, family and the caring staff.
ACKNOWLEDGEMENTS All checklists have been adapted from Regnard and Hockley,47 with permission.
REFERENCES Addington-Hall J, McCarthy M. Dying from cancer: results of a national population based investigation. Palliative Medicine. 1995; 9: 295-305. 2.. World Health Organization. Cancer pain relief and palliative care, Technical Report Series: 804. Geneva: World Health Organisation, 1990. 3. Faulkner A, Maguire P, Regnard C. In Breaking bad news. In: Regnard C, Hockley J (eds). Flow diagrams in advanced cancer and other diseases. London: Edward Arnold, 1995: 86-91. 4. Saunders CM. The management of terminal illness. London: Hospital Medicine Publications, 1967. 5. Twycross RG, Harcourt J, Bergl S. A survey of pain in patients with advance cancer. Journal of Pain and Symptom Management. 1996; 12: 237-82. 6. AI-Chaer ED, Traub RJ. Biological basis of visceral pain: recent developments. Pain. 2002; 96: 221-5. 7. Carter R, Pittam M, Tanner N. Pain and dysphagia in patients v.vith squamous carcinomas of the head and neck: the role of perineural spread. Journal of the Royal Society of Medicine. 1982; 75: 598-60. 1.
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Chiara S, Nobile MT, Vincenti M, Gozza A, Pastrone I, Rosso M et al. Sucralfate in the treatment of chemotherapy-induced stomatitis: a double-blind, placebo-controlled pilot study. Anticancer Research. 2001; 21: 3707-10. 9. Worthington HV, Clarkson JE, Eden OB. Interventions for treating oral mucositis for patients with cancer receiving treatment. Cochrane Database of Systematic Reviews. 2002; 1: CD001973. 10. Back IN, Finlay I. Analgesic effect of topical opioids on painful skin ulcers. Journal of Pain and Symptom Management. 1995; 10: 493. 11. Krajnik M, Zylicz Z. Topical morphine for cutaneous cancer pain. Palliative Medicine. 1997; 11: 325-6. 12. Twillman RK, Long TD, Cathers TA, Mueller DW. Treatment of painful skin ulcers with topical opioids. Journal of Pain and Symptom Management. 1999; 17: 288-92.
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Faull C, Woof R. Palliative care: an Oxford core text. Oxford University Press, 2002: 74. US Food and Drug Administration. Fentanyl transdermal system (marketed as Duragesic) information: FDA alert (7/ 2005) narcotic overdose and death. July, 2005. (see also:
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http://www.fda.gov/bbs/topics/N EWS/2005/ NEW01206.html) Twycross R, Wilcock A, Charlesworth S, Dickman A. PCF2: palliative care formulary. Abingdon: Radcliffe Medical Press, 2002. Also on www.palliativedrugs.com Torres SR, Peixoto CB, Caldas DM, Silva EB, Akiti T, Nucci M et al. Relationship between salivary flow rates and Candida counts in subjects with xerostomia. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics. 2002; 93: 149-54. Samaranayake LP, Yaacob HB. Classification of oral candidosis. In: Samaranayake LP, MacFarland TW (eds). Oral candidosis. London: Wright (Butterworth), 1990: 124-32. Reichart PA, Samaranayake LP, Philipson HP. Pathology and clinical correlates in oral candidiasis and its variants: a review. Oral Diseases. 2000; 6: 85-91. Finlay IG. Oral symptoms and candida in the terminally ill. British Medical Journal. 1986; 292: 592-3. Burnie JP, Odds FC, Lee W, Webster C, Williams JD. Outbreak of systemic candida albicans in intensive care unit caused by cross-infection. British Medical Journal. 1985; 290: 746-8. Regnard CA. single dose fluconazole versus five day ketoconazole in oral candidiasis. Palliative Medicine. 1994; 8: 72-3. Rademaker AW, Pauloski BR, Colangelo LA, Logemann JA. Age and volume effects on liquid swallowing function in normal women. Journal of Speech, Language and Hearing Research. 1998; 41: 275-84. Trier JS, Bjorkman DG. Esaphageal, gastric and intestinal candidiasis. American Journal of Medicine. 1984; 77: 39-43. Logemann JA. Evaluation and treatment of swallowing disorders. San Diego: College Hill Press, 1983.
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Leslie P, Carding PN, Wilson JA. Investigation and management of chronic dysphagia. British Medical Journal. 2003; 326: 433-6. Finucane TE, Bynum JPW. Use of tube feeding to prevent aspi ration pneu mon ia. The Lancet. 1996; 348: 1421-4. Radbruch L, Sabatowski R, Loick G, Kulbe C, Kasper M, Grond S et al. Constipation and the use of laxatives: a comparison between transdermal fentanyl and oral morphine. Palliative Medicine. 2000; 14: 111-9. Cleveland MV, Flavin DP, Ruben RA, Epstein RM, Clark GE. New polyethylene glycol laxative for treatment of constipation in adults: a randomized, double-blind, placebo-controlled study. Southern Medical Journal. 2001; 94: 478-81. Miller C. Skin problems in palliative care: nursing aspects. In: Doyle T, Hanks GW, McDonald N (eds). Oxford textbook of palliative medicine, 2nd edn. Oxford: Oxford University Press, 1998: 642-56. Visapaa JP, Tillonen JS, Kaihovaara PS, Salaspuro MP. Lack of disulfram-like reaction with metronidazole and ethanol. Annals of Pharmacotherapy. 2002; 36: 971-4. Parnham A. Moist wound healing: does the same theory apply to chronic wounds? Journal of Wound Care. 2002; 11: 143-6. Degardin M, Nguyen M, Beaurin D, Lesoin A, Fournier C, Lefebvre JL et al. [Hypercalcemia and squamous cell carcinoma of the upper respiratory-digestive tracts. Incidence and prognosis]. Bulletin du Cancer. 1995; 82: 975-80. Waterfield KE, Lee MA, Regnard CFB. Ionized calcium in isolation may not detect all cases of symptomatic hypercalcaemia. Palliative Medicine. 2005; 19: 1-2. Donato V, Bonfili P, Bulzonetti N, Santarelli M, Osti MF, Tombolini V et al. Radiation therapy for oncological emergencies. Anticancer Research. 2001; 21: 2219-24. Rowell NP, Gleeson FV. Steroids, radiotherapy, chemotherapy and stents for superior vena caval obstruction in carcinoma of the bronchus. Cochrane Database of Systematic Reviews. 2001; 4: CD001316. Moorey S, Greer S. Cognitive behaviour therapy for people with cancer. Oxford: Oxford University Press, 2002: 121-6. Hotopf M, Chidgey J, Addington-Hall J, Lan Ly K. Depression in advanced disease: a systematic review. Part 1. Prevalence and case finding. Palliative Medicine. 2002; 16: 81-97. Whooley MA, Avins AL, Miranda J, Browner WS. Casefinding instruments for depression. Two questions are as good as many. Journal of General Internal Medicine. 1997; 12: 439-45. Teasdale JD, Scott J, Moore RG, Hayhurst H, Pope M, Paykel ES. How does cognitive therapy prevent relapse in residual depression? .Evidence from a controlled trial. Journal of Consulting and Clinical Psychology. 2001; 69: 347-57. Lonergan E, Luxenberg J, Colford J. Haloperidol for agitation in dementia (Cochrane Review). The Cochrane
2802 II PART 17 HEAD AND NECK TUMOURS Library, 2002; Issue 2. Oxford: Update Software Ltd. (www.cochrane.org) 41.
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De Deyn PP, Rabheru K, Rasmussen A, Bocksberger JP, Dautzenberg PL, Eriksson S et 01. A randomized trial of risperidone, placebo, and haloperidol for behavioral symptoms of dementia. Neurology. 1999; 53: 946-55. Street JS, Clark WS, Gannon KS, Cummings JL, Bymaster FP, Tamura RN et 01. Olanzapine treatment of psychotic and behavioral symptoms in patients with Alzheimer disease in nursing care facilities: a double-blind, randomized, placebo-controlled trial. The HGEU Study Group. Archives of General Psychiatry. 2000; 57: 968-76. Randall F. Recent guidance on resuscitation: patients' choices and doctors' duties. Palliative Medicine. 2001; 15: 449-50.
* 44. * 45. 46.
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Regnard C, Randall F. A framework for making advance decisions on resuscitation. Clinical Medicine. 2005; 5: 354-60. Mencap. Considerations of 'quality of life' in cases of medical decision making for individuals with severe learning disabilities. Mencap, 2001 (summary available on www.mencap.org.uk/html/campaigns/health_pubs.htm) Fainsinger RL, MacEachern T, Miller MJ, Bruera E, Spachynski K, Kuehn N et 01. The use of hypodermoclysis for rehydration in terminally ill cancer patients. Journal of Pain and Symptom Management. 1994; 9: 289-302. Regnard C, Hockley J. A guide to symptom relief in palliative care, 5th edn. Oxford: Radcliffe Medical Press, 2004.
Medical negligence In head and neck surgery ARNOLD GD MARAN
Introduction Good medical practice Ascertaining the standard of care
2803 2804 2805
INTRODUCTION The standards of provision of medical, and especially surgical, care changed utterly in the last few years of the twentieth century. In 1997, in the so-called Bristol case, three doctors, two cardiac surgeons and a manager were found guilty of serious professional misconduct by virtue of having performed below their expected standard. Two were erased from the medical register, and one was suspended. Two years later, public mistrust of the medical profession was heightened when Harold Shipman was jailed for the murder of several of his patients. These two events led to an unprecedented number of complaints to the General Medical Council (GMC) regarding doctors. The previously established local disciplinary and local complaints mechanisms, which are a part of clinical governance, were augmented by the lowering of the threshold for the investigation of complaints by the GMC resul.:ing in many more doctors undergoing the stress of a process that could materially affect their career. The problem for doctors now is that they face several levels of jeopardy that they would not have previously expected. Formerly, an unsatisfactory outcome from an operation may at worst have resulted in an action being raised in the civil courts for alleged medical negligence. While the new regulations relating to the provision of legal aid have made this more difficult to obtain, it has nevertheless not halted the process because many legal firms are now taking cases on a contingency basis. Doctors now also face disciplinary action under clinical governance; a three-stage enquiry if the Wilson Complaint Procedure is invoked; inspection by Royal
Specific negligence issues in head and neck surgery Best clinical practice References
2807 2809 2809
College Inspection Teams; independent review panels; and possible referral to the National Clinical Assessment Authority. Independent hospitals are also required to set up a complaints procedure, which would be handled internally by the Medical Advisory Committee and externally by the National Commission for Care Standards. If there is a death, or a series of deaths, the police may be alerted by the coroner or may decide to investigate on their own. In the last few years the Crown Prosecution Service has brought many more charges of manslaughter against doctors who have had fatalities where recklessness has been alleged. Finally, a complaint may go to the GMC. The GMC will accept complaints from members of the public, relatives, trusts, doctors, public bodies and the courts. Complaints are looked at first by the office, and approximately 30 percent are deemed not to be pertinent to the GMC (these complaints would perhaps relate to general National Health Service (NHS), matters such as waiting times or poor service conditions). The remainder go to the case examiner who will carry out an initial investigation and decide whether it can be dealt with by a letter of advice to the doctor (not disclosable to the employer) or, in the case of a possible health problem, invite the doctor to be examined by two GMC appointed doctors. If standards of performance are involved in the complaint, the case examiner may invite the doctor to undergo a performance review. If the allegation might be likely to result in a decision that could affect the doctor's registration, then he will forward the case for further consideration by the investigation panel. After further investigation, they may issue a warning, which is
2804 III PART 17 HEAD AND NECK TUMOURS disclosable to employers, or they may send the case to the Fitness to Practise (FTP) panel (formerly called the Professional Conduct Committee). If the allegation is serious, then the doctor may well have his registration suspended pending the hearing. If there has been a conviction by a court, then the doctor will be referred directly to a hearing by the FTP panel. At this type of hearing, the public and press are admitted. The doctor will be represented by a counsel employed by his medical defence organization and the panel will consist of five or six people drawn from the GMC associates who will be a mixture of lay and medical people and it will take the form of a formal court hearing with examination in chief followed by cross examination. The hearing is likely to last several days. The FTP panel has powers to dismiss the case completely or to issue a warning but, if serious professional misconduct is found, they may put conditions on practice, suspend the doctor for a period of up to two years or erase him from the register. In recent years, the thresholds of judgements have been slightly altered so that if someone does have their name erased, then there is virtually no likelihood of being reinstated on appeal. Until 2007, the criminal standard of proof, i.e. beyond reasonable doubt, was used when adjudication was being applied to a doctor accused of serious professional misconduct. After the Shipman inquiry recommendations by Dame Janet Smith, the GMC agreed to lower the threshold to the civil standard, i.e. the balance of probabilities. It remains to be seen if this will result in more doctors losing their right to practise or if it will raise the threshold for the level of sanction imposed. Many doctors are concerned that a single unfortunate clinical incident might affect their registration. Although many such cases are pushed towards the GMC by unhappy or vengeful patients, a doctor would be advised to rely on a recent privy council judgement in the case of Rao v. the GMC 1 before Lord Millett, Rt. Hon. Justice Gault and Sir Philip Otton. Their lordships found this case to be 'a borderline case of serious professional misconduct based on a single incident. There was undoubted negligence but something more was required to constitute serious professional misconduct'.
GOOD MEDICAL PRACTICE A completely revised edition of the booklet Good medical practice2 was published after the Bristol case in 1998. It is much more precise and clear than previous editions and constitutes a good foundation for a safe medical practice. Since many cases of alleged negligence in head and neck surgery have common principles, it may be of use to address these principles from within the context of this publication.
Clinical situations Perhaps the two main clinical problems that obfuscate any case of negligence are communication and note keeping. Many cases begin because the patient or his relatives are unhappy at the way that they have been treated after what they perceive as a bad result. Local policies will differ depending on the Trust Risk Assessment policy but, in general, it is better to spend time talking to a patient and his relatives explaining what might have gone wrong, the implications and what you are going to do about it, rather than hide the fact and unrealistically think and hope that the problem will go away. An apology or an expression of sympathy at the plight of the patient is not an admission of liability and, while it may not make an allegation go away, it makes for a more convincing defence. What you must never do or attempt is any sort of cover up. This will inevitably be discovered as all the papers are recovered and collated. If you are found guilty of 'covering up', it is not only a charge that can lose you a legal claim but it is something that could also affect your registration since it is taken very seriously by the GMC and is regarded as dishonest, which the indicative sanctions list as one of the more serious departures from Good medical practice. One of the defence societies has the saying 'Good notes are good defence and no notes are no defence'. This is very true and no matter how pressed you are, you must always go the extra mile to write a note while thinking about how you would answer in a court of law. This may seem rather overprotective advice, but it is a good rule to follow. When writing up an operation, take care to address what you did with the vital structures. What did you do to protect them? Were they intact at the end and, if they were damaged, why? In the clinic, it is often easier to write very full letters after each consultation but the secretarial back up may not allow that. In that instance you should take care to make some note of important negative findings as well as positive ones. There are times when it may be important to add to a note that has already been written. There is nothing wrong with this provided that it is clearly indicated that the entry was added at a later date. To alter already written notes, no matter how minor the alteration, is an act that will require clear explanation and may well be deemed serious professional misconduct if it was altered in an attempt to 'cover up'. Clinical performance is the most usual cause of an allegation of negligence. The three major issues are: 1. not keeping skills and knowledge up to date; 2. not recognizing the limits of professional ability; 3. practising techniques without suitable training. In these days of appraisal, continual medical education (CME) and lifelong learning, the first is fairly obvious. However, it is linked to the other two. Let us say that the procedure that you carried out all your life for a condition
Chapter 203 Medical negligence in head and neck surgery
has been supplanted by a newer and more acclaimed procedure. In this instance you must be very careful that when you consent the patient for the procedure that you are accustomed to doing that you make it clear that there is the option of referral to a colleague for the more up-todate procedure. Similarly, if you carry out the 'new' procedure, you must tell the patient it is novel, that you have not done as many of this as of the other procedure that you used to do, and if you have had training in it, what that training was. Again, this might seem overprotective but is preferable to being accused of an unsatisfactory surgical outcome when it transpires that this was the first time that you had attempted the procedure, and the patient did not know this. This does not of course apply to an incremental step performed in an operation in which you are experienced. After the Bristol case, the presidents of the Royal Surgical Colleges signed a statement that declared that the patient should never form part of the surgeon's learning curve. However, what was omitted was detailing clearly what steps a surgeon had to take when he learned a new procedure, which is an integral part of lifelong learning! The primary causes of failure to refer to a colleague are trust policy (if the colleague is in another Trust), private practice jealousies and dysfunctional relationships. The latter two issues must be understood and answered for in the case of a claim.
Dishonesty Clear dishonesty issues such as charging private fees to NHS patients and making false claims on the NHS are answerable for locally, but will almost certainly find their way to the GMC. Less clear is research fraud. Many doctors have had their registration affected by proof of such charges. Scientific fraud is either major or minor. Major scientific fraud relates to either fabrication or falsification of data or events. Minor scientific fraud is subtler but potentially just as damaging to patients. This takes the form of using statistics to prove what you want to prove. This could lead to a result that may lead other doctors to treat patients differently as a result of the published findings - and they may be found to be harmfuL This also applies to false claims for novel operations. The author is reminded of the plethora of neoglottis operations that apparently could only achieve good results in the hands of the original author!
Relationships Otolaryngologists are no less prone than any other group to getting into problems with patients because of indecency or sexual advances.
I 2805
The commonest way to be negligent in regard to patient relationships is to abuse confidentialitl and while trust policies, medical ethical standards and the Data Protection Act go a long way to protect patient confidentiality, there are instances where doctors have appeared before the GMC through thoughtlessness. While one source of breach of confidentiality is 'tittle tattle' at overfuelled parties, the most dangerous situation is when a doctor has been involved in the management of patients in a high profile situation, for example a disaster, a criminal event, a situation involving 'a personality', or performing a unique novel operation. There is nothing wrong in talking to the media about any of these situations, but patient identity must never be compromised. Even the late Harold Shipman reported one of his examining doctors to the GMC because he had talked to a newspaper. On the other hand, 'people make good press' and so you will be pushed to provide, however inadvertently, what the journalists want.
Health issues Like any other medical practitioner, an otolaryngologist must take care to avoid drug or alcohol abuse. There are many agencies that supply confidential help to those unfortunate enough to have these problems. It is more preferable to avail oneself of these procedures prior to any untoward event occurring. It should be borne in mind that a conviction and disqualification for driving due to an excess level of alcohol will result in an interview with two psychiatrists and a public hearing.
ASCERTAINING THE STANDARD OF CARE The Bolam test This is the classic direction of McNair J to a jury in Bolam v. Priern Hospital Management Committee. 4 A doctor is not guilty of negligence if he has acted in accordance with a practice accepted as proper by a responsible body of medical men skilled in that particular art. In other words, a doctor is not negligent if he is acting in accordance with such a practice merely because there is a body of opinion that takes a contrary view.
Bolitho The modification of Bolam took place in the House of Lords in the case of Bolitho v. City and Hackney Health Authority.5 Lord Browne-Wilkinson said McNair J stated that the defendant had to have acted in accordance with a practice accepted as proper by 'a responsible body of medical men'. Later he referred to a 'standard of practice
2806 I PART 17 HEAD AND NECK TUMOURS recognized as proper by a competent reasonable body of opinion'. Lord Scarman refers to a 'respectable body' of professional opinion. The use of these adjectives responsible, reasonable and respectable - all show that the court has to be satisfied that the exponents of the body of opinion relied on can demonstrate that such an opinion has a logical basis. In particular, in cases often involving the weighing of risk against benefits, before accepting a body of opinion as being responsible, reasonable or respectable, the judge will need to be satisfied that, in forming their views, the experts have directed their minds to the comparative risks and benefits and have reached a defensible conclusion on the matter.
Sidaway In the case of Sidaway v. Board of Governers of the Bethlem Royal Hospital and the Maudsley Hospital. 6 This judgement made a number of important changes to perceived wisdom. The definition of a specialist was tightened up, and the phrase in Bolam 'no doctor of ordinary skill', was substituted by 'no specialist of ordinary skill'. Although still to be tested in otolaryngology, this would seem to suggest that if someone whose primary practice was in otology were to give an opinion on a complication of endoscopic sinus surgery, then he might be challenged on his claim to be a specialist. It also clarified the explanation of risk and consent. However, Lord Bridge stated that 'a decision what degree of disclosure of risk is best calculated to assist a particular patient to make a rational choice whether or not to undergo a particular treatment must primarily be a matter of clinical judgement'.
Recklessness With the Crown Prosecution Service becoming increasingly involved with fatalities within medical practice, another definition has assumed some importance. Recklessness, if proven, could result in a charge of manslaughter. It may be defined as identifying a particular risk, realizing the consequences of proceeding in the light of that risk, and a fatality occurring.
Human Rights Act This is becoming a common defence, especially Article 6, which concerns the right to a fair trial. The frequently cited passage from this Article is the right to a fair trial 'within a reasonable time'. On occasion, this has proved an extremely effective defence due to the backlog created by the flood of complaints submerging the GMC processes. Since November 2002, the rules now are that the GMC will not accept any complaint about any event
that is more than five years old from the time of the initial complaint.
Consent Until recently, informed consent could be thought of under four categories. 1. Telling the patient of your recommendation for treatment AND the alternatives. 2. Telling them of the likely consequences of not taking your advice. 3. Telling of the specific risks attached to the operation. 4. Making them aware of the risks of surgery in general.
The GMC booklet on consent issues 7 clarifies the following issues. The patient should be informed of: • information that will vary according to the complexity and risks of the procedure in question; • the details of the diagnosis and likely prognosis if the condition is left untreated; • the details of uncertainties about the diagnosis including options for further investigation prior to treatment; • the options for treatment including the option not to treat; • the common and serious side effects of any investigation; • the benefits and risks and the likely change in life style should any of the explained risks occur; • whether or not the treatment is new, novel or experimental; • whether doctors in training will be involved. The following points relate to doctors. • Do not exceed the authority given you by the patient except in an emergency. Thus, if nodes are found in the neck during a laryngectomy, you cannot go ahead and carry out a neck dissection unless this has been discussed with the patient. • You should not withhold information necessary for decision-making unless you judge that disclosure will cause the patient serious harm. In this context, harm does not mean that the patient would become upset or decide to refuse treatment. Although some patients refuse endoscopic sinus surgery when confronted with the possibility of intracranial complications that could lead to death, the information should never be withheld. • The doctor who gives consent must be suitably trained and qualified and must know all about the procedure. • You must use the patient's case record to detail key elements of the discussion with the patient, including
Chapter 203 Medical negligence in head and neck surgery I
the nature of the discussion with the patient and specific requests by the patient. • A signed consent form is not sufficient evidence that the patient gives or still gives consent for the procedure if it is more than three months since it was signed.
SPECIFIC NEGLIGENCE ISSUES IN HEAD AND NECK SURGERY Preoperative issues DELAY IN DIAGNOSIS
Although accusations of delay in diagnosis are usually directed towards the general practitioner, an otolaryngologist must have good arguments available if he is accused of failing to diagnose a condition within a reasonable time. The standard investigation of any head and neck condition will involve clinical assessment and one or more of the following - fine needle aspiration biopsy (FNAB), ultrasound, computed tomography (CT) scanning, magnetic resonance imaging (MRI) and endoscopic investigations. If a doctor works to a defined protocol in the use of these investigations then he has a stronger defence than if it appears that he is quite random in their use. While medicine cannot be 'done by numbers', the only alternative to the ultimately ludicrous defensive medical situation of investigating everyone is to show that you have a good reason for doing or not doing an investigation and that you can defend those reasons.
PROBLEMS ARISING BECAUSE OF SYSTEMS' FAILURES Pathology
The quality of service from the pathology departments throughout the country varies enormously when it comes to head and neck cytology. In a district general hospital it may not be possible to have a dedicated cytologist and the smears may 'do the rounds' of the department with a poor diagnostic harvest. An otolaryngologist caught in this trap may be criticized if he either stops carrying out FNAB on every 'lump' or fails to repeat 'negative' aspirations. The surgeon should attempt to take steps with the managers and with the department prior to reverting to a haphazard and episodic use of the technique. Imaging
In regard to imaging, the problem is the shortage of both radiologists and equipment in some hospitals. When the wait for scans for non urgent cases, such as parotids, is a matter of months, then the surgeon may well have to operate without a scan and if there is a subsequent
2807
'surprise' or a facial nerve paralysis then he could be in difficulty. Similarly, some hospitals run an enormous backlog of non urgent ultrasound investigations. The principle that the otolaryngologist should follow has to be the same as outlined above. Attempts should be made to draw the service deficiency to the attention of managers and colleagues. On no account should the surgeon be tempted into bad practice by frustration. Endoscopy
Endoscopy is a very responsible procedure both in the clinic and the day surgery unit. If it is required, then it is an important diagnostic step. Although it is an easy surgical procedure, the consultant in charge must make sure that, if indeed he delegates it, that he is confident to act on the findings of his specialist registrar because he, the consultant, is ultimately responsible.
Operative problems In the preceding sections we have dealt with consent issues and the performance of the correct operation on the correct patient by a surgeon competent to carry out that procedure. In this section, we will consider specific and frequent head and neck complications highlighting any negligence issues. ACCESSORY NERVE DAMAGE
The accessory nerve may be damaged in two main situations. In neck dissection, sparing the nerve is an option in the NO neck. However, patients must be made aware of the severe restriction on life style that an accessory nerve palsy causes. There will be limitations in regard to putting on clothes, to power in the arm, to cosmesis, to sporting activities and, most importantly, it may prevent future employment, thus making it a very expensive claim to settle. Damage to the nerve in cancer surgery has a certain logic in the mind of patients provided that the explanations have been clear enough. Damage to the nerve in procedures involving gland biopsy in the posterior triangle are a different issue. Firstly, there must be a very clear reason why open biopsy was preferred over FNAB, repeated if necessary. Small glands in that area seldom need to be biopsied because, unless they are multiple and tuberculosis or lymphoma is suspected, there are alternative means of rationalizing the situation. If the accessory nerve is damaged in such a procedure then that damage must be recognized, either at the time of surgery or in the immediate postoperative period. An ENT department has neither the expertise nor the investigative power to recognize and prognosticate in relation to this injury. As soon as the injury is suspected (and this should be soon after the recovery period), the patient should receive an explanation and be referred to
2808 II PART 17 HEAD AND NECK TUMOURS the regional peripheral nerve expert whose electromyography (EMG) facilities will be understood by them. If the nerve is traumatized and it is not just a neuropraxia, then the earlier the repair is carried out the better. Late referral is nearly always due to an unwillingness to inform the patient that something may have 'gone wrong'. When the only operation for the removal of metastatic neck nodes was the classical radical neck dissection, removal of the accessory nerve formed an integral part of every operation and while the majority of patients had problems, some did not. With the advent of various subtypes of neck dissection, the surgeon should always make a note of what the patient was told about shoulder function after the operation and the reasons for the surgeon to include the accessory nerve in the removed specimen. When modified neck dissection was included in everyday practice, perceived wisdom was that the accessory nerve should not be preserved in the N + neck if the nodes were in levels 2 or 3. There has been some slippage from this by some head and neck surgeons in the last few years and so there may be genuine disagreement between experts when reports are exchanged that will not be helpful to the court.
RECURRENT LARYNGEAL NERVE
Increasingly, otolaryngologists are performing thyroid surgery. If the nerve is damaged during thyroidectomy and the surgeon is regularly carrying out the operation, then he is at no more risk than any endocrine surgeon who creates the same problem. Where the otolaryngologist is at risk, is when he is an 'occasional' thyroidectomist. It would be extremely foolish to carry out an 'occasional' operation. The recognition of unilateral or bilateral recurrent laryngeal nerve (RLN) palsy is relatively simple and it would be difficult not to institute the correct treatment.
FACIAL NERVE PARALYSIS
The same applies to parotid surgery. In each region or Trust there should be someone who carries out the majority of the parotidectomies. There is no place here, as anywhere else, for the 'occasional' operator. Before any parotid surgery, every step should be taken to establish both the position and the nature of the parotid lump. If there is any suggestion of malignancy, then the consenting procedure should be specific in the explanation of a possible sacrifice of the facial nerve or one of its branches. If a branch of the facial nerve is permanently damaged without reason, then the resulting defect in the face is nowadays almost unacceptable. The injury happens even in the best of hands, but, unless preceded by clearly documented informed consent, then an allegation of negligence will be difficult to defend.
VAGAL NERVE INJURY
While this can be damaged during a neck dissection for the removal of metastatic nodes, it is most usually sacrificed after either biopsy or removal of a nerve sheath schwannoma. Provided consent has been obtained for this, and also consent for an immediate medialization of the vocal cord, then no charges should arise.
VASCULAR INJURIES
The most likely vessels to be injured are the carotid and the brachiocephalic trunk. If the carotid artery is breached in the removal of a chemodectoma, then questions may be asked as to why a vascular surgeon was not either present or at least available for call if required. If accidental breach occurs during the removal of malignant glands that may be attached to the artery, then it is unlikely that any charges would flow from any complication of the breach. Not so, however, if the artery is holed during a laser procedure in the tonsil/tongue base as occurred recently. The brachiocephalic artery may rupture with fatal results if a tracheostomy tube displaces from the trachea and erodes it. It would be negligent not to recognize that the tube had displaced.
AIRWAY PROBLEMS
The relief of airway obstruction by emergency methods other than tracheostomy forms part of every surgeon's basic training. Thus, to attempt tracheostomy (a difficult and complex operation) when simpler procedures would suffice until the arrival of more skilled help, might be considered negligent in the advent of an unfortunate result. Charges of negligence may arise from recognizing an airway problem too late, from not recognizing that a tube had displaced or from performing a tracheostomy that resulted in a tracheal stenosis.
LARYNGEAL PROBLEMS It is now appreciated that stripping of a vocal cord is an
operation that should never be performed, unless for suspected malignancy. Singers are now much more aware of their anatomy and physiology than before and they are well acquainted with the importance of the laryngeal mucosa in the production of higher partials on which their living depends. Another error that can expensively end the career of a performer is the misdiagnosis of a nodule for a cyst and subsequent problems that will occur with a recurrent scarred cyst. If operations are being performed on professional voice users it is essential to create and keep a video record of the 'before and after'.
Chapter 203 Medical negligence in head and neck
ORAL CAVITY PROBLEMS
Performing operations on the palate for snoring without carrying out sleep studies was formerly an activity that was a constant provider of negligence cases. These cases nearly always boil down to consent issues and an explanation of the alternative methods of treatment. While the palate may often be temporarily incompetent after one of these operations, the worst problem is the creation of a pharyngeal stenosis because it is a problem that almost always defies repair. Delay in diagnosis of tongue base tumours is frequent but, as an allegation of negligence, it very seldom fulfils the requirement of Bolam, unless the investigations have been crass.
Best clinical practice Make sure that you are fully acquainted with the standards laid down in the GMC booklet Good
medical practice. 2 Write everything down - 'good notes make good defence, no notes are no defence'. If a charge of dishonesty is proved at a Fitness to Practise hearing, then it is probable that the doctor may be erased from the register. Never 'cover up'. Always be open to patients when you have made an error. Practice within your limitations and experience. If a new procedure comes along, make sure you receive training that is documented before you carry out the procedure. Do not rely on crown indemnity; join a defence society.
-
REFERENCES 1. 2. 3.
4.
Rao v. the General Medical Council [2002] Privy Council Appeal No. 21 of 2002. General Medical Council. Good medical practice, 3rd edn. London: General Medical Council, 2001. General Medical Council. Confidentiality: Protecting and providing information. London: General Medical Council, 2004. Bolam v. Friern Hospital Management Committee [1957] All ER 118.
5. Bolitho v. City and Hackney Health Authority [1993] 4 Med LR 381.
6. Sidaway v. Board of Governers of the Bethlem Royal Hospital and the Maudsley Hospital [1984] QB 493. 7. General Medical Council. Seeking patients' consent: the ethical considerations. London: General Medical Council, 1998.
Index
An F following a page reference indicates that the reference is to a figure; a T indicates that the reference is to a table. A1 555G mitochondrial mutation 1 6-7 Abbe-Estlander flap, lip reconstruction 2545-6, 2546 F Abbreviated Performance with the Hearing Aid Benefit (APHAB) , middle ear implants 3663-4 Abciximab 1 14 abdominal wall flaps 2876-83 abducent nerve (VI) 39 1 8-22 anatomy 3918-9, 39 18 F, 39 19 F, 3920 F central anatomy 39 19 central mechanisms 39 1 9-2 1 diplopia 3945 examination, eye movements 3710-1 fascicles 39 19 meningiomas and 4009 vestibular schwannoma 3958-9 abducent nerve palsy 39 1 8-9 tumour-induced 3922 vestibular schwannoma removal 3980 abducent nucleus 3919, 3920 F ocular muscle innervation 322 1 ABO blood groups 253-4, 254 T antigens 253-4 incompatibility 260 inheritance 253-4 matching errors 253-4 Aboulker stent, laryngeal reconstruction 1 1 57-8, 1 1 58 F, 2279 abscess( es) Bezold's 922, 922 F cervical, children 12 13, 1 2 1 3 F dental see dental abscess oral mucosa 1 827-8 orbital see orbital abscess parapharyngeal see parapharyngeal abscess periosteal 1 087-8 peritonsillar see peritonsillar abscess (quinsy)
retropharyngeal see retropharyngeal abscess salivary 724 septal 1 076, 1572-3 subdural see subdural abscess subperichondrial 3359 subperiosteal 1 539, 1 540 Absidia, fungal rhinosinusitis 2 1 7 absolute threshold, sound 3250, 325 1 F absorbent devices, saliva collection 1 862 Acanthamoeba castellani 24 1-2 accelerated hyperfractionation 2755 Accent method, speech therapy 22 19-20, 2225 accents, speech rhythm 2 1 68 accessory devices, hearing 3666-72 communication aids 3667-8 current devices 3667-9 categories 3667 definitions 3666 elderly 3666 fitting strategy 3670-1 future developments 3669 hardwired systems 3667 induction loop systems 3668
accessory nerve (XI) damage cancer surgery 2807 neck dissection complication 2744, 2807-8 surgical, medical negligence 2807-8 in jugular foramen 390 1-3, 3903 F functional deficit, postoperative 404 1 lesions 3937 skull base lesions 3946 surface anatomy 1 741 accessory ostia 1 330 Access to Health Records Act ( 1990) 602 accreditation, continuing medical education points 555-6 acetazolamide episodic ataxia 3804 Meniere's disease 3799 migrainous vertigo 3803, 3803 T
infrared systems 3668 literature 3669 microphones 3667 nonauditory 3668 performance 3670 provision 3670 quality 3670 radio systems 3667, 3670 speech-to-noise ratio 3667 studies 3669 telephones 3668-9, 3669 text systems 3669 uses 3669 warning/alerting systems 3668 doorbells 3668 accessory meningeal- artery 3907
acetylcholine cilia, effects on 1361 nose, effects on 1 364 pubertal rhinitis 1077 vestibular hair cells 3238
side effects 3799 spinocerebellar ataxias 3774 acetic acid, otitis externa 430
acetylcysteine otitis media with effusion 3392 ototoxicity prevention 3302 achalasia 2066 aetiology 1288 children 1288-90 incidence 1288 treatment 1289-90 clinical features 1288, 2066 diagnosis 1288-9, 2066
Pages 1-1 3 1 2 are in Volume 1, pages 1 3 1 3-28 10 are in Volume 2, and pages 28 1 1-4147 are in Volume 3.
4 1 50 I I ndex
achalasia (continued) dysphagia 1288, 2032, 2066 pathogenesis 1288 radiological features 1288, 1289 F treatment 1 289-90, 2066 forceful dilatation 1 289-90 pharmacological 1 289 surgical 1 290, 2066 aciclovir 209 Bell's palsy 2 10, 3886 herpes zoster 1 700- 1 , 2005, 2079 herpes zoster oticus 434 juvenile-onset recurrent respiratory papillomatosis 1 178-9 mouth ulceration, advanced head and neck cancer 2789 ototoxicity 240-1 Ramsey Hunt Syndrome 434 loss 434 sudden sensorineural acid burns, pinna reconstruction 3035, 3037 F 'acid laryngitis' 2262 acid suppression therapy 1276 acinic cell carcinoma 2497 survival 2 5 1 2-3 acinus, salivary glands 1 852 secretions 1 860-1 acne vulgaris, external nose 1 7 1 5 acoustic admittance!compliance 3 168-9 acoustic brainstem evoked response (ABR) auditory neuropathy/ dyssynchrony 3839-40, 3842, 3844 F children 3839-40 latency-intensity studies 3 843 detection 3 842 multiple sclerosis 3846, 3847 F quinine administration 3850, 3850 F acoustic impedance 3 167-9 definition 713, 3 1 68, 3288-9 middle ear 3288-9 ultrasound 7 12, 7 1 3 acoustic interface 7 1 3 acoustic neuroma (AN) see vestibular schwannoma (VS) acoustic reflectometry, otitis media with effusion 889 acoustic reflexes, otitis media with effusion 941 acoustic rhinometry 1 358, 1 375 accuracy 1375 nasal blood flow measurement 1 363 normal values 1 375
rhinomanometry vs. 1375, 1 376-7 septal pathology 1 576, 1 577 F acoustics 3 1 58 see also sound acoustic shock 3552, 3552 T acoustic signals, voice 2 170 acoustic trauma definition 3548 glutamate neuroexcitotoxicity 3604 hyperacusis 3596 tinnitus 3599 see also noise-induced loss acoustic voice measures see voice evaluation acquired atresia, external ear 3346-50 aetiology 3347 bone-anchored hearing aids 3643 complications 3347-8 definition 3346 diagnosis 3346-7 epidemiology 3347 future research 3349 inflammation 3347 knowledge deficiencies 3349 management options 3348-9 medical 3348 membranous 3346, 3347 F pathogenesis 3347 surgery 3349 natural history 3347-8 outcomes 3349 pathogenesis 3347 solid 3346, 3346 F, 3347 F pathogenesis 3347 surgery 3348 F surgery 3348-9 with tympanoplasty 3349 surgery-induced 3347 ",rrl1,,,",,,t1 immune deficiency syndrome (AIDS) see HIV infection/AIDS
actinic keratosis external nose 1 705 squamous cell carcinoma, risk of 2398 Actinomyces 20 1 growth 20 1 Actinomyces bovis 2268 Actinomyces israelii 201 laryngeal infection 2268 nasal infection 1 703-4 paediatric cervicofacial infections 1 2 1 6 Actinomyces meyeri 2 0 1 Actinomyces odontolyticus 2 0 1 actinomycin D 38 actinomycosis 201 children 1 2 16 laryngeal manifestations 2268 neck manifestations 1 785, 1 786 F activated C protein, critical care 535-6 activated partial thromboplastim time (APTT) 280 activated partial thromboplastin time (APTT), lupus anticoagulant 28 1 active noise reduction 3554 acute bacterial rhinosinusitis (ABRS) complications 1443 diagnosis 1442 pathogenesis 1440 prevalence 1443 acute confusional states, palliative care patients 2797-8 causes 2797-8 clinical features 2797 treatment 2798, 2798 T acute epiglottitis see acute acute exacerbations of chronic rhinosinusitis 1 382, 1382 T, 1439-40 acute laryngotracheobronchitis (ALTB) see croup acute lymphoblastic leukaemia (ALL) clinical presentation 274 investigations 274 treatment 274 acute myeloid leukaemia clinical presentation 274 investigations 274 treatment 274 acute necrotizing ulcerative QinQivitis (ANUG) 1 8 1 9, 1 8 1 9 T cancrum oris 1 822 clinical features 1 8 1 9 gingival bleeding 1 8 1 9
Pages 1-1 3 1 2 are i n Volume 1 , pages 1 3 1 3-28 1 0 are i n Volume 2 , and pages 28 1 1-4 147 are i n Volume 3 .
I ndex I 4 1 5 1
acute pain management plans 463
embryology 295
aetiopathology 914-6, 3385, 3386 T
acute parotitis of infancy 1243, 1243F
antibiotics 431, 917-8, 918-9, 3386
acute renal failure (ARF)
hormones 300-2, 307, 4098 secretion 297, 308
acute otitis media (AOM) 3385-7
bacterial 915, 915 T
causes 530, 531 T
magnetic resonance imaging 305
children 912-27, 3527-8
critical care patients 530
pars tuberalis 296 structure 296, 307
acute episodes 917-8 auditory functioning 921 cumulative incidence 917
acute respiratory distress syndrome, aspiration-related 2094-5 acute rhinosinusitis (ARS)
venous drainage 297 adenoid(s) 1094-101, 2121-2
diagnosis 913-4
antibiotic treatment 438-9
differential diagnosis 914
bacteriology 1441
assessment 1096-7, 1096 F, 1097 T
environmental factors 916
children 1080
anatomy 2108
epidemiology 917, 3410-1, 3411 T
corticosteroid treatment 437
associated antibodies 2121 blood supply 2121
facial paralysis 1056, 1056F
definition 1382, 1382 T
clinical examination 1096
gastro-oesophageal reflux
histopathology 1441
corticosteroids 422
microbiology 1441F, 1442F
development 1094, 2121
symptom duration 1439-40
enlargement
disease 1274 incidence 917F management 917-21 medical prophylaxis 918-20
acute suppurative otogenic labyrinthitis 3692
natural history 921
acute unilateral peripheral vestibulopathy
outcomes 921
see vestibular neuritis acycloguanosine see aciclovir adamantiades syndrome see Behfet's
recurrent 913, 918-21 signs 913-4 speech development 921 symptoms 913, 913 T chronic otitis media development 3408, 3410-1 commensals, benign 920 complications 921-5, 3386 extracranial 921-3 intracranial 923-5 congenital atresia 981 corticosteroids 423 definition 912-3, 3385 diagnosis 3385-6 criteria 3386
syndrome adaptation, vestibular hair cells 3231-2, 3232 F, 3235, 3236 F, 3792 active motor model 3233-4, 3233 F, 3234F calcium-dependent closure model 3233 F, 3234-5
HIV patients 241 obstructive sleep apnoea 1104, 1105F paediatric rhinosinusitis 1082 history taking 1096 immune function 1094-5, 2121 infants 2121 neoplasia 1096 pathology associated 1095-6 regrowth, post-adenoidectomy 1098 adenoid cystic carcinoma (ACC) metastases, jugular foramen 4033-4 otalgia 3528
functions 3234
parotid gland 2503-4, 2504F
as high-pass filter 3234
salivary glands 2498-500, 2502
process 3231 adaptive immunity 133-4 lymphocyte activation 133 adaptive sleep drive 2306
chemotherapy 2499 histology 2498-9, 2498F lung metastases 2498-9 molecular biology 2496
facial nerve paralysis 923, 3882, 3890
Adcortyl see triamcinolone
perineural spread 2499, 2499F
genetics 916
Addison's disease
postoperative radiotherapy 2508
immune factors 916
adrenocorticotropin secretion 300
radiological work-up 2499
incidence 3385
clinical features 401
recurrence rates 2511
infection spread routes 915-6
adductor paralysis, larynx 2223
surgery 2499
infective agents 211, 914-5
adductor spasmodic dysphonia 2224
survival 2512-3, 2515-6
investigations 914
adenine 3
management 3386
adeno-associated virus (AAV ) gene
natural history 3386 otalgia 3527-8 outcomes research instruments 640 risk factors 916 alteration of 918 surgery 918 prophylactic 920-1
therapy cystic fibrosis 25 head and neck cancer 27-8 adenocarcinoma(s)
submandibular gland 2504-5 adenoid cystic sarcoma, external auditory canal 4068F, 4070 adenoidectomy 1097
ceruminous 4070
acute otitis media 920-1, 1095
salivary glands 2500
airway management 500-1
polymorphous low-grade 2500
syndromic associations 916
sinonasal 2420
tympanic membrane
see also specific types/locations
assessment 913-4, 914F
treatment 2499 sinonasal 2420
adenohypophysis 296-7, 307-8
anaesthesia 500-1 children 515-7 maintenance 501 recovery 501
vaccination 211, 919-20
blood supply 297
complications 903, 1097-8
Wegener's granulomatosis 1650
cell types 296
dental damage 1308
Pages 1-1312 are in Volume 1, pages 1313-2810 are in Volume 2, and pages 2811-4147 are in Volume 3.
4 1 52 I I ndex
adenoidectomy (continued) extubation 501 haemorrhage 1097-8, 1308 indications 1095-6 medical negligence 1308 obstructive sleep apnoea 1095 olfaction following 1096 otitis media with effusion 902-3, 1095 outcomes 902-3 preoperative investigations 1097
infection 27 respiratory tract 205 transmission 205 viral characteristics 27 adhesion molecule antagonists, multiple sclerosis 3772 adhesion molecules
adrenocorticotropin (ACTH) see adrenocorticotropic hormone (ACTH) adult epiglottitis see epiglottitis, adult advancement flaps 'bucket handle' 2821 F cervicofacial cheek 2837
allergic rhinitis 1391
nasal reconstruction 3019
head and neck tumour markers
Webster cheek 2547
2384-5, 2386-90 T
adverse drug reactions 414-5
rhinosinusitis 1084
nasal polyposis 1552
allergic (non-dose-related) 414-5
speech, effects on 993
see also individual types
dose-related 415
syndromic craniosynostosis 1028
adhesive otitis media 3426
drug interactions as cause 415
techniques 902
adhesives
long-term therapy 415
velopharyngeal insufficiency 1011
see also adenotonsillectomy adenolymphoma see Warthin's tumour adenoma(s)
endovascular embolization 733-4 prostheses retention 2931-2 adolescents, surgical scarring 3090
ceruminous 4069-70 parathyroid see parathyroid adenoma
adolescent transitional voice disorder
see puberphonia
parotid glands 723, 723 F
adrenal cortex stimulation 300
pituitary see pituitary adenomas
adrenal disease 401
pleomorphic see pleomorphic adenoma
see also individual diseases/disorders adrenalectomy
pseudoallergic 414-5 reporting 408 aerobic Gram-negative bacilli see
Enterobacteriaceae aerodynamic equivalent diameter (AED), occupational rhinitis 1416 aerodynamic measures, voice evaluation 2171, 2181-3
Aeromonas hydrophila (medicinal leech), skin flap survival 115
thyroid 330, 719-20, 719 F
Cushing's disease 4102
aesthesioneuroblastoma 2420-1
toxic see toxic adenoma
Nelson's syndrome induction
aesthetics 2944-6
adenomatoid odontogenic tumour
311 adrenaline
1928 adenosine deaminase (ADA) deficiency 175 adenotonsillar hypertrophy paediatric anaesthesia 508-9 sickle cell disease 271 adenotonsillectomy acute otitis media 920-1 analgesia, postoperative 515-6 day stay 516-7 Down's syndrome 1109 haemorrhage 516
beauty, concept of 2944-5 definition 2943-4
cilia, effects on 1361
facial plastic surgery 2943-9
critical care 529-30
facial proportion 2945-6
food allergy 1431 nasal vasculature 1365
historical aspects 2943-4 afficates 2167, 2167 T
performance anxiety 2212-3
aflatoxins, salivary glands tumours 2494
reduction rhinoplasty 2952
agarose gel electrophoresis 61
upper eyelid blepharoplasty 3057 adrenocortical insufficiency see Addison's disease adrenocorticotropic hormone (ACTH) 300-1, 309-11
agarose gels, electrophoresis 5-6 age-associated hearing loss
(AAHL) 3542
see also age-related (sensorineural) hearing loss
nausea and vomiting 516
circulating levels 300
age effects, orbital anatomy 1679
obstructive sleep apnoea 1111
Cushing's syndrome screening 309
ageing/age-related changes
outcome measures 1230-1
deficiency tests 300
paediatric anaesthesia 515
ectopic production 401
sleep-disordered breathing 1109
effects 300
auditory nerve fibre thresholds 3199-200 cochlear duct 3540-1
special needs children 787
excess secretion 300
drug prescribing 415-6
tonsillectomy alone vs. 1230
half-life 300
dysphagia aetiology 2034
variant Creutzfeldt-Jacob disease
medullary thyroid carcinoma 401
facial see ageing face
secretion control 300-1, 309
olfactory dysfunction 1670, 1670 F
transmission risk 517, 626
see also adenoidectomy adenovirus(es) 205 diseases caused 24 gene therapy cystic fibrosis 24-5 head and neck cancer 27 skin flap survival 114
circadian rhythms 308
olfactory epithelium 1328-9
stress 300
olfactory nerve 3914
structure 309
organ of Corti 3540-1, 3540 F
tumours secreting see Cushing's
parathyroid glands cells 373
disease adrenocorticotropic hormone (ACTH) stimulation test 300
pharynx, neurological disorders 2076 swallowing 1961 tympanic membrane 3317
Pages 1-1312 are in Volume 1, pages 1313-2810 are in Volume 2, and pages 2811-4147 are in Volume 3.
I ndex I 4153
vestibular hair cells 3239 vocal folds 2205 wound healing 94 ageing face 3068-76
Ahl gene, noise-induced hearing loss 3549 Aid for Children with Tracheostomies (ACT) 1204
nonintubation technique 1121 recovery phase 518 sedative premedication 517 stridor 1119-23, 1143 airway management
biology 3069
AIDS see HIV infection/AIDS
clinical evaluation 3070-1
Aintree catheter 475-6, 476F
anticipated or known difficulties 494
histological transformations 3069
air, characteristic impedance 3165
proportions 2946, 2947F
air-bone gap
critical care, adult 533 devices 467
inactive mucosal chronic otitis
surgery
media 3421
complications 3074-5
anaesthesia 492-5 choice influencing factors 493-5
historical aspects 3068-9
measurement procedure 3461
surgical factors 494-5
patient age and 3070
otitis media with effusion 889
laser endoscopy 519-20
techniques 3071-3
otosclerosis 3461
neck trauma 1766-7
see also individual techniques Agency for Health Care Policy and Research (AHCPR), dysphagia management review 2085 age-related changes see ageing/ age-related changes Age-related sensorineural hearing impairment 3539-47
surgical contraindication 3470
paediatric anaesthesia 510-1
surgical eligibility 3465
paediatric surgery 519
air-conduction (AC) hearing aid,
postoperative intensive care
bone-anchored hearing aid
vs. 3643 T, 3644-6 air-conduction tests, otitis media with effusion 889 air embolism
treatment 546 postoperative pain 495 special needs children 786 tonsillectomy 515 airway obstruction 2286-91, 477-83
aetiology 3543 T
skull base surgery 4136
acute 477-8, 478F
definition 3539
syndromic craniosynostosis
adenoidectomy 1095
surgery 1031
diagnosis 3542, 3544 environmental factors 3542 examination 3544 genetics 17, 3541-2 history 3543-4 investigations 3544
tracheostomy 2301 airflow
adult epiglottitis 2250 airway endoscopy procedures 517-8 alternative airways 2289-91
nasal see nasal airflow voice evaluation 2181-2 air pollutants
anaesthesia 493 children 508-9 assessment 2287-8
management 3544-5
occupational rhinitis 1419
capnograms 499F
pathology 3540-1, 3540 F, 3540 T,
olfactory dysfunction 1673-4
children see airway obstruction,
rhinitis 1383, 1411
3541F prevalence 3543 T tinnitus 3599 age-related typical audiograms (ARTA) 3560, 3561F, 3562 F, 3563F ageusia
air pressure, voice evaluation 2182-3 air travel, professional voice and 2212
evaluation 478
air volume, voice evaluation 2181
infectious mononucleosis 2253,
airway(s)
laryngopyocoele 2256
nasopharyngeal 1109, 2289, 2289F
management 478-83, 2288-91
oral 2289, 2289F
definition 1842
patency 2308, 2308F
post-traumatic 1846
protection during swallowing 1955, 2217
anatomy 1332 development 1319 nasofrontal recess obstruction 1507-8 pneumatization 1332 agonists (drugs) 411 agoraphobia
airway-clearing manouevres, children 1188, 1189F airway disorders, gastro-oesophageal reflux and 1273 airway endoscopy, children anaesthesia 517-9, 1120-2
posturography 3736
2254F
difficult see difficult airways
brainstem injury 1847
agger nasi
children chronic 478
maintenance 1121-2
acute laryngeal infections 1132-3 medical 2288-9 midtracheal obstruction 483 noninvasive procedures 2288-9 sleep-disordered breathing 1102 stridor 478, 1117, 1118F symptoms/signs 2286-7 tracheostomy 2293 children 1195, 1195 T turbulent gas flow 477-8 airway obstruction, children acute
vestibular disorders and 3814-5
cardiovascular monitoring 518
vestibular rehabilitation 3816
diagnostic 517-8
emergency tracheostomy 1124
induction 1120-1
humidification 1123
agranulocytosis antithyroid drugs 346
intubation 1121
management 1123-4
mouth ulcers 1834
jet ventilation 1121
medical management 1123
pharyngeal symptoms 2015
laryngeal mask 11t1
oxygen therapy 1123
Pages 1-1312 are in Volume 1, pages 1313-2810 are in Volume 2, and pages 2811-4147 are in Volume 3.
4 1 54 • I nd ex
airway obstruction, children (continued) pharmacotherapy 1123 surgery 1123-4 symptoms 1117 T intensive care 543
Alexander's law 3712, 3712F alginates
incidence 220 management 221-2
fungating wounds 453, 2794
nasal polyposis 1550
gastro-oesophageal reflux 1276
outcomes 222
tissue scaffolds 123
laryngeal causes 1115 T
aliphatic amine N-oxides 51
pathophysiology 1453 surgical debridement 221
nasopharyngeal causes 1115 T
alkaline phosphatase, pregnancy 403
symptoms 1116-7, 1117 T
alkylating agents 37
'allergic mucin' see eosinophilic mucin
tracheal causes 1116 T
alleles, recessive mutant expression 8-9
allergic reactions see allergy/allergic
airway oedema
allelic deletion 9
extubation 484
allelotyping 8-9
respiratory sleep disorders 2309
allergen(s) 145
airway pressure, perioperative monitoring 498 akinetic syndromes 3731 ala 3006 collapse 3010-1
treatment 1454
reaction allergic rhinitis 1386-407 aetiology 1388-92
allergic rhinitis 145, 145 T
allergens 145, 145 T
avoidance see allergen avoidance
avoidance 1083, 1396-7
early phase response 1390
sensitization 1388-9
food allergy 1426-7
allergy diagnosis 1393-5
indoor 1396
asthma 158, 1387-8, 1388, 1402
alar base reduction surgery 3091
inhaled 145 T
children 1080, 1401
alar cartilage( s)
late phase response 1390-2
classification 1381, 1381 T, 1387F
anatomy 1325, 2960-1, 2995-6, 2996F asymmetry, post-nasal tip surgery 3004
occupational exposure 1397
clinical presentation 1392-3
sensitization 1388-90
co-morbidities 1388
see also individual allergens
contact endoscopy 764-5
allergen avoidance 1396-7
corticosteroids 419-20
cleft lip and palate 1005, 1006F
allergic rhinitis 1396-7
intranasal 420
nasal tip delivery 2998, 2998F
occupational exposure 1397
systemic 420, 1398-9
nasal valve collapse 3007
primary prevention 1396
retraction, post-nasal tip
secondary prevention 1396-7
surgery 3004, 3092
immunotherapy 1399-400
suture techniques 3001F alar muscle paralysis, nasal valve
fungal rhinosinusitis 1454 allergic occupational rhinitis 1421
collapse 3007 albinism
rhinitis 421, 1399-400, 1564-5
topical 153, 421, 1398 decongestants 1398 definition 1386 diagnosis 1082, 1393-5 endoscopic appearance 764-5 endothelial cells 1391 environment and 1388
basal cell carcinoma 1705-6
children 1399
eosinophils 1390-1
squamous cell carcinoma 2398
contraindications 1400 T
epithelial cells 1391
Albright syndrome 1929
efficacy 1399
examination 1393
albumin
indications 1399, 1400 T
history 1387-8
malnutrition assessment 95
mechanisms 1400
fibroblasts 1392
thyroid hormone binding 323
novel
food allergy and 1397
alcohol
1400
practical immunotherapy 1399-400
epistaxis 1600 head and neck cancer 2351-2 beverage type 2352
seasonal
1399
side effects 1399
19B-independent responses 1392
sublingual administration 1400
immune response 1389F
biological mechanisms 2352
allergen-specific
quality of life 2776
allergic fungal rhinosinusitis (AFRS)
hypopharyngeal cancer 2634 laryngeal cancer 2348, 2351-2 olfactory dysfunction 1664 oral cavity tumours 2347-8, 2550, 2550F
20, 1387-8 history taking 1393
159-60, 160F, 169
220-2, 1450 T, 1452-4, 1453F aetiology 221, 1452-3 clinical manifestations 221, 221F, 1470
immunotherapy see allergen immunotherapy intermittent (seasonal) 1381, 1381 T, 1386 knowledge deficiencies 1402 mucus production 764-5
complications 222
nasal polyposis 1550
oropharyngeal tumours 2347-8 rhinitis 1383
definition 220-1
neutrophils 1392
diagnosis 220, 221
olfactory dysfunction 1667-8
upper aerodigestive tract
diagnostic criteria 1451 T, 1453,
pathophysiology 1388-92,
tumours 2352 alcohol-induced positional nystagmus 3701
1453 T
1389F
epidemiology 221
early phase response 1390
immunotherapy 1454
late phase response 1390-2
Pages 1-1312 are in Volume 1, pages 1313-2810 are in Volume 2, and pages 2811-4147 are in Volume 3.
I nd ex I 4 1 55
sensitization 1388-90
systemic 1563
systemic activation 1392
T cells 149-51 tests 158-61, 169-70
persistent (perennial) 1381, 1381 T,
1392-3 pregnancy 1401-2 prevalence 1381, 1386-7, 1387F quality of life 1388 risk factors 1387-8
ameloblastoma 1927-8, 1928F epidemiology 1927 incidence 1921 malignant (metastasizing) 1938
see also individual tests treatment 152-5
maxillary 1927 types 1927
novel strategies 155-8 alloplastic grafts 96
variants 1927
augmentation rhinoplasty 2971
ameloblasts 799-800
surgery 1400
allopurinol, skin flap survival 113
treatment 1396-400
all-trans retinoic acid (ATRA) 274
amenorrhoea, prolactinoma 4100
antihistamines 1397-8
allylamines 234
American Academy of
environmental control 1396-7
alopecia
amlelolgelrresIs imperfecta 1817
Otolaryngologists! Head and Neck
novel strategies 155
cyclophosphamide-related 1652-3
'111","<"1"\'1"
pharmacotherapy 1397-9, 1397 T,
post-rhytidectomy 3075
torlsIUlectOITlY guidelines 1232
1398F Allergic Rhinitis and its impact on Asthma (ARIA) 1080, 1381, 1386,
alpha l-antichymotrypsin 2495-6 ex-antiplasmin 279
asthma see asthma autoimmunity 141
alternative lengthening of telomeres
aetiology 144-6 allergens 145
basophils 149 blood tests 1394 chronic laryngitis 2258-9 dendrite cells 151-2
rhinosinusitis classification system 1439, 1439 T
UteJrlmage 2947F Alternaria, fungal rhinosinusitis 217 221, 1452-3 noninvasive 219
allergy!allergic reaction 144-66
American Academy of Otolaryngology Head and Neck Surgery,
syndrome 813 T, 3683 alprazolam 3617
1387F
(AAO HNS),
71
American Head and Neck Society, data collection coordination 2375 American Joint Committee on Cancer (AJCC), lymph node classification! staging 715, 715 T, 2360, 2363 American Sleep Apnoea
alternative lengthening of telomeres (ALT)-associated promyelocytic
Association 1106 American Society of Anesthesiologists, physical status grading 461 T
leukaemia bodies 71
C1Ia��nmas 160-1, 161 F, 1393-5
alternative splicing 4, 15-6
effector cell recruitment 149
alternobaric facial palsy 3513-4
Otolaryngologists (ASPO),
environment and 145-6
alternobaric oxygen
juvenile-onset recurrent respiratory
eosinophils 62, 149, 150F
alternobaric vertigo 3513
food see food allergy
aluminium acetate
reactions inactive squamous chronic otitis
Meniere's
disease 3800
epIstaXIs, children 1067
144-5, 145 T geographical tongue 1826 hypothesis 145-6 hYlJerSenlsitivi1ty see hypersensitivity
American Society of Pediatric
ear inflammation 430 furunculosis 3324
papillomatosis staging 1176 amethocaine gel (AMETOP) , nasal fractures 1612-3 AMETOP (amethocaine gel), nasal fractures 1612-3
alveolar arch 1341
amifostine 2536
alveolar bone 2907
aminoglycosides 232
secondary grafting 1006, 1006F alveolar cleft 1005-6
mechanism of action 232 Meniere's disease 3760, 3800
alveolar consonants 2166-7, 2167 T
nephrotoxicity 236
mast cells 148-9
alveolar nerves 3924
ototoxicity 236, 3299 T, 3424,
mechanisms 146, 146F
Alzheimer's disease (AD), olfactory
media 3427
nasal polyposis 1550
dysfunction 1669
otitis externa 3352
amalgam tattoos 1825, 1826 F
otitis media with effusion 3389
amantadine 210, 232
pathogenesis 146-52
ambient pressure, otitic
early!late phase response 146
barotrauma 3500-2
effector cells 148-52
ambroxol see acetylcysteine
IgG 148
amelanotic melanoma
sensory nerves 148 penicillin-induced 230
diagnosis delay 3093 nasopharyngeal carcinoma 2455
pollution 146
ameloblastic carcinoma 1938
rhinitis see allergic rhinitis
ameloblastic fibroma 1927-8
rhinosinusitis 1440-1
ameloblastic fibro-odontoma
sulphonamide-induced 231
1927-8
3567-70 aetiopathology 3298-300, 3299 F,
3567-9, 3568 T, 3676, 3764 drug monitoring 3570 genetic susceptibility 16-7,
3568 hearing loss, attribution to 3542,
3572 incidence 3300 medical negligence 3831 natural history 3569 potentiators 3568 prevention 3302 recognition 3571-3
Pages 1-1312 are in Volume I, pages 1313-2810 are in Volume 2, and pages 2811-4147 are in Volume 3.
4 1 56 I I nd ex
aminoglycosides (continued ) relative toxicity 3568-9 risk factors 3569-70 side effects 232 tympanic membrane perforation with discharge 937 vertigo induction, children 1047-8 vestibular hair cell transduction channel blockage 3239 aminopenicillins 230 amino precursor uptake decarboxylation (APUD) tumours 4030 amiodarone, goitre and 2668 amitriptyline midfacial segment pain 1727 migrainous vertigo 3803 T, 3804 motor neurone disease 2080 neuropathic pain, advanced head and neck cancer 2785 sialorrhoea 2080 tension-type headache 1725 tinnitus 3617 amoxicillin acute otitis media 918, 920 intermittent rhinosinusitis 437 amphotericin 233 candidiasis 224 fungal rhinosinusitis 218, 219, 1455 mycotic laryngitis 2254 nephrotoxicity 236 resistance 224-5 side effects 233 ampicillin hepatotoxicity 236 infectious mononucleosis 1225 amplifiers, hearing aids 3631-2, 3632 amplitude, sound 2165 amplitude distortion 3178 amplitude linearity 3178 amplitude perturbation (shimmer) 2165, 2179 amplitude reduction, tinnitus 3608 ampulla 3153-4 amputation 97 ear 3028, 3032F nose 2924-5 amputation neuroma 3685, 3685F amrinone 114 amyloidosis 190 cranial nerves 2080 larynx 2266 macroglossia 1828
amyotrophic lateral sclerosis (ALS) 2079-80 see also motor neurone disease anacusis, vestibular schwannoma 3959 anaemia(s) 267-72 clinical assessment 267-8 critical care 535 definition 267 haemolytic see haemolytic anaemia history taking 268 investigations 268, 268 T lead poisoning 269 macrocytic 268 T, 269 microcytic 268-9, 268 T nonmegaloblastic 269 normocytic 268 T, 269-70 radiotherapy 2756
total intravenous tubeless 2149 vocal fold injection 2240
see also individual drugs; individual procedures
anaesthesia 488-506 agents 490-1 balanced 489, 489F children see paediatric anaesthesia consent 462-3 conservative parotidectomy 2483 depth indices 500 explanation of (to patient) 462-3 fasting periods 465 high frequency jet-ventilation 2149 hypophysectomy 4106 induction 495-6 inhalational 496
analgesia dying child 1261 paediatric intensive care 544 pain management, head and neck cancer 2785 analogue-to-digital conversion, averaging 3279 analysis accumulation, voice evaluation 2183 analytical studies see epidemiology anaphylactic (type 1) drug reactions 414 anaphylatoxins 89 anaphylaxis antimicrobial-induced 236 food allergy 1431 latex allergy 1419 penicillin-induced 230 transfusion reactions 261 anastomotic stricture, oesophageal atresia repair 1286-7 androgenic drugs, laryngeal disorders and 2201 androgen receptors, juvenile angiofibroma 2437-8 androgens 302 anethole trithone 1909 aneurysmal bone cysts, jaw 1931 Angell James dissectors 4110 anger, palliative care patients 2795-6, 2796 T angina Ludwig's 1807, 1902 New York Heart Association
intravenous 495 post-airway securing 496 rapid sequence 496 inhalational agents 491 intravenous agents 490-1 monitoring 496-500 intraoperative 496-500 nasal endoscopy 1347 nasal fractures 1612-3, 1613 operative laryngoscopy 2148-9 paediatric imaging 1301-2 patient anxieties 463 phonosurgery 2236 premedication 489-90, 490 T preoxygenation 495 principles 488-9 reaction tests 169
classification 458 T patient preparation, surgery 459 Anginosus-Milleri group, streptococci 198 angioedema, corticosteroids 421 angiofibroma( s) juvenile see juvenile angiofibroma nasal involvement 1708 nasopharyngeal 1297 resection, historical aspects 2439-40 tumour embolization 734, 734-5 angiogenesis 93 dermal repair 93 macrophages 93 pericyte-endothelial cell interactions 93
see also individual types anaemia of chronic disease (AoCD) 268-9, 268 T anaerobes 200-1 detection 200
see also individual species
Pages 1-1312 are in Volume 1, pages 1313-2810 are in Volume 2, and pages 2811-4147 are in Volume 3.
I ndex 14157
pro-angiogenic factors 44F skin flaps 114 thyroid cancer research 2698-9 tumours 43 angiogenesis inhibitors 43, 44F as maintenance therapy 43 angiography children 1300, 1300 F glomus tumours 3950 F hyperparathyroidism, primary 392 jugular foramen tumours 4035 juvenile angiofibroma 2438-9, 2440 F, 3954 meningioma 736 paragangliomas 739, 3953 temporal bone squamous cell carcinoma 4090 vascular injury, neck 1772 angiomas tumour embolization 734 F angioneurotic oedema 3951 drug therapy 449 angiooedema, acquired, oral swelling 1828 angio-oedema, hereditary see hereditary angio-oedema (HANE) angiosarcoma, larynx 2604 angiotensin converting enzyme (ACE) , sarcoidosis 1648, 1711 angiotensin-converting enzyme (ACE) inhibitors angio-oedema induction 1828 rhinitis induction 1410 taste abnormalities 1847 angular cheilitis, oral mucosa 1827, 1827 F, 1837 T nutritional deficiencies 1827 treatment 1827
anosmia atrophic rhinitis 1465 corticosteroid treatment 421 definition 1664 nonallergic occupational rhinitis 1416-8 post-traumatic 1846 supportive measures 1671 taste sensations 3929-30 anotia 975 F, 976 treatment 979-80 antacids 1276, 2063 antagonists (drug) 411 anterior atlantoaxial ligament 2111 anterior belly of digastric transfer 3084-5, 3084F anterior clinoid process 298, 4120 anterior commissure tendon 2132-3 anterior condylar canal 3899 anterior cranial fossa (ACF) boundaries 4120 meningioma, diagnostic failure 4144 surgical anatomy 4120, 4122 F anterior craniofacial resection 4128-30, 4128 anterior cranial fossa floor exposure 4129 contraindications 4129 incisions 4129 indications 4129 pericranial flaps 4130 procedure 4129-30 sinonasal malignancy 2431-3, 2432F, 2433 F anterior cricoid decompression 2282 anterior cricoid split 1162, 1162 F
angular displacement, cupula 3212 angular frequency 3159 angular stomatitis see angular cheilitis angular vein 1325 angular vestibuloocular reflex (aVOR) 3213 animal laboratory workers, occupational rhinitis 1419 ankyloglossia (tongue tie) 994 Annexin-V 61 annular ligament, ear otosclerosis 3456 sound transmission 3182 anodontia (dental aplasia) 1817
anaesthesia 521 indications 1162 anterior ethmoidal artery absence 1335 anatomy 1334-5, 1574 skull base 3897-8 endoscopic sinus surgery 1598 iatrogenic damage 1605 epistaxis 1598 ligation 1604 anterior glottic webs acquired 1160, 2281 aetiology 1160 management 1160 congenital 1137 phonosurgery 223 7
see also specific techniques
anterior inferior cerebellar artery (ArCA) loops, vestibular pathology 3701 skull base surgery 4136 vestibular schwannoma compression 3958-9 anterior macula flava 2135 anterior nasal artery 1335 anterior olfactory nucleus (AON) 1367, 1663 anterior pituitary gland see adenohypop hysis anterior septal angle 1326 anterior skull base 3897-8 intracranial contents 4121 osteology 4120 subcranial relationships 4121-2, 4122 F surgical anatomy 4120-2 surgical approaches 3898 anterior superior alveolar (dental) artery 1798 anterior superior alveolar nerve 1328, 1338, 1341, 1802 anterior superior dental ( alveolar) artery 1798 anterior superior dental ( alveolar) nerve 1328, 1338, 1341, 1802 anterior synostoses 1025 anterior triangle, neck 1741-2, 1742 T muscular 1742 anterior tympanic artery 3907 anterolateral craniofacial resection 4130, 4131 F contraindications 4130 indications 4130 procedure 4130 anterolateral thigh flap 2879-81 advantages 2880 anatomy 2879-80, 2880F clinical applications 2881 disadvantages 2880-1 technical nuances 2881 anteroventral cochlear nuclei (AVCN) 3140 anthracyclines 38 antiadrenergic drugs, skin flap survival 113 antiangiogenic agents, radiotherapy and 51 antibacterial spectrum 431, 432 T antibiotic-inactivating enzymes 235 antibiotics 229-30 acute otitis media 431, 917-8, 3386 recurrent 918-9
Pages 1-1312 are in Volume 1, pages 1313-2810 are in Volume 2, and pages 2811-4147 are in Volume 3.
4 1 58 I I ndex
antibiotics (continued) acute rhinosinusitis 438-9 adult epiglottitis 2251 antibacterial spectrum 431, 432 T cerebrospinal fluid rhinorrhoea 1639-40 chronic otitis media, active mucosal 3424 chronic rhinosinusitis 1470-1, 1471 contraindications 432 croup 2251 cytotoxic 38 deep neck space abscesses 1786 dosage 432 furunculosis 3324 hypophysectomy 4105,4111 infectious mononucleosis 2253 interactions 441 jugular foramen lesions 4042 laryngeal trauma 2274 laryngitis, acute 2213 laryngology 448 malignant otitis externa 3339 mechanisms of action 431 otitis externa 3353 otitis media with effusion 895-6 otological disease 431 ototoxicity 3298-300,3299 T parenteral,malignant otitis externa 3339 persistent rhinosinusitis 439 pharyngitis 1222 precautions 432-3 radial neck dissection 2743 resistance antibiotic-inactivating enzymes 235 binding site alterations 235 retropharyngeal abscess, children 2001 rheumatic fever prevention 1985-6 rhinosinusitis 1543-4 side effects 433 sinusitis, HIV patients 242 sore throat 1984-5 surgical prophylaxis 448 taste abnormalities 1845 temporal bone fractures 3496 tonsillectomy 1237 upper airway obstruction 2288-9
see also individual drugs antibodies 135-6 classes 138, 138 T deficiency 176-7 tests 168 functions 138
monoclonal see monoclonal antibodies (MAb) structure 138 subclasses 138, 138 T see also immunoglobulin(s);
individual types antibody-dependent cellular cytotoxicity (ADCC) 41, 140 nasopharyngeal carcinoma 2448 anticancer drugs clinical response assessment 36 tumour products 36 tumour size 36 mechanisms 34-46
see also individual drugs anticholinergics drooling 788-9 mechanism of action 3795 nonallergic rhinitis 1506 vestibular attacks, acute 3795
see also individual drugs anticoagulants 282-3, 446-7 bleeding management 283,283 T drug interactions 283 excessive 283, 283 T mechanism of action 282,447F perioperative management 282-3 surgery and 282-3 thrombophilia 289 thyrotoxicosis 347
see also individual drugs anticonvulsants, trigeminal neuralgia 1830 anti-D antibodies 254 antidepressants globus 2040 tinnitus 3617 anti-diuretic hormone (ADH) diabetes insipidus 308 effects 308 function 300 secretion 308 post-pituituary surgery 308 antiemetics advanced head and neck cancer 2787 anaesthesia premedication 490 T migrainous vertigo 3801 vestibular attacks 3794-5
see also individual drugs antiepileptics,tinnitus 3617 antifungals 233-4 allergic fungal rhinosinusitis 222 candidiasis,cancer patients 2789 chronic rhinosinusitis 1472 invasive fungal rhinosinusitis 1454
mycotic laryngitis 2254 resistance 233 rhinological diseases 442
see also individual drugs antigen(s) presentation,T cells 136-7, 136F recognition 134-7 B cells 135-6 antigenic determinant 135 antihistamines acute otitis media 918 allergic rhinitis 1397-8,3392 allergy 152-3 drug interactions 411 food allergy 1431 nasal vasculature, effects on 1365, 1365 T nausea and vomiting 2787-8 nonallergic rhinitis 1412 otitis media with effusion 3392 rhinosinusitis 440 children 1083 chronic 1472 vertigo 433 vestibular attacks,acute 3795-7
see also specific drugs anti-HPA 1a 262 anti-immunoglobulin E monoclonal antibody,allergic rhinitis 1565 antileukotrienes 441-2 allergic rhinitis 1399 chronic rhinosinusitis 1472 antimalarials 1048 antimetabolites 37-8 cell cycle specificity 37 mechanism of action 37-8 antimicrobials 228-37 activity 229-34 concentration dependent killing 1471F concentration-dependent killing 1471 time dependent killing 1471F time-dependent killing 1471 adverse effects 235-6 cutaneous 236 gastrointestinal 236 haematological 236 liver toxicity 236 renal toxicity 236 bacterial target sites 228-9, 229F blood-brain barrier 228-9 excretion routes 228-9 pharmacokinetics 229-34 resistance 228, 234-5
Pages 1-1312 are in Volume 1, pages 1313-2810 are in Volume 2,and pages 2811-4147 are in Volume 3.
I ndex I 4 1 59
altered penetration 235 binding site alterations 235 genetic mutation 234 multiresistant organisms 234 sensitivity testing 234-5 sepsis 534 surgical prophylaxis 228-9 therapeutic principles 228-9
see also individual drugs antimitotic agents,dacryocystorhinostomy 1695-6 antimycotics,rhinosinusitis 441 anti-neutrophil antibody (ANA) 167 antineutrophil cytoplasmic antibody associated vasculitis 346 antineutrophil cytoplasmic antibody test (ANCA) interpretation guide 171 T vasculitis 171 Wegener's granulomatosis 1649, 1649-50,1651, 1652 antioxidants, ototoxicity and intrinsic pathways 3300, 3301F prevention 3302 antiphospholipid antibodies 290 antiphospholipid syndrome 171 er:-antiplasmin 279 antiplatelet agents, thrombocytosis 275-6 antiplatelet antibodies 262 antiproteases,nasal secretions 1360 antipsychotics, palliative care patients 2795, 2798 antireflux medication,laryngeal trauma 2274 antiretroviral therapy (ART) 233 HIV salivary gland disease 1901 antiseptics, tympanic membrane perforation 938 antisialogogue anaesthesia 489 awake fibreoptic intubation 479-80 antithrombin(s) 279, 279 T deficiency 290 antithyroid drugs 346,450-1 dose regimen 346 efficiacy 347 Graves' disease 346-7 pretreatment 348 side effects 346 agranulocytosis 346 antineutrophil cytoplasmic antibody associated vasculitis 346
surgical preparations 349-51
see also specific drugs antituberculous drugs 3449,3450 T
see also specific drugs antivascular agents haemorrhagic necrosis 51 radiotherapy and 51 antivertigo drugs,migrainous vertigo 3801 antivirals 209-10,232-3 idiopathic sudden sensorineural hearing loss 1,3584-8,3589, 3589 T labial herpes 208 otitis media with effusion 3392 side effects 236 target areas 209
see also individual drugs Antoni A pattern facial schwannomas 4078 vestibular schwannoma 3957, 3960-1 Antoni B pattern facial schwannomas 4078 vestibular schwannoma 3957, 3960-1 antral carcinomas 3927 antral lavage 1490-2 anaesthesia 1491 complications 1492 contraindications 1491 indications 1490-1 surgical technique 1491-2, 1492F antrum, imploding see imploding antrum syndrome anxiety globus 2039 head and neck cancer patients 2777 palliative care 2795, 2795 T muscle tension dysphonia 2204 posturography 3736 professional voice 2212-3 salivary flow 1861 vestibular disorders 3814-5 anxiety-related dizziness 3815F anxiolysis,anaesthesia premedication 489,490 T aortopexy, tracheomalacia 1287 AP-1 2380 'apathetic hyperthyroidism' 339 APECED (autoimmune polyendocrinopathy -candidiasis-ectodermal dystrophy) 180 � 181 aperiodic sound (noise) 2165
Apert syndrome 1027,1713,2120 clinical features 1027 incidence 1021 nasopharyngeal airway 1109 aphthae see recurrent aphthous stomatitis (RAS) aphthous ulcers,recurrent see recurrent aphthous stomatitis (RAS) apical jaw cysts 1922 apicoposterior bronchus 2141 Apligraf 126 apnoea definition 2317-8 gastro-oesophageal reflux 1273 apnoea/hyponoea index (AHI) 1106, 1106 T, 2319-20 apnoea termination 2309 apoptosis 56-65, 2383 biochemical changes 58 biochemical identification 60-1, 60 T cancer 62-3 carcinogenesis 62 caspase family 57, 2383 cell cycle 58 cell populations 57 chemotherapy 63 chromatin condensation 59, 60,60 F congenital defects 61 death receptors 57-8 detection 60-1 developmental processes 57 disease states 61-2,61 T congenital defects 61 non-neoplastic 61-2 disruption,restorative gene therapy 29 drug-induced 36 executors 57 extracellular signalling 57-8 historical aspects 56, 59F hypopharyngeal cancer 2636 inhibition, ototoxicity prevention 3302 intracellular signalling 58 measurement 60-1 mechanisms 36, 57-60, 57 T abnormalities 63 loss in malignancy 62-3 mitochondrial pathways 58 morphological changes 59-60,59 F, detection 60-1, 60 F, 60 T nasal polyps 62 necrosis vs. 57 T noise-induced hearing loss 3549 nuclear changes 58
Pages 1-1312 are in Volume 1,pages 1313-2810 are in Volume 2, and pages 2811-4147 are in Volume 3.
4 1 60 1 I ndex
apoptosis (continued ) oligosomal fragmentation 58, 61 ototoxicity 3300-1, 3301F p53 58 proteasome inhibition 44 radiotherapy-induced 47, 63 sensorineural deafness 61-2 thyroid diseases 62 tissue staining 60 triggers 57, 57 T, 58 T tumour growth 57 viral infection 61 apoptotic bodies 59-60 apoptotic index (AI) cancer 62-3 cellular turnover 62 radiotherapy 63 apparent latency 3288 apparent life-threatening events (ALTEs), gastro-oesophageal reflux 1273 apple jelly nodules, sarcoidosis 189F application specific integrated circuits (ASIC), ultrasound 713 apprenticeship model, surgical training 552 approximant consonants 2167, 2167 T aprotinin 283 AQ4N 51 arachnoid cysts aetiology 4013 clinical presentation 4013 CPA tumours 4013-4 definition 4013 diagnosis 4013, 4014F epidemiology 4013 pathology 4013 treatment 4014, 4014F arachnoid sheath, optic nerve 3914 arch bars 1622-3, 1623F arcuate eminence, middle fossa surgery 4019 arcus marginalis 3051 area under the curve (AUC), pharmacokinetics 410 argon plasma coagulation tonsillectomy 1992 argon plasma coagulator (APC) dissector 1992 Argyll Robertson pupils 3916-7 Arnold-Chiari malformation inner ear disorders 3683 pharyngeal manifestations 2080 treatment 2080 vocal fold paralysis 1138
Arnold's nerve 1751, 3527, 3910 arousal, sleep-disordered breathing 1103 arrhythmias, surgical preparation 459 arsenical ototoxicity 3571 Ars-Marquet procedure 946F arterial leg ulcers 98 wound dressings 102 arterial spin tagging 677, 677F arterial thrombosis antiphospholipid antibodies 290 pathogenesis 288 risk factors 289 T arterioles, nasal 1362 arteriovenous fistulae 4145 arteriovenous malformations (AV Ms) 726 articulation 992-3 disorders 993 artifact rejection 3279 artificial larynx electronic 2230 rehabilitation post-total laryngectomy 2227, 2228-30, 2228 T artificial saliva 449, 1912, 2788 aryepiglottic folds 2133 congenital disorders 1135 development 2130 aryepiglotticus 2136 T aryepiglottoplasty laryngomalacia 1136 paediatric anaesthesia 520 arytenoid cartilages 2133, 2133F arytenoidectomy 1159 arytenoid fixation and cricothyroid subluxation 2242-3 arytenoid granuloma 1170 F, 2196-7, 2197 F, 2220-1 aetiology 2196, 2220 botulinum toxin injections 2238 extra-oesophageal reflux 2196 mitomycin C 2238 phonosurgery 2238 speech therapy 2221 symptoms 2197 treatment 2197 arytenoid prolapse 1159 arytenoid swelling 2130 ASA difficult airway algorithm 472-3, 472F Asai's technique, laryngeal prosthesis placement 2625 ascending auditory pathway 3140-4, 3141F ascending cervical artery 2113
ascending (modified Hughson Westlake) method, pure-tone audiometry 3263-4 ascending palatine artery 2113, 3909 ascending pharyngeal artery 1947, 1951, 2113 technique, blood donation 260 Ashe's forceps 1613, 1613F aspartame allergy 1427 aspergillosis see fungus ball
Aspergillus cervicofacial infections, children 1216 fungus ball 1452 otomycosis 213 rhinosinusitis 217, 1381, 1452-3 HIV-associated 241-2
see also individual organisms Aspergillus flavus fungal rhinosinusitis 217, 1450 T otomycosis 213
Aspergillus fumigatus external ear infection, HIV-associated 240 fungal rhinosinusitis 217, 219, 1450 T otomycosis 213 Aspergillus niger, otomycosis 213, 214 F, 3355F aspiration 1277-8 barium in videofluoroscopy 1967 causes 1277 chronic see intractable aspiration definition 1277, 2085, 2094 diagnostic tests 1277-8 dysphagia 2085 neurological 2076 intractable see intractable aspiration laryngeal stenosis 1154, 1155 management 1278 stridor 1117 1277 symptoms and aspiration biopsy cytology (ABC) 1252-3 aspiration pneumonia 1284, 2085 aspirin chronic rhinosinusitis 1472-3 nasal administration 1473 oral administration 1473, 1473 T desensitization, nasal polyps 442 epistaxis, recurrent 1604 food allergy 1427 migrainous vertigo 3801 ototoxicity prevention and 3302 patient preparation, surgery 460 sensitivity 1472 testing 1395
1-1312 are in Volume I, pages 1313-2810 are in Volume 2, and pages 2811-4147 are in Volume 3.
I ndex I 4161
side effects rhinorrhoea 1410 tinnitus 3599-600 spontaneous otoacoustic emissions 3603-4 vocal fold haemorrhage induction 2213 aspirin triad see Samter's triad assessment, outcomes research see outcomes research assistive listening devices (ALDS) 3864-5 astemizole 1397-8 asthma allergen associations 145, 145 T allergic rhinitis 158, 1387-8, 1388, 1402, 1561 anti-immunoglobulin E monoclonal antibody 1565 causative agents 1561 Churg-Strauss syndrome 1653 costs 1565 diagnostic indicators 1395 disease continuum 1565 food allergy and 1428, 1429 future research 1402 genetic associations 145 T immunotherapy 1564-5 interleukin-5 155-6 molecular biology 1562 nasal inflammation 1561-2 bronchial inflammation vs. 1561-2 nasal polyposis 1553 bronchial hyperreactivity 1551 incidence 1553 omalizumab 1565 oral drugs 1564 paediatric anaesthesia 508 quality of life 1564 severity, rhinitis treatment 1565 sinus involvement 1561-2, 1562 therapeutic consequences 1564-5 topical drugs 1564 viral infection, nasal 1563 astomia 1811-2 astrocytomas 4015 A stronger local voice 574 asymmetric crying facies 1055 ataxia cerebellar see cerebellar ataxia children 1048-9 ototoxicity-related 3569 sensory 3778, 3780
ataxia telangiectasia (AT) 179-80, 180 T ATM gene 58, 188 radiotherapy dose response curves 48 ataxic nystagmus, internuclear ophthalmoplegia 3715, 3716F atelectasis 942, 942 T atenolol 3803-4 ateriography, sinonasal malignancy 2426 atlanto-axial instability 1308, 1308F atlantoaxial subluxation adenoidectomy-related 1098 nontraumatic 1236 atlantooccipital joints 3899 atlantooccipital movement 470 atlas 2111 ATM gene/protein 58, 179-80 atopic eczema dermatitis syndrome (AEDC) 1424-5 atopy 144, 145 T atresia acquired, external ear see acquired atresia, external ear congenital, external ear see aural atresia, congenital definition 3346 oesophageal see oesophageal atresia atrial fibrillation (AF), thyrotoxicosis 339 atrophic rhinitis 1383, 1411, 1465-6 aetiology 1411, 1465 clinical features 1411, 1465-6 drug therapy 443 investigations 1465-6 pathology 1465 primary 1383, 1411, 1465 secondary 1411 symptoms 1383 treatment 1466 medical 443, 1466 surgical 1466 atrophic vocal fold 2243, 2243F atropine airway endoscopy procedures 517 nasal vasculature, effects on 1365 paediatric anaesthesia 509 ATR protein 58 attention deficit hyperactivity disorder (ADHD), speech disorders and 991-2 attic cholesteatoma 950-1 attico-antrostomy 3432 atypical mole syndrome 2400 atypical mycobacteria 201 atypical naevi, external nose 1707
audiology cholesteatoma 951-2 chronic otitis media 3419 otitis media with effusion 3391, 3391 T paediatric cochlear implantation 863 skull base lesions 3946
see also specific tests audiometric scales 3171 audiometry audiometric scales 3171 auditory neuropathy/ dyssynchrony 3841F behavioural see behavioural audiometry congenital ossicular abnormalities 871 dizzy child 1042 facial nerve tumours 4080 Meniere's disease 3757, 3758F otitis media with effusion 889-90, 890, 3390, 3391, 3391 T psychoacoustic 3260-75 pure-tone see pure-tone audiometry screening methods 3264-5 speech see speech audiometry temporal bone squamous cell carcinoma 4090 visual reinforcement see visual reinforcement audiometry (VRA) see also sound audit, comparative 2376 auditory brainstem implant, vestibular schwannoma 3976-7 auditory brainstem responses (ABRs) auditory function monitoring 750, 751 central auditory dysfunction 3860, 3860-1, 3861F childhood deafness 848 paediatric cochlear implantation 863 skull base lesions 3946 auditory canal, external see external auditory canal auditory cortex 3143-4 projection to 3144, 3144F response types 3144 tinnitus 3602 auditory cortical potentials see auditory long-latency evoked potentials (ALEPs) auditory dyssynchrony see auditory neuropathy/dyssynchrony
Pages 1-1312 are in Volume 1, pages 1313-2810 are in Volume 2, and pages 2811-4147 are in Volume 3.
4 1 62 I I ndex
auditory event-related potentials (ERP) , tinnitus 3612-3 auditory evoked cortical magnetic fields (AEF),tinnitus 3613 auditory-evoked potentials 3278-88 averaging 3279 central auditory dysfunction 3862 classification 3278-9 definition 3278-9 endogenous 3279 exogenous 3278-9 intraoperative monitoring 3292 methodological considerations 3279-80 neurogenic 3278-88 recording system 3279 signal-to-noise ratio 3279 transient 3280 waveform analysis 3279-80, 3280F
see also individual types auditory filters 3246-9 asymmetric 3249 centre frequency 3248 characteristics 3247 definition 3245 excitation pattern 3249-50, 3250F masking patterns 3247 notched-noise shape determination 3248-9, 3248F, 3249F auditory function monitoring 750 efficacy 751-2 preoperative hearing requirements 750 techniques 751 auditory brainstem responses 750, 751 combined 751 direct cochlear nerve recording 751 electrocochleography 751 otoacoustic emissions 751 auditory hallucinations 3595 central auditory dysfunction 3863-4 tinnitus vs. 3595 auditory language processing, functional magnetic resonance imaging 680, 680F auditory late evoked potentials (ALEPs) see auditory long-latency evoked potentials (ALEPs) auditory long-latency evoked potentials 3285-7 children 3287 frequency-specific sensitivity assessment 3291 generators 3287
mismatch negativity (MMN) 3286-7 N200 -P300 complex 3287 N4oo 3287 negative peak (N1) 3286-7 neuro-otological evaluation 3292 'oddball paradigm' 3287 P 3a 3287 P 3b 3287 P 300 3287 schizophrenic patients 3292 positive peak P I 3286 processing (negative difference; Nd) 3286-7 recording 3285-6 vertex potential 3286 waveform 3286, 3287F auditory middle latency evoked potentials (AMEPs) 3285 40 Hz 3286F, 3288 frequency-specific sensitivity assessment 3291 neuro-otological evaluation 3292 sampling rate 3285 waveform components 3285, 3286F auditory nerve (V III) activity recording,tinnitus 3612 afferent fibres 3136 arachnoid cysts 4013 auditory neuropathyldyssynchrony 3837-8 CPA lipomas 4013 demyelination, multiple sclerosis 3846 electrical stimulation,auditory neuropathyl dyssynchrony 3852 epidermoids (primary cholesteatomas) 4011 fibres activation 3195 F, 3197-8 bestl characteristic frequency 3197 cochlea, nonlinear interactions 3198-9 efferent 3138F, 3139 frequency selectivity 3197-8 intensity responses 3198, 3198F phase locking 3197-8, 3197F responses 3197-200 pathological cochlea 3199-200 tuning characteristics 3197 type I 3849 type II 3849 glomus tumours (paragangliomas) 4015 intraoperative monitoring 3292-3, 3293F
meningiomas and 4009 organ of Corti innervation 3136 speech recognition post-cochlear implants 3650 tuning curves 3177F, 3190, 3191F, 3197 cochlear damage 3199, 3199F width 3199-200 vestibular schwannoma compression 3958-9 auditory nerve and brainstem evoked potentials CABEP) 3281-5 age-related changes 3284-5 amplitude rations 3284 T amplitude ratios 3284 T audiometric measures 3283 auditory sensitivity indicators 3291 3294 best clinical children 3284-5 frequency-specific stimuli 3291 gender 3285 generators 3283 high-frequency sensorineural hearing loss 3291 interpeak latency difference measures 3283, 3284 T intraoperative monitoring 3292-3 IV-V complex 3283 neonatal hearing 3291 neuro-otological evaluation 3292 neuro-otologic measures 3283 nonpathologic factors affecting 3284 peak I 3281-3 peak II 3283 peak III 3283 peak IV 3283 peak latencies 3283, 3284 T peak V 3281-3 peripheral hearing loss 3291 sampling rate 3281-3 stimulus intensity 3284, 3285 F troughs 3281-3 V II amplitude ratio 3292 waveform 3281-3, 3283F auditory nerve electrodes 3292-3, 3293F auditory neuropathyl dyssynchrony 3839-45 amplification strategies 3851-2 axonal neuropathy and 3848-9 brainstem neuropathy vs. 3851 Charcot-Marie-Tooth type 1 3849 children 824, 3845-6 causes 3845-6 genetic risk factors 3846
Pages 1-1312 are in Volume 1,pages 1313-2810 are in Volume 2, and pages 2811-4147 are in Volume 3.
I ndex I 4163
hearing screening programmes 3846 perinatal risk factors 3845-6, 3845 T prevalence 3839-40, 3840 T, 3845 clinical presentation 3840-1 diagnosis 3842-5 diagnostic criteria 3842 T differential diagnosis 3850-1 early language intervention 3851 hereditary sensory-motor neuropathy 3849-50 historical aspects 3839 impairment severity 3840, 3841 F lesion site 3849-50 axons 3849-50 cell bodies 3849-50 inner hair cell electromechanical transduction 3849 myelin sheaths 3849-50 olivocochlear feedback mechanisms 3850 neurological 3846-9 peripheral neuropathy and 3848-9 incidence 3848 nerve conduction studies 3848-9 psychophysical tests 3845 rehabilitation strategies 3851-2 speech 3840 speech recognition tests 3844 steady-state potentials 3843-4 temperature-sensitive hearing loss 3848-9 tests 3842-5, 3842 T total communication strategy 3851 see also hearing loss/impairment auditory pathways 3265 afferent 3601, 3602 F
auditory speech discrimination tests 841 auditory steady-state response (ASSR), central auditory dysfunction 3860 auditory system feedback mechanisms 3601, 3602 F modifier genes 817 noise-induced cochlear lesion 3601 see also ear(s) auditory thalamocortical potentials see auditory middle latency evoked potentials (AMEPs) auditory therapy (AT) , children 3865 auditory tube 2113 augmentation rhinoplasty 2970-8 ethnic variations 2970 implant materials 2970-4 semisynthetic 2973-4 synthetic 2972 T, 2973-4 infection 2971 Wegner's granulomatosis 2976 F augmentation tracheoplasty 1144 augmented reality 702, 702 F aural atresia, congenital 975-80 acute otitis media 981 audiological investigations 981 cholesteatoma 981 classification 976-7, 977 T examination 980-1
ascending 3140-4, 3141 F central masking 3265 descending 3144-5 efferent 3601, 3602 F future research areas 3145 knowledge deficiencies 3145 pure-tone audiometry errors 3265 auditory processing disorder (APD) 3857-8 Auditory Response Cradle devices 3290 auditory sensitivity, evoked physiological measurements 3276-97 audiogram estimation 3291-2 clinical utility 3290-3 evoked potentials see auditory-evoked potentials
history 980-1 imaging 981 otological surveillance 981 surgical candidacy scoring systems 977, 977 T surgical treatment 981-2 aural foreign bodies 3370-2, 3371 F children 1184-6 management 1185-6 presentation 1184-5, 1185 F clinical picture 3370 complications 3371 location 3371 managementlremoval ·1185-6, 3370-1, 3371 T patient considerations 3371 techniques 11 85
future research areas 3294 intraoperative monitoring 3292-3 knowledge deficiencies 3294 myogenic activity 3288-90 neonatal hearing screening 3290-1 neuro-otological evaluation 3292 otoacoustic emissions see otoacoustic emissions (OAEs)
see also specific tests
pathology 3370 types 1185, 3370-1 aural polyps active mucosal chronic otitis media 3397, 3425 cholesteatoma 950 removal 3425 medical negligence l307 aural toilet 33 l3-4 cholesteatoma 3432 chronic otitis media active mucosal 3424 children 935, 936 F, 937 inactive squamous 3428 malignant otitis externa 3338-9 microscopic 3314 otitis externa 3353 auricle see pinna auricular cartilage grafts laryngeal reconstruction 1156 septal perforations 1586-7 auricular implants 2908 F,2909, 2928 auriculotemporal nerve 3109, 3907-8, 3925 injury,taste abnormalities and 1846 auropexy 973-4 autoantibodies autoimmune screen 170, 170 T thyroid disease, in vitro tests 328, 328 T, 332,335 autocannabalism 530-1 auto-CPAP machines 2321 autografts augmentation rhinoplasty 2971, 2972 surgical harvesting 2972-3 tissue regeneration 75 autoimmune disease apoptosis 62 chronic otitis media 3409 inner ear 3680-1 basophilic amorphous deposits 3680-1 diagnosis 3754,3758-9 nonorgan specific 3680 management 170-2 otosclerosis 3459 autoimmune lymphocytic thyroiditis see Hashimoto's thyroiditis autoimmune lymphoproliferative syndrome (ALPS) 180 T, 181 autoimmune polyendocrinopathy -candidiasis-ectodermal dystrophy (APECED) 180 T, 181
Pages 1- l312 are in Volume 1, pages l3l3-281O are in Volume 2, and pages 2811-4147 are in Volume 3.
4 1 64 • I nd ex
autoimmune thrombocytopenia see idiopathic thrombocytopenic purpura autoimmune thyroiditis painless thyroiditis 352-3 thyroid lymphoma aetiology 2675 autoimmune thyrotoxicosis see Grave's disease autoimmunity 1 4 1 autoinflation, otitis media with effusion 896, 3392 autologous blood clots, as embolic agent 733 autologous grafts 96 automated auditory brainstem response
axial flaps 2845-6, 2848-53 blood supply 2844F, 2848, 2848F distant 2827, 2853-4, 2854-65 oral cavity tumours 2569
(AABR) testing, newborns 826, 848 automated otoacoustic emissions (AOAE) childhood deafness screening 848 newborn hearing screening 826 automatic noninvasive blood pressure monitoring 497 autonomic nervous system nose 1358, 1363, 1363F thyroid gland control 3 1 9 autonomy ( ethical principle) 561 -2, 582 autoradiography 6 autosomal dominant inheritance 1 8 autosomal dominant nonsyndromic sensorineural hearing impairment 3558-66, 852 associated hearing impairments 3560-2 DFNA diagnosis 3562 gene linkage strategies 3559 recent developments 3559 terminology 3559-60 autosomal recessive hereditary hearing loss 852-3 autosomal recessive inheritance 1 8 autosome 3-4, 18 Avastin 43-4
chronic rhinosinusitis 1471-2 nonallergic rhinitis 1412 otitis media with effusion 3392
Avellis's syndrome ( of brainstem) 3938 avian H5Nl influenza 205-6 awake extubation, difficult airways 484 awake fibreoptic intubation 479, 479F periglottic/glottic obstruction 481 premedication 479-80 sedation 480 supraglottic obstruction 479, 481 awake fibreoptic nasolaryngoscopy, juvenile-onset recurrent respiratory papillomatosis 1 175-6
see also specific types axis 2 1 1 1 axolotl 72 axoneme 3228 axonotmesis 3873 axon reflexes, nasal 1364 azathioprine Sjogren syndrome 1913 Wegener's granulomatosis treatment 1 652-3 azelastine
3' azid03' deoxythymidone zidovudine (AZT) 233, 239, 240 azithromycin ototoxicity 3571 syphilis 2008 azoles 233-4 acute fulminant rhino sinusitis 1455 babbling 2 168 bacillary angiomatosis 247-8 Bacillus subtilis 1 4 1 9 baclofen periodic alternating nystagmus 3804 tinnitus 3606-7, 361 7 bacteria anaerobes 200-1 colonization 195 definition 195 Gram-negative 199-200 Gram-positive 196-9 microaerophilic 201
see also individual species bacterial artificial chromosome (BAC) 5-6, 1 1 bacterial cell wall synthesis inhibitors 229 bacterial endocarditis, antibiotic prophylaxis 460 bacterial infection acute otitis media 915, 915 T blood transfusion 261 chronic laryngitis 2258-9 nasal 1 700, 1 703 olfactory dysfunction 1 673-4 oral 1833
otitis externa 3352, 3352 T pharyngitis 1982-3 wound healing 95
see also specific diseases bacterial interference 195-6 bacterial labyrinthitis 3691-2, 3691 F active chronic otitis media 3436 causative microorganisms 3692, 3692F, 3693 F, clinical features 3692 histopathology 3692 management 3436-7 bacterial laryngotracheobronchitis see pseudomembranous croup bacterial lysate preparations, rhinosinusitis 44 1 bacterial parotitis 1 2 1 2 bacterial protein synthesis inhibitors 23 1 -2 bacterial tracheitis see pseudomembranous croup bacterial vaccines, rhinosinusitis 1084, 1473 bacteriostatic agents 234 bacteriotherapy 195-6, 198 Bacteroides fragilis 200-1 bakers, occupational rhinitis 1 4 1 8 'balaclava' ( 'onion peel') sensory deficit 3926 balance evaluation 3706-47 dizzy child 1042 otitis media with effusion 894 balanced anaesthesia 489, 489F balance disorders/disturbances active chronic otitis media 3436 causes 3932-3 children, vestibular symptoms 1041 T, 1042 classification 3673-4 diagnostic flow chart, children 1043F examination 3710-36 eye movements 3710-23 neurofibromatosis 2 4000 posturography 3732-6 skull base lesions 3944 symptoms 3706-10 vestibulocochlear nerve 3932-3 see also vertigo ballistic gene delivery 25 balloon dacryocystoplasty 1 694 balloo n dilation oesophageal strictures 2064, 2064F tracheal stenosis 1 143-4
1 - 1 3 1 2 are in Volume 1, pages 1313-281 0 are in Volume 2, and pages 281 1-4 1 47 are in Volume 3.
I ndex I 4 1 65
balloon embolization 733 balloon myotomy, achalasia 2066 balloon occlusion test 2534, 3951 bar and clip arrangement,implant retention 2932, 2933F Barany, Robert 3154 Barany box 3317 270 'barbecue' manoeuvre 3813 Barclay's procedure 2283, 2283F barium swallow 1967 achalasia 1288, 1289 F, 2027F congenital oesophageal stenosis 1287-8 dysphagia 1967, 2026-8, 2027F contraindications 2026-8 laryngeal stenosis investigations 1151-2 modified see videofluoroscopy oesophageal injuries 177l corrosive 1291, 1291F 1296 paediatric pharyngeal pouch carcinoma 2048, 2728 sensitivity 1770-1 Barnett v. Chelsea & Kensington Hospital (1968) 596-7 baroreflex, vestibular system 3227-8 barotitis media see middle ear barotrauma barotrauma see otitic barotrauma barotraumatic facial palsy 3513-4 Barrett's cancer 2067 Barrett's oesophagus 2065-6, 2065F incidence 2065 malignant transformation 2065, 2065F management 2065 barrier membranes, guided tissue regeneration 2916, 2916F Bartholin's duct 1808 Bartonella henselae 1784 basal cell(s) cochlea 3186 olfactory neuroepithelium 1663F globose (light) 1662 horizontal (dark) 1662 basal cell carcinoma (BCC) 2395-8, 2396F associated syndromes 2396 genetic predisposition 2395-6 head and neck 2395-8 incomplete excision 2397-8 Moh's micrographic surgery 1706, 2397
nasal 1705-6 morpheaform 1706, 1706F nodular 1706, 1706F, 2396 pinna reconstruction 3028 premalignant lesions 2396 recurrence 2397-8 risk factors 1705-6, 2395-6, 2396 T environmental exposure 2396 skin type 1705-6, 2395-6 superficial 1706, 2396-7 treatment 1706, 2397 destructive 2397 medical 2397 surgical 2397 types 2396-7 wound healing 92F basal ganglia 2158-9 disorders 3777-8 base of tongue tumours see tongue base tumours base substitution 9-10, 16 basilar aneurysms cerebellopontine angle lesions 4014-5 middle fossa surgery 4024 basilar artery,aneurysm,CPA lesions 4014-5 basilar membrane 3127, 3128F frequency filtering 3189, 3191F function 3139-40 vibration amplitude, stimulus intensity and 3190-1, 3191 F, 3192F frequency filtering 3189 pathological cochlea 3199-200, 3199F basilar migraine 3771 children 1044 EEG changes 1044 family history 1044 genetic basis 1044 treatment 1044 video-nystagmography 1044 basiocciput 2110, 3899 basisphenoid 1944, 2110 juvenile angiofibroma 2443 basophil(s) allergic response 149 allergic rhinitis 1391 basophil histamine release test 160 'bat' ear 970-1, 971 F, 973F correction 971, 971F postoperative haematoma 3033, 3035 F, 3036F bathing, otitis externa and 3352
'battery' ('resistance modulation') theory 3193-4 Battle's sign 3495 Bazooka 68 B cell(s) activated, adaptive immunity 133 allergic rhinitis 1389 antibodies 135-6 disorders 175 T receptor 135 tonsil immune function 1220 B cell lymphoma Epstein-Barr infection 209 Hashimoto's thyroiditis and 331-2 positron emission tomography 694 B cell receptor 135 Bcl-2 apoptosis 56, 58 salivary gland tumours 2495 Beahrs' triangle 2664-5, 2665F beat frequency,cilia 1361 'beats' 3245-6 beauty,concept of 2944-5 Bechterew effect 3749 beclomethasone 420 allergic rhinitis, children 1401 frontal sinus inflammation 1508 bedside swallowing examination (BSE), dysphagia 2085 behavioural audiometry auditory neuropathyl dyssynchrony 3839-40 central processing disorders 3851 children 835 ototoxicity management 3573 behavioural observation audiometry (BOA) 835 Behfet's syndrome 189, 1831 clinical features 1831, 1832 T genetics 1831 Bekesy-audiometry 3264 'Belfast rules of thumb' 955 Bell's palsy 3883-6 aetiology 210, 1059, 3885, 3931 children 1059 incidence 1052 diabetes mellitus 401-2 diagnostic criteria 3883-4 epidemiology 3885 facial synkinesis 1845, 3931 herpes simplex virus 210, 3885 HIV patients 241 hyperacusis 3596
Pages 1-1312 are in Volume 1, pages 1313-2810 are in Volume 2, and pages 2811-4147 are in Volume 3.
4 1 66 I I ndex
Bell's palsy (continued) imaging 3881-2, 3883F, 4081, 4081F middle ear muscle reflexes 3183-4 prognosis 3885-6 sudden sensorineural hearing loss 3579 taste impairment 1845, 3929-30 treatment 210, 3886 corticosteroids 424, 3886 facial nerve decompression 4022 bell stage, tooth development 1922-4 bels 3174-5 belt-type singing style 2212 bendroflurazide,Meniere's disease 3799, 3799 T Benedikt's syndrome 3921 beneficence (ethical principle) 562, 582 beneficence model of healthcare 650 benign intracranial hypertension see otitic hydrocephalus benign migratory glossitis 1825-6, 1826F benign necrotizing otitis externa 3332-5 aetiology 3332-3 clinical features 3333, 3334 T complications 3334 definition 3332 diagnosis 3333-4 differential diagnosis 3333, 3334 T examination 3333 history 3333 investigations 3334 management 3334 natural history 3334 necrotic bone 3333, 3333F outcomes 3334 pathology 3332 tympanic membrane perforation 3333 benign paroxysmal positional vertigo (BPPV) 3760-3, 3767 aetiology 3760, 3760F, 3772 anterior semicircular canal (a-BPPV) 3809 positional manoeuvres 3722 treatment 3814 basophilic deposits 3679, 3679F, 3680F childhood lO41, lO44 clinical manifestations 3761 cochlear implant-related 3654 complications 3763, 3812 definition 3760 diagnosis 3761-2, 3809-10
differential diagnosis 3762 epidemiology 3760-1 horizontal semicircular canal (h-BPPV) 3809 positional manoeuvres 3722 treatment 3812-4, 3814 imaging 3809-10 management 3762-3 nystagmus 3750, 3761 otoconia detachment 3678-9 outcomes 3763, 3812 positional manoeuvres 3720, 3721F posterior semicircular canal (p-BPPV) 3756-7, 3809 positional manoeuvres 3721F, 3722 treatment 3810-2 post-stapedectomy 3476 post-traumatic 3497 presentation 3709 recurrence 3812 repositioning manoeuvres! exercises 3809-14 spontaneous resolution 3810 subjective 3812 surgery 3812-4 symptom duration 3706 vestibular neuritis 3760 vestibular rehabilitation 3808, 3810-2 head trauma 3812 treatment efficacy 3812 benign paroxysmal trigeminal neuralgia see trigeminal neuralgia benign skin lesions removal,medical negllge:nce 3090 Bentham,Jeremy 584 benzalkonium chloride 429 benzocaine 448 benzodiazepine(s) acute confusional states 2798 palliative care 2795 supraglottic obstruction 480 temporomandibular disorder 3530 tinnitus 3617 benzodiazepine withdrawal syndrome 3596 benzopyrines, salivary glands tumours 2494 benzydamine acute pharyngitis 1984 mouth ulcers 1830 benzylpenicillin peritonsillar abscess 1997-8 tonsillitis 1222 Bernard Soulier syndrome 288
Bernard-Webster flap 2547, 2547F Bernouilli's principle 1145 Bernoulli effect 2160 Accent method of speech therapy 2219-20 Bernoulli's equation 1357 Berry's ligament division, thyroidectomy 2690, 2690F beta-2-transferrin cerebrospinal rhinorrhoea diagnosis 1638 perilymphatic fistulae 3510 beta-adrenergic blockers, thyrotoxicosis 347 pre iodine treatment 348 f3-lactam antibiotics 229 methicillin-resistant Staphylococcus aureus 196 f3-lactamases 235 beta blockers migrainous vertigo 3803-4 performance anxiety 2212-3 betahistine contraindications 433 Meniere's disease 3799, 3799 T vertigo 433 betamethasone chronic rhinosinusitis 1471 croup 3165 betel nut chewing 2560-1, 2560F bethanechol radiotherapy -associated xerostomia 1909 Sjogren syndrome 1912 Betnovate leprosy 1464 medical negligence 3831 bevacizumab 43-4 Bezold's abscess 922, 922F f3-haemolysis 197F f3-haemolytic streptococci 197 bias critical appraisal 652, 659 epidemiological research 624-5 outcomes research 637 bicellular reserve cell theory, salivary gland tumours 2503 Bickerstaff 's 'brainstem encephalitis' 3778 bicoronal skin flap 2433F bifid epiglottis 1137 bilabial consonants 2166-7, 2167 T bilateral vestibular failure (BVF), vestibular rehabilitation 3808-9
Pages 1-1312 are in Volume I, pages 1313-28l O are in Volume 2, and pages 2811-4147 are in Volume 3.
I ndex I 4167
bilateral vestibulopathy 3764-6, 3767 aetiology 3764 children 1046 clinical manifestations 3764-6 complications 3766 definition 3764 diagnosis 3766 differential diagnosis 3766 management 3766 outcomes 3766 bile reflux resection 2064 measurement 2063, 2063F bilirubin, auditory neuropathy/ dyssynchrony 3845 Bilitec probe, gastro-oesophageal reflux 2063 Bill's bar 3120 bilobed flap 2840, 2843 nasal reconstruction 3019 binary data, systematic reviews 663 binaural interaction tests 3858-9 Binder's syndrome 1713 test 3318-9 bioactive glass bone repair 123, 124 T melt-derived 123 sol-gel-derived 123-4 tissue scaffolds 122F, 123-4 biofeedback (BF) dysphagia 2088 tinnitus 3616 biofilm chronic otitis media, childhood 931-2 coagulase-negative staphylococci 196 definition 1095 otitis media with effusion 1095 Bioglass 120, 123 biomaterials 118-30 bioactive 119 biocompatibility 119-22 definition 119 bioinert 119 biotolerant 119 ceramics see ceramic biomaterials classification 119 definition 118 historical aspects 118 immune responses 119 metals see metal biomaterials polymers see polymers reconstructive middle ear surgery 118 vascular surgery 121 biomedical approach, medical consultations 559-60
bioplastique 2240 Biopolaris 217, 221 biopsy chronic laryngitis 2260 epistaxis, children 1065 facial nerve tumours 4081 fungal rhinosinusitis 218 head and neck tumours 1931 children 1252-3 laryngeal tumours 2608 metastatic neck disease 2722 nasal endoscopy 1350-1 numbers required for diagnosis 755 odontogenic keratocysts 1925 olfactory dysfunction 1665 oropharyngeal tumours 2584 parathyroidectomy 393 salivary gland tumours 2506 2426 sinonasal temporal bone squamous cell carcinoma 4089 tonsil 1238, 1989 tuberculous otitis 3449
see also individual types bioreductive drugs 50-1 antivascular effects 51 tumour
50
see also individual drugs Bipolaris 1452-3 Birbeck's 4075 birch rhinitis 1428 biretrin��ence, polarization-sensitive OCT 756, 758 bisphosphonates bone pain, head and neck cancer 2784 hypercalcaemia 2794 disease 3489
see also specific drugs bisyllabic words, speech audiometry 3270, 3272 bitemporal hemianopia, optic chiasm lesions 3915 bitemporal superior quadrantanopia, pituitary tumours 312 bites, traumatic ear loss 3028, 3030F Bivona tubes 1199, 1201, 1201F 'Black Book; noise-induced hearing loss 3553 black hairy tongue 1825 blade implants 2904, 2905F Blair, Vilray 2944 Bland, Tony 588 blastocyst 68-9 Blastomyces dermatiditis 2268
blastomycosis 2268 bleeding see haemorrhage bleeding disorders 280-8, 281 T assessment 280-1 bleeding patterns 281 drug history 281 timing 280 diagnostic tests 281-2 inheritance patterns 280 management algorithm 282F spontaneous bleeding 280 bleomycin 38 blepharochalasis 3052 blepharoplasty 3048-67 applied anatomy 3048-53 complications 3064-6, 3095 cosmetic use 3064 lower eyelid 3057-64 examination 3058 eyelid laxity assessment 3058 history taking 3058 preoperative evaluation 3058 surgical approaches 3058-64 surgical technique 3058-64 medical negligence 3095-6 medicolegal pitfalls 3066 photographs, preoperative 3055 postoperative care 3064 postoperative haematoma 3095 preoperative assessment 3095 scar placement 3095-6 suture removal 3064 upper eyelid 3053-7, 3059F anaesthesia 3057 examination 3055-6 eyelid laxity assessment 3055 history taking 3054-5 patient 3055 preoperative evaluation 3054-6 skin closure 3057 skin crease marking 3056-7, 3057 F 3057 surgical 3056-7 surgical wound closure 3060 blepharoptosis 3053, 3066 blind eye consensual reflex 3916 direct reaction 3916 blinding, epidemiological research 621, 629 blindness embolic agents 3953 post-blepharoplasty 3064-5
Pages 1-1312 are in Volume 1, pages 1313-2810 are in Volume 2, and pages 2811-4147 are in Volume 3.
4168 I I ndex
blindness (continued) syndromic craniosynostosis surgery 1 03 1
blood oxygenation level-dependent resonance imaging 675
Wegener's granulomatosis 1 650 blisters gingival 1 8 1 9
contrast generation 678 haemodynamic change mechanisms 677, 677F
oral mucosa see oral mucosa 'blobogram' (Forrest plot) 664, 664 F Blom-Singer valve 2625, 2626 F, 2627 blood investigations 267 physiology 265
magnetic flux 678 neuronal activation and haemodynamic changes 677 physiological basis 677-8 blood pressure anaesthesia monitoring 497-8
blood-brain barrier
paediatric parameters 543 T
antihistamines 1 397-8 antimicrobial agents 228-9 blood cells formation 265-6
auditory nerve and brainstem evoked
(BOLD) functional magnetic
sleep-disordered breathing 1 103
potentials 3285 Boerhaave's syndrome 2070-1 boils, nasal vestibule 1 700 Bolam test 5 96, 600, 2805 Bolam v. Friern Hospital Management Committee ( 1957) 596, 2805 BOLD fMRI see blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging Bolitho v. City and Hackney Health Authority ( 1997) 596, 2805-6 bolus control exercises 2089, 2089 T
blood tests, deaf child 852
bolus escape 1 975
blood transfusion 253-64
bolus formation 1 954-7 bolus
2824
adverse reactions see transfusion reactions
bolus propulsion exercises 2089 T
white see white blood cells (WBC)
alternatives 262-4
bone(s)
blood components 255-60, 256F, 258 T
autologous 262-3
red see red cell(s)
bacterial infection transmission
acute normovolaemic haemodilution 263
hyperbaric oxygen, effects on 29 1 1 Paget's disease 3487
prevention 260 leukodepletion 260
cell salvage 263
1 ,25-dihydroxyvitamin D3 375
see also individual components
preoperative autologous
implant placement 29 1 5
blood donation 260
deposit 262-3
resorption
meningiomas 4008
aseptic technique 260
colloids 257
Creutzfeldt-Jacob disease 260
critical care 535
grouping 260
crystalloids 257
vestibular schwannoma 3957-8 skin grafts 2821
infection testing 260, 260 T, 284
fluid overload 262
tissue engineering 1 24
inherited platelet disorders 288
immunomodulatory effects 262
tissue scaffolds 1 24
massive 284 maximum surgical blood ordering
see also individual bones
blood flow 1 1 1-2 critical closing pressure 1 12 ultrasound see Doppler ultrasound
schedule 255, 255 T refusal, Jehovah's Witnesses 583,
humoral factors 1 12 hyperthermia 1 12
586 sickle cell disease 271
hypothermia 1 1 2
sinus surgery 257
laminar flow 1 1 1 red blood cell orientation 1 12
syndromic craniosynostosis surgery 1 030-1
vasoconstriction 1 1 2
f3 thalassaemia 271-2
vessel diameter 1 1 1 vessel wall tension 1 12 1 12 blood gas analysis, stridor 1 1 19 blood groups 253-5 ABO see ABO blood groups crossmatch 254
blood vessels flow dynamics see blood flow
parathyroid hormone 374
bone-anchored hearing aid (BAHA) 3642-8, 3640-1 active chronic otitis media 3435 advantages/disadvantages 3643 T audiological evaluation 985-6 children 854, 854F, 985-6 age at implantation 985 audiological criteria 985 otological criteria 985 patient selection 985 surgery 985
formation see angiogenesis
complications 3644
haemostasis 278
components 3642 F, 3643 F
'blue mantle,' otosclerosis 3454-5
congenital atresia 981-2
Bluetooth-enabled hearing aids 3669
congenital ossicular abnormalities 87 1
blunt trauma, larynx 2272
definition 3642
elective surgery 255
B lymphocytes see B cell(s)
eligibility 3643-4
emergency surgery 255, 256 F
body 2630
plasma incubation 254 260 Kell red cell antibodies 254
Rh see Rhesus (Rh) blood group screening see group and screen (G&S) test
post-laryngectomy 2624,
body motion sensing, neonatal hearing scr<::emlrlg 3290 body temperature anaesthesia monitoring 498 children 5 12-3
indications 3642-3 otitis externa 3 354, 3643 otosclerosis 3467 outcomes 3644-7 conductive impairment 3644-6, 3646 generic 3646-7
1-1 3 1 2 are in Volume I, pages 1 3 1 3-28 10 are in Volume 2, and pages 28 1 1-4 147 are in Volume 3.
I ndex I 4 1 69
mixed impairment 3646 other aids vs. 3643 T, 3644-6, 3644, 3646 other otological procedures
vs. 3647
bony pyramid, nose 2960-1 deviated nose 2990 external rhinoplasty 2963-4 border cells 3 1 30, 3 136 borderline leprosy, nasal 1464
sensorineural impairment 3646 total impairment 3646 surgical technique 3644, 3645 F vestibular schwannoma removal 3984 bone-anchored prosthesis, pinna reconstruction 3044, 3045 F bone collecting devices 2920, 2920 F bone-conduction (Be) hearing aids 3640-1 bone-anchored hearing aid vs. 3643 T, 3644
Bordetella bronchoseptica 1465 Bordetella pertussis 200, 2252 boric acid otitis externa 430 otomycosis 2 14
childhood 903 bone conduction pure-tone audiometry 3262 otitis media with effusion 889 bone distraction, implant placement 29 19, 29 1 9 F bone grafts augmentation rhinoplasty 2972, 2973
lip cancer 2548 tongue cancer 2553-4, 2557 bracketing method, pure-tone audiometry 3263-4 bradykinin 89 brain-derived neurotrophic factor 3 302 brainstem l oss 3 846-9
boron neutron capture therapy 24 l O
Borrelia 202 see also individual organisms Borrelia burgdorferi 202 Borrelia vincentii 202 acute necrotizing ulcerative
otitis media with effusion,
brachytherapy
gingivitis 1 8 1 9 bortezomib ( Velcade) 44 Bosker implants 2904, 2905 F bossa formation
swallowing control 1959 vestibular schwannoma compression 3958-9, 3958 F symptoms 3959 brainstem haemorrhage clinical manifestations 3769 management 3770 stroke aetiology 3768 brainstem infarction clinical manifestations 3768-9
medical negligence 3092 post-nasal tip surgery 3 004 botryoid odontogenic cyst 1925 botulinum toxin
management 3770 stroke aetiology 3767 brainstem lesions facial nerve damage 3930
arytenoid granuloma 2 197
Horner's syndrome 3937
blepharoplasty 3058
taste abnormalities 1847
bone graft substitutes 29 17
contraindications 449-50
vestibular schwannoma
bone marrow
cricopharyngeal muscle spasm 2098
implant placement 291 7-8
antimicrobial-induced suppression 236
drooling 789
removal 3978-9 brainstem neuropathy, auditory
frontalis 3078
neuropathy/dyssynchrony vs. 3851
haemopoietic stem cells 72
granulomas 2238
branchial abnormalities 1 779-82
lymphocyte development 133
hemifacial spasm, benign 393 1
branchial apparatus, development
mesenchymal stem cells 72
laryngeal dystonia 449
multipotent cell populations 72
lower lip depressor weakness 3 084
neural regulation 70
nonallergic rhinitis 1412 spasmodic dysphonia 64 1, 2203, 2224
derivatives 795 F, 796 T, 1740 T,
spasmodic dystonia 449-50
embryology 795-6, 8 1 3-4, 1 264
vocal fold injection 2240
fifth 1 740, 1 740 T
voice disorders 2 1 95
first 795, 796 T, 1 739, 1740 T,
bone marrow transplantation (BMT) 275 infection risk 275 bone morphogenic proteins ( BMP)
8 13-4, 8 14 F, 1 779 F branchial arch( es) 795-6, 1264, 1942 1943 F, 1 943 T
stem cells 67, 70, 74
botulism, dysphagia 2079
synthetic 2 9 1 7
Boveri, Theodore 6
ear development 3 12 1-2, 3 1 2 1 T
bone pain, cancer patients 2784
bovine spongiform encephalopathy
bone pins, intermaxillary 1 623
(BSE) 1 990 Bowen's disease 1 705
fistulae see first branchial arch fistula
bone repair 94 bioactive glasses 123 , 124 T
'bow-hunter' syndrome diagnosis 3769
metal plates 1 1 9
management 3 770
remodelling 94
provoked vertigo 3767
tissue engineering 1 24, 125 F
stroke aetiology 3 768, 3768 F
bone tumours, pituitary region 4 lO4
Bowman's glands 1 662
bony labyrinth, development 3 1 23 ,
Boyle-Davis gag SO l , 501 F Boyle's law 3 500, 3501 T
3 124 T 'schwannoma 3970, 3970 F bony palate 1 341 F
brachiocephalic artery see innominate artery
formation failures 3 122 fourth 795-6, 796 T, 1740, 1740 T, 1943 T
hydroxycarbonate apatite 123
bony labyrinthectomy, vestibular
1 943 T
•
brachycephaly 1 022 T, 1 02 5
abnormalities 1 267-8, 1 267 F, 1 779, 1 780 F innervation 1 942-3 mesoderm 2 1 30 preauricular sinus see pn�aulfl(:ul,if sinus second 795, 796 T, 1739-40, 1 740 T, 1943 T ear development 3 1 2 1 -2, 3 1 2 1 T
1-1 3 1 2 are in Volume I, pages 1 3 1 3-28 1 0 are in Volume 2, and pages 2 8 1 1-4147 are in Volume 3 .
4 1 70 I I ndex
branchial arch( es) (continued) fistulae see second branchial arch fistula formation failures 3 122 sixth 795-6, 796 T, 1 740, 1740 T, 1943 T terminology 1264 third 795, 796 T, 1267 F, 1 740, 1 740 T, 1943 T
Bristol Royal Infirmary Inquiry 594 British Association for Paediatric Otolaryngology (BAPO) 773, 773 F British Association of Day Surgery
remodelling, rhinitis 1 562 segmental 2 14 1 small 2 1 42 structure 2 14 1-2 venous drainage 2 142
(BADS) , head and neck procedure
bronchial agenesis 1 142
recommendations 458
bronchial arteries 2 1 42
British Association of Head and Neck Oncologists (BAHNO)
bronchial challenge, rhinitis 1 563 bronchial hyperreactivity, rhinitis 1561
comparative audit 2376
bronchial stenosis 1 142-4
branchial clefts 797, 8 14, 1 942
data collection coordination 2375
bronchial veins 2 1 42
branchial cysts 798 F, 1 758, 1 759 F,
National Cancer Data Set 2376
abnormalities 1267-8, 1 779
1 779-82, 1942-3
British Association of Otolaryngologists
differential diagnosis 1781
Head and Neck Surgeons
management 1781
(BAO-HNS) , tonsillectomy
nasopharyngeal 2 1 19
guidelines 123 1
origin, theories of 1780-1
British Association of
bronchioloitis 205 T bronchitis, viral agents 205 T bronchoalveolar lavage aspiration evaluation, laryngeal stenosis 1 1 54 PICU 547
otitis media with effusion 3389
Otorhinolaryngologists
bronchogenic carcinoma 685 F
presentation 1781
(BAOHNS) , clinical governance
bronchogenic cysts 1 147
guidance 574-5
bronchography
salivary glands 1 882, 1 883 F surgical removal 1781 ultrasound examination 724, 725 F branchial fistulae 1264-7 1 , 1779-80
British Committee for Safety in
stridor 1 1 19
200 1 256-7
tracheal stenosis 1 143, 1 143 F
embryology 797, 1 779
blood loss estimation 256-7
first arch see first branchial arch fistula
haemoglobin concentration
fourth arch 1 779, 1 780 F management 1779-80 presentation 1 779 second arch see second branchial arch
estimations 257 British Committee for Standards in Haematology splenectomy guidelines 276 British National Study of Hearing,
fistula surgery 1 779-80, 1 780 F third 1 779 branchial pouches 1 741 T
children 1296-7, 1298 F
Haematology guidelines
otosclerosis prevalence 3460, 3460 T British sign language (BSL) 566
bronchomalacia 1 144-5 bronchopulmonary lymph nodes 2 142 bronchopulmonary segments 2141 bronchoscopy anaesthesia 503-4, 1 1 52-3 children 5 1 8-9 flexible see flexible bronchoscopy laryngeal stenosis evaluation 1 152-3, 1 1 53 paediatric anaesthesia 5 1 9
development 8 1 3-4
broad nasal tip 3004
paediatric intensive care 547
lateral cervical cysts 1 780
bromhexine 1 9 1 2
stridor 1 122-3
branchiogenic carcinoma 1 78 1-2, 2728
bromocriptine 309
branchio-oto-renal syndrome 8 1 3 T,
bronchi
968, 1 267
tracheomalacia 1 122-3, 1 145, 1 145 F bronchus see bronchi
anatomy 2 140-4
brown hairy tongue 1 825, 1 825 F
Brandt Daroff positional exercises 3 8 1 0
anomalous bifurcations 1 147
'brown tumours' (osteitis fibrosa
BrdUrd 5 0
blood supply 2 1 42
breaking bad news 5 5 4 T , 565, 2782-3, 2783 T
circular muscle fibres 2 1 42
children 780 WARN, PAUSE, CHECK (WPC) 2782
congenital disorders 1 142-7 cysts 1 782 congenital 1 147
cystica) 390, 40 1 brow ptosis 3049 F, 3054 F bilateral 3055-6, 3056 F surgical approaches 3055 brucellosis 12 16, 1 784 Brun's nystagmus 3712-3, 37 1 3 F
breakpoint method, antimicrobial
development 2 1 3 1
sensitivity testing 234, 235 F breast cancer
foreign bodies 1 1 88
Bryce's sign 2255
inflammation
bubbles, decompression illness 3 5 14-5
Halstedian concept of treatment 27 1 7 pituitary involvement 4 1 04 breastfeeding allergic rhinitis 1 396
rhinitis 1562-4, 1 563
buccal artery 1 798
viral nasal infections 1 563
buccal carcinoma 2560-1
juvenile-onset recurrent respiratory papillomatosis 1 179, 1 1 80 F
epidemiology 2560-1 investigations 2561
food allergy prevention 1426 post-partum thyroiditis 359 breathing, neck trauma and 1 767
lymphatic drainage 2 142
precancerous lesions 2560-1
main, right 2 1 40 F, 2 141
presentation 2560-1 , 2560 F
mucous membrane 2 142
breathing systems, paediatric 5 1 0
obstruction 478
survival rates 2561 T treatment 2561
Pages 1-1 3 12 are in Volume 1 , pages 1 3 1 3-28 1 0 are in Volume 2, and pages 281 1-4147 are in Volume 3 .
I nd ex I 4171
buccal gland 1 808
first degree 96
buccal hemi-neglect syndrome 1 847
grafting techniques 96
buccal-lingual-masticatory syndrome 3939 buccal mucosa 1 792-3 reconstruction, forearm flap 256 1 , 2 5 6 1 F, 2 8 7 1 buccal nerve 1 795 F, 1 800, 1801 F, 3907, 3925 buccal space 1806 buccal vein 1 799
oral white lesions 1836 pinna reconstruction 3032-3, 3033 F second degree 96 third degree 96 tissue engineering 94 treatment 102 burning mouth syndrome (BMS) 1 829, 1 829 T, 1 848-9
calcitonin 375, 388, 3489 function 324 half-life 388 secretion 327, 375, 388 calcitonin gene related peptide (CGRP) 388, 3238 calcium biochemical analysis 379-80 interpretation 380, 380 T methodology 379-80 homeostasis 373, 375
Burow's triangle 2832, 2833 F
diurnal variation 380
2 108-9 innervation 1 795, 1803
bursa pharyngeal embryonalis
endocrinology 375 F
bucconasal membrane 1 3 15
bursa pharyngeal embryonalis
buccinator muscle 1 795, 1 795 F,
buccopharyngeal fascia 1 947, 2 108
(Thornwaldt's bursa) 2 1 22 (Thornwaldt's) cyst 1 074, 2 1 22
parathyroid function and 379 vitamin D role 45 1 , 45 1 F intestinal transport 374
buccopharyngeal membrane 3 120-1
Buscopan see hyoscine
metabolism 388
'bucket handle' advancement
bushy cells 3 1 40-1 , 3 142 F
reabsorption 374
button batteries (as foreign bodies) ears 1 1 85, 3371
renal excretion 388 salivary secretion 1 860
medical negligence 1 3 10
supplementation, post-
flap 282 1 F budesonide acute airway obstruction 1 123 allergic rhinitis, children 140 1
button therapy 2893
chronic rhinosinusitis 1470
bystander effect 28
croup 1 128-9 nasal polyposis 1 554 F, 1 555 F nonallergic rhinitis 1412 persistent rhinosinusitis 437 bulbar palsy 3939 differential diagnosis 3939 dysphagia 2033 motor neurone disease 2079-80 signs/symptoms 3939 speech 3939 bulbar poliomyelitis 2078-9
parathyroidectomy 395
see also hypercalcaemia; hypocalcaemia
C 1 esterase inhibitor deficiency see hereditary angio-oedema (HANE)
calcium channel blockers migrainous vertigo 3804
C1q deficiency 1 78, 1 79 T
tinnitus 36 1 7
C1r deficiency 1 78, 1 79 T
vestibular attacks, acute 3797
C2 deficiency 1 78, 1 79 T C3 139 deficiency 1 79 C3 convertase 139 C4 deficiency 1 78, 1 79 T
calcium channel dysfunction outer hair cells 3605 tinnitus 3605 calcium sensing receptor (CaR) 388, 389
C5 139
calculi, salivary glands see sialolithiasis
bulimia nervosa, salivary gland in 1 908
cabergoline 309
Caldwell-Luc procedure 1493-4
bulla ethmoidalis see ethmoidal bulla
cacosmia (dysosmia) 1664, 1666-7
bulla frontalis (frontal cells) 1 333, 1 500,
cadaverine, malodorous malignant
1501 F
ulcers 2792
Bullard fibrescope 473 bullous myringitis 3326-7 aetiology 3326 definition 3326 diagnosis 3326-7
cadaver tracheal homograft, tracheal stenosis 1 144 CADCAM models, implant osseo integration 29 1 1-2 cadherins 2384
investigations 3327
Caenorhabditis elegans 56
management 3327
caffeine, migrainous vertigo 380 1
outcomes 3327
calcifediol 45 1
pain 3326, 3527
calcification
pathology 3326
costal cartilage 3044-5
signs 3326
lymph nodes 7 1 7
symptoms 3326 bullous pemphigoid 1 7 1 Burkitt's lymphoma 208, 1 254 burn(s)
anaesthesia 1493 complications 1494 contraindications 1 493 indications 1493 medical negligence 1 733 modified 29 1 7 technique 1494, 1494 F callus formation, bone repair 94 Calman-Hine Report ( 1 995) 576 CaIman Report, surgical training 553 caloric test 3 1 54-5, 324 1 , 3727-9 astronauts 3 1 54 canal paresis, unilateral 3727, 3728 F
meningiomas 4009
chronic otitis media 34 1 9
vestibular schwannoma 3959-60
external auditory canal irrigation
calcifying epithelial odontogenic tumour, jaw 1928
classification 96
calcifying odontogenic cysts 1 925-6
dressings 102
calcimimetic drugs 393
methods 3727 labyrinthine stimulation 3750-1 perverted nystagmus 3729 posturography vs. 3733
Pages 1-1 3 12 are in Volume 1 , pages 1 3 1 3-28 10 are in Volume 2, and pages 28 1 1-4147 are in Volume 3.
4 1 72 I I ndex
caloric test (continued) response abnormalities 3727, 3727 T, 3728 F mechanisms 3727
cancer data see data collection, head and neck cancer cancer pain 2783-8 management 2782, 2785 analgesics 2783, 2785
skull base lesions 3946
WHO analgesic ladder 2785
vestibular neuritis 3752, 3756 F
see also specific drugs
vestibular schwannoma 3959
'total pain' concept 2783
VOR suppression 3728
types 2784-5, 2784 T
caloric vertigo 3506-1 1
cancer prevention 2345-6
mild hearing loss 3509-10
primary (risk avoidance) 2345
minimal hearing loss 3509
secondary (screening) 2345
moderate to severe hearing loss 3509 calretinin 3237 calvarial bone, augmentation rhinoplasty 2972 camouflage technique, deviated nose 2989 camptothecin 39 Canadian beaver ( Castor Canadensis), nasal cavity 1 322 F canaliculodacryocystorhinostomy 1 696 canalis sinosus 1341, 1 798 'canalith jam' 3 8 1 2 canalith repositioning procedure (CRP) 3 8 1 0-2 complications 3 8 1 2 gait instability, post treatment 3 8 1 2 outcomes 3 8 1 2
benchmark 2345-6 false positive tests 2345
vs. 3433 recurrence rates 3433 labyrinthine fistulae 3437 apoptosis 62-3, 63 T outcomes 63 apoptotic index 62-3 head and neck see head and neck cancer prevention see cancer prevention 'somatic mutation theory' 2354 stem cell theory of 69-70
see also individual types cancer antigen 1 5-3 (CA 1 5-3 ) 1 867 cancer care
oesophageal 244 oral 242, 244 T treatment 224, 242 hyperplastic 224 advanced head and neck cancer 2789 malignant transformation 224
Candida
oesophageal
antifungal resistant 233 cervicofacial infections, children 1 2 1 6 denture-related stomatitis 1 826 otomycosis 2 1 3
see also individual species Candida albicans 223
laryngeal see laryngeal candidiasis
barium swallow appearance 2027 F HIV patients 243-4, 244-5 symptoms 244-5 oral 1 836, 1837 F acute 1 826 acute pharyngitis 1983
oral infection 1 836
chronic 1 836-7
otomycosis 2 1 3
HIV-associated infection 242,
tracheo-oesophageal voice protheses 225 xerostomia 1 867
tracheo-oesophageal voice protheses 225
Candida krusei 223 HIV associated infection 1 826 tracheo-oesophageal voice protheses 225 candidal leukoplakia see candidiasis,
cancer
care 2789 HIV-associated infection 223, 20 1 3
management 224
see denture-related stomatitis Candida glabrata 223
intact canal wall mastoidectomy
gingival white patches 1 820 head and neck cancer, palliative
cancrum oris (noma) 1 822
canalolithiasis 3678-80, 3760, 3761 F
cholesteatoma 3432-3
epidemiology 223
immunocompromised patients 223
candida-associated denture stomatitis
canal wall down mastoidectomy
dysphagia 203 1
predictive value 2345, 2346 T cancer registration 2373
canal of Huguier 3 1 10 canalplasty, keratosis obturans 3344
diagnosis 224
hyperplastic
Candida parapsilosis 223 otomycosis 2 1 3
Candida tropicalis 223 otomycosis 2 1 3 tracheo-oesophageal voice protheses 225 candidiasis 223-5 aetiology 223 chronic atrophic see denture-related stomatitis
244 T mouth ulcers 1 833 mucosal redness 1 822, 1 826 types 1837 T white lesions 1 836-7 oropharyngeal 223-5 outcomes 224-5 pharyngeal 201 1 predisposing factors 20 1 1 T pseudomembranous 223 HIV patients 244 T treatment 224 throat 223-5 treatment 20 1 1 canine fossa 1 340 canines 1 803 deciduous 1 804-5 permanent 1 803 roots 1 803 caniniform teeth see canines canker sores see recurrent aphthous stomatitis (RAS) cannabis smoking, head and neck squamous cell carcinoma 235 1-2
multidisciplinary teamworking 576,
chronic mucocutaneous 180 T, 1 8 1
576-7 outcomes research 64 1
classification 223
Cannon's disease (white-sponge naevus) 1 824
clinical manifestations 223-4
canonical bubbling phase, speech/
standards 575
complications 224-5
language development 990-1 canthal (palpebral) ligaments 1679
see also clinical governance
definition 223
Pages 1-13 1 2 are in Volume 1, pages 1 3 1 3-2 8 1 0 are in Volume 2, and pages 2 8 1 1-4 147 are in Volume 3.
I nd ex 1 41 73
CAPE V scheme 2 1 75, 2 1 75 T anaesthesia 502 capillary ectasias, vocal folds 2203
nasopharyngeal see nasopharyngeal carcinoma (NPC) oesophageal see oesophageal carcinoma
capillary haem angiomas, nasal 1 708
parotid gland 723
capillary lymphangioma 1 782
taste abnormalities 1 845
capnograms 498, 499 F
thyroid see thyroid cancer
capillary bleeding, hypotensive
CAP RAST
1 394-5
carcinoma ex pleomorphic adenoma, salivary glands 2500-1, 2502
capsaicin 148 nonallergic noninfectious perennial rhinitis 1409
carotid body paragangliomas 2526,
skull base surgery 413 7 cardiac index monitoring 529 cardiac output, anaesthetic monitoring 500 cardiac risk, clinical predictors 459 T
glossopharyngeal neuralgia 208 1 ,
353 1-2
cardiogenic embolism 3767 cardiolipin antibodies 171
hemifacial spasm, benign 3931
cardiomyotomy, achalasia 1290
tinnitus 3617 tn§;enllllal neuralgia 1 830
cardiopulmonary resuscitation (CPR), palliative care 2798, 2799 T
cart)apt�nenns 230
cardiospasm see achalasia
carbimazole
cardiovascular disease
aetiology 2668 hypothyroidism 450 mechanism of action 346 side effects 346 thyrotoxicosis 346
obstructive
apnoea 23 14
patient preparation, surgery 458-60 cardiovascular support, critical care
528-30 children 543
carbogen 50
cardiovascular syncope 3732
carbon dioxide (C02) laser 743
CaR gene 389
blepharoplasty 3058, 3059 F juvenile-onset recurrent respiratory papillomatosis 1 176-7 laryngeal stenosis 2278 papillomas 2238 pharyngeal pouch 2054, 2058, 2058 T Reinke's oedema 2265 subglottic haemangioma 1 140 tympanic membrane fenestration, otitis media with effusion 3392-3 carboplatin 37 carcinoembryonic antigen 2495-6
2514-5
cardiac dysrhythmia
capsulotomy techniques,
carbachol 1 365
metastatic neck disease 2727 salivary gland tumours
carcinoma in situ, larynx 2609, 2609 F blepharoplasty complications 3065
tonsillectomy 1235
carotid artery resection head and neck cancer 696
carotid artery stenosis, diagnostic delay 4 144-5
capsofugine 1455
capular flap 2873-6
carotid artery aneurysm, endovascular embolization 739 carotid artery replacement 2727
mutations 389 Carhart effect 3461 Carhart notch 3185 otosclerosis 346 1-3, 3462 F mixed hearing impairment 3462-3,
3463 F sensorineural hearing impairment 3462-3, 3464 F total hearing impairment 3462-3,
2531 F imaging 725-6, 726 F, 2529-30 management 2532 surgical treatment 2532 carotid canal 3 1 16 carotid plexus lesions, Horner's syndrome 3937 carotid sheath 1 743, 1 757, 2 1 10 contents 2 1 10 T parapharyngeal abscess 2000 skull base 3901-3 carotid space see carotid sheath carotid triangle, neck 1 742 caroverine 36 1 8 carpal tunnel syndrome 355 Carpentf�r syndrome 1028 tack' sign 171 1-2 Joseph 1 10 r>lr·tl l �I UP
repair, tissue engineering
1 25 r"'r'h l �I O'''
triticea 2 133-4
case-control studies epidemiological research 627-8,
2344 evidence-based medicine 655 caspase(s) 57, 2383 activation pathways 57 caspase 3 57, 58 caspase 8 57-8
3464 F carina 2 140
caspase-activated DNase 58
Carlson-Crittenden device, saliva
caspase inhibitors 3302
collection 1 862-3
carcinogenesis, apoptosis and 62
Carnegie stages, head and neck
carcinogens, nasal malignancy 2418 carcinoma, primary 2702
embryology 793 T caroticocavernous fistula, acute 391 6
carcinoma(s)
carotid artery
caspase 9 58
Castor Canadensis (Canadian beaver), nasal cavity 1 322 F cat allergen avoidance 1 397 cataracts, neurofibromatosis 2 4000 CATCH-22 1 80-1 catch up saccades, unidirectional
acinic cell 2497
aneurysmal dilation 3927
ameloblastic 1938
in cavernous sinus 299
antral 3927
hypophysectomy and 4108
catecholamine metabolite assessment,
3713
branchiogenic 1 781-2, 2728
injury, surgery-induced 2743, 2743-4
bronchogenic 685 F
permanent balloon occlusion, jugular
glomus tumours 4028 beta-catenin mutations, juvenile
buccal see buccal carcinoma
. rs 4035 foramen tumqu surface anatomy 1 741
cathepsin -D 2637
hard palate see hard palate carcinoma
angiofibroma 2438
Pages 1-1 3 1 2 are in Volume 1, pages 1 3 1 3-28 10 are in Volume 2, and pages 281 1-4147 are in Volume 3.
4 1 74 I I nd ex
size 299
DNA damage 58 p53 58 control 2382 p53 role 2382, 2382 F growth phase ( G1 ) 35, 35 F, 238 1 growth phase 2 ( G2 ) 35, 3 5 F, 2381 interphase 238 1 mitosis 35, 35 F, 2381 restriction points/check points 58 synthesis phase (S) 35, 35 F, 238 1 tumour biology 34-5 cell cycle-nonspecific chemotherapy 37 cell cycle-specific chemotherapy 37 cell death 56-65 apoptosis see apoptosis cell population regulation 57 mechanisms 36 necrosis see necrosis ototoxicity 3300-1, 3301 F prevention 3302 radiation-induced 47 types 57 cell differentiation 1 6 ear development 8 1 5 cell division, anticancer drugs 34 cell-mediated drug reactions 4 14
tumours 2426 F
cell-mediated immunity (CMI),
catheter angiography skull base surgery 3949-51 indications 3949-50 risks 3951 stroke risk 395 1 catheters, endovascular 732-3 cat scratch disease 12 16, 1 70 1 , 1 784 cauliflower ear deformity 3373 causality 2343-4 caustic soda ingestion 1 290 caustic stricture, dysphagia 2034 cautery, epistaxis 1065 F, 1066 cavernous haemangioma nasal neoplasms 1 708 painful red eye 3916 cavernous lymphangioma 1 782 cavernous sinus(es) 299, 391 8 F blood supply 299, 303 corrosion casts 299 drainage 299 magnl�t1c resonance imaging 306 nervous relations 299 pituitary tumour extension 4100 hypophysectomy and 4 1 10 sampling, Cushing's disease 4 102
nasopharyngeal carcinoma 2448
cavernous sinus syndrome 4027-8
auditory brainstem responses 3860-1,
386 1 F auditory evoked potentials 3862 auditory hallucinations 3863-4 auditory steady-state response 3860 behavioural tests 3858-60 central deafness 3863 children, management 3864-6 compressed speech test 3860 definition 3857-8 dichotic digit test 3859-60, 3859 F dichotic speech tests 3862 electrophysiologic tests 3860-2 frequency pattern sequences 3859 interhemispheric lesions 3862-3 masking level difference test 3860 middle latency response 386 1-2,
3861 F, 3862 F peripheral hearing loss 3864 prevalence 3858 central auditory nervous system (CANS) 3857 evaluation 3858 peripheral hearing loss 3864 central deafness auditory hallucinations 3864 central auditory dysfunction 3863 central hyperventilation
cell membrane, apoptosis and 59-60
syndrome 1 154-5
orbital 1 540
cell migration, wound healing 89, 90
central hypothyroidism 357
symptoms 1 540-2
cell receptors 2383-4
central masking, pure-tone audiometry
treatment 1544
cell
cavernous sinus thrombosis 1088
autologous blood transfusion 263
Cavilon 100 cavity wounds 10 1
cell senescence 10
cavum conchae 3 105-6
cell signalling 36
Cawthorne-Cooksey exercises, vestibular rehabilitation 3806,
growth factors 36 transcription factors 36 cell survival curves, radiotherapy 48
3806 T
cellular radiosensitivity 47-8
efficacy 3807
acute effects 47-8
historical aspects 3805 C cells see parafollicular
cells,
thyroid gland
late effects 47-8 cellulitis
ced genes 56 cefotaxime 230 cefradine 230
orbital see orbital cellulitis,
ceftazidime, malignant otitis
perichondritis aetiology 3358
externa 3339
nasal infection 1 700 rhinosinusitis complication periorbital 1087-8
and 3265 central neck swellings, children 1 2 1 1 central nervous system (CNS) damage, voice disorders and
2222-5 pathways and processing, cochlear implants 3650 tumours, CPA impingement 401 5 central nystagmus, peripheral
vs.
3724 T central papillary atrophy, tongue 1 826-7 central pattern generators (CPGs), swallowing 1 959 central processing disorders (CAPD) 3851
ceftriaxone 230, 2008
cemento-osseous dysplasia 1 930
central scotoma 3914, 3914 F
cell adhesion molecules see adhesion molecules cell biology, molecular aberrations
Center for Epidemiologic Studies
central venous pressure, anaesthesia
8-10
Depression scale, cochlear implants assessment 3654-5 central apnoea 492
cell cycle 34-5, 35 F, 2380-1, 238 1 F apoptosis 58 arrest 10, 58
central auditory dysfunction
3857-69 aetiology 3858
monitoring 500 central vestibular disorders ( CVD) pharmacological treatment 3804-5,
3804 T vestibular rehabilitation 3809
see also vestibular diseases/disorders
Pages 1-1 3 1 2 are in Volume 1, pages 1 3 1 3-28 1 0 are in Volume 2, and pages 281 1-41 47 are in Volume 3.
I ndex I 4 1 75
central vestibular pathways 3 147, 3 147 F Centre for Involvement 574 Centres for Disease Control (CDC) HIV staging system 239 Universal Blood and Body Precautions 239-40 centromere 3-4 centromere antibodies 1 70-1 cephalic margin resection 2952 cephalic trim 2952-4, 2953 F cephalometry, snoring 2329 cephalosporins 229, 230
diagnosis 3752, 3756 F management 3770 stroke aetiology 3767 cerebellar medulloblastoma 3848 cerebellar syndromes aetiology 3775 postural reflexes 373 1 cerebellar tumours 3776 diagnosis 3776, 3776 F positional vertigo 3776 cerebellopontine angle (CPA) 3932 F,
3942 surgery
cerebral abscess acute otitis media 924-5, 925 F rhinosinusitis 1443, 1 540 cerebral air gas embolism (CAGE) 3519-20 cerebral arteriosclerosis 3768 cerebral cortex, sleep and 2306 cerebral oedema radical neck dissection complications 2745 syndromic craniosynostosis surgery 103 1 cerebral palsy
adult epiglottitis 225 1
auditory function monitoring 750
drooling 788
antibacterial spectrum 432 T
facial nerve palsy induction 3880,
dysphagia management 2086
cross-reactivity 230 pharyngitis 1 985, 1 986 rhinosinusitis 1 543-4 ceramic biomaterials 120 applications 120 bone tissue attachment 124 T glass 120
3889 middle fossa 402 1-2 tumours see cerebellopontine angle (CPA) tumours cerebellopontine angle (CPA) syndrome 3932, 4007-8 cerebellopontine angle (CPA)
tissue response 1 19 tissue scaffolds 123, 124 T applications 120
tumours 3776, 3777 congenital rest lesions 40 14 CPA syndrome 4007-8
ceramic microphone 3 169-70
diagnosis 3848
Ceravital 120
enterogenous cysts 4014
c-erbB-2
hearing loss 3943-4
adenoid cystic carcinoma 2496
incidence 3943, 4007
saliva screening 1 867
intraaxial tumours with CPA
cerebellar ataxia acquired 3775-6 definition 3775-6 acute-onset 3775 children 1048 dizzy child 1042 episodic see episodic cerebellar ataxia hereditary see hereditary cerebellar
impingement 401 5 choroid plexus papillomas 401 5 primary CNS tumours 401 5 nonacoustic (non-vestibular schwannoma) current knowledge/future research 4016
insidious-onset 3775-6 sporadic 3775-6 definition 3775-6 cerebellar disorders/lesions
cerebritis, vestibular schwannoma removal 3982 cerebrospinal fluid (CSF) flow, arachnoid cysts and 40 1 3 otorrhoea, vestibular schwannoma removal 398 1 cerebrospinal fluid fistula syndromic craniosynostosis surgery 103 1 traumatic 3390 vestibular schwannoma 3968-9 cerebrospinal fluid 'gusher,' stapes surgery 3474-5 cerebrospinal fluid leak encephalomeningocoele 1035 hypophysectomy complication 4 1 1 2-3 medical negligence 3830 middle fossa surgery 4023 nasal see cerebrospinal fluid
radiological characteristics 4008 T tumours originating in
rhinorrhoea post-craniofacial surgery 4132, 4132 F skull base surgery complication 4138
CPA 4008-15
vestibular schwannoma surgery 3981 ,
retrocochlear hearing loss 3848 vestibular schwannoma see vestibular
dysarthria 3940
schwannoma (VS)
nystagmus 3922
see also specific sites/tumours
posturography 3735
postoperative complications 1 1 1 0 pharyngeal problems 2080
management 4007-17 skull base origin 4015
ataxia
obstructive sleep apnoea 1 109
cerebellum
4138 cerebrospinal fluid rhinorrhoea 1636-44 aetiology 1636-7, 1637 T iatrogenic 1 636-7, 1637 F, 1640 F
saccade abnormalities 3716
epidermoids 401 1
definition 1636
stepping patterns 373 1
injury, vestibular schwannoma
diagnosis 1637-41
clinical manifestations 3769 management 3770
meningiomas and 4009
encephalocoele 1638, 1 638 F head injury 1636-7, 1637 F
movement control 2 1 58-9
imaging 1638, 1638 F, 1639 F
stroke aetiology 3768
vestibular schwannoma
laboratory investigations 1638
cerebellar haemorrhage
cerebellar infarction clinical manifestations 3768-9
removal 3978
expansion 395�-9, 3958 F symptoms 3959
intrathecal dyes/markers 1638-9,
1 639 F
Pages 1-1 3 1 2 are in Volume 1, pages 1 3 1 3-28 10 are in Volume 2, and pages 281 1-4147 are in Volume 3.
�-
4 1 76 • I ndex
cerebrospinal fluid rhinorrhoea
echogenic hilum 7 1 7-8 image-based classification 1 759
(continued) management 1 637-41, 1 639 F
jugular chain 1747
medical negligence 4144
levels 7 1 5, 7 1 5 T, 1 748-9, 1 748 F,
meningitis 1 636, 1638, 1639-40
2363, 2363 T, 271 2 F
cervical sympathetic trunk 1752,
3936-7, 3936 F clinical involvement 3937-8 lateral skull base 3903 cervico-aural fistula see first branchial
nasal endoscopy 135 1-2
level I 1 748
nasal fractures 1 6 1 2
level II 1 748
perilymphatic fistulae 3510
level III 1 749
physiology 1636
level IV 1 749
cervicofacial infections 1 783-5
pituitary tumours 305, 4100
level V 1 749
surgery 1 640-1, 1 640 F, 1 64 1
level VI 1 749
children 1210-8 assessment 12 10, 1 210-1
arch fistula cervicofacial cheek advancement flap 2837
temporal bone trauma 3496
level V II 1 749
transsphenoidal meningoen-
metastases 2714
examination 1 2 1 1-2
N stage definition 2363, 2363 T
fungal 1 2 1 6
organ-specific drainage 271 3-4
head and neck examination 1 2 1 2
cephalocoeles 2 1 1 6-7 vestibular schwannoma removal 398 1-2 cerebrovascular accident, pseudobulbar palsy 3939
bacterial 1 2 1 3-4
palpation 7 1 6-7
imaging 1 2 1 2
posterior nodes 1747-8
laboratory tests 1 2 1 2
primary tumour evaluation 2363
lymphoma simulating
cerumenolytics 431
submandibular 1 747, 1 799
ceruminous adenocarcinoma 4070
submental 1747, 1799
ceruminous adenoma 4069-70
tumour staging 2363-4, 2363 T
mycobacterial 1214-6
ceruminous glands 3 107
ultrasound 7 1 5-8, 7 1 6 F,
nature of 1 2 1 2
cervical abscess, children 1 2 1 3,
1 759-60
conditions 1 2 1 7 microbiology 1 214
noninfective inflammatory
calcified 7 1 7
1213 F cervical lymphadenopathy assessment 2719-20 diagnosis 2703 Epstein Barr virus 2703
children 1 297, 1 297 F
disorders 1 2 1 6-7 viral 1 2 1 2-3
cystic 717, 7 1 7 F, 7 1 8 F echogenic hilum 7 1 7-8
cervioocular reflex 3227
echogenicity 7 1 7
'ceteris paribus' principle,
see also individual diseases
examination 2703
FNAC and 7 1 6-7
genetics 2703-4
inflammatory nodes 7 1 6
cetirizine hydrochloride 4 1 1
epidemiological research 6 1 7
imaging 2703, 2705 F
metastatic nodes 7 1 7 T, 7 1 6, 7 1 6 F
cetuximab 43, 5 2 , 2760
irradiation 2706
prognostic value 7 1 6-7
cevimeline 1 9 1 2
management 2702-10
reactive nodes 7 1 5 , 7 1 6 F
Chagas disease 2032 Chaissaignac's triangle 2737
medical negligence 1 3 10
shape 7 1 7 size 7 1 7
molecular analysis 2703-4
vascular pattern 7 1 8
putative site 2706-7
nasopharyngeal carcinoma 245 1,
cervical lymphoma, children 1 254 cervical necrotizing fasciitis 1 785,
245 1 F panmucosal irradiation 2706-7 positron emission tomography 2704,
2705 F recent advances 2707 surgical management 2706 tuberculosis 1 783 unknown primary carcinoma 2704-5 cervical lymphatics 1 746-9 assessment 1 759-62 computed tomography 1 760-1 magnetic resonance imaging 1 761-2 normal measurements 1 759 palpation 1759 positron emission tomography 1 762 radiological staging methods 1 759
1785 F cervical oesophagostomy, oesophageal atresia repair 1 285 cervical oesophagus tumours see
Chaissaignac's triangle clearance, radical neck dissection
2737-8 chancre 1460-1 channelopathies 3773 characteristic impedance, air 3 165 charcoal dressings, fungating lesions 453
oesophageal carcinoma
Charcot-Leyden crystals 1 654
cervical plexus 1 752, 2739 F, 2740
Charcot-Marie-Tooth disease
cutaneous branches 1 752 muscular branches 1 752 cervical sinus 1 740, 1942-3 lateral cysts see branchial cysts cervical spine atlantoaxial subluxation, adenoidectomy-related 1 098 fractures, intubation-induced
2289 protection, neck trauma 1 766-7
auditory neuropathy! dyssynchrony
3849 vertigo, children 1048 CHARGE association 968, 1 046, 1 07 1 ,
3683 CHARGE syndrome 1 055 Charles's Law 3501 T CHART trial 2755 cheek(s) anatomy 1 792-3 blood supply 1 798
1-1 3 1 2 are in Volume 1, pages 1 3 1 3-281 0 are in Volume 2, and pages 281 1-41 47 are in Volume 3.
-�
I nd ex I 4 1 77
development 798 lymphatic drainage 1 799 mucous membrane 1 792-3 muscles 1 795, 1 795 F sensory innervation 1 800-1 swallowing 1954-5 venous drainage 1 799
see also entries beginning buccal cheek biting, (morsicatio buccarum) 1 836 cheilitis glandularis 1 9 1 5-6, 1 9 1 6 F cheilosis 1 827 chemical agents basal cell carcinoma 2396 olfactory dysfunction 1 670, 1 673-4 chemical burns, oral 1 836 chemical labyrinthectomy 3567 chemodectoma see glomus tumours chemogustometry 1 844 ct-chemokine family 89 chemoprevention 4 1 chemoradiation 4 1 chemoradiotherapy 2757 cervical lymphadenopathy 2707 meta-analyses 2757-8 chemosensitization bystander effect 28 head and neck cancer gene therapy
28 p53 transfer 28 chemosis, post-blepharoplasty 3066,
3066 F chemotactic factors 89, 89-90 chemotherapy adjuvant 40 head and neck sarcomas 1 933-4 adjuvant radiotherapy 5 1-2 administration, cell cycle synchronization 37 agents 452 classification 37-40 by mechanism 37-40 phase-specific toxicity 37-40 as radio sensitizers 52 resistance 63 site of action 452, 452 F
see also individual agents apoptosis 63 cell cycle-nonspecific 37 cell cycle-specific 37 combination 40 concurrent chemoradiation 41 drug dosing 36 Ewing's family of tumours 1936 future · deVelopments 41
head and neck cancers 40 drug choice 40 rhabdomyosarcoma 1935 agent treatment 40 head and neck sarcomas 1933-4 treatment regimens 1934 high-dose 4 1 hypopharyngeal cancer 2649 intraarterial 735 laryngeal cancer 452 mechanism of action 63 nasal malignancy 2427 nasopharyngeal carcinoma 2460 neoadjuvant head and neck sarcomas 1 934 phase III trials 40 oropharyngeal tumours 259 1 osteosarcoma 1936-7 ototoxicity 3298-300 phase-specific 37 principles 34 salivary gland tumours 2508 strategies 40-1 temporal bone squamous cell carcinoma 4094 cherubism 1 654-5, 1 654 F, 1 93 1 chewing exercises 2089, 2089 T chewing gum, Sjogren syndrome 1 9 1 2 chewing tobacco, buccal carcinoma 2560 Cheyne-Stokes respiration, obstructive sleep apnoea 2316-7 Chiari malformations 3777, 3777 F children 1048 chiasmatic sulcus, sphenoid bone 1338-9 chief cells, parathyroid gland 3 1 6 F,
320, 373-4 chilblains (perniosis) 1 7 15 childbirth, laryngeal effort closure 2 1 59 childhood deafness 844-59 aetiology 845-9 acquired causes 847 congenital causes 8 1 7-8, 845-7 perinatal factors 845-6 audiology 850 clinical examination 1 8 education 854-6 epidemiology 844-5 genetic causes 17, 845 genetic counselling 852-3 genetic screening 85 1-2 imaging 850- 1 , 8 5 1 F inheritance patterns 1 8 investigations 850':'2, 8 5 0 T, 8 5 1 T
newly diagnosed child 849-53 reactions to diagnosis 849 presentation 848-9 delayed 848 screening 851-2 serology 85 1 single-sided deafness 848 support 853-6 aids 854 rationale for intervention
853-4 child protection issues 780 children anaesthesia see paediatric anaesthesia consent issues 601 deafness see childhood deafness drug prescribing 4 1 5 hearing tests see hearing tests, children
see also entries beginning paediatric; individual diseases Children's Respiratory Study 1561 chimpanzee (Pan troglodytes), paranasal sinuses l321 F chin down posture, dysphagia 707-8 chitosan tissue scaffolds 1 23 chlamydia 201-2 definition 201 diagnosis 202 neonatal rhinitis 1 076-7 treatment 202 see also individual species Chlamydophila pneumoniae 202 Chlamydophila psittaci 201 Chlamydophila trachomatis 201 chloramphenicol 231 acute epiglottitis 1 13 1 chlorhexidine 448 denture-related stomatitis 1 826 dysgeusias 1 848-9 epistaxis 1 604 children 1066 mouth ulcers 1 830 mouthwashes 448 chloride ions endolymph 3 187 T nasal secretions 1 360 perilymph 3 1 89 T chloroquine ototoxicity 3571 chlorphenarimine 1397-8 chlorpromazine 4 1 5 chlorthalidone 3799, 3799 T choanae 2 1 10 primitive 1 3 1 5 choanal atresia 1070-2, 107 1 F, 1320 airway expansion 1071 , 1072 F
1-13 12 are in Volume 1 , pages 1 3 1 3-28 1 0 are in Volume 2, and pages 281 1-4 147 are in Volume 3.
4178 I I ndex
choanal atresia ( continued ) bilateral 107 1
pars tensa 3433
chondrovomerine 2989
pathology 3400- 1 , 3400 F
chorda tympani 3 1 1 6 , 3905, 3928
correction techniques 107 1-2, 1072 F
post-stapes surgery 3477
dysphagia aetiology 2029
presentation 34 1 3 F, 343 1
local anaesthetic injection 1847
paediatric anaesthesia 5 1 4-5 septum 1 570
prevalence 949 F
stapes surgery 3477
choanal polyp 1 554
primary auditory canal see primary auditory canal cholesteatoma
surgery 3432-4
choking
aims 3432
injury
taste abnormalities 1 844, 1846 temporal bone resection 4092 chordoma(s) clivus 4 1 26
glossopharyngeal nerve lesions 3937
complications 3434
CPA involvement 40 1 5
obstructive sleep apnoea 1 104
medical negligence 3829 problem mastoid cavities 3434
cranial 4 1 26
revision 3434
head and neck tumours,
recurrent laryngeal nerve lesions 3937 cholesteatoma 3430-4 aetiology 341 1-2 misplaced epithelium 341 1-2 squamous metaplasia 34 1 1 bone resorption 3399 children 947-54 acquired 948
see also epidermoids
cholesterol cyst, petrous apex 4047 drainage 4050- 1 , 405 1 F cholesterol granuloma 1655
dysphagia aetiology 2033 childhood 1 260 pituitary 4104 radiosurgery 3996 skull base 4 1 26
active mucosal chronic otitis
temporal bone 4072-3
media 3399, 3399 F
classification 4072
acquired vs. congenital 948
CPA involvement 40 1 5
anatomical features 949, 949 F,
definition 1655
incidence 4047, 4072-3
histology 1 6 5 5
management 40 5 1 , 40 52 F, 4073
classification 947, 948 T
imaging 1 6 5 5
open cavity surgery 4052
congenital 947-8
treatment 1 655
radiotherapy 405 1-2
949 T
differential diagnosis 4073
epidemiology 948-50, 949 F, 949 T
choline salicylate gel 2785
recurrence 4047
iatrogenic 948 investigation 95 1-2
cholinesterase inhibitors 2077
symptoms 4047
chondrectomy, perichondritis 3359-60
choreiform syndromes 3939
pathogenesis 947
chondritis, burnt ears 3032-3
choroid plexus papillomas 40 1 5
chondroblasts 94
Christmas disease see haemophilia B
chondrocytes 75
CHRNB 1, salivary gland tumours 2496
recurrence, prevention of 953-4, 953 F, 954 F
residual, risk factors for 952-3, 952 T
chondroethmoid junctions 2989
chromatin condensation 59
chondroma(s)
chromoblastomycosis 2 1 4
signs 950-1
CPA involvement 40 1 5
chromophobe cells, pituitary gland 297
special needs 786
larynx 2 6 0 0 T
chromosome(s) 3-4, IS, 2379, 2379 F
symptoms 950, 950 T
chondromucosal grafts 2827
treatment 952-4, 952 F, 952 T
chondroradionecrosis 3376
congenital 947-8, 947 F, 3683
chondrosarcoma( s)
congenital atresia 98 1
CPA involvement 3943, 40 1 5
definition 947
head and neck 1 937-8
diagnostic delay 1306-7
hyaline 4073
examination 343 1-2
larynx 2603, 2604
radiology 343 1-2
mesenchymal 1 937-8
chromosome Ib protooncogene 389 mutation 3 89 chromosome 6q 2496 chromosome 22 deletions 180-1 , 1 80 T neurofibromatosis 2 3998-9 chromosome breakage, craniofacial defects 792
hearing in 343 1
middle ear 4073
inactive squamous chronic otitis media and 3428
petrous apex 4024 F
chromosome spreads 2379 F
radiosurgery 3996
chromosome Xp 1 1 tumour suppressor
jugular foramen 4036 F
skull base 41 25-6
medical negligence 1306-7, 3 828-9 negligent management 1 307 natural history 3430-1
temporal bone 4050 F, 4073
active disease progression 343 1 bone erosion 343 1 progression towards healing 343 1 otalgia 3527 otoscopic diagnosis 34 1 8 , 3418 F, 3419 F
classification 4047, 4073 development 4073 grading system 4073
chromosome silencing 27
gene 389 chronic aspiration see intractable aspiration chronic atrophic candidiasis see denture-related stomatitis
incidence 4073
chronic autoimmune hypothyroidism
management 405 1
see Hashimoto's thyroiditis chronic granulomatous disease
symptoms 4047, 4073 T treatment 4073 chondrotomy, posterior 1 578, 1 579 F
(CGD) 1 77 T, 1 7 8 laryngeal manifestations 2266-8
Pages 1- 1 3 1 2 are in Volume I, pages 1 3 1 3-28 1 0 are in Volume 2, and pages 28 1 1-4147 are in Volume 3 .
I ndex I 4 1 79
chronic lymphocytic leukaemia ( CLL) 275 chronic myeloid leukaemia (CML)
275 chronic myringitis
see
granular
myringitis chronic nasal obstruction ( CNO) 1591-2 chronic nonpurulent otitis media see otitis media with effusion ( OME) chronic non-specific sialadenitis 1 903 chronic obstructive pulmonary disease ( COPD) hyperbaric oxygen 291 0 nasal inflammation 1 561-2 sinusal inflammation 156 1-2 chronic otitis media ( COM) 3395--445 active definition 3396 hearing aids 3435 prevalence 3408 active mucosal ( perforation with otorrhoea) 3423-5 aural polyps 3397 bacteriology 3424 cholesterol granuloma 3399, 3399 F diagnosis 341 5 F, 3416, 341 6 F, examination 3424 granulation tissue 3397 hearing in 3423--4 management 3424 natural history 3423--4 pathology 3397-9, 3398 F presentation 3424 progression with continuing activity 3423 resorptive osteitis 3397-9, 3399 F surgery 3425 topical mediation 3424 active squamous see cholesteatoma activity, factors influencing 341 0 aetiology 3408 environment 3409 racial factors 3409 arachnoid granulations 3402 assessment 3412 audiology 341 9 bacteriology 3420 bone-anchored hearing aid 3643 children see chronic otitis media ( COM) , children classification 3396 T complications 3435-8 . classification 3435-6 extracranial 3435 T, 3436-7
incidence 3435, 3435 T infection routes 3437 intracranial 3435 T, 3437-8 labyrinthine 3436 mortality from 3436 otogenic intracranial 3404, 3405 F pathology 3402--4 petrositis 3404, 3404 F definition 928-9, 3396 International Symposium on Recent Advances in Otitis Media 929 new classification 929, 931 F World Health Organization 929 diagnosis 3412 endoscopy 3420 epidemiology 3408 facial nerve paralysis 3404, 3890 children 1056 imaging 3882 management 3437 genetics 3409 healed 3425-6 definition 3396 diagnosis 3406 F, 3413--4, 3414 F,
341 5 F dimeric membrane 3398 F, 3401 examination 3426 fibrocystic sclerosis 340 1-2 fibro-osseous sclerosis 3400 F,
340 1-2, 3401 F hearing aids 3434-5 hearing in 3426 management 3426 natural history 3425-6 neo-osteogenesis 3401-2, 3402 F pathology 3401-2 presentation 3426 prevalence 3408 progression 3425-6 progression towards activity 3426 surgery 3426 tympanosclerosis see tympanosclerosis hearing aids 3434-5 histology 930 history taking 3418 inactive definition 3396 aids 3434-5 prevalence 3408 inactive mucosal (dry perforation) 341 5 F diagnosis 3414, 341 5 F examination 34"21
myringoplasty 3421-2 natural history 3420-3 pathology 3397, 3397 F, 3398 F presentation 3421 surgical management 3421-3 surgical objectives 3421 inactive squamous 341 6-7, 341 7 F,
341 7 F, 341 8 F, 3426 children 941-7, 941 F cholesteatoma and 341 1, 3428 definition 3426-7 examination 3427 pars flaccida retraction 3427 pars tensa retraction 3427 excision 946, 946 F, 946 T long-term results 946 F, 947 hearing levels, retraction and
3430 management 3428-30 adults 3430 nasal disease management 3428 natural history 3427-8 pathology 3400, 3400 F progression 3428 recurrence 3429 surgical treatments 3428 tympanic membrane management 3428-9 ventilation tubes 3429 infection 3410, 341 0 T bone erosion 3402 congenital defects and 3402 spread routes 3402 labyrinthine fistulae 3402-3 labyrinthitis 3403--4 management 3420 corticosteroids 423 mucosal 341 0- 1 natural history 3420 otosclerosis 3461 otoscopy 3412, 341 3-8 outcomes 3420 pathogenesis 930 pathology 3396, 3412-3 prevalence 3408, 3409 T radiology 341 9-20 resolution prevention 931-2 bacterial biofilm colonization 931-2 re}:,ealtea infection 931 surgery rates 3408 surgical pathology 3404-7 cartilaginous grafts 3405-6 cre:ep'lllg substitution, bone formation 3405-6
1-1 3 1 2 are in Volume 1, pages 1 3 13-28 1 0 are in Volume 2, and pages 281 1-4147 are in Voh.une
3.
4 1 80 I I nd ex
chronic otitis media (COM) (continued ) mastoidectomy cavities 3406-7,
3406 F, 3407 F ossicular grafts 3405-6, 3405 F ossicular implants 3405-6, 3406 F tympanic membrane grafts 3404-5,
risk factors 933-4 treatment 936-41 chronic renal failure ( CRF) , taste abnormalities 1 848 chronic rhinosinusitis ( CRS) acute exacerbations 1 382, 1 382 T,
1439-40
3405 F symptoms 3418, 341 9 T synonyms 3396 T tuberculous otitis 3448, 3448 1', 3449 tympanomastoid surgery adhesion formation prevention 3407 middle ear non-aeration 3407-8 success, factors determining 3400 F,
3401 F, 3402 F, 3407-8 vestibular assessment 3419 chronic otitis media ( COM), children 928-64 cholesteatoma see cholesteatoma complications 931 F ear discharge, profuse chronic 935 inactive squamous, management
3430 ossicular erosion 93 1 F, 954-7 classification 954-5 epidemiology 954 outcome measures 955 pathology 954 results 955-6, 956, 956 F, 956 T risk factors 955 timing of intervention 956-7 pars tensa atrophy 93 1 F, 941-7, 942 F classification 942-3 definitions 942-3 epidemiology 943, 943 F investigations 945 management 945 natural history 943-4, 943 T pathology 941-2 signs 944-5 surgical intervention 945-6 symptoms 944 tympanic membrane chronic perforation 931 , 931 F, 932,
932-41 age 933, 934 F classification 932-3 clinical examination 935 clinical presentation 934-5 definitions 932 epidemiology 933 investigation 936 microbiology 934 pathology 932
allergen avoidance 1470 antibiotics 1470-1 antifungals 1472 antihistamines 1 472 antileukotrienes 1472 aspirin 1472-3 bacteriology 1441 causative agents 1381 children 1 080-2 complications 1540 computed tomography protocols 1479 T contact endoscopy 764 corticosteroids 1470 decongestants 1 470 definition 1 382, 1 382 1', 1440 diagnosis 1442, 1469, 1474 dietary management 1473 enlarged turbinates 1 59 1-2 histopathology 144 1 immunotherapy 1473 investigations 1469 irritant avoidance 1470 lateral nasal wall anomalies 1 334 long-term prophylaxis 147 1-4 medical management 1469-77 surgery vs. 1 470 treatment aims 1470 mucocoeles 1 540 nasal polyps 437-8 postoperative treatment 438 systemic steroid use 438 topical steroid use 437-8 nitric oxide donors 1473-4 olfactory dysfunction 1 666, 1 667-8 ostiomeatal complex drainage 1474 paranasal sinus procedures 1482 T pathogenesis 144 1 predisposing factors 1469-70 systemic diseases 1469 prevalence 138 1 sinonasal malignancy 241 8 structural/anatomical abnormalities 1469 symptoms 1469 duration 1439-40 without nasal polyps 437 chronic sclerosing sialadenitis 1904
chronic suppurative otitis media ( CSOM) 935 F children balance problems 1 045-6 cochlear implantation 865 definition 929, 932 epidemiology 933, 934 F risk factors 933 T temporal bone squamous cell carcinoma 4087 see also chronic otitis media ( COM) chronic vestibular insufficiency (Dandy's) syndrome 3749, 3750 F Churg-Strauss syndrome 1 89, 1 653 Chvostek's sign 401 chylous fistula 2744 chylous injury 1 774 cidofovir juvenile-onset recurrent respiratory papillomatosis 1 178 laryngeal papillomatosis, paediatric 1 170 mechanism of action 1 178 papillomas 2238 cigarette smoking see smoking cilia larynx 763 replacement by squamous epithelium 763 nasal 764, 1360-1 action 1361 beat frequency 1 36 1 drugs, effects o f 1361 drying 136 1 microtubules 1 360 mucus flow 1361 septal 1327 structure 1 327, 1 327 F ultrastructure 1 360, 1361 F nasopharynx 766 cimetidine juvenile-onset recurrent respiratory papillomatosis 1 179 mucosal malignant melanoma 241 0 Cincinnati x-ray 1 143 cinnarizine Meniere's disease 3800 side effects 3797 vestibular attacks, acute 3796 1', 3797 ciprofloxacin dosage 432 malignant otitis extema 389 1 respiratory scleroma 1463 tympanic membrane perforation with discharge 937-8
1-1 3 1 2 are in Volume 1, pages 1 3 1 3-2810 are in Volume 2, and pages 281 1-4147 are in Volume 3.
I ndex . 41 8 1
circadian rhythms 2306 Circle of Willis, internal carotid artery test 3951 circumvallate papillae 1 794 cisplatin adjuvant radiotherapy 52 head and neck cancer 40 inner hair cell function 3849 mechanism of action 37 mucosal malignant melanoma 2410 nasopharyngeal carcinoma 2460 neoadjuvant 40 ototoxicity 3298-300, 3570-1 aetiopathology 3570 hearing loss attribution 3572 incidence 3300 natural history 3570 oxidative stress and 3300-1, 3301 F recognition 3571-3 risk factors 3570-1 salivary gland tumours, malignant 2 508 cisplatinum ototoxicity 3677 citrate phosphate dextrose (CPO) 255 Civil Procedure Rules ( 1 998) 598, 603,
604 Cladosporium 221 clarithromycin 23 1 chronic rhinosinusitis 1471-2 ototoxicity 3571 class switching, immunoglobulins 148 Claudius' cells 3 127, 3 1 28 F, 3 130 clavicular head 1 745 clavicular periosteal grafts 1 156-7 cleft lip see cleft lip and palate cleft lip and palate 996-10 1 8 airway and feeding 1002 associated syndromes 100 1 T bilateral 1 005, 1 005 F chronic otitis media 3409, 3428 classification 996-7 diagnosis 100 1 dysphagia 2030 embropathology 1 320 embryology 999, 1 320, 1 8 1 1-4 environmental factors 1000 epidemiology 997 gender differences 997 racial differences 997 genetic factors 999-1000, 999 T Greenspan model 1000 implant placement 2933-4, 2934 F labiomaxillary muscle function restoration 1 005, 1 006 F
management 1 00 1-10 general principles 1 002 presurgical orthopaedics 1 002-3 secondary surgery 10 10 surgery expectations 1 003 timing of surgery 1 004, 1 004 T normal 998-9, 998 F otitis media 1 003-4, 1 0 1 0-3 otitis media with effusion 903, 1 0 1 0-3 paediatric intensive care 546 pars tensa retraction 3428 Pierre Robin sequence 1 000-1, 1 00 1 F prenatal diagnosis 1001 research outcomes 1 002, 1 002 T septum abnormalities 1 570-1 speech disorders 993 syndromic 1 000 tympanic membrane disorders 934 unilateral 1004, 1 004 F, 1 005 F epidemiology 997 cleft lip nasal deformities, external rhinoplasty 2967, 2967 F bilateral deformity 2967 incisions 2962 unilateral deformity 2967 F cleft palate see cleft lip and palate click-evoked vestibular myogenic potentials (CEVMP) 3741-2 click sound, Fourier analysis 3 1 77 F,
3 178 clindamycin 1471
Clinical Evidence 653 clinical governance 568-80 basis for 570-1, 571 T definition 569, 569-70 implementation, barriers to 570,
570 T integration of approaches 569 F medical negligence 598, 2803 monitoring and inspecting 572-3 multidisciplinary teamworking 568,
576, 576-7 patient involvement 574-5 public involvement 574-5 quality assurance 573-4 standard setting 571-4 support 575-6 Clinical Governance Development Programme 575 Clinical Governance Support Team ( CGST) 654-5 clinical heterogeneity 663 clinical test of sensory integration and balance ('foam and dome' test) 3733-4, 3'734 F
clivus 298 clofazimine 1464 clonazepam diplopia 3804 idiopathic downbeat nystagmus 3804 tinnitus 361 7 cloning 19-20
Clostridium difficile 229 clot formation bone repair 94 disseminated intravascular coagulation 283-4 inflammation 89 clotrimazole 233, 430 clover leaf skull (Kleeblattschadel anomaly) 1028 cluster headache 1 722, 1 723 F c-myc, stem cell activation 67 CO2 laser see carbon dioxide (C02) laser coagulase-negative staphylococci 1 96-7 coagulase test, staphylococci 1 96 coagulation 279 coagulation disorders 281 T acquired 282-4 bleeding patterns 28 1 inherited 284-6, 284 T symptoms 280
see also individual disorders coagulation factors 279 activated platelets 278 fibrin formation 279
see also individual factors coagulation inhibitors 279 acquired 284 coagulation tests 280 epistaxis, children 1065 sodium citrate 280 co-amoxiclav 938 cobalt-chromium implants 1 19 coblation tonsillectomy 1 235, 1992 Coblator plasma field device 1097 'Coca Cola' bottle sign 1680 F cocaine cilia, effects on 1361 glossopharyngeal neuralgia 208 1 mouth ulcer induction 1 835 nasal surgery 442 nasal vasculature, effects on 1 365 septal perforation 1 582 COCH (DFNA9 ) gene mutations 3238 cochlea 3 126-46, 3 1 86-8 auditory nerve fibres, nonlinear interactions 3 198-9 conditions 3537-8
Pages 1-1 3 1 2 are in Volume 1, pages 1 3 1 3-28 10 are in Volume 2, and pages 28 1 1-4147 are in Volume 3.
4 1 82 I I ndex
cochlea (continued) drug-induced ototoxicity 3298-300,
3299 T fluid spaces 3 1 86, 3 186 F function otoacoustic emissions 3842 petro us apex lesion management and 4050 gross morphology 3 1 26, 3 127 F hair cells see cochlear hair cells hearing 3 186-8 electrical responses 3 196-7, 3 1 96 F mechanics 3 189-92 impedance 3 176, 3 1 8 1 implants see cochlear implants ( CI ) innervation, centrifugal 3200 lesions neurophysiology 3606 Pendred's syndrome 400 serotonergic system 3607 tinnitus 3606-7 tonotopic reorganization 3607 Mondini abnormality, CT imaging 1 298 F ossification, meningitis-related 3652 potassium ions 3 186-7 sharply sloping high frequency hearing loss 3850, 3850 F sound detection 3462, 3463 F conductive hearing impairment 3462 ultrastructure 3 127-32 future research areas 3 140 knowledge deficiencies 3 140 vestibular schwannoma invasion 3959-60 cochlear aqueduct bone conduction 3 1 85 vertigo, children 1046 cochlear blood flow, noise-induced hearing loss 3549 cochlear duct 3540-1 age-related embryology 806-7, 807 F lateral wall cells 3 1 30 structure 3 127-30, 3 128 F cochlear echoes 3 183, 3200-1, 3201 F cochlear endosteum, otosclerosis 3456-7 cochlear fluids composition 3 187-8 electrical potential 3 187-8 impedance 3 1 8 1 see also endolymph; perilymph
cochlear hair cells calcium channel dysfunction, tinnitus 3605 degeneration 20 drug-induced tinnitus 3600 drug/noise-induced ototoxicity 3298-300, 3299 F,
3299 T incidence 3300 molecular mechanisms 3300-1 see also ototoxicity electrical responses 3 194-6 inner see inner hair cells (IH C) innervation 3200 outer see outer hair cells (OHC) regeneration deafness 8 1 8 stem cell therapy 7 5 resistance 3 192-3 stereocilia tip links 3 1 92, 3 193 F transduction 3 192-4 ion channels 3 193-4, 3 1 94 F shear forces 3 192-3, 3 193 F vertebrate similarities 3301 cochlear implants (CI) 3649-59 auditory neuropathy/ dyssynchrony 3852 electrically evoked compound action potential 3852, 3853 F candidature 3650-1 audiological 3650-1 imaging 3651 medical 3651 otological 3651 psychological 3651 central pathways and processing 3650 children see paediatric cochlear implantation clinical outcomes/benefits 3654-6 predictive factors 3655-6 quality of life 3655, 3656 complications 3654 facial nerve stimulation 3654, 3655 incidence 3652 meningitis 3654 vertigo 3654 cost-effectiveness 3656 deafness duration and 3655 devices 365 1-2, 3653 T failure 3654 safety 3652 functional magnetic resonance imaging 681 glass ionomer cement fixation 120 hearing aids vs. 3636
medical negligence 1306 middle fossa surgery 4023-4 otological contraindications 3651 ototoxicity-related hearing loss 3573 rationale for 3649-50 silicone elastomer 1 22 speech processing strategies 3650 surgical approaches 3652-4 cochlea access 3652 cochlear abnormalities 3652-4 surgical outcomes 3652, 3654 tinnitus 3614-5
Cochlear implants: Principles and practices 3656 Cochlear Implant Study Group (CISG) , U K 3656 cochlear microphonics 3844 T auditory neuropathy/ dyssynchrony 3840, 3843, 3844 T definition 3843 transtympanic electrocochleogram 3843 cochlear nerve auditory function monitoring see auditory function monitoring surgical damage 750 vestibular schwannoma invasion 3957 cochlear nucleus complex 3 140-1 , 3 142 F cochlear potentials 3280-1, 3282 F decl)m]:)res�;ion 3516 ear canal recordings 3281 electrodes 3281 , 3282 F intraoperative monitoring 3292-3 invasive recording 3280-1 noninvasive 3281 surface reCiording 328 1 trarlstVn1p,:tlllC 3280-1 waveforms 3281 , 3282 F cochlear travelling wave 3 1 89, 3 1 90 F cochlear sensorineural hearing loss 3 1 99, 3 1 99 F components 3 1 9 1-2 cochleolabyrinthitis see bacterial labyrinthitis cochleosaccular abnormalities 8 1 1-2 cochleosaccular deafness 8 1 1-2 cochleostomy 3652, 3652-4 cochleotopic gradient of susceptibility 3569 cochleovestibular dysfunction, acute 3582 Cochrane Central Register of Controlled Trials 646
Pages 1-13 1 2 are in Volume 1, pages 1 3 1 3-28 1 0 are in Vol{:.me 2, and pages 281 1-4 147 are in Volume 3.
Cochrane Collaboration 647-8, 647 T,
662 Cochrane Database of Systematic Reviews 662 Cochrane Library 662 coded excitation, ultrasound advances 7 1 3 codeine 2786 codes of conduct 582 codominant inheritance 18 codon 3, 1 5 coeliac disease 1 7 1 cerebellar ataxia 3775 salivary gland physiology 1 866 Cogan's syndrome 3680-1, 3757 benign paroxysmal positioning vertigo aetiology 3760 clinical manifestations 3754 cognitive behavioural techniques ( CBT), tinnitus 361 4, 3616 cognitive function pure-tone audiometry and 3265 speech audiometry and 3273 743 coherent, laser cohort studies epidemiological research 627 evidence-based medicine 655 terminology 627 coils, embolization 733 coinheritance 1 1 COLlAl gene 3458 cold dry air (CDA) challenge, idiopathic rhinitis 1 409 cold receptors, nasal 1364 'cold steel' tonsillectomy 1 232-3,
1 233 F cold water exposure, exostosis and
3367 anima studies 3367 collagen(s) chemical modification 123 as embolic agent 733 hypertrophic scars 3090 keloids 289 1-2, 3090 polarization-sensitive OCT 758 remodelling, wound healing 93 tissue scaffolds 1 23, 123 F clinical applications 1 23 types 1 23 injections, vocal fold paralysis 450, 2240, 2245 T contraindications 450 Collet-Sicard syndrome 2080 T,
3938 collimated laser light 743
colloid goitre 331 , 720 colloids cardiovascular resuscitation 529 transfusion 257 colour-coded duplex ultrasonography (CCDU) 686-7 colour-flow duplex Doppler ( CFD) , vascular neck injury 1772 colour vision, thyroid eye disease
344 columella 1 325 anatomy 2996 retraction, surgical complication 3004, 3092 revision rhinoplasty 2982 short, management of 1005 columella strut 2964 F columnar cells, septum 1 327 combination chemotherapy 40 intraarterial 735 combined approach tympanoplasty see intact canal wall mastoidectomy 'Commission E' monographs, herbal medicines 408 Commission for Healthcare Audit and Inspection 569 Commission for Health Improvement
569, 572 Commission for Patient and Public Involvement in Health ( CPPIH) 574 Commission for Social Care Inspection (CSCI) 572 Committee on Professional Performance 606 Committee on Safety of Medicines (CSM) 408 common canaliculus 1 690 obstruction 1 696 canaliculodacryocystorhinostomy
1 696 Lester-Jones tube insertion 1 696 common carotid artery 1 749 common cold (infectious rhinitis) causative agents 205 T children 1076 corticosteroid treatment 42 1 common variable immunodeficiency ( CVI) 1 75 T, 1 76 communication palliative care, head and neck cancer 2782-3, 2783 T skills 554 T surgeons see surgical training voice quality and 2 1 70
communication, medical consultations 559-67 acquired hearing loss 566 bad news see breaking bad news biomedical approach 559-60 core skills 564-6 dealing with loss 565-6 eye contact 565 hearing loss 566 'heart-sink' patients 565 jargon 562 listening 564 with 565-6 loss, medical negligence and 2804 models/styles 559-60, 560 F, 563-4 doctor-centred 559-60, 563 F nonverbal cues 564, 565 paternalism 582 patient-centred approach 559-60,
560-4 compliance 562-3 ethical framework 56 1-2 Pendleton's model 563 power issues 560-1 seat/desk arrangements 564, 564 F training 554 T community effect 68 Community Health Councils 574 comparative audit 2376 comparative genomic hybridization ( CGH) 6-7 compensatory turbinate hypertrophy 1590-1 , 1 59 1 F complaints communication skills 554 T medical negligence issues 2803-4 complement 1 39 activity tests 1 69 alternative pathway 1 39, 139 F deficiencies 1 79 cellular cytotoxicity 4 1 classical pathway 1 39, 1 39 F deficiencies 178-9 deficiencies 1 78-9 mannan-binding lectin pathway
1 39 F nasal secretions 1 360 pathway levels, measuring of 1 69 terminal pathway defects 1 79, 1 79 T complement -dependent opsonization, acute otitis media 916 compliance communication, medical consultations 562-3 definition 562
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4184 . I n dex
composite cartilage grafts 2825 nasal reconstruction 3022-3, 3024 F size 30 1 8 composite fibular flap, mandibular resection 2558-9, 2558 F, 2559 F composite mandibular defects 2886-7 issues 2886-7 options 2887, 2887 T problems 2887 compound action potentials (CAP ) , auditory neuropathyl dyssynchrony 3844 T compound muscle action potentials (CMAP) facial nerve monitoring 748, 749 outcome prediction 749-50 facial nerve paralysis 3879 compressed speech test, central auditory dysfunction 3860 compression ( descent) injuries 3503 F, 3504-6 physiological consequences 3502-3 compression inner ear barotrauma see inner ear barotrauma computed tomography ( CT) adenoid cystic carcinoma 2499 arachnoid cysts 401 3 cerebrospinal fluid rhinorrhoea 1638, 1639 F
cervical lymph node assessment 1 760-1 children 1 297, 1 298 F choanal atresia 1297 cholesteatoma 343 1-2, 3432 T chronic otitis media 3419, 3420 T false positive findings 34 1 9-20 chronic rhinosinusitis 1479 T, 1480 F cochlear implantation 863 concha bullosa 1 592 craniosynostosis 1 022, 1 023 F dacryocystorhinostomy preoperative assessment 1691 dysphagia 1 967-8, 2028 ectopic parathyroids 392 encephalomeningocoele 1035, 1035 F epidermoids 40 1 1 epiglottitis 2250 external auditory canal exostosis 3367 facial nerve 388 1 , 3883 F frontal sinus 1 502 frontal sinus osteoma 1 502 F fungal rhinosinusitis acute fulminant 1455 allergic 221, 1453-4, 1453 F chronic invasive 2 1 8
invasive 2 1 8 noninvasive 2 19-20 fungus ball 1452, 1452 F glioma 1 505 F glomus temporale tumour 4032 head and neck sarcomas 193 1 hyperparathyroidism 392 hypopharyngeal cancer 2643-4, 2643 F
hypothyroidism 336 implant osseo integration 29 1 1-2 inverted papilloma 1 503 F, 1 523 jugular foramen lesions 4029, 4042 juvenile angiofibroma 2 124, 2438-9, 2439 F
laryngeal stenosis 2279-80 laryngeal trauma 2273 3D scans 2273 laryngeal tumours 2607, 2607 F laryngopyocoele 2255, 2256 F larynx 1 297 lipomas 401 3 malignant otitis externa 3338 meningiomas 736, 4009 metastatic neck disease 2720 mucocoeles 1 533-4 ethmoidal 1 533 F, 1 534 F frontal 1 533 F, 1 534 F sphenoid 1 534 F mucosal malignant melanoma 2409, 241 1 F
nasal endoscopy and 1 344 inflammatory diseases 1 350, 1 350 F nasal inflammation 1 3 50, 1 350 F nasal polyposis 1 553, 1 553 T nasopharyngeal carcinoma 2456-7, 2457 F
nasopharyngeal tuberculosis 2 1 2 1 neck 1 755 neck trauma 1769 neurofibromatosis 2 4002 nodular thyroid disease 333, 334, 3 6 1 , 362, 2677
objective tinnitus 360 1 oesophageal carcinoma 2068, 2068 F olfactory dysfunction 1666 orbital cellulitis 1 542-3, 1 545 F orbital floor fractures 1 630-1, 163 1 F otalgia 3534 otosclerosis 3464 disease 3488 paragangliomas 736-9 parapharyngeal space tumours 2525 F, 2530
parathyroid glands 384
peritonsillar abscess 1997 petrous apex chondrosarcoma 4049, 4050 F
petrous apex cysts 4047, 4048, 4048 F, 4049 F
petrous apex tumours 4048 pituitary gland 306 pituitary tumours 306 craniopharyngioma 4 103-4 malignant 4 1 04 nonfunctioning adenomas 4103 technological advances 307 prolactinoma 305 prosthetic reconstruction 2941 retropharyngeal abscess 1 223, 1 223 F
rhinosinusitis 1442-3 salivary gland calculi 1880, 1 880 F salivary glands 1 8 76-7, 1 877 F advantages/disadvantages 1 874 T artefacts 1 876-7 contrast media 1 876-7 indications 1 890 T slice thickness 1 876 salivary gland tumours, malignant 1 885, 2506-7, 2506 F sarcoidosis diagnosis 1648, 1649 F schwannomas facial nerve 4014 trigeminal nerve 40 14 vestibular 3959 sinus surgery 306 skull base lesions 3947 snoring 2329 subperiosteal implants 2902-3 surgical implications 5 5 1 temporal bone fractures 3495, 3495 F
temporal bone tumours 4069, 4090, 4090 F
thyroid cancer 333 thyroid eye disease 344 thyroid gland 328 tinnitus 3610 tuberculous otitis 3449 vestibular schwannoma 3959 Wegener's granulomatosis 1 65 1 F, 1652, 1 652 F
computed tomography cisternography 1638 computer-aided design, computer aided manufacture (CADCAM) , subperiosteal implants 2902-3 computer-assisted surgery rhinosinusitis 1484
Pages 1-1 3 1 2 are in Volume 1, pages 1 3 13-2810 are in Volume 2, and pages 28 1 1-4147 are in Volume 3.
computer assisted three-dimensional (3D) navigation systems, jugular foramen surgery 4034 computerized dynamic posturography (CDP) systems 3733 computer software, prosthetic reconstruction 294 1 concha bullosa 1 334 F, 1 335 T conchae see turbinates conchal cartilage grafting augmentation rhinoplasty 2973, 2974 F nasal reconstruction 3023 pinna reconstruction 3033 saddle nose 2975-6 conchal crest 1 34 1 condenser microphone 3 169-70 conditioned taste aversions, cancer treatment 1 844 conductive audiogram, otosclerosis 3827 conductive hearing impairment 8 1 1-2 active mucosal chronic otitis media 3423-4 bone-anchored hearing aids bilateral 3646 unilateral 3644-6, 3646 otitis media with effusion, childhood 892-3, 893 T otosclerosis 3456, 3465-6 aids 3467 post-stapes surgery 3475 tuberculous otitis 3448 conduit devices, nervous tissue engineering 1 26 condylar neck fractures 1622, 1 624-5 condylomas, oral 1 828 cones 3914 The Confidential Enquiry into Perioperative Deaths ( CEPOD) 478-9 confidentiality 602 data collection, head and neck cancer 2374 ethical issues 586-7, 589 medical negligence and 2805 see also disclosure confounding 624-5 confusional states, acute see acute confusional states congenital cytomegalovirus childhood deafness 846, 85 1 vertigo 1 048 congenital deafness 845-7 drug therapy 8 1 8 genetic manipulation 8 1 7-8
intervention timing 8 1 8 prenatal tests 8 1 8 congenital ear defects, paediatric anaesthesia 5 1 4 congenital hypothyroidism (cretinism) 400 clinical features 400, 2667 incidence 400 neonatal iodine deficiency 356 treatment 400 congenital isolated stapes ankylosis 870 T, 87 1-2 congenital nasal cysts 1 073-4 congenital nasal masses 1074-6 congenital nystagmus 3725, 3725 F, 3922
congenital oesophageal stenosis 1287-8 clinical features 1287 diagnosis 1287-8 treatment 1 288 congenital ossicular abnormalities classification 869-70, 870 T clinical presentation 87 1 definition 869 incidence 870-1 investigation 871 investigations 87 1 isolated non-stapes anomalies 870 T, 872
management 871-3 principles 871 congenital permanent bilateral hearing loss 823-4 risk factors 824 congenital rubella syndrome (CRS ) 846, 846 F
congenital sideroblastic anaemia 269 congenital stapes footplate fixation 872 congenital subglottic stenosis 1 139-40, 1 1 39 F
airway compromise 1 1 39 diagnosis 1 1 39 grading 1 139-40 surgical options 1 1 39 congenital syphilis childhood deafness 846 infant 1462 nasal 1462, 1 703 puberty 1 462 treatment 1462 congenital venous malformations, ultrasound examination 726
Conidiobolus coronatus 2 1 5 conjuctivochalasis, post blepharoplasty 3065
conjugate gaze palsy 3920
Connecting for Health 570 connective tissue diseases 1 7 1 1-3 ENA antibodies 170
see also specific disorders connexin(s) 68 definition 68 connexin 26 mutation 8 1 8 consensual light reflex, blind eye 3916
consent anaesthesia 462-3 children 585-6 medical research 589 ethical issues 585-6 research participation 589 facial plastic surgery 3089 Jehovah's Witnesses 601 laryngoscopy 2 1 47 medical negligence 600- 1 , 1 732, 2806-7
tonsillectomy 1308 mental incapacity 601 paediatric consultation 780-1 postoperative bleeding and 1 308 process 462 risk perception 563 surgery 46 1-2, 551-2 treatment refusal 586 consent forms 462 conservation neck dissection, N2c disease 2726 conservative parotidectomy cosmetic defects 2484 facial nerve identification 2485 F informed consent 2483-4 procedure 2484-7 consonant discrimination tests 841 consonants 2 166 manner of articulation 2167 paired 2 1 67 place of articulation 2 166-7 consonant-vowel sequences 2 172-4 constant domains/regions, antibodies 1 3 5 constipation, palliative care patients 2791 management 2791 , 2792 T symptoms 2791 constrictor muscles, pharynx 1 947, 1 947-9, 1 948 T, 1 949 F, 1955
construct validity 635 consultation communication see communication, medical consultations
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4186 1 I ndex
consumerism consultation style 560, 560 F doctor-patient relationship 582 contact dermatitis external nose 1 7 1 4-5, 1 7 1 5 food 1 contact endoscopy 762-8 chronic laryngitis 2260-1 current knowledge/future research 767 historical aspects 762 larynx 763-4 abnormal appearance 763-4, 765 normal appearance 763 method/technical details 763 methylene blue staining 762-3, 763 microvascular changes 762-3, 764 nasal cavity 764-6 abnormal appearance 764-6 normal appearance 764 utility 764 nasopharyngeal carcinoma 766-7 nasopharynx 766-7 abnormal appearance 766-7 normal appearance 766 oral cavity 767 utility 762-3, 767 microvascular changes 762-3 contact granuloma see arytenoid granuloma contact pachydermia see arytenoid granuloma 'contact point pain' 1 723-4 contact quotient measurement, voice evaluation 2 1 79 contact ulcer see arytenoid granuloma contact urticaria 1 content validity 635 continuing professional development see surgical training continuous positive airway pressure (CPAP) acute airway obstruction 1 124 compliance and troubleshooting 2321 masks 2320 obstructive sleep apnoea 1 1 08-9, 1 5 9 1 , 2320-1
paediatric tonsillectomy 5 1 5 side effects 2321 titration 2320-1 treatment failure 232 1 continuous renal replacement therapy (CRRT) 530 continuous-wave Doppler ultrasound 714
contralateral routing of signals (CROS) hearing aids 3640-1, 3646 contrast-enhanced CT (CE-CT) salivary gland tumours 1 885 sialadenitis, acute 1 880, 1881 F contrast swallow aspiration investigations 2096 pharyngeal pouch 2044, 2045 F conus elasicus 2 1 34 convection, nasal 1 356 Cooperative Study of Sickle Cell Disease 27 1 co-operative test, hearing 841 COOP-WONCA system, post laryngectomy rehabilitation 2630
Copenhagen allergy study 1 560-1 cophenalcaine( tm), epistaxis 1 064 coping skills, head and neck cancer patients 2777 'copper-beaten appearance,' raised intracranial pressure 1 023, 1 024 F coral, bone repair 124, 125 F cordal polyposis see Reinke's oedema cordectomy 26 1 3 Corlan see hydrocortisone corneal abrasion prevention, post blepharoplasty 3066 corneal irritation, post blepharoplasty 3065 corneal protectors eyelid surgery 3095 unilateral facial palsy 3079 corneal reflex 3923 absence 3923 skull base lesions 3946 corneal ulceration, thyroid eye disease 344 corniculate cartilages 2 1 33 coronal approach, zygomatic complex fractures 1629 T coronal synostosis 1025 bilateral 1 022 T, 1025 genetic testing 102 1 surgery 1025-6 unilateral 1 022 T, 1025 coronavirus 205 coroners medical jurisprudence 602-3
reportable deaths 602 cor pulmonale 1 1 36 corpus callosum, central auditory dysfunction 3857-8, 3862 corpus luteum 302
cortical mastoidectomy active mucosal chronic otitis media 3425 vestibular schwannoma, translabyrinthine approach 3969-70, 3969 F corticobulbar tract, phonation 2 1 58 corticosteroids 4 1 8-28 adenoids 422 allergic rhinitis 41 9-20, 1 398-9 allergy 1 53 angioedema 42 1 anosmia 42 1 Bell's palsy 424, 3886 chronic rhinosinusitis 1470 cilia, effects on 1361 critical care patients 536 croup 422, 1 128-9 density 4 1 8 ear drops 4 1 9 enlarged turbinates 1 592 eosinophil apoptosis induction 62 epiglottitis 422 facial palsy 424 hyposmia 42 1 idiopathic rhinitis 420 idiopathic sudden sensorineural hearing loss 1, 423, 3584-8, 3585 T, 3589, 3589 T
infectious mononucleosis 422, 1225, 2004
intramuscular depot-injection 419 intranasal 419 children 420 side effects 419 intravenous 4 1 8-9 jugular foramen lesions 4042 keloids 2893 laryngeal trauma 2274 Meniere's disease 423-4 mononucleosis 422 mucous membrane pemphigoid 1 834
myasthenia gravis 2077 nasal function 1 366 nasal polyposis 42 1, 437-8, 1470, 1554-5, 1 555
adverse effects 1 555 nasal airway patency 1 554 recurrence 1554-5 responsiveness 1 554 rhinitis symptoms 1 554 safety 1 555 sense of smell 1 554 size reduction 1 554, 1 554 F
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-�
I ndex I
obstructive sleep apnoea 1 1 10 oesophageal corrosive injury 1291 olfactory dysfunction 1 670-1 oral 4 1 9 otitis extema 422-3, 430 otitis media acute 423 chronic 423 otitis media with effusion 423, 895 pharmacodynamics 4 1 8 pharmacokinetics 4 1 8-9 pharyngitis 422 pregnancy 420 recurrent aphthous stomatitis 1 830-1 replacement after hypophysectomy 41 1 1 rhinitis medicamentosa 421 rhinosinusitis 436-8 sarcoidosis 424 scar revision 2898-9 sepsis 536 side effects 4 1 9 sinusitis 4 2 1 Sjogren syndrome 1 9 1 3 sudden sensorineural hearing loss 434 thyroid eye disease 345 tonsillectomy 422 topical allergy 1 53 medical negligence 3831 otitis media with effusion 895 rhinosinusitis, paediatric 1083 upper airway obstruction 2288 vestibular attacks, acute 3797 vestibular neuritis 3756 Wegener's granulomatosis 424
see also individual corticosteroids corticotrophs, pituitary gland 297 factor (CRF) corticotropin test 3 1 0 corticotropin-releasing hormone 300 cortilymph 3 1 89
Corynebacteria 195-6, 1 98-9 Corynebacterium diphtheriae 198-9, 199 F, 1 1 30, 2079, 2252
Corynebacterium ulcerans 1 98-9 Coryzal syndrome 207 cosmetics, scar revision 2899 costal cartilage augmentation rhinoplasty 2972, 2973 calcification 3044-5 laryngotracheal reconstruction 52 1 pinna reconstruction 3033-5, 3038 F h ", r"\Tpc1T ncr
3036
postoperative pain 3036
Costen's syndrome 3530 costochondral grafting, hemifacial microsomia 1033 cotrimoxazole 1653 Cottle and van Dishoeck nasal surgery 1 577 cough/ coughing larynx in 2 1 59, 22 17 pertussis 2252 cough medicines 449 over-the-counter preparations 449 cough suppressants 449 coup/contrecoup injury 1 667 cover/body theory 2 160 Cowden's disease 2671 cow's milk allergy 1425, 1 427 Coxsackie virus, mouth ulcers 1 833 Cox's proportional hazards model hypopharyngeal cancer 2653-5 mucosal malignant melanoma survival 24 12-3, 24 13 salivary gland tumour survival 2514
crack cocaine, septal perforations 1 582 Crane principle, skin grafts 282 1 cranialization, frontal sinus 1 5 1 8 fractures 1507 operative technique 1 5 1 8 postoperative complications 1 5 1 8 results 1 5 1 8 cranial nerve( s) 391 1 diabetic neuropathy 402 group 1 39 1 1-22 group 2 3923-33 group 3 3933-40 lower skull base lesions 3945 surgery-induced injury 4 1 37 neck trauma 1 767 otalgia 3527 preservation, vestibular schwannoma 3992 pretrematic branch 1 052 surgery-induced injury 4 136-7 meningioma surgery 40 1 0- 1
see also individual nerves cranial nerve 0 (terminal nerve) 1 662 cranial nerve palsy isolated 4 144 lower, vestibular schwannoma removal 3980-1 post-jugular foramen surgery 404 1 rabies 2079 temporal bone resection ' complication 4094
cranial neuropathies, vestibular schwannoma removal 3979-8 1 cranial root injury, glossopharyngeal neuralgia 353 1 cranial sutures 1 020 craniectomy craniosynostosis 1024 vestibular schwannoma 3974 craniofacial and skull base surgery 4 1 1 9-34 approaches 4 127-32 complications 4 132-3, 4 1 32 F historical aspects 4120 postoperative CSF leakage 4127 results 4 132-3 surgical anatomy 4 120-2 surgical principles 4 127 surgical team 4 1 20 survival figures 4 1 33, 4 133 T
see also individual techniques craniofacial anomalies 1 0 1 9-39 chronic otitis media 3409 classification 1 0 1 9-20 future research areas 1 037 genetics 1021 knowledge deficiencies 1037 management 1 0 19-39 principles 1 0 1 9 multidisciplinary team 1 020 T otitis media with effusion 903 prenatal diagnosis 1021 reconstruction 2926
see also individual anomalies craniofacial bone repair, tissue engineering 124, 125 F scaffold types 124 craniofacial clefts 799, 802 F, 1 035--6
aetiology 1 035 classification 997, 1 036 clinical features 1036, 1036 F management 1036 craniofacial resection, anterior see anterior craniofacial resection craniofacial resection (CFR) anterior see anterior craniofacial resection anterolateral see anterolateral craniofacial resection historical aspects 4120 lateral, sinonasal malignancy 2434
type 1 243 1 type II 243 1-3 type III 2433, 2433 F
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4 1 88 I I nd ex
craniofacial surgery paediatric intensive care 546 skull base surgery and see craniofacial and skull base surgery craniofrontonasal syndrome 1028 craniomandibular joint see temporomandibular joint (TMJ) craniopharyngiomas 2033, 4 103-4
craniosynostosis 1 020-7 aetiology 102 1 classification 1 020 clinical assessment 1 022, 1 022 T
clinical consequences 102 1-2 cranial volume 102 1-2 definition 1 020 differential diagnosis 1 024 endoscopic treatment 1 027 familial 102 1 genetics 8 1 3 1', 1 02 1 hydrocephalus 1 023 imaging 1 022, 1023 F incidence 1021 nonsyndromic aetiology 102 1 definition 1020 incidence 102 1 raised intracranial pressure 1 023 single suture 1 025-6 pathogenesis 1 02 1-2 prenatal diagnosis 1 02 1 primary 1 020 raised intracranial pressure 1 022-3, 1 024 F
restenosis 1 024, 103 1 secondary 1 020 surgical management 1 024-5 indications 1 024 timing 1 024 surgical outcomes 1 0 3 1 reoperation rates 103 1, 1 0 3 2 T syndromic 1027-3 1 aetiology 1 02 1 airway management 1 028 correction 1 029 definition 1 020 feeding problems 1029 incidence 102 1 management 1 028 raised intracranial pressure 1 023, 1 029
surgical complications 1 030-1 blood loss 1030-1 surgical procedures 1029
surgical timing 1 029 visual complications 1028-9 types 1 022 T craniotomy cerebrospinal fluid rhinorrhoea 1 636-7, 1 640 extended/basal frontal approach 4130-2 contraindications 4130-2 indications 4 1 30 middle fossa 3449, 4020 vestibular schwannoma 3975 C-reactive protein (CRP) 168 creaky voice (vocal pulse register) 2 1 6 1 , 2 1 62 T
creatine 380-1 crescentric advancement 2834, 2839 F CREST syndrome 1 7 1 2-3, 203 1 cretinism see hypothyroidism (cretinism) Creutzfeldt-Jakob disease (CJD) cerebellar ataxia 3775 variant see variant Creutzfeldt-Jakob disease (vCJD) criatricial tracheal stenosis 2283 cribiform plate 3897, 4 120 development 1 3 1 8 Crib-o-gram 3290 cribroethmoid foramen 4 1 20 cricoarytenoids 2 1 36 T cricoid cartilage 2 1 33 , 2 1 33 F development 2 130 integrity, tracheostomy 2301 surface anatomy 1740 cricoidectomy, intractable aspiration management partial submucosal 2 1 0 1 subperichondrial 2 1 00, 2 1 0 1 F cricoid grafting, posterior glottic stenosis 1 16 1 cricoid hook, tracheostomy 2296 cricoid pressure, anaesthesia 496 cricoid ring, children 1 1 5 1 cricopharyngeal myotomy intractable aspiration 2098, 2099-100 neurological dysphagia 208 1 pharyngeal pouch 2049, 2054, 2059 cricopharyngeal spasm barium swallow appearance 2027 F management 2097 cricopharyngeus 1 947, 1 948 1', 1955 innervation 1 948 1', 1950 spasm, pharyngeal pouch aetiology 2045-6 cricothyroid artery 2 1 39
cricothyroid ligament 2 1 34 cricothyroid membrane (CTM) 476 laryngeal trauma 2271-2 cricothyroid muscle 2 1 36 T muscle tension dysphonia 2204 paralysis, vagus nerve lesions 2223 pubertal changes 2205 cricothyroidotomy 2294 equipment 2294 F neck trauma 1766-7 upper airway obstruction 2288, 2290-1
cricothyrotomy,difficult airways 477 cricotracheal ligament 2 1 33-4 cricotracheal resection (CTR) 1 163-4, 1 163 F
cricovocal 2 1 34 cri-du-chat syndrome 1 138 Crile ( Y type) incision 273 1-3 criminal law 607-9 crista ampullaris 3 1 53-4, 3 153 F hair cells 3228 ototoxic drugs 3677 F crista ethmoidalis 1 598 crista galli 1 3 1 8, 4 1 20 criterion validity 635 critical appraisal skills 649-72 basic principles 65 1-2 bias 652, 659 diagnosis articles 654-8, 656 1', 668, 670 F
levels of evidence 649, 665-8, 666 question formation 650, 651-2, 652-4, 653 F
statistics 652 systematic reviews 649, 650, 661-5, 67 1 F
treatment articles 653, 658-6 1 , 668, 67 1 F
validity 649-52 , 654-5 value 649-50 worksheets 668, 669 F, 670 F, 67 1 F critical bandwidth (CB) 3247 critical bandwidth for loudness summation 325 1 critical care 526-41 activated C protein 535-6 airway management 533 cardiovascular support 528-30 children see paediatric intensive care communication with relatives 536 definition 526-7 early goal-directed therapy 535 end of life issues 536-7 ENT, interface between 533-4
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I nd ex . 4 1 89
evidence-based strategies 535-6
'cued speech' 3 8 5 1
fluid therapy 529, 532 T
cuffed tracheostomy tubes 2298
immunonutrition 532-3
anaesthesia 492-3
nutritional support 530-3, 532 T
children 1201
cutaneous lesions, neurofibromatosis 2 400 1 , 400 1 F
organ system support 527-33 post-head/neck trauma 533
cuneiform cartilages 2 133
cuticular plate, stereocilia 3 1 32-3, 3 132 F, 3 1 33 F organization 3 1 34
cup ears 973
Cyamopsis tetragonoloba 1 4 1 8
post-surgery care 533
cupula biomechanics 32 1 1
respiratory support 527-8
deflection 3 2 1 2
severe sepsis 534-5 investigations 534, 534-5 treatment limitations 537
deflection, head angular velocity 3 2 1 2
cyclic adenosine 3', 5 ' ,-monophosphate (cAMP) salivary secretion 1 859-60 thyroid cancer 2670
deviation 3 1 54-5
cyclical neutropenia 177 T, 1 78
displacement 3 2 1 2
cyclin(s) 58 cyclin A 2382
renal support 528-30
critical closing pressure, blood vessels 1 12 Crohn's disease dysphagia 2032 oral manifestations 1828 ulceration 1 828, 1 834 salivary glands 1 906
hair cell movement 3230 function 3 1 53-4 hair cells 3228
hypopharyngeal cancer 2636
structure 3 1 53-4 cupulolithiasis 3678-80, 3 760, 3761 post-rotation manoeuvres 3 8 1 4
Cronbach's alpha 636, 641
cupulometry 3740 curare notch, capnograms 499 F
cross-facial nerve graft 3080, 3080 F
curriculum development project,
cross-sectional studies, epidemiology 626-7 croup 1 1 28-9, 225 1 causative agents 205 T, 1 1 30, 225 1 clinical features 1 128, 225 1 incidence 1 128, 225 1
cyclin D 1 2382
training 553, 554 T, 555 T
cyclizine motion sickness 3795 nausea and
head and neck
cancer 2787-8 vestibular attacks, acute 3795, 3796 T
cyclo-oxygenase 2 (COX-2) inhibitors 41
Curvularia rhinosinusitis 22 1, 1452-3
fungal rhinosinusitis 2 17, 1450 T Cushing's disease 309-1 1 , 4 1 0 1-2
cyclophosphamide side effects 4 1 5, 1 652-3 Sjogren syndrome 1 9 1 3 Wegener's granulomatosis 1 652-3
investigations 2251
causes 401
cyfra 2 1 - 1 2386-90 T
management 1 128, 225 1
Cushing's syndrome vs. 3 10-1
cyst(s) arachnoid see arachnoid cysts
corticosteroids 422, 1 1 28-9
diagnosis 4 1 0 1
medical negligence 1 309
medical management 4 102
botryoid odontogenic 1 925
pac�d.latrlc intensive care 545 stridor 1 128
pituitary adenomas 304
branchial see branchial cysts
pituitary hyperplasia 304
bronchial 1 147, 1782
subglottic oedema 1 128, 225 1
presentation 4 1 0 1
bronchogenic 1 147
tests 3 10-1
bursa pharyngeal embryonalis
Crouzon syndrome 968, 1 027, 1 7 1 3,
postoperative period 3 1 2
2 120
clinical features 1 027
treatment options 4 102
(Thornwaldfs) 1 074, 2 122 CPA tumours 4014
distraction osteogenesis 1 030 F
medical treatment 4 1 02
definition 1 922
incidence 102 1 , 1027
radiotherapy 4 1 02
dentigerous 1074, 1924, 1924 F
nasopharyngeal airway 1 109 nasopharyngeal narrowing 2 120 cryoglobulinaemia 1 7 1 cryoprecipitate 2 5 8 T, 259 disseminated intravascular coagulation 259, 284 cryosurgery, basal cell carcinoma 2397 cryptococcal meningitis, HIV
see also Cushing's syndrome Cushing's syndrome 309-1 1 , 4 1 0 1
dermoid see dermoid cyst dysontogenetic cysts 724
aetiology 3 10, 40 1
frontal sinus see frontal sinus cysts
Cushing's disease vs. 3 1 0-1
gingival
diagnosis 309-10, 4 1 0 1-2 hypokalaemic alkalosis 3 1 0 screening 309
see also Cushing's disease cuspid teeth see canines
adults 1926 of infancy 1 926 globulomaxillary 1320-1 jaws see jaw cysts
cryptococcosis 1 703-4
cusplet of Carabelli 1 804
lateral cervical see branchial cysts lymph nodes 7 1 7, 7 1 7 F, 7 1 8 F
Cryptococcus neoformans, HIV
cutaneous axial median forehead
lymphoepithelial 245-6, 245 F, 1 9 14
patients 247
patients 247
flap 2846, 2848, 2844 F
'machinery oil' 4 103
cryptotia (hidden ear) 973, 974 F
cutaneous cysts, nasal 1 708-9
nasal 1073-4, 1 708-9
crystal arthropathies 1 8 8
cutaneous defect reconstructions 2887
nasolabial (nasoalveolar) 1074,
crystalloid fluids 529 crystalloids 257
issues 2887 options 2887
1 320- 1 , 1926
nasopalatine duct 1926 F
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4 190 I I ndex
cyst(s) (continued) odontogenic see odontogenic cysts palatal, of infancy 1926 parotid gland 1246, 1246 F periapical 1 8 1 7 petrous apex 4047, 405 1 F radicular see radicular cyst Rathke's pouch 4103 residual 1 8 17, 1924 saccular 1 1 36-7, 1 1 3 7 F simple (solitary) bone 1926-7 thyroglossal duct see thyroglossal duct cysts tracheal, congenital cysts 1 147 ultrasound 724-5, 1297, 1297 F lymph nodes 7 1 7, 7 1 7 F, 7 1 8 F, 724 ranulas 725 ventricular 220 1 vestibular schwannoma 3960-1, 396 1 F
vocal folds see vocal fold cysts
see also individual types cystic fibrosis (CF) bio-electric phenotype 24 children 1081 chloride channel defect 24 diagnosis 1 866 gene therapy 24-6 adeno-associated virus 25 adenovirus vectors 24, 24-5 animal models 24 clinical trials 24 intrapulmonary administration 24, 25
in vitro studies 24 lentivirus 25 liposomes 25-6 nasal model 24 nasal mucosa 24 nonviral vectors 24-5 pulmonary toxicity 24-5 vector-induced inflammation 25 genetics 24 nasal polyposis 1 550 histology 1 550 mucosal abnormalities 1 550 salivary glands 1866 cystic fibrosis sinus disease, gene therapy 24 cystic fibrosis transmembrane conductance regulator (CFTR) 24 cystic hygroma 1782-3 embryology 1269 histology 1270 F, 1 782 investigation 726, 1270
management 1782-3 natural history 1270 presentation 1269-70, 1 270 F, 1 782 treatment 1270 cystic lesions, neck 1777-9 lateral see branchial cysts cystic nodules, thyroid 363 cystic vestibular schwannoma 3960-1, 396 1 F
Cystophora cristata (hooded seal) , exostosis 3367 cytochrome P-450 4 1 0-1 cytogenetics 6-7 tumours 6 cytokines mucocoeles 1 532 nasal mucus 1 3 6 1 nasal polyposis 1552 salivary gland tumours 2495 stimulatory pathways, immune modulation 28 cytomegalovirus (CMV) congenital see congenital cytomegalovirus HIV-associated infection 240-1 oesophagitis 245 pharyngeal infection 2004 testing, donated blood 260 cytosine 3 cytoskeleton 2385 cytosolic infectious agents 140 cytotoxic agents adverse effects 40 apoptosis 36 ototoxicity 3677 therapeutic limitations 40 cytotoxic antibiotics 38 cytotoxic drug reactions 414
external 1 69 1 , 1692 T transcanicular 1689 variations 1694-5 post-surgical nasal endoscopy 1 352 preoperative assessment 169 1 inferior canaliculus probing 1 69 1 , 1691 F
surgical anatomy 1 690 dacryoscintigraphy, pre-dacryocystorhinostomy 169 1 daily personal noise exposure level 3 1 7 1 dairy free diet, chronic rhinosinusitis 1473 Dalton's Law 3501 T, 3 5 1 6 damages, medical negligence see medical negligence damper, hearing aids 3632 damping, vibrations 3 1 6 1 Danazol, laryngeal enlargement 2201 Dandy's (chronic vestibular insufficiency) syndrome 3749, 3750 F
Dandy's vein, surgical injury 3978 Dandy-Walker syndrome 1823-4, 2080 Danish Head and Neck Cancer Study Group (DAHANCA) 2754-5, 2756
dantron 279 1 dapsone leprosy 1464 relapsing polychondritis 3364 'dark' cells, vestibular labyrinth 3 1 55 dark-skin, face lifts 3094 Darwin's tubercle 972, 3 105-6 data collection, head and neck cancer 2372-7 coding classifications 2374-5 ICD-0-3 morphology 2374-5, 2375
dacrocystogram 1691 dacryocystitis 1689, 1 690 F dacryocystorhinostomy (DCR) 1689-98 antimitotic agents 1 695-6 children 1696 complications 1 695 historical aspects 1689-90 indications 1 690-1 operative techniques 169 1-4 balloon dacryocystoplasty 1 694 endonasal, conventional instruments 1692, 1692 F, 1692 T, 1693 F
endonasal laser see endonasal laser dacryocystorhinostomy (ELDCR)
T
ICD- lO tumour site 2374, 2374 T, 2375 T
operation and procedure 2375, 2375 T
comparative audit 2376 computerized database structure 2374 confidentiality 2374 developmental stages 2373-4, 2373 F
methods, historical 2373 minimum data set principles 2373 National Cancer Data Set 2375-6, 2376
national coordination, value 2375 national minimum data set 2375 purpose 2372-3
Pages 1-1 3 1 2 are in Volume 1, pages 1 3 1 3-28 1 0 are in Volume 2, and pages 281 1-4 147 are in Volume 3.
I ndex I 4 1 9 1
Data for Head and Neck Oncology (DAHNO) audit service 572, 2376 data protection, ethical issues 587, 589 Data Protection Act ( 1984) 587 Data Protection Act ( 1997) 602 Data Protection Act ( 1 998) 606 daunorubicin 38 daytime sleepiness assessment 23 1 5 DeIA-flaps, intra-oral reconstruction 2935, 2936 F DDAVP 308, 41 12 dead ear, cholesteatoma surgical complication 3434 deaf child see childhood deafness deaf community 566 deaf educational units 855 deafness categorization 8 1 1 children see childhood deafness genetic research 20 animal models 20 misdiagnosis 1306 morphogenetic defects 81 1-2 neuroepithelial 8 1 1-2 nonsyndromic 8 1 1 polygenic features 1 6 single gene mutations 16 sudden see idiopathic sudden sensorineural hearing loss (ISSNHL) tuberculous otitis 3447, 3447 T, 3450 T types 8 1 1-2 deaf schools 855 death domain (DD) 58 death receptor(s) (DR) 57-8 death receptor 5 (DR5) 57 decalcification, teeth 1 8 16 decibels (dB) 3 1 74-5 calculation 3 1 74-5 decibel scales 3 1 70 decibel sound pressure level ( dB SPL) scale 3 1 74 decibels sensation level 3 1 75 Declaration of Helsinki 589 decompression (ascent) injuries 3 5 1 3-4 physiological consequences 3503-4 decompression illness 3514-6 bubbles 3514-5 inner ear 3 5 1 6 hyperbaric oxygen therapy 3515-6 pathophysiology 3514-5 perip heral vasoconstriction 3 5 1 5 tissue perfusion rates 3 5 1 5
decongestants acute otitis media 9 1 8 allergic rhinitis 1 398 chronic rhinosinusitis 1470 otitis media with effusion 896 rhinitis induction 1410 rhinomanometry, normal nasal airflow effects 13 74 rhinosinusitis 439-40, 1543 children 1083 side effects 1398 sinusitis, HIV patients 242 deep auricular artery 3907 deep bronchial veins 2 142 deep cervical fascia 1743, 2 108 deep layer/prevertebral fascia 1743, 2 1 09 middle layer 1 743, 2 108 pretracheal/ visceral layer 3 1 6-7, 1743, 2 108 superficial/investing layer 1 743, 2 108 deep circumflex iliac artery flap 2878-9 advantages 2878 anatomy 2878, 2878 F clinical applications 2879, 2879 F, 2880 F disadvantages 2878-9 oral cavity reconstruction 257 1 , 2571 F technical nuances 2879 deep inferior epigastric perforator flaps 2876-8, 2877 F advantages 2876 anatomy 2876 clinical applications 2877-8 disadvantages 2877 technical nuances 2877 deep lingual artery 1 799 deep lingual vein 1793 F, 1 799 deep neck space abscesses 1785-6 airway compromise 1786 clinical features 1 786 investigations 1 786 management 1 786
see also individual types deep petrosal nerve 3903, 3910, 3928 deep vein thrombosis (DVT) heparin 447 perioperative management 289 treatment 288 defaecation, laryngeal effort closure 2 1 59 default consultation style 560, 560 F defence mechanisms [33-43
deferoxamine ototoxicity prevention and 3302 skin flap survival 1 13 deficiency glossitis 1 828-9 deformity surgery-induced 309 1 wound contraction 9 1
see also specific types degenerative vestibulopathy 3698, 3699 F deglutition see swallowing degrees of freedom 3208 dehiscent superior semicircular canal syndrome 1046-7 dehydrated alcohol, skull base tumour embolization 3952 dehydroepiandrosterone sulphate assay (DHA-S), salivary 1 867 Deiters' cell cup 3 1 32 F Deiters' cells 3 123, 3 1 30, 3 1 3 1 F, 3 132 F, 3 1 36 phalangeal process 3 1 32 F, 3 1 36 Delaire-type repair, cleft lip and palate 1004, 1005 F deletions (DNA) 1 6 Delivering the NHS Plan 570-1 Delphian node 260 1 deltopectoral flap 2853-4, 2854 F transfer planning 2854 De Meester score 2063-4 dementia, hyperparathyroidism and 39 1 demulcent cough preparations 449 demyelination, auditory neuropathy/ dyssynchrony 3848 denasalization, consonants 2 167 dendritic cells allergic response 1 5 1-2 nasal mucus 1361 denervation, stem cell proliferation 70 Denny's lines 1082, 1082 F dens, axis 2 1 1 1 dental abscess 1 8 1 7 bacterioids 1 8 1 7 children 1 2 1 3 , 1214 F diagnosis 1 8 1 7 discharge 1 8 1 7 drainage 1 807 granuloma formation 1 8 1 7 dental aplasia 1 8 1 7 dental bud 799-800 dental caries 1 8 1 6-7 causative agents 1 8 1 6 decay progression 1 8 1 6 infection spread 1 805
Pages 1-1 3 1 2 are in Volume 1, pages 1 3 1 3-28 1 0 are in Volume 2, and pages 28 1 1-4147 are in Volume 3.
----.........--------
---------------
4 1 92 I I ndex
dental caries (continued) otalgia 3529 differential diagnosis 3529 saliva and 1 866 Sjogren syndrome 1 9 1 1, 191 1 F dental consonants 2 1 66-7, 2 1 67 T dental disease benign 1 8 1 6-39 otalgia 3529 dental lamina 1922-4 dental pain 1721 dental papilla 799-800 dental plaque 1 8 1 6 dental prostheses ionomer cements 1 20 taste abnormalities 1 848 dental trauma adenoidectomy-related 1098 children 1633 dentatorubral-pallidoluysian atrophy (DRPLA) 3773 dentigerous cyst 1924, 1 924 F nasal obstruction, children 1074 dentinal pain 1 8 1 6 dentine 800-1 dentinogenesis imperfecta 1 8 1 8,
1818 F denture granuloma 1 828 denture-induced candidiasis see denture-related stomatitis denture-induced hyperplasia 1 828 denture-related stomatitis 224, 1 826 complications 1 826 treatment 1 826 dentures angular cheilitis 1 827 modification 29 12 deontology 583 deoxyribonucleic acid (DNA) see DNA (deoxyribonucleic acid) depression globus 2039 head and neck cancer patients 2777,
2796 muscle tension dysphonia 2204 salivary flow 1861 smell appreciation disorders 3913-4 tinnitus 3598, 3608 vestibular disorders 3814-5 depressor glabellae 1324 depressor septi nasi muscle 1322-4 De Quervain's thyroiditis see subacute thyroiditis dermabrasion 2898, 2899 F patient preparation 2898
patient selection 2898 re-epithelization 2898 Dermagraft 1 26 dermal grafts 2826-7 dermal sinus 1 502-3 dermatitis 1 86 external nose 1 7 14-5 dermatitis artefacta 1 02 dermatochalasis 3052-3, 3054 F, 3063 F genetic predisposition 3052-3 pathophysiology 3052-3 preoperative evaluation 3055 visual defects 3055 dermatofibromas, nasal 1 708 dermatomyositis 1712 dysphagia 203 1-2 septal perforations 1 584 dermatophytosis 214 dermatosis papula nigra 1 709 dermofat graft, Moebius syndrome 3086 F dermoid cyst CPA tumours 4014 epidermoids vs. 40 1 1 formation theories 1 320-1 cranial theory 1320-1 nasal 1320-1, 1 502-3, 1 708-9 external rhinoplasty 2968 nasolacrimal 1073-4, 1074 F nasopharyngeal 2 1 19 neck 1782 oropharyngeal 2579-80 surgical approaches 1 074 ultrasound 724 descendens hypoglossi 1752 descending auditory pathways 3144-5 descending palatine artery 2 1 1 3 descending vestibular nuclei (MVN) 3220 descent speed, middle ear barotrauma 3504 descriptive epidemiology 2343 descriptive studies, epidemiological research 624, 625-6, 2344 desferrioxamine 271-2 desloratadine 1402 detectable change in frequency (DLF) 3252 F detergent manufacturers, occupational rhinitis 1419 determinant odds ration 622 determination, otic field 8 1 5 deviated nose 2987-94 aetiology 2987-8 analysis 2989 F
assessment 2988-9 external rhinoplasty 2965-6, 2966 F facial asymmetries 2987 fractures 2988 management 2990-3 midline, defining 2988 post-natal trauma 2988 septal abnormalities 299 1-3, 2992 F surgical access 2990 surgical correction 2989-90 algorithm 2992 F lower third deviations 299 1-3 middle third deviations 2990-1 outcomes 2988 T upper third deviations 2990 three-dimensional laser facial scanning 2988 without hump 2990, 299 1 F deviated septum 1326-7, 3009 caudal displacement 299 1 correction 2990-1, 2992 F epistaxis 1 574 children 1067 Eustachian tube dysfunction 3506 devils ear deformity 3075 dexamethasone acute airway obstruction 1 1 23 chronic rhinosinusitis 1470 croup 422, 1 128-9 dysphagia, cancer patients 2790-1 idiopathic sudden sensorineural hearing loss 1, 3584, 3589 T laryngeal stenosis 1 1 52 liver capsule distension 2784 Meniere's disease 3800 nausea and vomiting, cancer patients 2788 pharyngitis 1984 spasmodic croup 1 1 29 stridor 2795 superior vena caval obstruction 2794-5 tonsillectomy 1237 tonsillitis 1222 dexamethasone suppression test 3 10 T accuracy 3 10 Cushing's syndrome 3 10 Dexa-Rhinaspray Duo 440 dextran idiopathic sudden sensorineural hearing loss 1, 3588, 3589 T skin flap survival 1 14 dextrocardia, primary ciliary dyskinesia 1081
DFNA9 3562
Pages 1-1 3 1 2 are in Volume 1, pages 1 3 1 3-28 1 0 are in Volume 2, and pages 28 1 1-4147 are in Volume 3.
I ndex I 4193
DFNAI I gene/protein 20 DFNB2 gene/protein 20 diabetes insipidus aetiology 308, 3 12 anti-diuretic hormone 308 hypophysectomy complications 4 1 1 2, 4 1 13 diabetes mellitus (DM) 40 1-2 acromegaly 4 1 00-1 acute fulminant fungal rhinosinusitis 2 1 6 auditory dysfunction 402 Bell's palsy 40 1-2 clinical manifestations 40 1 Cushing's disease 4101 implants 29 10 infection 402 macrovascular manifestations 401 malignant otitis externa 402, 3337 microvascular disease 401 ocular findings 401 orbital infections 3 9 1 6 periodontitis 1 8 1 8 pituitary tumours 4 1 00-1 , 4 1 0 1 rhino sinusitis 1082 taste abnormalities 1 845-6 type 1 401 disease presentation 40 1 prevalence 40 1 type 2 401 disease presentation 40 1 prevalence 401 taste abnormalities 1845-6 vestibular end organ 402 wound healing 95, 95 F diabetic nephropathy 402 diabetic neuropathy 401-2, 2080 diabetic retinopathy 40 1-2 diabetic ulcers 102 diabetic wounds 97 diagnostic wax up/models, implants 29 1 1 , 29 1 1 F 3,4-diaminopyridine (3,4-DAP) 3804 diamorphine, cancer pain management 2786, 2787 T diaphragm screening fluoroscopy 1 296 ultrasound 1 297 sleep 2307 diaphragma sellae 298, 304 diaphragm screening 1296 diarrhoea, antimicrobial-induced 236 'diaschisis' -type phenomenon 3793 diathermy burns 1 308
diathermy tonsillectomy 1233-4, 1991 diazepam 3796 T, 3797 dichotic digit test central auditory dysfunction 3 859-60, 3 859 F peripheral hearing loss 3 864 dichotic speech tests 3270 central auditory dysfunction 3858-9, 3862 Diclofenac, formulation choice 410 diclofenac, tonsillectomy 1993, 1 994-5 diet chronic rhinosinusitis 1473 dysphagia management 2087-8 hypopharyngeal cancer 2634 laryngeal cancer 2348 laryngeal trauma 2274 migrainous vertigo 3800-1 nasopharyngeal carcinoma 2346, 2354 oral cavity cancer 2348 oropharyngeal tumours 2348 vitamin K deficiency 282 voice disorders 2 195 differential amplifier 3279 difficult airways 467-87 definitions 467-8 difficulty prediction 471-2 emergency cricothyrotomy 476-7 evaluation 468-70, 468 T, 472 examination 469-70 extubation 483-4 failed ventilation 476-7 follow-up 484-5 gum elastic bougie 472-3, 473 F investigations 470 laryngeal masks 473 T, 475-6 management 467-87 alternative techniques 473-5 strategy 47 1 T, 472-3 morbidity/mortality 485 patient history 468-9 preoperative assessment 2 1 5 1 prevalence 468 recovery 483-4 tumours 47 1 difficult direct laryngoscopy 468, 47 1 , 472 difficult face mask ventilation definition 467 prevalence 468 difficult intubation definition 467 prevalence 468 difficult ventilation 468
Difflam 1984 diffraction, sound waves 3 1 67, 3 1 67 F diffuse goitre nontoxic 330 toxic see Grave's disease diffuse hyperplastic laryngitis 2259 F diffuse infiltrated lymphocytosis syndrome (DILS) 1900 diffuse Lewy body disease 3778 diffuse oesophageal spasm 2066 clinical features 2066 diagnosis 2066, 2067 F dysphagia aetiology 2032 manometry 2032 treatment 2066 diffusion-weighted imaging, salivary gland 1 876 digastric muscle 1 746, 2 1 3 5 T, 3910 digastric ridge 3873 Di George syndrome (anomaly) 1 80-1, 1267 digital planning camera specification 2947-8 facial plastic surgery 2943-9 digital substraction sialography 1 877 sialolithiasis 1 880 subtraction angiography (DSA), pituitary gland 306-7 postoperative imaging 306-7 dihaematoporphyrinether (DHE), juvenile-onset recurrent respiratory papillomatosis 1 177 dihydrocodeine advanced head and neck cancer 2786 postoperative pain 463 dihydroergotamine 3802-3 dihydrofolate reductase inhibition, methotrexate 3 8 2,3-dihydroxybenzoic acid 3302 l ,25-dihydroxyvitamin D3 ( 1,25- ( OHhD3 ) function 375 synthesis 374 diiodotyrosine (DIT) 322 dilatation, achalasia 1 289-90 dilator naris anterior strengthening 3012 dimenhydrinate migrainous vertigo 3801 side effects 3795 vestibular attacks, acute 3795, 3796 T dimethylsulfoxide (DMSO), skin flap survival 1 14
Pages 1-1 3 1 2 are in Volume 1, pages 1 3 1 3-28 1 0 are in Volume 2, and pages 2 8 1 1-4147 are in Volume 3.
4 1 94 1 I n dex
dimethyl triazeno imidazole carboxamide (DTIC) 241 0 Dingman supraorbital approach, zygomatic complex fractures 1 629 T, 1630 diphenylhydramine 1 397-8
haemorrhage, control of 1 99 1 techniques 1 99 1 disseminated intravascular coagulation (DIC) 283-4 causes 283-4 clinical manifestations 283-4
patient's description 3707 positional manoeuvres 3720-1
see also vertigo Dizziness Handicap Inventory (DH!) 640 DNA (deoxyribonucleic acid) 3-5, 1 5-6
cryoprecipitate 259, 284
amplification 7
aetiology 2252
fresh frozen plasma 258, 284
fragmentation techniques 5-8
clinical features 2252
laboratory tests 284
function 3-5
complications 2253
platelet transfusion 259, 284
identification techniques 5-8
treatment 284
radiation-induced damage 47
diphtheria 1 1 30, 2252-3
infection site 2252 investigations 2253
disseminating sclerosis 1 724
replication 4, 35 F
larynx 1 130, 2252-3
distortion product otoacoustic
sequence variations 1 6
management 2253 pharyngeal manifestations 2079 prevalence 2252
emissions (DPOAEs) 3278, 3278 F auditory neuropathy! dyssynchrony 3842
stability 5 structure 3-5, 1 5-6 DNA analysis
strains 1 130
neonatal hearing screening 3291
craniofacial anomalies 1021
symptoms 1 1 30
presentation 3278
neurofibromatosis 2 3999
transmission 2079 treatment 1 1 30, 2079 diphtheria toxin 198-9
recording 3278
DNA complexes, cancer treatment 26
distortion products 3597
DNA fragmentation factor 58
distraction osteogenesis
DNA helicase 4
diphthong 2 1 66
hemifacial microsomia 1 033
DNA ploidy, oral cancer 2552
diplacusis 3597
syndromic craniosynostosis 1029-30,
DNA polymerase 4
binaural 3597 Meniere's disease 3597
1030 F distraction test, hearing 835-7
DNA proofreading mechanism 4 dobutamine 529-30
monaural 3597
method 835-6, 836 F
docetaxel (taxotere) 39, 276 1
patient evaluation 3597
no sound control trials 837
doctor-patient relationship
diplophonia, subglottic cancer 2608-9
pitfalls 837 T
consumerism 582
diplopia
results 837
ethical issues 58 1-2
abducent nerve 3945 blepharoplasty-related 3066 orbital decompression-related
stimulus 836-7 frequency spectrum 836, 837 F diuresis DDAV P treatment 308
1 683 directive counselling, tinnitus 36 14 direct laryngoscopy anaesthesia 2236
post-hypophysectomy 308, 41 12 diuretics chronic rhinosinusitis 1473
doctors, dutieslresponsibilities 582-3 docusate, constipation 279 1 dog bite injury 2929 F doll's head manoeuvre 3718, 3719 F eye movement observation 37 1 8 vestibular ocular reflex testing 3 7 1 8 domains, outcomes research 634, 636
laryngeal trauma 2275
Meniere's disease 3759, 3799
domperidone 2787
laryngeal tumours 2608
ototoxicity 3568 T, 3569-70, 357 1,
Do Not Resuscitate (DNR) orders 537
supraglottic obstruction 479
3677
dopamine
direct light reaction, blind eye 39 1 6
diverticulae, oesophageal body 2072
noise-induced tinnitus 3604-5
disability (definition) 783
Divine Proportion 2944-5
prolactin secretion control 300, 301
disclosure
Diving Diseases Research
ethical issues 586 legal issues 602
see also confidentiality discoid lupus erythematosus (DLE) 1 7 1 1, 1 7 1 1-2 discourse, voice analysis 2 1 74
Centre 3517-8 Dix-Hallpike manoeuvre 3761 , 3762-3,
3762 F Dix-Hallpike positional tests 3809-10 dizziness 3706-7 children
vestibular neurones 3794 dopamine agonists, acromegaly 4101 dopamine antagonists, vertigo 433 children 1 049 dopaminergic cells, stem cell therapy 75 dopexamine 530 Doppler effect 7 14
disequilibrium, meningioma 4009
assessment 1 041-2
Doppler equation 714
dishonesty, medical negligence 2805
examination 1 042
Doppler shift frequency 7 1 4
disodium edetate 429
investigations 1 042
Doppler ultrasound
displacement, sound waves 3 1 74
chronic 3709-10, 37 1 0 T
dissection tonsillectomy 1991-3
medical negligence 3829-30
electrosurgery vs. harmonic scalpel 1 992
cervical lymph node assessment 1 759 perfusion patterns 1 760
neurofibromatosis 2 4000
continuous-wave 714
nonvestibular causes 3707 T
duplex scanners 7 14
Pages 1-1 3 1 2 are in Volume 1, pages 1 3 1 3-28 1 0 are in Volume 2, and pages 281 1-4147 are in Volume 3.
I ndex I 4 1 95
facial reanimation 3082-3 Grave's disease 335, 720-1, 721 F lymph nodes 7 1 8 physics/basic principles 7 14 pulsatility index 7 14 pulsed-wave 7 14 resistance index 7 14 thyroid papillary cell carcinoma 7 19 wound assessment 100 dorsal cochlear nucleus (DCN) 3 140 dorsal humps, nasal deviated nose 2989, 2990, 2990 F en bloc reduction 2955, 2955 F dorsal ling'ual artery 1799 dorsal lingual vein 1 799 dorsal onlay graft 2952 F dorsal reduction surgery 2954 dorsum sellae 298 dose response curves, radiotherapy 48 double aortic arch 1 146 double blind placebo controlled food challenges (DBPCFC) 1, 1429 double hearing see diplacusis double paddled radial free flap, buccal carcinoma 256 1, 2561 F double stranded DNA (dsDNA) 7 downbeat nystagmus, idiopathic 3804,
3804 T Down syndrome adenoidectomy 1097, 1098 adenotonsillectomy 1 109 characteristics 784 F, 2 1 1 9-20 ENT-related problems 784 T incidence 2 1 19-20 inner ear disorders 3683 medical negligence 1308 nasopharyngeal disorders 2 1 1 9-20 obstructive sleep apnoea 1 109 postoperative complications 1 1 10 olfactory dysfunction 1 669 tympanic membrane disorders 934 doxorub icin mechanism of action 38 salivary gland tumours 2508 DP-gram 3278, 3278 F Dramamine see dimenhydrinate dreams 2305
Drechsclera 22 1 dressings 100-3 burns 102 malignant wounds 101, 2794 see also individual types Driver and Vehicle Licensing Authority (DVLA), obstructive sleep apnoea 2322
drooling palliative care patients 2788-9, 2788 T salivary gland obstruction 789 special needs children 788-9 treatment 788-9, 2788-9 upper airway obstruction 2287 drop attacks 3758 droperidol 3795-6 Drosophila neural stem cells 68 drug(s) administration 407-17 delivery methods 408-9 adverse reactions see adverse drug reactions bioavailability 408, 410 development 407-8 dosing frequency 410, 410 F, 4 1 1 F dysphagia aetiology 2033-4 elimination 4 1 1 first pass effect 408 formulation choice 410, 410 F half-life 410 interactions 415 metabolism 410-1 monitoring see drug monitoring otology 429-35 pharmacology 409-12 potency 4 1 1-2, 412 F regulatory systems 408 rhinology 436-45 drug-induced conditions generalized oral mucosal hyperpigmentation 1 825 gingival pigmentation 1 8 1 9 gingival swelling 1 820, 1821 F hearing loss 3298-300, 3299 T factors affecting 3301 incidence 3300 molecular mechanisms 3300-1 pathology 3298-300, 3299 F prevention 330 1-2 see also ototoxicity mouth ulcers 1 835 olfactory dysfunction 1664,
1673-4 olfactory nerve damage 39 13 rhinitis 1383, 1410 taste abnormalities 1 847 treatment 1 848 tinnitus 3599-600 animal studies 3600 tongue discoloration 1 825 vertigo, children 1047-8
see also specific drugs/drug types drug licencing 40 8
drug-light interval (drug uptake period), photodynamic therapy 746 drug monitoring 412-4 compliance 4 1 3 factors affecting 4 1 3-4 improvement methods 414 methods 412-3 micro electromechanical systems 413 patient self-monitoring 412-3 physical 412 plasma concentration monitoring 4 1 3 drug prescribing 41 5-6 children 415 elderly 4 1 5-6 hepatic failure 416 infants 4 1 5 neonates 415 pregnancy 4 1 5 renal failure 4 1 6 drug uptake period (drug-light interval), photodynamic therapy 746 dry eye syndrome (keratoconjunctivitis sicca) 3065, 3095 'drying spells' 1 1 16-7 dry mouth see xerostomia dry skin dressings 100 dsDNA antibodies 170 dual phase single tracer scintigraphy, parathyroid imaging 383-4 Duchenne muscular dystrophy, stem cell therapy 73, 75-6 dufourmental flap 2838-40, 2842 F 'duplex theory; sound localization
3255 dural resection, nasopharyngeal surgery 4056 'dural tail sign' 4009-10 dural tears, syndromic craniosynostosis surgery 103 1 dura mater hypophysectomy 41 10 olfactory fossa 1 335 Dutch College of General Practitioners, acute otitis media diagnostic guidelines 3385-6 dwarf gueron (Miopithecus
talapoin) 1 322 F dyazide 3799, 3799 T dyclonine 1 848-9 dye test, toxoplasmosis 2010 Dynamic Gait Index (DGI) 3806
Pages 1-1 3 1 2 are in Volume 1, pages 1 3 1 3-28 10 are in Volume 2, and pages 28 1 1-4 147 are in Volume 3.
4 1 96 I I n dex
dietary 2087-8
Eagle's syndrome 208 1
technique 3718, 3719 F
evidence-based 2084-5
ear(s)
vestibular ocular reflex testing 3718-9
postural techniques 2086-7
clinical examination 33 1 1-20
dynorphins, tinnitus 3604-5, 3607
prosthetics 2088
collapsed 97 1
dysacuses 3594-628
rehabilitative therapy 2086,
deformity, hemifacial
dynamic visual acuity
definition 3595
see also specific disorders dysaethesia, oral (burning mouth syndrome) 1 829, 1 829 T, 1 848-9 dysarthria cerebellar disorders 3940 definition 2 192 dysarthrophonia 2 1 92 dysgeusia 1 843 physical examination 1 843-4 treatment 1 848-9 dyskeratosis, epithelial dysplasia 222 1 dyskinetic syndromes 3939-40 dysmorphophobia, litigation risk 3088-9 dysontogenetic cysts 724 dysosmia 1 664, 1 666-7 dysphagia 2025-36, 2084-93 aetiology 1964-5, 2029-35
2088-90, 2089 T, 2090 T swallowing manoeuvres 2089-90, 2090 T neurological 1975, 2033 assessment 2076 botulism 2079 feeding 208 1 investigations 2076 management 2081-2 Parkinson's disease 2078 pharyngeal pouch 2034-5, 2044 prevalence 2084 stroke 2077 surgery-induced 208 1 symptoms 1964-5 temporal bone squamous cell carcinoma 4087 dysphasia 2 192 dysphonia
microsomia 1032-3 development 805-8, 8 1 3-7, 965-7,
3 120-4 discharge see otorrhoea external see external ear foreign bodies see aural foreign bodies as frequency analyser 3245
HIV infection 240 incision placement 3312 F inner see inner ear middle see middle ear missing amputation of cancerous 3028-32,
3032 F causes 3028-33 trauma 3028, 3029 F, 3030 F mycotic diseases 2 1 3-4 outer see external ear
child's voice assessment 1 169
pain see otalgia
congenital 2029, 2029-30
chronic laryngitis 2259
prominent see 'bat' ear
foreign bodies 2034
definition 2 192
rheumatological diseases 184
head and neck cancer 2029
laryngeal amyloidosis 2266
temporal resolution 3254
2034
infectious 2030-1
nonorganic 221 9-20
inflammatory 203 1-2
organic 2220-2
earache see otalgia
neoplastic 2032-3
special needs children 787
Ear Buddies 974-5
tracheostomy-related 2035
temporal bone squamous cell
traumatic 2030
carcinoma 4087
bolus escape 1975
vocal nodules 1 169
chronic laryngitis 2259
see also individual types
definition 1964-5, 2025, 2085 diagnosis 2085 drug-induced 2033-4, 208 1
dysphonia symptom index ( DSI)
2 1 84 dysplasia
see also entries beginning aural
eardrops 429 eardrum see tympanic membrane early goal-directed therapy (EGDT) , critical care 535 earmoulds 3633-4 earmuffs 3554 ear piercing, perichondritis 625-6,
examination 2025-6
Barrett's oesophagus 2065
history 2025-6
epithelial 222 1
earplugs 3554 ear preparations, topical 429-33
3033, 3034 F, 3358
iatrogenic 2080-1
fibrous see fibrous dysplasia
incidence 2084
frontonasal 1036
contraindications 430-1
investigations 1 964-80, 2026-9,
laryngeal 763-4
inflammatory/infective
2027 F
oral, genetic analysis 1 1-2
good practice principles 1965 respiratory recordings 1 976 laryngeal candidiasis 224
round window 873 dysplastic naevus 2400 dyspnoea
conditions 430-1 side effects 431 steroids 430 ear prosthesis, children 980, 983 F
laryngectomy rehabilitation 2627-8
grading 459 T
ear protectors 3554
malignant, palliation 2069, 2070 T,
posterior glottic stenosis
earshells 3633-4
207 1 T intubation .2069 stenting 2069 management 2086 compensatory strategies 2086,
2086-8
1 160-1 sarcoidosis 1 648 stridor 1 1 16-7 dysstereoacusis 3597 causes 3597 dysthyroid eye disease 33 1
ear sprays 430 ear surgery anaesthesia 50 1-3 children 5 1 3-4 hypotensive 502-3 facial paralysis, childhood 1 057-8
Pages 1-13 1 2 are in Volume 1, pages 1 3 1 3-28 1 0 are in Volume 2, and pages 281 1-4 147 are in Volume 3.
special needs children 786 taste abnormalities 1 847
see also individual procedures ear swabs, chronic otitis media 936 ear syringing 3313, 3313 F medical negligence 3 826-7 ear toilet see aural toilet ear trauma 349 1-525
electrical stimulation, tinnitus 3615 T,
3618
electrophysiological monitoring
748-54
'electric larynx' 2624-5
auditory function see auditory
electrocardiogram (EeG) , anaesthesia monitoring 496, 497 F
function monitoring current knowledge/future
electrocautery
research 752
paediatric epistaxis 1066
facial nerve see facial nerve
tonsillectomy 199 1
monitoring
missing ear 3028, 3029 F, 3030 F
electrocochleogram 3280-1
types 3492-3, 3493 T see also individual types
electrocochleography 75 1 , 3280-1
see also specific techniques
Meniere's disease 3758
electroporation, head and neck
otosclerosis 3827
cancer 26 XI nerve see spinal accessory nerve (XI)
genetics 3 1 07
paediatric cochlear implantation 863
Eltroxin (thyroxine sodium!
production 331 1-2, 3313 F
transtympanic
earwax
removal 33 1 1 softening 3312-3
levothyroxine sodium) 450
cochlear microphonics 3843
EMBASE 646, 647 T
multiple sclerosis 3847
embolic agents 733-4, 733 T
electrodes
ebastine 1 397-8 E-cadherin 2385, 2385 F
balloons 733
auditory nerve 3292-3, 3293 F facial nerve 749
echinocandins 234 echocardiography, stridor 1 1 19
coils 733
electrodessication and curettage (EDC)
'echoing' tinnitus 3604, 3605 F
basal cell carcinoma 2397
ectodermal dysplasia, oral 1 8 1 8
squamous cell carcinoma 2399
ectoturbinals 1321
electroencephalography
ectropion anterior lamella shortening 305 1 post-blepharoplasty 3065, 3096 eczema, external nose 1 714-5 eczema herpeticum 1 700
categorization 733 liquid agents 733-4 particles 733
basilar
temporary vs. permanent 733 tumour embolization 734
migraine 1 044
skull base tumours 3952
electroglottography 2 1 7 1
embolism, medical negligence 383 1
electrogustometry 1844
embolization
electrolaryngography 2 1 7 1 , 2 1 73 F,
2 176-7, 2 178 F
epistaxis 1 604 therapeutic see interventional
electrolyte balance
edroponium 2077 education, deaf children 854-6
neuroradiology (INR)
hypophysectomy and 4 1 12
effectiveness analysis 823
newborn infant 544
effector cells, allergic response
paediatric parameters 544 T
148-52
electromyographic (EMG) biofeedback
effect size, outcomes research 636 effortful swallow, dysphagia 2090,
2090 T
training 2225
electroneurography (ENoG)
tumour associations 2384 EGFR receptor 2760
facial nerve 3878-9, 3879, 3888, facial nerve tumours 4080-1 electronic resources, evidence-based
(VIII) eight month IDT screen 828-9 Einstein's equivalence principle
medicine 646, 647 T electron microscopy, apoptosis 60,
ejection fraction 459
electronystagmography (ENG) 3213 facial nerve disorders 3879, 3880 T
elderly drug prescribing 41 5-6
ototoxicity recognition 3573
rhinoplasty 309 1
skull base lesions 3946
toxic multinodular goitre 345
68 embryonic stem cells coculture 73 lineage-specific gene transduction 74 origins 74 osteoblast generation 73 pluripotency 73 therapeutic uses 73-4
60 F
32 10-1
embryonic germ ( EG) cells 73
differentiation control 73
3946-7
VIII nerve see vestibulocochlear nerve
telomerase 7 1 embryonic disc 792, 793 F
embryonic human endothelial cells
facial nerve 748, 3878-9, 3879-80
inhibition 2760
embryogenesis 68-9
embryonic fibroblasts 73
electromyography (EMG) 3288 dysphagia 1 977
EGFR
tumours see tumour embolization
electrooculography ( EOG) 3723
emergency cricothyrotomy 476-7 emergency tracheostomy acute airway obstruction 1 124 extubation 484, 484 F principles of 2 1 5 1-2
electrical impedance 3 168
analysis 3724
recovery 484
electrically evoked compound action
routine 3 724
tube placement confirmation 482-3
potential
auditory
. neuropathy/dyssynchrony 3852,
3853 F
'eminence-based medicine' 646
technique 3723-4 electroolfactogram (EOG) 1 367 electrophoresis 5-6
p
emissary venous sphenoidal foramen 1 339
Pages 1-13 12 are in Volume I , pages 1 3 1 3-28 10 are in Volume 2, and pages 281 1-4 147 are in Volume 3.
4 1 98 I I nd ex
EMLA, nasal fractures 1 6 1 2-3 emotionally-induced rhinitis l 383,
endoscopes
endolymph absorption 3 1 86-7 composition 3 1 30, 3 187-8, 3 187 T
14 1 1
contact endoscopy 763 nasal endoscopy 1 346-7
electrolytes 3 187-8, 3 1 87 T
endoscopic balloon dilation, tracheal stenosis 1 143-4
emphysema, airway obstruction 2287
forces acting upon 32 1 1
endoscopic brow lifts, frontalis
ENA antibodies 1 70
formation 3 1 86-7
encephalitis, vestibular schwan noma
vestibular hair cells 3230-1
emotional states, nasal vasoconstriction 1 366
removal 3982 encephalocoele ( s) 1034-5 aetiology 1 034-5 cerebrospinal fluid rhinorrhoea 1 638,
1 638 F classification 1035 diagnosis 1 035
electric potential 3 1 87-8, 3 1 88 F
viscous drag 3 1 95 viscous forces 321 1 , 32 1 2
endoscopic parathyroidectomy 395
endolymphatic hydrops
anaesthesia 1482-3
auditory nerve fibre thresholds
children 1495-6 rhinosinusitis 1 085, 1 085 T
3200 delayed 3696-7
frontal sinus 1504
contralateral type 3697 ipsilateral type 3696-7
management 1 035 middle fossa surgery 4023
Meniere's disease 3687 F, 3695, 3696 F endolymphatic potential (EP ) 3 1 30 alle-relate:a hearing loss 3 130 endolymphatic sac
nasal 1709
endoscopic sinus surgery (ESS) 148 1-9
aetiology 3757
frontoethmoidal 1 503, 1 505 F incidence 1 034, 2 1 16
paralysis 3078-9 endoscopic laser surgery, hypopharyngeal cancer 2648
complications 1485-6, 1485 T contraindications 1 482 demographic data 1488 T failure rates 1488, 1489 F, 1489 T follow-up assessment (after 5 years) 1488 T Im�l2:e-llU1aea 708, 709 F
children 1075
endolymph homeostasis 3 1 87
indications 148 1-2
endoscopy l35 1-2, l352 F
labyrinth 3 1 47-8, 3 1 49 F
medical
surgery, Meniere's disease 3759
postoperative management 1484-5,
nasopharyngeal 2 1 1 9 outcomes 1035
endolymphatic sac tumours
3685-6, 3686 F, 407 l-2,
surgery 1 035, 1505 transsphenoidal 2 1 16-7 children 2 1 16-7
407 l F clinical features 407 1
1 73 1 , 1 732-5
1485 F results 1486-9 technique 1483-4, 1483 F endoscopic stapling, pharyngeal pouch 2049-50, 2052 F
incidence 2 1 16
differential diagnosis 407 1
intrasphenoidal 2 1 16-7
histology 407 1-2, 407 1 F
access problems 2052
treatment 2 1 16-7
progression 407 1
gun jamming 2053
true transsphenoidal 2 1 16-7
treatment 4072
historical aspects 2049
von Hippel-Landau disease 4072
Hopkins telescope 2050- 1 , 205 1 F,
encephalomeningocoele see encephalocoele( s ) end bulb of Held 3 1 40-1 , 3 1 42 F endocarditis, antibiotic prophylaxis 460 endochondral ossification 794-5 endocochlear potential 3 188, 3 1 88 F,
3230-1 endocrine diseases!disorders head and neck manifestations 398-404 pregnancy 402-3
endolymphatic space, cochlea 3 1 86,
3 1 86 F endonasal dacryocystorhinostomy comparison with other techniques 1 692 T, 1695
2053 Negus pharyngoscope 2052, 2053 F outcome studies 2056, 2058 T postoperative care 2054 septum division 2053
conventional instruments 1692,
tear prevention 2053
1 692 F, 1693 F laser see endonasal laser
tips and tricks 2052-4
dacryocystorhinostomy (ELDCR)
view maximization 2052 Weerda distending diverticuloscope 2050-1, 2050 F,
meningiomas 4008-9
endonasal flaps, septal
2051 F, 2058
olfactory dysfunction 1 670, 1673-4 pituitary tumours 4099
perforations 1 587
endoscopic surgery
endonasal laser dacryocystorhinostomy
rhinosinusitis 1 383 voice disorders 2201
see also specific diseases/disorders endocrine glands 398-9; see also individual glands end of life issues, critical care 536-7 endolaryngeal stents, intractable
(ELDCR) choice of laser 1 694 conventional endonasal dacryocystorhinostomy vs. 1 695 technique 1 692 T, 1 693 F, 1 694,
1 694 F endonasal ligation of the
aspiration management 2099,
sphenopalatine artery
2 1 00 F
(ESPAL) 1603, 1 603 F
cerebrospinal fluid rhinorrhoea 1 636-7, 1 640,
1 640-1 craniosynostosis 1 027 glottic cancer 26 12, 261 2 F laryngeal cancer 26 1 2
e n bloc 2599, 261 2 mucocoeles 1 535 pharyngeal pouch see pharyngeal pouch surgery
Pages 1-1312 are in Volume 1, pages 1 3 1 3-28 10 are in Volume 2, and pages 281 1-4147 are in Volume 3.
endoscopy achalasia 1288, 2066 airway see airway endoscopy aspiration investigations 2096 chronic otitis media 3420 contact see contact endoscopy croup 2251 dysphagia 1 968-70 frontal sinus 1501, 1 508 gastro-oesophageal reflux 1275-6, 1276 F, 2063 history 1479 infectious mononucleosis 1 784 stenosis 228 1 children 1 152-3 light 755 medical negligence and 2807 mucocoeles 1 532 nasal see nasal endoscopy oesophageal carcinoma 2067 F 353 1 pal�dl,atrlc consultation 777 sleep see sleep nasendoscopy subglottic stenosis 2282
see also specific techniques endosteal implants 2902 T, 2903-4, 2903 F endothelial cells, allergic rhinitis 1391 intercellular adhesion molecule 1 expression 1 39 1 vascular cell adhesion molecule 1 expression 1391 endothelin- l (ET- l ) , skin flaps 1 1 3 tissue necrosis 1 1 3 endotracheal intubation 2 1 5 1 , 2289 children 5 1 1, 512 F contraindications 2289 endotracheal tubes 5 1 1 endovascular catheters 732-3 microcatheters 732-3 endovascular embolization 73 1-2 balloons/coils 733 dynamic testing and 735 epistaxis 739 plastics 733-4 temporary vs. permanent 735 see also interventional neuroradiology (INR) endovestibular potential 3230- 1 'end replication problem' 2379 end-stage liver disease 1 848 end-tidal anaesthetic agent concentration 498 definition 498 energy 3 1 65
enlarged turbinates 1589-95 chronic rhinitis 1591-2 chronic rhinosinusitis 1 59 1-2 definition 1 590 management 1589-95 medical treatment 1 5 92 'nasal cycle' 1 5 90 sleep apnoea 1591 snoring 1591 surgery 1 592-4 children 1084-5 complications 1592-3 methods 1 593 T procedures 1 593 T reviews 1 592-3 submucosal resection 1 593, 1 593 F enlarged vestibular aqueduct syndrome (EVAS) see large vestibular aqueduct syndrome ( LVAS) enophthalmos, imploding antrum 1685 'en plaque' type meningiomas 4008 ENT and Audiology Library, National Library for Health and Clinical Evidence 646, 647 T enteral nutrition critical care patients 5 3 1 delivery method 532 timing 532 enteric reconstructions 2883-5 free gastro-omental flap 2884-5 free jejunal transfer 2883-4 Enterobacteriaceae 200 chronic rhinosinusitis 144 1 granulomatosis 200 prevalence 200
see also individual species enterococci 198 enteroviruses, oral infection 1 833 entomophthoramycosis 2 1 5 aetiological agent 2 1 5 clinical manifestations 2 1 5 definition 2 1 5 diagnosis 2 1 5 epidemiology 2 1 5 management 2 1 5 enucleation, jaw cysts 1 922 environmental factors, genetic predisposition 16-7 enzyme-linked immunosorbent assay (ELISA) allergy testing 1 3 94-5 heparin-induced thrombocytopaenia with thrombosis 287 EORTC 22791 trial 2 755
EORTC QLQ-C30/H&N35 2770 characteristics 2773, 2774 T development 2 773 outcomes research 641 purposes 2774 T eosinophil(s) 274 allergic rhinosinusitis 220 allergic response 149, 150 F allergic rhinitis 1 390-1 apoptosis 62 inflammation 62 corticosteroid-induced 62 cytokine release 1 39 1 nasal polyposis 1 552, 1 556 eosinophilia 274 T eosinophilic fungal sinusitis see allergic fungal rhinosinusitis (AFRS) eosinophilic granuloma see Langerhan's cell histiocytosis (LCH) eosinophilic mucin rhinosinusitis 220-1, 1453, 1472 eosinophilic oesophagitis, laryngeal stenosis and 1 1 56 ependymomas 3776, 3776 F CPA impingement 40 1 5 neurofibromatosis 2 4000, 4002 ephedrine adverse reactions 4 1 5 pharmacodynamics 4 1 1 rhinosinusitis 440, 1 543 epidemic parotitis see mumps epidemiology 6 1 5-32 analytical studies 626-30, 2344-5, 2344 case control (retrospective) studies 627-8, 2344 cohort (longitudional/prospective) studies 627, 2344 cross-sectional studies 626-7 causality 2343-4 'ceteris paribus' principle 6 1 7 classical 6 1 6-7, 6 1 7-8 clinical 6 1 7-8, 6 1 7 components 6 1 8-24 definition 6 1 6, 2343 determinant -occurrence relationship 6 16, 6 1 7 descriptive, definition o f 2343 descriptive studies 624, 625-6, 2344 head and neck cancer 2343-50 health services/public health 6 l 7-8 incidence (of a disease) 2344 interventional studies 2344, 2345 observational studies 625-6 pn;�vaJ.en(:e definition 2344 principles 6 1 6
Pages 1-13 1 2 are i n Volume 1, pages 1 3 1 3-28 1 0 are i n Volume 2 , and pages 2 8 1 1-4147 are in Volume 3 .
4200 I I n dex
epidemiology (continued) protocols 6 1 8-24 randomized controlled trials see randomized controlled trials ( RCTs) sino nasal surgery 6 1 9-20 study design 6 1 8-24, 6 1 9 F,
2343-4 bias and confounding 624-5 blinding 62 1 , 629 choice of 624-30 measurement of variables 620-1 questions 6 1 8 results analysis 62 1-3, 622 F,
622 T size 623-4 structure 6 1 9 subject selection and recruitment 619-20 tonsillectomy 6 1 5-6, 6 1 8, 622, 622 T,
627-8 epidermal growth factor receptor (EGFR) 42-3 hypopharyngeal cancer 2636 immunoglobulin G cetuximab 43 monoclonal antibodies against 43 signalling pathways 42-3, 42 F targeted small molecules 43 targetted therapies 52 epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI) 43 epidermization 3400 epidermodysplasia verrruciformis 2396 epidermoids (primary cholesteatomas) aetiology 40 1 1 clinical presentation 40 1 1 CPA tumours 4007, 40 1 1-2 definition 40 1 1 diagnosis 40 1 1 arachnoid cysts vs. 401 3 dermoids vs. 40 1 1 MRI 40 1 1, 40 12 F epidemiology 4007, 40 1 1 mortality 40 12 nasal 1 708-9 pathology 40 1 1 petrous apex 4047, 4049 F clinical features 4047 management 4050, 405 1 F resection 405 1 recurrence rates 40 12 treatment 40 12 ultrasound 724 vocal folds 220 1-2, 220 1 F
epidermolysis bullosa (EB) dysphagia 2032 oral lesions 1 823, 1 824 squamous cell carcinoma 2398 epidural anaesthesia 463 epiglottic flap closure 2099, 2 100 F epiglottic petiole prolapse 1 1 59-60 epiglottic plication 2099-100, 2 1 0 1 F epiglottis 2 133 bifid 1 137 development 2 1 30 innervation 2 1 56 laryngomalacia 1 1 35 optical coherence tomography 757,
757 F pubertal changes 2205 swallowing 1955, 1 957-8, 2 1 59 epiglottitis acute 1 1 30-2, 1 1 3 1 F corticosteroids 422 dysphagia 2030-1 Hib infection 1 1 3 1 immunocompromised individuals 1 1 3 1 incidence 2250 medical negligence 1309 paediatric intensive care 545 treatment 1 1 3 1 adult 2250-1 clinical features 2250 complications 2251 dysphagia 2030-1 examination 2250 incidence 2250 investigations 2250, 2250 F management 2250-1 microbiology 2250 paediatric vs. 2250 epiglottopexy, intractable aspiration 2099, 2 100 F epignathi, nasopharyngeal 2 1 1 9 epilepsy olfactory dysfunction 1 669-70 treatment 1 67 1 skull base surgery 4139 taste abnormalities 1 846 epiphora children 1 696 definition 1 689 maxillary sinus carcinomas 2424 nasolacrimal duct obstruction 1 689 orbital decompression-related
1 683-4 post-blepharoplasty 3065 treatment 3079
epipodophyllotoxin derivatives 39-40 epirubicin 38 episodic cerebellar ataxia (EA) 3773-5 aetiology 3773-4 clinical manifestations 3774 complications 3775 definition 3773 diagnosis 3774 differential diagnosis 3774 management 3774 type 2 3804, 3804 T outcomes 3775 epistat, facial fractures 1619-20, 1 620 F epistaxis 1 596-608 anaesthesia 503 anterior 1 599-600 assessment 1 60 1 children 1063-9, 1 599 acute bleed 1064 aetiology 1063-4, 1064 T assessment 1064--5 associated medical conditions 1067 clinical guidelines 1067 effects 1063 management 1064-5 management controversies 1065-7 medical negligence 1 3 1 0 prevalence 1063 recurrent 1064-5 research, Naseptin efficacy 651,
660 T seasonal variation 1063 classification 1 599-600, 1 599 T definition 1 596 head injuries 1 605 lateral wall bleeding 1 598 management 1 601-4, 1 60 1 F direct therapies 1 601-2 indirect therapies 1 602 nasal fractures 1 6 1 5 newborns 1065 posterior bleeding sites 1 598 F,
1 599-600, 1 602 post-surgery 1 605 presentation 1 599, 1 599 T primary 1 599, 1 600-4 aetiology 1 600-1, 1 600 T chronobiology 1 600 demography 1 600 secondary vs. 1 599 recurrent 1 604 resuscitation 1 60 1 secondary 1 599, 1 605-6 primary vs. 1 599 septal abnormalities 1 574, 1 583, 1 60 1
Pages 1-1 3 1 2 are i n Volume I , pages 1 3 1 3-2810 are i n Volume 2, and pages 281 1-4 147 are i n Volume 3 .
I ndex I 420 1
septal bleeding 1 598 septal surgery 1 604 surgical management
1603-4 embolization 1604
Epworth Sleepiness Scale (ESS) 2 3 1 5 T,
2327 F
essential thrombocytosis (ET) 275 Esteem -Hearing Implant(tm) 366 1
obstructive sleep apnoea 620-1 ,
etamsylate 2792-3
2315 snoring 2326
ethambutol 1 460
etanidazole 2756
ligation 1 603-4
equilibrium, physiology of 3207-44
ethanol see alcohol
septal surgery 1604
Equitest 3733
ether 49 1
equivalent continuous sound level
ethical issues 581-93
trauma 1605 tumours 1606 vascular anatomy 1 596-9 eplthe:l1al cells
3171
communication, medical
equivalent rectangular bandwidths (ERBs) , auditory filter 3245
allergic rhinitis 1 39 1 pleomorphic adenoma 2482 epithelial dysplasia 222 1 epithelial hyperplasia 222 1-2 gastro-oesophageal reflux disease 2222 speech therapy 2222 epithelial retention cysts, chronic otitis media 3406-7
normal (ERBN) 3245 calculation 3249 erbium:yttrium-aluminium-garnet
consultations 561-2 confidentiality 586-7, 589 consent and refusal 585-6 data protection 587, 589 disclosure 586
(Er:yAG) lasers, medical
doctor-patient relationship 58 1-2
negligence 3096
doctors' dutieslresponsibilities 582-3
Erb's point 1751, 2738-9
medical records 587, 589
ergotamine 3803 T
moral foundations 583-5
ergot drugs 3802-3
consequence-based 584
erlotinib
principle-based 583-4
epitheliazing wounds, dressings 100
mechanism of action 43
epithelium
side effects 43
patients' rights 582
as targetted therapy 52
purpose 581
contact endoscopy 762-3
virtue-based 584-5
keratinized, oral cavity 767
eruption cyst 1 925
research 588-9
larynx 763
erysipelas
resource allocation 5 89-91
wound healing 98
nasal infection 1 700
see also specific types epitope 1 35
perichondritis 3358
Epley's repositioning manoeuvre benign paroxysmal positional vertigo 3762-3, 3762 F, 3810-2,
38 1 1 F
erythema multiforme (EM ) , oral manifestations 1835 diagnosis 1 835
1 835 treatment 1 835
complications/adverse effects 3812
erythema nodosum 1710
efficacy 3812
erythematous candidiasis 223-4
modified, self-treatment 3812
erythrocyte sedimentation rate
Epstein-Barr virus (EBV) 208
(ESR) 267
facial nerve palsy 3887, 3887 F
raised 267
hairy oral leukoplakia 208-9
rheumatological diseases 1 85
infectious mononucleosis see
subacute thyroiditis 35 1-2
infectious mononucleosis
erythromycin 23 1
treatment withholding! withdrawal 587-8 ethical principles 582-3 autonomy 561-2, 582 beneficence 56 1-2, 562, 582 justice 562 nonmaleficence 56 1-2, 562, 582 ethmoid air cell, ethmoidal arteries anterior see anterior ethmoidal artery posterior see posterior ethmoidal artery ethmoidal artery ligation (EAL) 1 604 ethmoidal bulla
investigations 1 984
allergic rhinitis 1 397-8
malignancy and 208-9
chronic rhinosinusitis 147 l-2
development 1 3 1 9
nasopharyngeal carcinoma 2346,
drug interactions 4 1 1 , 433
overpneumatized 1 3 3 5 T
2353, 2447, 2448, 2456 oral infection 1 832-3 salivary gland tumours 2494,
2496 undifferentiated carcinoma 2501 X-linked lymphoproliferative syndrome 1 8 1 Epstein-Barr virus-associated nuclear antigen (EBNA), nasopharyngeal carcinoma 2456 epulides 1 820 epulis fissuratum 1 828
laryngitis, acute 22 1 3 nasal polyps 147l-2 ototoxicity 3568 T, 357l
anatomy 1 333-4
third pass endoscopy 1348 ethmoidal infundibulum 1 3 1 8-9,
1 3 1 8 F, 1 33 1-2, 1344-6
pan-bronchiolitis 147l-2
atelectatic 1332
peritonsillar abscess 1997-8
bony defects 1331
pertussis 2252 erythroplasia, oral mucosa 1825-6 erythropoiesis 266 erythropoietin (EPO) 266 normochromic/normocytic anaemia 270 Escherichia coli 200
803,
805 F
development 1 3 1 8 F, 1 3 1 9 ethmoidal sinusitis complications 1 540 medical negligence 1 735 ethmoidal sulcus 1 33 5 ethmoidal turbinates 1 3 19, 1 3 1 9 F ethmoidal veins 1337-8
Pages 1-1 3 1 2 are in Volume I, pages 1 3 1 3-28 1 0 are in Volume 2, and pages 28 1 1 -4147 are in Volume 3 .
4202 I I n dex
ethmoid bone 1 334-5, 1336 F anterior skull base 3897 development 1 3 1 6-7, 1 3 1 8 ossification centres 1 3 1 8 ethmoid complex posterior 1336-7 cells 1336-7 roof 1334-5 ethmoidectomy bilateral maxillary antral washout and 1087 intranasal see intranasal ethmoidectomy juvenile angiofibroma 244 1 , 2441 F Patterson's approach 1 678, 1 683-4 modified 1679-80 transantral see transantral ethmoidectomy ethmoid sinus blood supply 1 338 development 1 3 19, 1319 F innervation 1 33 8 lymphatic drainage 1338 ethmoid sinus tumours presentation 2424-5 spread patterns 2419, 2419 F staging 2423, 2424 T TNM classification 2367 T ethmolacrimal cell 133 1-2 ethmoturbinales 1 3 2 1 ethnicity augmentation rhinoplasty 2970 keloids 2892 nasal airflow resistance 1357-8 ethylene vinyl alcohol 733-4 European Agency for the Evaluation of Medicinal Products ( EMEA) 408 European Community Respiratory Health Survey (ECRHS) 1 564 burot)ean Convention on Human 606-7 see also Human Rights Act ( 1998) bUl'op�ean Laryngological Society, glottic cancer classification 2607 bUl'opi:an Organization for Research and Treatment of Cancer ( EORTC) lar�rng:ectomlY rehabilitation assessment 2630 Quality of Life Questionnaire for Head and Neck Cancer see EORTC QLQ-C30/H&N35 Quality of Life Study Group 641 European Position on Rhinosinusitis and Nasal Polyps 1469
EuroQol ( EQ-5D) 639, 639-40 Eustachian cushion 2 107 Eustachian locking 3502, 3503 F Eustachian tube 1344-6, 1346 F acute otitis media 9 14-5, 9 1 5 anatomy 3 1 1 6-8, 3 1 1 8 F, 3 1 19 F bony part 3901 cartilaginous part 3901 decompressicm 3503-4 dysfunction chronic otitis media 3409 septal deviation 3506 function tests, otitis media with effusion 888-9 isthmus 3901 lower end, 1944 middle ear surgery and 3423 muscles attached 3 1 1 8 obstruction barotrauma-related 3390 otitis media with effusion 3389-90 patulous, somatosounds 3600 surgical approaches 4054-66 anterior approaches 4056-9 anterolateral approaches 4059-61 classification 4054-6 combined approaches 4062-5 facial translocation 4064-5, 4064 F infratemporal approach type C 406 1 lateral approaches 406 1 maxillary swing technique 4059-61 preoperative assessment 4056 subtemporal-preauricular infratemporal fossa approach 4062-4 transcervical approach 4058-9 transmandibular approach 4058-9 transoral approaches 4056-8 transpalatine approaches 4056-8 euthyroid Graves' ophthalmopathy 343-4 Evans blue dye test 2097 event-related potentials see auditory evoked potentials Evidence Based Medicine 650 evidence-based medicine (EBM) 645-8 application 647-8 case-control studies 655 cohort studies 655 critical appraisal see critical appraisal skills current 646 definitions 645-7, 647 dysphagia management review 2085
electronic resources 646, 647 T limitations 647 principles 647, 650-1 conscientiousness 645-6 explicitness 646 judiciousness 646 tonsillectomy 1 229-32 Ewald's first law 3230 Ewing's family o f tumours 1936 children 1 259 T management principles 1936 presentation 1936 prognosis 1 936 staging 1 936 survival rates 1 936 exanthems, facial 1 70 1 excision biopsy cervical lymphadenopathy 2703 chronic laryngitis 2260, 226 1 F excretory duct, salivary glands 1 852 exhaust fumes, occupational rhinitis 1419 exon(s) 4, 1 5-6, 2378-9 sequencing 19-20 exophthalmos (exorbitism) Crouzon syndrome 1 027 thyroid eye disease 344 exophytic lip cancer 2544 F exostosis 1930 eXl)ansion phase, speech/language development 990-1 expectorant cough preparations 449 expert medical witnesses 603-5 clinical negligence 604 doctor as 604-5 nasal humidification 1 3 56 swallowing 1 960 vocal fold adduction 2 159 anaesthesia monitoring 498 end-tidal 498 exposure keratitis 3079 expressive disorders 99 1 , 992 T Exserohilum 2 1 7 extended field-of-view, ultrasound advances 7 13 extended maxillectomy 2428 extended supraomohyoid neck dissection 2747, 2747 T, 2748 F extended thyroid incision 2732 F external auditory canal anatomy 3 107-8, 3 1 09 F arterial supply 3 1 08 auricular implant placernelll 2908
Pages 1-1 3 1 2 are in Volume 1, pages 1 3 1 3-28 10 are in Volume 2, and pages 28 1 1-4 147 are in Volume 3.
I ndex I 4203
bony erosion 3334 T clinical examination 33 1 1 development 966, 3 122 disorder classification 332 1-2 exophytic masses 4089, 4089 F exostosis 3366-9, 3367 F aetiology 3367 cold water exposure 3367 definition 3366, 3366 F diagnosis 3367 epidemiology 3367 management 3367-8 natural history 3367 outcomes 3367 pathology 3366 stenosis 3367 surgery 3368 glandular tumours 4069-70 classification 4069 progression 4068-9
see also individual types hearing 3 1 78 HIV-associated lesions 240 hypothyroidism 400 Kaposi's sarcoma 240 lacerations, foreign body-induced 3371 mopping 331 3-4, 33 14 F occlusion 3035, 3037 F, 33 1 1 osteonecrosis see benign necrotizing otitis externa polyps, HIV-associated 240 relationships 3 108, 3 108 F restoration 3035 skin 3 107 external auditory meatus (EAM) see external auditory canal (EAC) external beam radiation lip cancer 2548 pituitary tumours 4 1 1 5 external carotid artery 1 749-50, 3904 branches 1749-50, 1750 T course 1853-4 epistaxis 1596-7 territories 1 597 external carotid artery ligation (ECAL) 1 604, 1 750 external ear abnormal folds 970, 970 F anatomy 3 105-25 atresia acquired see acquired atresia, external ear cOllgemt
972 clefts 972, 973 F collapsed 971 congenital deformities 965-89 aetiology 967-8 classification 975-6, 976 T epidemiology 967 range of 968-75 syndromic associations 967-8 treatment 977-80 embryology 808, 8 14, 3 120-2 extrinsic muscles 3 1 06 hearing 3 1 78-9 bone conduction 3 185-6 tympanic membrane pressure gains 3 178-9 hidden (cryptotia) 973, 974 F HIV 240 mycotic diseases 214 normal 967, 969 F otalgia 3527 positional problems 973-4, 974 F sound localization 3 1 79, 3 1 79 F splintage 972 F, 974-5, 975 F external ear barotrauma 3504 external ear squeeze 3504 external fixation Le Fort 2 fractures 1 627, 1 627 F mandibular fractures 1623, 1 624 F maxillary fractures 1627 external jugular vein 1 750 external laryngeal nerve 3935 external nares (nostrils) 1 325-6 HIV patients 248 external nose anatomy 1 322-4 1 , 1 323 F blood supply 1 325 cartilages 1 324 F, 1325 lower lateral see alar cartilage(s) upper 1 325, 2960-1 conditions of 1 699-7 17
see also specific disorders destructive lesions 1 7 1 3 development 1 3 1 5 innervation 1325 inspection 1 575, 1 576 F lymphatic drainage 1325 muscles 1322-4, 1 323 F neoplasms 1 704-10 fibroadnexal tumours 1 708 melanocytic 1 706-7 vascular lesions 1 708 skin 1322 venous drainage 1325 external occipital cr�st 3899
external palatine (paratonsillar) vein 1 793 external rhinoplasty 2959-69 applications 2963-8 bony pyramid 2963-4 cleft lip nasal deformities 2967, 2967 F deviated nose 2965-6, 2966 F historical aspects 2959-60 incisions 296 1, 2962, 2963 F indications 2960, 2960 T middle nasal vault 2964 nasal tip surgery 2964-5, 2965 F,
2998-9, 2999 F principles 296 1 retrograde approach 2999 revision surgery 2965 septal access 2962 soft tissue envelope dissection 2962,
2963 F surgical anatomy 2960- 1 , 2961 F technique 2962-3 tension nose 2966 transcolumellar incision closure 2962-3, 2963 F extracellular agents 137-40 89, 93 extracellular matrix cancer and 2385 extracorporeal circuits (ECC) 287-8 extracranial-intracranial bypass, jugular foramen surgery 4039,
4040 F extradural abscess, acute otitis media 924 extramedullary haemopoiesis 266 extraocular muscles 39 1 7 extra-oral prostheses construction 2930-1 stages 293 1 , 293 1 F treatment planning 2925 extrapyramidal disorders 3777-8, 3780
see also specific disorders extrapyramidal syndromes 3939 extrapyramidal system, phonation 2 158-9 extrauterine intrapartum treatment procedure 1 1 37-8 wounds, dressings 1 0 1 scars 2896 unilateral facial palsy 3079 Wegener's granulomatosis 1 650,
1651 F see also entries beginning orbital 'eyebags' 3054 F orbital fat removal 3057
Pages 1-1312 are in Volume 1, pages 1 3 1 3-28 1 0 are in Volume 2, and pages 28 1 1-4 147 are in Volume 3.
4204 . I ndex
eyebrow, ideal position 3048, 3049 F
facial cleft(s)
epidermoids 40 1 1
embryology 798-9, 1 320, 1 8 1 1-2
facial reanimation 3080
eyebrow ptosis, medial 3049
types 801 F
function assessment 3946-7, 4080-1
eye contact, medical consultations
see also individual types
eyebrow lifts 3078-9
565
eye cover test cranial nerve examination 3 7 1 0-1
imaging 3881
facial cosmetic units 2828, 2829 F facial defect(s)
intracranial portion 3 8 7 1
latent nystagmus 37 1 1
ablative surgery 2 937 F
spontaneous nystagmus 37 1 1
acquired 2926
eye disease, dysthyroid 3 3 1
traumatic burns injury 2926 F aetiology 2925-30
eyelid(s) hollowing 3065 lower see lower eyelid
congenital aetiology 2925
surgery see blepharoplasty
decision to treat 2925
upper see upper eyelid
psychological aspects 2927
eyelid ptosis, Horner's syndrome 3937 eyelid retraction, postblepharoplasty 3053 F, 3065
see also facial nerve monitoring
facial colliculus 3929
reconstruction delay 2927 patient follow-up 2933 facial defect reconstruction 2926-7
injury, blepharoplasty 3066 intraparotid 1 853-4, 1854-6, 1 8 5 5 F intratemporal portion 3871 jugular foramen surgery 4034, 4035-7 conservative management 4037, 4037 F
nerve transposition ear, canal wall up 4037-8, 40 38 F transposition ear, canal wall down 4038, 4038 F labyrinthine segment 387 1-2, 3882 F lateral skull base 3904
eyelid swelling, blepharochalasis 3053
auricular 2927-8
management, tumour surgery 4082
eye movements
bony defects 2926-7
morphology 4079-80 motor root 387 1
automatic 392 1
decision to not reconstruct 2926
balance disorders
firearms injury 2937-8, 2937 F, 2938 F
neurofibromatosis 2 4000, 4003
examination 37 10-23
polymers 1 2 1
neurological examination 3946
laboratory assessment 3723-30
prosthesis referral 2928
otalgia 3527
sites 2927-30
paediatric cochlear implantation 864
central control mechanisms 39 1 9, 3920 F
functional classes 3227 T optokinetic 3227 T rotationally induced 3 2 1 6 semicircular canal stimulation 32 1 6, 3 2 1 7 F, 3 2 1 8 F, 3 2 1 9 F, 32 1 9 T
torsional, control of 32 16 tracking 3921 vertical, control of 32 1 6 voluntarily controlled 3919
skeletal fixation 2926-7
parotid gland divisions 3873
small soft tissue defects 2926-7
protection, branchial arch fistula
surgical vs. prosthetic 2927 T facial injuries, children 1 632-3 anterior teeth 1633
rhytidectomy 3094
fronto-naso-ethmoid injuries 1633
salivary gland tumours
soft tissue injuries 1 633 facial nerve (VII) 3870-6, 3871 F, 3927-3 1, 3928 F
anatomy 1052-4 adults vs. children 1054 T anomalous course, middle ear 873,
face ageing see ageing face
surgery 1 266 recesses 3 872, 3 872 F
874 F
surgery 2 50 8-9 schwannoma see facial schwannoma sensory fibres 3927-8 skull base lesions 3945, 3946, 3946-7 stapedius muscle 3870 surgical anatomy 3870-3 surgical repair 2509
development 797-8, 1 8 10-2, 1 8 1 1 F
applied anatomy 4079-80
taste bud innervation 1841
gender differences 294 5 , 2945 F
blood supply 4080
trauma see facial nerve injury/trauma
face lifts see rhytidectomy face masks, anaesthesia 492 children 5 1 0 facets 703, 704, 7 0 5 F face validity 635 facial artery 1325 facial artery myomucosal flap (FAMM) 2850-1 facial assessment computer manipulation 2947, 2947 F
digital imaging 2946-8 facial baropareisis 35 1 3-4 facial bipartition, syndromic craniosynostosis 1029
branches 3928 patterns 1854, 1 855 F central connections 3920 F, 3929 cerebellopontine angle
tympanic cavity 3 1 12, 3 1 14 F facial nerve canal 3 1 1 1 , 3 1 1 2 F facial nerve disorders 3 870-94, 3930-1 classification 3835-6
syndrome 3932
clinical evaluation 3876-83
clinical testing 3931
coexisting trigeminal nerve
composition 3870
damage 3931
compression 3872
history taking 3876
cortical lesions 3930
imaging 388 1-3
cutaneous fibres 3928-9
inflammatory 3891
disorders see facial nerve disorders
investigations 3878-8 1 management 3883-9 1
electrophysiological monitoring see facial nerve monitoring embryology 966-7, 1 052-4 abnormalities 1 0 53
viral diseases 3886-7 middle ear infection complications 3890-1
Pages 1-1 3 1 2 are in Volume 1, pages 1 3 1 3-28 1 0 are in Volume 2, and pages 281 1-4147 are in Volume 3.
neuropathophysiology 3873-6, 3875 T physical examination 3876-8 topodiagnostic evaluation 3878, 3878 T
examination 1 054 history taking 1 054 iatrogenic 1057-8 idiopathic 1 059 infections 1 056-7 investigations 1055 neoplasms 1058 parotid surgery 1058, 1058 F penetrating trauma 1 057 traumatic 1057-8 cholesteatoma surgical complication 3434 chronic otitis media see chronic otitis
see also specific disorders/diseases facial nerve injury/trauma 3887-90, 393 1 gunshot injury 3887-8, 3887 F iatrogenic 3889 management 3887-90 maxillofacial trauma 3887 medical negligence 1 307, 3827-8 neonatal 3889-90, 3890 T petrous bone fractures 393 1 post-rhytidectomy 3074 post-stapes surgery 3476 salivary gland tumour surgery 2487, 2515 surgery-induced 749, 750 temporal bone trauma 3888, 3889 F vestibular schwannoma removal 3979-80 facial nerve (VII) injury/trauma, skull base surgery 4 137 facial nerve monitoring airway management 494-5 chronic middle ear disease surgery and 749 development/history 748-9 difficulties 750 electrodes 749 facial nerve paralysis 3878-81 children lOSS, 1057 intraoperative 3880- 1 , 388 1 T medical 3828 nonotological procedures and 750 outcome prediction 749-50 techniques 749 evoked facial twitch 748
media (COM) congenital 1 055, 3889-90 decompression surgery 4022 facial nerve tumours 4080 grading 3876-8 herpes zoster oticus 3380 HIV infection 3887 HIV patients 241 idiopathic see Bell's palsy imaging 388 1-3 ipsilateral recurrent 3876 jugular foramen lesions 4028 management 3078-85 surgical 3079-80 parotid gland tumours 2503-4 rhytidectomy 3094-5 skull base lesions 3945 surgery-related 2808 temporal bone fracture 3497-8 temporal bone squamous cell carcinoma 4088, 4094 temporal bone trauma 3496 tuberculous otitis 3448, 3448 T, 3450 T varicella zoster virus infection 3886 facial nerve preservation, vestibular nerve schwannoma 3688, 3688 F, 3689 F, 3690 F facial nerve stimulation, cochlear implant-related 3654, 3655 facial nerve surgery 4022 facial nerve tumours 4078-85 decompression 3891 epineurium 4079-80 facial weakness 4080 grafting technique 4082-3 hearing loss 4080 histology 4078-9 imaging 3883, 3884 F investigations 4080-1 malignant sheath tumours 4083 management 389 1 .,
see also individual techniques facial nerve paralysis acute otitis media 923, 3882, 3890 bilateral 3085 reanimation 3085 causes 1 , 3078 T children 1052-62 acquired 1 056-8 branchial cleft sinus and fistula excision 1 058 congenital 1055 diagnosis 1054-5 ear surgery 1057-8 electrophysiology lOSS, 1 057
Pages
1-1 3 1 2 are in
Volume
1,
pages
1 3 1 3-28 10
are i n Volume
2,
and pages
middle fossa surgery 4022, 4022 F near-total tumour removal 4083 patient counselling 4082 patient selection 408 1-2 presentation 4080 radiotherapy 4083 surgery 4082-3 tumour biology 4078-9 tumour stripping 4083 facial nucleus 1 052-3, 3920 F, 3929 facial pain associations 1 7 1 9 atypical 1 727, 1 829 clinical features 1 829 definitions 1829 patient traits 1 8 29 treatment 1 8 29 background 1 7 1 8-9 characteristics 1 7 19 daily life, effects on 1 7 1 9 dental 1 72 1 diagnosis 1 7 1 8-29 duration 1 7 1 9 history taking 1 7 1 9 management 1 7 1 8-29 neuralgias 1 724 psychological aspects 1 71 9 radiation 1 7 1 9 relief 1 7 1 9 rhinological 1 720-1 sarcoidosis 1 647-8 skull base lesions 3944-5 tumours 1 724 vascular 1 722-4 facial plastic surgery aesthetics 2943-9 bizarre requests 3089 complications 3089 digital planning 2943-9 medical negligence 3088 aggressive and violent patients 3089 complication management 3096 computer enhanced images 2948 consent issues 3089 patient selection 3088-9 objective 2948 patient dissatisfaction, previous surgery 3089 patient expectations 2948 preoperative cooling-off period 3089 risks 3089
see also specific procedures facial prominences (processes) 1 8 1 0- 1 28 1 1-4147
are i n Volume
3.
4206 I I ndex
facial proportions 2945-6 ageing 2946, 2947 F component widths 2946, 2946 F frontal view 2946 horizontal planes 2946, 2946 F facial prostheses, retention methods 293 1-2 adhesive 293 1-2 mechanical/anatomical 2932
see also individual prostheses facial rashes infective 170 1 nasal 1 7 1 5 rubella 1 70 1 facial reanimation 3077-87 adjustments 3083-4 congenital facial paralysis 1055 excessive muscle bulk 3083-4 future research areas 3086-7 knowledge deficiencies 3086-7 patient's age 3077, 3082 F results 3082, 3083 F facial reconstruction see facial defect reconstruction facial schwannoma 3883, 3884 F, 40 14,
4078 MRI appearance 4079 F surgical decompression 4083 tumour debulking 4083 facial skeleton fractures 1618-35 aetiology 1619 children 1633 frontal sinus 1 632 haemorrhage 1619-20 intervention, timing of 1620 management principles 1620 mandible see mandibular fractures maxilla see maxillary fractures naso-orbito-ethmoid see naso-orbitoethmoid (NOE) complex fractures orbital floor see orbital floor fractures primary care 1619-20 initial survey 1619-20, 1619 F radiographic evaluation 1620 soft tissue injuries 1632 upper facial third 1 632
facial vein 1325 facial weakness conservative parotidectomy
2483 facial nerve damage 3930 facial nerve tumours 4080 facio acoustic crest 1052 factor II (prothrombin) 279 factor V 279 factor V Leiden variant 290 factor VIla 279 factor VIII haemophilia 285 inhibition 284 venous thrombosis 290 factor X 279 factor XI deficiency 28 1 factor XIII 279 deficiency 281 Fahreus-Lindqvist affect 1 12 failed ventilation 476-7 Fallopian canal, facial nerve tumours 4079 false cords 757, 2132 falsetto voice, mutational see mutational falsetto voice falx cerebri 4121 famciclovir 208, 232, 2079 familial adenomatous polyposis juvenile angiofibromas 2438 thyroid cancer 267 1 familial dysautonomia 1 848 familial facial paralysis 1 055 familial paragangliomas 2526-7 Family Law Reform Act ( 1969), consent issues 60 1 famotidine 2262 farmers, occupational rhinitis 1418
zygomatic complex see zygomatic complex fractures facial slings, unilateral facial palsy 3079-80
fascia bulbi 1 679 fascial grafts 2827 Fas ligand (Fas-L) 57, 137 fast Fourier transform (FFT), voice evaluation 2 1 80 fasting, preoperative 465 children 509, 509 T fat atrophy facial ageing 3069 steroid injections 2898-9 fat grafts 2826-7 fat injection, vocal fold paralysis 2239,
facial synkinesis, Bell's palsy 1 845, 393 1 facial translocation 4064-5, 4064 F facial trauma intubation 2289 taste abnormalities 1 846
fat necrosis, blepharoplasty 3066 faucial pillar anterior 1944 posterior 1944
2245 T
FDG-PET imaging 686 best clinical practice 696-7 cervical lymphadenopathy 2702,
2704 indications 696 lymphoma 694, 694 F nononcological applications 696 occult primary tumours 69 1-2, 695,
696 oropharyngeal cancer 695 F parathyroid carcinoma 694 principles 685 F pulmonary lesions 694, 695 F salivary gland tumours 694 squamous cell carcinoma see squamous cell carcinoma ( See) thyroid cancer 334, 692, 693 F, 695,
696 febrile nonhaemolytic transfusion reactions 261 feeding problems, special needs children 786-7 feed thickeners 1 276 fenestrated tracheostomy tubes 1 199,
2299 fenestration procedures, historical aspects 3468 fentanyl 2786-7 ferritin 268 'festoons' 3060-1, 3063 F fetomaternal haemorrhage, anti-D
254 FGFR1 mutation, Pfeiffer syndrome 1027 FGFR2 mutation Apert syndrome 1 027 Pfeiffer syndrome 1027 FGFR3-associated coronal synostosis syndrome (Muenke craniosynostosis) 1027-8 fibreoptic assisted techniques, difficult airways 475-6, 476 F fibreoptic bronchoscopy paediatric anaesthesia 5 1 9 paediatric intensive care 547 fibreoptic endoscopic evaluation of swallowing (FEES) aspiration 1 277, 2096 dysphagia investigations 1965, 1965 T,
1968-70, 2028 advantages 1968 contraindications 1 970 equipment 1968 limitations 1970
Pages 1-1 3 1 2 are in Volume 1, pages 1 3 1 3-28 10 are in Volume 2, and pages 28 1 1-4147 are in Volume 3.
I ndex I 4207
procedure 1968, 1969 F risks 1970 neurological dysphagia 2076 fibreoptic endoscopic evaluation of swallowing with sensory testing (FEESST) aspiration 1277 dysphagia 1 968 fibreoptic orotracheal intubation (FOI) , supraglottic obstruction 48 1 fibrillogenesis, dermabrasion 2898 fibrin degradation 279 formation 279 inhibitors 279 skin graft adherence 282 1-2 fibrin glue 263 fibrinogen 279 fibrinolysis 279, 280 F fibroadnexal tumours, nasal 1 708 fibroblast(s) allergic rhinitis 1 392 fibroplasia 9 1 migration 9 1 phenotypic alterations 9 1 proliferation 89, 9 1 stimulation responses 90 wound healing 90, 9 1 fibroblast growth factor (FGF) goitre 2668 salivary gland tumours 2495 fibroblast growth factor-2 (FGF-2) skin flap survival 1 14 stem cell activation 67 stem cell differentiation 68 fibroblast theory, wound healing 92 fibroelastic membrane 2 1 32 F, 2 1 34, 2 1 34 F fibroma ameloblastic 1 927-8 ossifying see ossifying fibroma fibronectin 9 1 fibro-osseous lesions nasal obstruction, children 1077 skull base 4 123 fibroplasia proliferation 9 1 fibrosarcoma childhood 1 259 T larynx 2604 fibrous adhesions, post-stapes surgery 3475 fibrous atresia, external ear 3348 fibrous dysplasia 1 522-3 clinical types 1 522 definition 1 522-3
differential diagnosis 1 523 incidence 1 522 location 1 522-3 nasal obstruction, children 1077, lO77 F optic nerve decompression 1 523 polyostotic 1929 presentation 1 929 radiological appearance 1 929, 1929 F skull base 4124 proptosis 4 125, 4125 F radiological features 4 124-5 surgery 1523 symptoms 1 522-3 fibrous meningiomas 4008 fibula free flap, oral cavity reconstruction 257 1 , 2572 F Vth cranial nerve see trigeminal nerve (V) filiform papillae 1 794 fine needle aspirate biopsy (FNAB), lymphoepithelial cyst 245-6 fine needle aspiration cytology (FNAC) cervical lymphadenopathy 2703 head and neck tumours, childhood 1 252-3 metastatic neck disease 272 1 nasopharyngeal carcinoma 2456 nodular thyroid disease 36 1 , 36 1 F limitations 36 1 results 36 1, 362 T ultrasound-guided 361 salivary gland tumours benign 2479-80, 2480 F malignant 1 885, 1 892 F, 2506 temporal bone squamous cell carcinoma 4089 thyroid cancer 333, 2698
Fisch type C procedure, parapharyngeal space tumours 2533-4 Fisch type D procedure, parapharyngeal space tumours 2533-4 fish bone removal, oropharynx 1 187-8 fissural cysts 1926 fistula(e) arteriovenous 4 145
finger clubbing, Graves' disease 343 firearms injuries, neck trauma 1767 first branchial arch fistula 1264-6 histology 1265, 1265 F investigation 1265, 1265 F presentation 1 265, 1265 F treatment 1265-6, 1266 F first degree burns 96 1st nerve see olfactory nerve (I) first pass effect 408 first primary interturbinal furrow 1 332 Fisch staging system, juvenile angiofibroma 2438-9, 2439 T, 2441 Fisch technique 4020 Fisch type B infratemporal fossa approach, petrous apex lesion resection 405 1 , 4052 F
Fitness to Practise (FTP) panel 2803-4 fixation external see external fixation intermaxillary see intermaxillary fixation (IMF) internal see internal fixation 'flamingo flush: otosclerosis 3460-1 flavour enhancers, olfactory dysfunction 1671 flexible bronchoscopy laryngeal stenosis 1 1 53, 1 16 1 posterior glottic stenosis 1 16 1
branchial arch see branchial fistulae cerebrospinal fluid see cerebrospinal fluid fistula chylous 2744 endovascular embolization 733 frontal sinus see frontal sinus fistulae innominate artery 1203 labyrinthine fistulae see labyrinthine fistulae malignant see palliative care, head and neck cancer nasal see nasal fistula ( e ) oro antral 1085 palatal 1010 perilymphatic see perilymphatic fistulae salivary 2484, 2 5 1 5 thyroglossal duct see thyroglossal duct fistula tracheoarterial 2302 tracheocutaneous, persistent see tracheocutaneous fistula (TCF) , persistent tracheo-oesophageal see tracheo oesophageal fistula tracheostomy-induced 2302 fistula speech 2625 Fistula test chronic otitis media 3419 skull base lesions 3946
flexible endoscopic evaluation o f swallowing see fibreoptic endoscopic evaluation of swallowing (FEES)
Pages 1-13 12 are in Volume 1, pages 1 3 1 3-28 10 are in Volume 2, and pages 281 1-4147 are in Volume 3.
4208 1 I nd ex
flexible endoscopy oesophageal foreign bodies 1 188 stridor 1 120 upper airway obstruction 2289, 2290 F flexible intubating fibrescopes 473-4 flexible laryngoscopy 2 146-8, 2 1 47 F laryngomalacia 1 136 flexible nasendoscopy 2 147 airway management 470 head and neck tumours, childhood 1252, 1252 F flexible nasolaryngoscopy, chronic laryngitis 2259 flexible nasopharyngoscopy laryngeal stenosis 1 152, 1 16 1 posterior glottic stenosis 1 16 1 floating mass transducer ( FMT) , middle ear implants 366 1 floor of mouth carcinoma 2552-4, 2557-8 clinical presentation 2552 imaging 2552-3, 2557 investigation 2552-3 management 2557-8 presentation 2557, 2557 F survival rates 2558, 2558 T floppy 360 Nissen fundoplication, gastro-oesophageal reflux 2064 complications 2064 flow cytometric analysis, apoptosis 60 flow-directed microcatheters 732-3 flow-volume loop, airway management 470 flucloxacillin 236 fluconazole 233-4 candidiasis 224, 2789 entomophthoramycosis 2 1 5 mycotic laryngitis 2254 flucytosine 234, 442 resistance 234 disorders 993-4 fluent samples, voice evaluation 2 1 72, 2 1 74 T fluid management hypophysectomy and 4 1 1 2 newborn infant 543-4 paediatric intensive care 543-4, 544 T unwell child 544 flunarizine Meniere's disease 3800 migrainous vertigo 3804 side effects 3797, 3804 tinnitus 3 6 1 7 vestibular attacks, acute 3797
flunisolide 140 1 fluorescein lumbar puncture cerebrospinal fluid rhinorrhoea 1638-9, 1639 F complications 1639 fluorescence-activated cell sorter (FACS) 73-4 fluorescence in situ hybridization 6 fluorescent treponemal antibody (FTA), syphilis 146 1 , 2008 fluoride otosclerosis treatment 434, 3466 tooth discoloration 1 8 1 7 fluorine- 1 8 fluoroerythronitroimidazone ( FETNIM) , head and neck cancer imaging 696 2- [ 18F] fluoro-2-deoxy-D-glucose positron emission tomography see FDG-PET imaging fluoromisonidazole (FMISO) 696 fluoroquinolones 230-1 malignant otitis externa 3339 otitis externa 3354 pertussis 2252 tympanic membrane perforation with discharge 937, 937-8 fluoroscopy, children 1296-7 fluorosis 1 8 1 7 5-fluorouracil (5-FU) adjuvant radiotherapy 52 basal cell carcinoma 2397 dacryocystorhinostomy 1 695 mechanism of action 38, 39 F neoadjuvant treatment 40 salivary gland tumours, malignant 2508 temporal bone squamous cell carcinoma 4094 flutamide 244 1 fluticasone propionate allergic rhinitis 1398 children 140 1 nasal polyps 1470 nonallergic rhinitis 1412 persistent rhinosinusitis 437 rhinosinusitis, children 1083 flying, ear surgery and 3469, 3506 FM systems, education of deaf children 855, 855 F 'foam and dome' test 3733-4, 3734 F foam dressings, maxillectomy 2930, 2930 F focal bone marrow defect, jaw 1 927
focal dermal hypoplasia 1 824 focal otitic encephalitis, acute otitis media 924 foetal alcohol syndrome 968 foetal goitre, thionamide-induced 347 foetal haemoglobin 266-7 foetal surgical procedures, deafness 8 1 8 Fogarty embolectomy balloon catheter, foreign body removal 1 1 86 folate deficiency 269 Foley catheter, epistaxis 1 603 foliate papillae 1 794 foliate papillitis 1 828 folic acid cleft lip and palate 1 000 deficiency 269 encephalocoele 1 034-5 folic acid antagonists 38 follicle stimulating hormone (FSH) 301-2 circulating levels 301-2 effects 302 secretion 297, 302 structure 302 follicular dendritic cell tumour, parapharyngeal space 2527 folliculostellate cells 297 fontanelles 794 fonticulus frontalis closure, dermoid cyst 1073 food, adverse reactions 1, 1424 food additives food 1427 orofacial granulomatosis 1 828 food allergy 1 , 1424-38, 1425 F allergells 1426-7 avoidance 1 397 nickel 1426 pollen cross-reacting foods 1426, 1426 T children 1 397 clinical trials 1 cross-reactivity clinical 1427 food items 1426 T immunological 1427 definitions 1 424-5 delayed reaction IV) 1424 diagnosis 1 397, 1427-9, 1428 F case history 1427-8 diet 1 429 food additives 1427 food challenge 1429 children 1429 respiratory symptoms 1 , 1 429
Pages 1-13 1 2 are in Volume 1, pages 1 3 1 3-28 1 0 are in Volume 2, and pages 28 1 1-4147 are in Volume 3.
I ndex I 4209
investigations 1428-9 pregnancy 1426 prevalence 1427 primary prevention 1426 in infants 1426 sensitization 1425-6 infants 1425 ingestion 1425 inhalation 1425-6 intrauterine 1425 skin 1426 skin prick tests 1 394 symptoms 1428, 1428 T tolerance 1427 treatment 143 1 type I-mediated reaction 1424 food aversion 1, 1424 food intolerance 1424, 1425 F causes I , 1424 definition 1424 rhinitis 1 383 symptoms 1428, 1428 T food poisoning 196 food-processing workers, occupational rhinitis 1418 foot drop 373 1 footplate 1 326 foramen caecum 3 1 4-5, 1 794, 4120 foramen diaphragmatis 298 foramen lacerum 1 339, 2 1 1 1 , 3900 foramen magnum 3898, 3905 F foramen of Huscke 3 124 foramen of Vesalius 3899 foramen ovale 1 339, 4122 foramen rotundum 1339, 41 22,
41 23 F foramen spinosum 1339 forced expiratory volume (FEV) 1 375 'forced prolonged position' on healthy side 3812-3 Fordyce spots (granules) 1 792-3, 1 824,
1 824 F forearm flap 2869-72 advantages 2869 anatomy 2869, 2870 F applications 287 1-2 buccal carcinoma 256 1 , 2561 F disadvantages 2869-70 external skin 2871-2 oral cavity reconstruction 2570,
2570 F pinna reconstruction 3046 F technical nuances 2870-1 tongue cancer 2555-6, 2556 F foregut 1942, 1942 F
forehead flaps 2844, 2845-6, 2848-9,
2849 F nasal reconstruction 3022, 3024 F foreign bodies children 1 1 84-93 aero digestive tract 1 1 84-93 bronchial 1 1 88 larynx 546, 1 1 88 nose see nasal foreign bodies, children tracheo-bronchial tree 1 1 88-9 1 ear see aural foreign bodies ingested 1 1 86-9 1 management 1 1 87-8 inhaled 545-6 paediatric anaesthesia 5 1 9 removal 5 1 9 oesophagus see oesophageal foreign bodies pharyngeal see pharyngeal foreign bodies ultrasound examination 727 foreign speakers, speech rhythm 2 168 formal angiography, children 1 300,
1 300 F formaldehyde, occupational rhinitis 1419 formants 2 166, 2 1 79-80 singer's 2 1 78 F, 2 1 80, 22 1 1 fornix vestibuli 1793 Forrest plot 664, 664 F '40 Hz response' 3288 Fos-Jun protooncogenes 2380 fossa of Rosenmiiller see pharyngeal recess (fossa of Rosenmiiller) Foster-Kennedy syndrome 1668-9, 3915 four alternative auditory feature (FAAF) test 84 1 Fourier analysis 3 1 76-8, 3 1 76 F linear systems 3 1 78 nonperiodic sounds 3 1 77-8, 3 1 77 F periodic sounds 3 1 77, 3 1 77 F sinusoid waves 3 1 76 square waves 3 1 76-7, 3 1 77 F fourth branchial fistulae 1 779, 1780 F IVth nerve see trochlear nerve (IV) fovea ethmoidales ossid frontalis 1 328 fractional cell kill hypothesis 36 fractionated plasma products 260 fractionation 48-9, 48 F accelerated 2754-5 definition 48 early reactions 2754 fraction size 48 late tissue reaction; 2754
modifications 49, 2754 repopulation 2754 simultaneous chemotherapy and 2758-9 fracture(s) condylar neck 1622, 1624-5 facial skeleton see facial skeleton fractures hyoid bone 2272 mandible see mandibular fractures maxilla see maxillary fractures nasal see nasal fractures temporal bone see temporal bone fractures upper airway obstruction 2287 zygomatic complex see zygomatic complex fractures fragment antigen binding (Fab) regions 138 fragment crystallizable (Fc) region 138,
1 39-40 Framingham Heart Study, age-related hearing loss findings 3541-2 Framingham Offspring Study, age-related hearing loss findings 354 1-2 framycetin 937-8
Francisella tularensis 1216 Frankfort plane 2946, 2946 F Frazer's test 3509 free cartilage grafts, nasal reconstruction 3022 free-electron lasers 743 free-field speech testing 3317 otitis media with effusion 887 free flaps, head and neck reconstruction 2867-90 abdominal wall and pelvis 2876-83 classification 2867-8 defect-based options 2885-7 enteric reconstructions 2883-5 flap types 2869-72 forearm flap 2869-72 lateral arm flap 2872 free tissue transfer, considerations 2868-9 flap failure management 2869 perioperative management
2868 postoperative management
2868 recipient vessels 2868-9 perforator flaps 2867-8, 2868 F scapular system 2873-6 temporal bone 4093, 4094
Pages 1-1 3 1 2 are in Volume I, pages 1 3 1 3-28 10 are in Volume 2, and pages 281 1-4147 are in Volume 3.
421 0 I I ndex
free gastro-omental flap 2884-5 advantages 2884 anatomy 2884, 2885 F clinical applications 2884-5,
2885 F disadvantages 2884 technical nuances 2884 free grafts 2819-20 free jejunal transfer 2883-4 advantages 2883 anatomy 2883 clinical applications 2884, 2884 F disadvantages 2883 technical nuances 2883-4 free osseo cutaneous fibular flap
288 1-3 advantages 288 1 anatomy 288 1 , 2882 F clinical applications 2883,
2883 F
fresh frozen plasma (FFP) 257-60,
258 T ABO compatibility 258 characteristics 257-8 disseminated intravascular coagulation 284 haemophilia 285-6 indications 258-9 liver disease 258, 282 Rh D-compatible 258 shelf life 257 vitamin K deficiency 258 Frey's syndrome 1 846, 2484 post-parotidectomy 2484, 2484 F,
25 1 5 taste abnormalities 1 846 fricatives 2 1 67, 2 167 T Friedreich's ataxia 3773, 3774 Frisch bacillus see Klebsiella
rhinoscleroma tis
disadvantages 288 1 technical nuances 288 1-3 free radicals compromised skin flaps 1 1 3 ototoxicity and 3300-1, 3301 F free radical scavengers, ototoxicity prevention 3302 free skin grafts 2820-5 Frenzel's glasses/lenses Hallpike manoeuvre 3721 skull base lesions 3946 frequency discrimination 3252 centre frequency 3252, 3252 F frequency pattern sequences, central auditory dysfunction 3859 frequency resolution see frequency selectivity frequency response 3 1 70
frontal bone 1 340, 1 340 F development 1 3 1 8 fusion 1 3 1 8 orbital plate 3897 ossification 1 3 1 8 pneumatization 1 320 frontal bone osteomyelitis rhinosinusitis 1 545 sinusitis 1086 frontal bulla (cells) 1 333, 1 500, 1 501 F frontal cells (bulla) 1 333, 1 500, 1501 F frontalis, unilateral facial paralysis 3078-9 frontal lobes in anterior cranial fossa 4121 eye movement disorders 392 1 frontal lobe tumours, hyposmia 1668-9 frontal nerve 3923
frequency selectivity auditory filters 3246-9 auditory nerve fibres 3 197-8 cochlear hearing loss 3256 critical bands 3246-9 definition 3245 excitation pattern 3249-50 loudness perception 325 1-2 masking 3246-9 measurement 3245-50 audibility of partials in complex sounds 3245-6, 3246 F place coding 3 197-8 tuning curves bandwidths 3 198 frequency separation 3245-6 frequency threshold curves (FTCs) see tuning curves
frontal-orbital advancement and remodelling (FOAR), synostoses 1025-6, 1026 F frontal plagiocephaly 1022 T, 1025 frontal pneumosinus dilatans 1 5 1 9-20 aetiology 1 5 1 9-20 associated conditions 1 5 1 9 clinical symptoms 1 5 1 9 definition 1 5 1 9 differential diagnosis 1 520 frontal sinus obliteration I S I S , 1 520 pathogenesis 1 5 1 9-20 surgical therapy 1520 frontal recess 1 332-3 development 1 332 ostia 1332 shape/configuration 1 332
frontal rhinosinusitis complications 1539 intracranial 1 545 orbital cellulitis 1 544-5, 1 545 F medical negligence 1 735 orbital abscess 1 544-5 frontal sinus 1500-30 absence 1 340 accessory channels 1 340 anatomy 1 340, 1 500 at birth 1 320 blood supply 1340 clinical examination 1501 clinical pathology 1502-5 development 1 320, 1 500-1 disorders 1 500 clinical diagnosis 1 50 1-2 patient history 1501 drainage 1 368, 1 500 anatomical variation 1 507-8 frontobasal malformations 1502-5,
1 503 T closure defects 1 502 manifest malformations 1 504,
1 506 T occult malformations 1 504, 1 506 T histology 1340 imaging 150 1-2 infection, medical negligence 1735 inflammatory diseases 1 507-20 surgical therapy 1 5 1 8-9 innervation 1 340 inspection 1501 intersinus septum 1 340 lymphatic drainage 1 340 osteology 1340 oxygen tension 1 368 palpation 1501 pathophysiological considerations 1 500-1 surgical approaches 1 508-18 Fulda concept 1 509, 1 509-14 intra-extranasal 1514 nonresponsive inflammatory disease 1 5 1 8-9
see also individual techniques surgical drainage 1 507-8, 1510 F classification 1 509 endonasal median 1 5 1 1-3 endoscopic four-hand technique 1 509 extended 1509-1 1 indications 1510 T Lothrop procedure 1 5 1 2 neo-ostium diameter 1 509
Pages 1-1 3 1 2 are in Volume I , pages 1 3 1 3-28 10 are in Volume 2, and pages 281 1-4147 are in Volume 3.
I n d ex I 42 1 1
post-surgical packing 1 5 1 2 'rescue procedure' 1 5 1 1 , 1 5 1 2 F results 1 5 1 3-4, 1 5 1 3 F simple 1 509 type I 1509 type II 1 509- 1 1 , 15 1 1 F type III 1 5 1 1-3, 1 5 14 F trauma 1 505-7 variations 1 320, 1 340 frontal sinus cysts 1502-5, 1504 F, 1506 F diagnosis 1 504-5 extradural 1502-3 intradural 1 502-3 operative principles 1505 prognosis 1 505 frontal sinus endonasal surgery improvements 1 509 osteomas 1 522 results 1 5 1 3-4 studies 1 5 1 3 frontal sinus fistulae 1502-5, 1 504 F,
1 506 F diagnosis 1 504-5 operative principles 1505 prognosis 1 505 frontal sinus fractures 1505-7, 1 632 dural lesion 1 507 dural reconstructive techniques 1 507 imaging 1 506 reconstruction 1 507 surgery 1 506-7 frontal sinus osteomas 1 52 1-2 definition 1 52 1-2 differential diagnosis 1 522 imaging 1 502 F incidence 1522 location 1 52 1-2 surgery indications 1 522 T results 1 522 techniques 1 522 symptoms 1 52 1-2 frontal sinus rescue procedure 1 5 1 1 ,
1512 F frontal sinus trephination 1 508 medical negligence 1733 operative principles 1 508 frontal sinus tumours 1 520-4 benign 1 52 1-4 imaging 1 520-1 malignant tumour resection 1524 pneumatization 1 52 1 spread patterns 24 19 surgical approaches 1521 surgical indications 1 52 1 , 1521 F
frontal sinus wall osteoplasty, anterior 1 520, 1 520 F frontal (metopic) suture 1 3 1 8 frontal swallowing centre 1 958-9 frontoethmoidal encephalocoeles 1 503,
1 505 F frontoethmoidectomy, external 1 508-9 complications 1 508-9 operative principles 1 508 results 1 508-9 frontoethmoid suture 412 1-2 frontonasal dysplasia 1036 frontonasal malformation 1036 frontonasal process 1 570 frontonasal prominence 797, 1 8 10-1 frontonasal recess 1 500 frozen section biopsy, parathyroidectomy 393 frusemide chronic rhinosinusitis 1473 ototoxicity 3568, 3568 T, 3570 Fryn's syndrome 1 7 1 3 fucomucins, nasal mucus 1359 Fukuda test, vestibular neuritis 3752 full blood count (FBC) 267 bleeding disorders 281 mean corpuscular volume 267 normal cell ranges 267 T rhinosinusitis complications 1 543 full thickness burns, dressings 1 02 full-thickness skin grafts 2824-5 with cartilage see composite cartilage grafts donor sites 283 1 F healing 2825, 3093 eyelid carcinoma 2826 F nasal reconstruction 3019 pressure method 2827 F technique 2825, 2827 F Functional Assessment of Cancer Therapy-General/Head and Neck (FACT-G/H&N) 2773, 2774 T functional dysphonia see muscle tension dysphonia (MTD) functional hyposplenism 276 functional magnetic resonance imaging (fMRI) 675-83 analysis of imaging studies 678-9 auditory system 679-80, 680 F brain activation patterns 679 F brain region relations 680-1 cochlear implants 68 1 illustrative applications 679-8 1 image contrast generation 676-7 imaging drug re;ponses 681
imaging plasticity 68 1 individual voxels 679 left hemispheric dominance 680,
680 F MT activation 68 1 neuroanatomical interpretation 679 perfusion 677, 677 F practical details 678-9 relaxation rate 676 study designs 678
see also blood oxygenation level dependent (BOLD) functional magnetic resonance imaging functional voice disorders, children 1 169-70 fundamental frequency (Fo) 2 1 73 F, 2 1 76, 2 1 77-9, 2 1 78 F, 3 167 parameters 2 1 74 T, 2 1 78 range 2 1 77-9 reliability 2 178 speaking fundamental frequency 2 1 77-8 voice evaluation 2 1 77-9 fungal infection external nose 1 703-4 HIV patients cervical masses 247 nasal manifestations 24 1-2 paranasal sinuses 24 1-2, 24 1 F orofacial 1 833, 1 833 T tracheo-oesophageal voice prothesis valve failure 225
see also specific diseases fungal rhinosinusitis 1449-57 acute fulminant 2 16, 1450 T,
1454-5 aetiology 2 1 7 clinical features 2 1 7 diagnosis 2 1 8, 1455 epidemiology 2 1 7 fatalities 1455 immunocompromised patients 1454-5 infection sites 1455 symptoms 1455 treatment 2 1 8, 1455 allergic see allergic fungal rhinosinusitis (AFRS) classification 1450 T diagnostic criteria 145 1 T fungus ball see fungus ball invasive 2 1 6-9, 1454-5 active 2 1 6 aetiology 2 1 7 chronic 2 1 6-7, 1450 T, 1454
Pages 1-1 3 1 2 are in Volume 1, pages 1 3 1 3-28 1 0 are in Volume 2, and pages 281 1-4 147 are in Volume 3 .
42 12
• I ndex
fungal rhinosinusitis (continued) chronic granulomatous see paranasal granuloma clinical features 2 1 7-8, 1454 complications 2 1 9 definition 2 1 6-7 diabetes mellitus 402 diagnosis 2 1 8, 145 1 T epidemiology 2 1 7 granulomatous 1454 imaging 1454, 1454 F indolent 1454, 1454 F management 2 1 8-9 mouth ulcers 1 833 nongranulomatous 1454 outcomes 2 1 9 surgery 2 1 8-9, 2 1 9 treatment 1454 noninvasive 2 1 9-20, 1452-4 aetiology 2 1 9 clinical manifestations 2 1 9 complications 220 definition 2 1 9 diagnosis 2 1 9-20 epidemiology 2 1 9 management 220 outcomes 220 see also infectious rhinosinusitis;
individual conditions fungating wounds, management 1 0 1 , 453 fungi 2 1 3-27
see also individual species fungiform papillae 1794 fungus ball 1450 T, 1452 cultures 1452 diagnosis 145 1 T, 1452 imaging 1452 symptoms 1452 treatment 1452 furred tongue 1 825 furuncles, nasal vestibule 1 700 furunculosis 3323-5 aetiology 3324 definition 3323 diagnosis 3323-4, 3323 F epidemiology 3324 management 3324 outcomes 3324 recurrent 3324 Fusarium 2 1 7 fusidic acid 231-2 fusiform bacteria acute necrotizing ulcerative gingivitis 1 8 1 9 dental abscess 1 8 1 7
fusiform incisions, scar revision 2895, 2896 F Fusobacterium necrophorum 200- 1 , 1 2 14 G1 phase, cell cycle 238 1 G2 phase, cell cycle 238 1 gabapentin acquired pendular nystagmus 3804-5 herpes zoster 2005 tinnitus 36 17 gain, definition 3212 gait, clinical examination 373 1-2, 373 1 T, 3732 F gait disorders/disturbances acute unilateral vestibular deafferentation 3223 elderly 3732 neurological examination 3732 ototoxicity-related 3569 topographical classification 3730 T galactorhoea 4100 Galen's anastomosis 2 1 39 gallium (Ga-67) , malignant otitis externa 3338 gallium arsenide lasers 743 gamma-aminobutyric acid (GABA), vestibular neurochemistry 3794 gamma-aminobutyric acid (GABA) analogues, tinnitus 36 1 7 gamma-aminobutyric acid (GABA) receptors, vestibular compensation 3793 gamma knife stereotactic radiosurgery 3989-97 concerns with 3992-3 conformal plan 3990-1, 3990 F dose issues 3989-90, 3990 F knife components 3989-90 limitations 399 1 malignant transformation 3993 meningiomas 3993-4 neurofibromatosis 2 3994-5 patient treatment 3990-1, 399 1 F pituitary tumours 4 1 1 5 principles 3989-90 radiotherapy vs. 3989-90 skull-base meningioma 3993-4, 3994 T vestibular schwannoma 3992-3, 3992 T Gammaplan 3990-1 ganciclovir 28, 209, 232 ganglion mother cells (GMC) 68
gap detection, auditory neuropathy/ dyssynchrony 3852 gape 469, 470 F 'gap' theory 2767 Gardner's syndrome 1 708-9, 267 1 GaS, thyroid cancer 2670 gas analysis, anaesthesia monitoring 498 gas laws 350 1 T gastric alkalinizers 490 T gastric transposition hypopharyngeal cancer 2655-6 mortality 2656 gastrointestinal disorders antimicrobial adverse effects 236 oral manifestations 1 834 gastro-oesophageal reflux disease (GORD) 1272-8 1 , 2062-5 acute otitis media 1274 airway disorders 1 273 airway management devices 493-4 apnoeas 1273 Barrett's cancer 2067 cause 2062 child's voice assessment 1 1 69 chronic laryngitis and see laryngitis, chronic chronic otitis media 3409 clinical presentation 2063-4 complications 2064-5 contact endoscopy 763 definition 1272 dysphagia aetiology 203 1 epithelial hyperplasia 2222 globus 2037, 2038 investigation 1274-6, 1275 F, 1275 T, 2063 laryngeal cancer 663, 664 T laryngeal stenosis 1 1 54, 1 1 55, 2276 management 2063-4 natural history 1 272 otitis media with effusion 1274 otolaryngological manifestations 1 273-4 pathophysiology 1 273 pharyngeal pouch 2044, 2047 post-oesophageal atresia repair 1 287 prevalence 2062 rhinitis 1 383 rhinosinusitis 1274 self-medication 2063 spasmodic croup 1 129 stridor 1 1 19
Pages 1-1 3 1 2 are in Volume 1 , pages 1 3 1 3-28 1 0 are in Volume 2, and pages 28 1 1-4147 are in Volume 3.
_..:Z.
I ndex 1 42 1 3
surgery 2064 indications 2064 procedural choice 2066 symptoms/signs 1 273, 2063 taste abnormalities 1 848 treatment 1 276 gastropharyngeal reflux 1 272 gastrostomy dysphagia, advanced head and neck cancer 279 1 intractable aspiration 2097 oesophageal atresia repair 1285 oesophageal corrosive injury 1291 gastrulation 69 GAX-collagen, vocal fold injection 2240 gaze centres, midbrain 3 92 1 Q.a2:e-e�VOJKeQ nystagmus 3 7 1 2-3, 3713 F of 37 1 2 examination 3 7 1 2-3 laboratory assessment 3724-5 gaze holding 3225-7 gaze palsy, optokinetic nystagmus 3 7 1 7 gaze nystagmus 3 7 1 2-3, 3 7 1 2 F gaze stabilization 3207 3208 GDP, salivary secretion 1859 gefitinib (Iressa, ZD 1 839) 43, 52 gelatin micro spheres, as embolic agent 733 gelfoam, as embolic agent 733 tumour embolization, skull base 3952 gemcitabine 40 gene(s) amplification 9 definition 4, 1 5 disease associations 1 1 mapping methods 1 1 environmental factors and 16-7 expression 1 6 , 2380 disorders 3773 identification 1 9 hearing impairment 1 8 inactivation 9-1 0 interactions 1 6 mapping 1 1 , 19-20 non-coding sequences 1 6 positional cloning 1 9-20 transcription problems 2379 variant 16 gene arrays 12, 67 gene cloning 1 9-20 gene gun 23, 25 gene'ralized lymphadenopathy see HIV lymphadenopathy
General Medical Council (GMC) 573 consent issues 2806 medical negligence cases 2803 performance and complaints 605 gene therapy 23-33 ballistic gene delivery 23, 25 chromosome silencing 27 clinical trials 23 cystic fibrosis see cystic fibrosis deafness 8 1 8 head and neck cancer see head and neck cancer immune modulation 28 liposomes 25 neurofibromatosis 2 4004 vectors 23 genetic code 1 5 genetic counselling, childhood deafness 852-3 genetic deafness 8 1 1 mouse models 8 12-3 genetic disorders cell biology 8-10 stem cell therapy 73, 75-6 genetic manipulation congenital deafness 8 17-8 molecular otology 8 1 1-20 mutation 9 1 5-22 animal models 20 deafness 17, 20 childhood deafness 845 future developments 2 1 inheritance patterns 1 8-9 research 20 terminology 812 T testing childhood deafness 85 1-2 craniosynostosis 102 1 neurofibromatosis 400 1 , 4003, 4004 gene transfer congenital deafness 8 1 7 vectors 8 1 7 genial tubercles 2908 geniculate ganglion embryology 1 052, 1 053 facial nerve tumours 4079 geniculate neuralgia surgery 3532 geniculate neuralgia 3532 aetiology 3532 surgery 3532 genioglossus 1 796 F, 1 797, 1 797 F, 1 956--7 geniohyoid 1 796, 1 796 F, 1 797F, 2 1 35 T �.
genital warts, juvenile-onset recurrent respiratory papillomatosis 1 1 75 genome 3 human 4 mitochondrial 3, 4-5 structure 2378-9 genome scan 1 9-20 genomic rearrangements 1 0 gentamicin active mucosal chronic otitis media 3424 malignant otitis externa 3339 medical negligence 383 1 Meniere's disease 433, 3760, 3800 ototoxicity 3299F,3568-9, 3676, 3677 F, 3800 bilateral vestibulopathy aetiology 3764 incidence 3300 geographical tongue 1 825-6, 1 826 F geometric broken line closure (GBLC) 2896, 2897, 2898 F geometric primitives 704 Gerlach's (tubal) tonsil 1 094, 2 108 Gerstmann-Straussler-Scheinker syndrome 3775 giant cell granuloma 1 654-5, 1 930 clinical features 1 654 F, 1655 definition 1654-5 histology 1 655 1malging 1 655 treatment 1 655 cell reaction of bone' s e e giant cell granuloma 'giant cell reparative granuloma' see giant cell granuloma giant cell thyroiditis see subacute thyroiditis hairs 3676 giant hairy naevus 2400 giddiness see vertigo 'Gillick competence' 585-6, 601, 78 1 Gillick v. West Norfolk and Wisbech Area Health Authority ( 1 985) 601 Gillies fan flap, lip cancer 2547, 2547 F Gillies principles, reconstructive surgery 2847 Gillies procedure 3079 Gillies temporal approach, zygomatic complex fractures 1 629, 1629 T ginger, motion sickness 3797
Pages 1-1 3 12 are in Volume 1, pages 1 3 13-28 1 0 are in Volume 2, and pages 28 1 1-4147 are in Volume 3.
421 4 • I n dex
glatiramer acetate 3772
gingivae 1 79 1-2
Gleevec (imatinib mesylate) 44
blood supply 1 798
fossa reconstruction 4052
innervation 1801-2, 1802 T lymphatic drainage 1 799
cell-derived neurotrophic factor (GDNF) 2669, 3302
pigmentation 1 8 1 9 causes 1 8 19, 1 820 T
CPA impingement 401 5
venous drainage 1 799
anatomy/physiology 736, 738 F CPA involvement 40 1 5 carotid body
see
carotid body
paragangliomas catecholamine metabolite
glioma(s)
racial 1 820 F
glomus tumours (paragangliomas)
assessment 4028
frontal sinus 1 503, 1 505 F
chromaffin 4029-30
nasal 1 075, 1075 F, 1 709
clinical symptoms 736-9
adults 1 926
nasopharyngeal 2 1 19
embolization 3953
of infancy 1 926
neurofibromatosis 2 4000, 4002
familial 2526-7
pituitary region 4104
hearing loss 3943-4
gingival cysts
gingival disorders 1 8 18-20 bleeding 1 8 1 8-9, 1 8 1 9 T
global developmental delay, speech and
redness 1 8 1 9-20
'global' type meningiomas 4008 globulomaxillary cysts 1 320-1
causes 1 8 1 9 drug-induced 1 820, 1 8 2 1 F
jugular foramen 4029-30, 403 1 F,
4032 categorization 4029-30
globus 2037-42
swelling 1 820, 1821 T
histology 4029-30 incidence 3943
language 992
blisters 1 8 1 9
classification 4030, 4030 T
aetiology 2038-9
ulcers 1 820
behavioural control 2040
embolization 4034
white patches 1 820, 1 8 2 1 T
clinical recommendations 2040
incidence 4030
clinical studies 2038
localization 4029-30
gingivitis
definition 2037
radiotherapy 4043
necrotizing ulcerative gingivitis
diagnosis 2039-40
resection 4039-40, 4041 F
(ANUG)
differential diagnosis 2039
surgery, internal carotid artery
acute necrotizing ulcerative
see
acute
dysphagia 2026, 2035
chronic gingival bleeding 1 8 1 8-9, 1 8 1 9
T
gingival redness 1 8 1 9 HIV patients 243, 244 T Gingko biloba idiopathic sudden sensorineural hearing loss 1, 3589 T tinnitus 36 1 8
dysphagia aetiology 2026, 2035 epidemiology 2037-8
laryngeal 2600 T
follow-up 2040-1
malignant 2526
gastro-oesophageal reflux 2038
multiple 2526-7
gender 2038
nonchromaffin 4029-30
historical aspects 2037
otoscopy 3945
history taking 2039
tumour embolization 734, 736-9,
GJB2 gene 1 5-6, 18, 20, 845, 85 1-2
incidence 2037
glandular fever
management 2040
see
infectious
management 4039 symptoms 4028
738 F, 739 F 3953
nrp'An,or"irnTP
patient examination 2039
ultrasound examination 725-6, 726 F
glandular odontogenic cysts 1 925
prognosis 2040-1
vagal 2526, 2530
Glanzmann's disease 288
psychogenic causes 2039
Glasgow Benefit Inventory (GBI) 639,
radiology 2039-40
glomus tympanicum 4029-30
symptom persistence 2040
glomus vagale tumours 3953
mononucleosis
639 T bone-anchored hearing aids 3647
globus clinic 2040-1
vestibular schwannoma
globus pharyngeus
removal 3984-5 Glasgow Children's Benefit Inventory 895 Glasgow coma scale (GCS) maxillofacial injuries 1 620 neck trauma 1 766-7 Glasgow Hearing Aid Benefit Profile 640
bone-anchored hearing aids 3646 glass ceramics 1 20 synthetic tissue scaffolds 123 tissue scaffolds 1 24 T glass ionomer cements (GIC) 120,
121 F
globus pharyngis
glossitis 1 828-9, 1 843-4
see
see
vestibular nerve 3691
globus
globus
glossodynia (burning mouth syndrome) 1 829, 1 829 T, 1 848-9
glomeruli, olfactory bulb 1 663
glossoepiglottic fold 2 1 33
glomerulonephritis
glossopharyngeal-accessorius
antibiotic-induced 1 985-6 tonsillitis complications 1 224 glomus j ugulare 4029-30 tumours 2526, 2531 carotid angiography 3950 F complete particle embolization 3954 F radiosurgery 3995 surgery-induced injury
2222-3 glomus jugulotympanicum 4029-30
complex 2 155-6 glossopharyngeal nerve (IX) 1751,
1 797 F, 1 803, 3933-4, 3933 F autonomic parasympathetic fibres 3933-4 carotid branch 3933-4 central processes 3933-4, 3934 F clinical disorders 3937-8 clinical evaluation 3937-40 in j ugular foramen 3901 , 3903 F motor nucleus 3933-4
1-13 1 2 are in Volume 1 , pages 1 3 1 3-28 1 0 are in Volume 2, and pages 2 8 1 1-4147 are in Volume 3.
I ndex I 42 1 5
in neck 1 75 1 neuralgia 353 1-2 pharyngeal branches 1950, 2074 skull base lesions 3946 taste bud innervation 1 84 1 glossopharyngeal nerve block 480 glossopharyngeal nerve injuryllesions taste abnormalities 1 846-7 taste sensation impairment 3937 temporal bone resection complication 4094 glossopharyngeal neuralgia (GPN) 1 724, 208 1 , 3934 aetiology 353 1 cranial root injury 353 1 incidence 208 1 medical management 353 1-2 oropharyngeal 353 1 otalgia 353 1-2 pain sensation 3919 recurrence 208 1 surgery 3532 symptoms 208 1 , 353 1 treatment 2081 tympanic 353 1 glossopharyngeal nuclei 2075 F glossopyrosis (burning mouth syndrome) 1 8 1 8 T, 1 829, 1 848-9 glottal consonants 2 167 T glottal fry (vocal pulse register) 2 1 6 1 , 2 162 T glottal insufficiency 2 160 glottal signal characteristics 2 165 frequency 2 165 modification 2 165-6 quality 2 165 glottal-to-noise excitation (GNE) 2 1 8 1 glottal volume velocity waveform 2 1 82 glottic cancer clinical presentations 2608 diagnostic delays 2603 endoscopic resection 2612, 2612 F haemoptysis 2608 radiotherapy regimens 2610 referred otalgia 2608 spread 260 1 surgery vs. radiotherapy 2610, 2610 T TNM classification 2366 T treatment 26 1 0 glottic chink 1 1 5 1 glottic closure incomplete, phonation and 2 1 60-1 surgical, intractable aspiration 2 1 0 1-2, 2 1 0 1 F
glottic irritability 481-2 glottic obstruction 48 1-2 anaesthesia depth 48 1 glottic stenosis 228 1-2 posterior see posterior glottic stenosis glottic webs, anterior see anterior glottic webs glottis 2 1 34-7 anatomy 1 1 35, 2 1 32, 2 132 F, 2 134-7, 2 1 34 F children 1 1 5 1 congenital disorders 1 1 37-9 development 803-5, 2 1 30 laryngeal stenosis 2277 laryngeal trauma 2272 glucocorticoids allergic rhinitis 1398 asthma 1564 croup 1 128-9 Cushing's syndrome diagnosis 309 excess see Cushing's syndrome jugular foramen meningioma 4042 onset of action 1 398 rhinitis 1 564 rhinosinusitis 436-7 side effects 1 398 vestibular compensation 3793 wound healing inhibition 95 gluconeogenesis, critical care patients 530-1 glucose, newborn infant 544 glucose tolerance test 30 1 glue ear see otitis media with effusion (OME) glutamate noise-induced hearing loss 3549 olfactory receptor neurons 1662-3 tinnitus 3604 vestibular hair cells 3237, 3794 glutamine, critical care patients 532 glutathione 3302 glycaemic control, critical care 535 glycerine injection, vocal fold paralysis 2240, 2245 T glycopeptides 230 glycoproteins acidic 1 359 nasal secretions 1 359 neutral 1359 glycosaminoglycans (GAG) DFNA9 mutations 3238 Graves' disease 343 myxoedema 353 tissue scaffolds 12'3
goblet cells frontal sinus 1 340 maxillary sinus 1 34 1 nasal 1359, 1359 F nasal polyposis 1 5 5 1 otitis media with effusion 878 septum 1 327 sphenoid sinus 1339 goitre aetiology 2666-9 growth factors 2668 atrophic autoimmune thyroiditis 356 classification 2666 colloid 3 3 1 , 720 diffuse nontoxic 330 toxic see Grave's disease foetal 347 genetics 2667-8 Hashimoto's thyroiditis 356 hypothyroid 335 iodine deficiency 356 iodine-deficiency 2666-7 iodine-sufficient 2667 multinodular see multinodular goitre nodular with abnormal function 335 with normal function 330-1 ultrasound 719, 7 1 9 F prevalence 2666-7 thyroid neoplasms 400 thyrotoxicosis 339 WHO definition 2666 see also nodular thyroid disease goitrogens 2668 Goldenhar syndrome 1033, 1055, 3642-3 golden ratio 2944, 2944 F Goldman tip technique 295 1 F, 3001-2 columella struts 3002, 3002 F incision 300 1-2, 300 1 F shortening 3003 F suture 300 1-2, 300 1 F underprojected nasal tip 3002 vertical dome division 300 1 F, 3002 Goltz-Godin syndrome 1 824 gonadal diseases 402-3
see also individual diseases gonadal dysgenesis see Turner's syndrome gonadotrophinoma 3 1 1 , 4 103 gonadotrophs 297 gonadotropin(s) 30 1-2 circulating levels 301-2 effects 302
Pages 1-1 3 1 2 are in Volume 1, pages 1 3 1 3-28 1 0 are in Volume 2, and pages 281 1-4147 are in Volume 3.
421 6 I I ndex
gonadotropin(s) (continued) pituitary gland 297 puberty 30 1-2 secretion 308 control 302 in women 302, 308 structure 302 gonadotropin-releasing hormone (GnRH) 300 effects 302 gonococci 199
Good doctors, safer patients 573, 575 Good medical practice 573, 574, 576, 2804 Gore-Tex augmentation rhinoplasty 297 1 , 2974 complication rates 2975 T facial surgery 1 2 1 Godin's syndrome 1 705-6, 2396 Goundou 1 703 gp 120 glycoprotein, HIV 238-9 G-protein coupled receptors, olfaction 1 367 Gradenigo's syndrome 3 1 19, 3918-9, 4046, 4047 grafts alloplastic 96 autologous 96 failure, medical negligence 3093 free 2819-20 head and neck surgery 2819-46 heterologous 96 homologous 96 skin see skin grafts
see also individual grafts Gram-negative bacteria 1 99-200 aerobic see Enterobacteriaceae
see also individual species Gram-positive bacteria 1 96-9
see also individual species granular cell tumours, larynx 2600 T granular myringitis 3328-3 1 aetiology 3328 complications 3329 definition 3328 diagnosis 3329 investigations 3329 management 3329-30, 3330 T natural history 3329 outcomes 3329 pathology 3328 post-tympanic membrane grafting 3328 signs 3329, 3329 F symptoms 3328
granulating wounds, dressings 10 1-2 granulation tissue 90 F, 98 composition 93 formation 88, 89-90 proliferation 9 1-3 tracheostomy-induced 1203-4 granulocyte-colony stimulating factor (G-CSF), effects on stem cells 69 granulocyte-macrophage-colony stimulating factor (GM -CSF), effects on stem cells 69 granulocytes 273 granuloma(s) arytenoid see arytenoid granuloma cholesterol see cholesterol granuloma dental abscess 1 8 1 7 denture 1 828 giant cell see giant cell granuloma paranasal see paranasal granuloma vocal process see arytenoid granuloma granulomata formulation, vasculitides 1 87, 187 F granulomatous conditions, nasal see nasal granulomatous conditions granulomatous myringitis see granular myringitis granulomatous thyroiditis see subacute thyroiditis granulopoiesis 272-3 Graves' disease 340-5 acropachy 343 associated conditions 343 clinical manifestations 3 3 1 , 343, 400 dermopathy 343 drug treatment 346-7 combination 347 efficacy 347 extra thyroidal manifestations 343 eye disease see thyroid eye disease genetics 342, 2668 histology 343 F imaging 335 incidence 340 investigations 335 in vitro tests 328 T, 334-5 multinodular goitre and 3 3 1 , 335 natural history 343 pathogenesis 34 1-3 post-partum thyroiditis 358 pregnancy 359 diagnosis 359 symptoms 359 treatment 359
radioiodine therapy 347, 349 dosage 349 recurrent hyperthyroidism 349 relapse 347 prognostic factors 347 risk factors 340 surgery 351 thyroid autoantibodies 343 thyroid cancer association 267 1 treatment 343, 2670-1 tremors 400-1 vitiligo 343 F see also hyperthyroidism gravitoinertial acceleration (GIA) 32 1 1 gray (Gy) accelerated hyperfractionation 2755 accelerated radiotherapy 2754 elimination 2754-5 hyperfractionated radiotherapy 2755 GRBAS scheme 2 1 75, 2 1 75 T, 2 1 76 greater auricular nerve 1 853 pleomorphic adenoma recurrence 2489 greater cornua, hyoid bone 1 740, 2 1 32 greater palatine artery 1 328, 1 799 greater palatine nerve 1 80 1 , 1 802 T greater petrosal nerve 1 80 1 , 3928 greater superficial petrosal nerve 3910 middle fossa surgery 401 8-9, 4020 greater wing, sphenoid 3899 Greatest Happiness Principle (GHP) 584 Greenspan model 1 000 'grey baby' syndrome 231 Griesinger's sign 924 Grisel syndrome 1098, 1 236 griseofulvin 234 grommets see ventilation tubes Groningen valve 2625, 2626 F, 2627 Group A beta-haemolytic streptococci (GABHS) pharyngitis 1 982-3 antibiotic use 1 984-5 carrier state 1987 clinical findings 1983 complications following 1986-7 diagnosis article appraisal 654, 656,
656 T features 1 983 incubation period 1982-3 investigations 1984 M-proteins 1 982-3, 1 983 pathophysiology 1983 prognosis 1987
Pages 1-1 3 12 are in Volume 1, pages 1 3 1 3-28 1 0 are in Volume 2, and pages 281 1-4147 are in Volume 3.
I ndex I 42 1 7
rapid antigen testing 1 984 throat culture 1 984 rheumatic fever 1 986-7 tonsillitis 1 2 1 9-20, 1220-1, 1 220 F group and screen (G&S) test 254 elective surgery 255 emergency surgery 255, 256 F fresh frozen plasma transfusion 258 safe practice 255 group A streptococci see streptococci, group A group C streptococci 197 group G streptococci 197 growth factors cell signalling 36 goitre 2668 overproduction 36 stem cells 67, 71-2 growth fraction 238 1 growth hormone (GH) 297, 30 1 , 309 adenoma secretion see acromegaly anterior pituitary secretion 4098 circulating levels 301 deficiency 309 effects 301 half-life 30 1 insulin-like growth factor 1 301 secretion control 30 1 , 309 fluctuations 308 structure 309 tests 30 1 , 309 growth hormone releasing hormone ( GHRH) 300 GSTM 1 AB 2355 GTP binding protein cell receptors 2384, 2384 F Guangdong tumour 2445 guanine 3 guanine nucleotide-binding regulatory protein (G protein) , saliva 1 859 guar gum, occupational rhinitis 1418 guided bone regeneration 2920, 2920 F guided tissue regeneration (GTR) 2916, 2916 F Guillain-Barre syndrome facial nerve palsy 3887 pharyngeal dysfunction 2078 sensory ataxia 3778 guillotine tonsillectomy 1232-3, 1 992-3 gum elastic bougie, difficult airways 472-3, 473 F gumma 146 1 , 146 1 F, 1 703 gunning splints, mandibular fractures 1623, 1624 F
gunshot wounds facial nerve trauma 3887-8, 3887 F transcervical 1 766-7 gustatory agnosia 1843 gustatory auras 1 846 gustatory disorders see taste abnormalities gustatory lemniscus injury 1 847 gustatory mucosa, mouth 1 795 gustatory rhinitis 1 383, 14 1 1 gustatory structures, central 1 84 1-2 citric acid recognition 1 842 gut-associated lymphoid tissue (GALT), pharynx 1951 gyrus rectus 4 1 2 1 H I -antihistamines allergic rhinitis 1564 asthma 1 564 HTreceptor antagonists advanced head and neck cancer 2785-6 juvenile-onset recurrent respiratory papillomatosis 1 1 79 reflux oesophagitis 452 H5N1 influenza 205-6 habituation tinnitus 360 1-2, 3607-8 vestibular compensation 3792 hadrons 47 haemangioblastoma, embolization 734 haemangioma, parotid 1 247, 1247 F, 1248 F haemangioma (s) geniculate ganglion 408 1 larynx 2600 T middle ear 4072 differential diagnosis 4072 nasal 1 075-6, 1 075 F, 1 708 oral 1823, 1823-4 salivary glands 1 247, 1 247 F subglottic see subglottic haemangioma ultrasound examination 726 haemangiopericytoma( s) children 1 259 T epistaxis 1 606 middle ear 4072 radiosurgery 3996 sinonasal 2422-3 tumour embolization 734-5 haematocrit, polycythaemia 272 haematological diseases, oral manifestation� 1 833-4
haematoma 102 post-rhytidectomy 3074 post-vestibular schwannoma removal 3978 septal see septal haematoma skull base surgery 4 1 3 7-8 subdermal 3092 subdural 103 1 syndromic craniosynostosis surgery induced 1031 thyroidectomy complication 3 5 1 treatment 1 0 2 haematoma auris 3373-5, 3374 F aetiology 3373 clinical picture 3373 definition 3373 diagnosis 3373 management options 3374 outcomes 3373 pathogenesis 3373 pathology 3373 haemato-oncology 265-77 haematorrhoea, skull base fracture 3496 haematoxylin and eosin (H&E) , apoptosis identification 6 0 , 6 0 F haemin (X) 199 haemodialysis (HD), critical care unit 530 haemoglobin (Hb) 266-7 2,3-diphosphoglycerate 267 adult (HbA) 266-7 anaemia 267 blood oxygenation level-dependent fMRI 678 critical care, adult 535 erythropoiesis 266 foetal 266-7 oxygen delivery 267 synthetic allosteric modifiers 5 1 haemoglobin Barts (HbBarts) 271 haemoglobin electrophoresis 271 haemoglobinopathies 270 haemoglobin S (HbSS) 270 haemoglobin substitutes 263 haemolytic anaemia 270 causes 270 investigations 270, 270 T haemolytic disease of the newborn 254 haemolytic toxins 1 96 haemolytic uraemic syndrome (HUS) 286-7 diagnosis 286 treatment 287 haemophilia 285 bleeding patterns 281, 285 inheritance 280, 285
Pages 1-1 3 1 2 are in Volume I, pages 1 3 1 3-28 1 0 are in Volume 2, and pages 2 8 1 1-4147 are in Volume 3.
42 1 8 I I ndex
haemophilia (continued) pre-surgery management 285 blood tests 285 T elective surgery 285 emergency surgery 285-6 haemophilia A 284 T, 285 inheritance 280, 285 haemophilia B 284 T, 285 inheritance 280, 285 Haemophilus 199-200 Haemophilus inJluenzae 199-200 acute otitis media 9 1 5 acute sinusitis 1080 adult epiglottitis 2250 nasal infection 1 700 nasopharynx: 2 1 2 1 otitis media children 195-6 HIV-associated infection 240 rhinosinusitis 144 1 chronic 1471 HIV-associated 241-2 serology 1 99-200 tonsil flora 1 2 1 9-20 vaccination 199-200, 9 1 9, 920
Haemophilus inJluenzae type b meningitis 924
Haemophilus inJluenzae type b vaccine (Hib vaccine) 199-200, 1 1 3 1-2 epiglottitis 1 309, 2250 haemopoiesis 265-6, 266 F children 265-6 extramedullary 266 foetal 265-6 sites 265-6 haemopoietic malignancies 274 treatment 274 haemopoietic stem cells 67, 72, 266, 266 F classification 69 erythropoietin 266 lineage 266 pluripotency 266 haemoptysis, glottic cancer 2608 haemorrhage facial skeleton fractures 1 6 1 9-20 gingival 1 8 1 8-9, 1 8 1 9 T hypophysectomy 4 1 1 3 hypotensive anaesthesia 502 intracranial hypophysectomy complications 4 1 1 3 olfactory dysfunction 1667 malignant ulcers/fistulae, palliative care 2792-4, 2793 T
radical neck dissection complication 2743 perioperative 2743 postoperative 2743 skull base surgery complication 4 136 arterial 4 1 36 venous 4136 spontaneous 280 haemophilia 285 tonsil 1225 vestibular system 3698-9 tracheostomy 230 1 upper airway obstruction 2287 vestibular schwannoma 3959-60 haemorrhagic (solitary bone) cyst 1926-7 haemorrhagic necrosis, antivascular agents 5 1 haemosiderin 268 haemostasis 278-92 disorders 278-92 laboratory tests 280 mechanism 279 F neck trauma 1 767 tracheostomy 230 1 haemostatic clips 1 603, 1 603 F haemotympanum 3496 'haem pockets' 267 haem synthesis 267 Hageman factor 89 hair cell(s) cochlear see cochlear hair cells duplex activity 3 1 39 function 3 1 32-6 supporting cells of 3 1 30 ultrastructure 3 1 36 ultrastructure 3 1 32-6 vestibular system see vestibular hair cells
halothane endoscopy procedures 5 17, 1 1 2 1-2 periglottic! glottic obstruction 48 1 hamartomas, cerebellopontine angle 40 14 Hanafy lens 7 1 2 hand, foot and mouth disease 2005 handicap (definition) 783 Hand-Schuller-Christian disease see Langerhan's cell histiocytosis (LCH) Hansen's disease see leprosy H antigen 253-4 HAPEX implants 120, 120 F hard palate 179 1-2, 1 792 F blood supply 1799 centres of ossification 1 8 1 3 repair 1006-7, 1 007 F rugae 1 79 1-2 skeleton 1 79 1 hard palate carcinoma 2562-3, 2562 F investigations 2562 outcome 2563, 2563 T presentation 2562 treatment 2562-3 partial lateral maxillectomy 2562-3 hard tissue repair 87-109 hardwired systems, hearing impaired 3667 Hardy dissectors, hypophysectomy 4 1 10 Hardy retractor, hypophysectomy 4106, 4106 F 'harlequin eye,' craniosynostosis 1 022 harmonic oscillation 3 1 58-9 harmonics 3 167 spacing 3253
hairstyling, scar revision 2899 hairy leukoplakia (HL) 1 837, 1 837 F Epstein-Barr infection 208-9 HIV 208-9, 242, 244 T hairy polyp, nasopharynx: 2 1 19 Haller cells 1 334 F, 1 335 T Hallpike manoeuvre benign paroxysmal positional vertigo 372 1 , 3721 F nystagmus 3722 halogenated methyl-ethyl ethers 49 1 halogenated pyrimidines, as radio sensitizer 50 haloperidol, cancer patients acute confusional states 2798 anxiety 2795 nausea and vomiting 2788
harmonic scalpel dissection tonsillectomy 1992 harmonics of the frequency 3 1 77 harmonics-to-noise ratio (HNR) 2 165, 2 1 80-1 , 2 1 80 T Hashimoto's thyroiditis 355-6 atrophic autoimmune thyroiditis 356 goitre 356 histology 33 1-2, 356, 356 F investigations radionuclide scan 336 ultrasound examination 721 in vitro investigations 332 pathogenesis 356 prevalence 355-6 thyroid lymphoma 33 1-2, 336, 267 1 , 2676-7
Pages 1-1 3 1 2 are in Volume I, pages 1 3 1 3-28 1 0 are in Volume 2, and pages 281 1-4147 are in Volume 3.
-�
I ndex I 42 1 9
'Hashitoxicosis' 335 Hasner's valve 1 344-6, 1 690 hatchet flap 2869-70, 2871 F hayfever immunotherapy 1 399 HbH disease 271 headache acute otitis media 924 cluster 1722, 1 723 F glomus tumours (paragangliomas) 40 1 5 intracranial procedure, following 4145 nasopharyngeal carcinoma 2452 pituitary tumours 4100 skull base lesions 3944-5 skull base surgery 4139 tension-type 1724-5, 1 725 F head and neck embryology 792-8 1 0 Carnegie stages 793 T examination, skull base lesions 3945 head and neck cancer aetiology 235 1-8 AIDS defining 20 12-3 chemotherapy/radiotherapy developments, hypoxic cell sensitization 2756-7 children 1 25 1-63 assessment 1252-3 biopsy 1252-3 cardiac problems 1260 cognitive and psychological problems 1261 common types 1254-60 dying child 1261 effect on child 1253 epidemiology 125 1-2 follow-up 1261 growth 1260 imaging 1253 impact on family 1253 long-term treatment sequelae 1260-1 oncology services 1 253 otolaryngological manifestations 1 260-1 presentation 1252-3 reproductive function 1260 thyroid disorders 1260 complications 2655 data collection see data collection, head and neck cancer dysphagia management 2086, 2087-8 epidemiology 2343-50 principles 2343-6
facial defect reconstruction 2926 FDG-PET imaging see FDG-PET imaging gene therapy 26-9 adenoviruses 27, 29 chemosensitization 28 delivery 26 immune modulation 28 lentiviral vectors 27 nonviral vectors 26-7 p53 delivery 29 plasmid DNA 26-7 restorative 29 retroviral vectors 27 selective oncolytic virus 29 strategies 28-9 gene therapy-induced 27 HIV infection 20 12, 20 12 T markers 2385 metastatic see metastatic neck disease palliative care see palliative care, head and neck cancer photodynamic therapy 746 prognostic indications 2378-94 quality of life see quality of life radiotherapy 2753-65 serum markers 2378-94, 2385
see also individual types staging 2359-7 1 aims 2359-60 classification 2362 component definitions 2360 T grouping 236 1-2, 2361 T grouping limitations 2368-9 histopathological grading 2361 history 2360 lip and oral cavity 2364 method 2362-3 N staging limitations 2368 pathological classification 2364 preoperative investigations 1984 primary site evaluation 1984 sites 2363-6
see also individual head and neck regions TANIS score 2369 T staging limitations 2367-8 tumour-specific survival 2654 F
see also specific cancers Head and Neck Radiotherapy Questionnaire (HNRQ) 2773, 2774 T head and neck reconstruction historical perspective 2925
prosthetic and surgical combined approach 2924-42 case studies 2933-41 extra-oral prostheses construction 2930-1 future developments 2941-2 historical perspective 2924-5 patient assessment 2925 patient follow-up 2932-3 surgical resection planning 2925
see also individual techniques head and neck sarcomas 193 1-8 aetiology 1 93 1 , 1 933 T histological distribution 193 1 , 1 933 T imaging 1931 inherited disease and 1 93 1 , 1 933 T investigations 1931 lymph node metastases 193 1 management principles 193 1-4 pathogenesis 193 1 relapse 1 938 treatment 1938 risk factors 193 1 , 1 933 T soft tissue see soft tissue sarcomas (STS) surgery 1 933 surveillance 1 938 systemic therapy 1 933-4
see also individual types head and neck squamous cell carcinoma (HNSCC) aetiology alcohol 235 1-2 diet 2353-4 environment 2353 familial predisposition 2354-6 genetic disease 2354 molecular/genetic progression model 2355 F, 2356 occupation 2353-4 tobacco 235 1-2 viruses 2352-3 case-controlled study 2356 chemotherapy 40 GSTMI AB 2355 markers 2385, 2386-90 T, 239 1 T radiotherapy, dose-response curves 48 head and neck surgery drug therapy 446-54 grafts see grafts historical aspects 28 1 3-8 lasers see laser therapy local flaps see local flaps
Pages 1-1 3 1 2 are in Volume 1, pages 1 3 13-28 1 0 are in Volume 2, and pages 281 1-4147 are in Volume 3.
4220 1 I ndex
head and neck surgery (continued ) medical negligence 2803-10 diagnostic delay 2807
measures see outcomes research
measurement 3633
WHO definition 2767
mechanism of action 363 1
see also quality of life
multichannel compression 3634, 3637
operative problems 2807-9
Health Service Commissioner 605
multimemory 3637
preoperative issues 2807
health service research,
otitis media with effusion 3393
head angular acceleration calculation 32 1 2 semicircular canal 32 1 1 head angular velocity 3212 head eccentric rotation, otolith testing 3737 head impulse test 3224-5, 3226 F,
3719-20, 3 7 1 9 F bilateral vestibulopathy 3764
epidemiology 6 1 7-8 Health Utilities Index (HUI) 637, 639,
642 hearing 3 173-206 bone conduction 3 185-6 cochlear fluid movement 3 1 85 external ear factors 3 185-6 inner ear factors 3 1 85 middle ear factors 3 185
children 903 otosclerosis 3467 ototoxicity-related hearing loss 3573 outcome assessment 3638-9 patient assessment 3635-6 prescribing 3636-7 linear aids 3636 nonlinear aids 3636 problem solving 3637-8 selection 3637
catch up saccades 37 1 9-20
clinical assessment 3 3 1 7-9
unilateral peripheral vestibular
middle ear see middle ear
self-report measures 3639
physiological vs. behavioural
signal-to-noise ratio 3634
deficits 3719-20 vestibular neuritis 3752, 3753 F,
3756-7, 3756 F, 3769-70 vestibuloocular reflex 3224, 3719-20 head injury/trauma benign paroxysmal positioning vertigo 3760 cerebrospinal fluid rhinorrhoea 1 636-7, 1 637 F epistaxis 1 605 olfactory dysfunction 1 667, 1 668 F
assessment 3276
special needs children 786
physiology 3 1 73-206
systems 3632-3
see also ear(s); sound
tinnitus 3614-5
hearing aids 363 1-41
see also specific devices
adaptive arrays 3635
hearing dogs 3545
adjustment 3637
Hearing Handicap Inventory for the
advanced signal processing schemes 3635 age-related sensorineural hearing impairment 3544, 3545
Elderly (HHIE) 640 hearing loss/impairment acquired aetiology 3298-300
olfactory fasciculi lesions 3913
auditory neuropathy/dyssynchrony
noise-related 3298
taste abnormalities 1 846
permanent bilateral 824 age-related (presbycusis) 3298
headlight intranasal surgery 1636-7
385 1-2, 3852 T children 3852 bilateral fitting 3639-40
head movement, eye movements and
binaural considerations 3639-40
auditory hallucinations 3864
backwards tilt 3 2 1 9 F
Bluetooth-enabled 3669
bone-anchored hearing aids 3646
pitch forwards 32 1 8 F
children 854, 3640
children
temporal bone fractures 1057
sideways tilt 3218 F head orientation 3208-10
evaluation 3640 chronic otitis media 3434-5
animal models 3298, 3301-2, 3303
diagnostic delay 1 306 early deprivation and plasticity 825
internal model 32 1 0-1
active 3435
medical negligence 1 306
observation 3731
healed 3434-5
prevalence 823-5
head-out body plethysmograph, rhinomanometry 1 373
inactive 3435 communication training 3638
head-thrust test see head impulse test
comparisons 3643 T
head trauma see head injury/trauma
components 3632
healthcare beneficence model 650
compression systems 3634-5
Healthcare Commission
counselling 3638
clinical governance monitoring 572,
coupler targets 3637
risk factors 823-5 temporary 825 voice assessment 1 169 communication, medical consultations 566 conductive, otitis media with effusion 3391
coupling systems 3633-4
definitions 3298
head and neck cancer audit 572
electro acoustic performance 3633
devices see accessory devices
performance and complaints 605
feedback oscillation 3635, 3637
diabetes mellitus 402
572-3
Health Care Standards Unit ( HCSU) 571 health care workers, occupational rhinitis 1419 health information, internet 574 health-related quality of life (HRQoL) definition 634
fine tuning 3637-8
drug-related see ototoxicity
fitting, pure-tone audiometry 3267
epidermoids 401 1
gain adjustment, tympanometric
facial nerve tumours 4080
acoustic reflex measurement 3289
frequency selectivity 3256
1 7-8
loudness recruitment 3256
hair cell degeneration 20
maximum output 3636
high frequencies 3257
Pages 1-1 3 1 2 are in Volume 1 , pages 1 3 1 3-28 1 0 are in Volume 2, and pages 2 8 1 1-4147 are in Volume 3.
I ndex 1 422 1
HIV-associated 24 1 hypothyroidism 400 incidence 17 loudness perception 3256 loudness recruitment 3256 management 3629-30 masking 3256 measurement see audiometry meningioma 3943-4, 4009 mixed, bone-anchored hearing aids 3646 multiple sclerosis 3846-8 neurofibromatosis 2 4000, 4003 noise-related see noise-induced hearing loss (NIHL) otitis media with effusion 893 ototoxic see ototoxicity Paget's disease 3487-8 paraganglioma 3943-4 perilymph fistulae 1 047 peripheral, central auditory dysfunction 3864 pitch perception 3256 post-meningitic 824 postsurgical, medical negligence 383 1 prevention 3298-306 antioxidants 3302 cell death inhibitors 3302 clinical outlook 3302-3 limitations 3303 neurotrophic factors 3302 principles 3301 retrocochlear see retrocochlear hearing disorders rheumatoid arthritis 1 86 rheumatological diseases 1 84 sensorineural see sensorineural
hearing monitoring, intraoperative 3292-3 auditory/nonauditory structure differentiation 3293 patient preparation 3293 hearing rehabilitation, vestibular schwannoma 3984 hearing tests, children 82 1-33, 834-43 costs 826 definitions 82 1-3 developmental age 0-6 months 834-5 6-18 months 835 6-36 months 838 2-5 years 839 3 years onwards 840
hearing loss (SNHL) skull base lesions 3943-4 sound localization 3257 sound perception 3255-7 stereocilia disruption 20 temporal resolution 3256-7 tinnitus 3598 traumatic 824 tympanic membrane perforations 939 unilateral, vestibular schwannoma 3983-4 vertigo, children 1042 vestibular schwannoma 3837, 3943, 3959, 4007-8 resection, outcome prediction 749-50 see also deafness; specific causes; specific
otitis media with effusion 889 pure-tone audiometry 3260- 1 , 3263-4 heartburn 2063 heart rate, children 543 T 'heart-sink' patients 565 heat exchange, nasal 1355-6 heat moisture exchange devices 2628, 2630 F heavy metal chemotherapy 37 Heck's tumour 209 T Heerfordt's disease 389 1 Heimlich manoeuvre 2288
types
electrophysiological testing 834-5 late identification 825-6 linguistic age 1 8-30 months 841 30 months onwards 841 6 years and over 841 management 826 newborns see newborn hearing screening outcomes 825 parental wishes 826 principles 821-3 rationale 825-6 school-entry screen 829 special needs children 84 1 see also auditory sensitivity, evoked physiological measurements;
specific tests hearing threshold definition 3261
children 1 1 88, 1 1 89 F helical rim, folded-over 97 1-2 Helicobacter pylori, gastro-oesophageal reflux 1274 laryngeal manifestations 2262-3
helicotrema 3 1 30 Heliox airway obstruction 477-8, 2288 stridor treatment 449 tracheobronchial tree foreign bodies 1 1 89 helium-neon lasers 743 helium-oxygen mixture see Heliox hemifacial microsomia 967-8, 1032-3 aetiology 1032 classification 1032, 1032 T clinical features 1032-3, 1033 F diagnosis 1 032-3 management 1033 timing 1033 neuromuscular deficiencies 1032-3 orthodontic treatment 1033 surgery 1033 hemifacial spasm, benign 393 1 hemitransfixion, septum 1578, 1578 F hemizygosity 8 Henderson, John 473 Hennebert sign 1046-7, 3763 Henry's law 3501 T, 35 14, 3 5 1 6 Hensen's body 3 1 32 F, 3 1 34 Hensen's cells 3 128 F, 3 1 30-1 heparin 446-7 deep vein thrombosis 447 mechanism of action 279, 282, 447 F perioperative prophylaxis 290 skin flap survival 1 14 thrombophilia 289 heparin-binding growth factors 67 heparin-induced thrombocytopaenia (HIT) 260 heparin-induced thrombocytopaenia with thrombosis (HITT) 287 heparin sulphate proteoglycan (HSPG) 67 hepatitis drug-induced 236 salivary assay 1 868 hepatitis B surface antigen (HBsAg) , salivary assay 1 868 hepatitis C virus, salivary gland infection 1 90 1 hepatocyte growth factor (HGF), thyroid cancer 2669-70 hepatocyte proliferation 67 heptanucleotide 5 HER 2 oncogene 2384 herbal medicine regulation 408 Herceptin 44
Pages 1-1 3 1 2 are in Volume 1 , pages 1 3 1 3-28 1 0 are in Volume 2, and pages 281 1-4147 are in Volume 3 .
4222 • I nd ex
hereditary angio-oedema (HANE) 1 78-9, 1 79 T, 1 80 T airway obstruction 1 824 investigations 169 oral manifestations 1 824 hereditary cerebellar ataxia 3773-5, 3 779 aetiology 3773-4 children 1 048 clinical manifestations 3774 complications 3775 definition 3773 diagnosis 3774 differential diagnosis 3774 management 3774 outcomes 3775 hereditary familial telangiectasia (HFT) 443 hereditary haemorrhagic telangiectasia (HHT) epistaxis 1 574, 1605-6, 1708 children 1 067 nasal manifestations 1 708 oral manifestations 1 823 treatment 1 605 F hereditary hearing loss 852 autosomal dominant 852 autosomal recessive 852-3 hereditary sensory-motor neuropathy ( HSMN), hearing loss and 3848,
3849-50 heritability, auditory function 1 7 herpangina 1 833, 2005 herpes 1abialis 207-8, 1 825 HIV patients 242-3 herpes simplex encephalitis 39 1 3 herpes simplex stomatitis 1 832 herpes simplex thymidine kinase (HSV-TK) 28 herpes simplex virus (HSV) 207 Bell's palsy 2 1 0, 3885 children 2004 drug resistance 208 erythema multiforme 1 835 HIV patients dermatological manifestations 247 inner ear infections 240-1 I '1 r'irnn,,,,,,, I infection 244 oesophagitis 245 oral infections 242-3 n t'l
nasal infection 1 700 oral infection 207, 1 832 recurrent 1 832 pharyngeal infection 2004-5 reactivation 207 recurrent infections 207-8 replication 207 Steven-Johnson syndrome 2004 treatment 208 vaccines 208 vestibular neuritis 3678, 375 1 viruses 207-8 head and neck cancer gene therapy 28 herpes zoster ophthalmicus 39 16,
3916-7 herpes zoster oticus 3379-82, 3380 F,
3694, 3886 AIDS patients 241 , 247 auricular pain 3380 definition 3379 diagnosis 3379-80 facial palsy 3380, 3885, 3886 F, 3931 histopathology 3694 hyperacusis 3596 management 434, 3380 nomenclature 3379 outcomes 3380 pathology 3379 symptoms 241 , 332 1 taste abnormalities 1 845 herpes zoster virus facial nerve palsy 3886 facial pain 1 724 mouth ulcers 1 832 advanced head and neck cancer 2789 nasal infection 1 700-1 oral infection 1 832 pharyngeal infection 2005, 2079 treatment 2005 herpetic gingivostomatitis 207 F hertz 2 165 Heschl's gyrus 3863--4 heterogeneity, clinical and statistical 663 heterologous grafts 96 heterosmia 1 664 heterozygotes 1 8 Hetter incision 2731-3, 2732 F heuristics 563
Hevea brasiliensis 1419 hiatus hernia barium swallow appearance 2027 F paediatric reflux 1 273 rolling 2062
hiatus semilunaris 1 332, 1333 F,
1 344-6 third pass endoscopy 1348 Hib vaccine see Haemophilus injluenzae type b vaccine (Hib vaccine) high dependency unit definition 526-7 staffing, structure and role 527 high jugular bulb (HJB) 874 highly active antiretroviral therapy (HAART) 201 3 high molecular weight compounds (HMWC), allergic occupational rhinitis 145, 1 4 1 6, 1417 T high-pressure nervous syndrome 3 5 1 2-3 high resolution computed tomography (HRCT) cochlear implants assessment 365 1 facial nerve paralysis 3881 high-resolution manometry (HRM) analysis 197 1 conventional manometry vs. 197 1 dysphagia investigations 1971-2 sensor spacing 1974 H-incision 2732 F hindbrain segmentation, inner ear development and 8 1 5
HindII 5 HINT lists, speech audiometry 3270 Hirudo medicinalis, skin flaps 1 1 5 histamine allergic response 1390 allergic rhinitis 1 56 1 asthma 1561 food intolerance 1424 nasal polyposis 1 552 nasal vasculature, effects on 1 365, 1 365 T nonallergic rhinitis 1409 vestibular neurochemistry 3794 histiocytosis X see Langerhan's cell histiocytosis (LCH) histopathological records, cancer data collection 2373
Histoplasma capsulatum 1 2 1 6, 2267 histoplasmosis cervicofacial infections, children 1 2 1 6-7 diagnosis 2267 larynx 2267 symptoms 2267 throat 225 HN infection!AIDS 238-50 antiretroviral resistance 20 1 2
1-13 1 2 are i n Volume 1 , pages 1 3 1 3-2 8 1 0 are i n Volume 2, and pages 281 1-4 147 are i n Volume 3 .
I ndex I 4223
apoptosis 6 1 birth rate 20 1 1 candidiasis 20 1 1 candidiasis, oral manifestations 1 826 CD4 receptor binding 238-9 CD counts 239 chemoprophylaxis 240 children 20 13 chronic otitis media 34 10 dermatological manifestations 247-8 epidemiological data 20 1 1 facial nerve paralysis 3887 glycoproteins 238-9 head and neck cancer 20 12 head manifestations 240-1, 20 12 T AIDS defining 2012-3 healthcare workers, acquired infection 20 1 1-2 intravenous drug users 20 1 1 larynx 243-4 latency period 239 mouth ulcers 1 835 nasal manifestations 241-2 neck manifestations 246-7, 1 784, 20 12 T AIDS defining 2012-3 children 1 2 1 3 occupational exposure 239-40 oesophagus 244-5 olfactory dysfunction 1667 opportunistic infections 239, 20 13 oralloropharyngeal lesions 20 13 oral candidiasis 201 3 oral cavity 242-3, 20 1 3 oropharyngeal candidiasis 223 oropharyngeal squamous cell carcinoma 2580 otitis media with effusion 3389 otologic manifestations 240-1 external ear 240 inner ear 240-1 middle ear 240 paranasal sinuses 241-2 pharynx 243-4, 20 1 1-4, 20 12 T lymphoid tissue hyperplasia 20 1 3 neoplasms 20 1 3-4 post-exposure prophylaxis 201 1-2 primary infection 20 1 3 acute seroconversion illness 20 1 3 replication 238-9 saliva assay 1 868-9 salivary glands, children 1246 staging system 239 . symptoms 239 syphilis 2007
therapy 239 tuberculosis 1702, 2008 viral structure 238-9 HIV lymphadenopathy 247 cervical 246, 1 784 diagnosis 247 HIV salivary gland disease (HIV-SGD) 245-6, 1900- 1 , 1900 T children 1246 imaging 1 882, 1 882 F parotid gland cyst 1246, 1246 F HLA see human leukocyte antigen (HLA) HMB45 monoclonal antibody, mucosal malignant melanoma 2408 hMSH2, salivary gland tumours 2496 hoarseness aetiology 2025-6 assessment 2 165 definition 2 165, 2 192 features 2 1 84 laryngitis 2 196 perceptual factors 2 1 74 upper airway obstruction 2287 vocal fold cysts 2220 hoarseness diagram 2 1 84 Hodgkin's disease see Hodgkin's lymphoma Hodgkin's lymphoma children 1254 presentation 1254 treatment 1254 HIV-associated neck manifestations 246 salivary glands 250 1 'holding strategy,' 'heart-sink' patients 565 Holmes-Adie (myotonic) pupil 39 1 7 homeopathy otitis media with effusion 896 vestibular compensation 3805 homologous grafts 96 augmentation rhinoplasty 297 1 homo zygotes 1 8 hooded seal (Cystophora cristata), exostosis 3367 Hopkins rod endoscopes hypophysectomy 4106 nasopharyngeal carcinoma 2454-5 Hopkins rod telescope emergency tracheostomy 1 124 endoscopic sinus surgery 1483 pharyngeal pouch surgery 2050-1, 205 1 F, 2053 stridor investigations 1 120, 1 124 F
horizontal nystagmus 3219-20 horizontal-T (Hetter) incision 27 3 1 -3, 2732 F hormonal rhinitis 1383, 1410 oestrogen 1410 pregnancy 1410 hormone assays, postoperative pituitary gland function 3 1 2 hormones, effects o n nasal vasculature 1 365 Horner syndrome causes 3937 cerebellar infarction 3768 congenital 3937 external evidence 3936 pupillary light reactions 39 1 7 skull base lesions 3946 sweating loss 3936 Hospice Movement 2771 hot water irrigation, epistaxis 1602 hourglass tumours 4 1 26 House, William 3968 House-Brackmann's system facial function 3874-6, 3877, 3877 T, 3979 facial nerve tumours 4083 house dust mite avoidance/ reduction 1 396 children 1396 'houseman's suture' 2736 Howarth's elevators 1613, 1613 F Howarth's incision, external dacryocystorhinostomy 1691 5-HT see serotonin HT3 antagonists, childhood vertigo 1049 beta human chorionic gonadotropin (HCG) 359 human embryonic stem cells (ES) 68 Human Genome Mapping Project 10, 11 human immunodeficiency virus (HIV)
see HIV infection/AIDS human leukocyte antigen (HLA) acute otitis media 9 1 6 narcolepsy 23 1 0 nasopharyngeal carcinoma 2354, 2446-7 see also major histocompatibility complex (MHC) human papilloma virus (HPV) 209 head and neck squamous cell carcinoma 2352-3 hypopharyngeal cancer 2637-8 inverted nasal papilloma 2 1 0
Pages 1-1 3 1 2 are i n Volume 1, pages 1 3 1 3-28 10 are i n Volume 2, and pages 2 8 1 1-4147 are i n Volume 3.
4224 I I ndex
human papilloma virus (HPV)
(continued) juvenile-onset recurrent respiratory papillomatosis 1 174-5 laryngeal papillomatosis 222 1 , 2599 malignancy 208, 209, 209 T nasal infection 1 70 1 oral infection HIV-associated 243, 243 F mucosal disorders 1 828 respiratory papilloma 209 temporal bone tumours 4068 Human Rights Act ( 1998) 582, 590, 606-7 confidentiality 602 medical negligence 2806 performance and complaints 605 human telomerase reverse transcriptase (hTERT) 70-1 human telomerase RNA (hTR) 70-1 humidification, nose 1356 water production 1356 humps (nasal) removal techniques 2954-5 saddle nose 2975, 2976 F Hunter's syndrome 468-9, 469 F Huntington's chorea 3939 Hurler's syndrome 1 048 Hiirthle cell tumours 2673 T, 2674 FDG-PET imaging 694 Hutchinson's incisors 1 8 1 8 Hutchinson's triad 847 hyaline chondrosarcoma 4073 hyaluronan, palatal shelf elevation 1 8 14 hybridization 6, 6 F, 12 hydrocep halus craniosynostosis 1 023 normal-pressure 3778, 3780 postural imbalance 3778 skull base surgery 4139 vestibular schwannoma and 3958-9 hydrochlorthiazide 3799 hydrocortisone active mucosal chronic otitis media 3424 infected mouth ulcers, head and neck cancer 2789 post-hypophysectomy 4 1 1 1 recurrent aphthous stomatitis 1 830-1 hydrogel dressings, malignant wounds 2794 hydrogen peroxide mouthwash 448 hydromorphone, cancer pain 2786 doses 2787 T hydroxaminoacids, nasal mucus 1359
hydroxyapatite (HA) implants 1 20, 291 7 composites 1 20, 1 2 0 F extrusion rates 1 20 frontal sinus cranialization 1 5 1 8 historical aspects 1 18 root form 2904 subperiosteal 2903 tympanoplasty 120 hydroxycarbonate apatite (HCA) 1 23 hydroxychloroquine 1 9 1 3 1 ,25-hydroxycholecalciferol see vitamin D hydroxyethyl starch, idiopathic sudden sensorineural hearing loss 1 , 3588 hydroxyurea, jugular foramen meningioma 4042
secondary ear barotrauma 3519 tinnitus 3584 hyperbilirubinaemia auditory neuropathy/ dyssynchrony 3845-6 childhood deafness 845-6 hypercalcaemia acute treatment 393 biochemical analysis 379-80 PTH assay 382, 382 T causes 380 T medical therapy 393 palliative care, head and neck cancer 2794 hypercarbia sleep apnoea 1 105-6, 2309 sleep-disordered breathing 1 103 hyperemesis gravidarum thyrotoxicosis 359 transient hyperthyroidism 359 f3 human chorionic gonadotropin 359 thyroid stimulating hormone serum levels 359 hyperexcitability 495 hyperfractionated radiotherapy 2755 simultaneous chemotherapy combination implications 2758-9
hydroxyzine 1397-8 hygiene hypothesis 145-6, 1388 Hynes pharyngoplasty 1 0 1 1 hyoglossus 1 797, 1 797 F hyoid bone 2 1 32, 2 1 32 F cornua 1740, 2 1 32 fractures 2272 surface anatomy 1 740 swallowing 1956-7 hyoscine motion sickness 3795 trans dermal delivery 408-9 periodic cancer pain 2784-5 pharmacodynamics 4 1 1 salivary leakage, head and neck cancer 2788-9 vertigo 3795 vestibular attacks, acute 3796 T xerostomia, palliative care 414 hyperacusis 3595-6 evaluation 3596
hyperfractionation 49 accelerated 2755 hyperfunctional voice disorders 2225 hyperglycaemia, critical care patients 535 hyperglycexternal auditory canalia 3337 hypergranulation tissue 1 01-2
music-related sound exposure 3596 noise-induced hearing loss 3552 pathophysiology 3596 prevalence 3595-6 symptoms 3595-6 treatment 3596 hyperbaric oxygen therapy bone matrix production 29 1 1 decompression illness 3515-6 Eustachian tube obstruction 3390 idiopathic sudden sensorineural hearing loss I, 3584, 3589 T implant osseointegration 2910 indications 3516 T malignant otitis externa 3339 radiotherapy and 49-50
hyper IgE syndrome 1 80 T, 1 8 1 hyperkalaemia 262 hyperkeratosis 222 1 hypermagnesaemia biochemical analysis 3 8 1 causes 3 8 1 hypermethylation 8 hypernasal speech (rhinolalia aperta) 993, 1366, 2 166 hyperosmia causes 1666-7 definition 1664 epilepsy 1 669-70 hyperostosis, meningiomas 4008, 4009 hyperparathyroidism calcium levels 380 T clinical features 40 1 genetics 388-9, 401
see also individual types
Pages 1-1 3 12 are in Volume I, pages 1 3 1 3-28 10 are in Volume 2, and pages 2 8 1 1-4 147 are in Volume 3.
I nd ex I 4225
medical treatment 395 multiple endocrine neoplasia 388 oxyphil cells 373 persistent 395 phosphate levels 380, 38 1 T primary see primary hyperparathyroidism (pHPT) recurrent 395 secondary 395-6 renal transplantation 395 surgery 392-3 tertiary 389, 395-6 ultrasound 722 hyperphosphataemia 380, 38 1 T hyperprolactinaemia 301, 308 hyperreflexia, thyrotoxicosis 339 hypersalivation 3830 hypersensitivity reactions 140-3, 142 F, 147 mechanisms 14 1-3, 142 F type I 141 type II 141 type III 141-2 type IV 142 hypersomnia, idiopathic 23 1 0-1 hypertension benign intracranial see otitic hydrocephalus cerebrospinal fluid rhinorrhoea 1 64 1 epistaxis 1600-1 facial paralysis, childhood 1059 patient preparation, surgery 459 taste abnormalities 1 840 hyperthyroidism 323-4, 3 3 1 aetiology/pathology 330 apathetic 339 causes 339 T definition 338 pregnancy 358-9 subclinical see subclinical hyperthyroidism thyroid cancer and 3 3 1 transient of hypermesis gravidarum 359 vocal manifestations 220 1 see also Graves' disease; thyrotoxicosis hypertrophic scars 289 1-900 classification 289 1-2 face lift complication 3095 keloids vs. 289 1-2 medical negligence 3090-1 steroid treatment 2898-9 hyperventilation, capnograms 499 F hypoadrenalism 357 hypobranchial eminence 2 1 30
hypocalcaemia biochemical analysis 379-80 P TH assay 382, 382 T causes 380 T drug therapy 45 1 large volume transfusion 262 thyroidectomy-related 3 5 1 , 2692 hypocapnia, sleep 2307 hypochlorite, denture-related stomatitis 1 826, 1 827 hypocretin, narcolepsy 2 3 1 0 hypodermoclysis, palliative care 2800 hypodontia (dental aplasia) 1 8 1 7 hypogeusia 1 842 hypoglossal facial anastomoses 3078 hypoglossal nerve (XII) 1751-2, 1 797 F, 1 803, 3933 F, 3934 F, 3936-7 central connections 3934 F clinical disorders 3937-8 clinical evaluation 3937-40 fascicular fibres 3936 functional deficit, post-jugular foramen surgery 4041 in jugular foramen 3903, 3903 F motor fibres 3936 in neck 1 75 1-2 rootlets 3936 roots 3936 skull base lesions 3946 hypoglossal nerve lesions 3937 submandibular gland tumours 2488 hypoglossal nerve clival chordoma 4126 submandibular gland tumours 2504-5 hypogonadotropic hypogonadism (Kallmann's syndrome) 403, 8 13 1', 1 664, 1 670 hypokalaemic alkalosis 3 1 0 hypomagnesaemia biochemical analysis 3 8 1 causes 3 8 1 , 3 8 1 T hyponasal speech (rhinolalia clausa) 993, 1 366, 2 166 hypoparathyroidism calcium levels 380, 380 T Chvostek's sign 401 magnesium levels 3 8 1 thyroidectomy-related 2684 T hypopharyngeal cancer 2633-62 aetiology 2634 apoptosis 2636 benign lesions 2635 cell biology 2635:"7
chemotherapy 2649 radiotherapy and 52 complications 2655-6 diagnosis 2643-5 endoscopic assessment 2645 T endoscopic laser surgery 2648 epidemiology 2634-5 histology 2637-8, 2637 F imaging 2643-4 incidence 2633-4 investigations 2643-5 locoregional spread 2638-42 oesophagus 2639-40, 2640 F thyroid gland invasion 2640 F tracheal invasion 2639-40, 2640 F vocal fold palsy 2639 lymph node metastases 264 1 , 2642 1', 2652, 2654 F, 2655, 2656 molecular biology 2635-7 non-squamous 2637 T piriform fossa see piriform fossa postcricoid region epidemiology 2634-5, 2639 F neck node metastases 264 1 vocal fold palsy 2639 F postoperative survival rates 624 prognosis 2653-5, 2653 F, 2654 F quality of life issues 2775 radiotherapy 2647-8, 2650 chemotherapy and 52 complications 2655 recurrence 2652 F signs 2643-5 staging 2645, 2646 T stomach transposition 2655-6 surgery 2648, 265 1 symptomatology 2642-3, 2643 T TNM classification 2365 T treatment 2647, 2647 T combination protocols 2649-50 failure patterns 265 1-3 neck irradiation 265 1 T-stage 2654 F tumour markers 2636 see also oesophageal carcinoma hypopharyngeal diverticulum see pharyngeal pouch hypopharyngeal fibrolipomas 2635 hypopharyngeal injury 1 770 hypopharyngeal leiomyomas 2635 'hypopharyngeal suction pump' see upper oesophageal sphincter (UOS) hypopharynx 1944-5 acquired stenosis 2635
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4226 I I ndex
hypopharynx (continued) anatomy 2638 postcricoid region 2638 sub sites 2638 T lymphatic drainage 2714 mucous membrane 1947 otalgia 3530-1 postcricoid region 1944-5 structure 2365 walls 1944-5 hypophosphataemia 380, 3 8 1 T hypophosphataemic osteomalacia 382-3 hypophyseal cleft 295 hypophyseal veins 297 hypophysectomy anaesthesia 4106 biochemical investigations 4105 complications 4 1 10-1, 4 1 1 3 early postoperative 4 1 1 3 failure t o cure 4 1 1 3 intracranial haemorrhage 4 1 1 3 intraoperative haemorrhage 4 1 1 3 late postoperative 4 1 1 3 nasal/sinus 4 1 1 3 contraindications 4104 Cushing's disease 4 102 discharge after 4 1 1 3 diagnostic 4104 equipment 4 106, 4106 F, 4107 F, 41 10, 4111 F functioning adenomas acromegaly 4101, 41 14 Cushing's disease (ACTH excess) 4102, 4 1 14 prolactinomas 4100, 41 14 TSHomas 4102 hospital discharge 4 1 1 3 indications 4104 laboratory investigations 4105 nasal instruments 4 106, 4106 F nasal preparation 4105 non functioning adenomas 4103 outcomes 4105, 41 14-5 Cushing's disease 41 14 functioning adenomas 4 1 14 nonfunctioning adenomas 41 14 patient information/consent 41 04-5 patient positioning 4106 postoperative management 41 1 1-3 antibiotic cover 41 1 1 fluid balance and diabetes insipidus management 41 12 nasal pack 41 12-3 neurological assessment 41 12 steroid replacement 41 1 1
preoperative investigations 4105 biochemical 4 105 imaging 4 105 inferior petrosal sinus sampling 4 105 visual field assessment 4105 preparation for surgery 4105-6 revision surgery 4 1 1 5 specialization 4104, 4 1 1 5 surgical approaches 4 106-8 dual approach 4108 transcranial approach 4108, 41 10 F transsphenoidal approaches see transsphenoidal hypophysectomy surgical learning curve 4 1 1 5 therapeutic 4104 tumour management role 4104-1 3 written information 4105 hypophysiotropic neurones 307 hypophysis cerebri see pituitary gland hypopigmentation, laser skin resurfacing 3096 hypopituitarism 4103 hyposmia corticosteroids 42 1 epilepsy 1 669-70 frontal lobe tumours 1668-9 nonallergic occupational rhinitis 1416-8 hyposplenism, functional 276 hypotensive anaesthesia, ear surgery 502-3, 502 F hypothalamic-pituitary-thyroid axis 32 1 F hypothalamus feedback mechanisms 398-9 hormones 307 pituitary gland, effects on 300, 307 regulation 398-9 synthesis 307
see also individual hormones hypophysiotropic neurones 307 nasal reflexes 1 365 physiology 300-2, 307 target glands 398-9 hypothermia, paediatric anaesthesia 512 hypothyroidism 353-8 aetiology 330, 354 T, 355-7, 399-400 central 357 chronic autoimmune see Hashimoto's thyroiditis clinical features 355, 355 T
congenital see congenital hypothyroidism (cretinism) drug-induced 354 T epidemiology 353-5 goitre 335 iatrogenic 356 aetiology 356 incidence 399-400 investigations 331-2, 335-6 radio nuclide scans 336 ultrasound examination 72 1 in vitro tests 332, 335 iodine deficiency 356-7 nasal obstruction 1 366 neonatal 355 otologic symptoms 400 pathology 330 pregnancy 359-60 adverse effects 359 treatment 360 prevalence 353-5 radioiodine-induced 348, 356, 4 1 5, 2696 radiotherapy-induced 356 Reinke's oedema 2 1 99 rhinitis 400 subclinical see subclinical hypothyroidism symptoms 355, 399-400 taste abnormalities 1 846 thyroidectomy-induced 356 treatment 357, 450-1 tumour-induced 357 vestibular symptoms 400 vocal manifestations 400, 220 1 see also thyroid disease; specific causes hypoventilation capnograms 499 F sleep 2307 hypovolaemic shock 257 T hypoxaemia sleep apnoea 2309 stridor 1 1 1 9 hypoxia childhood deafness 845-6 obstructive sleep apnoea 1 105-6 sleep-disordered breathing 1 103 hypoxic cells sensitizers 50 tumours 49 x-ray resistance 49 hypoxic cell sensitization cellular hypoxia 2756 head and neck cancer 2756-7 research 2756
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I ndex
ibuprofen 380 1 icatibant 1 390 idiopathic facial nerve paralysis (IFNP) see Bell's idiopathic rhinitis see rhinitis, idiopathic idiopathic sudden sensorineural hearing loss (ISSNHL) 3577-93 aetiology 3580-2 definitions 3577, 3578, 3578 T diagnosis 3582-4, 3583 T epidemiology 3580-2 incidence 358 1 , 3582 bilateral 3582 investigations 3579, 3583 management 3584-9, 3585 T adverse events associated 3589, 3589 T corticosteroids 423, 3585 T efficacy 3589 evidence-based 3588-9 protocol 3588 randomized controlled trials 1 outcomes 3584 management effects 3584-9 pathology 3580-2 recovery 3584 idiopathic thrombocytopenic purpura 286 children 286 epistaxis 1065 treatment 286 idiopathic trigeminal neuralgia see trigeminal neuralgia iliac crest bone grafts 2972 image-guided surgery (IGS) 70 1-10 clinical applications 708 functional endoscopic surgery 709 F image data visualization 703-4 image reconstruction 703 volume averaging 703 infrared light sensors 707, 708 F pixels and voxels 703 registration 706 slices, concepts of 703 surface rendering 703-4 surgical planning 704 surgical simulation 704-5 tracking 706-8, 708 F imaging airway management 470 cerebrospinal fluid rhinorrhoea 1 638, 1638 F, 1 639 F children 1 295-304 interventional procedures 1 300
modalities 1295 T patient preparation 1 301-2, 1302 T radiation protection 1300-- 1 , 1 30 1 T cholesterol granuloma 1655 cochlear implants candidature 365 1 giant cell granuloma 1655 hypophysectomy 4105 incidentalomas, pituitary tumours 4 1 03 laryngeal stenosis evaluation 1 1 5 1-2 medical negligence and 2807 preoperative, purpose of 702 recent advances 755 T/NK cell lymphoma 1 656 Wegener's granulomatosis 1651 F, 1652, 1 652 F
see also specific modalities imatinib mesylate 44 imbalance, persistent in children 1 048 imidazoles 2 14, 2 33, 442 imitative test of speech pattern contrast perception (IMSPAC) 84 1 immitance 3289 185 immortalized immune complex disorders tonsillitis complications 1224
see also
disorders
immune con[lph�x (type 3) drug reactions 414 immune modulation r�7Tn ll"·, n '" stimulatory pathway 28 head and cancer treatment 28 multiple sclerosis 3772 immune response extracellular infectious agents 1 37-40, 138 F stages 1 34, 1 34 F vesicular infectious agents 137-40, 138 F immune system adaptive 133-4 evaluation 167-73 immunological tests see immunological tests innate 1 33-4 tonsils' role 1 220 immunization status, salivary assay 1 869 immunodeficiency childhood rhinosinusitis 1 0 8 1 chronic otitis media 3 4 1 0 combined 1 74-6 diabetes mellitus 401 investigations 167-9 genetic studieS 1 69
immunoglobulins 1 68 molecular studies 1 69
see also individual tests pathogen associations 1 68 T primary 1 74-82 B cell defects 175 T, 1 76 COlmp'lennerlt deficiencies 1 78-9, 1 79 T definition 1 74 immunological tests 1 77 T phagocyte defects 1 77-8, 177 T syndromes 1 79-8 1 , 1 80 T T cell defects 1 74-5, 175 T tests 1 68 T
see also individual disease!disorders secondary 1 74 immunoglobulin(s) 135-6 acute otitis media 9 16, 920 classes 1 3 8 class switching 148 immunodeficiency testing 1 68 nasal secretions 1 360, 1 36 1-2, 1361 in newborn infants 138 structure 1 35 F, 138 subclasses 1 38, 138 T deficiency 1 76-7 testing 168 surface 135 see also antibodies; specific types immunoglobulin A (IgA) class comparisons 138 coeliac disease 1 866 deficiency 1 75 T, 1 76 HIV infection 1 868-9 mucosal secretions 138 nasal secretions 1 362 spasmodic croup 1 1 29 immunoglobulin A2 (IgA2) 1 361-2 immunoglobulin A (IgA) subclass deficiency 108 1 immunoglobulin E (IgE) allergen-specific 1 59-60, 1 60 F in allergic reactions 144, 1 69, 1389 total 1 59 immunoglobulin G (IgG) subclass deficiency 108 1 immunoglobulin (Ig) -like adhesion molecules 2384 immunoglobulin M (IgM) 1 38 ABO blood groups 253-4 immunoglobulin replacement therapy, chronic rhinosinusitis 1473 immunohistochemistry p53 2382 F salivary gland tumours 2495
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4228 I I ndex
immunological tests 1 67-72 allergy 1 69-70 autoimmune disease 170-2 immunodeficiency see immunodeficiency lymphoproliferative disease 1 70--2 , 172 vasculitis 1 70-2
see also individual tests immunonutrition 532-3 immunosuppression basal cell carcinoma 2396 paediatric rhinosinusitis 108 1-2 relapsing polychondritis 3364 transfusion-associated graft-versushost disease 262 immunotherapy allergic rhinitis 1 564-5 allergy 153-5 nasopharyngeal carcinoma 2467 rhinosinusitis children 1 083-4 chronic 1473 impedance 3 167, 3 168 T sound 3 173-4 cochlea 3 1 76, 3 1 8 1 different media 3 175-6 tympanic membrane 3 1 78-9 impedance monitoring, facial reanimation 308 1-2 impetigo, nasal 1 700 implant bourne facial prostheses 29 1 5 implanted hearing aids 3640-1 implant osseo integration absolute contraindications 29 1 0 CADCAM models 291 1-2 counselling 29 1 1 CT-3D imaging 29 1 1-2 diagnostic wax: up/models 291 1, 291 1 F hyperbaric oxygen 2910 irrigation and cooling of bone 29 1 3 local factors 29 1 1 maintenance 29 1 5 medical factors 290 1 mucoperiosteal flap access 29 12-3 patient assessment 29 10-2 planning 2910-2 prophylactic antibiotics 29 12 radio-opaque markers 29 12 site, determination of 29 1 2 suitability 2910 surgical tapping and threading of bone 29 1 3-4 surgical techniques 2912-5 advanced 29 1 5-7 surgical template 29 12-3
implant-retained extra-oral prostheses 2933 T implant retention 2932 abutment type selection 2932 bar and clip arrangement 2932, 2933 F magnets 2932 implant salvage 2920-1 imploding antrum syndrome 1 685-6 complications 1 686 CT imaging 1685-6, 1686 F idiopathic 1 685-6 secondary 1 685-6 surgical techniques 1685-6 'impulsive' rotational test see velocity step test impulsive sounds, middle ear reflexes 3 1 83-4 incidence (of a disease) 823, 2344 incidentaloma(s) pituitary gland 4099, 4 103 thyroid gland 363 incident pain 2785 incisiform teeth see incisors incision wounds 97 incisive artery 1798 incisive papilla 1 79 1-2 incisivus labii inferioris 1 798 incisivus labii superioris 1 798 incisors 1 803 deciduous 1 804-5 permanent 1 803 roots 1 803 incisura jugularis 4026-7 incremental yield 823 incus 3 1 1 5, 3 1 1 5 F displacement, stapes surgery induced 3474 repositioning 3493 Indian technique, nasal reconstruction 30 1 5-6 indinavir 233, 239 indole-3-carbinol 1 1 79 indoloquinone E09 50-1 inducible nitric oxide synthase (iNOS) primary ciliary dyskinesia 1081 skin flap survival 1 13 induction loop systems 3668 industrial dusts, olfactory dysfunction 1673-4 indwelling protheses, orbital 2928 indwelling tracheostomy, laryngeal stenosis 2277 infant(s) drug prescribing 4 1 5 haemopoiesis 265-6
infant distraction test (IDT) 825-6, 848 eight month 828-9 infection(s) adenoidectomy-related 1098 bacterial see bacterial infection chronic otitis media 3410, 3410 T dental caries 1 805 diabetes mellitus 402 dysphagia 2030-1 fungal see fungal infection inactive squamous chronic otitis media 3427 intracranial, vestibular schwannoma removal 3982 jugular foramen 4034 malignant ulcers and fistulae 2792 maternal, childhood deafness and 846-7 mycobacterial see mycobacterial infections nasal see nasal infections neck 1783-5 neurological pharyngeal disease 2078-9 otitis media with effusion 3389 painful red eye 39 1 6 petrous apex 4047 pinna reconstruction 3033 sinonasal malignancy 2347 skull base surgery 4138 syndromic craniosynostosis surgery 1031 taste abnormalities 1 844-5 f3 thalassaemias 27 1-2 vestibular schwannoma surgery 3982 viral see viral infection voice disorders 22 19 wound healing 95, 98-9 wounds, dressings for 101
see also specific infections infections cervicofacial see cervicofacial infections salivary gland diseases/ disorders 1 899-900, 1 899 T infectious mononucleosis 2002-4, 2253 acute upper airway obstruction 2004 cervical lymphadenopathy 1 2 1 3, 1 783-4, 2703 clinical features 208, 1225 F, 2002-3, 2253, 2254 F facial rash 1 70 1 complications 2253 diagnosis 2003-4 dysphagia aetiology 2030
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I nd ex I 4229
epidemiology 2002 facial nerve palsy 3887, 3887 F investigations 2003-4, 2253 management 1 784, 2253 systemic manifestations 2003, 2003 T tonsils 208, 1 2 1 3, 1225, 1783-4 transmission 2002, 2253 treatment 208, 422, 2004 see also Epstein-Barr virus (EBV) infectious rhinitis (common cold) see common cold ( infectious rhinitis) infectious rhinosinusitis 138 1-2, 1382 T acute see acute rhinosinusitis (ARS) chronic see chronic rhinosinusitis (CRS) clinical forms 1 3 82, 1 3 82 T recurrent acute see recurrent acute rhinosinusitis (RARS) see also fungal rhinosinusitis inferior alveolar (dental) artery 1795 F, 1 798, 3907 inferior alveolar (dental) nerve 1 795 F, 1801 F, 1 802, 3907-8, 3925-6 injury, odontogenic keratocyst treatment 1 925 inferior alveolar vein 1 799 inferior canaliculus 1 690 probing, dacryocystorhinostomy 1691 F inferior cantholysis, orbital haemorrhage 3065 inferior circular sinus of Winslow 299 inferior colliculus 3 142-3, 3 143 F auditory neuropathy 3849 central nucleus 3 142-3 function 3 142-3 lesions 3921 sound pattern recognition 3 143 inferior constrictor, pharynx 1 947, 1 948 T, 1 949 F lateral relations 1 947-9 inferior constrictor strain swallow, globus 2038 inferior dental (alveolar) artery 1 795 F, 1 798, 3907 inferior dental nerve see inferior alveolar nerve inferior hypophyseal arteries 297 inferior labial vein 1 799 inferior laryngeal artery 3 1 7, 2 1 39 inferior laryngeal nerve 1 949-50, 3935 inferior laryngeal veins 2 140 inferior meatal antrostomy 1492-3 anaesthesia 1492 complications 1493
indications 1492 rhinosinusitis, children 1 084 surgical technique 1492-3, 1493 F inferior meatus 1329 inferior nuchal line 3899 inferior oblique muscle 3053 F inferior petrosal sinus 3909 inferior petrosal sinus sampling (IPSS) 3 1 0-1 Cushing's disease 3 1 0-1 hypophysectomy 4105 inferior thyroid artery 3 1 7, 372 inferior thyroid veins 3 1 7-8, 372-3 inferior tracheobronchial lymph nodes 2 1 42 inferior turbinate anatomy 1 329-30, 1329 F, 1 344-6, 1 346 F, 1 589 anatomy 1 599 blood supply, congestion state 1 5 89, 1 590 F reduction, chronic nasal obstruction 1 592 infertility, prolactinoma 4 100 inflammation 140-3 acquired atresia, external ear 3347 acute response 88 dysphagia 203 1-2 early 89 stages 98 late 89-90 nasal polyposis 1552 wound healing 88-90, 98 inflammatory disease/disorders facial nerve disorders 389 1 gingival hyperplasia, pregnancy 403 paranasal 1 344-6 nasal endoscopy 1 349-50, 1 349 F saddle nose deformity 2976 inflammatory lymphadenopathy, children 12 10, 12 1 1 T inflammatory response acute 88 embolic agents 733 influenza aetiology 205, 205 T complications 205-6 pandemic 205 at risk groups 205-6 influenza A treatment 2 10, 232 influenza neuraminidase inhibitors 209- 1 0, 232-3
see also individual drugs influenza vaccination 205-6 acute otitis media 2 1 1, 9 1 9 influenza virus 205-':6, 206 F
informed consent 585 categories 2806 genetic testing 1021 medical negligence 2806 see also consent infraglottis 803-5 infrahyoid muscles 2 134, 2 135 T infraorbital artery 1 798-9 infraorbital foramen 1340 infraorbital nerve 1 800, 1 80 1 F infrared light sensors, image-guided surgery 707 infrared oculography 3723 infrared systems, hearing impaired user 3668 infratemporal fossa 3905-8, 3905 F, 3906 F boundaries 3905 contents 3905 otalgia 3528 infundibular cells 133 1-2 infundibular entrance, third pass endoscopy 1 348 infundibulotomy 1483 infundibulum, pituitary gland 295 blood supply 297 magnetic resonance 305 inhalational agents, anaesthesia 49 1 , 496 inheritance, genetic 1 8-9 codominance 1 8 dominant 1 8 , 1 8-9 heterozygote 18 homozygote 1 8 maternal 18 recessive 18, 1 8-9 inherited immunodeficiency see immunodeficiency, primary inhibin 302 innate immune system 133-4 pattern-recognition molecules 1 33 inner ear congenital disorders 3683 deafness, pathology 8 1 1-2, 966 development 3 122-3 distortion products 3 1 98-9, 3201 embryology 806-7 HIV manifestations 240-1 otalgia 3528-9 trauma 368 1-2 vascular anomalies 3701 inner ear barotrauma 3507 differential diagnosis 3508 T hyperbaric oxygen treatment, secondary to 3 5 1 9
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4230 I I ndex
inner ear barotrauma (continued) inner ear haemorrhage 3507 pathoaetiology 3502-3, 3503 F inner ear decompression illness 3517-8 clinical signs 35 1 8 co-existing symptoms 3517 T diagnosis 3517, 3518 T differential diagnosis 3508 T investigations 3 5 1 8 treatment 3 5 1 8 inner hair cells (IHC) 3 1 30, 3 1 3 1 F auditory neuropathy/ dyssynchrony 3849 cell body 3 135-6, 3 1 35 F depolarization 3 1 36 electrical potential 3 1 94-5, 3 1 95 F electrical responses 3 194-5, 3 195 F electromechanical transduction 3849 function 3 1 35-6 innervation 3 1 36, 3849 stereocilia 3 135, 3 1 35 F lateral links 3 1 35 rootlets 3 135 tip links 3 135, 3 1 35 F transduction 3 1 35 synaptic pole 3 136 tinnitus 3605 ultrastructure 3 1 35-6, 3 1 35 F inner sulcus 3 127 innominate artery aberrant 1 146 paediatric tracheostomy 1 203, 1203 F rupture, surgery-related 2808
inspired anaesthetic agent concentration 498 inspired oxygen fraction (FI02), anaesthesia monitoring 498 inspired PC02, anaesthesia monitoring 498 insula, swallowing 1959 insulin-induced hypoglycaemia adrenocorticotropin testing 300
innominate artery fistula 1203 innominate foramen 3899 inosine-5-monophosphate dehydrogenase 209
growth hormone deficiency test 301 insulin infusion, critical care patients 535 insulin-like growth factor I (IGF- I ) acromegaly 4101 circulating levels 30 1 , 309 see also growth hormone (GH) insulin-like growth factor II (IGF-2) , juvenile angiofibroma 2437-8 insulin tolerance test, Cushing's syndrome 3 1 0 intact canal wall mastoidectomy, cholesteatoma 3433 canal wall down mastoidectomy vs. 3433 integrins 2384 head and neck cancer markers 2384 metastatic spread 36 intensity (definition) 3 1 65 intensity modulated radiotherapy (IMRT) 2759-60, 2760 F cervical lymphadenopathy 2707 nasopharyngeal carcinoma, children 1258 oropharyngeal tumours 2585 xerostomia 1909 intensive care admission indications 526 definition 526-7
1 ,4,5-inositol triphosphate (IP3), salivary secretion 1 859 inotropes, critical care patients 529-30 Inscutable 68 insects, removal from ears 1 1 85-6, 3370 insertion, DNA mutation 16 insertional mutagenesis, gene therapy 29 insertional plaque (plate) , vestibular hair cells 3228, 3234 F myosin 1/3 3234 in situ end labelling (ISEL) 6 1 i n situ hybridization 6 F, 2383 inspiration nasal humidification 1356 post-swallowing 1960
medical responsibility 527 patient management 527 staffing, structure and role 527 see also paediatric intensive care intention-to-treat analysis 629, 659 drug trials 4 1 3 interarytenoid adhesion 1 16 1-2 intercavernous venous sinuses 299 intercellular adhesion molecule 1 (ICAM- I ) , allergic rhinitis 1391 interferon (IFN) 209 basal cell carcinoma 2397 mucosal malignant melanoma 2410 interferon alpha 209 juvenile-onset recurrent respiratory papillomatosis 1 1 78 Sjogren syndrome 1 9 1 2-3
interferon alpha-2a 1 141 interferon beta, multiple sclerosis 3772 interferon-gamma 137 interforaminal atrophy 2919-20 interforaminal implant placement 2919 Intergroup Rhabdomyosarcoma Study (IRS) 4074, 4074 T Interim Orders Committee (10C) 606 interleukin(s), tumour markers 2388 T interleukin- 1 (IL- 1 ) , stem cells and 69 interleukin-3 (IL-3), stem cells and 69 interleukin-5 (IL-5 ) asthma 1 55-6 nasal polyposis 1 552 intermaxillary fixation (IMF) arch bars 1622-3, 1 623 F complications/problems 1 62 1 , 162 1 F incomplete dental arch 1622-3 intact dental arch 1 622 mandibular fractures 1621 F, 1622 maxillary fractures 1 627 intermediate olfactory striae 39 12-3 intermittent rhinosinusitis see acute rhinosinusitis (ARS) internal auditory canal (meatus) anatomy 3 1 1 9-20, 3 1 2 1 F facial nerve anatomy 3871 fundus dilation 872 middle fossa surgery 40 1 8 skeletonization, translabyrinthine vestibular schwannoma removal 3970-1, 3971 F stapes surgery 3474-5 internal carotid artery (ICA) 1 749-50, 390 1 , 3902 F, 3909 aberrant middle ear 874 nasopharynx 2 120, 2 120 F, 2 1 2 1 F balloon occlusion 3949, 3952 F epistaxis 1 597 jugular foramen surgery 4034, 4039 extracranial-intracranial bypass 4039, 4040 F petrous apex cholesterol cyst 4050-1 skull base tumours 4056 temporal bone tumours 4068-9 internal carotid artery test 3951 internal carotid territories, epistaxis 1 597 internal ear see inner ear internal fixation mandibular fractures 1624-5, 1624, 1624 F
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I n d ex I 423 1
maxilla fracture repair 1627 orbital access 1 627, 1628 T internal jugular vein 1 750, 390 1 , 3902 F lymph nodes, association with 1 747 relations 1 750, 1 750 T internal laryngeal nerve 1 803 internal maxillary artery ligation, epistaxis 1 603-4 embolization vs. 739 internal suspension, maxilla 1627 internal suspension, maxillary fractures 1627 International Association for the Study of Pain, pain definition 3526 International Classification of Disease (ICD) morphology codes 2374-5, 2375 T tumour site codes 2374 T, 2375 T International Classification of Diseases for Oncology (ICD-O) 2362 International Classification of Sleep Disorders 2307 International Journal of Pediatric Otolaryngology 773 international normalized ratio (INR) 280, 447 International Study of Asthma and Allergies in Childhood (ISAAC) 1 080, 1 386 International Symposium on Recent Advances in Otitis Media 1 978 929 International Symposium on Recent Advances in Otitis Media 1 999 929 International Union Against Cancer (UICC) laryngeal tumour staging 2603-7 TNM staging system 2360 International Union Against Cancer (UICC) , salivary gland staging 2507 T International Union Against Cancer (uicc)/American Joint Committee on Cancer (AJCC), Hart stage grouping 2360 internet 574 internuclear lesions, eye movement defects 3922 internuclear ophthalmoplegia (INO) ataxic nystagmus 3 7 1 5, 3716 F causes 3715 interphase, cell cycle 2381 interventional neuroradiology (INR) 73 1-41 applications 732, 734-5
dynamic testing and 735 epistaxis management 739 large artery occlusion 735 complications 734, 736, 739 current knowledge/future research 740 definition 73 1 equipment/agents used 732-4, 733 T embolization materials see embolic agents endovascular catheters 732-3 temporary vs. permanent agents 733 indications 732, 732 T clinical/anatomical factors 732 mechanism of action 733 preoperative treatment planning and 732 risk/benefit analysis 732 tumour embolization see tumour embolization
see also specific techniques/applications intonation 2 174 intraarterial chemotherapy 735 intracapsular partial tonsillectomy 1 993 intracerebral abscess, children 1089 intracochlear vector delivery 8 1 7 intracranial abscess active chronic otitis media 3437 management 3438 sinusitis, children 1088-9 intracranial ischaemia, olfactory dysfunction 1 667 intracranial pressure (ICP), raised barotrauma 3500-2 craniosynostosis 1022-3, 1 024 F diagnosis 1023 incidence 1023 syndromic 1029 intractable aspiration 2094-104 causes 2095 conservative management 2096-7 definition 2094 investigations 2096 pathophysiology 2094-5 surgical management 2097-103, 2098 T endolaryngeal stents 2099, 2 1 00 F vocal fold medialization techniques 2097-8 symptoms and signs 2095-6 intrajugular processe.s 4026-7 intralabyrinthine schwannoma 3685
intraluminal impedance testing, gastro oesophageal reflux 1275 intranasal ethmoidectomy 1494-5 complications 1495 contraindications 1495 indications 1494 surgical technique 1495 intraoral prostheses healing times 2914 insertion 2913 F nasal reconstruction 2928 progressive loading 2914 types 2915 intraorbital nerve injury, blepharoplasty 3066 intraparotid lymph nodes 1 853-4, 1 856 intrapharyngeal space 1 807 intrasphenoid sinus septae 300 intrathecal dyes/markers, cerebrospinal fluid rhinorrhoea 1638-9, 1 639 F intrathoracic obstruction, stridor 1 1 18 , 1 1 18 F intrathyroidal parathyroid glands 722 intravenous drug users (IDUs), HIV infection!AIDS 20 1 1 intrinsic factor (IF) 269 intrinsic sleep drive 2306 intron 4, 1 5-6 intubating laryngeal mask airway (ILMA) 474-5, 475 F intubation awake fibreoptic see awake fibreoptic intubation cervical spine fractures 2289 cricoid ring damage 1 15 1 difficult 467, 468 endoscopy 1 12 1 endotracheal see endotracheal intubation facial trauma, severe 2289 failed, upper airway obstruction 2 1 5 1-2 laryngeal endoscopy 2 1 5 1-2 laryngeal infections, acute 1 1 32-3 laryngeal reconstruction 1 1 58 laryngeal trauma 2289 malignant dysphagia palliation 2069 prolonged, otitis media with effusion 3390 tonsillectomy 5 1 5, 5 1 5 F tracheal see tracheal intubation vocal injuries, children 1 1 70, 1 1 70 F, 1 1 71 F
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4232 I I ndex
intubation granuloma see arytenoid granuloma invasive aspergillosis 2 1 7 F mycotic laryngitis 2254 invasive monitoring of blood pressure (IBP), perioperative 497-8 inverted papilloma middle ear 4072-4 sinonasal 1 523-4 clinical symptoms 1523 definition 1 523 endoscopic resection 13 50- 1 , 1351 F human papilloma virus 209 T, 2 1 0 imaging 1 503 F, 1 523 incidence 1 523 pathogenesis 1 523 recurrence 1 523 results/statistics 1 524 site of origin 1 523 surgery 1 523-4 surgical indications 1523-4 involuntary manslaughter 607-8 iodide mumps 1906-7 iodine daily requirements 356-7 metabolism 321 thyroid cancer aetiology 2671 thyroid gland physiology 321, 32 1-2 thyrotoxicosis 45 1 iodine, radioactive see radioiodine therapy iodine- 1 3 1 see radioiodine iodine deficiency dietary factors 356 goitre 345, 356 hypothyroidism 354 T, 356-7 neonatal cretinism 356 iodothyronine deiodinase isoenzymes 323, 324 T ionizing radiation 47 basal cell carcinoma 2396 ionomer cements 1 20 ions, nasal secretions 1360 iontophoresis, perichondritis 3360 Iowa Oral Performance Instrument (IOPI) , dysphagia 2088 ipratropium bromide allergic rhinitis 1398 nonallergic rhinitis 1412 pharmacodynamics 41 1 rhinosinusitis 442 ipsilateral coronoidectomy, trismus reduction 29 15 Iressa (gefitinib, ZD 1 839) 43, 52
irinotecan 39 iron daily requirements 268 overload, transfusion reaction 262 supplementation 268 tongue staining 1 825 iron chelation, f3 thalassaemia 271-2 iron-deficiency anaemia (IDA) 268, 268 T irritant-induced rhinitis 1383 Isaacs Report (2003) 574 isobaric gas counterdiffusion 3512-3 isomasking curves, tinnitus 3612 isoniazid hepatotoxicity 236 nasal tuberculosis 1460 isoprenaline 1 365 isoretinoin 2609 isosorbide dinitrate 1 289 Isshiki thyroplasty type I 2097 isthmus nasi 1 589 Itard, Jean- Marie Gaspard 3607, 36 15-6 itraconazole 233-4 candidiasis 224 entomophthoramycosis 2 1 5 fungal rhinosinusitis 2 1 8 histoplasmosis 225 mycotic laryngitis 2254 paracoccidioidomycosis 225 IUdR 50 Jackson, Chevalier 77 1-2, 772 F Jackson's syndrome 2080 T, 3938 Jacobson's nerve (tympanic nerve) 1 75 1 , 3 1 16, 3527, 3910 Jacobson's organ (vomeronasal organ) 1 3 1 6-7, 132 1 , 1 368, 1662, 1819 Jadad score, randomized controlled trials 650 Jansen's disease 389 jaw(s) lower blood supply 1 798 venous drainage 1 799 lower, development 798, 1 8 1 1-2 receding, airway management 469, 469 F swallowing 1954-5 upper adjunctive implant techniques 29 1 7 blood supply 1 798
development 1 8 1 1-2, 1 8 1 2 F venous drainage 1 799 jaw cysts 192 1-41 classification 1 92 1-2, 1923 T enucleation 1922 formation mechanisms 1 922 management principles 1922 large cysts 1922 marsupialization 1 922 nonodontogenic fissural (epithelium lined) 1 926 pseudo bone cysts (nonepithelium lined) 1926-7 observation 1922 odontogenic see odontogenic cysts jaw jerk test 3926 jaw slide 469-70 jaw tumours 1 92 1-41 benign 1927-3 1 giant cell lesions 1930-1 malignant 1 93 1-9 mesenchymal 1928-9 metastatic 1939 nonodontogenic 1929-30 odontogenic 1 923 T, 1927-8 tumour-like lesions 1927-8
see also individual types Jehovah's Witnesses blood transfusion refusal 583, 586 consent issues 60 1 jejunal loop procedure, hypopharyngeal cancer 2655 jelly nystagmus 3922 jerk nystagmus 37 1 1 F, 3712 F, 3725 CNS lesions 3712 F, 3725 peripheral vestibular lesions 3712 F, 3725 Jervell and Lange-Neilsen syndrome 8 1 3 T jet lag, professional voice 22 12 jet ventilation, endoscopy 1 12 1 jitter (pitch perturbation) 2 1 65, 2 1 79 Jobson-Horne probe 3008-9, 3009 F Jod Basedow phenomenon (effect) 345, 2667 John Hopkins/University of Miami programme, vestibular exercises 3807, 3807 T Joint Committee on Continuing Professional Development 556 Joint Committee on Infant Hearing guidelines 3291 Joll's triangle 2664, 2664 F Joseph reduction rhinoplasty 2950 josithromycin 1471-2
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I n d ex I 4233
jugular bulb 3909 anatomy 4027 disorders 4034 high 4034 injury, vestibular schwannoma removal 3977-8 jugular foramen surgery 4038-9 petrous apex cyst drainage 4050 jugular bulb diverticulum 4034, 4035 F, 4036 F jugular bulb skeletonization, vestibular schwannoma 3970 jugular chain 1 747 jugular foramen 3901 , 3903 F, 3933 F, 4026-7, 4027 F, 4028 F jugular foramen lesions 4026-45 diagnosis 4028-9 glomus tumours see glomus tumours history 4028 imaging 4029 infectious conditions 4034 symptoms 4028 metastatic lesions 4033-4 nonsurgical management 4041-3 medical therapy 4042 radiotherapy 4042-3 stereotactic radiosurgery 4043 'wait-and-see' policy 4042 palliation 4042-3 pathology 4029-34 neoplasia 4029-34 physical examination 4028 progression 4042 surgical management 4034-41 approaches 4039, 4039 T facial nerve conservation 4037 internal carotid artery management 4039 postoperative management 404 1 preoperative embolization 4034-5 rehabilitation 4041 sigmoid-jugular complex management 4038-9 transtemporal approach 4035-9, 4037 F tumour resection 4039-41 symptomatology 4027-8 jugular foramen syndrome 2222-3, 2528 jugular lymph nodes 1 747 jugular veins external 1 750 internal see internal jugular vein thyroid cancer 269 1
jugulodigastric lymph nodes 1 800, 27 1 3 jugulo-omohyoid lymph nodes 1 800, 2713 jugum sphenoidale 4 1 20 Jun and Fos (ATF) proto oncogenes 2380 junctional epithelium, mouth 1 795 junctional scotoma 3 9 1 5 jun kinase inhibition 3302 jurisprudence see medical jurisprudence Just-Follow-Conversion OFC) 3271 justice (ethical principle) 562 juvenile angiofibroma 2437-44 assessment 2438-9 blood loss 2440 chemotherapy, preoperative 2441 classification systems 2 1 23 T, 2438-9, 2439 T, 2440 T complications 2442-3 nasal crusting 2443 diagnosis 2 1 24 embolization 734, 734-5, 2440, 3954 epistaxis 1 606 expansion 2 1 24 familial adenomatous polyposis 2438 histology 2 122 incidence 2 1 22 pathogenesis 2437-8 presentation 2 122, 2438 radiotherapy 2442 recurrence 2 1 24, 2442-3 sites of involvement 2 1 22 surgical resection 2 1 24, 2441-2 endoscopic endonasal technique 244 1 , 244 1 F, 2442 F open approaches 2442 skull base approach 2442 treatment 2439-40 juvenile-onset recurrent respiratory papillomatosis OORRP) 1 1 74-83 clinical presentation 1 1 75 cold steel surgery 1 1 76 diagnosis 1 175-6, 1 1 76 F epidemiology 1 1 75 human papilloma virus 1 174-5, 1 1 75 malignant disease 1 1 80 natural history 1 1 79 staging 1 1 76 susceptibility factors 1 1 75 tracheobronchial disease 1 179 treatment 1 1 76-9 adjuvant therapy 1 1 77-9 surgical 1 1 76-7
juvenile ossifying fibroma 1 929-30 juvenile recurrent parotitis 1904 Kadish staging, nasal malignancy 2425 F, 2425 T Kallmann's syndrome (hypogonadotropic hypogonadism) 403, 8 1 3 T, 1 664, 1 670 kanamycin, auditory nerve fibre tuning curves 3 199, 3 199 F Kant, Immanuel 583-4, 2943-4 Kaposi's sarcoma children 1259 T external ear 240 larynx 244, 2604 nasal 24 1 , 1 707-8 neck 246 oral 243, 243 F, 244 T, 201 3-4 pharynx 244 skin lesions 248 Karapandzic flap, lip reconstruction 2546, 2547 F Kartagener's syndrome see primary ciliary dyskinesia ( PCD) Kawasaki syndrome 1 2 1 7 Kay swallowing workstation 2089 Kearns-Sayre syndrome (KSS) 8 1 3 T keels, laryngeal stenosis 2278 Keen (intraoral) approach, zygomatic complex fractures 1 629 T, 1630 keloids 2891-900 button/pressure therapy 2893 classification 2891-2 genetics 2892 hypertrophic scars vs. 289 1-2 laser excision 2893 medical negligence 3090-1 molecular biology 2892-5 radiation therapy 2893-4 surgery and 2894-5 recurrence rate 2893 steroids 2898-9 intralesional 2893 surgery 2893 radiation therapy and 2894-5 steroids and 2893, 2894 F treatment 2892-5, 3090 keratinocytes, wound healing 90-1, 90 F keratoacanthoma 1 704-5, 1 704 F keratoconjunctivitis sicca (dry eye syndrome) 3065 keratocysts 1 922 keratosis with cellular atypia 222 1
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4234 I I ndex
keratosis (continued) laryngeal 763 nasal cavity 764 keratosis obturans 3342-5, 3344 F aetiology 3343, 3343 T definition 3342 diagnosis 3343-4 differential diagnosis 3334 T epidemiology 3343 management 3343 T, 3344 natural history/complications 3344 pathology 3342, 3343 T primary auditory canal cholesteatoma vs. 3343 T symptoms 3332, 3343 T types 3343 'keratosis tympanicum' 3343 Kernahan and Stark classification, facial clefts 801 F, 996, 997 F ketoconazole 233 allergic rhinitis 1 397-8 candidiasis 224, 2789 entomophthoramycosis 2 1 5 histoplasmosis 225 mycotic laryngitis 2254 paracoccidioidomycosis 225 Ki 67 hypopharyngeal cancer 2636 salivary gland tumours 2495 kidney(s) antimicrobial-induced toxicity 236 calcium reabsorption 374, 375 Wegener's granulomatosis 1 650 Kiesselbach's area 1 572 F, 1 574 Kiesselbach's plexus 1 328 Kikuchi's disease (subacute necrotizing lymphadenitis) 12 17, 1 784-5 killer activating receptors (KAR) 140 -
killer inhibitory receptors (KIR) 140 Killian, Gustav 771-2 Killian's dehiscence 1947, 2043, 2046 F pharyngeal pouch aetiology 2045, 2045-6 Killian's infundibulum 1 500 Kimmelstiel-Wilson disease 402 King-Kopetsky syndrome (obscure auditory dysfunction) 3273 kinins 1 390 kino cilium 3 1 50 F, 3 1 53 F, 3228, 3229 F Kinyoun stain 3449 Kirschner (K) wires, nasal fracture reduction 1614 Kit oncogene 2384 Klebsiella ozaenae 1 383, 1465 Klebsiella pneumoniae 2250
Klebsiella rhinoscleroma tis 200 infectious rhinosinusitis 1 3 8 1 respiratory scleroma 1462-3 rhinoscleroma 2 122, 2268 Kleeblattschadel anomaly (clover leaf skull) 1 028 Klippel-Feil syndrome 2080 Klippel-Trenaunay-Weber syndrome 1 708 Knudson's 'two hit' hypothesis 8 koilocytes, laryngeal 764 Koplik's spots 1 70 1 , 1 837 Korsakoff's psychosis 3775 Krien's coding, cleft lip and palate 996 KTP laser adenoidectomy 1097 juvenile-onset recurrent respiratory papillomatosis 1 1 77 Kundin gauge 100 Kuttner tumour 1 904 Kveim test 1648, 1 7 1 1 labial gland 1 808 labial mucosa 1 793 labial veins 1 799 labiodental consonants 2 1 66-7, 2 167 T labiomandibulotomy oral cavity tumours 2566-7, 2566 F tongue base carcinoma 2554-5 labour, oxytocin 308 labyrinth, vestibular see vestibular labyrinth labyrinthectomy 'chemical' 3567 vestibular compensation 3793 labyrinthine fistulae active chronic otitis media 3436 cholesteatoma 343 1-2, 3432 T chronic otitis media 3402-3 histology 3402-3, 3403 F management 3437 labyrinthine infarction 3768 aetiology 3753-4 labyrinthine ischaemia 3768 labyrinthine tears 3507 labyrinthitis acute otitis media 923 acute suppurative otogenic 3692 bacterial see bacterial labyrinthitis chronic otitis media 3403-4 sensorineural hearing loss 3403-4 serous 3403 suppurative 923, 3403, 3403 F viral see viral labyrinthitis
labyrinthitis obliterans, imaging 365 1 labyrinthitis ossificans, cochlear implants assessment 3651 labyrinths 3897 lesions, optokinetic nystagmus 3717 orientation 3209, 3209 F lacrimal bone 1690 lacrimal canal 1 34 1 lacrimal cell 1 690 lacrimal drainage system 1 690 lacrimal fossa 1 690 lacrimal gland prolapse 3049, 3050 F lacrimal nerve 3923 lacrimal notch 1 340-1 lacrimal sac 1 690 f3-lactamase inhibitors 230 lactase, occupational rhinitis 1419 lactation oxytocin 308 prolactin 30 1 , 308 radioiodine contraindication 348 lactic dehydrogenase (LDH) 1255 Lactobacilli 1 8 1 6 lactoferrin nasal secretions 1 360 saliva 1 866 lactulose 279 1 lagophthalmos 3048-9, 3049 F, 3096 post-blepharoplasty 3066 LAHSHAL, cleft lip and palate classification 996, 997 F lambdoid synostosis 1026-7 positional plagiocephaly vs. 1026 F lamina cribrosa 1334-5 lamotrigine 3617 lamuvidine 233 resistance 235 Langenbeck flap 1006-7, 1 007 F Langerhan's cell histiocytosis (LCH) 1 653-4 clinical features 1 653-4 definition 1 653 histology 1 654 imaging 1 654 temporal bone 4075 incidence 4075 prognosis 4075 radiological appearance 4075 symptoms 4075 treatment 1654 Langerhan's cells 1 654, 4075 allergy 1 388-9 Langerhans' granulomatosis see Langerhan's cell histiocytosis (LCH) Langer's lines 2829-30
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I nd ex I 4235
language development 990-1 otitis media with effusion 621 , 893-4 stages 990- 1 , 99 1 F ventilation tubes 899 language disorders, children 990-5 lanreotide 4 1 0 1 lansoprazole cancer pain management 2785-6 gastro-oesophageal reflux 2063 laryngitis, chronic 2263 Laplace's law 1 1 2 large cannula cricothyrotomy, difficult airways 477 large vestibular aqueduct syndrome (LVAS) 8 5 1 , 3683-5 associated conditions 3684-5 children 1 046 Mondini malformation 3684 laryngeal airway resistance, consonant-vowel sequences 2 1 72 laryngeal arteries 3 1 7, 2 1 3 9 laryngeal atresia 1 13 7-8 laryngeal candidiasis 2267 clinical features 224, 2254, 2267 immunocompromised patient 2268 treatment 224, 2267 laryngeal carcinoma adenosquamous 2604 human papilloma virus 209 T laryngeal carcinoma in situ 2609, 2609 F trauma 2272 laryngeal laryngeal chondroma 2600 T laryngeal clefts 1 141-2, 1 14 1 F associated abnormalities 1 141 dysphagia 2030 gastro-oesophageal reflux 1273 mortality 1 1 42 paediatric anaesthesia 520-1 severity 1 14 1 -2 stridor 1 14 1 -2 suspension microlaryngoscopy 1 142 tracheo-oesophageal fistula 1 14 1 treatment approaches 1 142 laryngeal cysts 1 136-7 paediatric anaesthesia 520 laryngeal diphtheria 1 1 30, 2252-3 laryngeal disorders androgenic drug-induced 220 ] drug therapy 446-54 inflammatory 2 196 symptoms 2 1 96 special needs children 787
see also individual diseases/disorders
laryngeal dysplasia 763-4 laryngeal framework surgery 2241-3, 2245 T arytenoid fixation 2242-3 cartilage suture 2242-3, 2243 F cricothyroid subluxation 2242-3 developments 2242-3 materials 2241-2 patient selection 224 1 prosthesis 2241-2, 2242 F techniques 2241-2 thyroid cartilage window 224 1-2, 2242 F voice disorders 2 1 96 laryngeal infections, acute 2248-57 children 1 1 27-34 airway management 1 1 32-3 clinical features 2248-9
see also individual infections laryngeal inlet, swallowing 1 955, 1957 laryngeal keel 1 160 laryngeal keratosis 763 laryngeal leiomyoma 2600 T laryngeal leiomyosarcoma 2604 laryngeal leukoplakia 763 , 22 1 8 laryngeal lymphoma 2602 laryngeal mask (LM) difficult airways 475-6, 475 T endoscopy 1 1 21 intubation via 475-6 professional voice surgery 22 13 laryngeal mask airway (LMA) 492, 492 F paediatric anaesthesia 5 10, 5 10 T, 511 F tonsillectomy 5 15 laryngeal mechanoreceptors 2 1 56-8, 2 1 59 articular 2 1 58 myotatic 2 1 58 subglottic mucosal 2 1 56 laryngeal microdebrider 2278 laryngeal nerve(s) external 3935 inferior 1949-50, 3935 internal 1 803 nonrecurrent 3 1 8 recurrent see recurrent laryngeal nerve (RLN) superior see superior laryngeal nerve (SLN) laryngeal papilloma/ papillomatosis 222 1 , 2599, 2600 T children 1 1 70 •
contact endoscopy 764 human papilloma virus 209 T laryngeal polyps 2265-6 see also vocal fold polyps laryngeal prominence 2 132 laryngeal reconstruction, children see laryngotracheal reconstruction, children laryngeal sarcomatoid carcinoma 2604 laryngeal skeletal injuries 2272 laryngeal squamous cell carcinoma Department of Veterans Affairs Cooperative studies 261 ] tobacco implications 235 1-2 laryngeal stenosis 2271-85 assessment 2279 children 1 1 50-66 anatomical considerations 1 15 1 aspiration evaluation 1 154 evaluation 1 1 5 1-5 examination 1 15 1 gastrointestinal evaluation 1 154 history taking 1 15 1 imaging 1 1 5 1 -2 presurgical considerations 1 1 55 treatment 1 1 55-64 chronic 2276-83 aetiology 2276, 2277 T classification 228 1-3, 228 1 T pathological considerations 2277 treatment 2277-8 1 , 228 1 T classification 1 152, 1 1 53 T, 228 1-3 eosinophilic oesophagitis 1 156 examination 2279 gastro-oesophageal reflux 1 1 54, 1 1 55 imaging 2279-80 investigations 2279-8 1 paracoccidioidomycosis 225 post-intubation 2293-4 scar tissue formation 2277 treatment children 1 1 55-64 laryngeal reconstruction see laryngotracheal reconstruction medical 1 155-6, 2278 resection techniques 2277-8 tracheotomy 1 1 56, 1 1 59 laryngeal stents laryngeal stenosis 2278-9 laryngeal trauma 2275
see also individual types laryngeal surgery 2234 paediatric intensive care 546-7 voice-related see phonosurgery
Pages 1-1 3 1 2 are in Volume 1 , pages 1 3 1 3-28 10 are in Volume 2, and pages 2 8 1 1-4147 are in Volume 3.
4236 1 I nd ex
laryngeal trauma 227 1-85 assessment 2272-3 classification 227 1 , 2274 T epidemiology 2271 examination 2273 follow-up 2275-6 fracture repair 2275, 2275 F gender and 2271 glottic competence 2272 impact velocity 2271 high 2272 low 2272 incidence 2271 injury biomechanics 227 1-2 intubation 2289 investigations 2273 medical management 2273-4 open operative intervention 2275 paediatric intensive care 544 pathological consequences 2272 prognostic indicators 2273 stents 2275 surgical management 2274-6 treatment principles 2272-3, 2273 laryngeal tumours 2598-622 age 2348 benign 2599 uncommon 2599, 2600 T biopsy 2608 clinical guidelines 2603-7 clinical presentations 2608-9 combined chemotherapy and radiotherapy 52 contact endoscopy 764, 765 diagnosis 2603-9 diagnostic delays 2603 endoscopic resection 26 1 2 , 26 1 2 F, 26 1 3 F endoscopy 2608 FDG-PET imaging 688 F, 690 F follow-up 2 6 1 8 gastro-oesophageal reflux disease 663, 664 T gender 2 2 1 8, 2348 incidence 2348 malignant 2600-3 uncommon 2602-3, 2604 mucosal melanoma 2407 neck management 2615-7 open surgical tracheostomy 2295-6 pathology 2599-603, 2612 F quality of life issues 650, 2772, 2775, 2777 radical neck dissection 2743 radiology 2607-8
rehabilitation 2598, 26 1 7-8 post-treatment, early stage disease 26 1 7-8 pretreatment planning 26 1 7 risk factors 2348, 2349 1', 2603 occupation 2348 salivary gland type 2600 T, 2604 spread 2601-2 , 2602 T stage NO neck treatment 26 1 5-7, 2724 stage T3/T4 chemotherapy 26 1 1-2 choice of treatment 26 1 0-2 operative treatment 26 1 0- 1 , 2614 F quality of life studies 26 1 1 radiotherapy 26 1 1 staging 2603-7 surgery 2612-5 voice preserving 2614 TNM classification 2366, 2366 T upper respiratory tract management 2 1 5 1 viral implications 2348 voice rehabilitation, postoperative see voice rehabilitation, post laryngectomy
see also individual tumours laryngeal ulcers, syphilis 2267 laryngeal veins 2 140 laryngeal ventricle 2 1 34 laryngeal vestibule 803-5 laryngeal voice 2228 T laryngeal webs anterior glottic see anterior glottic webs congenital 1 137, 1 1 38 F speech therapy 2222 laryngectomy 26 1 5 , 26 1 6 airway during surgery 505 anaesthesia 504-5 dysphagia 2086 intractable aspiration 2099 laryngeal tumours 2 6 1 5, 26 1 6 narrow field 2099, 2099 F preoperative patient state 505 prophylactic antibiotics 448 quality of life issues 2 630, 277 1 rehabilitation 2623-32, 2618, 26 1 8 F aims 2623-4 body image issues 2624, 2630 psychosocial 2630 swallowing problems 2627-8 voice see voice rehabilitation, post laryngectomy
tracheal intubation 505
see also specific techniques laryngismus stridulus 1 129 laryngitis 'acid' 2262 acute 2249 , 2249 F aetiology 2 2 1 9 bacterial superinfection 2249 causes 2249 clinical features 2249, 2249 F examination 2249 management 2249 pathophysiology 2249 professional voice 2249 residual dysfunction 2249 speech therapy 22 1 9 chronic see laryngitis, chronic contact endoscopy 763 definition 2 1 96 diagnosis 2 196 see mycotic laryngitis spasmodic 1 129 symptoms 2 196 treatment 2 196 laryngitis, chronic 2258-70 24 hour monitoring 2263 aetiology 2258-9 allergy 2258-9 assessment 2259-61 biopsies 2260 operative 2260-1 outpatients 2259-60 bacterial infection 2258-9 clinical presentation 2259 definition 2258-9 diagnostic inaccuracy 2260 gastro-oesophageal reflux 2258-9, 2262 lifestyle modifications 2263 pathophysiology 2262 treatment 2262, 2264 F voice therapy 2263 grading systems 2260, 2260 T, 226 1-2, 2262 T Helicobacter pylori 2262-3 histological features 226 1-2 immunocompromised 2268 inflammatory process 2258 intralaryngeal abnormalities 2259-60 malignant transformation 226 1-2, 2264 microlaryngeal specimen processing 226 1 , 226 1 F
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I ndex I 4237
nonspecific 2262-4 aetiology 2262 symptoms 2262 treatment 2262 occupational exposures 2258-9 oesophagitis 2263 proton pump inhibitors 2263 radiation-induced 2268 treatment 2268 smoking 2258-9, 2268 smoking cessation 2264 speech therapy 2219, 2263 symptoms 22 19, 2259 treatment algorithm 2264 F laryngocoeles 1 1 36-7 classification 1 1 36-7 diagnosis 1 1 37 ultrasound 724 laryngofissure, posterior glottic stenosis 1 16 1 laryngomalacia 1 1 35-6, 1 136 F cor pulmonale 1 136 diagnosis 1 1 36 dysphagia 2030 gastro-oesophageal reflux 1273 paediatric anaesthesia 520 stridor 1 1 16, 1 1 35 treatment 1 136 laryngopathia premenstrualis 2212-3 laryngopharyngeal reflux (LPR) globus 2038-9 laryngeal carcinogenesis 2348, 2354 upper GI diseases 2263 voice disorders 22 19 laryngopharynx, in swallowing 1958 laryngoplasty intractable aspiration 2099-100, 2101 F medialization 2242 T laryngopyocoele 2255-6 clinical features 2255, 2255 F, 2256 F definition 2255 investigation 2255 management 2256 surgery 2256, 2256 F Valsalva manoeuvre 2255, 2255 F laryngoscopy 2 146 anaesthesia 503 blade designs 473 child's voice assessment 1 1 69 difficult direct 468, 47 1 , 472 endoscopic 2 146 contact 2 1 50 difficult airway 2 1 50-1 flexible 2 146-8, 2 1 47 F
rigid 2 149-50, 2 149 F, 2 1 50 F ultrasonography 2 1 50 indirect 2 146 operative 2 148-9 anaesthetic considerations 2 148-9 paediatric anaesthesia 5 1 1 laryngospasm, fibreoptic endoscopic evaluation of swallowing 1970 laryngostroboscopy 2 1 72 laryngotomy, posterior glottic stenosis 1 1 6 1 laryngotracheal reconstruction, children 1 1 56-9 aims 1 154-5 anaesthesia 521 complications 1 165 contraindications 1 165 cricotracheal resection 1 163-4, 1 163 F decannulation problems 1 1 54-5 extubation 1 1 59 grafts 1 163 anterior cartilage 1 162, 1 1 63 expansion cartilage 1 1 57 F materials 1 1 56-7 posterior cartilage 1 163 laryngeal webs 1 1 37 presurgical considerations 1 1 55 revision surgery 1 1 65 single-stage 1 1 58-9 stents 1 1 57-8, 1 1 58 F laryngotracheal separation, intractable aspiration 2 1 02-3, 2 1 02 F laryngotracheal stenosis paediatric anaesthesia 52 1 post-intubation 2293-4 laryngotracheobronchitis ( LTB) see croup laryngotracheobronchoscopy ( LTB) 1 120, 1 12 1 F laryngotracheoesophageal clefts 1 14 1-2 laryngo- tracheo-oesophageal clefts, gastro-oesophageal reflux 1 273 larynx 2 1 30-44 anatomy 1 1 35-42, 2 1 3 1-40, 2 132 F adult vs. child 1 167, 1 168 F, 1 168 T, 2 1 3 1-2 children 1 1 5 1 siteslsubsites 2366 arterial supply 2 137 F, 2 139 assessment, post-anaesthesia 1 123 congenital disorders 1 1 35-42 contact endoscopy 763-4 abnormal appearance 763-4, 765 normal appeara�ce 763
'descent' 2045 divisions 2 132, 2 1 32 F effort closure 2 1 59 'electric' 2624-5 embryology 803-5, 1 167-8, 2 130-1, 2131 F evolution 2 1 30 examination, mirror use 2 1 93 foreign bodies, children 546, 1 188 framework 2 1 32-3 functions 2 1 59-6 1 , 22 1 7 fungal infections see mycotic laryngitis growth 1 167-8, 2 1 3 1-2 HIV associated lesions 243-4 infantile 2 1 3 1-2 innervation 2 1 37 F, 2 1 39, 2 1 55-9, 2 1 57 F Kaposi's sarcoma 244 ligaments 2 1 33-4 extrinsic 2 1 32 F, 2 1 33-4 intrinsic 2 134 lymphatic drainage 2 140, 271 3-4 medical negligence issues 2808 membranes 2 1 33-4 mucous membranes 2 137-8 muscles 2 1 34 extrinsic 2 134, 2 135 T, 2 1 59 intrinsic 2 134, 2 1 36 T, 2 1 37 F, 2 138 F, 2 159 neoplastic lesions 2 197-203 paediatric consultation 778-9 physiology 2 1 55-63 pseudocysts 2 1 99 relations 2 1 39 F rheumatological diseases 1 84 sound production 22 1 7 spaces around 1950 spaces within 2 1 38 structural lesions 2 197-203 diagnosis 2 198 T swallowing 1 955, 1957, 2 1 59 topical anaesthesia, airway endoscopy procedures 5 1 8 tuberculosis 2266, 2267 F ultrasound imaging 1297, 2 1 50 vasculature 2 139-40 venous drainage 2 140 visual assessment mirror use 2 193 voice evaluation 2 1 7 1 , 2 1 8 1 Wegener's granulomatosis 1651 laser( s) 743 dacryocystorhinostomy 1 692 T, 1693 F, 1694, 1694 F solid state 743
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4238 I I ndex
laser-assisted uvulopalatoplasty 2330 postoperative care 2332 success rate 2332-3 laser capture microdissection (LeM) 7-8 laser scanning, image guided surgery 706, 707 F laser skin resurfacing medical negligence 3096 postoperative infection 3096 laser stapedotomy minus prosthesis (STAMP) procedure 3472 laser supraglottoplasty, obstructive sleep apnoea 1 1 09, 1 1 10 F laser surgery airway management 494 children 5 1 9-2 1 , 520 F anaesthesia 503-5 keloids 2893 vocal folds 2236 laser therapy 742-7 applications 745 delivery devices 743-5, 744 F articulated arm 743 fibreoptic fibre 744 micromanipulators 744 robotized scanners 745 sharp tip 744 .
.
see also individual devices history 742 laser-tissue interaction 745 output patterns 743 'active laser medium' 743 continuous wave 743 pulsed 743 Q-switch 743 photo ablative reactions 743 photodynamic therapy see photodynamic therapy principles 742-3 safety 745 skin flap 1 1 5 tissue interaction 743 laser tonsillectomy 1235, 199 1 , 1992 laser vapourization arytenoid granuloma 2 197 glottic cancer 2610, 2610 F Lashley cups, saliva collection 1 862-3, 1 863 F latent interval 2344 latent nystagmus 37 1 1 lateral arm flap 2872 advantages 2872 anatomy 2873 F clinical applications 2872
disadvantages 2872 technical nuances 2872 lateral bone cyst 1927, 1927 F lateral bulge (torus lateralis) see nose, lateral wall lateral canthal angle 3048 lateral canthal tightening suture 3060, 3061 F lateral canthotomy, orbital haemorrhage 3065 lateral canthus rounding 3065 lateral cervical cysts see branchial cysts lateral cricoarytenoid 2 1 36 T lateral crural onlay graft 3010, 30 1 0 F, 30 12 F lateral crural spanning graft 3009 F, 30 1 0, 3010 F lateral crural steal, underprojected nasal tip 3003 lateral crus anatomy 2996 collapse 301 1 F nasal tip surgery 2964 tripod mechanism 2996, 2997 F lateral efferent system 3 145 lateral flap pharyngoplasty 1 0 1 2 F lateral gaze centres, pons 3921 lateral lemniscus 3 142 lateral ligament of the thyroid (suspensory ligament of Berry) 3 1 6-7 lateral medullary swallowing centre 1959 lateral nasal process 1 8 1 1 lateral neck swellings, children 1 2 1 1 lateral neck triangle 1 743 lateral olfactory striae 39 1 2-3 lateral olivary nucleus 3 1 41-2, 3 14 1 F lateral olivo cochlear system 3200 function testing 3200 lateral osteotomy 2955-6, 2956 F lateral periodontal cyst 1925 lateral pharyngeal space see parapharyngeal space (PPS) lateral pterygoid muscle 1 339, 1 809-10, 2 1 1 2-3, 3905, 3907 F lateral pterygoid plate 2 1 1 1 , 3900 lateral rectus 322 1 lateral rhinotomy nasal malignancy 2428, 2428 F nasopharyngeal carcinoma 2462 lateral skull base 3899-909 arteries 3902 F articular area 3905 auditory area 3904-5
infratemporal fossa see infratemporal fossa muscles deep 3904, 3904 F superficial 3907 F superficial to 3907 F, 39 1 0 nerves 3903 F neurovascular area 3898 F, 390 1-4 pharyngeal area 3900-1 subdivision 3898 F, 3900-9 surgical approach 3910 tubal area 3898 F, 390 1 veins 3902 F lateral superior olive 3 1 38 F, 3 145 lateral utility incision 2732 F lateral venous sinus thrombophlebitis, chronic otitis media 3437-8 lateral venous sinus thrombosis, chronic otitis media 3437-8 management 3438 lateral vestibular nuclei ( LVN) 3220 lateral vestibular tract 3227 latex allergy 1419 patient preparation, surgery 464-5 latissimus dorsi flaps 2858-6 1 , 2859 F, 2860 F, 2862 F, 2863 F laxatives 279 1 lazy 'S' incision, superficial parotidectomy 2478 F, 2484-5 lead poisoning 269 'leak test' 1 1 32 leeches 1 1 5 Lee Silverman Voice Program 2225 Le Fort 1 fractures 1625, 1 626 F management 1 627 Le Fort 1 osteotomy, nasopharyngeal carcinoma 2463 Le Fort 2 fractures 1 625, 1 626 F external fixation 1 627, 1 627 F Le Fort 3 fractures 1 625, 1 626 F Le Fort 3 osteotomy, syndromic craniosynostosis 1029 left anterior-right posterior (LARP) plane 3209 eye movements 32 1 7 F left main bronchus 2 1 40 F, 2141 leg ulcers 97-8 arterial 98, 102 venous 97, 1 02 leg weakness assessment 3732 leiomyoma hypopharyngeal 2635 laryngeal 2600 T leiomyosarcoma, laryngeal 2604 leishmaniasis 1 703-4
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1 4239
Lemierre's syndrome 1214, 1223-4, 1 224 I\ 2002 lentigo maligna 2400 I\ 2401 T lentigo melanoma 1 707 lentivirus gene therapy cystic fibrosis 25 head and neck cancer 27 Leonard button 1 622, 1 622 P lepromatous leprosy, nasal 1464, 1 703 leprosy 1463-4, 2010 disease parameters 1463-4 epidemiology 1 463 laryngeal 2267 nasal 1463-4 clinical features 1464 diagnosis 1464 treatment 1464 pharyngeal 20lO transmission 1 464 treatment 1464 Leser-Trelat sign 1 709 lesser cornua, hyoid bone 2 1 32 lesser palatine artery 1 799 lesser palatine nerve 1 80 1 lesser petrosal nerve 3933-4 superficial 3908 Lester-Jones tube insertion 1 696 Lethal discs large 68 Lethal giant larvae 68 Letterer-Siwe disease see Langerhan's cell histiocytosis leukaemia ( s) acute 274-5 pharyngeal symptoms 201 5 chronic 275 dysphagia 2033 vestibular labyrinth 3686, 3687 P
see also individual types leukaemia-inhibitory factor (LIP) 73 leukaemoid reaction 273 leukocyte( s) digestive 1 39-40 inflammatory 139-40 mycobacterial defects 1 77 T, 1 78 nasal mucus 1362 leukocyte adhesion defects (LAD) 1 77 T, 178 leukoerythroblastic blood film 273 leukopaenias, mouth ulcers 1 834 leukoplakia epithelial dysplasia 222 1 gingival white patches 1 820 laryngeal
contact endoscopy 763 prevalence, gender effects 221 8 oral cavity tumours 255 1 , 255 1 P leukotriene receptor antagonists (LTRAs) , rhinosinusitis l O83 leukotrienes, allergic response 1 390 Levant frame 1 627, 1627 P levator aponeurosis 3050, 305 1 P levator labii superioris alaequae nasi 1 324 'levator of the thyroid gland' 3 16 levator palatini muscle 1007-8, 1 009 I\ 1 946 T, 2 1 1 2 , 3909 Eustachian tube 3 1 1 8 soft palate repair 1 009 levocetirizine 1 397-8, 1402 levodopa 2078 levomepromazine, palliative care patients acute confusional states 2798 anxiety 2795 nausea and vomiting 2788 levothyroxine sodium (thyroxine 450 sodium, liberatory manoeuvres benign paroxysmal positional vertigo 3814 contraindications 3814 lichen planus (LP ) , oral 1 836, 1 836 P lidocaine airway endoscopy 5 1 8 endoscopic sinus surgery 1482 nasal vasculature, effects on 1365 ototoxicity 3677 reduction rhinoplasty 2952 side effects 36 18 sprays 448 supraglottic obstruction 480, 481 P tinnitus 3602, 3603 I\ 3609, 36 1 8 lifestyle modifications migrainous vertigo 3800-1 voice disorders 2 195 ligation, DNA fragments 5 'light amplification' 742 lighted stylets, intubation 475 light endoscopy 755 light microscopy, apoptosis 60 lignocaine see lidocaine likelihood ratios 656, 657 nomograms 657, 657 P Likert scale 636 Benefit Inventory 639 Limberg flap 2841 pI'
limen nasi 1 32 5 Lindsay-Hemenway syndrome 3699-700 linea alba 1 792-3 linear acceleration tests 3737-42 devices 3 737, 3738 P, 3739 P otolith testing 3737 linear predictive coding (LPC) 2 1 80 linear vertigo 3706-7 linear vestibuloocular reflex (IVOR) 3 2 1 3 lingual artery 1 797 I\ 1 799 1 825-6, lingual erythema 1 826 P lingual frenum 1 793 lingual glands 1 808 parasympathetic innervation 1801 I\ 1 803 lingual mandibular salivary gland defect 1 927, 1 927 P lingual nerve 1 795 P, 1 796 I\ 1 797 I\ 1 80 1 , 1801 P, 1 802-3, 3907-8, 3925 lingual nerve injury salivary gland tumour surgery 25 15 submandibular gland tumours 2488 lingual pressure recording, dysphagia 1977 lingual thyroid 3 14-5, 1 268-9, 1 824 carcinoma 2579 imaging 1 824 investigation 1 269, 1 269 P presentation 1 269, 1 269 P symptoms 1824 treatment 1 269 lingual tonsil 1 794 linguistic skills, speech audiometry and 3273 lingula 298 lingular bronchus 2 14 1 lining mucosa, mouth 1 795 linkage analysis 1 1 cleft lip and palate 999-1000, 1 000 T late-onset hearing loss 1 7 neurofibromatosis 2 3998-9 liothyronine sodium ( Tertroxin) 450 lip(s) 1 793 blood supply 1 798 cancer see lip cancer development 1 8 1 1-2, 1 8 1 2 P anomalies 1 8 1 1-2 lymphatic drainage 1 799 mucous membrane 1 793 muscles 1 798 sensory innervation 1800-1
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4240 . I ndex
lip(s) (continued) swallowing 1 954-5 venous drainage 1 799 lip cancer 2543-9 clinical characteristics 2543-4 distribution 2544 F epidemiology 2543 investigations 2544 occurrence 2550 T survival rates 2549, 2549 T TNM staging 2364, 2364 T, 2544, 2544 T treatment 2544-9 choice of 2544 defect repair 2544 lower lip see lower lip reconstruction neck dissection 2548 upper lip 2547-8 tumour types 2543 lipids, nasal secretions 1360 lipodermal grafts, facial reanimation 3083-4 iX-lipoic acid 3302 lipoma(s) clinical presentation 40 13 CPA tumours 40 12-3 definition 40 1 2-3 diagnosis 40 13, 40 13 F epidemiology 40 13 laryngeal 2600 T malignant transformation 40 13 pathology 40 12-3 treatment 401 3 ultrasound 725, 725 F lipoproteins 323 liposarcoma, larynx: 2604 liposomes, cystic fibrosis gene therapy 25 liposuction, rhytidectomy 3073-4, 3094 lip repair, cleft lip and palate 1 003 lip shave and mucosal advancement 2544-5 liquid lasers 743 listening, medical consultation 564 lithium, as goitrogen 2668 lithotripsy, sialolithiasis 1905 Little's area 1599-600 liver, antimicrobial-induced toxicity 236 liver disease fresh frozen plasma 258 haemostatic disorders 282 treatment 282 liver failure, drug prescribing 4 1 6
Ljubljana classification, laryngeal lesions 226 1-2 lobules, salivary glands 1 852 local anaesthesia nasal fractures 1 6 1 2-3 nasal vasculature, effects on 1365 sprays 448 vocal fold injection 2240 local flaps advancement 2832 head and neck surgery 2827-46, 283 1 F planning considerations 2828-46 Local Involvement Networks (LINks) 574 local research ethics committees (LRECs) 588-9 local sialagogues, saliva collection 1862 'locus of control,' head and neck cancer 2770 LOD score 1 1 Loefflerella mallei 1 3 8 1 lofepramine 2796 loft register (falsetto) 2 1 6 1 , 2 162 T logatoms, speech audiometry 3269, 3272 Lombard effect 22 12 longitudinal muscles, tongue inferior 1 798 superior 1 798 long stay ventilation tubes see T-tubes long-term average spectrum (LTAS) 2 1 80, 3270-1 longus capitis 1 746, 2 1 12 longus capitis anterior 1 746 longus capitis lateralis 1 746 longus colli 1 746 loop diuretics, ototoxicity 3568 T, 3569-70, 357 1 , 3677 lop ears 972, 972 F loratadine allergic rhinitis 1 399 chronic rhinosinusitis 1472 lorazepam acute confusional states 2798 anxiety 2795 vertigo 3795-6 loss of heterozygosity (LOH) 8-9, 9F loudness bandwidth increases 325 1-2 calculation 325 1 scaling 325 1 units 325 1 voice perception 2 1 74
loudness discomfort levels (LDL) hyperacusis 3596 noise-induced hearing loss 3553 loudness perception 3250-2 absolute threshold 3250, 325 1 F cochlear hearing loss 3256 equal-loudness contours 3250-1, 325 1 F frequency selectivity 325 1-2 loudness recruitment cochlear hearing loss 3256 hearing aids 3256 loud noise discomfort, post-stapes surgery 3477 low dose unfractionated heparin (LDUH) 463 low energy helium-neon laser irradiation, skin flaps 1 1 5 Lowenstein-Jensen media 1459-60 lower eyelid anatomy 305 1-3, 3052 F blepharoplasty see blepharoplasty fat compartments 305 1-2, 3053 F fat herniation 3055 retractors 3053 F skin crease 305 1 unilateral facial palsy 3079 lower jaw see jaw(s) lower jugular lymph nodes 1 747 lower lip depressor weakness 3084 F botulinum toxin injections 3084 correction 3084 treatment 3084-5 lower lip reconstruction 2545-7, 2545 F Abbe-Estlander flap 2545-6, 2546 F defect involving less than one third 2545 defect involving more than two-thirds 2546-7 defect involving one-to-two thirds 2545-6 Karapandzic flap 2546, 2547 F lower lobe bronchus left 2 14 1 right 2 14 1 lower oesophageal sphincter, gastro oesophageal reflux 2062 lower respiratory tract, relationship with upper tract 1 560-8 epidemiological evidence 1 560-1 low molecular weight compounds (LMWC), allergic occupational rhinitis 145, 1416, 1417 T
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I ndex I 4241
low molecular weight heparin (LMWH) deep vein thrombosis 288 prophylaxis 447 mechanism of action 282 pulmonary embolism 288 venous thromboembolism prophylaxis 463 low (residue) pitch 3252-3 low tidal volume ventilation, critical care patients 535 lozenges 448 Ludwig's angina 1 807, 1902 lumbar drainage
Lyell's disease 1 700 Lyme disease 1056, 389 1 lymphadenopathy cervical see cervical lymphadenopathy HIV see HIV lymphadenopathy rheumatological diseases 185 ultrasound examination 715, 716 F lymphangioma(s) 1 137, 1269-7 1 , 1 782-3
jugular foramen tumour resection 4041 nasopharynx surgery 4056 lumbar puncture, fluorescein see fluorescein lumbar puncture Lund and Mackay staging system, rhinosinusitis 1490 T radiologic staging 1489 T surgery score 1490 T lung(s) development 2 1 3 1 hilum 2 1 44, 2 144 F innervation 2 142 pharyngeal pouch-related complications 2044 Wegener's granulomatosis 1650 lung buds 2 1 3 1 lung cancer, pituitary involvement 4104 lung hyperinflation, bronchial obstruction 1 1 88, 1 1 90 F lupus anticoagulant 290 lupus erythematosus 171 1-2 discoid 1 7 1 1 , 1 7 1 1-2 dsDNA antibodies 1 70
embryology 1269 macro cystic lesions see cystic hygroma management 1 782-3 microcystic disease 1 1 37, 1269, 1270 oral 1 824 presentation 1 782 ultrasound examination 726 lymph node(s) cervical see cervical lymphatics cystic transformation 1 78 1 ultrasound examination 717, 7 1 7 F, 7 1 8 F, 724 enlargement see lymphadenopathy neck see cervical lymphatics surgical identification 371 T lymphocyte(s) activation 133-4 development 133 nasal polyposis 1552 lymphocyte phenotyping 1 68 lymphocyte proliferation test 1 68-9 lymphocytic carcinoma, larynx 2604 lymphocytosis 274, 274 T lymphoepithelial carcinoma, larynx 2604 lymphoepithelial cyst 245-6, 245 F, 1914 lymphoepithelioma, oropharyngeal 2580
oral manifestations 1 836 systemic see systemic lupus erythematosus (SLE) lupus pernio 1645, 1647 F, 1648 F, 1 7 10, 1 7 1 0 F see also sarcoidosis lupus vulgaris basal cell carcinoma vs. 1 703 nasal 1458-9, 1459 F, 1 702-3, 1 702 F squamous cell carcinoma vs. 1 703 Lushka's tonsil see adenoid luteinizing hormone (LH) 30 1-2 circulating levels 30 1-2 effects 302 secretion 297, 302 structure 302 women 302
lymphoma(s) B cell see B cell lymphoma Burkitt's 208, 1254 children 1254 CPA involvement 40 1 5 cranial nerve neuropathies 2080 dysphagia aetiology 2033 FDG-PET imaging 694, 694 F Hodgkin's see Hodgkin's lymphoma non-Hodgkin's see non-Hodgkin's lymphoma (NHL) olfactory dysfunction 1668-9 reticuloendothelial 275 salivary glands 250 1 , 2503 thyroid see thyroid lymphoma T/NK cell see TINT} cell lymphoma tonsils 1226
ultrasound 1 759-60 vestibular labyrinth 3687 lymphopenia 274 lymphoproliferative disease 1 72 immunoglobulin level analysis 1 72 paraprotein levels 172 phenotyping 1 72 lymphoscintigraphy, oral cancer 2565 Lynch-Howarth frontoethmoidectomy medical negligence 1 733 mucocoeles 1 535 orbital cellulitis 1544-5 lysine aspirin 1473 lysogenic bacteriophage 1 98-9 lysozyme nasal secretions 1 360 saliva 1 866 Sjogren syndrome 1 865 Mabthera ( ritiximab) 44 MacEwens triangle 3 1 1 9 'machinery oil cysts' 4103 Macintosh curved blade 473 MacNaughton Jones, Henry 3594 macrocytic anaemias 268 T, 269 macroglossia 1 828 macrolide antibiotics 2 3 1 activity spectrum 2 3 1 mechanism o f action 147 1-2, 1472 T side effects 23 1 macrophage( s) nasal mucus 1 362 wound healing 89-90 macrophage-colony stimulating factor (M-CSF) 69 macrostomia 1 8 1 1-2 macrotia 972-3, 974 F macular hair cells 3 1 50 F, 3228-30, 3230 F macula sacculi 3 1 5 1-2, 3 1 52 F macula utriculi 3 1 5 1-2, 3 1 52 F macule 1699-700 Maffuci's syndrome 1 708 magnesium biochemical analysis 3 8 1 , 381 T parathyroid function and 379 see also hypermagnesaemia; hypomagnesaemia magnesium-ATP, skin flap survival 1 1 3 magnetic-activated cell sorter (MACS) 73-4 magnetically retained prosthesis, orbital 2936, 2936 F 'magnetic feet' 373 1
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magnetic resonance angiography (MRA) children 1 299 glomus temporale tumour 4032 jugular foramen glomus tumours 4029 skull base lesions 3947 thyroid cancer 2691 magnetic resonance imaging (MRI) adenohypophysis 305 arachnoid cysts 401 3, 4014 F cavernous sinuses 306 cerebrospinal fluid rhinorrhoea 1 638 cervical lymph node assessment 176 1-2 children 1 298-9, 1 299 F, 1302 F cholesteatoma 3432 chronic otitis media 3419 cochlear implants assessment 365 1 contrast, forms of 676 F craniopharyngioma 4103-4 Cushing's disease 4 1 02 cystic hygroma 1 298, 1 299 F, 1782-3 dysphagia 1 967-8, 2028 epidermoids 401 1 , 40 1 2 F facial nerve 388 1 , 3883 F facial nerve schwannomas 4014 facial paralysis, children 1055 frontal sinus 1 502 fungal rhinosinusitis 2 1 8 acute fulminant 1455 invasive 1 454 F glomus temporale tumour 4032 hyperparathyroidism 392 hypopharyngeal cancer 2643-4 hypothyroidism 336 infundibulum, pituitary gland 305 intralabyrinthine schwannoma 3685 inverted papilloma 1 503 F, 1 523 jugular foramen lesions 4029, 403 1 F, 4042 juvenile angiofibroma 2438-9, 2439 F large vestibular aqueduct syndrome 3683-4, 3684 F laryngeal trauma 2273 laryngeal tumours 2607, 2607 F laryngopyocoele 2255 lipomas 401 3 , 401 3 F meningiomas 736, 4009-10, 4009 F, 401 0 F mucocoeles 1 533-4, 1 534 F, 1 535 F mucosal malignant melanoma 2409 multiple sclerosis 3846, 3847-8, 3847 F 'nasal cycle' 1 590
nasopharyngeal carcinoma 2456-7, 2457 F nasopharyngeal tuberculosis 2 1 2 1 neck 1 755-6 benign tumours 1 782-3 metastatic disease 272 1 neurofibromatosis 2 3962, 3963 neurohypophysis 305 nodular thyroid disease 333, 334, 362 objective tinnitus 360 1 olfactory dysfunction 1666 open bore scanners 307 optic chiasm 306 oral cavity tumours 2552-3, 2553, 2553 F orbital cellulitis 1 542-3 otitis media with effusion 3390 paragangliomas 736-9 parapharyngeal space tumours 2530 parathyroid glands 3 84 parotid gland pleomorphic adenoma 1 882, 1 885 F, 1 886 petrous apex lesions chondrosarcoma 4049, 4050 F chordoma 4049 cysts 4048, 4048 F, 4049 F pituitary gland 304 F, 305-7 pituitary macroadenomas 306 pituitary microadenomas 305, 306 pituitary tumours 305-7 contrast use 306 malignant 4 1 04 nonfunctioning adenomas 4 1 03 T 1-weighted images 305 T2-weighted images 305, 306 pleomorphic salivary adenoma 1 299 F Rathke's pouch cysts 4 103 respiratory scleroma 1463 rhinosinusitis 1442-3, 1480 salivary glands 1 875-6 advantages/disadvantages 1 874 T children 1 886, 1 893 F, 1 894 F contraindications 1 876 dental artefacts 1 876, 1 876 F fat suppression techniques 1 875, 1 875 F gadolinium contrast 1 875, 1 875 F, 1 876 F indications 1 890 T salivary gland tumours benign 1 884 extension 1 884, 1 890 malignant 1 884, 1 887, 1 889 F, 1 892 F, 1 895 F, 2506-7
sinonasal malignancy 2425-6 skull base lesions 3947 2328-9 sphenoid sinus 305 F, 306 temporal bone tumours 4069, 4090 temporomandibular disorder 3530 thyroid cancer 333, 2677, 2677 F, 2678 F thyroid eye disease 344 thyroid gland 328 thyroid stimulating hormone secreting adenomas 3 1 1 tinnitus 3610 trigeminal nerve schwannomas 4014 vestibular neuritis 3752 vestibular schwannomas 1 298, 3544, 3687-8, 3959 Wegener's granulomatosis 1 652 magnetic resonance proton spectroscopy, salivary glands 1 876 magnetic resonance sialography (MRS) conventional sialography vs. 1 879 indications 1 8 90 T salivary glands 1 876 sialolithiasis 1 879 magnetic stimulation, tinnitus 3615 T, 3618 magnets foreign body removal 1 186 implant retention 2932 magnitude estimation test 3251 magnitude production test 3251 mainstream education, deaf children 855 major histocompatibility complex (MHC) 1 36 antigen presentation 136 class I molecules 136 class II molecules 1 36, 137 allergic response 149-50 hypopharyngeal cancer 2637 see also human leukocyte antigen (HLA) malar augmentation, medical negligence 3095 malaria 208 malignancy hyperparathyroidism 401 telomerase activity 10 virus-associated 208-9 see also tumour(s) malignant fistulae see palliative care, head and neck cancer
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I ndex I 4243
malignant histiocytoma, larynx 2604 malignant melanoma 2399-402, 2399 F acral lentiginous 240 1 T CPA lesions 40 1 5 distant disease 2402 ear amputation 3028, 3032 F environmental exposure 2400 family history 2400 genetic predisposition 2400 incidence 2406-7 laryngeal 2604 local disease 240 1-2 mucosal see mucosal malignant melanoma nasal 1 706, 1 707, 1 707 F parotid metastases 250 1-2 pinna reconstruction 3032 F prognostic factors 2400 recurrence 2402 regional disease 2402 risk factors 2396 T, 2400 sinonasal 2422 staging 240 1 T syndromes 2400 treatment 240 1 types 2400-1 malignant odontogenic tumours (MOT) 1938 malignant otitis externa 3336-41 bacteriology 3337 clinical features 3334 T, 3337-8 complications 3338 definition 3336 diabetes mellitus 402, 3337 diagnosis 3337-8, 3337 F differential diagnosis 3334 T facial nerve paralysis 3890 F, 389 1 management 3338-9 treatment comparisons 3339 nomenclature 3336 outcomes 3338 pathology 3336-7 predisposing factors 3337 radiology 3338 staging 3336, 3337 T surgery 3339 malignant teratoma 1259 malignant wounds, dressings 101 Maliniak, Jacques 2944 mallampati 470 malleostapedotomy 3479-80 malleus anatomy 3 1 14-5, 3 1 1 5 F denuded, tuberculous otitis 3447, 3448 T, 3450 T
head fixation, otosclerosis 3474 lateral process 3 1 14-5 otoscopic examination 3 3 1 5-6 malnutrition albumin levels 95 indicators 95 rhinosinusitis, paediatric 1082 wound healing 94 malodorous wounds 1 0 1 malonyldialdehyde 1 1 3 Maltz, Maxwell 2944 mammosomatotrophs 297 mammotrophs 297 Manchester picture test 84 1 mandible development 1 739 elevation, swallowing 1956-7 osseointegration 2908 surface anatomy 1 740 tumours see mandibular tumours mandibular advancement splints (MAS) children 1 109 snoring 2333 mandibular cleft 1 8 1 1-2 mandibular condyle fractures 1622, 1624-5 temporomandibular joint 1 809 mandibular fractures 162 1-5 closed reduction techniques 1622-3 incomplete dental arch 1622-3 intact dental arch 1 622 displacement 162 1-2 external fixation 1623, 1624 F internal fixation 1624-5 principles 1624, 1624 F signs/symptoms 1622 surgical anatomy 162 1-2, 1621 F mandibular nerve (V3) 1750-1 , 1 802, 1802 T, 3924-7, 3925 F anterior division 3907, 3925 damage, tumour-induced 3927 in infratemporal fossa 1801 F, 3903 F, 3907-8 posterior division 3907-8, 3925 mandibular prominences 798, 1 8 1 0-1 mandibular protrusion, airway management 469-70 mandibular reconstruction fibula free flap 257 1 , 2572 F oral cavity tumours 2569-70 mandibular resection 2558-9, 2559 F, 2939-40, 2939 F rim 2559 mandibular swing, nasopharyngeal · carcinoma 2463
mandibular tumours 2558-9 imaging 2558 management 2558-9 mandibular nerve damage 3927 presentation 2558 rim resection 2559 segmental resection 2558-9, 2559 F survival rates 2559 T treatment outcome 2559 mandibulofacial dysostosis see Treacher Collins syndrome mandibulotomy 2586, 2587 lateral 2586-7 parapharyngeal space tumours 2533 segmental resection 2588 zigzag-stepped technique 2587-8 mandrill (Mandrillus sphinx), paranasal sinuses 1321 F mannan-binding lectin (MBL) pathway 1 39 F mannitol, ototoxicity prevention 3302 mannose binding lectin deficiency 1081 manofluoroscopy 1972-5 advantages 1972 analysis 1975, 1 975 F, 1976 F calibration 1975 contraindications 1975 equipment 1972-4, 1973 F methodology 1974-5, 1974 F procedure 1972-4 manometry analysis 1975, 1975 F diffuse oesophageal spasm 2067 F dysphagia investigations 1965, 1965 T, 1970-5, 2028 disadvantages 1971 T high-resolution 197 1-2 measurement problems 1971 T oesophageal 1 970 pharyngeal 1 970-1 gastro-oesophageal reflux 2063 interpretation 1975 nasal see rhinomanometry sensor spacing 1973-4, 1973 F with videofluoroscopy see manofluoroscopy manslaughter, involuntary 607-8 Manteaux test 1460 Marcain, blepharoplasty 3057, 3059 Marcus-Gunn pupil reaction 39 16 marginal cells, stria vascularis 3 1 86 marginal mandibular nerve of facial nerve 1750-1 surface anatomy 1741 maribavir 2004
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4244 I I ndex
marsupialization jaw cysts 1 922 odontogenic keratocysts 1925 masking 3246-9 cochlear hearing loss 3256 definition 3246 excitation pattern 3247 F, 3249 narrow frequency range 3247, 3247 F sinusoidal tone 3247 tinnitus 36 12 white noise 3247 masking level difference (MLD) test, central auditory dysfunction 3860 masseter muscle 3 9 1 0 wasting 3926 massive transfusion 284 Masson's tumour 2527 mast cells allergic response 148-9 degranulation, allergic rhinitis 1 390, 1392 function 140, 140-1 nasal polyposis 1 552 mastication 1956 Parkinson's disease 3939 masticator space 1 757, 2 1 10, 2 1 10 T, 2523 tumours 2530 masticatory mucosa 767, 1794-5 mastoid air cell system 3 1 1 8-9, 3 120 F mastoid cavities, paediatric cochlear implantation 865 mastoidectomy facial nerve palsy 923 otitis media with effusion 3393 paediatric anaesthesia 5 14 tuberculous otitis 3449, 3450 T
see also individual types mastoiditis, acute acute otitis media 922-3, 922 F AID patients 240 differential diagnosis 923 investigations 923 organisms 923 otalgia 3528 symptoms 922-3 mastoid obliteration, cholesteatoma 3434 mastoid pneumatization middle ear barotrauma 3504 otitis media with effusion 3390 mastoid process 1053-4 embryology 1053-4 surface anatomy 1740
mastoid . stimulation, ocular tilt reaction 375 1 mastoid surgery facial nerve palsy 3889 medical negligence 1 307 mastoid vent, percutaneous 3393 mastoid vibration 3 8 1 2 maternal genital warts, juvenile-onset recurrent respiratory papillomatosis 1 1 75 maternal infection, childhood deafness 846-7 maternal inheritance 1 8 maternally inherited diabetes and deafness (MIDD) 8 1 3 T matrix disruption enzymes 2387 T matrix-metalloproteases (MMP), hypopharyngeal cancer 2637 maxilla 1 340-1, 1 340 F, 1341 F adjunctive implant techniques 29 1 7 body 1 340 development 1 3 1 7 grafting 29 1 8 ossification centres 1 3 1 7 processes 1 340 maxillary alveolectomy 2560 maxillary antral washout, paediatric rhinosinusitis 1 084 maxillary artery 1 798 epistaxis 1 574 in infratemporal fossa 3902 F, 3906-7 in nose 1 363 parts 2 1 1 3, 3907 maxillary cyst 799, 802 F maxillary fractures 1 625-7 emergency treatment 1 627 fixation 1627 management 1 627 reduction 1 627 signs/symptoms 1 625 F, 1626-7, 1626 F surgical anatomy 1625-6 maxillary hiatus 1 330, 1341 maxillary nerve (V2 ) 3923-4, 3924 F branches 3923 nasal 1 325 damage, tumour-induced 3927 maxillary prominences (processes) 798, 799 F, 1 3 15, 1 8 1 0-1 maxillary protheses 2907-8, 2934 F maxillary resection 2925, 2929 maxillary rhinosinusitis 1 540 maxillary sinus 1 340-1 barotrauma 1 369 blood supply 1341
comparative anatomy 132 1-2 development 803, 805 F, 13 18-9, 1318 F drainage 1368 enlargement 1 3 18-9 growth 1 3 1 8-9 histology 1341 innervation 1341 lymphatic drainage 1341 noninvasive fungal rhinosinusitis 2 1 9 osteology 1 340-1 oxygen tension 1 368 pressure changes 1 369 relations 1341 size 1 3 1 8-9 maxillary sinus ostium 1332 maxillary sinus tap, acute bacterial rhinosinusitis 1442 maxillary sinus tumours epiphora 2424 patterns of spread 24 19 staging 242 1 , 2424 T TNM classification 2367 T maxillary swing technique 4059-6 1 , 4060 F nasopharyngeal carcinoma 2463 maxillary tuberosity 1341 implant placement 2907 maxillary tumours quality of life issues 2771 surgery 2427-8 maxillary veins 3907 maxillectomy 2429-30 case study 2933, 2934 F, 2936-7 extended 2428 lateral rhinotomy approach 243 1 , 243 1 F osteomies 2429, 2430 F otitis media with effusion 3390 partial 2428 hard palate carcinoma 2562--3 prosthetic reconstruction 2930 rehabilitation 2429-30 resection completion 2429 sinonasal malignancy 2429-30 soft-tissue approach 2429, 2430 F total 2428 maxillofacial surgery, 3D imaging 702-3 maxillofacial trauma, facial nerve injury 3887 maximal stimulation test (MST), facial nerve 3878-9, 3879 T maximum phonation time (MPT) 2 1 82
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I ndex 1 4245
maximum speech recognition score 3271 maximum surgical blood ordering schedule (MSBOS) 255, 255 T Mayfield clamp fixation 4056 McCormick toy test 841 McCoy blades 473, 474 F McCune-Albright syndrome 1 522 McFee incision 273 1-3, 2732 F McGill Pain Questionnaire 64 1 McKenzie, Morrel 771 McLaughlin's lateral tarsorrhaphy 3079 mean airflow rate (MFR) 2 1 8 1-2 mean arterial blood pressure (MABP) , hypotensive anaesthesia 502 mean corpuscular volume (MCV) 267 anaemia 268, 268 T measles 206-7 childhood deafness 847 chronic otitis media 34 10 complications 206-7 otosclerosis 3458-9 symptoms 206-7, 847, 847 F, 1701 vaccination 206-7 measles-mumps-rubella (MMR) vaccine 206, 1243 mechanical impedance 3288-9 mechanical ventilation indications 528 weaning from 528 mechanical wounds 97 mechanoreceptors laryngeal see laryngeal mechanoreceptors oral cavity 1959 Meckel's cartilage 1 739 meclizine 380 1 medial crura strut, underprojected nasal tip 3002 medial crus 2996 F anatomy 2960-1 buckled, correction of 2962 incisions 3002 tripod mechanism 2996 medial edge epithelium (MEE) 998 medial efferent system 3 145 medial geniculate nuclei 3 143-4 divisions 3 143-4 medialization laryngoplasty 2242 T medialization thyroplasty 1 1 7 1 medial medullary swallowing centre 1959 medial nasal process 1 8 1 1 medial nucleus of the trapezoid body 3 141-2
medial olfactory striae 3912-3 medial olivary nucleus 3 14 1-2, 3 14 1 F medial olivo cochlear reflex 3850 medial olivo cochlear system 3200 tinnitus 3606 medial pterygoid muscle 1 339, 2 1 13, 3905, 3907 F medial pterygoid plate 2 1 1 1 , 3899-900 medial rectus 322 1 medial vestibular nuclei (MVN) 3220 acute unilateral vestibular deafferentation 3222 neuron recovery 3224, 3225 F type 1 neurons 3220 type 2 neurons 3220 vestibular compensation 3793 median cleft 1 8 1 1-2 median clefts, true 997 median rhomboid glossitis 1 826-7 median thyrohyoid ligament 2 133-4 median thyroid anlage 3 1 4-5, 3 1 6 F mediastinitis parapharyngeal abscess 2000 peritonsillar abscess 1998 retropharyngeal abscess 2002 Medical Advisory Committee, medical negligence cases 2803 medical consultations children see paediatric consultation communication see communication, medical consultations seat/ desk arrangements 564 F medical ethics see ethical issues medical jargon 562 medical jurisprudence 594-6 12 assault and battery 595, 609 definitions 600 confidentiality see confidentiality consent see consent coroner's role 602-3 criminal law 607-9 European Convention on Human Rights 606-7 expert medical witnesses 603-5, 604, 604-5 Human Rights Act 2806 negligence see medical negligence patient's rights 609 performance and complaints 605-6 tort 595 medically unexplained symptom (MUS) atypical facial pa!n 1 829 burning mouth syndrome 1 829
medical negligence 595-600 Bolam test 596, 600, 2805 care standard ascertainment 595-6, 2805-7 Bolitho 2805-6 Sidaway 2806 causation 595, 596 clinical governance and 598, 2803 clinical situations 2804-5 communication issues 2804 note keeping and 2804 confidentiality breaches 2805 consent issues 600-1, 2806-7 criminal standard of proof 2804 damages 594, 595, 597-8 general 597-8 punitive 609 special 598 definition 595 dishonesty issues 2805 expert medical witnesses 604 facial plastic surgery see facial plastic surgery funding of claims 600 head and neck surgery see head and neck surgery Human Rights Act 2806 otology see otology paediatric otorhinolaryngology see paediatric otorhinolaryngology practitioners' health issues 2805 proof 596-7 protocol for claims 598-600 recklessness 2806 relationships 2805 rhinology see rhinology skull base surgery 4142-8 tort 595 trials 599-600 Medical Outcome Study Short-Form 36-Item Health Survey (SF-36) see SF-36 medical practitioners' health, medical negligence and 2805 medical records, ethical issues 587, 589 medical witnesses, expert see expert medical witnesses medicinal leech (Aeromonas hydrophila), skin flap survival 1 1 5 MEDLINE 646, 647 T Medpore 1 2 1 augmentation rhinoplasty 2973-4 nasal reconstruction 1 2 1 medulla, swallowing control 1 959 medullary swallowing centres 1959
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medullary thyroid carcinoma (MTC) 3 3 1 , 2673 T, 2674-5 children 1256 ectopic adrenocorticotropin production 401 genetic studies/screening 2687 imaging 720, 720 F, 2678 F long-term follow-up 2697 Ret mutations 2669, 2671 , 2687 serum calcitonin levels 36 1 treatment 2686-7 medulloblastomas 401 5 megaloblast 269 megaloblastic anaemias 269 megavoltage external radiotherapy nasop haryngeal carcinoma 2459-60, 2460 F syndrome (oromandibular syndrome) 3939-40 meiosis 2379 melanin, tinnitus 3598 melanocyte-stimulating hormone 4098 melanocytic lesions, external nose 1 706-7 melanocytic naevi, external nose 1 706-7 melanoma, malignant see malignant melanoma melanotic macule, oral mucosa 1 82 3 melatonin 2 306 Melkersson-Rosenthal syndrome 3876, 3876 F children 1059 facial nerve decompression surgery 4022 memantine 3804-5 membrane attack complex (MAC) 139 membranous labyrinth, embryology 806, 807 F, 3 1 22, 3 12 3 F membranous laryngotracheobronchitis see pseudomembranous croup memory loss, hyperparathyroidism 3 9 1 MEN-1 (MENIN) gene 389 MEN-2A 389, 2526 MEN-2B 389 MEN-2B syndrome 2526-7 MEN -2 gene see RET protooncogene ( cRET, MEN-2) Mendelian pattern of inheritance 1 8, 1 8-9 Mendelsohn manoeuvre 208 1 , 2090, 2090 T Meniere-like symptoms, DFNA9 mutations 3238
Meniere's disease 3695-6, 3757-60 aetiology 3757 aminoglycoside ototoxicity 3567, 3568-9, 3676 benign paroxysmal positioning vertigo 3760 children 1046, 1049 clinical manifestations 3695, 3709, 3757-8, 3758 F complications 3760 definition 3757 diagnosis 3754, 3756, 3758, 3758 F, 3759 F, 3771 diet 3798 differential diagnosis 3758-9 diplacusis 3597 drug therapy 423-4, 3798-800, 3799 T histopathology 3695-6, 3696 F, 3697 F hyperacusis 3596 immunological suppression 3800 management 433, 434, 3759-60 medical negligence 3830 motion intolerance 3707-8 otalgia 3528 outcomes 3760 stapes surgery contraindication 3469 sudden sensorineural hearing loss 3579 symptoms duration 3706 and stress 3798 tinnitus 3599 treatment 3798-800, 3798 F vestibular rehabilitation 3808 vestibuloocular reflex 3239, 3239 F meningcocoele 1 3 5 1-2 meningeal artery accessory 3907 middle 3907 MENIN gene 389 meningioma, sphenoid 1685 meningioma( s) 4008-1 1 abducent nerve 4009 aetiology 4008-9 anatomy/physiology 735-6 vascular supply 736, 737 F calcification 4009 classification 735-6, 4008 clinical presentation 736, 3943-4, 4009 collision tumours 4002 CPA tumours 4007, 4008-1 1 definition 4008
diagnosis 4009-10, 4009 F, 40 10 F embolization 3954-5 (en plaque' type 4008 epidemiology 4007, 4008-9 extracranial 4126 failure to diagnose 4144 fibrous 4008 gamma knife stereotactic radiosurgery 3993-4 hearing loss 3943-4 incidence 4032-3 intracranial 4126 jugular foramen 4032-3 intraoperative haemorrhage 4035 medical therapy 4042 radiotherapy 4043 resection 4039-40, 404 1 F tumour extension 4033 malignant transformation 4032-3 meningotheliomatous 4008 mortality 40 10 neurofibromatosis 1 4008-9 neurofibromatosis 2 4000, 4002, 4008-9 olfactory groove 3954-5, 4 144 orbital 3 9 1 5 parapharyngeal space 2527 pathology 4008 petrous apex 4047-8 posterior fossa 4 144 postural imbalance associated 3776 recurrence rates 40 10 skull base 1 684, 4 1 26 transitional 4008 treatment 40 10-1 tumour embolization 734, 735-6, 737 F vestibular imbalance 3777 vestibular nerve 3690-1 WHO classification 4032-3, 4033 T meningitis abducent nerve damage 391 8-9 active chronic otitis media 3437 management 3438 acute otitis media 924 cerebrospinal fluid rhinorrhoea 1636, 1 638, 1639-40, 4 144 childhood deafness 847 cochlear implantation 3654 children 864-5 cochlear implants candidature 365 1 hearing loss 824 hearing loss, genetic disposition 16-7 hypophysectomy complication 4 1 1 3 1306, 3830-1 medical
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I ndex I 4247
mumps 1900 pituitary tumours 305 post-stapes surgery 3477 sinusitis, children 1088 vestibular schwannoma removal 3982 meningococci 199 meningocoele frontal sinus malformations 1 504 nasal, children 1075 resection 1 505 meningoencephalocoeles see encephalocoele ( s) meningotheliomatous meningioma 4008 menstruation, vocal fold oedema 221 2-3 mental artery 1 798 Mental Health Act Commission 572-3 mentally incapacity, consent issues 601 mental nerve 1801 F, 1 802 menthol 1377, 1 377 F mentoplasty, medical negligence 3095 6-mercaptopurine (6MP) 38 merlin (NF2 protein; schwannomin) 3999 Mersilene 1 2 1 meso-tetra (hydroxyphenyl) chlorin (mTHPC), juvenile-onset recurrent respiratory papillomatosis 1 177 messenger RNA (mRNA) 4, IS, 2378-9 meta-analyses see systematic reviews metabolic disorders, olfactory dysfunction 1 673-4 metabolic rate, sleep 2307 metabolic syndrome associated disorders 391 hyperparathyroidism 39 1 obstructive sleep apnoea 23 14-5 premature death 391 metaiodobenzylguanidine (MIBG) neuroblastoma imaging 1258 thyroid nodule imaging 2676-7 metal biomaterials 1 19 advantages 1 19 applications 1 19 biocompatibility 1 19 disadvantages 1 19 properties 1 19 tissue response 1 19
see also individual metals metallothionein 2495-6 metastasis 2716-7 molecular detection methods 2 7 1 5-6 skip 2715
spread 36 integrins 36 surgery 2716
see also individual tumours metastatic neck disease 271 1-52 assessment 27 1 9-20 biopsy 2722 clinical examination 2720-2 clinical staging 2719-20, 2720 T current system criticisms 2 7 19 difficult neck 2727 arterial tree invasion assessment 2727 imaging 2727 distant metastases predictors 2719 evolution of 2 7 1 2-3 extracapsular nodal spread 2 7 1 8 treatment 2718 future research areas 2750 host factors 2712 knowledge deficiencies 2750 literature assessment 271 1-2 bias 271 1-2 locoregional control 2716 lymph node levels 2712, 2 7 1 2 F macrometastases 2718 metastatic process 2716-7 micrometastases 2 7 1 8 molecular detection methods 271 5-6 natural history 2 7 1 2-3 untreated neck 2 7 1 3, 2722 occult nodal disease 2717-8 treatment 2724 pathology 272 1-2 report standardization 272 1-2 physical examination sensitivity 2720 postoperative radiotherapy, extracapsular nodal spread 2718 primary tumour site prediction 2712, 2713 T prognosis extracapsular nodal spread 27 1 8 N2c disease 2726 nodal features 271 9 recurrence 2 7 1 8 retropharyngeal nodes 271 8-9 survival 27 1 8 systemic tumour burden index 271 5-6 treatment see metastatic neck disease treatment tumour biology 2714-9 bloodbourne metastases 271 5 cell destruction i n lymph " nodes 2 7 1 5
extranodal extension 2714 growth patterns 2714 malignant embolus 2714 premetastatic lesions 2714 secondary metastases 2714 skip metastases 271 5 tumour vascularization 2715 metastatic neck disease treatment 2722-7 bilateral and contralateral nodes (N2c) 2726 chemoradiation 2730 quality of life 2730 controversies 2722 interval contralateral lymphadenopathy 2726 large (greater than 3 cm and less than 6 cm nodes) 2726 massive nodes (greater than 6 cm; N3) 2727 multiple unilateral nodes (N2b) 2726 neck dissection see neck dissection occult metastases 2724 patient with no palpable node (NO) 2723, 2725 T delayed treatment 2723-4 elective neck investigations 2725 elective neck irradiation 2724-5, 2725 T elective surgery 2723-4, 2725 T 'wait and see' policy 2723-4, 2725 quality of life 2730-1 chemoradiation 2730 elective surgery vs. irradiation, NO neck 2730 node positive disease 2730 postoperative radiotherapy 2730 psychosocial issues 273 1 surgical extent 2730 radiotherapy 2728-9 clinically N- neck 2729 clinically positive neck 2729 elective, post-surgery 2729 quality of life 2730 recurrent disease 2729 surgery and 2729 salvage surgery 2728 single palpable metastasis, unilateral, less than 3 cm diameter (Nl ) 2725-6 conservation neck surgery 2725-6 radial neck dissection 2725-6 radiotherapy 2726 metastatic potential 2716
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methacholine tests allergic rhinitis 1561 asthma 1561 idiopathic rhinitis 1409 methadone, cancer pain management 2787 methicillin -resistant Staphylococcus au reus (MRSA) 196 otitis externa 3352 skin grafts 282 1-2 treatment 442-3 D-methionine, ototoxicity prevention 3302 methotrexate head and neck cancer 40 lupus pernio 1 7 1 1 mechanism of action 37, 38, 38 F Sjogren syndrome 1 9 1 3 (2-methoxyisobutyl-isonitirile) technetium-99m (MIBI) , thyroid cancer imaging 334, 694 methylation 10 methylcellulose solutions 2788 methylene blue staining, contact endoscopy 762-3, 763 methylprednisolone idiopathic sudden sensorineural hearing loss 1, 3584 vestibular neuritis 3756 methysergide 3803 T, 3804 metoclopramide migrainous vertigo 380 1 nausea and vomiting 2787 vestibular attacks, acute 3796 T, 3797 Met oncogene 2384 metopic synostosis (trigonocephaly) 1022 T, 1025-6 metronidazole 23 1 , 43 1 anaerobe detection 200 interactions 433 malignant ulcers/fistulae, cancer patients 2792 mechanisms of action 43 1 as radio sensitizer 50 rhinosinusitis 1 543-4 side effects 23 1 metyrapone, Cushing's disease 4102 metyrapone stimulation test 300, 3 10 MHC see major histocompatibility complex (MHC) microadenomas, pituitary gland see pituitary micro adenomas microaerophilic bacteria 201
microbial cultures fungus ball 1452 nasal endoscopy and 1 349-50, 1349 F microbubble contrast agents 714 microbubbles, decompression injuries 3 5 1 5 micro calcifications, papillary thyroid carcinoma 719 micro catheters 732-3 tumour embolization, skull base 395 1-2 micrococci 196 microcolpophysteroscope, chronic laryngitis 2260-1 microcytic anaemias 268-9, 268 T microdebrider adenoidectomy 1097 juvenile-onset recurrent respiratory papillomatosis 1 176, 1 177 F phonosurgery 2236 micro electromechanical systems (MEMS) 413 microfibrillar collagen, as embolic agent 733 microflora nasopharynx 195-6, 1 96 T, 2 1 2 1 normal 195-6 tonsils 1 2 1 9-20 microimmunofluorescence, Chlamydiae 202 microlaryngoscopy 2234-8 aims 2 1 95 anaesthesia 503 direct laryngoscopy vs. 2236 exposure 2235-6 history 2234-5 instrumentation 2235 laryngeal clefts 1 142 laryngeal tumours 2608 pathology 2236-8 surgical anatomy 2235 tubes 2 148, 2 1 50 voice evaluation 2 1 8 1 microlaryngotracheobronchoscopy (MLTB) 1 1 2 1 F; 1 122 microorganisms 1 95-203 host risk factors 195-6
see also individual species microphones 3 169-70 voice evaluation 2 1 76 micro satellite markers 8-9 microsatellite repeats 4 microstomia 1 8 1 1-2 microtia 967, 967-8, 975-80 bilateral 2927
classification 975-6 conchal type 975, 976 F prosthetic reconstruction 2928 surgical reconstruction 978 treatment 979-80 unilateral 2927 microtubules, cilia 1 360 microvascular flap reconstruction 1 10 microvascular free tissue transfer, oral cavity tumours 2569 microvilli olfactory neuroepithelium 1662, 1663 F septal columnar cells 1 327 taste buds 1841 Miculicz disease 1 9 14 Miculicz syndrome 1 9 14 midazolam cancer patients acute confusional states 2798 bleeding malignant ulcers and fistulae 2792-3 paediatric anaesthesia 509 midbrain gaze centres 392 1 midbrain lesions, eye movement defects 392 1 middle clinoid process 298 middle constrictor, pharynx 1947-9, 1 948 T middle ear acoustic impedance 3288-9 anatomy 3 105-25, 3 1 1 7 F blood supply 3 1 1 8 T compartments 3 1 16, 3 1 1 7 F congenital abnormalities 869-76 management 965-89 nonossicular 873-4 ossicular see congenital ossicular abnormalities development 3 105-25, 807-8, 814-5, 966, 3 120-2 folds 3 1 16, 3 1 17 F glandular tumours 4070-2
see also individual types hearing/ sound transmission 3 1 79-86 bone conduction 3 1 85 damaged ear 3 184-5 high frequencies 3 1 82-3 impedance transformer action 3 1 8 1-2 low frequencies 3 1 82 mode of vibration 3 179-8 1 muscles, influence of 3 1 83-4 transfer function 3 1 82-3, 3 1 82 F transformer action loss 3 1 84-5
Pages 1-1 3 12 are in Volume 1, pages 1 3 1 3-28 10 are in Volume 2, and pages 2 8 1 1-4 147 are in Volume 3 .
I ndex 1 4249
HIV infection 240 mucosa 3 1 16 otosclerosis 3456 muscles myogenic somatosounds 3600 reflexes 3 183 otalgia 3527-8 differential diagnosis 3528 relationships 3 1 14 F surgery see middle ear surgery type I malformations 808 see also tympanic membrane middle ear adenoma 4070-1 middle ear barotrauma 3504-6 differential diagnosis 3508 T hyperbaric oxygen treatment related 3 5 1 9 mucosal oedema development 3505 prevention 3505-6, 3506 treatment 3505 tympanic membrane 3505, 3505 T middle ear cleft 3 108-20 middle ear effusion acute otitis media 92 1 rheumatological diseases 1 84 middle ear haemangiopericytoma 4072 middle ear implants 3660-5 coupling mechanism 3661 current devices 366 1 device development 3660-1 future devices 366 1-2 history 3660-1 mode of transmission 3661 patient selection 3662 results 3663-4 middle ear infection, facial nerve damage 3931 middle ear squeeze see middle ear barotrauma middle ear surgery diving, postoperative 3506 facial nerve palsy 3889 flying, postoperative 3506 paediatric anaesthesia 5 14 reconstructive 982-4 anterior approach 983-4 ceramic biomaterials 120 complications 984 historical aspects 1 1 8 modified approach 984 preoperative considerations 982-3 transmastoid approach 984
see also individual procedures
middle fossa craniotomy, tuberculous otitis 3449 middle fossa-petrosectomy extension 402 1 middle fossa surgery 401 8-25 apex lesions 4024 basilar aneurysms 4024 cerebellopontine angle surgery 402 1-2 cerebrospinal fluid leaks 4023 clinical applications 402 1-4, 402 1 T closure 402 1 cochlear implantation 4023-4 craniotomy 4020 encephalocoele (meningoencephalocoele) 4023 facial nerve tumours 4022, 4022 F historical perspective 40 18 incision 4019-20 informed consent 4024 internal auditory canal 402 1-2 exposure completion 4020-1 lateral end 4020 medial end 4020 landmarks 401 8-9, 40 19 F medial approach 401 9 middle fossa floor 4022-4 exposure 4020 patient position 40 1 9 petroclival lesions 4024 petrous apicectomy 4024 superior semicircular canal dehiscence syndrome 4023 surgical anatomy 40 1 8-9 surgical technique 40 18-2 1 tegmen defect repair 4023, 4023 F transtemporal middle fossa approach 401 9 vestibular neurectomy 4021-2 middle jugular lymph nodes 1 747 middle latency response (MLR), central auditory dysfunction 3860, 3861-2, 3861 F, 3862 F middle lobe bronchus, right 2 14 1 middle meatus 1 330-1 pathophysiology 1501 rhinosinusitis 1442 middle meningeal artery 3907 middle nasal vault, external rhinoplasty 2964 middle pitch, note production 2 1 60-1 middle superior alveolar ( dental) artery 1 798 middle superior alveolar (dental) nerve 1341, 1 802 •
middle superior dental (alveolar) artery 1 798 middle superior dental (alveolar) nerve 1 341, 1 802 middle thyroid veins 3 1 7-8, 372-3 middle turbinate doubled 1332 osteomeatal complex 1 592 paradoxical 1335 F, 1335 T rhinosinusitis 1 592 midfacial degloving juvenile angiofibroma 2442, 2442 F maxillary tumours 2428, 2429 F nasopharyngeal carcinoma 2463 septal perforations 1 587 midfacial segment pain 1 725-7, 1 726 F midline flap pharyngoplasty lOl l, lO12 F midtracheal obstruction 483 migraine 1 722, 1722 F basilar see basilar migraine olfactory dysfunction 1 669-70 treatment 1 67 l taste abnormalities 1 848 migraine-related vestibulopathy (MRV) see migrainous vertigo migrainous vertigo 3770-2, 3779 aetiology 3770 children 1049 clinical manifestations 3771 complications 377l-2 definition 3770 diagnosis 3754, 3762, 377 1 , 3800, 3802 F, 3802 T dietary modifications 3800-1 differential diagnosis 377l lifestyle modifications 3800-1 management 377l outcomes 3771-2 over-the-counter medications 3801 pathogenesis 3801 F treatment 3800-4, 3803 T prophylactic 3803-4 symptomatic/abortive 3801-3 vestibular rehabilitation 3808 migratory glossitis, benign 1 825-6,
1826 F Mikulicz cells 1462-3 milia 1709 'milk nasendoscopy' see fibreoptic endoscopic evaluation of swallowing (FEES) Millard rotation, cleft lip and palate 1 004, 1004 F Miller Fisher syndrome 3778
Pages 1-1 3 1 2 are in Volume 1, pages 1 3 1 3-28 1 0 are in Volume 2, and pages 2 8 1 1-4 147 are in Volume 3.
4250 1 I nd ex
minimal bactericidal concentration 234 minimal inhibitory concentration (MIC) 234, 147 1
modified radical neck dissection 2564 F, 2746-7 complications 2749
molluscum sebaceum 1 704-5, 1704 F mometasone 437, 1 398, 1401 monaural low-redundancy speech
minimum audible field 3250, 325 1 F
contraindications 2733
minimum audible pressure
indications 2746
Mondini deformity 851 F, 1298 F
operative technique 2746-7 accessory nerve
monobactams 229, 230
(MAP) 3250 mini-Penning orthopaedic fixator 1 623, 1 624 F minitracheostomy 2294 commercial kits 2294, 2294 F Miopithecus talapoin (dwarf
gueron) 1 322 F
preservation 2746-7 internal jugular vein preservation 2747 sternomastoid muscle
mirror ear (polyotia) 969, 970 F
preservation 2746-7 postoperative management 2749
misonidazole 2756
single palpable metastasis, unilateral,
misopristol 36 1 8 mitochondria, apoptosis 5 8 mitochondrial DNA (mtDNA) 4-5, 18 acidosis and stroke-like episodes (MELAS) 8 1 3 T mitochondrial genome 3, 4-5 A 1 555G mutation 1 6-7 amino glycoside-induced hearing loss 1 6-7 deafness-associated mutations 1 6-7, 1 8, 853 inheritance 18 mitomycin C (MMC) 50-1 arytenoid granuloma 2238 choanal atresia 1 072 dacryocystorhinostomy 1695 laryngeal stenosis 2278 mechanism of action 38
monoclonal antibodies (MAb) 4 1 , 52 antibody-dependent cellular cytotoxicity 4 1 epidermal growth factor receptor 43 ideal target properties 41
( N1 ) 2725-6
murine 4 1
type 1 2745 T, 2746, 2746 F type 2 2745 T, 2 746, 2746 F indications 2745 T, 2746 type 3 2745 T, 2746, 2746 F indications 2745 T, 2746 modifier genes 16 auditory system 8 1 7 modulation transfer function, auditory neuropathy/dyssynchrony 3852 Moebius syndrome facial reanimation 3085, 3086 F muscle graft 3080-1 Moffatt's solution 1680-1 endoscopic sinus surgery 1482-3 Moh's micrographic surgery basal cell carcinoma 2397 medical negligence 3093
mitotic spindle poisons 38-9
postoperative nasal
mitral cells 1 663, 3 9 1 2
craniosynostosis 1 029 monochromatic 743
mechanism of action 4 1
toxicity 50-1 mitosis 35, 35 F, 2379, 238 1 mitoxantrone 3772-3
monobloc procedures, syndromic
less than 3 cm diameter
indications 2745 T, 2746
mitochondrial encephalopathy, lactic
tests 3858-9
nasal 1 706
reconstruction 30 1 7, 302 1 F, 3023 F, 3024 F
skin flap survival 1 14 sources 4 1 vascular endothelial growth factor receptor 43-4 monocytes differentiation 89-90 wound healing 89 monoiodotyrosine (MIT) 321 secretion 322-3 mononeuropathy, neurofibromatosis 2 4000 monophosphoryl lipid A (MPL) 1 5 7-8 monosodium glutamate allergy 1427 monospot test Epstein-Barr virus 1225, 1984 lymphocytosis 274 monosyllabic words, speech audiometry 3270, 3 272 Montgomery stent, laryngeal stenosis 2279, 2280 F mood disorders, tinnitus 3608 Moon's molars 1 8 1 8
'mixed rhinitis' 1408-9
molariform teeth see molars; premolars
morality see ethical issues
mizolastine 1 397-8 MMR vaccine 206, 1 243
molars 1 803
Moraxella catarrhalis 199
sensorineural hearing loss 2 1 1
cusps 1 804
acute laryngitis 2249
deciduous 1 804-5
HIV-associated otitis media 240
mobile phones, salivary gland tumours 2476
permanent 1 804
Mobius syndrome lOSS, 3085, 3086 F
roots 1 804
modal register 2 1 6 1 , 2 162 T
roots 1 804-5
molecular biology 3-1 4
Modernising medical careers 553
future research areas 1 1-3
modified Hughson-Westlake
knowledge deficiencies 1 1-3
(ascending) method, pure-tone audiometry 3263-4 modified neck dissection, medical negligence 2808 modified radical mastoidectomy, cholesteatoma 3432
methods 5-8 molecular cytogenetics 6-7 molecular displacement, sound 3 1 73 molecular otology 8 1 1-20, 8 1 3 T molluscum contagiosum 247, 1 7 0 1 , 1701 F
nasopharynx 2 1 2 1 rhinosinusitis 1 44 1 acute 1080 chronic 147 1 HIV-associated 241 -2 vaccination 9 1 9, 920 Morel-Fatio springs 3079 Moro response 1040-1 morphine acute pain management 463 cancer pain management 2786 doses 2787 T
Pages 1-13 1 2 are in Volume 1, pages 1 3 1 3-28 1 0 are in Volume 2, and pages 281 1-4 147 are in Volume 3.
I nd ex . 4251
morphoeic basal cell carcinoma 2397 m orphogenetic deafness 8 1 1-2 morsicatio buccarum (cheek biting) 1 836 mosaicism, neurofibromatosis 2 3999, 4001 motion sickness 3239-40, 3707-8 children 1 044 DFNA9 gene mutations 3238 passive forms of motion 32 1 1 transdermal hyoscine 408-9 vestibular system anatomical differences 3209-10 motor cortex, swallowing 1 958 motor delay, hearing tests and 841 motor neurone disease 2079-80 diagnosis 2079-80 dysphagia 2033 pharyngeal symptoms 2079-80 pseudobulbar palsy 3939 treatment 2080 motor tinnitus 3606 moulding helmets, posterior skull deformity 1026-7 mouth anatomy 1 79 1-8 15 development 799-802, 802 F dry see xerostomia floor 1 793, 1 793 F, 1 796 F blood supply 1 799 carcinoma see floor of mouth carcinoma muscles 1 795-6, 1 796 F sensory innervation 1 795 F, 180 1, 1801 F, 1 802-3 oral mucosa 1794-5 primitive see stomodeum tissue spaces 1 805-7, 1 807 F see also oral cavity mouth breathing, sleep-disordered breathing 1 104 mouth ulcers 1 823, 1 830-2 causes 1 822, 1 822 T, 1 830 Crohn's disease 1 828, 1 834 drug-induced 1 835 fungal infections 1 833 haematological diseases 1 833-4 head and neck cancer, palliative care 2788 T, 2789 HIV 1835 infected 2788 T, 2789 inherited disorders 1 824 local aetiology 1 830 malignant neoplasms 1 832 pemphigus 1 834 F
syphilis 1 833 tuberculosis 1 833 mouthwashes 448 movement detection otolith organs 32 1 0-1 semicircular canals 32 1 1 vestibular system 3 2 1 0-3 Movicol (polyethylene glycol) 279 1 M-proteins 1982-3, 1 983 MRSA see methicillin-resistant Staphylococcus aureus (MRSA) MT activation, functional magnetic resonance imaging 681 MUC2 gene 1 359 MUC5AC gene 1 359 mucin genes 1 359 acute otitis media 9 1 6 mucinous adenocarcinoma, salivary glands 2500 survival 25 12-3 mucins, nasal mucus 1 359 mucocoeles 1 53 1-8 aetiology 153 1-2, 1 532 T affected sites 1 53 1 , 1 5 3 1 T bone dynamics 1 532, 1 533 F children 1 537 frontoethmoid 1086 sinusitis 1086 chronic rhinosinusitis 1 540 clinical features 1 532-3 definition 1 5 3 1 differential diagnosis 1 533-4 ethmoidal 1 533 F, 1 534 F external frontoethmoidectomy complication 1 508-9 fibrous dysplasia 1 522-3 frontal 1 533 F, 1 534 F glandular tissue cystic degeneration 1 532 histology 1 532, 1 532 F imaging 1 533-4 immune factors 1 532 maxillary sinus 1532-3, 1 535 F nasolacrimal 1 689, 1 690 F, 169 1 oral blisters 1 822, 1 825 pathogenesis 1 53 1 , 1 532 F retention 1 9 1 5 salivary glands 1 9 1 5, 1 9 1 5 F sphenoid 1532-3, 1534 F surgery 1535 complications 1 535, 1 536 T guidelines 1 5 1 9 recurrence rates 1 535, 1 536 T results 1535, 1 535 T, 1 536 T , treatment 1 53 5
mucoepidermoid carcinoma larynx 2604 salivary gland 2497-8, 2498 F children 1 249 F treatment 2498 mucolytics otitis media with effusion 896 rhinosinusitis 440 mucoperichondrium trauma 1 573, 1573 F mucopolysaccharides, otosclerosis 3459 mucopolysaccharidosis 468-9, 469 F mucopus, olfactory dysfunction 1 664-5 mucopyocoeles 1 506 Mucorales, fungal rhinosinusitis 2 1 7, 1450 T mucormycosis 2 1 8 mucosa contact endoscopy 762-3 middle ear 3 1 16 nasal see nasal mucosa nasopharynx 1 947, 2 1 08 oral see oral mucosa vocal folds 2 1 93-4 mucosa-associated lymphoid tissue (MALT) tumour, Sjogren syndrome 1 9 1 1, 1 9 1 1 F mucosal barrier injury see mucositis mucosal bridge, vocal folds 2201-3, 2202 F mucosal flap repair, septal perforations 1 586, 1 586 F mucosal malignant melanoma 2406-16 aetiology 2409 biology 2409 complications 241 3 diagnosis 2408, 2408 F host factors 2407-8, 2408 T incidence 2406-7 metastasis 24 10-1, 241 1 F presentation 2407, 2407 F recurrence 2410-1, 24 1 1 F site 2407, 2408 T staging 2409 survival 241 1-3 Cox's proportional hazards model 2412...;.3 , 2413 melanotic vs. amelanotic 24 12, 241 2 F observed 241 1-2, 24 1 2 F treatment effects 2412, 2412 F tumour-specific 241 1-2, 2412 F treatment 2409-10 tumour factors 2407-8, 2408 T types 2407
Pages 1-13 1 2 are in Volume 1, pages 1 3 13-2 8 1 0 are in Volume 2, and pages 281 1-4147 are in Volume 3.
4252 I I ndex
mucosal pain, advanced head and neck cancer 2785 mucosal wave, vocal folds 2 193 mucositis 1835 causes 1 835 clinical features 1835 diagnosis 1 835 oral manifestations 1835 palliative care, head and neck cancer 2789 treatment 1835 mucous cysts 1074 mucous glands larynx 2 1 37-8 nasal cavity 764 mucous membrane pemphigoid (MMP), oral 1 834, 1 834 F mucus, nasal see nasal mucus mucus retention cyst, vocal folds 220 1 , 2201 F Muenke craniosynostosis (FGFR3associated coronal synostosis syndrome) 1027-8 Muir-Torre syndrome 1704-5 mulberry molars 1 8 1 8 Miiller, Johanes 3594 multicentre regional ethics committees (MRECs) 588-9 Multidimensional Voice Program (MDVP) 2 1 84, 2 1 84 T multidisciplinary audit 568 multidisciplinary teamworking cancer care 576, 576-7 clinical governance 568, 576, 576-7 craniofacial anomalies 1020 T multi drug resistant (MDRTB) tuberculosis 1460 multifluor FISH (M-FISH) 6 multimemory hearing aids 3637 multinodular goitre 3 3 1 Grave's disease and 331 imaging studies 334 nontoxic 360-1 thyrotoxicosis 341 tracheal compression 363 treatment 362 physical examination 36 1 prevalence 360-1 symptoms 36 1 tracheal compression 363 treatment 363 treatment-induced hypothyroidism 363
multiple endocrine neoplasia (MEN) children 1256 genetics 40 1 hyperparathyroidism 388, 40 1 thyroid cancer aetiology 267 1 , 2674-5, 2687 medullary cell carcinoma 3 3 1 , 720 multiple myeloma, larynx 2604 multiple papillomatosis 209 T multiple sclerosis (MS) 3772-3, 3779 acoustic brainstem evoked responses 3846 aetiology 3772 clinical manifestations 3772 complications 3773 definition 3772 diagnosis 3772, 3773 F differential diagnosis 3772 dysphagia 2033, 2078 gaze defects 3922 hearing loss 3846-8 magnetic resonance imaging 3846, 3847-8, 3847 F management 3772-3 olfactory dysfunction 1 669 treatment 1671 outcomes 3773 taste abnormalities 1 847 treatment 2078 vertigo 3754, 3773 voice disorders 2222 multiple step saccades, saccadic hypometria 3715 multiple systems atrophy (MSA) 3775 mumps 206, 1 2 1 2 children 1243 deafness 847 complications 206 meningitis 1 900 salivary gland involvement 1243, 1 900 symptoms 206 vaccination 206, 1243 vestibular system 3694 mupirocin 442-3 murine oncogenic retroviruses, gene therapy 27 muscle biopsy, neonatal facial paralysis 1055 muscle grafts facial reanimation 3080-2 choice of muscle 3080-1 complications 3082-4
first stage 3080 results 3082, 3082 T, 3083 F second stage 3080-2 lower lip depressor weakness 3085 muscle nerve pedicle reinnervation, laryngeal 2244 muscle-only axial distant flaps 2854-5 muscles of facial expression innervation 3928-9 lips 1 798 muscle stem cells 74 muscle tension dysphonia (MTD) 2203-5, 2204 F aetiology 2204 clinical manifestations 2203--4 contact quotient measurement 2 179 disorder hypotheses 2204 symptoms 2204 treatment 2 195, 2204
see also individual types muscular tension, tinnitus 3616 musculoperiostial flap, translabyrinthine vestibular schwannoma surgery 3969 Mustarde pinnaplasty technique, medical negligence 3092 mutation causative 19-20 'crossing over' 1 9-20 definition 16 DNA rearrangement 1 6 mitochondrial 1 8 neurofibromatosis 2 3999 nonsyndromic deafness 1 8 screening 19-20 syndromic deafness 1 8 types 9-10 X-linked 1 8 mutational falsetto voice 2204-5, 2226 speech therapy 2226 mutuality, consultation style 560, 560 F myasthenia gravis acetyl choline receptor antibodies 1 72 bulbar type 3939 causes 2077 dysphagia aetiology 2033 hyperacusis 3596 pharyngeal dysfunction 2077 symptoms 2077 thymona 1 72 treatment 2077 mycetomas see fungus ball mycobacteria 201 atypical 201
see also individual species
Pages 1-1 3 1 2 are in Volume 1 , pages 13 1 3-2 8 1 0 are in Volume 2, and pages 2 8 1 1--4 147 are in Volume 3 .
I n dex I 4253
mycobacterial infections neck, children 1214-6 salivary glands, children 1 244-5 Mycobacterium avium complex (MAC) 247
Mycobacterium Mycobacterium Mycobacterium Mycobacterium
avium intracellulare 20 1 bovis 20 1 kansasii 20 1 leprae 1463, 20 10
infectious rhinosinusitis 1381 nasal infection 1 3 8 1 , 1463, 1 703 Mycobacterium malmoense 20 1 Mycobacterium scrofulaceum 201 Mycobacterium tuberculosis 20 1 , 20 1 F cervical swellings 12 14-5 detection 20 1 HIV-associated cervical masses 246-7 infectious rhinosinusitis 1 3 8 1 nasal tuberculosis 1458 rifampicin resistance testing 235 specimen handling precautions 201 mycophenolate mofetil 1 653 mycoplasma(s) 20 1 cell structure 20 1
see also individual species Mycoplasma orale 20 1 Mycoplasma pneumoniae 201 bullous myringitis 3326 erythema multiforme 1 835 otitis media 20 1 pneumonia 20 1 Mycoplasma salivarum 201 mycotic diseases ear 2 1 3-4 nose 2 1 5-6 paranasal sinuses 2 1 6-22 throat 223-5 tracheo-oesophageal voice protheses 225 mycotic laryngitis 2254 aetiology 2254 clinical features 2254 immunocompromised patients 2254 investigations 2254 management 2254 predisposing factors 2254 recurrent infection 2254 myelin sheaths, auditory neuropathy/ dyssynchrony 3849-50 myelodysplastic syndrome (MDS) 269 myelogenous carcinoma, larynx 2604 myeloperoxidase, skin flap survival 1 1 3-4
Myer-Cotton grading system, laryngotracheal stenosis 1 1 39, 1 1 52, 1 153 T, 1 160-1 mylohyoid muscle 1 795-6, 1 796 F, 1 803, 2 135 T mylohyoid nerve 1 803, 3907-8 mylohyoid ridge, mandible implants 2908 MY07A gene mutations 1 5-6, 20 myocardial ischaemia, surgical preparations 459 myocarditis, diphtheria and 2253 myoclonic epilepsy and ragged red fibres (MERRF) 8 1 3 T myocutaneous axial distant flaps 2854-5, 2855 F, 2855 T myoepithelioma 2483 myofascial pain advanced head and neck cancer 2784 facial 1 72 1 myofibroblasts 9 1 myofibroblast theory 9 1-2 myogenic somatosounds 3600 myopathy dysphagia 2077 hypothyroidism 355 myosin, vestibular hair cells 3234 abnormalities 3238 myosin If3 3234 myosin-V 3238 myosin VI 3238 myosin VII 3238 myosin VIlA gene mutations 3238 myotonic dystrophy 2076-7 myringitis bullosa haemorrhagica see bullous myringitis myringitis granulosa see granular myringitis myringoplasty active mucosal chronic otitis media 3425 complications 3422 inactive mucosal chronic otitis media 342 1-2 hearing outcomes 3422, 3422 T revision 3422 procedure 342 1 tympanic membrane take rate 342 1-2, 3422 T myringotomy acute mastoiditis 923 acute otitis media 9 1 8 cerebrospinal fluid fistula 3390 otitis media with, effusion 339 1 , 3392 paediatric anaesthesia 5 1 3-4
myringotomy with aspiration, otitis media with effusion 896 myxoedema definition 353 glycosaminoglycans 353 Graves' disease 344 F hypothyroidism 355 sensorineural hearing loss 400 myxoedema coma 350 T 'myxoedema madness' 355 myxoid chondrosarcoma 4073 myxoma, odontogenic 1928-9 NI potential, cochlea 3 1 96, 328 1 N2 potential, cochlea 3 196, 328 1 naeVI dysplastic 2400 external nose 1 706-7 melanocytic 1 706-7 oral mucosa 1 823 Spitz 1 707 naevoid basal cell carcinoma syndrome 1 705-6 naevus flammeus 1 708 naftidrofuryl, idiopathic sudden sensorineural hearing loss 1, 3588 Na+-K+-2CI cotransporter, saliva secretion 1 860 nalidixic acid 230-1 Nanog 68-9 narcolepsy 2310 narcotic analgesia, obstructive sleep apnoea 1 1 10 Narcy test 1 122 narrow field laryngectomy, intractable aspiration 2099, 2099 F nasal agenesis 1073, 1 320 nasal airflow 1 357-8 expiration 1 357, 1 357 F inspiration 1357, 1357 F measurement 1372-9, 2 146 best clinical practice 1 378 current knowledge/future research 1 378 subjective 1376-7, 1377 F
see also individual techniques menthol, effects on sensation 1 377, 1377 F normal 1374-5 peak 1 375 resistance 1 357-8 septum, role of 1570, 1571 F nasal allergen challenge 1 395 measurements 1395 occupational rhinitis 1420-1
Pages 1-1 3 1 2 are in Volume 1, pages 1 3 1 3-28 1 0 are in Volume 2, and pages 281 1-4147 are in Volume 3.
4254 I I ndex
nasal amputation 2924-5 nasalance 1 375-6 nasal balloon inflation, barotrauma 3506 nasal bones 1324, 1324 F, 1325 F nasal bridge implants 2907 nasal cavity anatomy 1 325-6, 1 344-6, 1944 F comparative 132 1-2, 1321 F, 1322 F floor 1 325-6 roof 1 326 anomalies 1 346 development 803, 13 1 5, 1 3 16 F, 1811 F diffuser effect 1 589 drainage 1 344-6, 1346 F endoscopy see nasal endoscopy function 1 66 1 lymphatic drainage 27 1 3 synechiae 1 344-6, 1 346 F tumours see sinonasal malignancy variations 1 325-6 vascular supply 1 599 F see also nose nasal conduction 1356 nasal consonants 2 1 67, 2 1 67 T nasal cycle 1 358, 1376 children 1358 enlarged turbinates 1 590 mucosal swelling 1 590 olfactory sensitivity 1 66 1-2 nasal cysts 1073-4, 1 708-9 nasal defects aetiology 3 0 1 6 T reconstruction see nasal reconstruction nasal diseases/disorders olfactory dysfunction 1 667-8 otalgia 3530
see also individual diseases nasal dorsum autologous cartilage grafts 2972, 2973 T deviation 2983 F irregularities 2982, 2983 F over-resection 2970 reduction 295 1 F sagging 2984 F nasal douching allergic rhinitis 1 399 chronic rhinosinusitis 1470 nasal encephalocoele (meningoencephalocoele) 1 709
nasal endoscopy 1344-54 adenoid assessment 1096, 1096 F airway management 470 anatomical aspects 1 344-6 anomalies 1 346 previously operated patients 1346, 1 346 F cancer surveillance 1351 cleaning guidelines 2 147 clinical uses 1 349-53 complications 1347 contact see contact endoscopy CT and 1344, 1 350 current knowledge/future research 1353 epistaxis 1 352-3, 1 602, 1 602 F equipment 1346-7 historical aspects 1 344 infection control 2 147 inflammatory disease 1349-50 CT and 1350, 1350 F cultures 1349-50, 1 349 F differential diagnosis 1 349 F, 1 3 5 1 F postoperative care and evaluation 1350 prognosis 1 350 midfacial segment pain 1 72 7 nasopharyngeal carcinoma 339 1 neoplastic disease 1350-1 , 1351 F olfactory dysfunction 1 664-5 ophthalmologic procedures 1352, 1 353 F patient positioning 1 347 polyposis 1 55 1 , 1 553, 1 553 T rhinosinusitis 1442 role 1 344 septal perforations 1 583 sinusitis 1 720, 1720 F skull base lesions 135 1-2, 1 352 F technique 1 347-8 blue light endoscopy 135 1-2, 1352 F first pass 1347-8 fluorescein endoscopy 135 1-2, 1 352 F preparation 1347 second pass 1348, 1 348 F third pass 1348, 1 348 F trauma due to 1 347 visualization 1 347 nasal fistula(e) 1 502-5, 1 504. F, 1 506 F diagnosis 1 504-5 operative principles 1 505 prognosis 1 505 nasal folds 1 3 1 5, 1 3 16 F
nasal fontanelle, anterior 1 330 nasal foreign bodies, children 1 1 86 epistaxis 1065 management 1 1 86 medical negligence 1 309-10 presentation 1076, 1 1 86, 1 1 86 F nasal fossa 1321 nasal fractures 1 609-17 aetiology 1 609 classification 1 609-1 1 class 1 1 6 10, 1610 F class 2 1 6 10-1, 1 6 1 1 F class 3 see naso-orbito-ethmoid (NOE) complex fractures clinical presentation 1 6 1 1-2 complications 1 6 14-5 poor cosmetic result 1614-5 septal 1 6 1 5 deformity, extent o f 1 6 10 epidemiology 1 609 examination 161 1-2 history taking 1 6 1 1 injury, nature of 1 609-10 investigations 1 612 children 1296 medical negligence 1 3 10, 1 730 pathophysiology 1 609-1 1, 1 610 F, 161 1 F patterns 1 6 10-1 reduction methods 161 3-4 instruments 1613, 1 6 1 3 F, 1 6 14 F surgical indications 1 612 treatment 1612-4 anaesthesia 1 612-3 septal management 1614 nasal glands, contact endoscopy 764 nasal glioma 1 709 children 1075, 1075 F nasal granulomatous conditions 1 645-59, 1 646 T definition 1 645 primary vasculitis 1 646 T
see also specific disorders nasal haemangioma 1075-6, 1075 F, 1708 nasal implants 2971 magnetic retention 29 1 0 F, 2935 F nasal bridge 2907 osseointegration 2909-10 placement, ablative surgery and 2928 polymer 1 2 1 synthetic 297 1 nasal infections acute 1700-2 bacterial 1 700 viral 1 700-1
Pages 1-13 12 are in Volume 1, pages 1313-2810 are in Volume 2, and pages 281 1-4147 are in Volume 3.
I ndex I 4255
bacterial 1 700 chronic 1458-68, 1 702-4 endoscopy 1 349-50, 1349 F lupus vulgaris 1 702-3, 1 702 F protozoal 1703-4 viral 1700-1
see also specific conditions nasal inflammation asthma 1 56 1-2 chronic obstructive pulmonary disease 1 56 1-2, 1 562 endoscopy see nasal endoscopy nonallergic, noninfectious 1 382-3 polyposis 1 552 rhinitis 1 563 nasal inlet restriction 3007 nasal inspiratory flow rate (NIPF), occupational rhinitis 1420-1 nasalis muscle 1 322-4 strengthening 3012 nasal masses, congenital 1074-6 nasal mastocytosis, nonallergic rhinitis vs. 14 1 1 nasal meatus inferior 1 344-6 first pass endoscopy 1347 middle 1344-6, 1 345 F second pass endoscopy 1 348 third pass endoscopy 1348, 1348 F superior 1344-6 nasal mucosa allergic rhinitis 1 393 oestrogens, effects on 402-3 olfactory dysfunction assessment 1 664-5 dryness 1 667-8 pregnancy-related changes 402-3 surgical preparation 442 nasal mucus composition 1 359 elasticity 1359-60 odourant-binding proteins 1662 rheology 1 359-60 surface cells 1 362 viscosity 1 359-60 measurement 1 360 nasal mycoses, epistaxis 1065 nasal neoplasms see sinonasal malignancy nasal obstruction ACE inhibitor-induced 1410 atrophic rhinitis 1 465 children 1 070-8 acquired disorders 1071 T, 1 076-7 congenital disorders 1070-6, 1071 T
examination 1070 fibro-osseous disease 1 077 foreign bodies 1 076 nasal masses 1 074-6 osseocartilagenous deformity 1 076 physiological rhinitis 1 076-7 septal haematoma/abscess 1 076 severity 1 070 skeletal anomalies 1 070-3 systemic diseases 1071 T chronic rhinitis 1591 continuous positive airway pressure 1 59 1 HIV patients 241 hypothyroidism 1 366 nasal cysts 1 073-4 nasal fractures 1 61 2 , 1 6 1 5 newborns 1 070 pregnancy 402-3 septal pathology 1 575 septoplasty indication 1576-7 see also nasal polyposis nasal packing epistaxis 1 602 children 1064 posterior 1 603 hypophysectomy 4 1 12-3 nasal papillas 764 nasal pits 1 8 1 1 nasal placode 1 3 15, 1 8 1 1 nasal polypectomy 1 555-6 medical negligence 1 733 nasal polyposis 1 549-59 aetiology 1 550-1 fungal rhinosinusitis 2 2 1 associated diseases 1 550- 1 , 1 550 T characteristics 1 549 children 1550 clinical presentation 1 552-3 definition 1 549 diagnosis 1 553-4, 1553 T differential diagnosis 1 553-4 epidemiology 1 550 epithelium 1 55 1 defects 1 5 5 1 inflammatory role 1 5 5 1 type 1 5 5 1 formation sites 1 5 5 1 genetic factors 1470 goblet cells 1 5 5 1 imaging 1 553 inflammation 1 552 innervation 1 55 1 pathogenesis 155 1-2
pathology 155 1-2 prevalence 1 550 recurrence 1 550 staging 1 553-4 submucosal glands 1 552 surgery 1 555-6 treatment 42 1 , 437-8, 1554-6, 1 556 vascularity 1 552 see also nasal polyps nasal polyps anterior cranial fossa meningioma 4 144 aspirin desensitization 442 endoscopy contact endoscopy 765 CT vs. 1350, 1350 F eosinophil apoptosis 62 olfactory dysfunction 166 1 persistent rhinosinusitis and systemic steroid treatment 438 topical steroid treatment 438 unilateral 1 383-4 see also nasal polyposis nasal reconstruction 3015-27 aesthetic subunits 30 16, 30 1 7 F anatomy 30 16 composite cartilage grafts 3022-3 distant pedicled flaps 302 1-2 dorsal nasal flap 30 1 9 excision 3 0 1 8 fixture placement 2928 flap design 3019 healing by secondary intention 301 8 historical aspects 1 10, 301 5-6 local flaps 3019 malignancy 301 7 midline forehead flap 3022 nasolabial flap 3020, 302 1 F osseointegration, midface region 2928 paramedian forehead flap 3022 physiology 3017-8 graft healing 3017 pinna, free sandwich graft 3022 polymer implants 1 2 1 primary closure 301 8 principles 3016-7 prosthetic 2928 regional pedicled flaps 302 1-2 septal flaps 3020-1 skin flaps, historical aspects 1 10 skin grafts 30 19 techniques 3018-23, 301 8 T vascular bud growth 3017-8
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4256 1 I ndex
nasal reflexes 1 364-5 axon reflexes 1 364 central control 1 365 cutaneous stimulation 1 365 stimulus-induced 1 364 nasal resistance, airflow 1 3 57-8 infants 1 357-8 racial differences 13 57-8 snoring 1591 nasal resonance, speech 2 166 nasal sac 1 3 15, 1 3 1 6 F nasal secretions 1 359 granules 1 359, 1 359 F mucus see nasal mucus proteins 1 360 nasal septum see septum nasal speech (rhinolalia) 993 nasal spine 2996 nasal splints septal perforations aetiology 1 584-5 septal stabilization 1 580 nasal sprays epistaxis, paediatric 1065 septal perforations aetiology 1584-5 snoring 2329 nasal surgery anaesthesia 503 children 514-7 cleft lip and palate 1003 paediatric intensive care 546
see also individual procedures nasal tickle 1665 nasal tip anatomy 2995-7, 2996 F deviations 2993 skin 2995 supporting mechanisms 2996-7 nasal tip surgery 2964-5, 2995-3005 l1l
nasal trauma, medical negligence 1 3 10-1 nasal tumours see sino nasal malignancy nasal turbinates see turbinates nasal valve 1 358, 1 589, 3006-7 nasal valve collapse 3006-14 cartilaginous abnormalities 3007 causes 3007 T diagnosis 3008-9 lateral 301 0 pathology 3007-8 physiology 3007 primary valve 3007, 3008 F secondary valve 3007 transmucosal separation 3007 treatment options 3009-12 nasal valve stenosis 30 12, 3 0 1 2 F nasal valve suspension 301 2 nasal vestibulitis 1064, 1064 F, 1 186, 1 186 F nasendoscopy see nasal endoscopy Naseptin 65 1 , 660 T nasoalveolar (nasolabial) cyst 1 074, 1 320-1, 1926 nasociliary nerve 1 328, 3923 nasogastric tubes dysphagia management, cancer patients 279 1 intractable aspiration 2097 nasogastric tube syndrome 2635 nasolabial angle anatomy 2995-7 nasal tip rotation 3004 skin 2995 nasolabial (nasoalveolar) cyst 1074, 1 320-1, 1 926 nasolabial flaps 2830, 2840, 2849-50, 285 1 F nasal reconstruction 3020, 3021 F nasolabial muscle repair, cleft lip 1003, 1003 F nasolacrimal duct 1 690 cysts 1074 development 1 3 1 5 obstruction aetiology 1689 children 1 696 incidence 1 689 surgery see dacryocystorhinostomy (DCR) opening 1 329, 1 344-6 nasolacrimal mucocoele 1 689, 1 690 F, 1691 nasometry 1 375-6 nasooccipital acceleration 3214 F
naso-orbito-ethmoid complex fractures 1 6 1 1 , 1631-2 classification 1 6 1 1 , 1 6 3 1 , 163 1 T definition 1 6 3 1 management 1632 signs/symptoms 163 1-2, 1632 F nasopalatine duct cyst 1926, 1 926 F nasopalatine nerve 1 328, 1801, 1 80 1 F, 1 802 T nasopharyngeal airway 2289, 2289 F obstructive sleep apnoea 1 109 nasopharyngeal angiofibroma 1297 nasopharyngeal branchial cysts 2 1 19 nasopharyngeal carcinoma (NPC) 2445-74 aetiology 2446-8 age-related 2346 amelanotic melanoma 2455 biopsy 2455, 2455 F cervical lymphadenopathy 716, 2451 , 245 1 F chemotherapy 2460 children 1257-8 clinical features 2450-2 diagnosis 2452-8, 2453 F diagnostic delays 2455--6 differential diagnosis 2455 d.ysph(lgla 2033 environmental carcinogens 2447-8 epHlerrlloi,ogy 2445--6, 2446 F bDstem-·.ljarr virus 208, 2346, 2353, 2447, 2448, 2456 examination 2453-5 follow-up 2460-1 fossa of Rosenmiiller 2454-5, 2454 F genetics 2 346, 2446-7 headache 2452 histological classification 2449-50, 245 1 F history 2453 HLA associations 2354, 2446-7 imaging 2456-8, 2457 F immunochemistry 2456 immunology 2448 cell-mediated immunity 2448 immunotherapy 2467 incidence 2 346 infiltrative type 2449, 2450 F investigations 2456-8 metastases, parapharyngeal space tumours 2527, 2536 N stage definition 2364, 2364 T orbital disease 2452 F
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I ndex I 4257
otitis media with effusion 3388-9, 3389 pathogenesis 2448 pathology 2448-9, 2450 F, 245 1 F photodynamic therapy 2467 pituitary involvement 4104 prognosis 2464 radiotherapy 2459-60, 2460 F complications 2464-7, 2465 F, risk factors diet 2346, 2354 infection 2346 occupation 2346 tobacco 2346 salvage treatment 246 1-4, 246 1-2 anterior approaches 2462-3 disseminated disease 2464 inferior approaches 2463 lateral approach 2463 local failures 2461-2 local persistence 246 1-2 local recurrence 2462 regional failure 2462 simultaneous locallregional failure 2464 surgery 2462 transnasal transmaxillary approach 2462 transpalatal approach 2463 serology 2448, 2456 staging 2458 AJCC classification 2459 T Ho classification 2458, 2459 T TNM 2362 T, 2365 T treatment 2458-64 primary 2459-61 trismus 2452 undifferentiated 245 1 F Yankauer nasopharyngeal speculum 2455 nasopharyngeal dermoid 2 1 19 nasopharyngeal swabs, acute otitis media 9 14 nasopharyngeal tonsil see adenoid(s) nasopharyngeal tumours carcinoma see nasopharyngeal carcinoma (NPC) ontogenetic 2 1 1 9 trigeminal nerve damage 392 7 WHO classification 2449 T nasopharyngoscopy flexible see flexible nasopharyngoscopy nasopharyngeal carcinoma 2454, 2454 F
nasopharynx anatomy 2 1 07-15, 1 344-6, 1 944, 2365 arterial supply 2 1 1 3 benign conditions 2 1 1 6-29 acquired 2 1 2 1-2 acquired cystic 2 1 22 neoplastic lesions 2 122-4 tortuous vessels 2 1 20, 2 1 20 F, 2121 F biopsy 2455, 2455 F blood clot, adenoidectomy-related 1098 blood vessels 2 1 1 3 bones 2 1 1 0-1 communication 2 1 07 congenital conditions 2 1 16-20 form deficits 2 1 19-20 contact endoscopy 766-7 abnormal appearance 766-7 normal appearance 766 epithelium 2 1 08 examination 2453-5 fascial relations 2 1 08-10 cervical fascia layers 2 1 09 F, 2 1 1 0-1 cervical fascial spaces 21 09-1 0, 2 109 F, 2 1 10 T floor 2 1 07 inferior wall 1 944 innervation 2 1 14 lateral wall 2 1 07, 2 108 F muscles 2 1 12 F lymphatic drainage 2 108, 2 1 1 3-4, 2713 micro flora 1 95-6, 1 96 T, 2121 mucosa 1 947, 2 108 muscles 2 1 1 1-3 masticator 2 1 12-3 palatal 2 1 1 2, 2 1 1 2 F pharyngeal 2 1 1 1-2 prevertebral 2 1 12 muscular layer 21 08 posterior wall 1944, 2 107 roof 2 1 07 submucosa 2 1 08 surgery, paediatric anaesthesia 514-7 surgical approaches 4054-66 anterior approaches 4056-9 anterolateral approaches 4059-6 1 classification 4054-6 combined approaches 4062-5 facial translocation 4064-5, 4064 F infratemporal approach type C 406 1 lateral approaches 406 1 preoperative �ssessment 4056
subtemporal-preauricular infratemporal fossa approach 4062-4 transcervical approach 4058-9 transmandibular approach 4058-9 transoral approaches 4056-8 transpalatine approaches 4056-8 venous drainage 2 1 1 3 wall layers 2 1 08 nasopulmonary reflexes 1364 nasotracheal intubation 1 1 32-3 naso-turbinal see agger nasi natalizumab 3772 natal teeth 1 8 1 7 National Anonymous Tonsil Archive (NATA) 1238 National Cancer Data Set, head and neck cancer data collection 2375-6, 2376 National Clinical Assessment Authority (NCAA) 605 National Clinical Assessment Service (NCAS) 572 National Clinical Audit Support Programme (NCASP) , head and neck cancer audit 572 National Commission for Care Standards 2803 National Confidential Enquiry into Perioperative Deaths (NCE-POD) 2049, 2058-9 paediatric anaesthesia 507 National Health Service (NHS) accessory devices, hearing impaired 3670 Centre for Involvement 574 Community Health Councils 574 performance ratings 572 National Institute for Health and Clinical Excellence (NICE) 588 patient preparation for surgery guidelines 46 1 , 46 1 T, 462 T quality assurance 571, 572 tonsillectomy guidelines 1 235 National Institute on Deafness and Other Communication Disorders (NIDCD) 3701 National Laryngectomee Association 2623 National Library for Health and Clinical Evidence, ENT and Audiology Library 646, 647 T national minimum data set (NMDS) 2375
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4258 1 I n d ex
National Patient Agency (NPSA) 573, 605 National Prospective Tonsillectomy Audit (NPTA) 123 1 , 1232, 1234 T National Reporting and .w'-
see also individual techniques infections see cervicofacial infections Kaposi's sarcoma 246 lymphadenopathy see cervical lymphadenopathy
lymphatics see cervical lymphatics muscles 1 745-6 nerves 1 750-2 palpation 1 754-5 reliability 1 755 root of see root of the neck surface anatomy 1 745 surgical anatomy 1 739-53 triangles 1 74 1-3, 1742 F tumours, benign 1782-3, 1 783 T zones 1 768 neck dissection 273 1-49 accessory nerve damage 2807 contraindications 2727-8 elective 2723-4 arguments against 2723 arguments for 2723 incision 273 1-3, 2732 F 'less than five level: Nl disease 2726 lip cancer 2548 oral cavity tumours 2564-5 staging 2564-5 patient positioning 273 1 preoperative preparations 273 1 radical see radical neck dissection salivary gland tumours 2510 salvage surgery 2728 selective see selective neck dissection sternomastoid muscle removal 2726 tracheostomy 273 1 tumour recurrence rates 2726, 2728 types 273 1 see also metastatic neck disease neck lymphadenopathy see cervical lymphadenopathy neck masses, medical negligence 1 3 10 neck spaces 1 743-5, 2 1 09-10, 2 109 F, 2 1 10 T abscesses see deep neck space abscesses midline 2 109
see also individual spaces neck swelling 1 777-88 benign 1 739 children assessment 1 2 1 0 examination 1 2 1 1-2 nature of 1 2 1 2 sites o f 1 2 1 1-2 examination 1 754 neck trauma 1 766-76 active observation 1 769 aetiological classification 1 768 airway protection 1 766-7 breathing 1 767 cervical spine protection 1 766-7
circulation 1 767 emergency surgery indications 1 769 exploration mandatory 1 768-9 mandatory vs. selective 1 768-9 principles 1 774 selective 1769, 1 770 F history 1 767-8 investigations 1769 management, selective conservative 1 769 T neurological injury 1 774 perfusion 1 767 primary survey 1 766-7 adjuncts to 1 767 secondary survey 1 767-8 treatment delay 1 7 7 1 vascular injury 1 772 venous injuries 1773-4 zones of neck 1 768, 1 768 F neck tumours, benign 1 782-3, 1 783 T necrobacillosis 200-1 necrosis 36, 57, 57 T apoptosis vs. 57 T noise-induced hearing loss 3549 necrotic bone, benign necrotizing otitis externa 3333, 3333 F necrotic tissue healing 98 101 necrotic wounds, necrotizing external otitis see malignant otitis externa necrotizing fasciitis neck 1 785, 1 785 F parapharyngeal abscess 2000 necrotizing otitis externa see malignant otitis externa necrotizing sialadenitis, subacute 1 9 1 5 necrotizing sialometaplasia 1 9 1 5 needle aspiration o f pus, peritonsillar abscess 1997 needle cricothyrotomy 476-7 needle stick injuries 239-40 negligence (definition) 1 305 Negus pharyngoscope 2052, 2053 F Neisseria 1 99
see also individual species Neisseria gonorrhoeae 199 Neisseria lactamica 199 Neisseria meningitidis 1 99 adult epiglottitis 2250 associated diseases 1 99 vaccine 199 Neisseria sicca 199 nelfinavir 239 Nelson's syndrome 300, 3 1 1 , 4102, 41 1 5
Pages 1-1 3 1 2 are i n Volume 1 , pages 1 3 13-28 1 0 are i n Volume 2, and pages 2 8 1 1-4 147 are i n Volume 3.
Neo-Mercazole (carbimazole) see carbimazole neomycin 232 active mucosal chronic otitis media 3424 chronic rhinosinusitis 1471 ototoxicity 3239 see newborn neonatal hearing hearing scrieenmg neonatal intensive care unit (NICU), deafness and 845-6 neonatal necrotizing tracheobronchitis see pseudomembranous croup neonatal rhinitis 1076-7 neonatal teeth 1 8 1 7 neonate(s) drug prescribing 4 1 5 facial nerve injury 3889-90, 3 890 T neoplasia/neoplasms adenoid 1 096 dysphagia aetiology 2032-3 facial paralysis, childhood 1 058 HIV associated cervical 246 nasal 241 jugular foramen 4029-34 mouth ulcers 1 832 multiple endocrine see multiple endocrine neoplasia (MEN) nasal see sinonasal malignancy nodular thyroid disease 361 oral mucosa 1 823 salivary glands, children 1 248 tonsils 1225, 1226 tumourigenesis mechanisms 8 vestibular labyrinth see vestibular labyrinth vestibular nerve 3687-9 1 nephrotoxicity, antimicrobial induced 236 nerve(s) demyelination 3848, 3848 F ephaptic transmission 3848-9 tissue engineering 1 26 nerve excitability test (NET), facial nerve 3878-9, 3879 T nerve-muscle pedicle graft, vocal folds 2 1 96 nerve of the pterygoid canal 3 9 1 0, 3924, 3928 nerve of Wrisberg 3871 nerve sheath tumour see schwannoma( s) nerve to stapedius 3928 nerve transfer, facial nerve repair 2509
nervus intermedius 3871 geniculate neuralgia surgery 3532 vestibular schwannoma removal 3980 nervus spinosus 3907 nervus terminalis 1 662 netilmicin 3676 neural crest cells ear development 8 1 5 facial development 1 8 1 0-1 neural dyssynchrony see auditory neuropathy/ dyssynchrony neuralgia( s) facial pain 1 724 geniculate 3532 glossopharyngeal see glossopharyngeal neuralgia ( GPN) otalgia 353 1-3 postherpetic 1 724 post-herpetic 2079 Sluder's 1 723-4 sphenopalatine ganglion 1 723 trigeminal see trigeminal neuralgia (TN) neural response telemetry (NRT), auditory neuropathy/ dyssynchrony 3852 neural stem cells 67 differentiation 68 nervous tissue regeneration 75 neural synchrony disorders 3849 neurapraxia 3873 neurectomy, special needs children 789 neurilemoma see schwannoma(s) neurinoma see schwannoma(s) neuroanatomy 391 1-41 neuroblastoma 1258, 1258 F olfactory 2420-1 neurodegenerative diseases, olfactory dysfunction 1669, 1673-4 neuroendocrine carcinoma, larynx 2604 neuroepithelial deafness 8 1 1-2 neurofibroma( s) larynx 2600 T neurofibromatosis 2527, 4002 orbital 3 9 1 5 parapharyngeal space 2527 ultrasound examination 726 neurofibromatosis 3688-90 history 3998 incidence 2527 molecular analysis 12 pontine tumours 3922 type 2 (NF2) see neurofibromatosis 2 (NF2) neurofibromatosis 1 (NF l ) 3689, 3998 meningiomas 4008-9
soft tissue sarcomas 1 93 1 type 2 vs. 4001 neurofibromatosis 2 (NF2) 3998-4006, 3689-90 adults 4000 aetiology 3689-90 childhood presentation 4000 clinical management 4002-3 risk assessment 4003, 4003 F clinical manifestations 3690, 3945, 4000-1, 4000 T adult vs. paediatric presentation 4000 cutaneous/subcutaneous 4001, 4001 F neuropathies 4000 ophthalmic 4000 clinical outcomes 4003 current knowledge/future research 4004 diagnosis/ differential diagnosis 4000-1 criteria 400 1 NFl vs. 400 1 diagnostic delay 4143 epidemiology 3999-4000 birth incidence vs. diagnostic prevalence 3999 gene therapy 4004 genotype-phenotype correlation 3999, 4000 histopathology 3690 historical aspects 3998 imaging 4001 molecular genetics and NF2 gene 3998-9 diagnosis and screening 4001 , 4003, 4004 maternal gene effects 4000 mosaicism 3999, 400 1 penetrance 4000 neurofibromas 4002 neuroradiology 4002 NF2 protein (merlin; schwannomin) 3999 pathology 4000 T, 4002 radiosurgery 3994-5 malignant transformation 3993, 3995 screening 4003-4 two hit theory of tumourigenesis 3995 vestibular schwannoma 3957, 3998, 4000, 4002, 4003 radiosurgery 3994-5 neurofibrosarcoma 1259 T
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4260 I I nd ex
nellUclge:mc stem cells see neural stem cells nel1rCllrelnic tumours neurofibroma see neurofibroma(s) parapharyngeal space 2525-6 schwannoma see schwannoma(s) ultrasound 726 neurohormones, hypothalamic see hypothalamus neurohypophysis 297, 308 associated nerves 297 embryology 295 hormones 297, 300, 308
see also individual hormones magnetic resonance imaging 305 children 3 05 neurosecretory phospholipid granules 305 neurolabyrinthitis see vestibular neuritis neurological gait disorders, balance problems and 3707 neuroma see schwannoma(s) neuromuscular blockage 494-5 airway management 494 intravenous induction 495 monitoring 500 paediatric anaesthesia 5 1 3 neuronavigation, skull base tumours 4056 neuropathic pain, advanced head and neck cancer 2785 neuropathy auditory see auditory neuropathy! dyssynchrony diabetic 40 1-2, 2080 neurofibromatosis 2 4000 neuropeptides, thyroid gland 3 1 9 neuropeptide Y (NPY) 1 364 neuroplasticity, paediatric cochlear implantation 861-2 neuroradiology CPA tumours 4007 interventional see interventional neuroradiology (INR) neurofibromatosis 2 4002
see also individual modalities; specific indications neurorrhaphy, facial nerve repair 2509 neuroticism, globus 2039 neurotmesis 3873 neurotransmitters auditory nerve fibres 3 197 inner hair cells, auditory neuropathy! dyssynchrony 3849
nasal 1 364 parasympathetic 1 364 olfactory receptor cells 1662-3 sleep patterns 2306
see also individual transmitters neurotrophic factors, ototoxicity prevention 3 302 neurotrophism 70 neurulation 69, 792-3, 793 F neutropenia 273 causes 273 T cyclical 1 77 T, 1 78 severe congenital 177 T, 1 78 neutrophil(s) 89, 273 allergic rhinitis 1 392 wound healing 89 neutrophilia 273 newborn ear splintage 975 fluid management 543-4 nasopharyngeal bacterial colonization 195 newborn hearing screening 826-8, 848, 3290-1 acoustic brainstem evoked responses 3846 'at risk' screening 827 auditory neuropathy! dyssynchrony 3846 cost-effectiveness 828 costs 826 cut-off level 827 evoked physiological measurements 3290-1 'family friendliness' 828 models 827 otoacoustic emissions 3846 performance 827-8 principles 3290 programme sensitivity 828 quality assurance 828, 828 T Newborn Hearing Screening Programme 824, 848 Newton's first law 3 2 1 0 Newton's second law 3 2 1 0 New York Heart Association (NYHA) angina classification 458 T NF2 gene 3998, 3998-9 diagnosis and screening 400 1, 4003 maternal gene effects 4000 mosaicism 3999 nonpenetrance 4000 NF2 protein (merlin; schwannomin) 3999 The NHS Plan 570-1
nickel 1426 food sino nasal malignancy 2418 nicorandil 1835 nicotinamide, as radio sensitizer 50 nicotinamide adenine dinucleotide 199 nicotinic rx-9-cholinergic receptor 3606 nifedipine achalasia 1289 skin flap survival 1 13 nimodipine 3617, 3797 nimorazole 50, 2756 IXth nerve see glossopharyngeal nerve ( IX) Nissen fundoplication 2262 nitric oxide chronic rhinosinusitis 1473-4 haemostasis inhibition 278 nitric oxide donors, chronic rhinosinusitis 1473-4 nitric oxide synthase salivary gland tumours 2495 skin flap survival 1 13 nitro blue tetrazolium test 169 nitrogen, decompression illness 3 5 1 5 nitroglycerin (GTN) 1 13 nitro imidazole 50, 2756 nitrous oxide anaesthesia, ear surgery 502 children 5 1 3-4, 5 14 N-methyl-D-aspartate (NMDA) receptor, tinnitus 3600 Nocardia species 1 785 nodular melanoma 240 1 T nodular thyroid disease 330, 360-3 adenomatous 330, 7 1 9-20, 719 F aetiology 3 60, 360 T antibody status 361 cystic nodules 363 cystic vs. solid 330 differential 72 1-4 epidemiology 360 Grave's disease and 3 3 1 , 335 investigation 36 1-2, 361 F in vitro investigations 332 malignant 360, 360 T, 362, 2669, 2676 T see also thyroid cancer medical management 362-3 multinodular 360-1 prevalence 360 radioiodine therapy 349, 362-3 serum calcitonin 3 6 1
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I ndex I 426 1
solitary nodules 2668-9, 2668 F imaging 335 nontoxic, management 363 toxic 33 1 , 335, 363 surgery 351 thyroid functioning tests 36 1 thyroid peroxidase antibodies 36 1 ultrasound scanning 362, 7 1 8 nodule(s) definition 1 699-700 thyroid see nodular thyroid disease vocal folds see vocal nodules noise 2 165 see also sound noise exposure levels 3 1 7 1 measurement 3 1 7 1 noise generators, tinnitus 3615-6 treatment length 36 16 noise immission level 3171 noise-induced hearing loss (NIHL) 3548-57 audiometry findings 3550 F claims 3554-5 definition 3548-9 diagnosis 355 1 , 3553 equal energy principle 3 1 7 1 examination 3552-3 history 355 1-2 incidence 3300 light microscopy findings 3550 F loudness discomfort levels 3553 management 3553 non-specifc 3554 specific 3554 mechanism 3300-1, 3301 F medicolegal aspects 3553 pathology 3549-5 1 apoptosis 3549 metabolic mechanisms 3549 necrosis 3549 predisposing factors 3549-5 1 structural mechanisms 3549 prevention 330 1-2, 3553-4 report writing 3553 social issues 3552 temporal threshold shifts 3298 tinnitus 3599, 360 1 noise levels, communication abilities 3552 T noise ratios 2 180-1 noma (cancrum oris) 1 822 Nomarski technique 3239 nomograms, likelihood ratios 657 F
nonallergic noninfectious perennial rhinitis (NANIPER) see rhinitis, idiopathic nonallergic rhinitis 1408-14 diagnosis 1412 differential diagnosis 141 1 food-induced 1383, 141 1 pathophysiology 1409 perennial 1408-14 pollution 141 1 surgery 1412 symptoms 1408 therapy 1412 nonconventional 1412 types 1409-1 1 nonallergic rhinitis with eosinophilia syndrome (NARES) 1382-3, 1410-1 prevalence 141 1 Samter's triad 141 1 nonauditory devices 3668 non-coding sequences, genes 16 non-Hodgkin's lymphoma (NHL) adenoid 1096 children 1254-5 diagnosis 1255 prognosis 1255 staging 1 255 treatment 1255 FDG-PET imaging 694, 694 F HIV patients nasal obstruction 241 neck 246, 246 F oral 243 larynx 2604 oropharynx 2580 pinna 3359 salivary glands 2501 thyroid 720 tonsil 2580, 258 1 F nonimmunological contact urticaria (NICU) 1424-5 noninsulin dependent diabetes mellitus (NIDDM) see diabetes mellitus, type 2 noninvasive blood pressure monitoring 497 nonmaleficence (ethical principle) 562, 582 nonmegaloblastic anaemia 269 non-nucleoside analogues 239 non-nucleoside reverse transcriptase inhibitors 233 nonopioids cancer pain management 2785-6
see also specific drug;
nonrapid eye movement sleep (non-REM) 2305 airway activity 2308-9 neural activity 2306-7 nonrecurrent laryngeal nerve 3 1 8 nonrespiratory sleep disorders 2310-1 nonsense mutation 9-10 nonspecific immunity, nasal 1361 nonsteroidal antiinflammatory drugs (NSAIDs) adenotonsillectomy 5 1 5-6 adverse effects epistaxis 1 600 mouth ulcers 1835 platelet dysfunction 287 anaesthesia premedication 490 T dosage, children 5 1 6 T epistaxis 1600 intolerance, nasal polyposis 1 553 pain management, advanced head and neck cancer 2785-6 pharyngitis, acute 1 984 tonsillectomy 1 993 nonsyndromic autosomal dominant inherited hearing impairment 3559 T, 3560 T nonsyndromic autosomal recessive inherited hearing impairment 3559 T nonsyndromic cleft lip 999 nonsyndromic deafness classification 8 1 1 genetic mutations 1 8 nonsyndromic recessive auditory neuropathy (NSRAN) 3846 nonsyndromic X-linked inherited hearing impairment 3559 T nontuberculous mycobacteria (NTM) 12 14-5, 1 2 1 5 F, 1244 Noonan syndrome 968 noradrenaline critical care patients 529-30 nasal vasculature 1 364, 1365 vestibular neurochemistry 3794 'no reflow phenomenon' 1 1 3 normalized noise energy (NNE), voice evaluation 2 1 8 1 normochromic anaemia 269 preoperative management 270 normocytic anaemias 268 T, 269-70 preoperative management 270 Norrie syndrome 8 1 3 T Northern blotting 6
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North of England and Scotland Study on Tonsillectomy and Adenoidectomy in Children (NESSTAC) 1 2 3 1 nortriptyline migrainous vertigo 3804 side effects 3804 tinnitus 36 1 7 nose absent 1073, 1320 anatomy 1 3 1 5-43, 1 66 1-3 comparative 132 1-2 cosmetic 2928 sense of smell and 1 661-2, 1661 F subunits 2960-1, 296 1 F anthropoid 1321 arteries 1 362 autonomic nervous system 1 363, 1 363 F motor nerves 1 363 sensory nerves 1 363 bones 1 324, 1324 F, 1 325 F comparative anatomy 1 32 1-2 development 803, 1 3 1 5-2 1 , 1 3 16 F anomalies 1320-1 deviated see deviated nose examination, children 778, 779 F external see external nose HIV infection 24 1-2 humidification 1 356 hypophysectomy�and 41 05, 4 1 1 3 immunology 1 36 1-2, 1 362 T acquired immunity 136 1-2 nonspecific immunity 1361 innervation 1 362-5 lateral wall anatomy 1 329-38, 1329 F blood supply 1 337-8, 1 337 F bony structures 1 330 F clefts 1 332 histology 1 337 innervation 1 338, 1338 F lymphatic drainage 1338 middle meatus 1330-1, 1 330 F spaces 1 332 variations 1334, 1334 F, 1335 F, 1 335 T venous drainage 1 337-8 lower airway protection chemical 1 358-6 1 mechanical 1 358-6 1 lymphatic drainage 241 8 mycotic diseases 2 1 5-6 neural systems 1662
neuroepithelium see olfactory (neuro ) epithelium neurotransmitters 1 364 physiology 1 355-7 1 , 1 356 T, 166 1-3 current knowledge deficiencies 1 369 future research 1369 respiration 1355 retronasal airflow 166 1 rheumatological diseases 1 84-5 vasculature 1 362-5, 1 596-7 drugs acting on 1 365-6, 1 365 T flow measurement 1 363 flow variations 1 363 microanatomy 1 362-3, 1 362 F, 1363 F venous drainage 1 597 voice production 1366
see also entries beginning nasal; entries beginning olfactory; olfaction; specific components nosebleed see epistaxis nostrils see external nares (nostrils) Nothnagel's syndrome 3921 notifiable diseases, ethics 587 Nottingham Health Profile 637, 638-9 NPL tables, noise-induced hearing loss 3553 N -ras mutation 2409 nuclear medicine children 1 299-300, 1 300 F parathyroid gland assessment 1299-300, 1 300 F
see also specific techniques nuclear membrane 2379-80 nucleic acid synthesis inhibitors 230-1 nucleoside analogues 232 3' azid03' deoxythymidone zidovudine 239 HIV 239 mechanism of action 239 side effects 232, 233, 239 nucleoside reverse transcriptase inhibitors 233 nucleotide deletion 9-10 nucleotide insertion 9-10 nucleus ambiguus 2 1 55, 3935 pharyngeal innervation 2075 swallowing 1959 nucleus of the tractus solitarius 3935 nucleus prepositus hypoglossus, gaze holding 3225-7 nucleus raphe interpositus lesions 3715 nucleus retroambigualis (NRA) 2 1 58
nucleus tractus solitarius (NTS) injury 1 847 taste 1 841-2, 1 843 F Numb 68 number-letter combination speech testing 3 3 1 7 numbers needed t o treat (NNT) 652, 660 calculation 661, 665 nutcracker oesophagus 2032, 2066 nutritional disorders, olfactory dysfunction 1 673-4 nutritional status assessment 94-5 wound healing 94-5 nutritional support, critical care patients 530-3 Nyquist sampling theorem 2 1 79-80 nystagmus 3 2 1 3, 3922 acute unilateral vestibular deafferentation 3219-20 benign paroxysmal positioning vertigo 3750, 376 1 benign paroxysmal vertigo of childhood 1044 congenital 3725, 3725 F, 3922 definition 3 2 1 3 left 3 2 1 3, 3 2 1 5 F Meniere's disease 3757 recording 32 1 3 semicircular canal 3749, 3749-50 skull base lesions 3946 superior semicircular canal dehiscence 3763 vestibular disorders 379 1 vestibular neuritis 3752 waveforms 3725
see also individual types nystagmus quick phase 3227 T nystatin 233 candidiasis 224, 2789 otomycosis 214 obesity airway management 494 obstructive sleep apnoea 2308, 2314, 2 3 1 5 obesity hypoventilation syndrome 2 3 1 3-4 oblique arytenoids 2 1 36 T obliterated cochlea, paediatric cochlear implantation 865 obscure auditory dysfunction (King-Kopetsky syndrome) 3273
Pages 1-1 3 1 2 are in Volume 1, pages P 1 3-28 1 0 are in Volume 2, and pages 2 8 1 1-4 147 are in Volume 3.
I ndex I 4263
observational studies, epidemiology 625-6 observer bias 2344 obstructive 'awake' apnoea 1 106 obstructive emphysema, foreign bodies 1 1 88, 1 190 F obstructive sleep apnoea (OSA) 2307-9 age and 2308 anaesthesia 492 children 1 102-13 adenoids 1 104, 1 1 05 F anaesthesia 509, 5 1 5 clinical examination 1 104-5 craniofacial disproportion 1 104 imaging 1 107-8, 1 108 F investigations 1 105-8 postoperative complications 1 1 10 prevalence 1 103 recommendations for investigations 1 106 T, 1 108 risk factors 1 103, 1 103 T special needs 787, 788 F surgery 1 1 09-10 symptoms 1 1 04 tonsillar involvement 1226 tonsillectomy, biopsy purposes 1 990 treatment 1 108-10 clinical examination 2315 daytime sleepiness assessment 2 3 1 5 definitions 1 102-3, 1 1 03 diagnosis 2 3 1 5-20 criteria 2 3 1 9-20 Down's syndrome 1 109 driving 2322 enlarged turbinates 1591 epidemiology 1 102-3, 2 3 14-5 follow-up 2322 gender 2308 home multichannel testing 2 3 1 6-8, 2319 F investigations, choice of 2 3 1 8-9 legal issues 2322 long-term consequences 2310 F long-term postoperative followup 1 1 10-1 medical conditions associated with 23 14-5 medical management 2 3 1 3-24, 1 1 08-9 morbidity 1 103 nasal obstruction 2 3 3 1 nasal surgery 2331 nasopharyngeal airway 1 109 obesity 2308
obstruction sites 2307, 2308 F occasional procedures 233 1-2, 2331 T oxygen saturation levels 2331 pathogenesis 2308-9 pharyngoplasty 1 0 1 1-3 post-intervention sleep study 1 1 1 1 risk factors 2314-5 sleep position 2309 snoring vs. 2327-8 symptoms 2 3 1 3, 2 3 1 5 tonic muscle activity 2308-9 upper airway shape 2309 upper airway size 2308 vascular overperfusion 2309 obstructive sleep apnoea/hypopnoea (OSAH) see obstructive sleep apnoea (OSA) obturation, septal perforations 1 585 obturator 29 1 5 occipital area 3898 occipital bone 3898 squamous part 3899 occipital condyle 3899 occipital plagiocephaly 1024, 1026 occupational asthma 1415, 1561 occupational rhinitis (OR) 1415-23 , 1 382 air pollution 1419 allergic 1 382, 1416 causative agents 1416, 1417 T IgE mechanism 1416 causes 1 382, 1416 definition 1415 diagnosis 1420-1 examination 1420 exposure response 1420 high risk occupations 1418-9 history taking 1420-1 immunotherapy 142 1 investigations 1420-1 latency period 1416 management 142 1 medical therapy 142 1 nonallergic (irritant) 1 382, 1410, 1416-8 causative agents 1416-8, 1418 T corrosive reactions 1416-8 neurogenic inflammation 1416 olfactory disorders 1416-8 symptoms 1410, 1416 triggers 1410 pathogenesis 1416-8 prevalence 141 5-6 prevention 142 1
risk factors 1416 symptoms 1420 octave confusion, tinnitus 3612 octopus cells 3 141 octreotide 4101 ocular motility blepharoplasty, upper eyelid 3055 frontoethmoidectomy 1 509 ocular tilt reaction labyrinth destruction 3749 mastoid stimulation 375 1 vestibular neuritis 3752, 3754 F oculoauriculovertebral dysplasia 1033, 1055, 3642-3 oculocardiac reflex 3065 oculography 3723-30 indications 3723, 3723 T techniques 3723-4 visually guided eye movements 3726 oculogyric crisis, postencephalitic Parkinson's disease 392 1 oculomotor nerve (III) 3 9 1 7 anatomy 3917, 3 9 1 8 F, 3919 F, 3920 F central anatomy 3 9 1 7, 3920 F central mechanisms 3919-2 1 examination 3710-1 fascicles 3917 frontal sinus fractures 1 507 inferior ramus 3917 lesions pituitary tumour extension 4100 pupillary 3 9 1 6-7, 3 9 1 7 pupillary fibres 3 9 1 7 superior ramus 3917 oculomotor nucleus 3 9 1 7, 3920 F odds ratio 663-4 epidemiological research 622, 622 T, 628 systematic reviews 663-4 odonto-ameloblastoma 1927-8 odontoblasts 799-800 odontoclasts 1 804-5 odontogenic abscess see dental abscess odontogenic cysts 1922-6 botryoid 1925 calcifying 1925-6 definition 192 1 development 1922 glandular 1925 odontogenic keratocysts 1 924-5 diagnosis 1 925 incidence 1924-5 presentation 1925 squamous cell cancer 1938-9 treatment 1925
Pages 1-1 3 1 2 are in Volume 1 , pages 1 3 1 3-28 1 0 are in Volume 2, and pages 2 8 1 1-4 147 are in Volume 3.
4264 I I ndex
odontogenic myxoma 1928-9 odontogenic tumours adenomatoid 1928 benign 1923 T classification 1 923 T incidence 192 1 malignant 1923 T
see also individual types odontoid 2 1 1 1 odontomes 1929 odourant-binding proteins 1 662 odours classification 1368 nervous inhibition 3913 O'Dwyer, Joseph 772 odynophagia advanced head and neck cancer 2790 chronic laryngitis 2259 dysphagia-related 2025-6 odynophonia, chronic laryngitis 2259 oedema angioneurotic see angioneurotic oedema cerebral see cerebral oedema chronic, vocal folds see Reinke's oedema Graves' disease 343 nasal polyposis 1 552 post-blep haroplasty 3064 subglottic 1 1 28, 1 129, 225 1 uvula 2006 oedematous wounds, wound dre�ssings 1 0 1 oesophageal atresia 1282-7 associated anomalies 1 283, 1283 T VACTERL complex 1283-4 diagnosis 1284, 1 284 F, 1285 F prenatal 1284 dysphagia 2030 embryology 80 1-2 gastro-oesophageal reflux 1287 incidence 1283 management 1284-5 mortality 1283, 1283 T pathogenesis 1 283, 1943-4 prognosis 1285 respiratory infection 1287 surgical repair 1284-5, 1286 F anastomotic leaks 1285 complications 1285-7 results 1285 types 80 1-2, 805 F, 1283, 1283 T see also tracheo-oesophageal fistula oesophageal biopsy, laryngeal stenosis 1 1 54
oesophageal body diverticulae 2072 oesophageal carcinoma 2067-9 aetiology 2633-4 anatomical subsites 2638 T barium swallow appearance 2027 F cell biology 2635-7 cervical node metastases 264 1 cervical tumours 2640 endoscopic appearance 2067 F genetic alterations 2635 histology 2637-8 imaging 2068 F incidence 2067 molecular biology 2635-7 mucosal melanoma 2407 multimodal therapy 2069, 2069 T oesophageal perforation 207 1 palliation 2069, 2070 T, 207 1 T staging 2068, 2068 F, 2643 T, 2646 T surgery 2067, 2068 T, 2069 T total pharyngolaryngooe sphagectomy 2649 see also hypopharyngeal cancer oesophageal diseases 2062-73 children 1282-94 inflammatory, HIV patients 243-4 oesophageal foreign bodies children 1 1 87, 1 187 F medical negligence 13 10, 1 3 10 F dysphagia aetiology 2034 oesophageal injuries 1 770-1 complications 177 1 diagnostic accuracy 1 770-1 exploration, need for 1771 surgical technique 177 1 treatment delay 177 1 oesophageal manometry achalasia 1 288-9, 1 289 F, 1290 F snoring 2328 oesophageal motility disorders 2066 dysphagia 2032 globus 2038-9
see also specific disorders oesophageal motility studies achalasia diagnosis 1290 F normal findings 1 289 F oesophageal perforation 2070-1 diagnosis 2026-8 high 207 1 management 207 1 mid/lower perforation 2071 oesophageal cancer 2071 spontaneous (Boerhaave's syndrome) 2070-1 surgery 207 1
oesophageal pH monitoring, dysphagia 1976-7, 2028-9 oesophageal speech 2228, 2228 T, 2624 definition 2227 pharyngo-oesophageal segment 2227 oesophageal sphincters 195 1-2 oesophageal stenosis, congenital see congenital oesophageal stenosis oesophageal strictures 2064 oesophageal ulcers cytomegalovirus 245 gastro-oesophageal reflux 2064 idiopathic, HIV patients 245 oesophagectomy 2068 T oesophagitis, laryngeal disorders and 2263 oesophagogastroduodenoscopy, laryngeal stenosis 1 1 54 oesophagoscopy candidiasis 203 1 gastro-oesophageal reflux disease 203 1 hypopharyngeal cancer 2644-5 laryngeal trauma 2275 oesophageal injuries 1 770-1 oesophagotracheal septum 2 1 30 oesophagus anatomy 195 1-2 blood supply 1 952 constrictions 1951 corrosive injury 1290-1 clinical presentation 1290, 1291 F diagnosis 1 290-1, 1291 F pathophysiology 1290 treatment 1291 embryology 801-2, 1282, 1943-4, 2131 F epithelium 195 1 external adventitia 1952 foreign bodies medical negligence 13 10, 1 3 10 F paediatric 1 1 87, 1 1 87 F HIV manifestations 244-5 innervation 1952 sympathetic 1952 lymphatic drainage 1952 muscular coat 195 1-2 muscularis mucosa 1951 pain 1952 relations 1952 submucosa 1951 swallowing 1955, 1958 transit times 1956 vasculature 1952
Pages 1-1 3 12 are in Volume 1, pages 1 3 1 3-28 10 are in Volume 2, and pages 28 1 1-4 147 are in Volume 3.
I nd ex 1 4265
venous drainage 1952
clinical evaluation 1 664-6
wall 195 1-2
conductive/transport impairments 1 666
oestrogen(s) hormonal rhinitis 1410
treatment 1 670-1
olfactory groove meningiomas 3954-5 diagnostic failure 4144 olfactory nerve damage 3 9 1 3 olfactory hallucinations
lactation 301
diminished 'taste' 1660
(phantosmia) 1664, 1666-7,
nasal mucosa, effects on 402-3, 1 366
endocrine disorders 1 670, 1673-4
3913-4
animal studies 403 oestrogen therapy, juvenile angiofibroma 2441
epilepsy 1 669-70
olfactory nerve (I) 391 1-4
future research areas 1 672
age-related changes 3914
head trauma 1 667, 1668 F
anatomy 391 1-3, 3912 F
off-frequency listening 3248
history taking 1 664
Office Population and Censuses
imaging 1 666
(OPCS) 2375, 2375 T off-vertical axis rotation ( OVAR) 3737,
knowledge deficiencies 1 672
olfaction 1662
mass lesions 1 668-9
physiology 3913
medicolegal issues 1660-1, 1671
3 739 F
nasal lesions 1673-4
ofloxacin 938
applied 3 9 1 3-4 injury, skull base surgery 4136
applies 3913-4 pigmentation 391 1-2
OFU 51
nasal passage inspection 1 664-5
olfactory neuroblastoma (OAN) 2420-1
OK 432 1 270
neurodegenerative diseases 1 669,
olfactory pit 1 3 1 5
olanzepine 2798 older people see elderly olfaction 1 366-8
olfactory placode 1 3 1 5, 1 8 1 1
1673-4 neurological evaluation 1 665 physical examination 1 664-5
olfactory receptor cells 1 366-7, 1 662,
1 663 F, 391 1-2 axons 1 662-3, 3912
adaptation 1 367
prevalence 1 660
ageing 1 368
prognosis 1 671
neurotransmitters 1 662-3
cross adaptations 1 367
quality of life issues 1 660
renewal 74
discrimination 1 367
quantitative testing 1 665-6
septal 1 327
disorders see olfactory disorders/
sensorineural impairment 1666
signal transduction 1662-3
dysfunction
viral conduits 1663
treatment 1671
eating 1 368
supportive measures 1671
olfactory reference syndrome 1 666-7
higher brain centres 1 367
surgery 1670-1
olfactory striae 1 329
nervous pathways 1367
treatment 1670-1
olfactory system
odour classification 1 368
tumours 1 668-9, 1673-4
paranasal sinus development 1369 post-adenoidectomy 1096 receptors 1 367 sexual behaviour 1368 stimulus 1367 testing 1 366
olfactory ensheathing cells 74 therapeutic uses 74 olfactory (neuro)epithelium 1662-3,
central projections 1663 renewal 74-5 olfactory testing quantitative 1665-6 unilateral 1666
391 1-2 biopsy, olfactory dysfunction
olfactory tracts 1 329, 3912 oligonucleotide-mediated mismatch
1 665
ligation assay, metastases
threshold 1367
cell types 1662, 1 663 F
trigeminal input 1367
lateral nasal wall 1 337
see also nose
location 166 1
oligosomal fragmentation, apoptosis 58
metaplasia 1 662
olivocochlear bundle 3200
olfactory agnosia
detection 2715
causes 1 666-7
nasal cavity 1 326
feedback mechanisms 3145, 3850
definition 1 664
neural transduction 1 662-3
noise damage protection 3200
olfactory area 1 366-7
septum 1 327, 1 327 F
olfactory auras 1 669-70
age-related changes 1 328-9
olfactory bulb 1 329, 1 367, 1 663
nerve fibres 1 328-9
glomeruli 1 663 stem cells 70 olfactory cilia 39 1 1-2 olfactory cleft 391 1-2 olfactory disorders/ dysfunction 1 660-76, 1 366 T age-related 1670, 1 670 F causes 1 666-70
olivocochlear feedback loop 3 1 45 olivocochlear suppression test ( OAE) 3606
supporting cells 1 662, 1 663 F
OM6, outcomes research 640
ultrastructure 1 662, 1 663 F
omalizumab 1 565
olfactory event-related potentials (OREP) 1 666
ombudsman 605 vU" ,-"",,,
olfactory fasciculi 3912 traumatic lesions 3 9 1 3
J
fatty acids, critical care
patients 532-3 OMENS classification, hemifacial microsomia 1 032, 1 032 T
olfactory fila 1 662-3
omeprazole
injury 1667 ,
chemical agent exposure 1 670, 1673-4
olfactory fossa 1 335
classification 1 664
olfactory glomeruli 1367
chronic laryngitis 2262 globus 2040
Pages 1-1 3 1 2 are in Volume 1, pages 1 3 1 3-2 8 1 0 are in Volume 2, and pages 28 1 1-4147 are in Volume 3.
4266 1 I n dex
omohyoid 1 746 oncocytoma larynx 2600 T salivary glands 2483 oncogenes 36, 2380 viral 208 oncogenic transformation 9-10 ondansetron nausea and vomiting 2788 tonsillectomy 1237 vestibular attacks, acute 3797 'onion peel' Cbalaclava' ) sensory deficit 3926 29 1 8 onlay anterior maxillary deficiency 29 1 9, 291 9 F posterior maxillary ridge 291 7 underprojected nasal tip 3003 Online Mendelian Inheritance in Man (OMIM) 1 8 Onodi cells (sphenoethmoidal cells) 1336-7, 1 67 8 ONYX-0 1 5 1 2-3, 2 9 open rhinoplasty see external rhinoplasty open tracheostomy 2295-7 complication rate 2297 incision 2295, 2296 F closing 2297 percutaneous vs. 2297-8 procedure 2295 thyroid isthmus division 2295, 2296 F tracheal exposure 2295, 2296 F tracheal lumen opening 2295-6, 2297 F tracheal stenosis 2295-6 tube choice 2295 ophthalmic disorders neurofibromatosis 2 4000 pituitary tumours 4099, 4 100 ophthalmic examination, blepharoplasty 3055 ophthalmic nerve (Vd 3918 F, 3919 F, 3923 branches 1 32 5, 3923 damage 3927 ophthalmologic procedures, nasal endoscopy 1 352, 1 353 F ophthalmopathy Graves' disease 343, 400, 400 F see also thyroid eye disease ophthalmoplegia, Graves' disease 400 ophthalmoscopy, vestibular ocular reflex testing 3719, 3719 F opiates 489-90
opioids cancer pain management 2786, 2 786-7 doses 2787 T periodic pain 2784-5 see also specific drugs 'opportunistic adherence; chronic otitis media 34 1 0 opthalmopathy, radioiodine treatment 349 optical coherence tomography (OCT) 755-61 adjuncts 7 59 polarization-sensitive OCT 756, 757-9 current knowledge/future research 760 laryngeal imaging: preliminary results 757, 757 F, 758 F basement membrane integrity 757 principles 756-7 image representation 757 Michelson interferometer 756-7, 756 F ultrasound analogy 756 resolution 755-6 utility/potential advantages of 756, 759 vocal folds 757, 758 F, 759 F optical grabbing forceps 1 190 F, 1 19 1 optic canal 4122 lesions, visual disturbances 3915 optic chiasm bitemporal hemianopia 39 1 5 hypophysectomy 4 1 1 0-1, 4 1 1 2 F magnetic resonance imaging 306 pituitary tumour expansion 4099 optic foramen 3914 optic ganglion 3934 optic nerve (II) 39 14-7 anatomy 3914, 3914 F damage orbital lesions 39 14 skull base surgery 4 1 36 hypophysectomy and 4 1 08, 4 1 1 0-1, 41 12 F myelinated fibres 391 4 papillomacular fibres 39 1 4 screening tests 3946 sheaths 39 14 optic nerve decompression 1 684-5 complications 1 685 diagnostic nasal endoscopy 1 352 indications 1684
surgical techniques 1 684-5 endoscopic 1 685 external 1 685 results 1685 optic nerve sheath tumours 4000 optic placode 1 8 1 1 optokinetic eye movement 3227 T optokinetic (after) nystagmus (OKN) 3 214-5 brainstem lesions 37 17, 3 7 1 8 F clinical examination/ investigation 37 1 6-7 hand held drum method 3717, 37 1 7 F magazine/newspaper use 3717, 3717 F direction 3717 directional preponderance 3726 child 1042 laboratory assessment 371 2 F, 3726 neuroanatomy 3717 optokinetic reflex 32 1 4-5 oral airway 2289, 2289 F oral allergy syndrome (OAS) 1 428, 1 82 8 birch rhinitis 1428 sensitization 1425-6 oral cavity anatomy 1 758 arterial supply 1 798-9 contact endoscopy 767 development 1 8 1 0-1, 1 8 1 1 F HIV manifestations 242-3 innervation 1 800-3 motor 1 803 sensory 1 800-3 lymphatic drainage 1 799-800, 27 1 3 mechanoreceptors 1959 medical negligence issues 2809 muscles 1 795-8, 1 800 T rheumatological diseases 1 84 swallowing 1954-5 vascular supply 1798-803 venous drainage 1 799 Wegener's granulomatosis 1650 see also mouth oral cavity reconstruction 2 568-72, 2885-6 deep circumflex iliac artery flap 257 1 , 2571 F distant pedicled flaps 2569 fibula free flap 2571 flaps 2885-6 issues/potential problems 2885-6, 2886
Pages 1-1 3 1 2 are in Volume 1 , pages 1 3 1 3-28 10 are i n Volume 2, and pages 281 1-4147 are in Volume 3.
I ndex I 4267
forearm flap 2871, 2871 F, 2872 F local flaps 2569 mandibular reconstruction 2569-70 microvascular free tissue transfer 2569 options 2886, 2886 T osseointegration 2572 osteoradionecrosis 2572, 2572 F primary closure 2568-9 prostheses 2929-30 quality of life issues 2776 scapular free flap 2570-1, 2571 F split skin grafts 2569 vascularized bone grafts 2572 oral cavity squamous cell carcinoma, stage NO neck treatment 2724 oral cavity tumours 2543-76 clinical presentation 255 1 diet 2550 epidemiology 2549-50 incidence 2347 infection 2348 lymph node groups 2565 management 2929 neck dissection 2564-5 radical 2743 staging 2564-5 nodal staging 2564, 2564 T nutrition 2550 occupation 2348 occurrence 2550 T oral hygiene 2348, 255 1 pathology 255 1 premalignant conditions 255 1 reconstruction see oral cavity reconstruction resection, visor flap approach 2567, 2567 F risk factors 2349 T, 2550-1 second primary tumours 2550 sentinel nodes 2565 sites 2549 T smoking 2347-8 surgical approaches 2566-8 labiomandibulotomy 2566-7, 2566 F peroral 2566 TNM classification 2364, 2364 T, 255 1 , 2551 T viruses 255 1 oral condylomas 1828 oral contraceptives rhinitis induction 1410 venous thromboembolism 290 oral disease benign 1 8 1 6-39 otalgia 3530-1
oral dysaethesia (burning mouth syndrome) 1 8 1 8 T, 1 829, 1 848-9 oral hairy leukoplakia (OHL) 20 12 T, 20 13 oral hygiene, oral cavity tumours 2348, 255 1 oral implants anatomical considerations 2907-10 bone volume 2907 classification 2902-4, 2902 T inflammation 2907 local anaesthetic 29 1 2 overloading 2907
see also individual implants oral mucosa 1 794-5 blisters 1 822 acquired 1 825 causes 1821 T, 1 822 inherited disorders 1823 contact endoscopy 767 morphological variation 767 pigmentation 1822 acquired lesions 1 825 hyperpigmentation see oral mucosal hyperpigmentation inherited conditions 1 823 oral mucosal disorders 1 822-3 acquired 1 825-8 ulcers 1 830 inherited 1 823-4 redness 1822-3 acquired 1 825-7 inherited conditions 1 823-4 swelling 1 823 acquired 1 827-8, 1 827 T inherited disorders 1 824 white patches 1 82 1 T, 1 823 acquired 1 835-7 inherited conditions 1 824 yellow lesions 1 824 oral mucosal hyperpigmentation 1 825 generalized 1 825 causes 1820 T, 1 825 drug-induced 1 825 localized lesions 1 825 oral/nasal airflow ratio 2 1 82 oral pain 1 828-37 oral papillomas 209 T, 1 828 oral petechiae 1 822 oral resonance, speech 2 166 oral soreness 1828-37 oral (viridans) streptococci 195-6, 198 oral thrush see candidiasis, oral oral trauma, taste abnormalities 1846 oral ulcers see mouth iIlcers
oral vestibule 1 793 Orasure 1 862 orbicularis muscle 3050, 305 1 ptosis 3060 orbicularis muscle flap 306 1 F, 3062 F orbicularis oris 1 803 orbit anatomy 1 677-9, 1 678 F, 4 1 2 1-2, 4 122 F age effects 1679 boundaries 412 1-2 inferior wall 1678 lateral wall 1679 medial wall 1677-8 periorbital 1 679 superior wall 1678 contents 3919 F infection classification 1087 T radiological evaluation 1679 orbital abscess 1 540 drainage 1 544-5 frontal rhinosinusitis 1544-5 sinusitis, children 1087-8 orbital apex decompression 1684-5 indications 1684 portals 4122 orbital apex syndrome 2 1 7-8 orbital blowouts, nasal endoscopic repair 1352 orbital cellulitis, rhinosinusitis complication 1 540-2 CT imaging 1297 disease stages 1 540, 1 54 1 ethmoid sinus 1540 examination 1 542, 1 545 F management 1 546 F radiological investigations 1542-3 surgery 1544-5 treatment 1 544 visual problems 1 540-2 without abscess 1 540 orbital decompression 1679-84 complications 1683-4 indications 1679, 1 680 nasal endoscopy 1352 orbital haemorrhage 3065 preoperative assessment 1680, 1680 F radiological evaluation 1679 surgical anatomy 1 677-9, 1678 F surgical techniques 1 680-2 endoscopic 1680-3, 1682 F results 1682-3, 1682 F, 1683 F three-wall, minimal incision 168 1-2, 1 682-3, 1683 F
Pages 1-1 3 1 2 are in Volume 1 , pages 1 3 1 3-28 1 0 are in Volume 2, and pages 28 1 1-4147 are in Volume 3.
4268 I I ndex
orbital exenteration case study 2936-7 nasal malignancy 2434 orbital fat advancement 3059, 3060 F atrophy 3049 removal 3057 orbital floor fractures 1630-1 imaging 1630-1, 163 1 F management 163 1 signs/symptoms 1630 orbital foramina 39 1 8 F orbital haemorrhage, post blepharoplasty 3064, 3064-5 orbital implants magnetic positioning 2909 F, 2929 F osseo integration 2909 orbital plate, frontal bone 3897 orbital prosthesis 2928-9 magnetically retained 2936 F surgery requiring 2929 T orbital pseudotumour 3916 orbital reconstruction 2928-9, 2938 F case study 2938 sinuses 2929 orbital roof fractures, frontal sinus trauma 1 507 orbital roof meningiomas 3954-5 orbital septum anatomy 3051 fat bulging 3054 F skin-muscle flap dissection 3059, 3059 F orbital tumours benign 3916 malignant 39 1 6 metastatic 3 9 1 6 optic nerve damage 3 9 1 5 orbitofrontal cortex olfactory projections 1663 taste 1 842 orbitomaxillary free bone flap 4065 orchitis 1900 organ of Corti 3 123 age-related changes 3540-1, 3540 F as amplifier 3 1 3 1 cellular architecture 3 128 F, 3 1 30-2, 3131 F development 806-7 fluid in, ionic concentrations 3 1 89-97 function 3 1 26, 3 1 30-2, 3 1 39-40 innervation 3 1 36-9, 3 1 38 F travelling waves, effects of 3 1 3 1 organ replacement, stem cells 75
organ-specific autoimmune inner ear disease 3680 organ system support, critical care 527-33 oro antral fistula 1085 orofacial defects, prosthetic rehabilitation 2929 orofacial granulomatosis (OFG) 1 828 oromandibular syndrome (Meige's syndrome) 3939-40 oronasal cavity skin grafts 2824 oronasal membranes 1 8 1 1 , 1 8 1 1 F oropharyngeal aspiration see aspiration oropharyngeal dysphagia see dysphagia oropharyngeal isthmus 1 792 F, 1 793 oropharyngeal manometry see manometry oropharyngeal membrane 1 8 1 1 oropharyngeal squamous cell carcinoma 2580 aetiology 2580 epidemiology 2580 HIV implications 2580 oropharyngeal tumours 2577-97 benign 2579-80 biopsy 2584 chemotherapy 2591 clinical presentation 2579 complications 259 1 distant metastases 259 1 follow-up 2592 imaging 695 F, 2584 incidence 2347 malignant 2580-1 mandibular nerve damage 3927 metastatic disease 2581 neck management 2588, 2590-1 organ-preserving approaches 2591 pathology 2579-8 1 patient evaluation 2583-4 physical examination 2583 radiotherapy 2585 recurrence 2592 risk factors 2347-8 infection 2348 occupation 2348 oral cavity hygiene 2348 smoking 2347-8 surgery 2585-8 radical neck dissection 2743 transmandibular approaches 2586-8, 2587 transoral approaches 2586, 2586 F
transoralltranscervical combined approach 2586 transpharyngeal approaches 2586 symptoms 2583 TNM classification 2365 T, 2581-2, 258 1 T, 2582 T treatment factors affecting choice 2584-5 functional outcome 259 1-2 options 2585-8 policy 2584-5 sequelae 2591-2
see also individual tumours oropharynx anatomy 1 792 F, 1793-4, 1 944, 2364-5, 2577-9, 2578 F blood supply 2579 embryology 80 1-2, 803 F fascial spaces 2579 innervation 2578 lymphatic drainage 2579, 2 7 1 3 mucous membrane 1947 otalgia 3530-1 relations 1950 F swallowing 1957 tumours see oropharyngeal tumours walls 1 944, 2577 oropharynx reconstruction, forearm flaps 2871 orthodontic treatment, hemifacial microsomia 1033 orthopaedic surgery, 3D imaging 702-3 orthopantonogram (0 PG) mandibular ossifying fibroma 1930 F oral cavity tumours 2553 orthostatic intolerance 3227-8 orthostatic tremor postural imbalance syndrome 3779, 3780 posturography 3735-6, 3735 F 'oscillating veins; skin flap 1 1 1 oscillation harmonic (sinusoidal) 3 158-9, 3 1 59, 3 1 59 F mechanical systems 3 1 6 1 , 3 1 6 1 F vibrations vs. 3 1 58-9 oscillopsia causes 3708, 3708 T labyrinth destruction 3749 ototoxicity-related 3569 paroxysmal 3708 symptoms 3708 oseltamivir 209-10 Osler-Weber-Rendu disease 739, 1 574, 1 823
Pages 1-1 3 1 2 are in Volume 1 , pages 1 3 1 3-28 1 0 are in Volume 2, and pages 281 1-4 147 are in Volume 3.
I ndex I
osmophobia 1664, 1669-70 osseocarti1agenous septal deformity, children 1 076 osseointegration 290 1-23 adjunctive implant techniques 29 1 7-20 extra oral implant sites 2908-9 healing, final stages 2906 history and background 290 1 -2 implant 2920-1 ImDlanI- tissue interface 2906-7 inductive materials 29 1 7 mandible 2908 maxilla 2907-8 metal selection 2904-6 molecular level 2906 neighbouring tissue, effects on 2906 oral cavity reconstruction 2572 percutaneous implants 2941 process 2904-6 progressive loading 2914 surface characteristics 2904-6 surgical salvage, bone loss 2920 time before loading 2914-5 titanium implants 1 19 ossicle dislocation 3681-2, 368 1 F development 966 ossicles axis of rotation 3 1 80, 3 1 80 F congenital abnormalities see congenital ossicular abnormalities development 814-5 lever action 3 18 1 ligaments 3 1 80 mode of movement 3 1 8 1 vibration 3 1 80
see also individual bones ossicular chain fixation 3289 ossicular chain reconstruction 954 ossicular chain trauma 3492 associated injuries 3492-3 surgical management 3493 results 3493, 3494 T types 3493 ossicular grafts, chronic otitis media 3405-6, 3405 F ossicular implants, chronic otitis media 3405-6, 3406 F ossicular replacement prostheses extrusion rates 1 19 HAPEX 1 20, 1 20 F historical aspects 1 1 8 hydroxyapatite devices 1 20
polymers 1 2 1 titanium 1 1 9 ossiculoplasty cholesteatoma 3433-4 inactive mucosal chronic otitis media 3422 outcomes 3422 medical negligence 3829 ossifying fibroma juvenile 1929-30 mandible 1929, 1930 F skull base 4 1 24, 4124 F osteitis deformans see Paget's disease osteitis fibrosa cystica ('brown tumours') 390, 40 1 ostelamivir 209-10, 232-3 osteoarthritis 186 osteoblasts activation 94 bone repair 94 osseointegration biocompatibility 2906, 2906 F osteoconduction 291 7 osteodistraction, hard palate carcinoma 2563 osteogenesis imperfecta 3474 type 1 3458 osteoinductive materials 2 9 1 7 osteolysis, mucocoeles 1 532 osteoma(s) frontal sinus see frontal sinus osteomas jaw 1930 mandibular 1 930 middle ear 4072 skull base 4123 osteomyelitis frontal see frontal bone osteomyelitis medical negligence 1 735 sinusitis, children 1086 osteoplastic bone flap procedure, frontal sinus 1 5 14-8, 1515 complications 1 5 1 6-7 indications 1 5 1 4 limitations 1 5 1 7-8 results 1 5 1 7-8 sinus obliteration 1 5 16-7 technique 1 5 1 5-7 osteoporosis hyperparathyroidism 390 implants 2910 PTH assay 382-3 subclinical hyperthyroidism 353 thyrotoxicosis 400- i
osteoradionecrosis, oral cavity reconstruction 2572, 2572 F osteosarcoma craniofacial 1 936-7 grading 1 936 management 1936-7 presentation 1 936, 1937 F subtypes 1936 survival rates 1936 larynx 2604 pituitary region 4 1 04 osteosclerosis, tinnitus 3598 osteotomy complications 309 1 deviated nose 2965-6, 2990, 2991 F dorsal humps 2955 lateral 2955-6, 2956 F Le Fort 1 2463 Le Fort 3 1029 rhinoplasty 3091 ostia, accessory 1 330 ostiomeatal complex 1 344-6 otalgia 3526-36 acute 3527 autonomic innervation and
3533-4 bullous myringitis 3326, 3527 children 3527-8 deep temporal bone 3528 definition 3526 dental disease 3529 diagnosis 3534 external ear disease 3527 geniculate neuralgia 3532 hypopharyngeal disease 3530-1 inner ear disease 3528-9 middle ear disease 3527-8 differential diagnosis 3528 nasal disease 3530 neuralgias 353 1-3 neuroanatomy 3527 occult malignancy 3530-1 oropharyngeal disease 3530-1 post-tonsillectomy 3530, 3530 F skull base lesions 3527, 3944-5 special needs children 786 stylohyoid syndrome 3533 temporomandibular joint dysfunction 3529-30 tuberculous otitis 3447, 3447 T, 3450 T otic cup 8 1 5 otic disc (placode) 806, 806 F, 8 1 5, 3 1 22, 3 1 23 F 3908 otic
Pages 1-13 12 are in Volume 1, pages 1 3 1 3-28 10 are in Volume 2, and pages 2 8 1 1-4147 are in Volume 3.
4270 I I nd ex
otic pit 806, 806 F, 3 1 22, 3 123 F otic placode (disc) 806, 806 F, 8 15, 3 1 22, 3 123 F otic vesicle see otocyst otitic barotrauma 3499 cerebral air gas embolism 3 5 1 9-20 clinical features 3504-6 definition 3499 diving, postoperative 3506 Eustachian tube dysfunction 3506 flying, postoperative 3506 historical perspective 3500 hyperbaric oxygen therapy, secondary to 35 1 9 inner ear see inner ear barotrauma maxillary sinus 1 369 middle ear see middle ear barotrauma otitis media with effusion 3390 pressure/volume relationships 3495 F, 3 500-4, 3502 F septal deviation 3506 stable depth injuries 3 5 1 2-3 otitic hydrocephalus active chronic otitis media 3438 management 3438 acute otitis media 925 cerebrospinal fluid rhinorrhoea 1 641 otitis, tuberculous see tuberculous otitis otitis extema 335 1-7 aetiology 3352 allergic reactions 3352 benign necrotizing see benign necrotizing otitis extema classification 3351 complications 3352-3 definition 332 1 , 3351 diagnosis 3352 epidemiology 3352 fungal see otomycosis with granulations myringitis HIV patients 240
see
granular
malignant otitis extema management 422-3, 3353-4 systemic antibiotics 3353 topical medication 3353 treatment comparisons 3354-5, 3354 T outcomes 3352-3 pathology 3352 predisposing factors 335 1 T recurrence prevention 3353-4 symptoms/signs 3352, 3353 F
UU'Cll&U(UH see
otitis extema granulosa
see
granular
myringitis otitis media acute see acute otitis media (AOM) adhesive 3426 chronic see chronic otitis media (COM) chronic suppurative s e e chronic suppurative otitis media (CSOM) classification 930 T cleft lip and palate 1 0 10-3 HIV patients 240 secretory see otitis media with effusion (OME) otitis media with effusion ( OME) 3388-94 adenoidectomy 902-3, 1 095 aetiology 3388-9 autoinflation 3392 biofilm infection 1 095 children s e e otitis media with effusion (OME), childhood chronic otitis media development 3408 clinical presentation 3390 complications 339 1 definition 877-8, 3388 diagnosis 3390-1 audiology 339 1 , 339 1 T clinical 3390-1 radiology 3390 surgery 339 1 hearing aids 3393 management 339 1-3 medical 423, 3392 surgical 3392-3 nasopharyngeal pathology 2464-5, 3391 outcomes research instruments 640 pathology 3389-90 prevalence 3388 surgery-induced 3390 Wegener's granulomatosis 1 650 otitis media with effusion (OME), childhood 877-9 1 1 acute otitis media 88 1 age-related 880-1 allergy 879 bacteriology 878, 879 T behavioural problems 894 cleft palate 1 0 1 0 cognition 894 congenital atresia 981 contact with other children 882, 882 T
craniofacial abnormalities 879 definition 877-8 diagnosis 884-91 hearing assessment 890-1 ideal strategy 890 reference gold standard 884 tools 885-90 effusion characteristics 878 epidemiology 880-4 clinical applicability of evidence 884 episode durationlrecurrence children over three 883 children under three 882-3, 883 F Eustachian tube dysfunction 878-9 fluid level 886 F gastro-oesophageal reflux 880, 1 274 gender 882 hearing loss parental perception of 884, 884 F temporary 825 hereditability 882 histology 878, 878 F, 879 F history 884-5 language development measurement 62 1 management 895-903 counselling 895 hearing tactics 895 medical 895-6 surgery 896-903 natural history 891-2 otoscopy 885-7, 885 F air bubbles 886 F malleus handle retraction 885, 885 F tympanic membrane discolouration 885 F, 886 F outcomes 891-5, 892 T parental smoking association 626, 882 pathology 878-80 preschool surveillance 830 prevalence 880-1, 880 F, 8 8 1 T race 882 risk factors 881 , 882 for persistence 883-4 seasonal 8 8 1 vertigo 1045-6 otoacoustic emissions (OAEs) 3276-8, 3842, 3844 T ambient noise reduction 3277 auditory function monitoring 751 auditory neuropathy/dyssynchrony 3840, 3844 T
Pages 1-1 3 1 2 are in Volume 1 , pages 1 3 1 3-28 1 0 are in Volume 2, and pages 2 8 1 1-4 147 are in Volume 3 .
I n d ex I 427 1
contralateral suppression 3843 hearing aid status 3852 T infants 3840 classification 3276-7 definition 3276-7 detection 3277 frequency analysis 329 1 neonatal hearing screening 329 1 pathological factors affecting 3290 recording 3276-7 separation from other signals 3277 stimulus 3843 tinnitus 3605 F, 3610, 361 1 F types 3276-7
see also individual types otoconia 3210, 3228-30 benign paroxysmal positioning vertigo 3760, 3760 F, 3762-3 embryology 807 otocyst 806, 806 F, 8 14-5, 8 1 5, 815 F, 3 122, 3 1 23 F otoferlin (OTOF ) gene 3846 otogenic brain abscess, chronic otitis media 3436 otogenic sepsis, chronic otitis media 3437 otolithic crises, Meniere's disease 3 758 otolithic membrane 32 10 otolith-ocular reflexes 3737 otolith organs hair cells 3228-30, 3230 F linear acceleration detection 32 10 tilt differentiation 3210- 1 , 3210 F loss, vestibuloocular reflex and 3223 movement detection 32 1 0-1 orientation 32 1 0 orthostatic tolerance 3227-8 see also saccule; utricle otolith testing 3737-42 difficulties in 3 73 7 movement artefacts 3737 Otologic( tm) middle ear transducer 3661 otology drug therapy 429-35 ear drops 429 ear wax removal 43 1-3 topical preparations see ear preparations, topical image-guided surgery 708 medical negligence 3826-34 cholesteatoma 3828-9 dizziness 3829-30 ear syringing 3826-7 loss 3 830-1
iatrogenic facial nerve damage 3827-8 Meniere's disease 3830 ossiculoplasty 3 829 otosclerosis 3827 sudden sensorineural deafness 3829
see also specific diseases!conditions otomycosis 2 13-4, 3355 aetiological agents 2 1 3 clinical findings 2 14, 3355, 3355 F complications 2 14 definition 2 1 3 diagnosis 2 1 4 epidemiology 2 1 3-4 management 2 14, 3355 outcomes 2 1 4 otorhinolaryngology, paediatric see paediatric otorhinolaryngology otorrhoea active chronic otitis media 3436 active mucosal chronic otitis media 3424' cholesteatoma 343 1 medical 4 144 retropharyngeal abscess 2002 skull base lesions 3944 tuberculous otitis 3446, 3447, 3447 T, 3450 T tympanic membrane perforation and 936-41 ventilation tube insertion 900, 900 T otosclerosis 3453-85 aetiology 3458 biochemistry 3459 chronic otitis media 346 1 clinical definition 3454 incidence 3460, 3460 T cochlear definition 3454 diagnosis 3465 clinical otosclerosis and 3465 conductive impairment absence 3465 pathology 3457 cochlear implantation 3480, 3655 assessment 3480 pitfalls 3480 T conductive hearing impairment 3465-6 hearing aids 3467 definitions 3454 diagnosis 3460 histological 346 1 . surgical 3455 F, 346 1 , 3471
genetic predisposition 3458 hearing aids 3467 as rescue treatment 3467 surgery and 3467 histologic definition 3454, 3458 incidence 3459-60 histopathology 3454-5, 3455 F history 3463 incidence 3459 management, fluoride 434, 3466 medical negligence 3827 natural history 3465 pathology 3454-8 conductive hearing loss 3456 lesion distribution 3456 sensorineural hearing loss 3456-7 tenlpclral bone 3456 vestibular symptoms 3457-8 pure-tone audiometry 346 1 , 3462 F radiology 3464 surgery 3468 age and 3469 audiological eligibility 3464-5 children 3469 contraindications 3469 hearing outcomes 3477-80 historical perspectives 3468 leisure activities 3469 occupation and 3469 postoperative complications 3475-7 second side 3469-70, 3470 F techniques 3470-3 unilateral 3469 type II collagen autoimmunity 3459 otosclerotic foci 3454-5 otoscopy 3314-7 active vs. inactive ear 3413, 3414 F attic, wide view 3314 F bullous myringitis 3326, 3327 F chronic otitis media 3412, 34 1 3-8 closed pneumatic 3314 F ear position 3312 F external auditory canal 3314-5 healed chronic otitis media 3426 open mastoid cavities 34 13, 3413 F, 34 14 F otitis media with effusion 884, 885-7, 885 F, 886-7, 887 T, 890, 3390-1, 3391 T otosclerosis 3460-1 pathological sites 3412-3, 3412 F, 3413 F principles 3314
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4272 I I n dex
otoscopy (continued) simulated, otitis media with effusion 886 skull base lesions 3945 structured 3 3 1 5-6 temporal bone fractures 3495, 3495 F tuberculous otitis 3447, 3448 T video 887 otosyphilis 3694-5 clinical picture 3694-5 histopathology 3695, 3695 F HIV patients 240-1 ototoxicity 3567-76, 3676-7 aetiology 3298-300, 3299 T, 3568 T, 3676 animal models 3298, 330 1-2, 3303 cochleotopic gradient of susceptibility 3569 hearing loss, attribution to 3572 HIV patients 240-1 incidence 3300 management 357 1-3 medical negligence 383 1 pathology 3300-1, 3301 F prevention 330 1-2, 3571 antioxidants 3302 reactive oxygen species 3300-1, 3301 F recognition 357 1-3 vestibular monitoring 3573 risk factors 3300 tinnitus 3599-600 treatment 3573 vestibular monitoring 3573
see also specific drugs/drug types Otovent balloons 896 outcome odds ration 622 outcomes research 633-44 assessment 634-7, 634 T acceptability 637 appropriateness 634-5 feasibility 637 interpretability 637 precision/ sensitivity 636-7 reliability 635-6 responsiveness to change 636 validity 635 bias 637 definition 634 domains 634, 636 future development 642 instruments 637, 638 T choice of 641-2 condition-specific 640-1 dimension-specific 64 1
disease-specific 640-1 generic 637-40, 642 site-specific 641
see also specific instruments odds ratio see odds ratio quality of life 2770 sinonasal disease 641 value 634 outer hair cells (OHC) 3 1 30, 3 1 3 1 F, 3132 F apical surface 3 1 32, 3 1 3 2 F calcium channel dysfunction, tinnitus 3605 cell bodies 3 1 32-3, 3 1 32 F, 3 1 34 drug-induced tinnitus 3600 efferent inputs 3 145 electrical responses 3 1 95-6 electromotility 3 1 34 function 3 1 32-5 innervation 3 13 8 F, 3 1 39 input-output function 3 195 F, 3 196 mitochondria 3 1 34 nucleus 3 1 34 otoacoustic emissions 3842 plasma membrane fluidity 3549 stereocilia 3 1 32, 3 1 32 F, 3 1 33 F actin filaments 3 1 32-3 , 3 1 33 F contact region 3 1 33 deflection 3 1 33-4 mechanical amplification 3 1 34 membranes 3 1 3 3-4 rootlets 3 1 32-3 , 3 1 33 F tip links 3 1 33, 3 1 3 3 F ultrastructure 3 1 32-5 oval window 3 126 anatomy 3 1 1 0-1 bone conduction 3 1 85 congenital aplasia 873 rupture 3497 overnight oximetry, obstructive sleep apnoea 23 1 6 overnight polysomnography 23 1 8 overshortened noses 2982-5, 2984 F, 2985 F grafts 2985 F over-the-wire micro catheters 732-3 overtones 3 1 67 Overview and Scrutiny Committees (OSC) 574 ovulation 302 oxaliplatin 37 oxazolidinones 232 methicillin resistant Staphylococcus aureus 232
oxidative stress cellular responses 3301 ototoxicity 3300-1 , 3301 F oxycodone, cancer pain management 2786, 2787 T oxygen, upper airway obstruction 2288 oxygen desaturation index (OD!) 23 16, 2316 F, 23 17 F oxygen 'dips,' obstructive sleep apnoea 2 3 1 6, 2 3 1 6 F, 2317 F, 23 1 8 F oxygen saturation levels critical care, adults 528 obstructive sleep apnoea 233 1 oxymetazoline 439, 3505-6 oxyphil cells 373 oxyphilic adenoma 2483 oxytocin effects 300, 308 secretion 308 ozaena 14 1 1 P I artificial chromosomes (PAC) 1 1 p53 apoptosis 58 cell cycle control 58, 2382 exons 2378-9 head and neck squamous cell carcinoma 29, 2386 T hypopharyngeal cancer 2635-6 immunohistochemistry 2382 F mechanisms 2382 F mutations 58 oesophageal cancer 2635-6 squamous cell carcinoma 58 thyroid cancer 2670 p53 transfer, chemosensitization 28 pacemakers, surgical preparation 459 pachydermia oralis (white-sponge naevus) 1 824 paclitaxel (taxol) 39, 276 1 paediatric anaesthesia 507-25 adenoidectomy 5 1 5-7 airway endoscopy procedures 517-9 airway surgery 5 1 9 anaesthetist's role 507 breathing systems 5 1 0 day case surgery 508 ear surgery 5 1 3-4 equipment 5 1 0-3 airway management 5 1 0-1 foreign body removal 5 1 9 heat conservation 5 1 2-3 induction 5 1 3 inhalational induction 5 1 3
Pages 1-13 12 are in Volume 1, pages 1 3 1 3-2810 are i n Volume 2, and pages 2 8 1 1 -4147 are i n Volume 3 .
I ndex I 4273
laryngotracheal reconstruction 52 1 laryngotracheal stenosis 52 1 laser endoscopy 5 19 nasal surgery 5 14-7 nasopharyngeal surgery 5 14-7 parental presence 5 1 3 pharyngeal surgery 5 14-7 physical examination 508 physiological monitoring 5 1 3 premedication 509 preoperative assessment 508-9 preoperative fasting 509, 509 T psychological preparation 508 respiratory assessment 508-9 sedative premedication 509 techniques 5 10-3 tonsillectomy 5 1 5-7 tracheostomy 52 1 tube sizing 5 1 1 vascular access 5 1 1-2 paediatric cochlear implantation 860-8 adolescents 866 anaesthesia 5 14 assessment 863 audiological tests 863 auditory neuropathy/ dyssynchrony 3852 aural rehabilitation 866 bilateral 866 candidacy 866 post-lingual 862-3 chronic suppurative otitis media 865 cochlear anatomical abnormalities 865 current status 860-1 devices 86 1 failures 865 implantation 861, 86 1 F microphone 861 history 860 management controversies 866 medical assessment 863 MRI following 866 neurodevelopmental issues 863 obliterated cochlea 865 older children 866 open mastoid cavities 865 ossification 865 perilingual deafness 86 1 post-meningitic patients 863 postoperative habilitation 865 prelingual deafness 86 1-2 preoperative counselling 864 quality of life measures 866-7
special surgical circumstances 865 surgery 864-5 complications 864-5 technique 864 timing 86 1-3 early 862 paediatric consultation 776-82 breaking bad news 780 child protection issues 780 clinic requirements 777 rooms 777 'special' clinics 777 waiting area 777 consent 780-1 competence 780-1 parental responsibility 78 1 consultation preparation 777 decision to seek advice 776 endoscopy 777 examination 778 functional problems 780 history 778 management plan 779-80 otoscopy 778 outcome documentation 780 prescribing for children 780 paediatric intensive care 542-8 admission issues 543 T analgesia 544 anatomical/physiological considerations 542-3, 543 T bronchoscopy 547 ENT emergencies 544-6 evaluation 543 fluid management 543-4 major surgery 546-7 trauma 544 upper airway obstruction 544-5 paediatric intensive care unit (PICU) 774 paediatric otolaryngologists 774 general 774-5 special children 774 special hospitals 774 specialist 774-5 'special problems' 774 training 775 paediatric otorhinolaryngology 77 1-5 disease spectrum 773 history 77 1-3 medical negligence 1305-12 acute epiglottitis 1309 adenoidectomy 1308 atlanto-axial instability 1308 cholesteatoma 1 306-7
epistaxis 1 3 1 0 establishing damages 1306 foreign bodies 1309-10 hearing disorders 1306 nasal trauma 1 3 1 0-1 neck masses 1 3 1 0 negligence causation 1306 stapes, congenital fixation 1307 tonsillectomy 1308 tracheostomy 1309 scope of practice 773 service development 774 societies 773 paediatric reflux 1273 paediatric special needs see special needs children paediatric tonsillectomy 1229-41 anaesthesia 5 1 5-7, 1236-7 at risk children 1235-6 analgesia 1237 antibiotics 1237 antiemetic drugs 1237 blood loss 1232-3 complications late 1236 perioperative 1236 current practice 1231 day-case surgery 1237 dental damage 1308 education, effect on 1232 efficacy 1229-3 1 evidence-based medicine 1229--32 guidelines 123 1-2 haemorrhage 1236, 1308 health economics 1232 indications 1232 infection 1236 morbidity 1235-6 mortality 1235-6 nonsurgical alternatives 1237-8 pain 1235 peri operative management 1236-7 psychosocial morbidity 1235 rates 1988 recurrent sore throat 1988 sociocultural factors 1231 steroid therapy 1237 techniques 1232-5 capsulotomy 1235 dissection 1232-3, 1233 F haemorrhage rates 1234 T ultrasonic 1235 variant Creutzfeldt-Jacob disease 123 1, 1238
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4274 I I nd ex
Paget's disease 3486-90, 188-9 aetiology 3486-7 bone changes 3487 complications 3489 definition 3486 diagnosis 3488 epidemiology 3486 hearing loss 3487-8 imaging 188-9, 1 89 F, 3488 laboratory investigations 3488 management 3488-9 indications 3488, 3488 T medical 3489 outcomes 3489 pathophysiology 3487-8 symptoms/signs 3487-8 tinnitus 3487 vestibular disturbance 3488 Paget's seed and soil hypothesis 2714 pain cancer see cancer pain ear see otalgia facial see facial pain neurophysiology 3526-7 oesophageal 1952 oral 1 828-37 otalgia 3526-7 trigeminal neuralgia 1 829-30, 3927 painful teeth 1 7 2 1 thyroiditis 352-3 palatal consonants 2 166-7, 2 1 67 T palatal cysts of infancy 1926 palatal fistula 10 10 palatal lift 2088 palatal muscles, myogenic somatosounds 3600 palatal myoclonus 2078 palatal processes 1 3 1 5-6 fusion 1 3 1 5-6, 18 1 2-3 palatal shelf 1 8 1 2, 1 8 1 3 F elevation 1 8 14 fusion 1 8 14 palatal snoring surgery 2333 T palate anatomy 1 79 1-2 damage, surgery-related 2809 development 798-9, 800 F, 1 3 1 5-7, 1 3 1 6 F, 1 3 1 7 F, 1 8 1 2-4, 1 8 13 F anomalies 1 320, 1 8 1 3-4, 1 8 14 muscles 1 8 13 hard see hard palate minor salivary gland tumours 2505, 2505 F primitive 1 3 15-6 sensory innervation 1 800-1, 1 801 F
soft see soft palate vagal nerve lesions 3937 palate repair s0 150 1 0 1 2 F palatine aponeurosis 1 792, 1 945, 1945 F, 3908-9 palatine arteries ascending 2 1 13, 3909 descending 2 1 13 greater 1 328, 1 799 lesser 1 799 palatine bone 2 1 1 1 palatine canal 1 799 palatine glands 1 808 palatine process 1 34 1 palatine raphe 179 1-2 3937 palatine sensation palatine tonsil see tonsil(s) palatoglossal arch 1 793 palatoglossal folds 1 944 palatoglossal glands 1808 palatoglossus 1 797, 1946 1; 2 1 12 palatopharyngeal arch 1 793 palatopharyngeal fold 1944 palatopharyngeal sphincter see velopharyngeal sphincter palatopharyngeus 1007-8, 1 009 F, 1946 1; 1 949 F, 2 1 12, 2 135 T soft palate repair 1 009 palliative care, head and neck cancer 278 1-802 breaking bad news 2782-3, 2783 T children 1261 definition 2782 dysphagia 2789-9 1, 2790 T examination 2790 management 2790- 1 hypercalcaemia 2794 malignant ulcers and fistulae 2788 T, 2789, 279 1-4 bleeding 2792-4, 2793 T dressings 2794 infection and odour 2792 management 2793 T nausea and vomiting 2787-8, 2787 T oral problems 2788-9, 2788 T candidiasis 2789 mucositis 2789 salivary leakage 2788-9, 2788 T ulceration 2788 T, 2789 xerostomia 2788 pain see cancer pain psychological problems 2795-8 acute confusional states 2797-8, 2798 T anger 2795-6, 2796 T
anxiety 2795, 2795 T withdrawal 2796-7, 2797 T sinonasal malignancy 2427 stridor 2795 "1 1 '"\"''''''1'' vena caval obstruction 2794-5 terminal phase 2798-800 resuscitation issues 2798, 2799 T Pallister-Hall syndrome 1 1 37 palpebral fissures, blepharoplasty 3058 palpebral (canthal) ligaments 1 679 pamidronate 2794 pancreatic islet cell disease see diabetes mellitus pancreatic polypeptide, nose 1 364 pancytopenia 273, 273 T panic attacks 3709 panic disorder, vestibular disorders and 3814-5 panniculus carnosus 9 1 panthographic expansion 2832 pantoprazole 2263 Pan troglodytes (chimpanzee), paranasal sinuses 1321 F papaverine-induced skin reactivity 1409 papillae, tongue 1 794, 1 84 1 , 1 84 1 F
see also individual types papillary adenocarcinomas, nasal 2420 papillary cystadenocarcinoma 2500 papillary cystadenoma lymphomatosum see Warthin's tumour papillary thyroid cancer (PTC) 3 3 1 , 2672-4, 2673 T cervical nodal metastases 1 76 1 children 2693 cystic nodes 1 76 1 cytological appearance 2679 F extent 2673 T genetics 2669, 2670 histopathological features 2674 F imaging 2677 F, 2678 F microcalcifications 7 1 9 nodal metastases 1761 prognostic variables 2682 T treatment 2685 ultrasound examination 7 1 9, 720 F papilloma(s) CO2 laser excision 2238 inverted see inverted papilloma laryngeal 764, 2600 T laser plume 2236 oral 1 828 phonosurgery 2238, 2239 respiratory 209 sinonasal 1 1-2
1-1 3 12 are in Volume 1, pages 1 3 13-2 8 1 0 are in Volume 2, and pages 28 1 1-4 1 47 are in Volume 3.
I ndex I 4275
papule 1 699-700 parabrachial nucleus 3 8 1 6 paracetamol anaesthetic premedication 490 T children 509 dosage, children 5 1 6 T head and neck cancer pain 2785-6 migrainous vertigo 380 1 pharyngitis, acute 1984 tonsillectomy 1 993 paracoccidioidomycosis 225 paracrine signalling, embryonic myogenesis 68 paracusis 3596-7 Paradise study 1230 paradoxical embolism, brainsteml cerebellar infarction 3756 F, 3767 parafollicular (C) cells, thyroid gland 324, 327 embryology 3 1 5, 368 function 324 microscopic anatomy 320, 320 F paragangliomas see glomus tumours (paragangliomas) paraglottic space 2 1 37 F, 2 1 38, 2 1 39 F parainfluenza virus (PlV) 207 parainfluenza virus vaccination, acute otitis media 9 1 9 paramedian forehead flap, nasal reconstruction 3022, 3024 F paramedian mandibulotomy 2566 F paramedian pontine reticular formation, saccade abnormalities 3715 parameningeal sarcoma 2527 paramyxovirus antigens, Paget's disease 3486 paranasal bones, development 1 3 1 7-2 1 paranasal granuloma 2 1 7 clinical features 2 1 8 epidemiology 2 1 7 management 2 1 9 nasal tuberculosis 1459, 1460 F outcomes 2 1 9 treatment 2 1 9 paranasal sinuses anatomy 1 3 1 5-43 comparative 132 1-2 asthma 1 562 development 803, 1 3 1 5-2 1 , 1368 anomalies 1320-1 olfaction 1 369 drainage 1368 endoscopy see nasal endoscopy functions 1 369
granulomatous conditions 1 646 T HlV infection 241-2 hypophysectomy complications 4 1 1 3 infections chronic 1458-68 orbital involvement 3916 inflammatory disease 1 344-6, 1 349-50, 1 349 F lymphatic drainage 2418, 2713 malignancy see sino nasal malignancy mucosa 1 368 mycotic diseases 2 1 6-22 nonallergic, noninfectious inflammation 1 382-3 olfactory dysfunction 1 667-8 ostium size 1 369 oxygen tension 1 368 physiology 1 368-9 pneumatization 1 5 1 9 pressure changes 1 369
see also individual sinuses paranasal sinus inflammation asthma 156 1-2 chronic obstructive pulmonary disease 1 56 1-2 paranasal sinus surgery anaesthesia 503 blood transfusion 257 complications 1485 T training issues 551 paraneoplastic cerebellar degeneration 3775 paraneoplastic pemphigus (PNP) 1834 parapharyngeal abscess 1223, 1 998-2000 bacteriology 1 999 clinical features 1 999 complications 2000 carotid sheath vessel thrombosis 2000 mediastinitis 2000 necrotizing fasciitis 2000 CT imaging 1223 F differential diagnosis 1 999 dysphagia 203 1 , 203 1 F epidemiology 1 999 investigation 1 999 treatment 1999-2000 needle aspiration 2000 surgical abscess drainage 1 999-2000 parapharyngeal space (PPS) 1 744, 1 745 F, 1 756, 1 806-7, 1 950, 1 950 F, 2 1 10, 2 1 10 T, 2�23, 2523 F, 2579, 3908-9
poststyloid compartment 2523, 2579 prestyloid compartment 2523, 2579, 3905 F, 3906 F, 3908-9, 3909 F retrostyloid compartment 3909 parapharyngeal space (PPS) tumours 2522-42 angiography 253 1 , 253 1 F carotid body paraganglioma 2525-6, 2525 F chemotherapy 2534 diagnosis 2529-32 fine needle aspiration cytology 2529-30 histopathology 2524-7 imaging 2530-1 investigations 2529-32 masticator space 2530 metastases 2527-8 nasopharyngeal carcinoma 2527 neck 2535 neurofibromas 2527 patterns of failure 2535-6 prognosis 2535-6 radiotherapy 2534 rare forms 2527 salivary gland 2525 schwannomas 2527 spread 2524-7 adjacent to PPS 2528 within PPS 2528 staging 2529-32, 253 1-2 surgical treatment 2532-4 definitive 2532-4 extended trans mandibular approach 2533 trans cervical approach 2533 transparotid approach 2533
see also individual procedures survival 2535-6, 2535 F symptomatology 2528-9, 2529 T syncope 2529 treatment 2532-5 complications 2536 trismus 2528-9 xerostomia 2536 paras accessoria 1 853 parascapular flap 2873-6 parasitosis 1 2 1 6 epistaxis 1065 parasympathetic nervous system nose 1363 thyroid gland control 3 1 9 parasympathomimetics 1365, 1 365 T parathyroid adenoma 390 histology 390
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4276 1 I nd ex
parathyroid adenoma (continued) hyperparathyroidism 40 1 investigations 39 1 MEN- l gene 389 ultrasound 722, 722 F parathyroid adenoma- l (PRAD - l ) gene 388 parathyroid carcinoma 390 FDG-PET imaging 694 parathyroidectomy 393 approach 373 benefits 392-3 bilateral neck exploration 393 complications 395 conventional 393 endoscopic 395 hyperparathyroidism 393-5, 396 inferior gland location 394 mediastinal exploration 394 mediastinotomy and 394 minimally invasive 383, 384 persistent hyperparathyroidism 395 preoperative imaging 383, 384 radio-guided 395 recurrent hyperparathyroidism 395 results 395 cure rate 395 scan-directed minimally invasive open 394 sternal split 372 superior gland 393-4, 394 F criteria 393 video-assisted 395 parathyroid glands 367-78 anatomy 369-73, 387, 2665-6, 2665 F macroscopic 369-7 1 microscopic 3 1 9-2 1 bilobed 369-70 blO(:hermstry 379-81 blood supply 372 calcium sensing receptor 388 cells 373 ::lcr"'-rp'l
see also individual cell types descent 368, 370 F development 367-9, 368 F, 387 disease 401
see also individual diseases dysfunction 387-97 ectopic 370 F, 371 blood supply 372 imaging 392 fat lobules vs. 370- 1 , 371 T function, normal 379
function testing 379-86 methods 379 hyperplasia 390 imaging 383-4, 722, 1299-300 best clinical practice 385 indications 384 infarction 372 inferior (parathyroid III) anatomical location 371 development 367-8, 387 maldescent 372 surgical location 394 undescended 394 injury, post-thyroidectomy 351 innervation 373 intrathyroidal 722 'kissing pair' 369-70 location 370 F, 37 1-2 asymmetrical 372 variations 368, 371 number of 369 physiology 373-5, 388 PTH see parathyroid hormone (PTH) removal (parathyroidectomy) see parathyroidectomy shape 369-71 size 369 superior (parathyroid IV) anatomical location 371 development 368, 387 migration 368 surgical location 393-4, 394 F supernumerary 369 surgical identification 370, 371 T venous drainage 372-3 weight 369 parathyroid hormone (PTH) 373-4, 388 action 374 active form 388 biochemistry 382-3 in clinical practice 382-3 intraoperative, gamma probe localization 384 therapeutic strategies and 382 bone, effects on 388 end organ resistance 383 half-life 388 hypercalcaemia 382, 382 T hyperparathyroidism 389 hypocalcaemia 374, 382, 382 T kidney, effects on 388 metabolism 374 pseudohypoparathyroidism 383
regulation 374 secretion 373-4, 388, 389 structure 373-4 parathyroid hormone receptors (PTH) 388 parathyroid hormone-related protein (PTHrP) 375, 388 parathyroid hyperplasia 390 paratracheal nodes 2 143 Pare, Ambroise 2924-5 'parent's kiss' 1 1 86 parietal lobe lesions, eye movement defects 392 1 Parinaud's syndrome 3921 Parkinsonian syndromes, gait 373 1 Parkinson's disease 3939 aetiology 2078 arm swing loss 373 1 balance problems 3778 dysphagia 2033, 2078 mastication 3939 olfactory dysfunction 1669 postencephalitic, oculogyric crisis 392 1 posturography 3735-6 sialorrhoea 3939 speech 3939 stem cell therapy 75 symptoms 2078 voice problems 2222, 2224-5 Lee Silverman Voice Program 2225 parosmia (dysosmia) 1 664, 1 666-7 parotid duct 1 807-8, 1 854 imaging 1 87 1-2, 1 872 F, 1 873 F ligation, drooling 789 parotidectomy 409 1 conservative see conservative parotidectomy superficial 2484-6, 2485 F parotid glandes) 1 853-4 accessory 1 87 1-2 anatomy 1 807-8, 1 853-4, 1 853 F autonomic nerve supply 1 855, 1 856 benign tumours 2475 blood supply 1 856 capsule 1 854 embryogenesis 1 852 fascia 1 854 HIV patients 245, 245 F imaging 1871 children 1 297 ultrasound 722-3, 723 F, 724 inflammation 724 innervation 1 807-8, 1 856
Pages 1-1 3 1 2 are in Volume 1, pages 1 3 1 3-28 1 0 are in Volume 2, and pages 2 8 1 1-4147 are in Volume 3.
I ndex I 4277
lymphatic drainage 1 856 saliva collection 1 862-3 salivary flow rates 1 807 surgery, facial paralysis and 2808, 3880-1, 3889 children 1058, 1058 F swelling, children 1212 venous drainage 1 856 parotid gland cysts, HIV infection 1246, 1 246 F parotid gland tumours 2503--4, 2504 F, 2525 F adenoid cystic carcinoma 2503-4, 2504 F best clinical practice 2505-6 deep lobe 1 758 F, 2528 surgical treatment 2532 imaging 723, 723 F, 1 883 malignant 2503-4 metastatic disease 250 1-2 molecular biology 2496 mucoepidermoid carcinoma 2503--4, 2504 F parapharyngeal space 2524-5, 2524 F presentation 2476-7, 2477 F sites 1 854 surgery 2483-7, 2503--4 transpharyngeal approach 2486-7, 2487 symptoms 2503-4 treatment 2483-7 parotid haemangioma 1247, 1247 F, 1248 F parotid space 1 757, 1758 F, 1806, 2 1 10, 2 1 1 0 T, 3905 F, 3908, 3908 F parotitis acute see mumps bacterial 1 2 1 2 paroxysmal hemicrania 1723 pars flaccida 3 1 08 otoscopy 3 3 1 5-6, 3 3 1 5 F retractions 3417 F examination 3427 stage one 3417, 34 1 8 F stage two 3417, 3418 F stage three 3417, 3418 F stage four 3418 F stage four 3417 pars intermedia, pituitary gland 295 pars tensa anatomy 3 108 atrophy, childhood 90 1 , 93 1 F, 94 1-7, 942 F classification 942-3 definitions 942-3
epidemiology 943 investigations 945 management 945 natural history 943-4, 943 T pathology 941-2 signs 944-5 surgical intervention 945-6 symptoms 944 ventilation tubes 892 chalk patch 33 1 5-6, 3 3 1 6 F cholesteatoma 3433 examination 3 3 1 5-6, 3 3 1 5 F retractions children 901 examination 3427 management 945 otoscopic diagnosis 3416-7, 34 1 7 F, skin 3 107 subdivisions 3412-3, 3412 F, 3413 F pars tuberalis 296 partial anosmia 1664 partial chromosome deletions 792 partial cricotracheal resection (PCTR) 1 1 39, 2282, 2282 F partial laryngectomy, laryngeal tumours 26 12-5 complications 26 1 5 vertical procedures 26 13 partial ossicular replacement prosthesis (PORP) ear reconstruction 983--4 HDPE implants 1 2 1 Soundbridge device and 3662 partial submucosal cricoidectomy, intractable aspiration 2 1 0 1 particulate embolic agents 733 parvalbumin 3237 Passavant's ridge 2 1 1 1-2 Pasteurella multocida 1465 pastilles 448 paternalism consultation style 560, 560 F, 562, 563, 582 ethical issues 586 evidence-based medicine influence 562 Paterson-Brown Kelly syndrome 2353 pathologic reflux (definition) 1272 pathology services, medical negligence 2807 patient administration systems, cancer data collection 2373 Patient Advice and Liaison Services (PALS) 574
patient-based outcomes research see outcomes research patient controlled analgesia (PCA) 463 patient information medical negligence 3089 nasal endoscopy 1 347 patient preparation, surgery 457-66 ambulatory case suitability 457-8 cardiovascular disease 458-60, 459 T communication, loss 464 consent 46 1-2 day case suitability 457 T explanations 46 1-2 hypertension 459 latex allergy 464-5 medications 465 National Institute for Clinical Excellence guidelines 46 1 , 46 1 T, 462 T nutrition 464 on day of surgery 465 oral intake 465 pathway 457-8 postoperative care planning 464-5 preoperative assessment/tests 458-60, 460-1 previous problems 458 risk indices 459 special requirements 464 theatre planning 464-5 patient recall, information 563 Patient's Charter 582, 590 patient's rights 582, 609 pattern-recognition molecules 1 33 pattern recognition tests, central auditory dysfunction 3858-9 Patterson-Brown-Kelly syndrome 2027 F, 203 1 , 2634-5 PDGFR, tumour marker 2384 peak inspiratory flow (PIFR) 1 375 peak nasal flow 1 375 peak velocity, sound 3 1 74 pectoralis major flap 2855-8, 2856 F, 2858 F modifications 2857 technique 285 1-3, 2856-8 pectoralis minor facial reanimation 3080-1, 308 1 F insertion 308 1-2, 308 1 F pedicled flaps, head and neck surgery 2847-66 advantages/ disadvantages 2848 T axial flaps see axial flaps Gillies principles 2847
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4278 • I ndex
pedicled flaps, head and neck surgery
(continued ) types 2847-8
see also individual types pedigree analysis 1 8-9 peduncular infarct, vestibular schwannoma 3977, 3977 F project 2626, 2627-8, 2630 peg-shaped teeth 1 8 1 7, 1 8 1 8 F pegvisomant 4101 flaps 2876-83 pemphigoid dysphagia 2032 nasal 1 7 1 5 pemphigus 1 7 1 oral manifestations 1 834-5, 1 834 F pemphigus vulgaris (PV) 1 834 pencil tip sign, croup 1 128, 1 128 F Pendleton's model, doctor-patient relationship 563 Pendred's syndrome 330, 400, 8 1 3 T, 849, 2667-8 pendular nystagmus 3725, 3725 F treatment 3804-5, 3804 T pendulum model, semicircular canal 321 1 penetrating wounds, laryngeal 227 1-2 penicillin(s) 229-30 absorption 229-30 allergic reactions 230 indications 230 mechanisms of action 43 1 natural 230 parapharyngeal abscess 1 999 penicillinase-resistant 230 pharyngitis 1985 resistance 2 30, 235 rheumatic heart disease prevention 1986 side effects 230 syphilis 1462, 2008 penicillinase-resistant penicillins 230 pentoxifyllin 1, 3588 peptic granuloma see arytenoid granulo ma percentage irregularity score, voice evaluation 2 179 perceptual tests, vestibular function 3737-40 perceptual voice evaluation 2 1 7 1 , 2 174-6, 2 1 75 T harmonics-to-noise ratio and 2 18 1 perchlorate discharge test 1299-300,
1 300 F
percutaneous endoscopic gastrostomy 2097 percutaneous endoscopic jejunostomy 2097 percutaneous fluoroscopic gastrostomy (PFG ) , dysphagia 279 1 percutaneous tracheostomy 2295 complications 2295 rate 2297 dilatational technique 2295 open surgical vs. 2297-8 time intubated 2293-4 percutaneous tumour embolization 734-5 perennial intrinsic rhinitis see nonallergic rhinitis with eosinophilia syndrome (NARES) perennial nonallergic noninfectious rhinitis see rhinitis, idiopathic perfluorocarbons (PFC) 263 performance test, hearing 839-40 method 839-40, 840 F stimulus 840 F perfusion functional magnetic resonance imaging 677, 677 F perfusion monitoring 529 periapical abscess see dental abscess periapical cyst 1 8 1 7 periapical osseous (cemental) dysplasia 1930 periaqueductal grey matter (PAG ) , phonation 2 158 perichondritis external ear 3 358-6 1 , 3359 F aetiology 3358 classification 3358 complications 3359 definition 3358 diagnosis 3359 differential diagnosis 3359 management 3359-60 pathology 3358-9 prevention 3359 trauma-induced 3358 treatment resistant cases 3 359-60 tracheostomy 2302 perichondrium, tracheal cartilage 2 1 4 1-2 pericoronitis 1 805, 1 8 2 1 pericyte-endothelial cell interactions, angiogenesis 93 periglottic obstruction 481-2 anaesthesia depth 481 peri-implant infections 2920
peri-implant mucosal inflammation 2920 F peri-implant sulcus 2906-7 perilabyrinthitis 923 perilingual deafness, cochlear implantation 861 perilymph absorption 3 1 87 composition 3 188-9, 3 1 89 T electric potential 3 1 88-9 formation 3 1 87 perilymphatic fistulae children 1047 audiograms 1047 congenital 874 diagnosis 1047, 3764 post-stapes surgery 3476 traumatic 3507-10 children 1047 diagnosis 3507-8 differential diagnosis 3508, 3508 T investigations 3509 management 3507-8 surgery 3 5 1 0-1 symptom onset 3508 treatment options 3509 tympanic membrane examination 3508 perilymphatic space, cochlea 3 1 86, 3 186 F perinatal anoxia, bilirubin encephalopathy 3845-6 perinatal trauma, facial paralysis 1 057 periodic alternating nystagmus 3804, 3804 T periodic complex tones 3 246 periodic limb movement disorder (PLMD) 2310 periodic pain, cancer 2784-5 periodic sound analysis 3252-3 periodic sound signal 2 1 65 periodontal breakdown 1 8 19 periodontal disorders 1 820-2 periodontitis accelerated 1 8 1 9 chronic 1 8 1 9 T, 1 820, 1 82 1 F management 1 82 1 tooth loosening 1 820 HIV patients 243 peri olivary nuclei 3 14 1-2 perioral flare reaction 1424-5 periorbital cellulitis 1087-8 periosteal abscess, childhood sinusitis 1087-8
Pages 1-1 3 12 are in Volume 1, pages 1 3 1 3-28 1 0 are in Volume 2, and pages 2 8 1 1-4147 are in Volume 3.
m
I n dex I 4279
periosteal stem cells 74 periosteal tunnel creation, deviated nose 2990 peripheral nerve disease sensory ataxia 3778, 3780
see also specific disorders peripheral nerve fibres, degrees of injury 3873-4, 3874 F peripheral nerve stimulator 494-5, 495 F peripheral neuropathy auditory neuropathy! dyssynchrony and 3848-9 diabetes mellitus 402 posturography 3735 pel:lpJler;ai nystagmus, cental vs. 3724 T disordered, post-oesophageal atresia 1287 peristomal granulations, tracheostomy induced 1203 peritonsillar abscess (quinsy) 1 222-3, 1996-8 abscess tonsillectomy 1 998 bacteriology 1 996-7 clinical features 1 222, 1 222 F, 1997 complications 1998 differential diagnosis 1997 dysphagia 2030, 2030 F epidemiology 1996 investigation 1 997 management 1989 outpatient management 1997-8 tonsillectomy 1 222-3, 1998 treatment 1997-8 children 1997-8 knife drainage 1 998 needle aspiration 1 998 peritonsillar space 1744, 1 807 perivertebral space 1 758 permanent balloon occlusion internal carotid artery 395 1 , 3952 F stroke risk 395 1 permanent childhood hearing impairment (PCHI) causes 845-9, 845 T epidemiology 844-5 illness, due to 849 meningitis 847 presentation 848-9 see also childhood deafness permanent threshold shift (PTS) 3298, 3548 permanent tracheostomy 2293
pernicious anaemia 269 perniosis (chilblains) 1 7 1 5 perpendicular plate, ethmoid bone 3897 per protocol analysis 629 persistent acute otitis media 9 1 3 persistent generalized lymphadenopathy see HIV lymphadenopathy persistent rhinosinusitis (PRS) see chronic rhinosinusitis persistent stapedial artery 873 F, 3473-4 persistent vegetative state (PVS) 588 personal databases, cancer data collection 2373 person -centred counselling, tinnitus 36 14 salivary gland pertechnetate uptake 1 878 pertussis (whooping cough) 2252 causative organism 200 clinical features 2252 incidence 2252 investigations 2252 management 2252 pathophysiology 2252 vaccination 2252 pertussis toxin 200 perverted nystagmus 3729 pes anserinus minor 1325 petechiae, oral 1 822 petroclival lesions 3690 F middle fossa surgery 4024 petroleum jelly, epistaxis 1 066 petromastoid 3 1 24 petrosal bone, vestibular schwannoma invasion 3959-60 petrosal vein injury, surgical 3978 petrosectomy petrous apex lesions 405 1 temporal bone post-resection reconstruction 4093 petrositis, chronic otitis media 923, 3404, 3404 F petrosphenoccipital suture of Gruber 4026-7 petrosquamous fissure 3900 petrotympanic fissure 3900 petrotympanic ·fissure of Glaser 3904 petrous apex anatomy 4046-7, 4046 F cysts 4047, 405 1 F erosion, otalgia 3528 infection 4047 lesions 4046-53 complications '4052
investigations 4048-9 management 4050-2 resection 4051-2 pneumatization 4046-7 surgical approaches 4050-2 tumours 4047-8 resection 405 1 petrous apex chondrosarcoma 4024, 4024 F petrous apex mucosal cyst 4047, 405 1 F petrous apicectomy 4024 Peutz-Jegher's syndrome 1 823 Pfeifer's classification, cleft lip! palate 996, 997 F Pfeiffer syndrome 8 1 3 T, 1 027 Pfu polymerase 7 Phadiatop test 1 394 phaeochromocytomas 2526-7, 2671 phage-clone technique, metastases detection 27 1 5 phagocyte disorders 1 77-8, 1 77 T
see also individual disorders phagocytosis 1 39-40 phagocytosis and killing test 1 69 phalangeal cells 3 13 0 inner 3 1 36 outer see Deiters' cells phantogeusia 1 843 phantom taste, chorda tympani nerve injury 1 844 phantom tooth pain 1 72 1 phantosmia 1 664, 1 666-7, 3 9 1 3-4 pharmacodynamics 409, 41 1-2 corticosteroids 4 1 8 dose-related adverse reactions 415 pharmacogenetics 409, 4 1 2 pharmacokinetics 409, 409-10, 409 F antimicrobials 229-34 dose-related adverse reactions 4 1 5 pharyngeal arches see branchial arch( es) pharyngeal area, lateral skull base 3900-1 pharyngeal clefts 797, 8 1 3-4, 1942 pharyngeal diverticulum 797 bodies pharyngeal children 1 187 dysphagia aetiology 2034 pharyngeal hypophysis 2 1 1 7-9 pharyngeal infection(s) 198 1-2024 acute see pharyngitis, acute blood diseases 20 1 5 chronic nonspecific 2006-7 2007- 1 5
Pages 1-1 3 1 2 are in Volume 1 , pages 1 3 1 3-28 1 0 are i n Volume 2, and pages 2 8 1 1-4147 are i n Volume 3 .
4280 I I n dex
pharyngeal infection(s) (continued) lymphoid tissue hyperplasia 2013 viral 2002-5
see also specific infection/disease pharyngeal injuries 1 770 pharyngeal mucosal space (PMS) 1 756-7, 1 757 F, 2 1 09, 2 1 10 T pharyngeal neoplasms 201 3-4 pharyngeal nerve 2 1 56, 2 1 57 F pharyngeal pituitary 295 pharyngeal plexus nervous 1947, 1950, 2075, 2 1 14, 2 1 56 venous 1951 pharyngeal pouch 2043-61 aetiology 2045-7, 2046 F cricopharyngeus muscle spasm 2046 incoordination theories 2046-7 Killian's dehiscence 2045-6, 2046 F definition 2043 diagnosis 2026, 2027 F, 2044 differential diagnosis 2044 dysphagia 2034, 2034-5, 2044 incidence 2043-4 management 2048 pathology 2047-8 regurgitation 2044 surgery see pharyngeal pouch surgery symptoms 2044, 2044 F pharyngeal pouch (embryonic) 796-7, 797 F, 1942 derivatives 796 T, 1 943 T first 1 943 T fourth 368, 1 943 T second 1 943 T third 367-8, 1943 T pharyngeal pouch carcinoma 2047-8, 2728 barium studies 2048, 2728 post-surgery 2048, 2058 pharyngeal pouch surgery 2048 access problems 2050, 2050 F, 2052, 2053 F CO2 laser technique 2054, 2058, 2058 T cricopharyngeal myotomy procedure 2049, 2054, 2059 endoscopic see endoscopic stapling, pharyngeal pouch historical aspects 2048-9 outcome studies 2055-9, 2056, 2058 T postoperative care 2054 pouch excision 2054-5, 2055-8, 2056, 2058 T pouch inversion 2055-8, 2055, 2056
pharyngeal recess (fossa of Rosenmiiller) 1094, 1944, 3900-1 nasopharyngeal carcinoma 2454-5, 2454 F, 3900-1 pharyngeal reconstruction 2886 issues 2886 options 2886 problems 2886 pharyngeal resection, hypopharyngeal cancer 2648 pharyngeal space, swallowing 1957 pharyngeal stenosis 2014 causes 2014 T surgery-related 2809 treatment 2014 pharyngeal tubercle 3899 pharyngeal tumours barium swallow appearance 2027 F posterior wall 2589-90 radical neck dissection 2743 staging 2364-5 pharyngitis, acute 1982-7 aetiology 1982-3 antibiotics 1984-5 cross infection prevention 1 986 recurrent infections 1985 suppurative complication prevention 1986 symptom relief 1 986 USA choice 1986 bacterial pathogens 1982-3 see also Group A beta-haemolytic streptococci (GABHS) carrier state 1987 children 1 982-3 clinical findings 1983-4 complications 1986-7 corticosteroids 422, 1 984 definition 1982 differential diagnosis 1984 dysphagia 2030 epidemiology 1 982 hospital admission 1986 investigations 1984 pathophysiology 1983 prognosis 1987 treatment 1984-6 costs 1 982 viral 205 T, 1 983 pharyngobasilar fascia 1 947, 2 1 1 1 , 2 1 1 1 F, 2 1 1 2 F, 3898 F, 3900, 3901 pharyngocutaneous fistula repair 2862 F pharyngolaryngectomy, hypopharyngeal cancer 2648-9
pharyngolaryngooesphagectomy (total) hypopharyngeal cancer 2649 oesophageal cancer 2649 pharyngomaxillary space see parapharyngeal space pharyngo-oesophageal (PE) segment 2227 Pharyngoplasty complications 1 0 1 1-3 velopharyngeal insufficiency 1 0 1 1 , lO12 F Pharyngoscopy dysphagia investigations 2028 globus 2039-40 pharyngeal injuries 1 770 pharyngotomy, hypopharyngeal stenosis 2635 pharyngotonsillitis, infectious mononucleosis 1225 pharynx 1 942-53 anatomy 1944-5 1, 1 944 F blood supply 195 1 embryology 1 942-3 HIV associated lesions 243-4 hypopharynx see hypopharynx innervation 1950-1, 2074-5, 2075 F afferent fibres 2074-5 Kaposi's sarcoma 244 lymphatic drainage 1951 lymphoid tissue 1951 muscles 1945 F, 1 946 T, 1 947, 1948 T, 1949 F, 1 950, 1955 nasopharynx see nasopharynx neurodevelopmental disorders 2080-1 neurological disease/ disorders 2074-83 ageing 2076 causes 2077 T clinical presentation 2076, 2077 T cranial nerve neuropathies 2080, 2080 T demyelinating disorders 2078 incidence 2075 management 208 1-2 movement disorders 2077 T, 2078 myogenic disorders 2076-8, 2077 T patient examination 2076 patient history 2076 peripheral nerve lesions 2080 physiology 2075-6 stroke 2077-8 surgery 208 1 systemic infection 2077 T, 2078-9 see also dysphagia; specific disorders oropharynx see oropharynx
Pages 1-1 3 12 are in Volume 1, pages 1 3 1 3-28 10 are in Volume 2, and pages 28 1 1-4 147 are in Volume 3.
I ndex . 428 1
paediatric consultation 778-9 peristasis 1958 relations 1947-50 structure piercing 1949-50 rheumatological diseases 1 84 swallowing 1955 vasculature 1951 venous drainage 1951 vesicular/bullous eruptions 2005 wall 1947, 1955 buccopharyngeal fascia 1947 mucous membrane 1947 pharyngobasilar fascia 1947 phase (definition) 32 12 phase angle 3 160, 3 160 F phase coherence 3288 phase dispersion optical coherence tomography 759 phase-specific chemotherapy 37 'phenomenon of the missing fundamental' 3252-3 phenothiazines dysphagia 2789-90 salivary flow 1861 vertigo, children 1049 vestibular attacks, acute 3795 phenotype 18-9 phenylephrine, effects on cilia 1361 phenytoin adverse reactions 415 glossopharyngeal neuralgia 353 1-2 pheromones 1368 Phi 2944, 2944 F, 2945 philtrum 1793 pH monitoring gastrointestinal evaluation, laryngeal stenosis 1 1 54 globus pharyngeus 2038 phon 3250-1 phonation 992-3, 2 1 70-1 biomechanics 2 159-6 1 vibratory cycle 2 1 60-1 voice initiation 2 160 involuntary 2 1 58 neuroanatomy 2 1 58-9 prephonatory inspiratory phase 2 160 reflex control 2 1 59 vegetative 2 1 58 see also speech; vocal fold(s); voice phonation quotient 2 1 82 phonation stage, speech and language development 990-1 phonation threshold pressure 2 160, 2 1 82 phonemes 3267
phonetograms 2 1 79 phonosurgery 2234-47, 2 1 95-6 anaesthesia 2236 anterior webs 2237 best clinical practice 2238-9 electrode pacing 2 196 granulomas 2238 intracordal cysts 2237 laryngeal framework 2 1 96 laryngeal injection 2 1 95 laser, microsurgical instrumentation, vs. 2236 micro deb rider 2236 microlaryngoscopic see microlaryngoscopy nerve-muscle pedicle graft 2 196 nodules 2236-7 papillomas 2238 pathology 2236-8 polyps 2237 professional voice 22 13 Reinke's oedema 2237, 2239 reinnervation 2 1 96, 2244, 2245 T laryngeal neuromuscular physiology 2244 surgical techniques 2234 ventilation 2236 vocal sulcus 2238 voice rest 2236 phosphate homeostasis biochemical analysis 380-1, 381 T creatine clearance 380-1 parathyroid function and 379 renal tubular absorption and 380 phospholipase C, saliva 1 860 photoablative reactions, laser therapy 743 photoageing 3069 photochemical reactions, laser therapy 743 photodynamic therapy (PDT) 745-6 clinical reports 746 drug uptake period (drug-light interval) 746 head and neck cancer 746 juvenile-onset recurrent respiratory papillomatosis 1 1 77 lip cancer 2548-9, 2548 F nasopharyngeal carcinoma 2467 photosensitizer 745-6 principles 745-6 singlet oxygen 745-6 photographs, facial assessment 2946-7 photons 47, 742
photosensitivity, antimicrobialinduced 236 photosensitizer 745-6 pH probe study, stridor 1 1 1 9 phrenic nerve 1752 physiologic reflux 1272 pial sheath, optic nerve 3914 Pierre Robin sequence 1000-1, 100 1 F, 1 109, 2 1 5 1 pig bronchus 1 147 pigmented basal cell carcinoma 2397 pillar cells 3 1 30, 3 1 3 1 F, 3 1 36, 3 1 37 F inner 3 1 3 1 F, 3 1 36 microtubular bundles 3 1 36 outer 3 1 3 1 F, 3 1 36 pillars of the fauces 1793 pilocarpine nasal vasculature, effects on 1365 salivary gland stimulation 1 862 Sjogren syndrome 1912 taste abnormalities 1 848 xerostomia 4 14, 1908-9 pinch grafts 2825 pinch test 2829-30 pineal tumours 392 1 pink noise therapy, hyperacusis 3596 pinna anatomy 3 105-6, 3 105 F, 3312 F clinical examination 33 1 1 congenital abnormalities 3643 development 808, 808 F, 965-6, 3 122 disorders, classification 332 1·-2 grafting, augmentation rhinoplasty 2973 infant 808 F Kaposi's sarcoma 240 keloid removal 2893 non-Hodgkin's lymphoma 3359 perichondritis see perichondritis, external ear reconstruction see pinna reconstruction removal, temporal bone squamous cell carcinoma 409 1-2, 4092 sensory innervation 3 1 06, 3 106 T sound localization 3 1 79, 3255 pinna carcinoma 250 1-2 pinnaplasty cartilage scoring technique 3092 haemostasis 3092 medical negligence 3092 Mustarde technique 3092 pinna reconstruction 3028-47 autogenous vs. prosthetic 3045 bone-anchored prosthesis 3044
Pages 1-1 3 1 2 are in Volume 1, pages 1 3 1 3-28 1 0 are in Volume 2, and pages 28 1 1-4 147 are in Volume 3.
4282 I I ndex
pinna reconstruction (continued) burns 3032-3, 3033 F cancer resection 3028-32 case study 2940 complications 3033, 3044-5 costal cartilage 3029 F, 3030 F framework assembly 3035-9, 3038 F bilateral ear loss 3035-6 free flaps 3044 hair problems 3045 implant retention 2932 infection 3033, 3044 local flaps 3039-40, 3040 F projection 3039 F radiotherapy 3045 release 3039 scalp dissection 3044 silicone drains 3039 skin cover 3039, 3039-44 skin loss 3044 smoking and 3044 squamous cell carcinoma 2926 F suture extrusion 3045, 3047 F techniques 3033-44 temporoparietal fascia 3042-4 tissue expanders 303 1 F, 3040-1, 3041 F piperazines 3795 piribedil 3604-5 piriform cortex 1663 piriform fossa 1 945, 2638 cancer/carcinoma 2639 F, 2644 F complications 2655 cricoarytenoid joint invasion 2638-9, 2639 F epidemiology 2634-5 neck node metastases 264 1 pitch 2 165 changes, children 1 1 68 definition 3252 disorders 2226-7
see also specific disorders harmonic spacing 3253 range, paralinguistic features 2 168 sound wave frequency 3 1 75 vocal 2217 voice perception 2 1 74 pitch perception 3252-3 cochlear hearing loss 3256 complex tones 3252-3, 3253 F place theory 3252 pure tones 3252 temporal theory 3252 pitch perturbation ('jitter') 2 1 65, 2 1 79 pitch registers see vocal registers
Pittsburgh algorithm 888, 889 T Pittsburgh staging, temporal bone squamous cell carcinoma 4090-1, 409 1 T, 4095, 4095 T pituitary adenomas 399 F acromegaly 399 appearance 41 10 asymptomatic 304 biochemical investigations 308-12 extension pathways 399 functioning 304, 4098, 4099, 4100-3 follow-up 4 1 1 3 tests 3 12 haemorrhage 4100 incidence 304 malignant transformation 4104 mesoadenomas 4099 nonfunctioning 308, 3 1 1-2, 4099, 4103, 4 1 1 3 children 3 1 1 follow-up scans 4103, 4 1 1 3 identification 3 1 1 tumour locations 399
see also specific types pituitary apoplexy 4100 pituitary fossa anterior wall 299, 303 boundaries 303 floor 303 lining 298 relations 299, 299-300 lateral 299, 303 posterior 299 superior 299, 304 tumour expansion 4099 pituitary gland anatomy 295-302, 296 F imaging-related 303-4 anterior see adenohypophysis blood supply 297, 297 F, 307 capsule 297 development 295, 296 F, 2 1 1 7-9, 2 1 18 F disease 399 function tests 303-13 postoperative 3 1 2 hypothalamic hormones, effects of 300 imaging 303-13 related anatomy 303-4 normal appearance 4 1 1 0 pharyngeal 295, 2 1 1 7-9 physiology 300-2 functional test-related 307-8 posterior see neurohypophysis
Rathke's pouch cysts 4103 tumours see pituitary tumours venous drainage 297, 307 pituitary gland macroadenomas 4099 pituitary infarction 4100 pituitary macro adenoma 304-5, 304 F biochemical investigations 308 definition 304-5 haemorrhage 305, 305 F imaging 306 post-surgical imaging 306 visual field assessment 3 1 2 pituitary micro adenomas 304, 4099 definition 304 digital subtraction angiography 306-7 endocrine assessment 306-7 pituitary stalk see infundibulum, pituitary gland pituitary tumours adenomas see pituitary adenomas chordomas 4 1 04 classification 4098-9 functional 4098-9 histological 4098 size 4099 clinical features 4099-103 endocrine effects 4099 infarction 4100 visual defects 4099 craniopharyngiomas 4103-4 current knowledge/future research 4 1 1 6 epidemiology 4099 gliomas 4 104 imaging 304-5 extrinsic abnormalities 304-5, 304 F intrinsic abnormalities 304, 304 F lateral extension 304 F, 305 post-surgical 306-7 superior extension 304, 304 F, 305 F technological advances 307 malignant 4104 management 4098-1 1 8 adrenal resection 4102 recurrence after 4 1 1 3 surgical resection see hypophysectomy
see also specific treatments Rathke's pouch cysts 4 103 secondary (metastatic) 4 1 04 space-occupying effects 4099-100 inferior expansion 4100 lateral expansion 4100 superior expansion 4099-100
Pages 1-1 3 12 are in Volume 1, pages 1 3 1 3-28 1 0 are in Volume 2, and pages 281 1-4147 are in Volume 3 .
I ndex I 4283
visual field assessment 3 1 2
see also specific sites/tumours
plasma imbibition, nasal reconstruction 3017
pityriasis versicolour 1 7 1 5
plasma products, fractionated 260
Pityrosporum ovale 1 7 1 5
plasma viscosity 267
pivot principle 2832-40
plasmid DNA 26
local flaps 2827-8
plasmin 279
transposition flaps 2834-40, 2840 F
plasminogen 279
pizotifen 3 803 T, 3804 placebos 629, 658-9 research use, ethics 589 place coding, frequency selectivity 3 197-8 place theory, pitch perception 3252 placodal competence 8 1 5 plain radiography adult epiglottitis 2250, 2250 F airway management 470 aspiration 2096
reduced platelet production 287 sepsis 259 surgical prophylaxis 259 thrombocytopaenia 259 platinum agents, chemotherapeutic 37 platysma flap 2865, 2865 F
plasminogen activator inhibitor type 1 (PAl- I ) 279
platysmaplasty 3070-1 play therapy 1 30 1 pleasure calculus 584
plasticity, vestibular compensation 3792
pleomorphic adenoma
Plastipore 1 2 1
external auditory canal 4070
plateau-seeking method, pure-tone
salivary glands see pleomorphic
audiometry 3264
salivary adenoma (PSA)
platelet ( s)
pleomorphic adenoma gene I -related
adhesion 278
protein 2503
aggl:egation 278
pleomorphic salivary adenoma (PSA) 2480-2
thrombotic thrombocytopaenia 286
capsule 248 1
bronchial stenosis 1 143
antibody sensitization 287
children 1296
collection 259
categorization 248 1
craniosynostosis 1 022, 1023 F
disorders see platelet disorders
cells 2482 children 1248, 1248 F
cartilage 2482
croup 1 128, 1 128 F
haemostasis 278
dysphagia 2028
lifespan 278
clinical features 248 1 , 248 1 F
epidermoids 40 1 1
sequestration 278
epidemiology 2476
frontal sinus 1501 head and neck sarcoma follow-up
1938
storage 259
fine needle cytology 2480 F
platelet count 280
historical aspects 2480-1 , 248 1 F
heparin monitoring 447
juvenile angiofibroma 2438-9, 2438 F
normal range 280
laryngeal trauma 2273 mandibular tumours 2558
platelet-derived growth factor
meningiomas 4009
platelet disorders 275-6, 281 T
(PDGF) 89
imaging 723, 723 F, 1 882, 1 885 F, 1 886 recurrent lesions 1 883 postoperative follow-up 2490 presentation 2477 F, 2478 F recurrent 2482, 2482 F, 2489-90
nasal fractures 1 6 1 2
acquired 286-8
management 2489-90
nasopalatine duct cyst 1926
bleeding patterns 2 8 1
revision parotidectomy 2489-90,
neck trauma 1 767
diagnostic tests 281-2
obstructive sleep apnoea 1 107-8,
increased consumption!
1 108 F
destruction 286-7
oesophageal atresia 1 284 F, 1285 F,
1288
inherited 288
raised intracranial pressure, 'copper beaten' appearance 1024 F
plica fimbriata 1 794 plicatic acid 1419
treatment 288
Paget's disease 3488
2490 F stroma 248 1-2
plosion noise 2 167
reduced production 287 treatment 287
plosives 2 167, 2 167 T Plummer's disease see toxic adenoma
platelet dysfunction 287-8
. Plummer-Vincent syndrome 2027 F,
rhinosinusitis 1442
drug-induced 287
salivary glands 1 877-8
extracorporeal circuit -induced 287-8
plunging ranula 1 246
renal failure 288
pluripotency, stem cells 68 pneumatic dilatation, achalasia 1289-90 pneumocephalus 4 139
malignant tumours 2506-7 sarcoidosis 1 649 F, 1 7 1 1
203 1, 2634-5
platelet factor 4
89
thyroid nodule evaluation 2676-8
platelet plug 278
tuberculous otitis 3449
platelet-rich
Wegener's granulomatosis 1 649 F
platelet transfusion 259-60
plaque accumulation, oral implants 2906-7 definition 1699-700 plasma cell dyscrasias 275 plasmacytomas extramedullary 275 1"'\1t111t,, 1""
region 4 1 04
(PRP) 2920
pneumococcal meningitis 197-8 pneumococci 1 97-8
complications 262
pneumococcus vaccination 3654
contraindications 259-60
Pneumocystis carinii, HlV patients
cross-reactivity 262
external ear infections 240
disseminated intravascular
neck manifestations 246
coagulation 259, 284 indications 259 liver disease 282 "
pneumolarynx 2230 pneumomediastinum, paediatric tracheostomy 1202-3
Pages 1-1 3 1 2 are in Volume I, pages 1 3 1 3-28 1 0 are in Volume 2, and pages 2 8 1 1-4147 are in Volume 3.
4284 1 I n d ex
pneumonia aspiration 1284, 2085 viral agents 205 T pneumoparotitis 1 908 pneumosialadenitis 1908 pneumotachograph 2 1 8 1 pneumothorax paediatric tracheostomy 1202-3 radical neck dissection complications 2744 Pneumovax 1084 Poiseuilles' law 1 1 1 , 3007 polarization-sensitive optical coherence tomography (PS-OCT) 757-9 advantages/potential applications 758 principles 756, 758 vocal folds 758, 759 F poliomyelitis aetiology 2078-9 pharyngeal dysfunction 2078-9 pollens avoidance 1 397 oral allergy syndrome 1428 seasonal rhinitis 1396 pollution, rhinitis and 1 3 83 allergic 1 3 88 nonallergic 141 1 pollybeak deformity 2982, 2983 F medical negligence 3092 post-nasal tip surgery 3004 predisposing factors 2982 F polyacrylamide gels, electrophoresis 5-6 polyamide mesh, augmentation rhinoplasty 2973-4 polychondritis relapsing see relapsing polychondritis septal perforations 1 584 polyclonal antibodies, Paget's disease 3486 polycythaemia 272 absolute 272 causes 272 T investigations 272 relative 272 polycythaemia rubra vera (PRV) 272 polydioxanone tissue scaffolds 123 polyenes 233, 442 polyethylene glycol (Movicol) 2791 polyglutamine expansion disorders 3773, 3775 polyglycolide (PGA) tissue scaffolds 123 polygons 703, 704, 705 F polyhydramnios, oesophageal atresia 1 284
tissue polylactide-coglycolide scaffolds 123 polylactide (PLA) tissue scaffolds 1 23 polymerase chain reaction (PCR) 7-8, 7F chlamydiae detection 202 parainfluenza virus 207 respiratory tract viral infections 204-5 polymerization 4 polymers 12 1-2 advantages 1 2 1 disadvantages 1 2 1 extrusion rates 1 2 1 nasal reconstruction 1 2 1 nervous tissue engineering 1 26 synthetic 1 2 1 tissue response 1 1 9 tissue scaffolds 123
see also individual types polymorphic marker 19-20 polymorphism 1 6 polymorph leukocytes 1 85 polymorphonuclear leukocytes see neutrophil(s) polymyositis 1 86 polyneuropathy, neurofibromatosis 2 4000 polyotia (mirror ear) 969, 970 F polypectomy cerebrospinal fluid rhinorrhoea aetiology 1 636-7 'medical: nasal polyposis 1 555, 1 556 medical negligence 1 307, 1733 polypeptide synthesis 4 polypoid corditis see Reinke's oedema polypoid degeneration see Reinke's oedema polypoid hypertrophy see Reinke's oedema polypoid vocal cord see Reinke's oedema polyps/polyposis aural see aural polyps choanal 1554 frontal sinus 1 5 1 9 hairy, nasopharynx 2 1 1 9 laryngeal 2265-6 nasal see nasal polyps vocal folds see Reinke's oedema; vocal fold polyps polysomnography obstructive apnoea 1 106, 23 1 8, 2327 sleep disorders, children 1 1 04
snoring 2327 special needs children 787 polytetrafluoroethylene (PTPE) augmentation rhinoplasty 2974 facial reconstruction 1 2 1 vascular surgery 1 2 1 polye ethylmethacrylate) / tetrahydrofurfuryl methacrylate (PEMNTHPMA) 125 polyurethane foam dressings 2794 polyvinyl alcohol (PVA) 733, 3952 pons, vascular syndromes 3922 pontine cistern, vestibular schwannoma expansion 3958-9, 3958 F, 3959 pontine disorders 3922 pontine lesions 3922 pontine tegmentum injury 1 847 pores, tongue 3929 porokeratosis 2398 'port-wine stains' 1708 positional cloning 1 1 , 19-20 positional manoeuvres, balance disorders 3720-3, 3721 F positional plagiocephaly 1026 lambdoid synostosis vs. 1026 F positional cerebellar tumours 3776 presentation 3709 recurrent 3781 repositioning manoeuvres!exercises 3 809-14 treatment 3 809-14 (PVP) position vestibular neurones 3 2 1 5 positive intrathoracic pressure 528 positive predictive value (PPV), difficult airways 47 1 positron emission tomography (PET) 684-700 brain imaging 675 cervical lymph node assessment 1 762, 1 763 F citric acid recognition studies 1 842 2- [ 18 p] fluoro-2-deoxy-D-glucose positron emission tomography see PDG-PET imaging [ 15-0 ] H20 696 hyperparathyroidism 392 recurrent 392 hypopharyngeal cancer 2644 laryngeal tumours 2607-8 nasopharyngeal carcinoma 2457-8
Pages 1-1 3 12 are in Volume 1, pages 1 3 13-28 10 are in Volume 2, and pages 2 8 1 1-4147 are in Volume 3.
neck 1 756 metastatic disease 272 1 oral cavity tumours 2553 paragangliomas 4029 principles 684-6, 685 F standardized uptake value 684-6 skull base lesions 3947 thyroid cancer recurrence detection 2697 tinnitus 3602, 3603 F post-auricular microphones 366 1 post-auricular muscle, electromyograp hic recording 3289-90 postauricular scars, chronic otitis media assessment 3412 posterior alveolar (dental) artery 1 798 posterior auricular nerve 3928 posterior chondrotomy 1 578, 1579 F posterior condylar canal 3899 posterior cranial fossa, vestibular schwannoma surgery 3971 posterior cricoarytenoid 2 136 T posterior dental (alveolar) artery 1 798 posterior ethmoidal artery 1 574, 3897-8 ligation, epistaxis 1 604 posterior fossa malformations 3777, 3777 F, 3780 posterior fossa syndrome 2222-3 posterior fossa tumours 3776-7, 3779-80 definition 3776-7 diagnostic failure 4144
see also specific tumours posterior glottal chink 2 1 60-1 posterior glottic stenosis 228 1-2 aetiology 1 160 children 1 160-1 classification 228 1 management 1 1 6 1 , 2282 posterior nasal fontanelle 1 330 posterior nasal packs, epistaxis 1603 posterior pituitary gland see neurohypophysis posterior skull deformity 1026-7 surgery 1026 posterior superior alveolar (dental) nerve 1 341, 180 1-2 posterior superior dental (alveolar) nerve 1341, 1 80 1-2 posterior synostotic plagiocephaly, true 1022 T posterior triangle 1 742-3, 1743 T lymph nodes 1 747-8 swellings, children 1 2 12
posteroventral cochlear nuclei (PVCN) 3 140 post-exposure tinnitus 3552 post-functional endoscopic sinus surgery (FESS) 1350 postherpetic neuralgia 1 724, 2079 post-intervention sleep study I I I 1 postnasal packing, adenoidectomy 1097 post-nasal space carcinoma, medical negligence 1 73 1 post-partum thyroiditis 358-9 Graves' disease 358 histology 358 iodine uptake 359 management 359 post-post nystagmus 3213-4 post-rotational nystagmus 3729 postseptal orbital cellulitis 1 540 poststyloid parapharyngeal space see carotid sheath post-transcriptional processing see splicing post-transfusion purpura ( PTP) 262, 287 clinical manifestations 287 diagnosis 287 treatment 287 post-translational modification 4, 10 post-traumatic vertigo 1045 post-trematic nerve 3 1 20-1 postural balance examination 3730-2 clinical 3 730-2, 373 1 T postural control ankle strategy 3733 strategy 3733 postural imbalance syndrome 3748, 378 1 aetiology 3773, 3776 cerebellar ataxias 3775 hydrocephalus 3778 orthostatic tremor 3779, 3780 posterior fossa malformations
3777 vestibular schwannoma 3776 postural reflexes, examination 373 1 postural techniques, dysphagia 2086-7 posturography 3732-6 caloric test vs. 3733 clinical usefulness 3736 dynamic 3 732-3 neurological disorders 3735--6 peripheral vestibular disorders 3733-5, 3734 F bilateral 3734-5 psychological unsteadiness 3736
psychophysiological unsteadiness 3736 static 3732-3 vestibular rehabilitation 3736 Poswillo hook 1 629 T, 1 630 potassium cochlea 3 186-7 endolymph 3 1 8 7-8, 3 1 87 T perilymph 3 1 89 T potassi um channels cochlear hair cells 3 193-4, 3 194 F mutations, hearing loss and 3 1 86-7 potassium hydroxide, otomycosis 2 1 4 potassium iodide entomophthoramycosis 2 1 5 thyroidectomy 349-5 1 potential doubling times ( Tpot), tumours 57 Pott's tumour see subperiosteal abscess (Pott's puffy tumour) POU3F4 gene mutations 1 6 power 3 162 definition 3 165 powered microdebrider, juvenile-onset recurrent respiratory papillomatosis 1 176 power issues, medical consultations 560-1 PRAD- l ( parathyroid adenoma- I ) gene 388 Prandtl number 1 356 pRB 2382-3, 2383 F preaponeurotic orbital fat 3050, 3050 F preauricular sinus 970, 970 F, 1 267-8 embryology 1267 presentation 1267 treatment 1267-8 preauricular type D approach 406 1 precedence effect reflections 3255 sound localization 3255 precentral gyrus 2 1 58 predictive value 823 prednisolone Bell's palsy 2 1 0 idiopathic sudden sensorineural hearing loss management 3589 T nasal polyposis 1 555 oesophageal corrosive injury 1 29 1 Sjogren syndrome 1 9 1 3 Wegener's granulomatosis 1 652-3 prednisone rhinosinusitis 1 454 allergic Bell's palsy 424 Meniere's disease 3800
Pages 1-13 1 2 are in Volume 1, pages 1 3 1 3-28 1 0 are in Volume 2, and pages 28 1 1-4 1 47 are in Volume 3.
4286 . I ndex
preepiglottic space 2 1 32 F, 2 1 33, 2 1 38 pregnancy allergic rhinitis 140 1-2 consent issues 60 1 dietary restriction 1426 drug prescribing 4 1 5 foo d allergy prevention 1 426 Graves' disease see Graves' disease head and neck complaints 402-3 hyperthyroidism 358-9 transient 359 hypothyroidism 359-60 adverse effects 359 child defects 359-60 treatment 360 inflammatory gingival hyperplasia 403 nasal mucosal changes 402-3 alkaline phosphatase 403 succinic dehydrogenase 403 nasal obstruction 402-3 post-partum thyroiditis see post-partum thyroiditis prolactin 3 0 1 , 308 radioiodine contraindication 348 rhinitis 1410 rhinorrhoea 402-3 thyroid disease 358-60 thyroxine therapy 357 'pregnancy tumour; gingival 403 Preliminary Proceedings Committee ( PPC) 606 prelingual deafness 566 paediatric cochlear implantation 86 1-2 premature neonates auditory nerve and brainstem evoked potentials 3 284-5 bilirubin encephalopathy 3845-6 tracheostomy 1 195 premaxilla development 803 ossification centres 1 3 1 7 premolars 1 803, 1 803-4 roots 1 803-4 prenatal diagnosis, craniofacial anomalies 102 1 preoperative autologous deposit ( PAD) 262-3 Preoperative Transfusion Study, sickle cell disease 2 7 1 preperiosteal dissection 3060-1 prephonatory inspiratory phase 2 160 prephonatory tuning 2 1 59 pre-proPTH 373-4
presbyacusis/presbycusis see age-related (sensorineural) hearing loss presbydysphagia 2034 presbylaryngis 2205 presbyosmia 1 664 presbyphagia 196 1 preseptal cellulitis, orbital 1540 pressed (strained) voice 2 1 65 pressure therapy, keloids 2893 pressure ulcers 95 F, 97 classification 97, 98 F dressing 100, 102 3 1 34 presyncopal dizziness 3709 pretracheal (visceral) fascia 3 1 6-7, 1743, 2 10 8 pretracheal space 1 74 5 tracheostomy tube displacement 2301 prevalence, (definition) 823, 2344 prevertebral fascia 1743, 2 109 prevertebral muscles 1 74 6 prevertebral space 1 745, 2 1 1 0, 2 1 10 T primary auditory canal cholesteatoma 3342-5 aetiology 3343, 3343 T clinical symptoms/findings 3334 T, 3343 T definition 3342 diagnosis 3343-4 differential diagnosis 3334 T epidemiology 3343 keratosis obturans vs. 3343 T management options 3343 T, 3344 natural history/complications 3344 pathology 3342, 3343 T primary ciliary dyskinesia ( PCD) chronic rhinosinusitis 138 1-2 nasal polyposis 1 5 5 1 paediatric 1 0 8 1 primary endpoint 629-30 primary gingivo-periosteoplasty ( GPP) 1 006 primary hyperparathyroidism (pHPT) 389-95 biochemical investigations 391 clinical features 390-1 gastrointestinal 391 musculoskeletal 390 psychological 391 renal 391 diagnosis 390 familial/hereditary 390 incidence 390 gender differences 390
investigations 391-2 localization studies 39 1-2 management 393-5 metabolic syndrome 391 nonfamiliallsporadic 390 osteoporosis 390 pathology 390 Sestamibi scintiscan 391 surgery asymptomatic patients 393 indications 392-3 strategies 393-5 symptomatic patients 392-3 see also parathyroidectomy venous sampling 392 primary immunodeficiency see immunodeficiency, primary primary lateral sclerosis (PLS) 2079-80 primary olfactory cortex 1 367, 39 12-3 primary ossification, skull 794 primary palate 803 primary taste cortex 1842 primitive articulation stage, speech/ language development 990-1 principle-based morality 583-4 principle cells 3 1 6 F, 320, 373-4 principlism 56 1 prion protein PrP 1238 prions blood transfusion 260 variant Creutzfeld-Jakob disease 1 990 proboscis lateralis 1 320 procaine 1, 3588 procaspase 8 58 procaspase 9 58 procerus muscle 1324 processus cochleariformis 3 1 1 1-2, 3 1 1 5 prochlorperazine acute labyrinthine attack 408-9 dysphagia aetiology 2789-90 vertigo 433 vestibular attacks, acute 3795, 3796 T vestibular neuritis 408-9 professional codes of conduct 582 Professional Conduct Committee (PCC) 606 professional voice 2 2 1 1-5 acute illness 2213 classification 22 1 1 confidence ( in diagnosis) 22 1 3 demands 22 1 2 professional versatility 2212 disorders, prevalence 2217-8 environment 2 2 1 2 Lombard effect 2212
Pages 1-1 3 1 2 are in Volume 1, pages 1 3 1 3-28 1 0 are in Volume 2, and pages 281 1-4147 are in Volume 3.
I ndex I 4287
formants 2 1 78 F, 2 1 80, 22 1 1 frequency patterns 22 1 1 humidity 2212 laryngitis, acute 2249 lifestyle 22 12 microphone placement 2212 performance anxiety 22 12-3 personality 221 1-2 supralaryngeal constriction 221 1-2 travel 22 12 upper respiratory tract infection 22 1 3 vocal abuse 221 1-2 vocal physiology 221 1-3 vocal tract configuration 221 1-2 vocal tract surgery 22 13 progesterone respiratory sleep disorders 2308-9 salivary assay 1 867 programme sensitivity 822-3 progressive (solitary) bone cyst 1926-7 progressive bulbar palsy (PBP) 2079-80 progressive hearing loss, childhood 848-9 progressive supranuclear palsy (PSP) 3777-8 progressive systemic sclerosis see scleroderma prokinetics anaesthesia premedication 490 T gastro-oesophageal reflux 1276 prolactin 301 , 308-9 circulating levels 30 1 , 308 effects 30 1 , 308 half-life 301 lactation 301, 308 pituitary adenomas 308 pregnancy 301, 308 secretion 297 control 30 1 , 308 drugs, effects on 301 structure 308 prolactinoma 308-9, 4 1 00 diagnosis 41 00 presentation 41 00 treatment 309, 4100 medical 4 1 00 radiotherapy 4100 surgical 4100, 41 14 proliferating cell nuclear antigen (PCNA), salivary gland tumours 2495 promethazine migrainous vertigo 3801 vestibular attacks, acute 3795, 3796 T proof puncture 1 734 pro-opiomelanocorticotropin 297
propagation velocity 712 propanolol migrainous vertigo 3803-4, 3803 T pre-thyroidectomy 349-5 1 side effects 3803-4 thyrotoxicosis 347 Proplast 121 propofol anaesthesia 490-1 supraglottic obstruction 480 propranolol, effects on cilia 1 36 1 proPTH 373-4 proptosis Graves' disease 400 juvenile angiofibroma 2 1 22 skull base fibrous dysplasia 41 25, 4125 F propylthiouracil (PTU) 346 prospective studies 2344 Prospera 68 prostacyclin analogues, idiopathic sudden sensorineural hearing loss I, 3588 prostacyclin 1Gb compromised skin flaps 1 1 3 prostaglandin analogues 3618 prostaglandin D2 1 390 prostaglandin -E1 1 1 3 prostaglandin E2 1289 prostaglandin 12 278 prostheses children, optimum age for 2927 construction 2930-1 , 2930 F, 293 1 F decision to use 2925 dysphagia management 2088 failure, coagulase-negative staphylococci-induced 196-7 nasal 2909 osseointegration see osseointegration . placement during ablative surgery 2930-1 retention options 2930, 293 1-2 soft-tissue examination 2930
see also individual types prosthetic heart valves, surgical preparation 460 prosthetic nose 2909 protease inhibitors 233, 239 proteasome 44 proteasome inhibitors 44 protein(s) nasal secretions 1 360 synthesis 35 F protein C 279
protein C deficiency 290 warfarin 282 'protein C pathway' 279 protein S 279 protein S deficiency 290 warfarin 282 proteoglycans 2384 osseointegration 2906 proteomics 10 prothrombin (factor II) 279 prothrombin complex concentrate (PCC) liver disease 258 warfarin reversal 258, 283 prothrombin time (PT) 280 anticoagulant monitoring 447 proton pump inhibitors (PP1s) Barrett's oesophagus 2065 gastro-oesophageal reflux 452, 1276, 2063, 2262 laryngitis and 2263 head and neck cancer pain 2785-6 reflux oesophagitis 452 protooncogenes 36 protoporphyrin 269 protozoal infection, nasal 1 703-4 provocation testing 1 60 provoked vertigo syndrome 3748 aetiology 3776 'bow-hunter' syndrome 3767 posterior fossa malformations 3777 subclavian steal syndrome 3767 Provox valve 2625, 2626 F, 2627 pruritus, otomycosis 2 14 psammoma bodies 4008 pseudo allergic drug reactions 414-5 pseudoaneurysms, neck 1 772, 1 773 F, 1 774 F pseudobulbar palsy 3939 dysphagia 2033 pharyngeal manifestations 2077 stroke 2077 voice disorders 2222 pseudo-conjunctivitis 3079 pseudocroup 1 129 pseudo cysts larynx 2 1 99 tonsil 2005-6 vocal folds 2 1 99 pseudoephedrine 3505-6 pseudo-Foster-Kennedy syndrome 1668-9 pseudohump 2952, 2984 F pseudohypoparathyroidism 383
Pages 1-1 3 1 2 are in Volume I, pages 1 3 1 3-28 10 are in Volume 2, and pages 28 1 1-4147 are in Volume 3.
4288 I I ndex
pseudomembranous croup 1 129-30 diagnosis 1 1 29, 1 130 F paediatric intensive care 545 Pseudomonas 200 chronic otitis media 3410 HIV-associated otitis media 240
see also individual species Pseudomonas aeruginosa 200 chronic rhinosinusitis 147 1 cystic fibrosis 1081 diabetes mellitus 402 HIV-associated ear infection 240 malignant otitis externa 3337, 3337-8 otitis externa 3352 diabetes mellitus 402 perichondritis 3358, 3359 skin grafts 282 1-2 tympanic membrane perforation 934 pseudomyxoma see Reinke's oedema pseudomyxomatous laryngitis see Reinke's oedema pseudoptosis 3055 pseudotumour, orbital 39 1 6 pseudowhisper 2624 psoriasis, tonsillitis-related 1 224 psychiatric disorders, olfactory dysfunction 1 669, 1673-4, 391 3-4 psychoacoustic audiometry 3260-75 definition 3260 pure-tone audiometry see pure-tone audiometry tinnitus 3612 psychoacoustic tuning curves (PTC) 3267 psychogenic vertigo, children 1 045 psycholinguistic ability testing, auditory neuropathy! dyssynchrony 3839-40 psychological disorders, tinnitus 3607 psychological issues cochlear implants candidature 365 1 laryngectomy rehabilitation 2630 palliative care see palliative care, head and neck cancer pure-tone audiometry errors 3265 quality of life, head and neck cancer 2777 speech audiometry errors 3273 psychological profiling, tinnitus 3613 psychological tuning curves (P TCs) 3247 determination 3247-8, 3248 F interpretation assumptions 3248 psychosocial issues childhood deafness 849
metastatic neck disease treatment 273 1 post-laryngectomy 2630 psychotherapy, tinnitus 3615 T, 3616 psychotropic drugs, taste abnormalities and 1 847 pterygoid fossa 2 1 1 1 pterygoid fovea 1 809 pterygoid hamulus 1 792 nTPTVU..,lil plates, implant placement 29 1 9 pterygoid plexus, venous 2 1 13, 3902 F, 3907 communicating veins 3907 pterygoid process, sphenoid bone 1 339, 21 1 1 3926 pterygoid pterygomandibular raphe 1 792-3, 1795, 1810 pterygomandibular space 1 806 pterygomaxillary fissure 2 1 1 1 pterygomaxillary space see parapharyngeal space (PPS) pterygopalatine fossa 2 1 1 1 pterygopalatine ganglion 3924 pterygopalatine nervous 1 80 1 , 1 8 0 1 F, 1 950-1 pterygopharyngeal space see parapharyngeal space P TH-receptor gene 389 mutation 3 89 puberphonia 2204-5, 2226 clinical manifestations 2205 speech therapy 2226 treatment 2205 pubertal rhinitis 1077 puberty, voice changes 1 169-70, 2204-5 Public Health Act ( 1984) 587 public health research, epidemiology 6 1 7-8 pulmonary artery catheter (PAC) 529 pulmonary artery sling 1 147, 1 147 F pulmonary artery wedge pressure, perioperative monitoring 500 pulmonary embolism capnograms 499 F treatment 288 pulmonary function tests laryngeal stenosis 2280 stridor 1 1 1 9 pulmonary plexus, nervous 2 1 42 pulmonary toxicity, cystic fibrosis gene therapy 24-5 pulmonary ventilation, bronchoscopy 503
pulpitis 1 8 1 6 pulsatile tinnitus 3944 aetiology 3944 T, 4028 arteriovenous fistulae 4 145 diagnosis delay 4144-5 glomus tumours 40 15 pulsatility index (PI) 7 14 pulsed carbon dioxide lasers basal cell carcinoma 2397 medical negligence 3096 pulsed-dye laser, juvenile-onset recurrent respiratory papillomatosis 1 1 76-7 pulsed-wave Doppler ultrasound 7 1 4 pulse oximetry anaesthesia monitoring 496-7 obstructive sleep apnoea 1 105-6 pulse plethysmography 497 pulse register, vocal 2 1 6 1 , 2 1 62 T pulse transit time, sleep-disordered breathing 1 103 punctum 1 690 pupillary abnormalities 3 9 1 6-7 pupillary escape phenomenon 391 6 pupilloconstriction, Horner's syndrome 3937 pure-tone audiometry 3260-7 active mucosal chronic otitis media 3424 auditory neuropathy! dyssynchrony 3842-3, 3843 F bone conduction 3262 children 840 chronic otitis media healed 3426 inactive mucosal 342 1 clinical applications 3266-7 complete audiograms 3266-7 co nfounding factors!errors 3265-6 bone conduction 3262 methodological 3265 physical!acoustical 3265-6 physiological 3265 psychological 3265 equipment 3261-2 attenuator 3262, 3269 bone vibrator 3262, 3265-6 calibration!verification 3263, 3266 po:tMnhn,np<;! 3262, 3268 PIll1CIJ)lesJ'de�agn 326 1 , 326 1 F tone 3329 granular threshold 3260-1, 3263-4 jugular foramen lesions 4028
1-1312 are in Volume 1, pages 1 3 1 3-28 1 0 are in Volume 2, and pages 28 1 1-4147 are in Volume 3.
I ndex I 4289
masking 3262-3, 3264 noise-induced hearing loss 3552 objective tinnitus 360 1 otosclerosis 346 1 , 3462 F pars tensa retraction 945 purpose/role 326 1 quinine administration 3850, 3850 F screening audiometry 3264-5 skull base lesions 3946 test environment 3263 ambient sound levels 3263, 3263 T, 3266 test method 3263-4 loudness scaling 3267 problems 3265 screening 3265 special tests 3267 tracking method 3264 verbal instruction 3265 test reliability 3266 averaging 3266, 3267 F quantification (test-retest differences) 3266, 3266 F see also speech audiometry purine analogues 38 purpura oral pigmentation 1 825 post-transfusion see post-transfusion purpura (PTP) 'pushing exercises,' vocal fold paralysis 2223 putrescine, malodorous malignant ulcers 2792 'p-value' 623 pyocoele, chronic rhinosinusitis 1 540 pyogenic granuloma 1 708 pyogenic streptococci 1 97 pyorrhoea, chronic periodontitis 1 82 1 pyostomatitis vegetans 1 834 pyramidal tracts, phonation 2 1 58-9 pyrazinamide 1460 pyridostygmine 1 9 1 2 pyriform aperture 1 324-5 stenosis 1072-3, 1073 F pyrimidine analogues 38 'Q lOdB' 3 1 98 quality adjusted life year (QALY), cochlear implants 866 quality assurance see clinical governance quality of life asthma 1 564 cancer patients see quality of life, head and neck cancer
cochlear implants 3655, 3656 children 866-7 concepts 2767-71 definition 2767-8 'gap' theory 2767 head and neck cancer 2766-80 alcohol consumption 2776 attitude changes 277 1 characteristics 2767 T, 2768-70 coping skills 2777 cultural, religious and spiritual factors 2769, 2777 demographic characteristics 2776-8 disease site/stage impact �775 historical developments 277 1-2 instruments 277 1-2 measurement 2772 methodological issues 2770-1 performance status 2778 premorbid patient characteristics 2776 psychological factors 2777 sexual functioning 2777 social support 2777-8 terminology 277 1-2 time impact 2769-70, 2775 tobacco 2776 treatment effects 2775-6 laryngectomy rehabilitation 2630 measurement 2767-71 multidimensional 2769 problems associated 2767 subjectivity 2768-9 metastatic neck disease treatment 2730-1 otitis media with effusion 894-5 outcomes research 2770 prosthetic reconstruction 2933 rhinitis 1 564 ventilation tubes 899 vestibular schwannoma removal 3984-5 voice evaluation measures 2 1 7 1 , 2 1 83, 2 1 83 T Quality of Life Instrument for Head and Neck Cancer (QL-H&N) 2774 T Quality of Life Questionnaire for Advanced Head and Neck Cancer (QLQ) 2774 T Quality of Life - Radiation Therapy Instrument Head and Neck Module (QL-RTI/HN) 2774 T quantitative trait loci rQTL) 16
questionnaires head and neck cancer quality of life 2773-4, 2774 T development guidelines 2773 generic vs. diagnosis-specific 2770-1 methodological issues 2770-1 self-administered 2768 terminology 2773 T septal perforations assessment 1 583, 1584 F voice and quality of life 2 1 83, 2 1 83 T
see also specific types quinine ototoxicity 357 1 , 3850 F tinnitus induction 3599-600 quinolone antibiotics 230-1 active mucosal chronic otitis media 3424 adverse effects 230-1 mechanism of action 230-1 quinsy see peritonsillar abscess (quinsy) Quorom statement 650 rabies 2079 rabies encephalomyelitis 2079 radiation cell survival curves 48-9 DNA damage induction 4 1 dose response curves, acute vs. latereacting tissues 48 exposure see fractionation in nose 1 356 protection, paediatric imaging 1 300-1, 1301 T temporal bone tumour induction 4068, 4087 radiation mucositis, HIV patients 243, 244 T radiation therapy see radiotherapy Radiation Therapy Oncology Group 2755 anaemia 2756 radiation thyroiditis 348, 362-3 radical neck dissection 2733-42 accessory nerve identification 2738-9 carotid sheath opening 2736 cervical plexus identification 2739 F, 2740 Chaissaignac's triangle clearance 2737-8 closure 2742 suture placement 2734 combined procedures 2742 complications 2743 accessory nerve division 2744
Pages 1-1 3 1 2 are in Volume 1, pages 1 3 1 3-28 10 are in Volume 2, and pages 2 8 1 1-4147 are in Volume 3.
4290 I I ndex
radical neck dissection (continued) carotid artery rupture 2743-4 cerebral oedema 2745 chylous fistula 2744 haemorrhage 2743 local 2743 nerve injury 2744-5 pneumothorax 2744 wound infection 2743 contraindications 2733 corners of consternation 2734 digastric muscle retraction 2740-1, 2740 F drains 2742 extended 2745 indications 2745 facial nerve preservation 2735 flap raising 2733-5, 2735 F hypoglossal nerve identification 2740-1, 274 1 F incisions 2732 F, 2733-4, 2735 indications 2733 internal jugular vein bleeding 2736-7, 2743 ligation 2736, 2736 F lower end 2735-7, 2738 F tears 2736-7 upper end, division of 2740-2, 2740 F, 2741 F lingual nerve identification 2742 marginal mandibular nerve preservation 2735, 2735 F modified see modified radical neck dissection mylohyoid muscle retraction 2742 nasopharyngeal carcinoma 2464 occipital artery ligation 2741 omohyoid division 2737-8 phrenic nerve identification 2737-8 platysma muscle 2734 posterior triangle dissection 2738-40, 2739 F single palpable metastasis, unilateral, less than 3 cm diameter (Nl ) 2725-6 sternomastoid muscle division 2736, 2736 F, 2740 submandibular triangle dissection 2742, 2742 F supraclavicular dissection 2737-8, 2738 F venae nervi hypoglossi comintantes 2740-1, 2741 F
radicular cyst 1922, 1 924 eggshell cracking sign 1 924 radiographic appearance 1924, 1924 F radioactive iodine ( 131 1) see radioiodine therapy radioallergosorbent test (RAST) 1394-5 allergic fungal rhinosinusitis 1453-4 allergy diagnosis 1 59-60, 1394-5 food allergy 1429 occupational rhinitis 1420 skin prick test vs. 1393 T radiofrequency ablation, snoring 233 1-2 radio frequency tissue volume reduction, snoring 2330 device types 2330 success rates 2333 radiofrequency tonsillotomy 1 235, 199 1 , 1 99 1-2 radio-guided parathyroidectomy 395 radioiodine therapy administration 347 adverse reactions 4 1 5 antithyroid medication pretreatment 348 contraindications 348 dosage 347-8 efficacy 347-8 elderly 348 follicular destruction 348 follow-up 348-9 Graves' disease 349 hyperthyroidism 347-9, 347-8 hypothyroidism induction 356 multinodular goitre 362-3 nontoxic 363 nodular thyroid disease 349, 362-3 side effects 362-3 opthalmopathy 349 safety 348 children 348 side effects 347, 348 thyroid cancer 2693-6, 2694, 2694 F, 2695 F thyroid gland studies 32 1-2 thyrotoxicosis 346 T transient hypothyroidism 356 radioisotope salivary function tests 1 863, 1 864 F radio nuclide scans gastro-oesophageal reflux 1274 Graves' disease 335 hypothyroidism 336 metastatic neck disease 272 1
parathyroid glands dual isotope subtraction scans 383 dual phase single tracer scintigraphy 383-4 intraoperative PTH assay with gamma probe localization 384 tracer choice 383 parathyroid imaging 383 skull base lesions 3947 thyroglossal cysts 1 778 thyroid gland imaging 328, 329 T developmental disorders 332 nodular/malignant disorders 333-4, 335 parathyroid imaging and 383-4 thyroiditis 335 thyrotoxicosis 335 see also positron emission tomography (PET) radiosensitizers 49-50 antiangiogenic agents 5 1 apparent sensitizers 50 enhancement ratio 50 glutathione depletion 50 mechanisms of action 50 true sensitizers 50 radiosurgery glomus juglare tumours 3995 jugular foramen lesions 4043 neurofibromatosis 2 3994-5 vascular malignant tumours 3996 see also gamma knife stereotactic radiosurgery radio systems, hearing impaired user 3667 radiotherapy 47-55 accelerated treatments 49 acromegaly 4101 adjuvant chemotherapy 5 1-2 clinical trials 52 complication incidence 5 1-2 meta-analysis 5 1-2 advances in 2759-6 1 adverse effects apoptosis-related 63 salivary gland dysfunction 1908-9 taste abnormalities 1 845 apoptosis 47, 63 basal cell carcinoma 2397 benign skin disease 2894-5 bioreductive drugs 50-1 cell replication 63 cellular radiosensitivity 47-8 Cushing's disease 4102 definition 47 I
Pages 1-13 1 2 are in Volume 1, pages 1 3 13-2810 are in Volume 2, and pages 281 1-4147 are in Volume 3.
I n dex I 4291
47
DNA
Ramsay-Hunt syndrome (herpes zoster
dosage 48
oticus) see
zoster oticus
dose response curves 48, 48 F
Rand device 2624-5
endolymphatic sac tumours 4072
randomized controlled trials
(RECD) 3633
(RCTs) 628-30
fractionation see fractionation
critical appraisal worksheets 668,
head and neck
implant osseointegration 2910-1
669 F, 670 F, 671 F ethical issues 589 Jadad score 650 methodology 650 questions 653 F otitis media 649 placebo control 658-9
jugular foramen lesions 4042-3
see also evidence-based medicine
rhabdomyosarcoma 1935 hyperfractionated 2755 hypopharyngeal cancer 2647-8 hypothyroidism induction 356
random pattern flaps 2828
juvenile angiofibroma 2442
rebreathing, capnograms 499 F receding jaw, airway management 469,
head and neck cancer 2753-65
head and neck sarcomas 1933
real-ear insertion gain (REIG) 3633 real ear to coupler difference
469 F receivers, hearing aids 3632 receptive language disorders 99 1 , 992
T
receptive language skills 99 1 receptor cells olfactory see olfactory receptor cells taste buds 3929 receptor tyrosine kinase (RTK) 2383-4 recessive mutant alleles 8-9, 9 F recessus terminalis 133 1
keloids 2893-4
blood supply 2828, 2844 F
recklessness, medical
lip cancer 2548
design 2828
recombinant erythropoietin (rEpo) 263
technique 2828 F
recreational drugs, septal perforation
meningiomas 4008-9
random transposition flaps 2840
mucosal malignant melanoma
and 1 582 rectus abdominus flaps 2876-8
ranitidine 2785-6
2410
2806
nonfunctioning adenomas 4 103
ranula(s) 1 246
advantages 2876
oropharyngeal tumours 2585
725, 1882, 1 884 F Rao v. the GMC (2003) 2804
anatomy 2876, 2876 F
otitis media with effusion 3389 perichondritis 3360
antigen testing (RAT)
peripheral lymphocyte count 2716-7
pharyngitis 1984
pinna reconstruction 3045
tonsillitis 1221
technical nuances 2877, 2877-8 rectus capitus posterior major 3899
rapid eye movement sleep (REM) 2305
pituitary tumours 4 1 1 5 adverse effects 4 1 1 5
airway activity 2308-9
nonfunctioning adenomas 4103
narcolepsy 2310
radiosensitizers see radiosensitizers salivary gland tumours 2507-8, 2510
tumour 2426 F recurrent acute rhinosinusitis
sleep-disordered breathing 1 103 rapid sequence induction,
(RARS) 1382
T
definition 1 382 symptom duration 1 439-40
anaesthesia 496
skin grafts 2821
rectus capitus posterior minor 3899 rectus palsy, cavernous sinus
neural activity 2306-7
prolactinomas 4100
clinical applications 2877-8 disadvantages 2877
skull base chondrosarcoma 4 126
RAS genes, thyroid cancer 2669
soft tissue sarcomas 1936
Rathke's pouch 295, 2 1 1 7-9, 2 1 1 8 F
recurrent aphthous stomatitis (RAS) 1 830-1, 1 8 3 1 F
subglottic haemangioma 1 140
cysts 4103
aetiology 1 830
targetted therapies 52-3
embryology 803
AIDS patients 242, 244 T
temporal bone chordoma 4073
remnants 295, 2 1 17-9
clinical features 242, 1 83 1
Ravussin style cricothyrotomy
temporal bone squamous cell
differential diagnosis 1 830
cannula 477 F
carcinoma 4094 thermal wounds 96, 96 F
RB gene 389
thyroid cancer
RBH scheme 2 1 75 , 2 1 75
nutritional deficiencies 1 830
T
aetiology 2670-1
RD4 receptor 57
treatment see thyroid cancer
reactionary haemorrhage, post tonsillectomy 1 994-5
thyroid eye disease 345 treatment interruptions 49
reactive lymphadenopathy 1 252
TSHomas 4 102
reactive oxygen species (ROS) ,
Radix graft, septal
2952 F
Radkowski staging system, juvenile angiofibromas 2438-9, 2440
T
RADPLAT 735
compensation 3793 syndrome (RUDS) 1416
ramp test 32 1 3 Ramsay Hunt syndrome see herpes zoster oticus
ototoxicity 3300-1, 3 3 0 1 F reactive synaptogenesis, vestibular reactive upper airways dysfunction
RAE tube 493 F
T
diagnosis 1830-1
systemic factors 183 1 types 1 830
ulceration 1 830, 1 830 F recurrent laryngeal nerve (RLN) 3 18,
320 F, 1 75 1 , 2 157 F, 3935 development 2 1 30-1 , 2 1 3 1 F distribution 1949-50, 2 1 56, 2 156 F,
2 157 F, 2664-5, 2665 F identification 3 1 8 left 2 1 39, 2 1 56
Read codes 464-5
lesions 3937
read text, voice analysis 2 1 72-4
relations 2665 F
real-ear aided gain ( imAG) 3633
T
treatment 242, 1 830-1
right 2 1 39, 2 1 56
1-13 1 2 are in Volume 1 , pages 1 3 1 3-28 10 are in Volume 2, and pages 281 1...,4 147 are in Volume 3.
�........------
------------
4292 1 I ndex
recurrent laryngeal nerve (RLN)
(continued) terminal branches 3 1 8 thyroid surgery 2664-5, 2665 F tracheal innervation 2 142 recurrent laryngeal nerve injury/palsy dysphagia 2033 left nerve 2 1 56 medical negligence 2808 thyroidectomy-related 3 5 1 , 2692 recurrent parotitis of childhood 1 903 recurrent respiratory papillomatosis (RRP) 2599 juvenile see juvenile-onset recurrent respiratory papillomatosis red cell(s) 266-72 abnormalities 270 antibodies 254 erythropoiesis 266 fragmentation 270 life span 266 nucleated 266 storage 255 red cell transfusion 255-6, 258 T acute blood loss 256-7 alternatives 262-4 British Committee for Safety in Haematology guidelines 2001 256-7 haemoglobin concentration estimations 257 indications 255-6 patient assessment 255 premature cell destruction 262 preoperative preparation 255 red eye, painful differential diagnosis 3915-6 infective causes 39 1 6 inflammatory causes 39 1 5-6 neoplastic causes 39 16 vascular causes 3916 'red man' syndrome 230 reduction glottoplasty, Reinke's oedema 2200 reduction rhinoplasty 2950-8 aims 2950-1 complication avoidance 2952-7 contraindications 295 1-2 future directions 2957 indications 2950-1 outcome assessment 2957 techniques 2952-7 re-epithelialization, wound healing 90-1, 90 F refeeding syndrome 532
reference standard 655 reflexes, nasal see nasal reflexes reflux oesophagitis 45 1-2 Refsum's disease 1048 regional accents, speech rhythm 2 168 regional taste testing 1 844 rehabilitation dysphagia 2086, 2088-90, 2089 T, 2090 T post-laryngectomy see laryngectomy Reichart's cartilage 1 739-40 reinforcement tympanoplasty 946 Reinke's oedema 2 199-200, 222 1 , 2264-5, 2265 F aetiology 2 199, 2265 definition 2 1 99 grading system 2200, 2200 T histology 2 199 malignant transformation 2265 menstruation 2212-3 phonosurgery 2200, 2237, 2239, 2265 postoperative complications 2200 prevalence 2200 speech therapy 222 1 symptoms 2200 treatment 2200, 2265 vocal fold appearance 2 1 99 F, 2200, 2265 voice analysis 2 178-9, 2 179 Reinke's space 2 l34-5, 222 1 Reinke's oedema 596, 222 1 Reissner's membrane 3 127-30, 3 1 29 F rupture 3507 relapsing acute parotitis 1243-4, 1244 F imaging 1 244, 1 244 F surgery 1 244 relapsing polychondritis 3362-5, 190 aetiology 3362 definition 3362 diagnosis 3362-4 diagnostic criteria 3363 differential diagnosis 3364 larynx 2266 management options 3364 nasal 1 7 1 3 noncartilaginous structures 3363 outcomes 3364 pathology 3362 symptoms 3359 relative loudness method 3 3 1 8, 3318 F relative risk 660-1 relatives, critically ill patients 536 relaxed skin tension lines (RSTL) 2832 F
scar revision 289 1 , 2895 skin grafts 2829-30 reliability, outcomes research 635-6 religion, cancer patient's quality of life 2777 religious morality 583 see also ethical issues remifentanil awake intubation 480 supraglottic obstruction 480 tracheal intubation 494-5 remodelling bone repair 94 wound healing 93-4, 98-9 collagen 93 renal bone disease 382 renal failure drug prescribing 416 parathyroidectomy 395 platelet dysfunction 288 renal lithiasis 391 renal replacement therapy, critical care patients 530 renal stones 391 renal support, critical care patients 530 renal transplantation, hyperparathyroidism 395 Rendu-Osler-Weber disease see hereditary haemorrhagic telangiectasia (HHT) reparative granuloma, post-stapes surgery 3476-7 repetitive apnoea 2 3 1 6-7, 2 3 1 9 F repetitive low-frequency transcranial magnetic stimulation (rTMS) , tinnitus 3 6 1 8 Reporting Systems o n Vestibular Schwannomas 3959, 3980 Repose tongue base suspension suture 233 1-2 research consent 589 epidemiological see epidemiology ethical issues 588-9 outcome measures see outcomes research voluntariness 589 see also evidence-based medicine research fraud 2805 research hypothesis 623 residual cyst 1 8 1 7, 1924 residual inhibition 3 6 1 2 tinnitus 3612 residue pitch 3252-3
Pages 1-l 3 1 2 are in Volume I, pages l 3 l 3-28 1 0 are in Volume 2, and pages 2 8 1 1-4147 are in Volume 3.
I ndex I 4293
resistance exercises, dysphagia 2088, 2089 T resistance index ( RI) 714 'resistance modulation' (battery) theory 3 1 93--4 resistant acute otitis media 9 1 3 resonance 992-3, 3 167 resonance frequency 3 162 resorptive osteitis, chronic otitis media 954, 3397-9, 3399 F resource allocation ethical issues 589-9 1 levels 590-1 respiration dysphagia investigations 1 976 nose in 1 355 swallowing and 1959-6 1, 1960 F respiratory arrest, adult epiglottitis 225 1 respiratory centre, sleep 2306-7 respiratory disease, surgical preparation 460 respiratory distress, acute epiglottitis 1 1 30 Respiratory Disturbance Index (RDI) 233 1 special needs children 787 respiratory epithelial cysts 40 14 respiratory epithelium frontal sinus 1340 lateral nasal wall 1 337 septum 1 327, 1 327 F respiratory gases 3 5 1 5 T respiratory monitoring, airway endoscopy 5 1 8 respiratory papilloma 209 respiratory rate, children 543, 543 T respiratory scleroma (rhinoscleroma) 1462-3 clinical features 1463 diagnosis 1463 epidemiology 1462 histology 1462-3 infection stages 1463, 2268 laryngeal 2268 nasal 1462-3, 1 703 nasopharyngeal 2 1 22 pathology 1462-3 treatment 1463 respiratory sleep disorders 2307-9 respiratory support, relatives 527-8 respiratory syncytial virus (RSV) 207 acute otitis media 9 1 5 symptoms 207 vaccination 9 1 9
respiratory tract viral infections 204-7, 205 T children 1 2 1 2 diagnosis 204-5 incidence 204 pathogenesis 204 host-cell interaction 204 serology 204-5 respiratory-type epithelium larynx 2 1 37 nasopharynx 2 1 08 response time (RT), speech audiometry 3272 resting strain, vestibular hair cells 3236 F restless legs syndrome (RLS) 23 10 restlessness, airway obstruction 2287 restorative gene therapy 29 restriction endonucleases 5, 5 F resuscitation critical care, adult 534 palliative care patients 2798, 2799 T retention cysts, nasopharyngeal 2 1 22 reticular activating system, sleep 2306 reticular dysgenesis 1 75 reticulocytes 266 reticuloendothelial lymphoma 275 reticuloendothelial malignancies, cytogenetic analysis 6 retinacular ligament 1 8 1 0 retinoblastoma, genetics 8 retinoblastoma gene 2382-3 exons 2378-9 hypopharyngeal cancer 2636 pocket protein family 2382-3 13 cis-retinoic acid dermabrasion 2898 retinoids, chemoprevention 41 retinopathy, diabetic 401-2 RET protooncogene ( cRET, MEN-2) 389, 2384 mutations 389 thyroid cancer 2669, 267 1 , 2687 retraction pocket see chronic otitis media (COM), inactive squamous retrobulbar haematoma, post blepharoplasty 3064-5 retrobulbar haemorrhage, postblepharoplasty 3059-60 retrobulbar neuritis, acute 39 16 retrobullar recess 1 333--4 retrocochlear hearing disorders 3837-56 causes 3837, 3839 acquired 3839 T congenital 3838 T genetic 3838 T
cerebellopontine angle tumours 3848 classification 3835-6 definition 3837 Paget's disease 3487-8 speech audiometry 3273 retromandibular vein 1 853--4, 3904 retro-orbicularis orbital fat (ROOF), descent 3049 retropharyngeal abscess 2000-2 bacteriology 2000-1 children 1 2 1 3--4, 1214 F, 1223, 200 1 surgical drainage 200 1 clinical features 1 786, 200 1 complications 2002 differential diagnosis 200 1 epidemiology 2000 investigations 47 1 F, 200 1 children 200 1 surgical drainage 2001 treatment 200 1-2 retropharyngeal lymph nodes lateral (nodes of Rouviere) 2 1 13 medial 2 1 13 metastatic neck disease 27 1 8-9 evaluation 2719 retropharyngeal space 1 744-5, 1 745 F, 1 757-8, 1 806-7, 1950, 1950 F, 2 1 09, 2 1 10 T, 2579 anterior compartment 2 1 09-10 posterior compartment 2 1 09-10 retrospective studies 2344-5 retrovirus gene therapy head and neck cancer 27 biosafety 27 insertional mutagenesis 29 retrovirus replication 27 reversed ear 3504 reverse ear squeeze 3504 reverse genetic cloning technique 1 1 reverse transcriptase inhibitors 233 reverse triiodothyronine (rT3) 32 1 , 323 Revised European American Lymphoma (REAL) 1254 revision rhinoplasty 2979-86 classification 2980, 298 1 T deformity frequency 2980, 298 1 T external approach 2965 prevention, factors affecting 2980-1 revision rates 2980, 2980 T surgical procedures 2979 treatment strategies 2982-5 Reynell development language scales 62 1 Reynolds number 1 357 rhabdomyoma, larynx 2600 T, 2604
Pages 1-1 3 1 2 are in Volume 1, pages 1 3 1 3-28 1 0 are in Volume 2, and pages 28 1 1-4147 are in Volume 3.
4294 1 I nd ex
rhabdomyosarcoma
(RMS) 1934-8
children 1 255-6, 1256 F
drug-induced 1 383, 1410
histological investigations 173 1-2
emotional 1 383, 1 4 1 1
incompetent surgical
assessment 1 255-6
food-induced 1 383, 1 429
presentation 1255
gastro-oesophageal reflux 1 383
prognosis 1256
hypothyroidism 400
postoperative monitoring 1735
staging 1 255-6, 1 256 T
idiopathic 1 383, 1409-10
pre-referral care,
treatment and prognosis 1 256 ear 4074
technique 1732-4
aetiology 1 409-10
intraoperative monitoring 1 734-5
inadequate 1730-1
corticosteroids 420
presurgical management,
classification 4074, 4074 T
diagnostic tools 1409
diagnosis 4074
neonatal 1076
radiological investigations 1731
site of origin 4074
pathophysiology 1409
tumour recurrence 1734
symptoms 4074 T
symptoms 1409-10
treatment 4074
inadequate 173 1
tumour resection 1 734
irritants 1 383
types 4074
video use in theatre 1 73 3
'mixed' 1408-9
epistaxis, children 1065, 1065 F
molecular biology 1562
management principles 1934-5
oral drugs 1 564
rhinomanometry 1 3 5 8 , 1 358 F,
1 372-5 active 1373
outcomes 1935
topical drugs 1 564
presentation 1934
treatment, asthma
prognosis 1934 T
treatment costs 1 565
definition 1 372-3
skull base 3943
see also rhinosinusitis; specific
disadvantages 1 376-7
1 934, 1934 T, 1935 T
anterior l 37 3 and 1565
ethnic differences 1 374
conditions
rhagades 1 827
rhinitis medicamentosa
Rhesus (Rh) blood group 254, 254 T fetomaternal haemorrhage 254 rheumatic fever
head-out body plethysmograph 1 373
assessment 1 376
normal nasal airflow 1 3 74-5
corticosteroid treatment 42 1
age effects l 3 74
decongestant-induced 1383, 1 398, 1410
decongestant effects l 3 74
prevention, antibiotics 1 985
rhinitis sicca 1 466
tonsillitis complications 1 224
'rhinobasis' 1505-6
rheumatoid arthritis 185-6
passive 1 373 septal pathology 1 576, 1 577 F
rhinocerebral mucormycosis see fungal
dysphagia aetiology 2032
rhinosinusitis, invasive
rheumatoid factor 1 70
rhino frontal sinuseptotomy
serological tests 185
technique 1 5 14
rheumatological diseases 183-92 aphthous ulceration 184
rhinolalia (nasal speech) 993 rhinolalia aperta (hypernasal
diagnostic paradigms 1 87 T
speech) 993, 1 366, 2 166
drugs 190
rhinolalia clausa (hyponasal
ENT manifestations 1 83, 1 84 imaging 1 85
T
inflammatory diseases and infections 1 89
rhinometry, acoustic see acoustic rhinometry
(RFS) 1 5 14
results 1 5 1 4
rheumatoid factor 1 70
posterior 1 373, 1373 F
speech) 993, 1 366, 2 166
rhinophyma 1 714, 1 71 4 F medical negligence 3096 rhinoplasty augmentation see augmentation rhinoplasty enlarged turbinates 1 590 external see external rhinoplasty infections 309 1
rhinolith 1 186
medical negligence 3091-2
rhinological pain
nasal fractures 1 6 14
post -surgical 1721
nasal valve collapse 3007
investigations 1 8 5
post-traumatic 1721
open see external rhinoplasty
overlap syndromes 1 89
sinusitis 1720-1
patient expectations 3091
symptoms and signs 1 84-5
see also specific diseases rhinectomy 2933, 2934 rhinitis
postoperative concerns 309 1
rhinology drug therapy 436-45
postoperative deformities 2979-80
antibiotics 438-9
postoperative nasal obstruction 1 590
antifungal agents 442
postoperative oedema 309 1
aetiology 1561
immune response improving 441
reduction see reduction rhinoplasty
allergic see allergic rhinitis
see also individual drugs
revision see revision rhinoplasty
asthma link 1 58, 1 560-1 disease continuum 1 565
image-guided surgery 708
revision rate 309 1
medical negligence 1 730-6
septal perforations 1 587
atrophic see atrophic rhinitis
consent 1 732
bronchial challe nge 1 563
conservative treatment, failure to
bronchial inflammation 1 562-4 bronchial remodelling 1562 definition 1380-1
consider 1732 conservative treatment, inadequate 1 735
rhinorrhoea aspirin-induced 1 4 1 0 cerebrospinal fluid see cerebrospinal fluid rhinorrhoea pregnancy 402-3
Pages 1-1 3 1 2 are in Volume 1, pages 1 3 l 3-28 1O are in Volume 2, and pages 281 1-4147 are in Volume 3.
I ndex 1 4295
skull base lesions 1 35 1-2 watery, nasal fractures 1 6 1 1 rhinoscleroma see respiratory scleroma (rhinoscleroma) rhinoscopy adenoids 1 096 frontal sinus 1 50 1 nasal polyposis 1 553 rhinosinusitis 1439-48 acute see acute rhinosinusitis (ARS) adenoidectomy 1096 allergy 1440-1 antimicrobial resistance 1441-2 children 1079-93, 1495-6 acute sinusitis 1 080 complications 1085-9, 1086 T diagnosis 1 082 epidemiology 1080 examination 1 082 immunotherapy 1083-4 inflammation pattern 1 079 intracerebral abscesses 1 089 investigations 1082-3 orbital complications 1 086-8, 1088 F pharmacotherapy 1083 predisposing factors 1079 prevalence 1443, 1444 radiology 1082-3 subdural infection 1088, 1 088-9 surgery 1084-5 treatment 1083-4 viral rhinitis 1 080 chronic see chronic rhinosinusitis (CRS) classification 1 380-5, 1 380 T, 1 439, 1439 T complications see rhinosinusitis complications definitions 1439-40 diagnosis 1442-3, 1478-80 differential diagnosis 1 380-5, 1 3 8 1 T economic impacts 1444-7 endoscopy 1479 enlarged turbinates 1 59 1-2 frontal see frontal rhinosinusitis fungal see fungal rhinosinusitis gastro-oesophageal reflux 1274 hormones, effects of 1 383 inflammatory response 1440-1 intermittent see acute rhinosinusitis (ARS) investigations 1 3 84 T mierobiology 1 44 1 , 1441 F, 1442 F nasal polyposis 1 552-3
natural history 1443 obstructive apnoea 1 104 parasympathetic nervous system blockers 442 pathophysiology 1440-2 environmental factors 1440 persistent see chronic rhinosinusitis (CRS) prevalence 1443-4 quality of life 1444-7 radiology 1479-80 recurrent acute see recurrent acute rhinosinusitis (RARS) saline irrigation 441 signs/ symptoms 1440 T staging system 1489 T, 1490 T surgical management 1478-99 computed tomography 1479 T, 1480 F historical aspects 1 480-1 magnetic resonance imaging 1480 procedures 148 1-95, 1482 T results 1486-9
see also individual procedures symptoms 1469 treatment antibiotics 438-9 antihistamines 440 antimycotics 441 corticosteroids 436-8 costs 1444 decongestants 439-40 mucolytics 440 sodium cromoglicate 440 rhinosinusitis complications 1 539-48, 1 54 1 T acute 1 539-40 chronic 1 540 classification 1 539-40 clinical presentation 1 540-2 definitions 1 539 distant 1 540 haematological investigation 1 543 intracranial 1542 examination 1 542 ,. 1 543 ' """ ''''yn.....
incidence 1 542 morbidity 1 546 mortality rate 1 546 prognosis 1 546 surgery 1 545 symptoms 1 542 investigations 1 542-3 local 1 539-40 •
medical management 1 543-5 orbital 1 54 1 imaging 1 542-3 prognosis 1 546 see also orbital cellulitis prognosis 1 546 surgery 1 544-5 Rhinosinusitis Disability Index (RSDI) 1444-7, 1445 Rhinosinusitis Outcome Measure ( RSOM-3 1 ) 64 1 rhinosporidiosis 2 1 5-6 aetiological agents 2 1 5 clinical manifestations 2 1 6 definition 2 1 5 diagnosis 2 1 6 epidemiology 2 1 5-6 nasal infection 1 703-4 outcomes/complications 216 treatment 2 1 6 Rhinosporidium seeberi 2 1 5 rhinostereometry 1 376 rhinovirus 205 Rhizmucor 2 1 7 Rhizopus arrhizus 2 1 7 Rhomberg's test, skull base lesions 3946 rhomboid flap 2838-40, 2841 F rhombomeres 8 14 rhytidectomy anaesthesia 307 1, 3094 complications 3074-5 contraindications 3070 facial skeletal structure 3070 haematoma 3094 historical aspects 3068-9 incision design 3071 incision placement 3094 lobule incision 307 1-2 long flap 3069 3093-5 medical medications 3070 nerve damage 3074 patient selection 3070 physical examination 3070 platysmaplasty and submental liposuction 3073-4 post-auricular incision 3072 F postoperative complications 3094 post-tragal closure 3072, 3073 F post-tragal incision 307 1 , 3071 F preoperative assessment 3094 sensory changes 3094-5 short flap technique 3069 skin flap elevation 3069
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4296 I I n dex
rhytidectomy (continued ) superficial musculo-aponeurotic system incision 3072, 3072 F surgical technique 307 1-3 ribavirin 2 1 0 juvenile-onset recurrent respiratory papillomatosis 1 1 78 ribbon synapse 3 1 36 ribonucleic acid (RNA) see RNA (ribonucleic acid) ribosomal RNA 2379-80 ridge expanders 29 15-6 Riedel's operation, frontal sinus fractures 1506-7 rifampicin atrophic rhinitis 1466 hepatotoxicity 236 leprosy 1464 respiratory scleroma 1463 tuberculosis 1460 rifamycins 23 1 right anterior-left posterior (RALP) plane 3209 eye movements 3217 F right main bronchus 2 140 F, 2 141 rigid bronchoscopy anaesthesia 504, 504 F low tracheal obstruction 483 paediatric intensive care 547 ventilation 483, 483 F rigid endoscopy laryngeal stenosis 1 1 52 oesophageal foreign bodies 1 1 88 tracheo-bronchial foreign bodies 1 190 rigid fibrescopes 473 rigid Hopkins rod system, laryngoscopy 2 146 rigid laryngobronchoscopy, obstructive sleep apnoea 1 1 07 rigid laryngoscopy 2 149-50, 2 149 F, 2 1 50 F child's voice assessment 1 169 chronic laryngitis 2259-60 Riley-Day syndrome 1288 riluzole 2080 rimantidine 2 1 0 rima olfactoria 1 344-6 rim incision external rhinoplasty 2999, 2999 F nasal tip delivery 2997-8, 2998 F Rinatec see ipratropium bromide Ring, Adair, Eluyn (RAE) tube 5 1 1 , 5 12 F Rinne tuning fork test 33 1 8
Rion partially implantable hearing aid (PIHA) 3662 risedronate 3489 risk indices, surgery 459 risk perception, surgery-related 563 ritiximab (Mabthera) 44 ritonavir 233, 239 rizatriptan 1049 RNA (ribonucleic acid) 4 HIV virus 238-9 ribosomal 2379-80 RNA polymerase 4 Robin complex 1000-1 Rochester study, thyroid cancer 2670 rods 39 14 rods of Corti see pillar cells Rogers v Whitaker 1732 rolling hiatal hernia 2062 roll test 3809-10 Romberg's sign 3778 Romberg test 373 1 ROM (oral) exercises 2088, 2089 T root form implants 2903-4 root mean square (RMS) values 3 162, 3 174 root of the neck anatomy 2737 F radical neck dissection 2737 surface anatomy 174 1 root sheath o f Hertwig 1 922-4 rosacea 1 7 1 4 Rosai Dorfman disease (sinus histiocytosis) 1 2 17 rostrum, sphenoid bone 1339 rotational movements, semicircular canals 32 1 1 rotational tests ototoxicity recognition 3573 vestibuloocular reflex 3728 F, 3729-30 rotational vertigo patient's description 3707 presentation 3709 rotation flaps 2832-4, 2835 F, 2836 F nasal reconstruction 3019 round window anatomy 3 1 1 1 , 3 126 bone conduction 3 1 85 congenital aplasia 873 dysplasia 873 otosclerosis 3456, 3457 F total obliteration 347 1 rupture 3497 roxithromycin 147 1-2 Royal College of Anaesthetists, paediatric NSAIDs use guidelines 516
Royal College of Surgeons, tonsillectomy surgical mortality audit 1235-6 RSR1 3 5 1 RTOG ETA (RTOG 85-27) trial 2756 rubella 170 1 Russel bodies, respiratory scleroma 1462-3 Rye classification, Hodgkin's lymphoma 1254 S 100 protein, mucosal malignant melanoma 2408 saccades 392 1 balance disorders 37 14-6 corrective 37 1 5 examination 3714-6 accuracy 3715 conjugacy 371 5-6 techniques 37 14, 3714 F function 3227 T medial longitudinal faciculus lesions 3 7 1 5 oculographic recording 3715 F, 3716 F, 3726 velocity examination 3714-5 neurodegenerative disease 3712 F, 3714-5, 3 7 1 5 F saccadic hypermetria 3715, 3716 F saccadic hypo metria 3715, 3715 F saccular cysts 1 1 36-7, 1 1 37 F saccule 3 1 5 1-2, 3 1 5 1 F endolymphatic potential 3230-1 orientation 32 10 vestibular hair cells 3228-30 see also otolith organs saccule of the larynx 2 1 34 saccus decompression surgery, medical negligence 3830 saddle nose deformity 2970, 297 1 F aetiology 2970, 2971 T antibiotic prophylaxis 2974 management 2974-7 medical negligence 1733, 309 1-2 nasal fractures 1 6 1 5 splinting 2974 surgery 2974, 2976 F augmentation 2974 graft fixation 2974 graft preparation 2974 traumatic 2970 Saethre-Chotzen syndrome 1 028 sagittal synostosis see scaphocephaly
Pages 1-1 3 1 2 are in Volume 1 , pages 1 3 1 3-28 1 0 are in Volume 2, and pages 2 8 1 1-4147 are in Volume 3.
I nd ex I 4297
salicylates ototoxicity 3568 T, 3571 prevention and 3302 tinnitus induction 3599-600 salicylic acid ototoxicity 3677 saline-adenine-glucose-mannitol (SAGM) medium 255 saline irrigation, rhinosinusitis 441 saliva antibacterial substances in 1 866-7 artificial 449, 1 9 1 2 , 2788 collection 186 1-3 drainage methods 1862 method comparison 1 863 mixed whole saliva 1 862 parotid gland 1 862-3 stimuli 1 862 submandibular gland 1 863 composition 1 865 T inorganic ion concentration changes 1 866 T pepti des 1 842 T proteins 1 842 T variables affecting 1 865 T, 1 866 T diagnostic assays 1 867-9 drug monitoring 1 868, 1 868 T hormone monitoring 1 867-8 malignancy screening 1 867 microbial antigens and antibodies 1 868-9 discolouration, drug-induced 1 907 flow rates 1 807 factors affecting 1861 functions 1 859 T in taste 1 84 1 , 1 842 T secretion 1 858-61 autonomic control 1 858-9 mechanisms 1 859-60 salivary calculi see sialolithiasis salivary cysts, congenital 1242 salivary fistula 2484, 2 5 1 5 salivary gland(s) absence 1 242, 1 899 agenesis 1 242, 1 899 anatomy 1 852-7, 1 807-8 microscopic 1 852 aplasia 1 242, 1 899 drug-induced pain 1 906 T, 1 907 ectopic 1 243 embryology 799, 1 852 excretory duct 1 852 HIV patients 245-6, 1 882
imaging 187 1-97, 722-4 children 1 886-7 normal anatomy 187 1-2, 1 872 F, 1 873 F techniques 1 872-8
see also individual techniques major 1852 minor 1 792, 1 808, 1 852 physiology 1 858-70 primary fluid secretion 1 860-1 secretory cells 1 852 surgery anaesthesia 503 operation and procedure codes 2375 T
see also individual glands salivary gland diseases/disorders children 1242-50 granulomatous 1244-7 inflammatory 1 243-4 congenital 1 242-3, 1 899 drug-associated 1906-7, 1906 T swelling 1906-7, 1906 T ductal anomalies 1 242 infections 1 899-900, 1899 T non-neoplastic 1 898-920, 1 899 T imaging 1 878-82 radiotherapy-associated dysfunction 1 908-9 rheumatological diseases 1 84 stones see sialolithiasis
see also specific diseases/disorders salivary gland lymphoma 250 1 , 2503 salivary gland tumours benign 2475-92 aetiology 2476 assessment 2478-80 children 1 248 distribution 2475-6, 2476 T epidemiology 2475-6 fine needle aspiration cytology 2479-80 histopathology 2480-3 imaging 1 882-4, 2478-9, 2478 T malignancy risks 2476 molecular mechanisms 2476 presentation 2476-8 recurrent 2478, 2478 F secondary malignancies 2476 treatment 2483-90 children 1247-9 benign 1248 imaging 1 886 investigation 1249 malignant 1248-�
management 1 249 medical negligence 1 3 1 0 neoplasms 1 248 vasoformative lesions 1247 HIV-associated 245 imaging 723, 723 F, 1 882-5 malignant see salivary gland tumours, malignant minor glands 2505, 2505 F recurrence rates 251 1 , 25 1 1 F, 25 12 F survival 25 12-3, 2513 F in oropharynx 2580-1 parapharyngeal space 2525, 2530,
2536 TNM classification 2366, 2368 T salivary gland tumours, malignant 2493-521 cell biology 2494-6 chemotherapy 2508 children 1248-9 classification 2496-502 diagnosis 2506-7 epidemiology 2494 histogenesis 2503 histology 2496-502 imaging 1884-5, 1 889 F incidence 2494 investigations 2506-7 metastatic disease 2501-2 , 2503 molecular biology 2494-6 neck treatment 25 1 0 radiotherapy 2507-8 postoperative 2507-8 recurrence rates 25 1 1 , 25 1 1 F, 2 5 1 2 F squamous cell carcinoma 2501 2507 T surgery 2508-9 complications 2515 facial nerve 2508-9 middle ear sacrifice 2508-9, 2509 F survival 25 1 1-4, 2 5 1 2 F by histology 2 5 1 2-3, 25 1 3 F major glands 2 5 1 2-3, 2 5 1 2 F, 25 1 3 F minor glands 2 5 1 2-3, 25 1 2 F, 2513 F, 2 5 14 F treatment 2507-10 complications 2514-5 undifferentiated carcinoma 2501
see also individual glands; individual tumours salpingopharyngeal fold 1 944, 2107 salpingopharyngeus 1945 F, 1948 T, 2 1 12, 2 135 T, 3 1 18, 3901
Pages 1-1 3 1 2 are in Volume 1 , pages 1 3 1 3-28 1 0 are in Volume 2, and pages 28 11-4147 are in Volume 3.
4298 • I nd ex
salted fish, nasopharyngeal carcinoma risk 2346, 2354 Samter's triad 1472 frontal sinus surgery 1 5 1 9 NARES 141 1 nasal polyposis 1 550 Sanders injector 476-7, 477 F, 504, 504 F 'sandpaper rash' 1983 saquinavir 233, 239 sarcoidosis 1 89-90, 1645-9 aetiology 1646-7 apple jelly nodules 1 89 F cervicofacial infections, children 1 2 10-1 clinical features 1647-8, 1 647 F, 1648 F corticosteroids 424 diagnosis 1648 dysphagia aetiology 2032 extrapulmonary organ involvement 1 647 T facial nerve disorders 3891 granulomata 1 87 F histology 1 647 Kveim test 1 648, 1 7 1 1 laryngeal 2267 nasal 1 645, 1647-8, 1 647 F, 1 648 F, 1 649 F, 1 7 l 0- 1 , 1 7 1 0 F symptoms 1 647 T nodes involved 1 759-60 orallperioral lesions 1 828 prevalence 1 645 pulmonary infiltrates 1649 F salivary glands 1 906 children · 1 245 treatment 1 648-9 sarcoma( s), soft tissue see soft tissue sarcomas (STS) sarcomatoid carcinoma, larynx 2604 satellite cells 69, 7 1 Satisfaction with Life Areas scale, cochlear implants 3654-5 ear deformity 3075 saw-tooth nystagmus see jerk nystagmus scala media 3 1 27, 3 128 F scala tympani 3 127, 3 128 F access, cochlear implant surgery 3652 scala vestibular 3 1 27, 3128 F 'scalded skin syndrome' 1700 scalds, dressings 102 scalene muscles 1 746 scalenus anterior 1 746 scalenus medius 1746
scalp flaps 2848-9, 2850 F scalp recorded electric responses 3280 scan-directed minimally invasive open parathyroidectomy 394 scaphocephaly 794, 794 F, 1022 T, 1 025 clinical features 1 025, 1 025 F incidence 102 1 , 1025 surgery 1025 flap systems 2873-6 anatomy 2873-4, 2874 F clinical applications 2875-6, 2875 F disadvantages 2874-5 oral cavity reconstruction 2570-1 technical nuances 2875 S-carboxymethyl cysteine 3392 scar camouflage 2895, 2895 F scarlet fever 1222 Scarpa's ganglion 3 148-9 otosclerosis 3457-8 vestibular compensation 3793 vestibular neuritis 3678 scar revision 2895-9 2899 adjunctive excision 2895, 2896 F expansion with 2895-6 serial 2895-6 indications 2895, 2895 F irregularization 2896-7 techniques 2895-9 tissue expansion 2896 scars/scarring 87, 93 benign skin lesions 3090 chronic otitis media assessment 34 12 ear 3 3 1 1 , 3 3 1 2 F chronic otitis media assessment 3412 final appearance, influencing factors 289 1 tensile strength 93, 99, 99 F Schaumann bodies 1 647 Schilling test 269 Schirmer test 3878 F, 3878 T schizophrenia 1 669 Schneiderian papillomas 2420 Schobinger incision 273 1-3, 2732 F school-entry screen, hearing loss 829 schwannoma(s) collision tumours 4002 CPA tumours 40 14 facial nerve see facial schwannoma jugular foramen 4030-1 affected nerves 4030 classification 4030, 4030 T, 403 1 T histology 403 1 resection 4039-40, 4041 F
site of origin 4030 stereotactic radiosurgery 4043 laryngeal, benign 2600 T lower cranial nerves 40 14 malignant transformation 4002 nasopharyngeal 2 1 24 neurofibromatosis type 2 4000, 4002, 4003 parapharyngeal space 2527 trigeminal nerve see trigeminal nerve (V) tumour embolization 734 ultrasound examination 726 vestibular see vestibular schwannoma (VS) schwannomin (NF2 protein; merlin) 3999 Schwartz-Bartter syndrome 2529 Schwartz sign 3460-1 scintigraphy dysphagia 1977 frontal sinus 1 502 Graves' disease 340 T, 341 jugular foramen infections 4029 nodular thyroid disease 36 1-2 salivary glands 1 878, 1 878 F, 1 879 F advantages/disadvantages 1 874 T, 1 878 children 1 299-300 function tests 1 864 F indications 1 890 T subacute thyroiditis 352 thyroid neoplasia 36 1-2 thyroid nodule evaluation 2676 thyrotoxicosis 340, 340 T, 34 1 Scl-70 antibodies 1 70-1 scleral search coils 3723 scleroderma 1 70-1 , 1 86 avsunallna 203 1 nasal 1 7 1 2 oesophageal 2066 scleroma 2010 respiratory see respiratory scleroma sclerosants endovascular embolization 733-4 lymphangioma 1 782-3 sclerotherapy, hygroma 1 270 scopolamine see hyoscine scotoma 39 1 5 Scottish Intercollegiate Guideline Network tonsillectomy recommendations 1 230-1, 1 996 Scottish Tonsillectomy Audit 1231
1-13 1 2 are in Volume 1 , pages 1 3 1 3-28 1 0 are in Volume 2, and pages 2 8 1 1-4147 are in Volume 3.
I ndex I 4299
screening definition 82 1-2 principles 822 scneenmg audiometry 3264-5 screening programmes, coverage of 822 screen result 822 screen result 822 screen CPl1IC,t"U,t" 822-3 scrofuloderma infection 1702 scrotal tongue 1 825-6 scuba diving, ear surgery and 3469, 3506 sea sickness 3240 seasonal rhinitis, pollens 1396 sebaceous glands, external auditory canal 3 107 seborrhoeic dermatitis HIV-associated 247 external ear 240 treatment 240 nasal 1 7 1 5 seborrhoeic keratoses 1 709 secondary olfactory cortex 3912-3 second branchial arch fistula 797, 1 266-7, 1 779 investigation 1266 presentation 1266, 1266 F surgical removal 799 F, 1266-7, 1779-80, 1780 F treatment 1266-7, 1267 F second degree burns 96 second law of Newton 32 1 0 lInd nerve see optic nerve (II) secretory otitis media (SOM) see otitis media with effusion COME) sedation acute laryngeal infections 1 128 awake fibreoptic intubation 480 paediatric imaging 1301-2, 1302 T paediatric intensive care 544 see also anaesthesia segmental bronchi 2141 seizures childhood disorders 1 045 vestibular schwannoma removal 3979 selectins 2384 allergic rhinitis 1391 selective glutamate receptor antagonist, tinnitus 3617-8 selective immunoglobulin immunodeficiency 1 75 T, 176-7 selective neck dissection 2747-9, 2747 T, 2748 F anterior compartment (level VI) 2747 T, 2748, 2748 F, 2749
complications 2749 incisions 2732 F indications 2747-9, 2747 T lateral 2747, 2747 T, 2748 F, 2749 level VII 2748-9, 2749 N1 disease 2726 operative 2749 posterolateral 2747-8, 2747 T, 2748 F, 2749 postoperative management 2749 selective oncolytic virus, head and neck cancer treatment 29 selective serotonin reuptake inhibitors (SSRIs) migrainous vertigo 3804 tinnitus 3617 vestibular attacks, acute 3798 selective 235-6 selenium 32 1 self maps, voice evaluation 2 1 84 298 sella sella turcica 298-300, 298 F content 298 dural reflections 298-9 landmarks 298 semicircular canal(s) anatomical design 32 1 1 , 32 1 1 F embryology 807, 8 1 6, 8 1 6 F forces acting upon 32 1 1 hair cells 3228, 3230 F head-impulse test 3224 mean resting discharge 3237 mechanical stimulation 3749-50 movement detection 32 1 1 antagonistic responses 3 2 1 5 biomechanics 32 1 1-3, 3 2 1 3 F rotational 32 1 1 nystagmus 3749, 3749-50 sinusoidal rotations, response to 32 1 3 F stimulation 3 2 1 5-20 anterior canal, eye movements and 32 1 7-9, 32 1 7 F, 32 1 8 F eye movements 3 2 1 6, 3217 F, 32 1 8 F, 3219 F, 3219 T horizontal canals 3 2 1 5 posterior canal 3217-9, 3 2 1 7 F, 32 1 8 F, 32 19 F vertical canals 32 1 5 semi-conservative replication 4 semi-implantable middle ear electromagnetic hearing device (SIMEHD) 366 1-2 semispinalis capitis 38 99
semi-vowels 2 167, 2 1 67 T Semont's liberatory manoeuvre benign paroxysmal positional vertigo 3 8 10, 3 8 1 0 F complications/adverse effects 3 8 1 2 efficacy 3 8 1 2 senile keratosis see actinic keratosis sensation levels ( SLs) , temporal resolution assessment 3256 'sense of coherence' 2770 senses, reliance on 3240 T sensitivity 822-3 sensorineural hearing loss (SNHL) 3577-8 active chronic otitis media 3436 age-related see at!€�-rc:!laltea (sensorineural) hearing loss aminoglycoside ototoxicity 3569 apoptosis 6 1-2 autosomal dominant nonsyndromic see autosomal dominant nonsyndromic sensorineural hearing impairment bone-anchored hearing aids 3646 children 848 definition 8 1 1-2 desferrioxamine-induced 271-2 glomus temporale tumour 403 1 F, 4032 idiopathic 3579-80 idiopathic sudden see idiopathic sudden sensorineural hearing loss (ISSNHL) labyrinthitis 3403-4 midfrequency 3562 molecular analysis 12 myxoedema 400 otitis media with effusion 893, 339 1 otosclerosis 3456-7 ototoxicity-related 3542 petrous apex surgery 4052 post-stapes surgery 3475-6 recruitment 3 199-200 speech audiometry 3267 sudden see sudden sensorineural hearing loss (SSNHL) tinnitus 3599 tuberculous otitis 3448 vestibular schwannoma 3943, 4 143 viral aetiology 2 1 0-1 sensory ataxia 3778, 3780 stepping patterns 373 1 sensory hair derangement, ototoxic drugs 3676, 3677 F sensory nerve monitoring, skull base surgery 4145
Pages 1-13 12 are in Volume 1 , pages 1 3 1 3-28 10 are in Volume 2, and pages 28 1 1-4 147 are in Volume 3.
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4300 I I n dex
sensory organization test 3733 sensory organs, origin of 8 1 6 sensory tinnitus 3606 sentences, speech audiometry 3270 sentinel lymph node biopsy ( SLNB) malignant melanoma 2402 metastatic neck disease 2722 oral cavity tumours 2565 sepsis antimicrobial treatment 534 critical care patients 534-5 haemodynamic manipulations 534 leukaemoid reaction 273 nucleated red cells 266 post-blood transfusion 262 post-splenectomy 276 severe 534 Staphylococcus au reus 1 96 septal abscess 1 572-3 children 1 076 septal cartilage grafts, alar collapse 3010 septal deformities 1 574-5 compensatory turbinate hypertrophy 1 590-1, 1591 F deviated nose 2987, 2989 ePl�)ta:}ilS 160 1 mucosal turbinate hypertrophy 1 590-1 septal deviation see deviated septum septal flaps, nasal reconstruction 3020-1 septal fractures 1 573, 1 6 1 4 septal haematoma 1 572, 1 6 1 5 children 1076, l 3 1 1 F medical negligence l 3 1 1 nasal fractures 16 12, 1 6 1 5 septal abscess 1 572-3 septal luxation, newborn 1 574 septal perforation questionnaires 1 583, 1 5 84 F septal perforations 1 582-8, 1 573-4 aetiology 1 582, 1 583 T cautery and 1066, 1066 F clinical assessment 1 583, 1 584 F definition 1 582 epistaxis, children 1 066 investigations 1 584 management 1 585 nonsurgical 1 585 medical 1 733-4 nasal fracture complication 1 6 1 5 obturation 1 585 prevalence 1 582, 1 584-5 prevention 1 585 saddle nose deformity 1 6 1 5
surgery-induced 1 573-4, 1584-5 surgical 1 585 surgical repair 1 574, 1 586-7, 1 586 F external rhinoplasty 2967-8 symptoms 1 574, 1 582-3 septal tubercle (intumescence) l 328, 1 328 F septal tunnels 1 578, 1 579 F septicaemia, rhinosinusitis 1 540 septoplasty access 1 578 cerebrospinal fluid rhinorrhoea aetiology 1636-7 compensatory turbinate hypertrophy 1 590-1 indications 1 576-7 maxilla-premaxilla approach 1 578 1 577, open approach 1 578 F reconstruction 1 579 septal stabilization 1 580 supratip depression 3092 turbinates surgery and 1 590-1 septorhinoplasty aims 2979 medical negligence 309 1-2 patient expectations 3091 post-nasal fracture 1 6 14 septum 1569-8 1 anatomy 1 326-9, l 344-6 , l 345 F anterior l 326 augmentation rhinoplasty 2972 bleeding disorders 1 574 blood supply l 328, l 328 1; 1 570, 1 572 F bones 1326, l 326 F reshaping 1 579 cartilage 1 326, l326 F development l 3 1 6-7 harvesting 2972, 2975-6 reshaping 1579 deflections 1 326-7 development 803, 1 3 1 5-7, 1569-70 surrounding structures 1 570-1, 1 572 F developmental disorders 1 570-1 deviated see deviated septum growth 1 569-70, 1 570 F histology 1 327-8, l 327 F inferior 1326 innervation l 328-9, l 329 F investigations 1 576 lymphatic drainage l 329 mucosa l327 trauma 1 573
nasal function 1 570 ossification l 3 1 6-7, 1 570 pathology 1570-5 correction 1 578 diagnosis 1 575-6 removal 1 578-9 symptoms/signs 1 575 systemic disorders 1 575, 1 575 T posterior l326 sinusoid system l328 stem cells 75 superior l 326 tip shortening 3004, 3004 F trauma 1 569-72 vascular disorders 1 574 1 328 venous Serenocem 1 20, 1 2 1 F Serious Hazards of Transfusion ( SHOT) reporting scheme, ABO incompatibility 261 seromucinous glands maxillary sinus 1341 septum 1327 serotonin tinnitus 3608 vestibular neurochemistry 3794 serotonin agonists, migraine 1722 serous glands of Von Ebner 1 808 serous labyrinthitis 923, 3692 serous otitis media see otitis media with effusion COME) Servox 2624-5 sesamoid cartilage l 325 sestamibi parathyroid imaging 383, 384 primary hyperparathyroidism 391 VIIth nerve see facial nerve (VII) severe combined immunodeficiency ( SCID) 174-5, 1 75 T gene therapy 23, 27 severe congenital neutropenia (SCN) 177 T, 178 sevoflurane endoscopy 1 12 1-2 periglottic!glottic obstruction 48 1 tracheostomy 482 sex hormones, effects on nasal mucosa l 366 sexual behaviour, olfaction and 1 368 sexual functioning, cancer patients 2777 SF-6D 638 SF-36 634-5, 637, 638, 638 T, 639-40, 642 shaker- l mice, Usher syndrome model 3238
Pages 1-l3 1 2 are in Volume 1 , pages l 3 1 3-28 1 0 are in Volume 2, and pages 2 8 1 1-4147 are in Volume 3.
I n d ex
Shaker manoeuvre 2090, 2090 T sham surgery 3830 shared airways 494 Sheehan's syndrome 4 1 00
sickle cell disease 270 adenotonsillar hypertrophy 27 1 blood transfusion, iron overload 262 perioperative management 27 1 surgical complications 2 7 1
shield graft cleft lip nasal deformities 2967, 2967 F
sickle solubility test 2 7 1
nasal tip surgery 2965, 2965 F
sickling disorders 270- 1
I 4301
silver nitrate cautery epistaxis, children 1 065-6, 1 065 F medical negligence 1 3 1 0 silver splints, mandibular fractures 1 623, 1 623 F silver staining nucleolar organizer regions (AgNOR) 2494-5
blood transfusion 2 7 1
simple (solitary) bone cyst 1 926-7
Shiley tubes 1 1 99
clinical manifestations 270
shimmer (amplitude
investigations 27 1
simple sequence length polymorphisms (SSLP) 8-9
underprojected tip 3003-4
perturbation) 2 1 65, 2 1 79 shingles, pharyngeal manifestations 2079 Shipman, Harold 594, 602 Shipman Inquiry 2804
Sickness Impact Profile (SIP) 638
simple snoring 1 1 02-3
Sidaway v. Board of Governors of the
sine function 3 1 59, 3 1 59 F
Bethlem Royal Hospital and the
singer's formants 2 1 78 F, 2 1 80 , 22 1 1
Maudsley Hospital ( 1 985) 600,
single photon emission computed
2806
tomography ( SPECT)
shock 528
side-lying tests 3809- 1 0
malignant otitis externa 3338
short message service (SMS) 3669
sigmoid-jugular complex 4027
parathyroid glands 384
short Synachthen test 3 1 2 short tandem repeat polymorphisms ( STRP) 8-9 shoulder syndrome 2744 Shprintzen syndrome 1 139 sialadenitis, imaging 724, 1 8 80 sialagogues 1 862 sialochemistry 1 863-7
surgical management 4037 F, 4038-9, 4038 F
thrombosis 4027-8 venous drainage 4027 sigmoid sinus thrombosis, acute otitis media 924 signal accumulation, voice evaluation 2 1 83
skull base lesions 3947 singlet oxygen 745-6 sinonasal malignancy 241 7-36 aetiology 24 1 8 biopsy 1 350- 1 , 2426 clinical evaluation 2425-6 endoscopy 1 35 0-1 , 2425, 2426 F postoperative surveillance 1 35 1
antibacterial substances 1 866-7
signal filtering, hearing aids 3632
resection 1 350- 1 , 1 3 5 1 F
diseased states 1 864-6, 1 866 T
signal-to-noise ratio
site of origin and surgical
normal 1 863 sialography 1 877
averaging 3279 signal enhancement 3279
planning 1 350- 1 , 1 3 5 1 F visualization 1 350-1
acute suppurative sialadenitis 1 902
speech audiometry 3270, 3271
epidemiology 2347, 24 1 7-8
advantages/disadvantages 1 874 T,
voice evaluation 2 1 8 1
epistaxis 1 606
1 877
sign bilingualism 855-6
contraindications 1 877 indications 1 890 T magnetic resonance sialography
vs. 1 879 paediatric imaging 1 297
sign language
genetic analysis 1 1-2 imaging 2425-6, 2426 F, 2427 F
deaf children 855-6
incidence 2347
forms 566
medical negligence 1 73 1
visual-spatial axis 566
olfactory dysfunction 1 668-9, 1 673-4
Silastic 1 2 1
presentation 2424-5
relapsing acute parotitis 1 244, 1 244 F
dorsal nasal implants 2973
prognosis 24 1 7, 2434, 2434 T
sialolithiasis 1 8 79
maxillary resection 2930
risk factors 2347
sialolithiasis 1 904-5 children 1 246-7
Silastic sheet (Swiss roll), laryngotracheoplasty 2279
occupation 2347 social class 2347 spread patterns 24 1 8-20, 241 9 F
clinical features 1 904-5
silent reflux 1 2 72
imaging 1 878-80
silent sinus syndrome 1 345 F
distant metastases 2420
investigations 1 905
silent substitution 9-1 0
local invasion 24 1 8-9, 24 1 9 T
treatment 1 905
silent thyroiditis 352-3
ultrasound 723, 723 F, 724 F, 1 879,
silicone implants 1 2 1
regional spread 24 1 9-20 staging 24 1 7, 2420, 2424 T, 2425 T
advantages for use 1 22
surgical anatomy 24 1 8
augmentation rhinoplasty 2971
surgical pathology 2420-3
sialomucins, nasal mucus 1 3 59
complications 1 2 1
TNM classification 2366, 2367 T
sialorrhoea 1 9 1 4
dorsal nasal 2975 T
treatment 24 1 7, 2427-3 1
1 8 80 F
sialoliths 1 904-5
Parkinson's disease 3939 sialosis 1 907-8, 1 907 F Sicca syndrome 1 245 sick building syndrome (SBS) 1 420 sickle cell( s) 270
intracochlear electrodes 1 22
contraindications 2427
paralysed vocal folds 1 2 1-2
maxillary tumours 2427-8
silicone injection, vocal fold paralysis 2240, 2245 T silicone sheeting, keIoids 2892-3
principles 2427 surgical approaches 2428-9
see also specific typesllocations
Pages 1-1 3 1 2 are in Volume 1, pages 1 3 1 3-28 1 0 are in Volume 2, and pages 2 8 1 1-4 1 47 are in Volume 3.
4302 I I ndex
Sino-Nasal Outcome Test (SNOT-20) 620-1, 64 1 sinonasal papilloma 1 1-2 sino nasal surgery, epidemiological research 6 19-20 sinonasal undifferentiated carcinoma (SNUC) 2422 sinus( es) , paranasal see paranasal sinuses sinuscopy see nasal endoscopy sinus grafting 291 7, 291 8 F sinus histiocytosis (Rosai Dorfman disease) 1 2 1 7 sinusitis corticosteroids 42 1 facial pain 1 720-1 children 1 720-1 frontal sinus, iatrogenic 1 5 1 9 HIV patients 241-2 antibiotic treatment 242 endoscopy 242 imaging 306, 1 720 otitis media with effusion 3389 referral delay 1 730-1 see also rhinosinusitis sinus mycetoma see fungus ball sinusoidal rotation test 3728 F, 3 729-30 sinusoidal tone masking 3247 sinus tympani 3 1 12-4, 3 1 13 F Sipple syndrome see multiple endocrine neoplasia (MEN) Sir Harold Gillies' fifteenth principles 1 12 Sistrunk's operation 2686 VIth nerve see abducent nerve (VI) 68kD protein 3680 Sjogren syndrome 1 86, 1909-13 children 1 245 classification 1 9 10 T dental carries 1 9 1 1, 1 9 1 1 F diagnosis 1 863, 1 864-5 dietary supplementation 1 9 1 3 drug induced 1 906 T dysphagia aetiology 2032 electro stimulation 1 9 1 3 investigation 1 9 1 1 salivary gland imaging 724, 1 882 gland lymp homa 250 1 treatment 1 9 12-3 skeletal muscle denervation 70 skew deviation, thalamic nuclei lesions 3921 skier's nose 141 1 Skills for the new millennium 552
skin antimicrobial side effects 236 HIV patients 247-8 nasal 1 322 rheumatological diseases 1 83-4 stretching properties 2829 tissue engineering 1 26 wound dressings 100 skin biopsy, wound healing 97 skin cancer, head and neck 2395-405 diagnostic delays 3092-3 3092-3 medical risk factors 2396 T
see also individual types 102 skin care, wound skin diseases, oral manifestations 1834-5 skin eruptions, high-pressure nervous syndrome 3512 skin flap(s) 1 10-7 blood flow 1 1 1-2 animal models 1 13 distribution control 1 12 fluid mechanics 1 1 1 microcirculation 1 12 vessel diameter 1 1 1 viscosity 1 12 'choke vessels' 1 1 1 compromised 1 12-4 appearance 1 12-3 extrinsic factors 1 12-3 intrinsic factors 1 13-4 physical interventions 1 14-5 definition 1 10 design 1 1 1 length to width ratio 1 1 1 facial skin transfer 2829-30 historical aspects 1 10-1 nasal reconstruction 1 10 laser treatment 1 1 5 leeches 1 1 5 medical negligence 3093 musculocutaneous blood supply 1 1 1 necrosis, rhytidectomy 3094 'no reflow phenomenon' 1 13 oscillating veins 1 1 1 physiology 1 10-7 'retiform anastomoses' 1 1 1 surgical delay 1 14-5 'choke vessels' 1 14 tissue expansion 1 1 5 survival angiogenesis 1 1 4 combined therapy 1 14 drug treatment 1 13
gene therapy 1 14 monoclonal antibodies 1 14 surgically induced neutrophil recruitment 1 13-4 vascular endothelial growth factor 1 14 sympathetic innervation 1 12 vasospasm 1 1 3 vessel wall tension 1 1 2
see also individual types skin adherence 2820, 282 1-2 application 2823 bleeding, excessive 2823 constituents 2820 F crusting 3093 donor sites 2822, 299 1 F head and neck 2825 dressings 2823 free 2820-5 full thickness see full-thickness skin grafts harvesting 2820 instrumentation required 2822 medical negligence 3093 movement prevention 2823 nasal reconstruction 2 9 28, 30 19 pressure methods reconstruction ladder 2824, 2825 F secondary 2823-4 granulations 2823 : infections 2824 split thickness see split thickness skin grafts technique 2822-3 timing 2823
see also specific types/areas skin necrosis splint-induced 3091 warfarin-induced 282 skin prick tests (SPT) 158-9, 159 F, 169, 1 393-4 allergic fungal rhinosinusitis 1453-4 allergic rhinitis 1082, 1087 F, 1 393-4 food allergy 1 394, 1428-9 method 1394 occupational rhinitis 1420 patient exclusion 1 394 RAST vs. 1393 T rationale 1 393-4 sensitivity 1 394 specificity 1 394 skin regeneration, stem cell therapy 75 skin tag, ear 967, 969, 969 F
Pages 1-1 3 1 2 are in Volume 1, pages 1 3 13-28 10 are in Volume 2, and pages 281 1-4147 are in Volume 3.
I nd ex I 4303
skin types melanoma 2400 squamous cell carcinoma 2398 skip metastases 2 7 1 5 ski-slope deformity 309 1-2 skull embryology 794-5, 2 1 1 7 F expansion, Paget's disease 3489 normal growth 1 020 UH".llF,lHUH
skull base anatomy 3897-91 0, 3942
see also specific components anterior see anterior skull base boundaries 3897 defects/lesions see skull base defects/ lesions imaging 4123 lateral see lateral skull base middle 4122, 41 23 F posterior 3898-9 structures within 3909-10 surgery see skull base surgery tomography 3897, 3898 F skull base defects/lesions audiology 3946 common 3943 T current knowledge/future research 3948 epidemiology 3943 evaluation 3942-8 examination 3945-6 head and neck 3945 neurological 3945-6 vestibular 3946 facial function tests 3946-7 family history 3945 hearing loss 3943-4 investigations 3946-7 medical history 3945 radiology 3947 symptoms 3942-3, 3943-5 lower cranial nerves 3945 neurological 3944-5 ophthalmic 3945
see also specific symptoms tumours see skull base tumours vestibular function tests 3946
see also specific lesions skull base fractures cerebrospinal fluid rhinorrhoea 1636-7, 1637 F inner ear trauma 368 1-2 1684, 3994 T skull base skull base osteomyelitis see malignant otitis externa
skull base surgery catheter angiography 3949-5 1 complications 4 1 35-4 1 , 4 1 37-9 cardiac dysrhythmia 4 1 37 epilepsy 4139 haematoma 4 137-8 headaches 4 1 39 hydrocephalus 4139 infection 4138 intraoperative 4136-7 pneumocephalus 4 1 39 postoperative 4 145 vascular 4136 consent 4146 craniofacial surgery and see craniofacial and skull base surgery image-guided surgery 708 , 708 F internal carotid artery test 395 1 medical negligence 4142-8 monitoring 4145 tumours embolization see tumour embolization, skull base vascular assessment and management 3949-56 vascular management 3949-56 skull base tumours 41 23-7 dysphagia aetiology 2033 extracranial lesions 4123 hereditary syndromes 3945, 3945-6 incidence 3943 intracranial 41 23, 4126-7 benign 4 1 26-7 pathology 4123-7 primary lesions 4123-6 benign 4 1 23-5 malignant 4 1 25-6 surgery 41 27-32 follow-up 4127 principles 4127 recurrence 4127 symptoms 3943-4 vascular assessment 3949
see also individual types sleep definition 2305 optimal duration 2306 2305 physiology 2305-12 respiration, effects on 2306-7, 2306 F efferent output 2307 clinics, special n;eds children 787-8
sleep-disordered breathing 23 13-4 adenotonsillectomy 1 1 09 arousal 1 1 03 home monitoring 23 1 6-7 mechanism 1 1 03-4 physiological effects 1 103-4 termination 1 103-4 upper airway obstruction 1 1 02 see also obstructive sleep apnoea (OSA) sleep disorders 2305-12 full polysomnography 1 1 04 nonrespiratory 2 3 1 0-1 respiratory 2307-9
see also individual disorders sleep nasendoscopy children 1 106-7 treatment options 1 109-1 0 grading 1 106, 1 107 F, 2328 T snoring 2328, 2328 T sleep studies obstructive sleep apnoea 1 105-6 paediatric laryngeal stenosis 1 1 54-5 slide tracheoplasty, tracheal stenosis 1 144 ' slipping clutch phenomenon' 373 1 slough 9 9 F post-rhytidectomy 3075 wound dressings 1 0 1 wound healing 9 8 Sluder's neuralgia 1 723-4 small cannula cricothyrotomy 476-7 small cavity mastoidectomy, cholesteatoma 3432 smell see olfaction smell abnormalities/disturbances see olfactory disorders/dysfunction Smell Identification Test ( tm) see University of Pennsylvania Smell Identification Test smell threshold tests 1 666 smoke (artificial), professional voice and 22 12 'smoker's larynx' see Reinke's oedema smoking allergic rhinitis 1386-7, 1 396 candidiasis 223 chronic laryngitis 2258-9 radiation-induced 2268 Graves' disease 340 hypopharyngeal cancer 2634 implant osseointegration 2 9 1 0 laryngeal cancer 2348 laryngeal changes 763 occupational rhinitis 1 4 1 6
1-1 3 1 2 are i n Volume 1 , pages 1 3 1 3-28 1 0 are in Volume 2, and pages 28 1 1-4147 are i n Volume 3 .
4304 I I ndex
smoking (continued) olfactory dysfunction 1 664, 1 670 oral cavity tumours 2550, 2550 F otitis media with effusion 626, 882, 883-4 pinna reconstruction 3044 Reinke's oedema 2265 rhytidectomy 3070, 3094 sinonasal malignancy 24 1 8 taste abnormalities 1 848 thyroid eye disease 340 voice disorders 2195 see also tobacco smoking cessation, chronic laryngitis 2264 smooth pursuit eye movements 3227 T balance disorders 37l3-4 brainstem lesions 3713 examination 3 7 l 3-4 global abnormalities 3714 laboratory assessment 3726 pandirectional 37l4 saccadic tracking 3713, 3713 F sneezlIlg 1 364 SnNOut mnemonic 656 SNOMED CT ( Standard Nomenclature of Medicine and Clinical 2375 snoring ag��ra'iTatmg factors 2325-6 clinical presentation 2326 definitions 2307, 2325-6 enlarged turbinates 1 5 9 1 epidemiology 2325-6 examination 2326 full polysomnography 2327 history 2326 nasal obstruction 233 1 nasal resistance 1 59 1 nonsurgical treatments 2333 obstructive sleep apnoea 1 104, 2327-8 obstructive sleep apnoea vs. 2327-8 preoperative investigations 2326-9 severity 2327-9 simple 1 102-3 site identification 2328-9 surgical management 2325-40 complications 2332 indications 2329 occasional procedures 233 1-2, 233 1 T outcomes 2332-3 postoperative care 2332 techniques 2329-32 upper airway wall vibration 2307, 2325
snuffles 1462 treatment 1462 societies, paediatric otorhinolaryngology 773 Society for Biomaterials 1 1 8 sodium endolymph 3 187-8, 3 1 87 T nasal secretions 1 360 perilymph 3 189 T restriction, Meniere's disease 3759 sodium bicarbonate, ear wax removal 43 1 sodium chloride testing, regional taste deficits 1 844 sodium citrate, coagulation tests 280 sodium cromoglicate allergic rhinitis 1 398 rhinosinusitis 440 children 1 083 sodium fluoride, otosclerosis 434 sodium iodide (NA+/n symporter 32 1-2 sodium metabisulphite 429 sodium thiosulphate, ototoxicity prevention 3302 Softband hearing aid childhood deafness 854, 854 F otitis media with effusion, childhood 903 soft palate anatomy 1 007-9, 1 009 F, 1 792, 1 792 F, 1945-7 development 1 8 12-3 function 1 007-9, 1 009 F innervation 1 947 lymphatic drainage 1 947 muscles 1945 F, 1 946 T paralysis, diphtheria 2253 repair 1008 F, 1009- 10 structure 1 945 swallowing 1 954-5, 1 956 tumours 2589 vasculature 1 799, 1947 soft tissue facial injuries (level 3) 1632 pain, cancer patients 2784 transcutaneous electrical nerve stimulation 2784 soft tissue flap mobilization 2920 soft tissue neoplasms, ultrasound 725-7 soft tissue sarcomas ( STS) adult type 1935-6 anatomical sites 1 935, 1935 T lymph node metastases 1935
management 1935-6 resection 1935-6 children 1 259, 1 259 T, 1 260 F classification 1932 T solar keratosis see actinic keratosis solid state lasers 743 solid tumours, Halstedian concept of treatment 271 7 solitary bone cyst 1926-7 solutions 448-9 somatic mutation 135 'somatic mutation theory' of cancer 2354 somatic nuclear transfer/cloning 74 somatosensory system disturbances 3240 T somatosounds 3600-1 aetiopathophysiology 3600-1 myogenic 3600 vascular 3600 somatostatin 300 somatostatin analogues, acromegaly 301, 4 1 0 1 somatotrophin see growth hormone somatotrophs 296 somnoplast device, diathermy vs. 2330 T sone 325 1 sonography see ultrasound sore throat, acute onset see pharyngitis, acute sound 3 158-72 absolute threshold 3250, 325 1 F acoustic admittance/ compliance 3 168-9 acoustic 7 l2, 7 l3, 3 165, 3 167-9 acoustic radiation 3 162 analysis 3 1 73-8 intensity 3 165, 3 173-5 definition 3 1 74 superior olivary complex 3 142 voice evaluation 2 1 77 measuring audiometric scales 3 1 7 1 decibel scales 3 170 microphones 3 1 69-70 noise exposure 3 171 sound level meters 3 170 weighting 3 1 70-1 see also audiometry 'particles' 3 162 perception 3245-59 frequency see frequency selectivity
1-1 3 1 2 are in Volume 1, pages 1 3 1 3-28 1 0 are in Volume 2, and pages 28 1 1-4147 are in Volume 3.
I nd ex I 4305
hearing impairment 3255-7 loudness see loudness perception reflection 7 1 1 , 3 1 75-6 see also ultrasound resonance 3 1 67 vibration 3 1 58-62 adding (superposition) 3 165-7 forced vibrations 3 1 6 1 resonance frequency 3 162 see also vibration(s) voiced 2 1 70 waves see sound waves see also noise sound desensitization, hyperacusis 3596 sound energy density 3 165 sound-evoked vestibulocollic reflex 374 1 sound exposure level 3 1 7 1 sound field 3 162, 3 1 63, 3 164 sound localization 3255 binaural cues 3255 cochlear hearing loss 3257 'duplex theory' 3255 external ear 3 1 79, 3 1 79 F, 3255 sound source elevation 3 1 79 high frequency sound 3255 intensity differences 3255 phase differences 3255 precedence effect 3255 superior olivary complex 3 14 1-2 sound 'particles' 3 162 sound power level 3 1 70 sound pressure 3 1 62, 3 168, 3 1 69-70 sound pressure level (SPL) 2 1 77, 3 1 73 sound production disorders 992-4 sound retraining programme, hyperacusis 3596 Soundtec Direct Drive Hearing System (DDHS) 3661 sound waves 7 1 2, 3 162-5 diffraction 3 1 67, 3 167 F Fourier analysis see Fourier analysis frequency 3 1 75 sensation and 3 175 velocity 3 1 75 wavelength 3 1 75 interference patterns 3 166-7 lo ngitudinal waves 3 163 medium density effects 3 163 nodes/antinodes 3 166-7, 3 166 F plane progressive 3 164 pressure 3 1 62, 3 1 68, 3 1 69-70, 3 1 73-5, 3 1 74 F propagation 3 163, 3 1 75-6
attenuation by distance 3 1 75 transmission between different media 3 1 75-6 sound field 3 162, 3 1 63 far field 3 1 64 near field 3 1 64 objects within 3 164 speed 3 164 standing waves 3 1 66-7, 3 166 F transmission 3 1 73, 3 1 74 F wavefront 3 1 64 distance and 3 1 75 wavelength constant (k) 3 164 Southern blotting 6 space and motion discomfort see visual vertigo spasmodic croup 1 129 spasmodic dysphonia 2203, 2224, 3940 diagnosis 2203 treatment 64 1, 2203, 2224 types 2203 spasmodic dystonia 449-50 spasmodic laryngitis 1 129 spasticity, stepping patterns 373 1 spatial coding definition 3235 vestibular hair cells 3235 spatial compounding, ultrasound advances 713 spatula test 778, 779 F speaking fundamental frequency (SFF) 2 1 77-8, 2 1 78 F special care baby unit (SCBU) 774 specialist registrars, training issues 553 special needs children 783-9 1 clinical environment 783-4 communication and rapport 784-5 drooling 788-9 ear and hearing 785-6 ethical issues 785 hearing assessment 785, 841 prognosis 785 terminology 783 upper aerodigestive tract 786-8 specification, otic field 8 1 5 specificity (definition) 823 specific language impairment (SLI) 99 1 spectacle-retained prostheses 2932, 2932 F, 2934, 2936 F spectrograms, voice analysis 2 1 78 F, 2 1 79-80 spectroscopic optical coherence tomography 759 speech bulbar palsy 3939 •
development 990-1 otitis media with effusion 893-4 stages 991 F ventilation tubes 899 dynamic range 3267 fundamentals of 2 1 66-7 nasalance assessment (nasometry) 1 375-6 paralinguistic features 2 167-8 Parkinson's disease 3939 phonemes 3267 production 2 164-9, 992-3 disorders 992-4 organic factors 2 1 64-5 phonetic factors 2 164-5 sound source characteristics 2 165 quality 2 165 rate, paralinguistic features 2 168 rhythm 2 168 voice evaluation 2 1 72-4, 2 1 73 F consonant-vowel sequences 2 1 72-4 fluent speech 2 1 72, 2 1 74 T percentage irregularity score 2 1 79 see also voice speech and language therapists (SLT) 990 speech audiometry 3267-73 audiovisual aspects 3269, 3271-2 background noise 3270-1 applications 3273 frequency spectrum 3270-1 signal-to-noise ratio 3270, 3271 unmodulated random noise 3271 bisyllabic words 3270, 3272 bone-conduction hearing aid assessment 3644 clinical applications 3273 complexity 3267-8, 3273 confounding factors/error 3272-3 cognitive 3273 psychological/linguistic 3273 statistical 3272, 3272 F diagnostic power 3270 equipment 3268-9 calibrationlreliability 3269 masking 3268, 3270 monosyllabic test words 3270, 3272 psychometric function curve 3268, 3268 F reference data 3273 scoring 3272 skull base lesions 3946 sound field audiometry 3269 speech level 3269
Pages 1-1 3 1 2 are in Volume 1, pages 1 3 1 3-28lO are in Volume 2, and pages 281 1-4147 are in Volume 3 .
4306 I I nd ex
speech audiometry (continued) terminology/definitions 3268, 3269, 3271 test environment 3269 ambient noise levels 3269 test material 3269-70 connected/continuous speech 3270, 327 1 dialogue 3272 dichotic 3270 logatoms 3269, 3272 sentences 3270 test method 327 1-2 see also pure-tone audiometry speech delay 992 speech discrimination cochlear implants, children 863 definition 3268 speech disorders, children 990-5 adenoids and 993 classification 99 1-2, 992 T expressive 991 , 992 T presentation 991-2 tonsils and 993 speech intelligibility 3 268 speech intelligibility rating ( SIR) 3271 speech reception threshold (SRT), central auditory dysfunction 3859 speech recognition auditory neuropathy 3844 definition 3268 maximum score 3271 scores 3564 F sigmoid curve of 3268, 3 268 F threshold level 327 1 , 3273 Speech Studio Programme 2 177-8 speech therapy 2 2 1 6-33, 2 195 Accent method 2219-20, 2225 aims 2 195, 2218 efficacy 2 2 1 8, 22 19-20 hyperfunctional voice disorders 2225 laryngitis 22 1 9 acute 2 2 1 9 chronic 2 2 1 9 , 2264 radiation-induced 2268 neurologically-based voice disorders 2222-5 nonorganic voice disorders 2219-20 organic voice disorders (benign) 2220-2 outcomes, goal-based 2 2 1 8 pitch disorders 2226--7 psychogenic voice disorders 2225-6 techniques 2 1 95 velopharyngeal insufficiency 1 0 1 1
vocal fold cysts 2202 vocal hygiene techniques 2220 speech-to-noise (SIN) ratio 3667 sneecrl-trackinQ' 3271-2 S phase, cell cycle 2381 sphenoethmoidal cells (Onodi cells) l336-7, 1 678 sphenoethmoidal recess 1 337, 1 344-6 second pass endoscopy 1 348 sphenoid bone 1338-9, 1339 F in anterior cranial fossa 41 20, 4122 F at birth l 3 1 8 body 1338-9 development 1 3 1 8 fusion 1 3 1 8 lateral skull base 3 899-900 nasopharynx 2 1 1 0 plates 1 338-9 pneumatization 1 3 1 9-20 premature ossification 1 320 pterygoid process 2 1 1 1 sella turcica see sella turcica wings 1 338-9 sphenoid meningioma 1685 sphenoid os, endoscopy 1 348 sphenoid sinus anatomy l 338-9 associated structures 4108 asymmetry 1 3 19-20 blood supply 1 339 development 1 3 19-20 drainage 1 368 histology l339 innervation 1 339 intrasphenoid sinus septae 300 lymphatic drainage 1 339 magnetic resonance imaging 305 F, 306 opening 1 339 osteology 1 338-9 pituitary tumours 4100 hypophysectomy 41 06, 4 106 F, 41 08-1 1, 4 1 08 F pneumatization 299-300, 1 320 F, 1 339 prominences l 33 9 rhinosinusitis 2 19, 2 2 0 F, 1 540 tumours, patterns of spread 2419, 2420 F sphenomandibular ligament 1 8 1 0, 3908 sphenooccipital junction 794-5 sphenopalatine artery 1 328, 1 337 endonasal ligation 1 598, 1603, 1603 F epistaxis 1 597 embolization 739
sphenopalatine foramen 1 33 7, 1 598, 3897-8 sphenopalatine ganglion 2 1 1 1 sphenopalatine ganglion neuralgia 1 723 spherical cells 3 1 40-1 , 3 142 F spinal accessory nerve (XI) 1 75 1 , 3 9 3 3 F, 3934 F, 3935 central connections 3934 F clinical disorders 3937-8 clinical evaluation 3937-40 cranial part 1 75 1 , 3935 rootlets 3935 spinal root 3935 vascular lesions 3935 spinal epidural abscess 2002 spindle naevi, nasal 1707 spindle poisons 38-9 SPIN lists, speech audiometry 3 270 spinocerebellar ataxias (SeA) 3773 aetiology 3 773 clinical manifestations 3774 diagnosis 3774 management 3774 spin-spin time, functional magnetic resonance imaging 676 spiral ganglion neurons 3 1 36, 3 1 38 F action potentials 3 137-9 speech recognition, post-cochlear implants 3650, 3655 threshold frequencies 3 13 9 type I 3 13 6 type II 3 13 8 F, 3 139 spiral ligament 'hyalinization,' otosclerosis 3455 F, 3456-7 spiral limbus, longitudinal ridge 3 1 2 7 spirochetes 202 spirometry aerodynamic voice measures 2 1 8 1 nasal airway measurement l 376 spitting, saliva collection 1 862 Spitz naevi, nasal 1707 splenectomy 276 sepsis 276 thrombocytopenia 287 vaccinations 276 splenomegaly, thrombocytopenia 287 splicing 4 alternative 4, 1 5-6 split thickness skin grafts 97, 2820-3 adherence 2820 buccal carcinoma 256 1 depth, effect of 2820 donor site healing 3093 lifespan 2820 nasal reconstruction 3019
Pages 1-l3 12 are in Volume 1 , pages 1 3 l 3-281O are in Volume 2, and pages 2 8 1 1-4147 are in Volume 3.
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surfaces that take well 282 1
histopathological grading 236 1
'take' requirements 2820
I CD- 0 3 morphology codes 2374-5, -
technique 2823 F
2375 T
spondylarthropathy 186
laryngeal 2600-2, 2601
spontaneous nystagmus
F, 2608 F
epidemiology 2602
acute unilateral vestibular
management 2609-18
deafferentation 3222-3
l i p 2543
balance disorders 37 1 1-2
lupus vulgaris
convergence absence 37 1 1
1703
vs.
metastasis 2399
dynamic visual acuity 3 7 1 8
cervical lymphadenopathy 2703
examination 37 1 1-2 central lesions 37 1 1-2, 37 1 1
F, 37 1 2 F
per ipheral vestibular lesions 3 7 1 1 ,
37 1 1 F 5 labora tory assessment 3724-5, 372 F visual suppression 3724-5
waveforms 37 1 1 , 37 1 1 F
lpOotaneo us otoacoustic emissio ns
(SOAE) , tinnitus 3600- 1 , 3603-4 auditory disinhibition 3604 sound interaction 3604 .tan�eO\lS ventilation , airway
nasal 1 705, 1 705
F, 2420
differential diagnosis 1 705 odontogenic keratocysts 1 938-9
p53 mutations 58 paranasal sinuses 2420 perineural spread 2399 poorly differentiated tumour 2399 premalignant conditions 2398 recurrence 2399 risk factors 2398 salivary glands 250 1 , 2503 recurrence rates 25 1 1 survival 25 1 2-3 salivary gland tumours,
ICIlta1tl01G, post-first attack 378 1 .tatic)ll during attack 3780 378 1
malignant 2501 syndromes 2398 temporal bone see temporal bone squamous cell carcinoma tonsils 1 226 treatment 2589 tracheal 2602 treatment 2398-9 types 2398 squamous cell carcinoma antigen
2386 T squamous epithelium larynx 763 replacement of ciliated epithelium 763 nasal cavity 764 nasopharynx 766 squamous odontogenic tumour, jaw 1 928 Stafne's bone cyst 1 927, 1927 F stage grouping, tumours 236 1-2, 236 1 T Stahl's bar deformity 970, 970 F stainless steel implants 1 1 9 stance dise ase 687- 90,
oral cavity 2634
pharynx 26 3 4
value (S UV) , standardized uptake ion SS positron enll 84 6, 1 756 tomography 6 . ure of Medicme at cl Stand ard NoIU en N . al Terms (S OMED and Cll' illC .
CT) 237 5 alth 578 Standard5 fior better he stapedectomy
'tremulous' 373 1 standardized incide:pce ratio (SIR )
38 27
am bilateral audio gr 3 468 ts c pe historical as partial 347 1 -2
nsorineural hearing postoperatI. ve se
5 6 damage 3 47 -
3 73 F procedure 34 72 , 4 stapedotomy
vs.
3 477-8, 3478 T
's 342 3 tympanosclerosl ss ified 872 stapedial tend on, o stapedius 3 1 1 5
83, 3 289
, reflex 3 1 acoustiC d ers 3870 facial nerve disor
hearing 3 1 8 3
.
hresh olds, audItory , stapedms refleX t / ssynchrony 3844 neuropathy dy , , pr eservatIOn 3479 stapedlUs tend0n stapedotomy
60 1 consent iss ues 6 00, 3 es 4 78-9 . heanng outcO m ' 3478-9 omp anson equipm ent c 3477-8, vs. . stapedectomY 347 8 T I, ce 1 307 eg gen
medical n I ' , , enson neural heanng postoperauve s
75 6 damage 3 4 2 , 3472 F procedure 3 4 7 1 tion 347 1 -2 prosthesis selec stapes
anatomy 3 1 1 5 ,
31 15 F
crus 3 1 1 5 tP iate c apes 100 footplate see st 3 1 8 1 t en mode of m o vem stapes ankylos is rIIllu es 872 associated d efo "
isolated 87 0
T,
87 1 2 -
stapes footp late , . al fucat i O n congemt g medical n eg li
enCe 1 3 07
surgery 87 2
deafferentation 3223 observation 373 1
I 4307
lung 2634
acute unilateral vestibular 'bouncy' 373 1
floating 34 74
6 otosclerosis 3 45
'rice grain' 3 4 7 4 rative hazards surgery, pe n. ope
3474- 5
cancer
1 -1 3 1 2
I ndex
------
' H are m vO1ume 1 , page . Volume 3 . s 1 3 1 3-2 8 1 0 are in Volume 2, and pages 2 8 1 1-4 1 47 are ill .
4308 . I nd ex
stapes mobilization 3472 historical aspects 3468 tympanosclerosis 3423 stapes piston see total ossicular replacement prosthesis ( TORP) stapes protheses, historical aspects 3468 stapes surgery anaesthesia 3470-1 general 347 1 local 347 1 contraindications 3468-70 exposure 347 1 hearing outcomes 3477-80 connective tissue seals 3479 prosthesis type 3479 stapedius tendon preservation 3479 technique comparisons 3477-9 incisions 347 1 medical prophylaxis 3470 perioperative hazards 3473-5 anatomical 3473-4 comorbities 3474 ossicular problems 3474 stapes footplate 3474-5 surgical approach 3473 postoperative complications 3475-7 incus necrosis 3475 prothesis displacement 3475 revision 3473, 3479-80 clinical indications 3473 T laser use 3479 sound transmission mechanism restoration 347 1 suprastructure fixation 872 techniques 3470-3 tinnitus outcome 3480 tympanic membrane perforation 3473
see also individual procedures staphylococci 1 96 chronic rhinosinusitis 1441 coagul:ase-·ne��ati''le 196-7 coa,guJ.ase test 196 Gram stain 1 96 growth conditions 196 HIV-associated otitis media 240 morphology 1 96
see also individual Staphylococcus aureus 1 96-7 adult epiglottitis 2250 blood agar cultures 1 96 coagulase test 1 96 facial infection 1 700 food poisoning 1 96 furunculosis 3 324
HIV-associated infection dermatological manifestations 248 pinna 240 host-cell adhesion 1 96 infections caused 1 96 methicillin-resistant see methicillinresistant Staphylococcus aureus (MRSA) nasal infection 1 700 perichondritis 3358 V L ..· v aJ' ,;; 196 rhinosinusitis chronic 1 44 1 , 1471 HIV patients 241-2 1 96 tonsil flora 1 2 1 9-20 toxic shock syndrome 196 virulence factors 1 96 Staphylococcus epidermidis 196 Staphylococcus pneumoniae 1 700 663 statistical ...H....
steady-state evoked potentials ( SSEP) 3287-8 auditory neuropathy/ dyssynchrony 3843-4 steady state responses (SSRs) 3280, 3287-8 40 Hz AMEPs 3286 F, 3288 amplitude fluctuations 3288 frequency-specific sensitivity assessment 3291-2 neonatal hearing screening 329 1 transient evoked potentials vs. 3288 Steele-Richardson syndrome 3939 steeple sign 1 128, 1 128 F stem cell( s) 66-84 activation adult tissue 67 nerves and 70 tissue repair 67 apoptosis 67-8 asymmetric division 67, 67-8 carcinogenetic potential 69-70 coculture 68 connexin expression 68 deafness treatment 8 18 differentiation 67, 67-8 community effect 68 specificity 68 embryonic development 68-9 embryonic origins 7 1 growth factors effects of 69 production 7 1-2 growth signals, response to 69
haemopoietic see haemopoietic stem cells hierarchies 68-9 migration 7 1 mucosal malignant melanoma aetiology 2409 multipotency 69 neural see neural stem cells niches 67 olfactory system 74-5 organ replacement 75 pluripotency 70 proliferation 67 properties 67, 76 purification 73-4 telomerase activity 70-1 therapeutic uses 66, 72-3 embryonic stem cells 73-4 genetic disorders 73, 75-6 regeneration support 74-6 tissue/organ regeneration 69, 72 adult teeth 75 cartilage 75 cochlear hair cells 75 mechanisms 72 neural stem cells 75 skin 75 therapeutic intervention 72 tissue-specific committed 69 stem cell factor ( SCF) 69 stem cell theory of cancer 69-70 Stemetil see prochlorperazine <..:+£>·...,.. 1"'·" 'Voice Function Exercise I:'rogralffi111le' 2225 Stenson's organ 1 325-6 stent(s) laryngotracheal reconstruction, children 1 1 57-8, 1 1 58 F Lua.Ul"l".
see also individual types step initiation impairment 373 1 'stepping on the spot test' see Unterberger test stereocilia cochlear hair cells 3 130, 3 13 1 F, 3 1 92 tip links 3 1 92, 3 1 93 F 20 hearing membranes ion channels 3 1 3 3-4 transduction 3 1 3 3-4 vestibular hair cells 3228, 3229 F tip links 3228, 3229 F
see also individual cell types
Pages 1-1 3 1 2 are in Volume 1, pages 1 3 1 3-28 1 0 are in Volume 2 , and pages 28 1 1-4 147 are in Volume 3 .
I ndex I 4309
stereotactic amygdalotomy, epilepsy related olfactory dysfunction 1671 sternal head 1 745 sternocleidomastoid 1745 surface anatomy 1741 weakness, spinal accessory nerve lesions 3935 sternohyoid 2 1 35 T sternomastoid 3910 vestibular-evoked myogenic potential 375 1 sternomastoid flap 2861-3, 2864 F sternothyroid 2 1 35 T sternothyrolaryngeal triangle 2664, 2664 F steroids see corticosteroids stertor definition 1 1 14 obstructive sleep apnoea 1 104 Stevens-Johnson syndrome 236, 2004, 2033-4 Steven's power law 325 1-2 STI 571, chronic myeloid leukaemia 275 Stickler syndrome 813 T, 968 'stimulated emission' 742 stimulus frequency otoacoustic emissions (SFOAEs) 3276-7 Stokes method 234, 235 F stomatococci 1 96 stomodeum 799, 799 F, 802 F, 1 8 10-1, 1942, 1942 F pituitary gland development 295 Stool, Sylvan 772 Storz scopes 5 1 8 , 518 F 'stove-pipe' microtrachea 1 144 strained (pressed) voice 2 165 strap muscles 1 746 'strawberry skin' 1647-8, 1 647 F streptococci 197-8 Anginosus-Milleri group 1 98 classification 1 97 group A beta-haemolytic streptococci (GABHS) see Group A beta haemolytic streptococci (GABHS) group C 197 group G 197 morphology 197 oral (viridans) 195-6, 198 pyogenic 197 related species 197
see also individual species streptococci, group A 197 adult epiglottitis 2250 diseases caused 197
haemolysins 197 serotypes 197
Streptococcus agalactiae 197 Streptococcus anginosus 1 98 Streptococcus constellatus 198 Streptococcus intermedius 198 Streptococcus milleri 198 Streptococcus pneumoniae 1 97-8, 197 F acute otitis media 924 adult epiglottitis 2250 diseases caused 197-8 a-haemolysis 1 97-8, 198 F HIV-associated otitis media 240 morphology 197-8 nasopharynx 2 1 2 1 otitis-prone children 1 95-6 penicillin-resistant 197-8 prevention 197-8 rhinosinusitis 144 1 acute 1080 chronic 147 1 HIV-associated 24 1-2 sensitivity 1 97-8 vaccination 197-8, 9 1 9 Streptococcus pyogenes 197, 1 97 F diseases caused 1 97 facial infection 1 700 nasal infection 1 700 otitis-prone children 195-6 skin grafts 282 1-2 Streptococcus viridans 1471 streptogramins 232 streptokinase 283 streptomycin 232 ototoxicity 3239, 3569, 3676 respiratory scleroma 1463 stress adrenocorticotropic hormone secretion 300 Meniere's disease 3798 tinnitus 3604 F, 3607 stretch receptors, carotid artery 1 749 stria vascularis 3 129 F, 3 1 30, 3 1 86 stridor 1 1 14-26, 2286-7 acute laryngeal infections 1 127, 2248-9 assessment 1 1 1 5-23 associated features 1 1 1 6-7, 1 1 1 7 T, 1 1 18 biphasic 1 1 1 8, 2286 bronchoscopy 1 122-3 characteristic sounds 1 1 1 8 children 1 1 14-26 examination 1 1 1 8 feeding history· 1 1 1 7
history 1 1 16-7 intensive care 544-5 management 1 1 14-5 perinatal history 1 1 16 definition 1 1 14 differential diagnosis 1 1 1 5 T, 1 1 1 6 T, 1 127 endoscopy 1 1 1 9-23 expiratory 478, 2286 extrathoracic obstruction 1 1 18, 1 1 18 F head and neck cancer palliative care 2795 imaging 1 1 19 inspiratory 2286 investigations, pre-endoscopy 1 1 19 laryngeal cleft 1 141-2 laryngeal stenosis 1 1 5 1 laryngomalacia 1 1 35 management 449 patterns 1 1 16 periglottic/glottic obstruction 48 1-2 posterior glottic stenosis 1 1 60-1 special needs children 787 tracheobronchomalacia 1 145 tracheomalacia 1 145 striola, saccule 3230 strip craniectomies, craniosynostosis 1027 strobovideolaryngoscopy see videolaryngostroboscopy stroke 3767-70, 3779 aetiology 3767-8, 3768 F clinical manifestations 3768-9 complications 3770 definition 3767 diagnosis 2078, 3769 differential diagnosis 3769-70 dysphagia aetiology 2033 dysphagia management 2086 management 3770 neurological disorders, pharynx 2077-8 symptoms 2077 outcomes 3770 postoperative carotid angiography 395 1 permanent balloon occlusion 395 1 prevention by endovascular embolization 735 sleep apnoeas 2314 taste abnormalities 1 847, 1 848 F stroke volume, hypotensive anaesthesia 502 stromal cell-derived factor 1a 7 1
Pages 1-13 1 2 are in Volume 1 , pages 1 3 1 3-28 10 are in Volume 2, and pages 281 1-4147 are in Volume 3 .
43 1 0 I I n dex
stromal cells, bone marrow 266 Sturge-Weber syndrome 1 708 stuttering 993-4 Stycar test 841 styloglossus 1 797, 1 797 F, 3904 stylohyoid 1956-7, 2 1 3 5 T, 3904 stylohyoid ligament 3904 stylohyoid syndrome 3533 investigation 3533, 3533 F otalgia 3533 presentation 3533 surgery 3533 styloid apparatus 3904 styloid process, temporal bone 3900 development 3 124 stylomandibular ligament 1 8 1 0, 3904 stylomastoid foramen 3904 stylopharyngeus 1 945 F, 1 948 T, 1949 F, 1950, 2 135 T, 3904 subacute necrotizing lymphadenitis ( Kikuchi's disease) 1 2 1 7, 1 784-5 subacute necrotizing sialadenitis 1 9 1 5 subacute thyroiditis 33 1 , 35 1-2, 3 5 2 F, 720, 72 1 disease course 352 F follicular destruction 352 histology 352 hypothyroidism 352 imaging 335, 352, 72 1 symptoms 35 1-2 tests 35 1-2 transient thyrotoxicosis 33 1 treatment 352 viral aetiology 352 subarachnoid space 3914 subcarinal lymph nodes 2 143 subclavian steal syndrome diagnosis 3769 management 3770 aetiology 3767 provoked stroke aetiology 3768 subclavian triangle, neck 1 743 subclinical hyperthyroidism 345, 353 complications 353 diagnosis 353 treatment 353 subclinical hypothyroidism 357-8 aetiology 358 autoimmune disease 358 definition 357-8 management 358 pregnancy 359-60 prevalence 357-8 thyroid peroxidase antibodies 358 subcupular meshwork 3228-30
subdermal haematoma, post septoplasty 3092 subdural abscess acute otitis media 924 chronic otitis media 3404, 3405 F, 3437, 3438 subdural haematoma, syndromic craniosynostosis surgery 103 1 subdural space, optic nerve 3914 subepithelial immune bullous diseases, oral manifestations 1 834 subepithelial tissue imaging limitations/problems 755 OCT see optical coherence tomography ( OCT) subglottic allergic oedema 1 1 29 subglottic cancer clinical presentations 2608-9 laryngectomy 2602 spread 2602, 2602 T TNM classification 2367 T subglottic haemangioma 1 140-1, 1 140 F CO2 laser vaporization 1 140 interferon alpha-2a 1 141 intralesional steroid injection 1 14 1 radiotherapy 1 140 submucosal excision 1 14 1 systemic steroids 1 140 tracheostomy 1 140 subglottic obstruction 483 subglottic oedema acute 1 129 croup 1 1 28, 225 1 subglottic pressure 2 1 82 subglottic reconstruction 1 162-4 techniques 1 162-4
see also individual procedures subglottic stenosis 2282 acquired 1 1 50 acute laryngeal infections 1 1 32 congenital 1 1 50 gastro-oesphageal reflux 1273 intubation 1 170 nasotracheal intubation-induced 1 1 32 surgery 1 1 62-4 sub glottis anatomy 1 1 35, 2 132 children 1 1 5 1 congenital disorders 1 1 39-42 subjective postural vertical 3738 F, 3741 subjective vertical testing 3737-40 subjective visual horizontal (SVH) test 3752, 3754 F
subjective visual vertical (SW) 3740-1, 3741 F central vestibular lesions 3741 hemisphere lesions 3741 peripheral vestibular lesions 374 1 sublingual artery 1 799 sublingual ducts 1 808 sublingual folds 1 793, 1 808 sublingual glands 1 856-7 anatomy 1 793 F, 1 808, 1 856-7 blood supply 1 856-7 embryogenesis 1 852 excretory ducts 1 808 imaging 1 873 F innervation 1 856-7 salivary flow rates 1 807 tumours 2505 sublingual immunotherapy (SLIT) , allergic rhinitis 1 084 sublingual papilla 1 793, 1 793 F sublingual space 1 758, 1796 F, 1 806 sublingual vein 1799 submandibular duct 1 796 F, 1 797 F, 1 808, 1 856 ligation 789 transposition, drooling 789 submandibular ganglion 1 808, 3929 submandibular glands 1 856 anatomy 1 796 F, 1 808, 1 856 blood supply 1 856 capsule 1 856 embryogenesis 1 852 imaging 722-3, 1 872, 1 873 F calculi 723, 723 F, 724 F children 1 297 innervation 1801 F, 1 808, 1 856 lymphatic drainage 1 856 resection 2487-9, 2489 F saliva collection 1 863 salivary flow rates 1 807 surfaces 1 808, 1 856 swelling, children 1 2 1 2 venous drainage 1 856 submandibular gland tumours 2504-5 adenoid cystic carcinoma 2504-5 benign epidemiology 2475, 2476 T presentation 2477-8, 2477 F mucoepidermoid carcinoma 2504-5 treatment 2487-9, 2489 F submandibular lymph nodes 1 747, 1 799 submandibular space 1 744, 1 758-9, 1 805 submandibular triangle, neck 1 742, 2742 F
Pages 1-1 3 12 are in Volume 1 , pages 1 3 1 3-28 10 are in Volume 2, and pages 2 8 1 1-4 147 are in Volume 3.
I ndex I 431 1
submasseteric spaces 1 806 submental island flaps 2850, 2852 F submental lymphatics 1 747, 1799 submental tissue space 1 743, 1 805 submental triangle, neck 1 741 submersion reflex 1 364 submucosal glands, nasal polyposis 1 552 submucosal implants 2902, 2902 T submucosal resection (SMR) 1 577 epistaxis 1 604 medical negligence 1 734 septal perforation 1 573-4 see also septoplasty submucous cleft 1 8 1 4 suborbicularis oculi fat (SOOF) 3052 lifting 3060-1, 3062 F subperichondrial abscess 3359 subperichondrial cricoidectomy, intractable aspiration 2 100, 2 10 1 F subperiosteal abscess (Pott's puffy tumour) frontal rhinosinusitis 1 539 children 1086 orbital cellulitis 1 540 subperiosteal dissection 3060-1, 3062 F subperiosteal implants 2902-3, 2902 T substance P nose 1 364 type II vestibular hair cells 3237 subtectorial space 3 189-97 subtotal glossectomy defects, reconstruction 2556, 2556 F subtotal laryngectomy, laryngeal tumours 2614 subventricular zone (SVZ), stem cells 67 succinic dehydrogenase, pregnancy 403 succinyl choline 4 1 2 suck-swallow exercise 2089 T sucralphate, malignant ulcers 2792-3 suction, saliva collection 1862 sudden sensorineural hearing loss 3578-9, 3579-80 active chronic otitis media 3436 categorization 3580 T causes, postulated 3579 T, 3580 T, 3582 definitions 3578 T idiopathic see idiopathic sudden sensorineural hearing loss (ISSNHL) management 434 sulCus terminalis 1 794 sulcus vergeture 2202, 2202 F, 2203
sulcus vocalis 2202, 2202 F sulphamethoxazole-trimethoprim 1463 sulphasalazine 1 9 1 3 sulphatide, skin flap survival 1 14 sulphonamides 2 3 1 allergic reactions 2 3 1 resistance 235 sumatriptan 380 1-2, 3803 T summating potential 3 196, 328 1 sun exposure basal cell carcinoma 1 705-6, 2395-6, 2396 lip cancer 2543 squamous cell carcinoma 2398 Superbass HC220 body-level aid 3642 superficial musculo-aponeurotic system (SMAS) 3069, 3073 F, 3094 superficial spreading melanoma 2401 T superglue, foreign body removal ear 1 1 85 nose 1 186 superior alveolar (dental) nerve 1 801-2 superior canaliculi 1 690 superior constrictor, pharynx 1 945 F, 1 948 T, 1 949 F, 2 108-9, 2 1 1 1 lateral relations 1 947-9, 1950 F superior dental (alveolar) nerve 1 80 1-2 superior flap pharyngoplasty 1 0 1 2 F superior hiatus semilunaris 1 332, 1 333 F superior hypophyseal arteries 297, 307 superior labial vein 1 799 superior laryngeal artery 2 1 39 superior laryngeal nerve (SLN) 3 1 8, 3 19 F, 2 139, 2 1 56, 2 157 F, 2664, 2664 F, 3935 external branch 3 1 8-9, 2 1 56, 2664, 2664 F internal branch 2 1 56 local anaesthesia 2 139 superior laryngeal nerve block 480 superior laryngeal veins 2 140 superior meatus 1 335-6 superior nuchal line 3898 F, 3899 superior oblique muscle 3899 superior olivary complex 3 141-2, 3 14 1 F sound localization 3 14 1-2 superior olivocochlear system 3602 F, 3606 superior parathyroid artery 3 1 7 superior semicircular canal dehiscence (SCD) 3682-3, 3763-4 aetiology 3682-3, 3763 clinical manifest;tions 3682, 3763
complications 3764 definition 3763 diagnosis 3763-4, 3765 F, 3766 F differential diagnosis 3764 management 3764 outcomes 3764 superior semicircular canal dehiscence syndrome click-evoked vestibular myogenic potentials 3742 middle fossa surgery 4023 superior temporal quadrantanopia, pituitary tumours 304 superior thyroid artery 3 17, 3 17 F, 372 superior thyroid veins 3 17-8, 372-3 superior tracheobronchial lymph nodes 2 1 43 superior vena caval obstruction (SVCO) , tumours 2794-5 superior vestibular nerve 3871, 3871 F superior vestibular nuclei (SVN) 3220 supermarket syndrome see visual vertigo superoxide dismutase, skin flap survival 1 1 3 super-supraglottic swallow, dysphagia management 2090, 2090 T suppurative labyrinthitis 923, 3403, 3403 F suppurative meningogenic labyrinthitis 3692 suppurative parotitis see suppurative sialadenitis, acute suppurative sialadenitis, acute 190 1-2 causative organisms 1902 children 1 243 clinical features 1 90 1-2, 1 90 1 F complications 1 902 therapy 1 902 suppurative stomatitis glandularis 1 9 1 5-6, 1 9 1 6 F suprabullar recess 1 333-4 supracricoid laryngectomy with cricohyoidopexy 2614 supraglottic airway devices (SAD) 492 supraglottic laryngectomy 504, 2613, 2614 F supraglottic obstruction 479-8 1 nerve blocks 480 spontaneous respiration 48 1 topical anaesthesia 480 supraglottic stenosis 228 1 children 1 159 supraglottic swallow 2090, 2090 T
Pages 1-1 3 1 2 are in Volume 1, pages 1 3 1 3-28 10 are in Volume 2, and pages 2 8 1 1-4147 are in Volume 3.
4312 1 I ndex
supraglottic tumours 2601-2 clinical presentations 2608 diagnostic delays 2603 risk factors 2603 spread 2602 T TNM classification 2366 T treatment 26 10 supraglottis 1 135, 2 1 3 2 congenital disorders 1 1 35-7 lymphatic drainage 2713-4 supraglottitis see epiglottitis suprahyoid muscles 2 1 3 5 T supralaryngeal constriction, professional voice 22 1 1-2 supraomohyoid neck dissection 2564, 2564 F, 2738 F, 2747, 2747 T extended 2747, 2747 T, 2748 F
N 1 disease 2726 technique 2749 supraorbital nerve 3923 supraparamagnetic iron oxide ( SPIO) 1 76 1-2, 1 762 F Supraskin 100 suprasternal retraction, airway obstruction 2287 suprastomal granulation, tracheostomy induced 1 203-4 removal 1204 supratrochlear nerve 3923 supreme turbinate 1336 sural nerve, facial reanimation 3080 surface electromyography dysphagia 1 977 surface immunoglobulin (sIg) 1 3 5 surgical ciliated cysts 1 926 surgical cricothyrotomy 477 surgical decompression, facial schwannoma 4083 surgical emphysema, tracheostomy induced 230 1-2 children 1 202-3 surgical negligence see medical ne��hg,en(:e surgical training 55 1-8 appraisal and revalidation guidelines 556-8 clinical care 556-7 future directions 558 working with colleagues 557-8 communication skills 55 1-2, 553 appraisal and revalidation guidelines 557 continuing professional development 554-6 accreditation 555-6 applications review 556 T
categories 555, 556 T participation 556 T requirements 555, 556 T system review 556 historic perspective 551, 552-3 UK 552-3 apprenticeship model 552 CaIman Report 553 current 553 curriculum development project 553, 554 T, 555 T future 553 historic 552-3 surveillance definition 8 2 1 hearing loss 829-30 suspensions 448-9 suspensory ligament of Berry (lateral ligament of the thyroid) 3 16-7 suspensory ligament of Lockwood 1 679 sustained vowels, voice evaluation 2 1 72 suturectomy 1024 suture marks, litigation and 3090 sutures care of 102-3 fibre scaffolds 1 24 swabs, retained during adenoidectomy 1098 swallow apnoea 1 957, 1 960, 1960 F swallowing 1954-63, 2075 age-related changes 196 1 airway protection 1 955 sphincteric mechanisms 1955 disorders see dysphagia expiration 1960 future research 1961 glossopharyngeal nerve lesions 3937 kinematics 1 967 knowledge deficiencies 196 1 multiple, post-bolus 1958 neural control 1 958-9 feedback regulation 1958 oesophageal phase 1958-9 reflex activity 1958 voluntary control 1958 oesophageal phase 1958, 2076 oral phase 1956-7, 2075, 2 1 59 preparatory 1 956 proper 1 956-7 pharyngeal phase 1 957-8, 2075, 2 1 59 neural control 1958-9 reflex 1 956 physiology 1954-63, 1 964 post-oesophageal atresia repair 1 287
respiration and 1959-6 1 , 1 960 F continuous vs. single swallows 1961 monitoring problems 1 960 phase 1 960 research problems 1960 sequence of events 1956-8, 1956 F timing 1956 structures involved 1954-5, 1955 F thyroid movements 3 1 6-7 video fluoroscopy 2076 swallowing manoeuvres, dysphagia 2089-90, 2090 T sway platforms 3732-3 Swedish nose 1 197-8, 1 198 F swimming chronic otitis media 936, 937 otitis media with effusion 901-2 Swiss Study on Air Pollution and Lung Diseases in Adults (SAPALDIA) 1386-7 Sydenham's chorea 3939 sympathetic nervous system nasal innervation 1 363 parathyroid gland innervation 3 1 8-9 skin flap innervation 1 12 thyroid gland innervation 3 1 9 sympathetic neurotransmitters, nose and 1 3 64 sympathetic ophthalmitis 1732 sympathomimetics, effects on nasal vasculature 1365, 1365 T synaptic ribbons, inner hair cells 3 1 36 syncope, parapharyngeal space tumours 2529 syndrome of inappropriate antidiuretic hormone (SIADH) , pituitary surgery-induced 308, 4 1 1 2 syndromic cleft lip 1 000 syndromic deafness definition 8 1 1 genetic causes 1 8, 845 synechiae, nasal cavity 1344-6, 1 346 F synkinesis, Bell's palsy 1 845, 393 1 synostoses anterior 1025 coronal s e e coronal synostosis lambdoid see lambdoid synostosis metopic 1022 T, 1025-6 sagittal see scaphocephaly surgery 1025-6, 1026 F synovial sarcoma children 1259 T larynx 2604 synthetic nasal implants 297 1 synthetic oxygen carriers 263-4
Pages 1-1 3 1 2 are in Volume 1, pages 1 3 1 3-28 10 are in Volume 2, and pages 28 1 1-4147 are in Volume 3.
I ndex I 431 3
syphilis children 1 2 1 6 congenital see congenital syphilis dental defects 1 8 1 8 diagnosis 2008 hereditary see congenital syphilis HIV infection/AIDS 2007 laryngeal 2267 mouth ulcers 1 833 nasal 1460-2, 1 703 clinical features 1460-2 pharyngeru 2007-8 primary 2007 diagnosis 1461 nasru manifestations 1460-1 secondary 2007 diagnosis 1461 nasal 146 1 , 1 703 serological tests 2008 sudden sensorineural hearing loss 3582 tertiary 2007 diagnosis 146 1-2 nasru manifestations 146 1-2, 1461 F symptoms 1461 tonsil 1225 treatment 1462, 2008
see also Treponema pallidum syphilis enzyme immunoassay 202 syringing see ear syringing syringobulbia 2080 syringomyelia 2080 syrups 448-9 systematic reviews binary data 663 critical appraisal 649, 650, 66 1-5, 671 F see also evidence-based medicine odds ratio 663-4 Quorom statement 650 sources 662 validity 662-3 systemic inflammatory response syndrome (SIRS) 534-5 systemic lupus erythematosus (SLE) 186, 1 7 1 2 diagnosis 1 7 1 2 dysphagia 203 1 mruar rash 1712, 1 7 1 2 F nasal 1 88, 1 7 1 2 septal perforations 1 584 thrombotic thrombocytopaenia 286 systemic sclerosis 1 7 1 2-3
T1 root lesions, Horner's syndrome 3937 T2 relaxation time 676 'T3 toxicosis' 340 T4-binding prealbumin 323 tabetic gait 373 1 tachypnoea capnograms 499 F stridor 1 1 1 6-7 tamoxifen 4042 TANIS score 2369 tannins, taste thresholds 1 841 Tapia's syndrome 3938 Taprosten 1 , 3588 Taq polymerase 7 target controlled infusion (TCl) devices 480 TARGET study adenoidectomy 897, 1095 otitis media with effusion 825, 890 ventilation tubes 897 targetted therapies cancer treatment 52-3 epidermal growth factor receptor 52 monoclonal antibodies 52 tyrosine kinase receptor 52 tarsus, lower eyelid 305 1 tartrazine 1427 taste anatomical structures 1841-2 central pathways 3929 mechanisms 3929-30 peripheral pathways 3929-30, 3930 F physiology 1 841-2 saliva, role in 1 841 taste abnormalities 1 840-5 1 associated conditions 1 843 causes 1 844-8 classification 1 842-3 clinical assessment 1 843-4 clinical presentation 1 840 diabetes 1845-6 epilepsy 1 846 glossopharyngeal nerve lesions 3937 hypertension 1 840 hypothyroidism 1846 iatrogenic causes 1 846-7 imaging 1 843-4 management 1 848-9 medication-induced 1 847 patient examination 1 843-4 patient history 1 843 perception ruteration 1 843 post-stapes surgery 3477 prevalence 1 840 •
quantitative testing 1844 regional taste deficits 1 844 spontaneous resolution 1 848 stroke 1 847, 1 848 F trauma-induced 1846 treatment 1 848-9 taste buds 1841, 3929, 3930 F anatomy 1 84 1 innervation 1 84 1 , 3929 life span 3929 location 1 841 maintenance, sruiva 1 841 receptor cells 3929 replacement 70 ultrastructurru appearance 1 841 taste pit 1 841 taste pore 1841 taste-salivary reflex, Bell's palsy 1 845 taxanes 52, 2760-1 taxoids 39 head and neck cancer 40 mechanism of action 39 taxol (paclitaxel) 39, 276 1 taxotere (docetaxel) 39, 276 1 T cell(s) allergic response 149-5 1 allergic rhinitis 1391 antigen presentation 136-7, 136 F disorders 1 75 T nasal mucus 1361 TCOF1 gene mutations 1034 T cytotoxic (Tc) cells 136 apoptosis 137 TdT-mediated nick end labelling (TUNEL) 6 1 tear film assessment, blepharoplasty 3055 tearing, excessive see epiphora 99mtechnetium-based radionuclide scans cervicru lymph node metastases 1762 malignant otitis externa 3338, 3338 F parathyroid imaging 383 thyroid cancer 334, 694 tectorial membrane 3 1 27, 3 128 F teeth 1 803-5 blood supply 1 798 decalcification 1 8 1 6 decay see dental caries deciduous 1 804-5 chronology 1 805, 1 805 T development 75, 799-801, 1922, 1924 F discoloration 1 8 1 7, 1 8 1 8 F, 1 8 1 8 T diseases see dental disease disorders 1 8 1 6-7 eruption 1 805, 1 806 F, 1 807 F
Pages 1-1 3 1 2 are in Volume 1, pages 1 3 1 3-28 10 are in Volume 2, and pages 281 1-4 147 are in Volu me 3 .
4314 I I ndex
teeth (continued) eruption disorders 1 8 17-8 premature eruption 1 8 17 retarded eruption 1 8 17 extractions, taste abnormalities 1 846-7 innervation 1801-2, 1 802 T loosening 1 8 1 8, 1 8 19 T, 1 820-1 periodontitis 1 820 loss, maxillary arch 2907-8 lymphatic drainage 1799 malformation 1 8 17, 1 8 1 8 F maxillary rhinosinusitis 1 540 missing 1 8 1 7 natal 1 8 17 neonatal 1 8 1 7 peg-shaped 1 8 17, 1 8 1 8 F permanent 1 803-4, 1 804 F chronology 1 805, 1 806 T premature loss 1 8 1 8, 1 8 1 9 T replacement, osseo integration 2905 supernumerary 1 8 1 7 tissue regeneration 7 5 venous drainage 1 799
see also entries beginning dental; individual types teething 1 8 17 Teflon 1 2 1 vocal fold paralysis 1 2 1-2, 2239, 2245 T tegmen defects, middle fossa surgery 4023, 4023 F teicoplanin 230 telangiectasia gingival bleeding 1 8 1 9 T gingival redness 1 820 oral mucosal redness 1 822 telephones, hearing impaired user 3668-9 amplified handset 3668 problems of 3668 text 3669 video 3668 telomerase 10 embryogenesis 71 oral cavity tumours 10 oral leukoplakia 10 stem cells 70-1 telomeres 3-4, 2379 temazepam 2795 temperature, anaesthesia monitoring 498 temporal arteritis 1723
temporal bone 3900 autoimmune inner ear disease 3680 child 1 054 F CPA lesions originating from 401 5 development 808, 3 124 imaging, cholesteatoma 9 5 1 , 9 5 1 T imaging, cochlear implants assessment 365 1 lateral skull base 3900 necrosis and sequestration see benign necrotizing otitis externa neonatal 1 053 F osseointegration 2908-9 otalgia 3528 Paget's disease 3487 parts 3900 petromastoid 3900 petrous portion 2 1 10 osteoradionecrosis 3376, 3377 F resorption, vestibular schwannoma 3957-8 squamous 3900 studies 3701 tuberculosis see tuberculous otitis vertigo, children 1 046 temporal bone fractures external auditory canal lacerations 3496 facial nerve palsy 3497-8 children 1 057 imaging 3882-3, 3883 F labyrinth injury 3497 longitudinal 1 057 ossicular disruption 3496-7 prophylactic antibiotics 3496 radiology 3495 taste abnormalities 1 846 tympanic membrane perforation 3496 vestibular labyrinth damage 368 1-2, 3682 F vestibular vascular injury 3699 temporal bone osteoradionecrosis 3376-8 aetiology 3376 clinical picture 3377, 3377 F definition 3376 diagnosis 3377 diffuse necrosis 3378 incidence 3376 localized necrosis 3377-8 management options 3377 natural history 3377 outcomes 3377 pathogenesis 3376
pathology 3377 risk reduction techniques 3376 temporal bone resection en bloc 4093 F 409 1 survival rate 409 1 , 4095 extended 4092-3 lateral 4093 F post-resectional reconstruction 4093-4 4093, 4094 free patient history 4093 pedicled flaps 4093 surgical criteria 4093 techniques 4093 temporal bone squamous cell carcinoma 4086-97 aetiological theories 4087 audiometry 4090 chemotherapy 4094 clinical features 4087-8 diagnosis 4088-90 differential diagnosis 4089 epidemiology 4086-7 examination 4089 histology 4089, 4089 F historical aspects 4086 history 4088, 4089 T imaging 4090 investigations 4088-90 metastases 4087, 409 1 palliative care 4095 prognosis 4095-6, 4095 F carotid involvement 4095-6 cerebral involvement 4095 dural involvement 4095 surgical margins 4095 tumour differentiation 4095 quality of life 4096 radiation-induced 4068, 4087-8 radiotherapy 4094 spread 4087, 4088 F staging 4090-1 , 4090 T, 409 1 T surgical anatomy 4087-8 surgical management complications 4094 neck 409 1 postoperative appearance 4094 F primary site 409 1-2 survival rates 4095 treatment 409 1-5 outcomes 4095-6 temporal bone trauma 3494 cerebrospinal fluid leak 3498 classification 3494
1-13 1 2 are in Volume 1 , pages 1 3 1 3-28 1 0 are in Volume 2, and pages 281 1-4147 are in Volume 3.
I ndex I 43 1 5
clinical features 3494-5 definition 3494 diagnosis 3494-6 epidemiology 3494 facial nerve involvement 3496, 3 888, 3889 F hearing assessment 3495 investigations 3495-6 management 3496-8 vestibular assessment 3495-6 temporal bone tumours 4067-77 children 4074-5 chronic suppurative otitis media 4068 classification 4070 T clinical evaluation 4068-9 genetic 4067-8 head and neck examination 3945 investigation 4069 management 4069-74 presentation 4068-9 progression 4068-9 radiation-induced 4068 risk factors 4067-8 secondary tumours 4073-4 clinical presentation 4074 prognosis 4074 sites of origin 4074 T treatment 4074 staging 4069 vestibular schwannoma 3962-3 resorption 3957-8
see also individual types temporal coding 3 197 F, 3235 temporal gaps cochlear hearing loss 3256 detection experiments 3254 thresholds 3254 temporalis fascia grafts (TGF) 983 temporalis muscle 3910 temporal lobe injury, vestibular schwannoma removal 3979 temporal modulation transfer function (TMTF) 3254, 3254 F cochlear hearing loss 3257 temporal paragangliomas, diagnostic delay 4145 temporal resolution, ear 3254 assessment 3254, 3256 cochlear hearing loss 3256-7 sensation levels 3256 temporal theory, pitch perception 3252 temporary threshold shift (TTS) 3298, 3 548 temporary tracheostomy 2292-3
temporomandibular disorder (TMD) clinical features 3529 comorbidity 3530 Costen's syndrome 3530 management 3530 temporomandibular joint (TMJ) 1 808-10, 1 809 F articular disc (meniscus) 1 809-10 attachments 1 809 central (intermediate) zone 1 809 retrodiscal tissue 1 809 bones 1 808-9 condylar cartilage 1 8 1 0 facial pain 1 72 1 innervation 1 8 1 0 joint capsule 1 809 ligaments 1 8 1 0 accessory 1 8 1 0 movements 1 808-9 otalgia 3 529-30 rheumatological diseases 1 84 somatosounds 3600 synovial fluid 1 809 synovial membrane 1 809 vascular supply 1 8 1 0 temporomandibular (lateral) ligament 1 8 1 0 temporoparietal fascia flaps 285 1-3, 2852 F, 2853 F hair problems 3045 pinna reconstruction 3042-4, 3043 temporoparietal fascial flaps 285 1-3, 2852 F, 2853 F Tenon's capsule 1 679 Tensilon test, myasthenia gravis 2077 tension nose definition 2966 external rhinoplasty 2966 tension pneumothorax 1 767 paediatric tracheostomy 1201 tension-type headache 1 724-5, 1 725 F tensor palati 1 946 T, 2 1 12, 2 1 1 2 F, 3908-9 Eustachian tube 3 1 1 8 sleep 2308-9 tensor tympani anatomy 3 1 1 5 development 3 1 22 hearing 3 1 83 myogenic somatosOl.;t nds 3600 reflex arc 3 1 83 X nerve see vagus nerve (X) tentorium cerebelli" 298-9
teratoma( s) airway compromise 1 147 malignant 1259 nasopharyngeal 2 1 19 ultrasound 724 terfenadine allergic rhinitis 1 397-8 drug interactions 41 1 terminal deoxynucletidyl transferase (TdT) 6 1 terminal duct carcinoma, salivary glands 2500 terminal nerve (CNO) 1 662 tertiary olfactory cortex 3912-3 Tertroxin (liothyronine sodium) 450 Tessier classification, craniofacial clefts 802 F, 997 testosterone, salivary assay 1 867-8 test sensitivity 822-3 tetracycline(s) 2 3 1 adverse effects 2 3 1 contraindications 2 3 1 respiratory scleroma 1463 tooth discoloration 1 8 1 7 3,5,3' ,5' -tetraiodothyronine see thyroxine (T 4 ) tetranucleotide 5 tetrofosmin radionuclide scans parathyroid imaging 383 thyroid cancer 334 text systems 3669 tezosentan 1 1 3 Th 1 cells allergic response 149-50, 1 5 1 interferon-gamma 1 37 Th 2 cells, allergic response 149-50, 1 5 1 , 1 52 F thalamic nuclei lesions, eye movement defects 392 1 thalamic taste nucleus (TTN) 1 842 thalassaemias 27 1-2 causes 271 HbH disease 271 iron overload 262, 271-2 (J. thalassaemias 271 f3 thalassaemias 271-2 thalidomide jugular foramen meningiomas 4042 recurrent aphthous stomatitis 242, 1830-1 thalidomide tragedy 408 201 thallium radionuclide scans parathyroid imaging 383 thyroid cancer 334
Pages 1-1 3 1 2 are in Volume 1, pages 1 3 1 3-28 1 0 are in Volume 2, and pages 281 1-4147 are in Volume 3.
43 1 6 I I nd ex
The clinical use of red cell transfusion 255-6 'the neglected cranial nerve' see glossopharyngeal nerve Therabite system, dysphagia management 2088 therapeutic index, drugs 4 1 2, 4 1 2 F therapeutic range, drugs 4 1 1 thermal ablation, snoring 2330 thermal imaging, wound assessment 100 thermo-tactile stimulation, dysphagia 2087 Thermus aquaticus 7 thioguanine 38 thionamides 346, 450 'block and replace' regimen Graves' disease 347 pregnancy 347 side effects 347 dosage regimen 346 Graves' disease 346-7, 347 hypothyroidism 450 side effects 450 thyrotoxicosis 346 T toxic adenoma 347 toxic multinodular goitre 347 third branchial fistulae 1 779 third burns 96 IIIrd nerve see oculomotor nerve ( III) thoracic lymphatic duct 1 750 Thornwaldt's bursa 2 1 22 Thornwaldt's cyst 1074, 2 1 22 3D computer-generated models extra-oral protheses construction 2930 facial reconstructive methods 2941 prosthetic reconstruction 2941 3D conformal radiotherapy 2759, 2759 F 3D laser facial scanning, deviated nose 2988 3D planning and reconstruction 701-10 CT data 70 1, 702 F image data visualization 703-4 image reconstruction 703 pixels 703 slices, concepts of 703 surgical planning 704 surgical simulation 704-5 voxels 703 throat infections, mycotic 223-5 throat lozenges 448 throat pastilles 448 throat swabs, diphtheria 2253
thrombin 279 thrombin time (TT) 280 thrombocytopenia autoimmune see idiopathic thrombocytopenic purpura causes 259 epistaxis, children 1067 post-blood transfusion 262 thrombocytosis 275-6, 276 T thrombophilias acquired 290 inherited 290 investigations 289 perioperative management 289 thrombosis jugular foramen lesions 4028 pathogenesis 290 thrombotic disorders 288-90 perioperative management 289 heparin 290 thrombotic episode management 288-9 thrombotic micro angiopathies 286 thrombotic thrombocytopaenia purpura (TTP) 286-7 clinical manifestations 286 diagnosis 286 platelet transfusion contraindication 260 treatment 287 thromboxane A2 (TXA2) 278 'thumb sign' 1 1 3 1 , 1 1 3 1 F, 2250 thymine 3 thymoma(s) airway compromise 1 147 myasthaenia gravis 1 72 thymus, ectopic tissue 727 thyroarytenoid 2 1 36 T thyroepiglotticus 2 1 36 T thyroglobulin 327 autoantibodies 335, 343 degradation 323 iodification 322 thyroglossal duct cysts 1268, 1777-8 clinical features 1 268, 1268 F, 1 778, 1 778 F embryology 3 14--5 , 805, 1 268, 1 778 investigation 1 268 management 1 778-9 pathology 1 778 sites 806 F surgical treatment 1 778 recurrent cysts 1 778 treatment 1268 ultrasound examination 724, 725 F
thyroglossal duct disorders 1268 thyroglossal duct fistula embryology 1 268 pre�sent.aticm 1 268, 1268 F treatment 1268 thyrohyoid ligament, lateral 2 l 33-4 thyrohyoid membrane 2 1 33-4 laryngeal trauma 227 1-2 thyrohyoid muscle 1 803, 2 1 35 T thyroid ala grafts, laryngeal reconstruction 1 156, 1 162 thyroid artery inferior 3 1 7, 372 superior 3 1 7, 3 1 7 F, 372 thyroid autoantibodies, Graves disease 343 thyroid cancer 2663-701 anaplastic tumours 2673 T, 2675 treatment 2688 ultrasound 720 children 1256-7, 2693 classification 7 1 9, 2672 T, 2679, 2679 T systems comparison 2682 T WHO 2673 T clinical assessment 2675-8 dietary iodine consumption 267 1 differentiated long-term follow-up 2697 recurrence 2696, 2697 F risk groups 2684 T surgical treatment 2685 T treatment failure 2685 F examination 2675-6, 2676 T family history 2671 follicular carcinoma 331, 2673 T, 2674 imaging 7 1 9-20, 2677 F treatment 2686 follow-up, long-term 2697 histopathological types 2366 history 2675 imaging 2676-8, 2677 F, 2678 F
see also individual techniques incidence 2663, 2668-9, 2672 F, 2683 laboratory investigations 2678-9 cytology 2678-9, 2679 F, 2679 T literature, problems with 2663-4 lymphoma see thyroid lymphoma medullary see medullary thyroid carcinoma (MTC) molecular genetics 2669-75 mortality rates 2666, 2694 F N stage definition 2364, 2364 T occurrence 330, 7 1 9 outcome measurements 2697-8
Pages 1-1 3 1 2 are in Volume 1, pages 1 3 1 3-28 10 are in Volume 2, and pages 28 1 1-4 147 are in Volume 3.
I ndex I 43 1 7
papillary see papillary thyroid cancer (PTC) pre-existing thyroid disease and 2671 prognosis 2679, 2679 T; 2680 F, 2682 T; 2683 radiation-induced 2670-1 radiology 2676-8 radiotherapy 2693-6, 2694 F external beam 2696 serum thyroglobulin measurements 2695-6 side effects 2695 T recurrence 2696-7, 2697 F research areas 2698-9 2679-82, 2680 T; 268 1 T; 2682 T histological types 2681-2 pathology 2671-2 surgical techniques 2688, 2688 F, 2689 T
see also specific operations thyroglossal cyst 1 778-9 thyrotoxicosis and 3 3 1 TNM classification 2362 T; 2366, 2368 T; 2680 T; 268 1 T treatment complex problems 2693 controversies 2683 failure,incidences and patterns 2685 F guidelines 2685 T policy 2682-93, 2683 T tumour suppressor genes 2670 thyroid cartilage 2 1 32-3, 2 137 F development 2 1 30 inferior cornu 2 1 32 laryngeal framework surgery 2241-2, 2242 F pubertal changes 2205 superior cornu 2 1 32 surface anatomy 1 740 trauma 2272 thyroid disease aetiology 327-8 apoptosis 62 developmental disorders 330 imaging studies 332
in vitro investigations 332 diffuse changes 330, 720-1, 72 1 F diffuse goitre with abnormal function 3 3 1 diffuse goitre with normal function 330 in vitro investigations 332
drug therapy 450-1 dysphagia aetiology 2035 functional disorders 330, 33 1-2 head and neck manifestations 399-40 1 hormonal preparations 450 hyperthyroidism see hyperthyroidism hypothyroidism see hypothyroidism investigations see thyroid functional tests/imaging malignant see thyroid cancer pathology 330-2 pregnancy 358-60 structural disorders with abnormal function 33 1-2 diffuse goitre 330 goitrous see imaging studies 332-4 nodular see nodular thyroid disease 330- 1 nodular nodular vs. diffuse 7 1 8 with normal function 330-1
see also individual diseases; specific conditions thyroidea ima artery 372 thyroidectomy complications 35 1 , 2684 T; 2692-3 accessory nerve damage 2808 haematoma 3 5 1 recurrent laryngeal nerve damage 2692 hypothyroidism induction 356 indications 349, 349 T parathyroid gland injury 351 preparations 349-5 1 surgical personnel issues 2693 surgical preparations 349-5 1 technique 2690 F thyroid cancer treatment 2683, 2683 T; 269 1 hypoparathyroidism incidence 2683, 2684 T vocal fold paralysis incidence 2683, 2684 T thyroid hormone replacement 356 thyroid exophthalmos 344, 3 9 1 5-6 thyroid eye disease 343-4, 344 F, 345 F clinical features 344 colour vision 344 CT imaging, 'Coca Cola' bottle sign 1680 F exophthalmos 344 imaging 344, 344 F orbital effects 1 6i9
phases 344 radioiodine therapy 349 signs 344-- 5 therapy 1 680 medical 1 680 orbital decompression see orbital decompression transconjunctival fat excision 3063 F treatment 345 visual acuity 344 thyroid follicles 3 1 9 connective tissue 320 destruction radioiodine therapy 348 subacute thyroiditis 352 fibroblasts 320 thyroid functioning tests ( TFTs) see thyroid gland,functional tests/ imaging thyroid gland 3 14-26 anatomy 3 1 4-2 1 , 327, 2664 F, 2665 F intrathyroidal parathyroid glands 722 macroscopic 3 1 6-9, 3 16 F microscopic 3 1 9-21 ultrasound examination 7 1 8 arterial supply 3 17, 3 1 7 F, 2664-5, 2664 T assessment see thyroid functional tests/imaging benign enlargement 267 1 current knowledge deficiencies 324 disease see thyroid disease ectopic tissue 3 1 4-5 embryology 3 14--5 , 327-8, 805 lateral anlage 3 15, 3 1 6 F, 368 fascia 3 1 6-7 follicular cells 3 1 9, 320 F, 327 development 3 1 6 F enlargement 3 19--20 microvilli 3 1 9-20 reabsorption lacunae 3 1 9-20 function 327-8 future research 324 historical aspects 3 1 5 T hormones see thyroid hormones innervation 3 1 8-9 autonomic control 3 19 356-7 iodine iodine trapping 32 1-2 isthmus 3 1 6 lingual see lingual thyroid lobes 3 1 6 lateral 3 1 5, 368, 368 F lobules 3 1 9
Pages 1-13 1 2 are i n Volume 1, pages 13 13-2810 are i n Volume 2 , and pages 28 1 1-4 147 are i n Volume 3 .
43 1 8 I I n dex
thyroid gland (continued) lymphatic drainage 3 1 8, 3 1 8 F, 2666, 2666 T maldescent 3 14-5, 330, 332 maldevelopment 330 median anlage 3 14-5, 316 F neuropeptides 3 1 9 nonmalignant disease 338-66 eurythoid conditions 360-3 nuclear medicine assessment 1 299-300, 1300 F parafollicular cells see parafollicular (C) cells, thyroid gland physiology 32 1-4, 321 F iodine 321 metabolism regulation 321 selenium 321 pyramidal lobe 3 16, 316 F surface anatomy 1 741 surgery 349 T surgical anatomy 2664-6, 2664 F, 2664 T, 2665 F tumours see thyroid cancer venous drainage 3 1 7-8, 2664-5, 2664 T thyroid gland, functional tests/ imaging 327-37, 340 T imaging 328, 332 developmental disorders 332 hypothyroidism 335-6 structural disorders 332-4 with abnormal function 335 nodular changes 332-4 thyrotoxicosis 335
see also specific imaging techniques in vitro tests 328, 328 T, 332, 334-5 nodular thyroid disease 361 palpation vs. 330, 332 patterns 340 T subacute thyroiditis 352 subclinical hyperthyroidism 353 developmental abnormalities 332 diffuse changes 332 free T3/T4 levels 328 Grave's disease 334-5 nodular changes 332 thyroid hormones 321 biosynthesis 322 F deactivation 324 intracellular effects 323-4 metabolism 323-4 replacement administration 357 monitoring 357 pharmacology 357
secretion 322-3, 322 F colloid droplets 322-3 endosomes 322-3 serum levels 323, 323 T transport proteins 323 functions 323
see also individual hormones thyroid hormone suppressive therapy 363 'block and replace' 347 thyroid incidentalomas 363 thyroid inferno (storm) see thyroid storm thyroiditis 35 1-3 acute suppurative 720 autoimmune see autoimmune thyroiditis chronic lymphocytic see Hashimoto's thyroiditis classification 3 5 1 , 352 T De Quervain's see subacute thyroiditis giant cell see subacute thyroiditis granulomatous see subacute thyroiditis Hashimoto's see Hashimoto's thyroiditis imaging 335 radio nuclide scans 335 ultrasound examination 720, 72 1 , 72 1 F painless 352-3 subacute see subacute thyroiditis
see also specific types thyroid lobectomy 2688-92 gland mobilization 2689 gland removal 2690-1 incision 2688-9 parathyroid gland localization and preservation 2689, 2690 F recurrent laryngeal nerve identification 2689 thyroid vein division 2689 F upper/lower poles mobilization 2689-90, 2690 F thyroid lymphoma 720, 2673 T, 2675, 2687-8 aetiology 2671 Hashimoto's thyroiditis and 33 1-2, 336 primary 720 staging 2687, 2688 T treatment 2688 thyroid peroxidase (TPO) 322 autoantibodies 335, 343 thyroid releasing hormone (TRH) 327
thyroid stimulating hormone (TSH) 327 goitre aetiology 2668 G-protein mediation 2670 in vitro tests 328, 328 T, 332, 334-5 recombinant 2696 thyrotoxicosis 339-40 TSHomas see TSHomas thyroid stimulating hormone receptor (TSHR) 341-2 thyroid stimulating hormone secreting adenomas see TSHomas thyroid storm 335, 339, 349-5 1 clinical features 350 T management 350 T thyroid veins 3 1 7-8, 372-3 thyromental distance 470, 470 F thyropharyngeus muscle 1 947, 1 948 T pharyngeal pouch 2045 thyroplasty medialization 1 1 7 1 type I 2097, 224 1-2 thyrotoxicosis 338-5 1 aetiology/pathology multiple toxic nodules 3 3 1 solitary toxic nodule 3 3 1 , 335 toxic nodular goitre 335 TSHomas 4102 atrial fibrillation 339 autoimmune (Grave's disease) see Grave's disease cardiovascular manifestations 339 clinical manifestations 338-9, 400 definition 338 epidemiology 338 Graves' disease see Graves' disease imaging studies 335 investigations 339-40, 340 T iodine-induced 335 ocular manifestations 400 prevalence 338 primary 338 proximal myopathy 339 scintigraphy 340, 340 T, 341 secondary 338 serum TSH levels 340 signs 339, 339 T surgery 346 T, 349-51 complications 3 5 1 preparations 349-5 1 symptoms 338-9 thyroxine 338 transient 3 3 1 , 35 1-3 treatment 346-5 1 , 346 T drug 346-9 medical 346
Pages 1-1 3 12 are in Volume 1, pages 13 13-2 8 1 0 are in Volume 2, and pages 28 1 1-4147 are in Volume 3.
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I ndex I 43 1 9
triiodothyronine 338
tinnitus 3594-628
vocal manifestations 400-1
pathophysiology 3601-8, 3604 F
thyrotrophs 297
aetiology 3598-600, 3599 T age-related sensorineural hearing impairment 3544, 3 545
abnormal afferent excitation 3603-5
thyrotropin 30 1
animal studies 3600
see also
types/causes
abnormal central neural auditory
hypothyroidism 301
aetiology 3609
activation 3606 abnormal peripheral neural auditory activation 3606 auditory feedback system 3601 , 3602 F
iodine uptake regulation 32 1-2
management 3609
calcium channel
secretion control 301, 321
,... ...£.",, 1 0 " ,-0
effects 301
auditory assessment 3610
half-life 301
auditory control areas 3602
hyperthyroidism 301
children 3609
serum levels 30 1 , 323 T structure 301 thyrotropin-releasing hormone
300, 321 thyroxine ( T4) 327 foetal secretion 3 1 4 function 3 2 1 i n vitro tests 328, 3 2 8 T, 334-5 nose, effects on 1 366 Pendred's syndrome 2667-8 secretion 322-3 serum levels 323 T thyrotoxicosis 338, 340 transport proteins 323 thyroxine-binding protein ( TBG) 323 thyroxine (T4) therapy 450-1 absorption 357 cardiac disease 357 dosage 357 elderly 357 pregnancy 357 half-life 357 hypoadrenalism 357 poor compliance 357 triiodothyronine therapy vs, 3 57 tic douloureux of the nervus intermedius see geniculate neuralgia
3609 definitions 3595 depression 3598, 3608 'echoing' 3604, 3605 F epidemiology 3597-8 associated conditions 3598 delTIOgraphlc features 3598 socioeconomic status 3598 patients 3598 functional imaging 3 6 1 3 3606 systems 36 1 3 habituation 360 1-2, 3607-8 impairment and 3598 historical aspects 3594-5 history taking 3609-10 hVl'1erhar'lC oxygen therapy 3584 imaging 3610 investigations 3609-13 laterality 3598 loudness 3612 masking 3 6 1 2 medical evaluation 3 6 1 0 melanin pigmentation 3598 meningioma 4009 mood disorders 3608 motor 3606 nervous system examination 3610
3605 central neuronal network 3601-2 efferent dysfunction 3606 GABA downregulation 3606
glutamate neuroexcitotoxicity 3604 mechanisms underlying 3602-8 neural hyperactivity 3606-7 N-methyl-D-aspartate receptor modulation 3604-5 spontaneous activity alterations 3606-7 spontaneous neural activity
3601-2 tonotopic reorganization 3606-7 presence authentication 3610-3 psychoaco ustical measurements 36 12 prevalence 3597-8, 3599 T psychological disorders 3607 psychological model 3608 psychological p rofiling 3 6 1 3 psychotherapy 36 1 6 pulsatile see pulsatile tinnitus residual inhibition 3612 sensory 3606 severity authentication 3613 skull base lesions 3944, 3944 T 'spontaneous' 3597-8, 3605 F
neural activity recording 3603 F,
spontaneous cochlear activity 3595
3612-3 neurofibromatosis 2 4000
spontaneous otoacoustic
neurootological evaluation 36 10
stapes surgery 3480
Tietze's syndrome 1 90
noise-induced hearing loss 3552
stress 3604 F, 3607
timbre
objective 3595, 3600-1
tidal volume, anaesthesia monitoring 498
emissions 3600-1, 3603-4
definition 3253-4
aetiopathophysiology 3600-1
subjective 3595 sudden sensorineural hearing
dull 3254 mellow 3254
causes 3595 diagnosis 3601
treatment 361 3-8, 3615 T
perception 3253-4 sharp 3254
imaging 3601
instrumentation 3614-6
physical examination 360 1
pharmacological 3 6 1 5 T, 36 1 6-8
sound properties 3253-4
treatment 360 1
psychotherapy 3 6 1 5 T
vocal tract dimensions 2 166
see also somatosounds
voice perception 2 1 74
otitis media with effusion 3390-1
loss 3582
surgical 3614 tuberculous otitis 3447 T
TIMP hypopharyngeal cancer 2637
ototoxic drugs 3599-600
vestibular assessment 3610
tinea interclinoidea 298 Tinel sign, sural nerve
outcomes research 641 . Paget's disease 3487
vestibular schwannoma 3944, 3959 removal 3983
3080
1-1 3 1 2 are in Volume 1, pages 1 3 1 3-2810 are in Volume 2, and pages 281 1-4147 are in Volume 3.
4320 I I nd ex
tinnitus instruments (combination units) 3616 tinnitus loudness match 3 6 1 2 tinnitus maskers 3 6 1 6 tinnitus pitch match 3612 tinnitus retraining therapy 3614, 3615 T tirapazanine 24 10 tissue engineering 1 1 8-30, 122 F advantages for use 122 applications 1 22 blood vessels 126, 1 26 F bone 1 24 cartilage 1 25 cellular sources 1 22 clinical applications 1 24-6 nerve 126 scaffolds see tissue scaffolds skin 1 26 tissue expanders 2896 tissue expansion 2896 pinna reconstruction 303 1 F scar revision 2896 skin, effects on 2896 skin flap delay 1 15 tissue factor 279 tissue harmonic imaging, ultrasound 713, 714 tissue homeostasis 57 tissue regeneration, stem cells 72 tissue scaffolds 122-3 bone 124 cartilage repair 125 characteristics 122-3 clinical applications 1 24-6 fibre 1 24 function 1 22 materials 1 23-4 natural 123 synthetic 1 23-4
see also individual materials skin repair 94 types 124 tissue-specific committed stem cells 69 tissue staining, apoptDsis 60 titanium implants 1 1 9 biocompatibility 1 19 craniofacial bone repair 124 osseointegration 1 19, 2905, 2906 T lymphocytes see T celI(s) TNFCl. receptor 1, apoptosis 57 T/NK cell lymphoma 1 655 clinical features 1 656, 1 656 F diagnosis 1 656
imaging 1 656 treatment 1656-7 TNM classification/staging aims 2359-60 certainty factor (C factor) 2361 clinical (pretreatment, cTNM) 2360 components 2360 definition 2359, 2360 T G category definition 236 1 , 2361 T grouping 2361 T histopathological grading 2361, 236 1 T historical aspects 2360 limitations 2368-9 M category definition 2359, 2360 T method 2362-3 N category definition 2359, 2360 T pathological (postsurgical histopathological, pTNM) 2360 primary tumours 2360 T recurrent tumour 236 1 regional lymph nodes 2360 T related classifications 2362 residual tumour 236 1 sinonasal malignancy 2420, 242 1 stage grouping 2361-2, 2361 T exceptions 236 1 TANIS score 2369 T category definition 2359, 2360 T tumour sites 2360 T
see also individual tumours tobacco Asian countries 235 1-2 head and neck cancers 235 1-2, 2776 laryngeal squamous cell carcinoma 235 1-2 pan chewing 235 1-2 sinonasal malignancy 2347 voice disorders 22 1 9 see also smoking tobramycin chronic rhinosinusitis 1471 malignant otitis externa 3339 ;x-tocopherol (vitamin E) 3302 11:'-(Hrram 1 296 tongue 1 794 anatomy 1 794, 1 841-2 base 1 794 tumours see tongue base tumours blood supply 1 799 bolus formation 1 954-5 central papillary atrophy 1 826-7 contact endoscopy 767 discoloration, drug-induced 1 82 5 dorsum 1 794, 1 794 F
embryology 801 , 802 F, 1 8 12 descent 798 inferior surface 1 793 F, 1794 lymphatic drainage 1799-800 muscles 1 797-8, 1 797 F extrinsic 1797 innervation 1 803 intrinsic 1 798 swallowing 1 954-5
see also individual muscles paralysis, hypoglossal nerve lesions 3936, 3937 pharyngeal (postsulcal) part 1 794 pigmentation, acquired 1825, 1 825 F sensory innervation 1802-3 squamous cell carcinoma 1 762 F swallowing 1 956-7 venous drainage 1 799 vowel sound production 2 166 tongue, carcinoma of 2552-4 base of tongue see tongue base tumours clinical presentation 2552 F imaging 2552-3 investigation 2552-3 management 2553-4 stage I-II 2553-4 stage III-IV 2554 tumour thickness 2553 T survival rates 2558, 2558 T tongue base exercise, dysphagia 2089 T tongue base tumours 479 F, 2554-7 carcinoma 2554-7 diagnostic delay 2809 inoperable 2555 intubation difficulties 479 otalgia 353 1 quality of life issues 2775 reconstruction techniques 2555-7 primary closure 2555, 2555 F resection techniques 2555-7 treatment 2589, 2590 F upper respiratory tract management 2 1 5 1 tongue reconstruction 2555-7, 2871, 287 1 F tongue tie (ankyloglossia) 994 tonsil(s) anatomy 1 793-4, 1 944, 1951 asymmetry 1225, 2006 blood supply 1 799 diseases 1 2 1 9-28 inflammatory 1 220-5 noninflammatory 1 225-6
see also individual diseases/disorders
1-1 3 12 are in Volume 1 , pages 1 3 1 3-28 10 are in Volume 2, and pages 2 8 1 1-4147 are in Volume 3. '"
I ndex I 432 1
flora 1 2 1 9-20 function 1220 histology 1 994 immune function 1220 obstructive sleep apnoea 1 104, 1 105 F, 1226 pseudocysts 2005-6 at puberty 1 794 spontaneous haemorrhage 1225 structure 1 2 1 9 syphilis 1225 tuberculosis 1 225 tumours see tonsillar tumours ulceration 2006 unilateral enlargement 2006 children 2006 tonsil biopsy indications 1 989 variant Creutzfeld-Jacob disease 1 238 tonsillar tumours ICD- 10 site codes 2375 T mandibular nerve damage 3927 neck irradiation 2589, 2729 neoplasia 1225, 1 226 treatment 2589
see also individual types tonsillectomy 1988-96 adjunctive therapy 1 994 airway management 500-1 anaesthesia 500-1 extubation 50 1 maintenance 50 1 recovery 501 biopsy purposes 1989 blood transfusions 1 994-5 children see paediatric tonsillectomy complications 1 994-6, 1 995 T corticosteroids 422, 1 994 day case criteria 1993 drooling 789 emergency readmissions 1988 epidemiology 6 1 5-6, 6 1 8, 622, 622 T, 627-8 FDG uptake 692 fever, postoperative 1995-6 haemorrhage 495, 1994-5 monitoring 1 993 reactionary 1994-5 secondary 1 995 historical aspects 1229, 1 230 F immune function and 1 220 indications 1 988, 1 989-90 infectious mononucleosis 1 784 1 308 medical otalgia, postoperative 3530, 3530 F
otolaryngological assessment 1989 outcomes 1 996 pain cessation 1 993-4 peritonsillar abscess 1 222-3, 1998 postoperative care 1993-4 antiemetic therapy 1 994 diet 1994 painl analgesia requirements 1 993-4 rates 1988 recurrent sore throat 1988 referral 1 988-9 SIGN guidelines 1 989 speech, effects on 993 techniques 1 99 1-3 dissection see dissection tonsillectomy nondissection 1991 variant Creutzfeld-Jakob disease 1 238, 1990 'tonsillectomy embargo' 1231 tonsillitis acute 1220-2 aetiology 1 22 1 clinical evaluation 1 22 1 complications 1222-5 diagnosis 1 22 1 epidemiology 1 2 2 1 flora 1 220-1 , 1 220 F management, primary 122 1 microbiological investigation 122 1 presentation 1 220-1, 1220 F treatment 1222 chronic 1224-5 dysphagia aetiology 2030 infectious mononucleosis 208, 1 2 1 3 , 1 783-4 psoriasis association 1 224 recurrent 1 224 subacute 1 224 tonsillolingual sulcus 1951 tonsillopharyngitis 1220- 1 , 1 220 F tonsil plugs 2005-6 tooth see teeth tooth bud 799-800 topetecan 39 topical anaesthesia administration routes 480 children 509 lower airways 5 1 8-9 topoisomerase(s) 39, 2379 topoisomerase inhibitors 39-40 topoisomerase I inhibitors 39 topoisomerase II inhibitors 39-40, 5 1
torsades de pointes 4 1 1 torsional nystagmus 3220 tort 595 torticollis 1044 torus lateralis (lateral bulge) see nose, lateral wall torus tubarius 2 1 07 total conservative parotidectomy 2486, 2486 F, 2490 F total IgE tests, allergy 1 59, 1394 totally implantable cochlear amplifier C TICA) 3662 total maxillectomy 2428 total ossicular replacement prosthesis
(TORP) 120 F, 1 2 1 Soundbridge device and 3662 total parenteral nutrition (TPN) critical care, adult 5 3 1 intractable aspiration management 2097 tourniquet hypoxia 50 'tower skull' 2 120 toxic adenoma 345-6 aetiology 345 clinical manifestations 345 drug treatment 347 epidemiology 345 genetics 345 toxic diffuse see Graves' disease toxic multinodular goitre 345-6 cardiovascular effects 345 clinical manifestations 345 drug treatment 347 elderly 345 epidemiology 345 in vitro tests 335 iodine deficiency 345 pathogenesis 345 thyrotoxicosis 340 T toxic shock syndrome rhinosinusitis 1 540 Staphylococcus aureus 1 96 Toxoplasma gondii 246, 1 2 16, 1 784, 2009 toxoplasmic encephalitis 246 toxoplasmosis 2009-10 cervical lymphadenopathy 246, 1784 children 1 2 1 6 diagnosis 2 0 1 0 HIV and 246 immunocompromised patients 246, 2009-10 pregnancy 2009 symptoms 2009 treatment 2010
1-13 1 2 are in Volume 1 , pages 1 3 1 3-28 1 0 are in Volume 2, and pages 281 1-:4147 are in Volume 3.
4322 I I ndex
\ toy discrimination tests 841 Toynbee, Joseph 3595 T-piece breathing systems 5 1 0, 5 10 F trachea agenesis 1 142 anatomy 2 140-4 bifurcation 2 140 blood supply 2 142 cartilages 2 14 1 development 2 1 30 children 2 140 congenital cysts 1 147 congenital disorders 1 142-7 embryology 803-5, 1282, 2 130 fibrous membrane 2 141-2 innervation 2 142 juvenile-onset recurrent respiratory papillomatosis 1 1 79, 1 1 80 F lymphatic drainage 2 142 mucous membrane 2 142 nonstriated muscle fibres 2 142 pressure changes during breathing 2286 relations 2 143-4, 2 1 43 F infantile 2 143 structure 2 14 1-2 surface anatomy 1 740 thyroid cancer 269 1 venous drainage 2 142 Wegener's granulomatosis 1651 tracheal autotransplantation 2614, 26 14 F tracheal carcinoma, FDG- PET imaging 686 F tracheal compression, nontoxic multinodular goitre 363 tracheal disease, special needs children 787 tracheal injury 1 77 1-2 intubation 1771 symptoms 1771 tracheal intubation anaesthesia 494-5 laryngectomy 505 laser endoscopy 520 middle ear surgery 5 14 paediatric anaesthesia 5 10-1 trachealis muscle 2 142 tracheal obstruction, low 483 tracheal rings, laryngeal stenosis 1 1 52 tracheal squamous cell carcinoma 2602 tracheal stenosis 1 142-4, 2282-3 anterior wall collapse 2283 complete 2283 congenital 1 142-4, 1 143 F respiratory distress 1 143
surgical management 1 143-4, 2302 end-to-end anastomosis 1 144 tracheostomy-induced 2295-6 tracheal toilet 1 196 tracheal tubes anaesthesia 492-3, 493 F cuffed 492-3 preformed 493 F, 500-1 uncuffed 492-3 tracheal veins 2 142 tracheoarterial fistulae 2302 tracheobronchial diverticulum 803 F, 1943-4, 2 1 30, 2 1 3 1 F tracheobronchial septum 1 943-4 tracheobronchial stents, laryngeal stenosis 2279 tracheobronchial tree 2 1 30-44, 2 140 F blood supply 2 142 embryology 2 1 3 1 innervation 2 142 lymphatic drainage 2 142-3 relations 2 143-4 vasculature 2142-3 see also bronchi; trachea tracheobronchomalacia 1 145 tracheobronchoscopy, tracheal injury 1 771 tracheocutaneous fistula (TCF) , persistent children 1206 closure 1207 tracheostomy-induced 2302 tracheogenic cysts 1 147 tracheomalacia 1 144-5 aetiology 2097 bronchoscopy 1 1 22-3, 1 145, 1 145 F classification 1 144-5 investigations 1 145 oesophageal atresia repair 1287 open surgical tracheostomy 2295-6 stridor 1 145 tracheo-oesophageal anomalies 1283, 1283 T
see also specific disorders tracheo-oesophageal diversion, intractable aspiration 2 1 02-3, 2 1 02 F tracheo-oesophageal fistula 1 145-6, 1 146 F, 207 1 congenital anomalies associated 1 283, 1 283 T development 80 1-2, 1282-3, 1943-4 imaging 1296 incidence 1283 T
laryngeal atresia 1 1 37-8 laryngeal clefts 1 14 1 , 2030 recurrent, oesophageal atresia repair 1287 surgical 2625, 2627 F, 2628 F surgical repair 1 284-5, 1 286 F complications 1285-7 tracheostomy 2302 types 80 1-2, 805 F vocal fold palsy 1287 see also oesophageal atresia tracheo-oesophageal prothesis 2625, 2626 F mycotic colonization 225 valve failure 225 tracheo-oesophageal puncture (TEP) 2227 free jejunal transfer 2883 surgical decision-making flowchart 2229 F voice rehabilitation, post laryngectomy 2099, 2627, 2629 F tracheo-oesophageal speech 2227, 2227-8, 2228 T tracheostomy 2292-304 adult epiglottitis 225 1 aspiration 1278 children see tracheostomy, children complications 2300-2, 2628-9 early 2301 intermediate 230 1-2 late 2302 rates 2301 congenital subglottic stenosis 1 1 39 decannulation 2302 definition 2292-3 dysphagia aetiology 2035 effects 2293 emergency see emergency tracheostomy extubation 2301 historical aspects 2292 humidification 2300 indications 2293-4 indwelling, laryngeal stenosis 2277 intractable aspiration 2097 juvenile-onset recurrent respiratory papillomatosis 1 1 79 laryngeal infections 1 1 33 laryngeal stenosis 2277 laryngeal trauma 2274-5 local anaesthesia 482-3 local damage 230 1 medical negligence 2808 neck dissection 273 1
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I ndex I 4323
neurological dysphagia 208 1-2 as part of other procedure 2294 permanent 2293 postoperative management 2300 prolonged ventilation 2293-4 secretion removal 2293, 2300 subglottic haemangioma 1 140 swallowing 2300 techniques 2294-7 temporary 2292-3 tracheal injury 1771 tracheal stenosis 2302 translaryngeal 2298 tubes see tracheostomy tubes upper airway obstruction 2288, 229 1
see also individual types/procedures tracheostomy, children 1 194-209 anaesthesia 521 care 1 197-9 humidification 1 197-8, 1 198 F suction 1 197 complications 1 20 1-4, 1201 T, 1202 T bleeding 1203 suprastomal collapse 1204 decannulation 1205-7 accidental 1 202 decision to 1205-6 immediate 1 206 scar revision 1207 staged 1 206 technique 1206 discharge 1204 historical perspective 1 194-5 home care 1204-5 physical requirements 1205, 1205 T home ventilation 1 195-6 indications 1 1 95-6 intensive care 546-7 laryngeal reconstruction 1 1 59 laryngeal stenosis 1 1 5 1, 1 1 56 long-term ventilation 1 1 95-6 medical negligence 1309 prolonged intubation 1 195 skin care 1 198 special needs children 786-7, 788 F speech development 1 1 7 1 , 1204 techniques 1 196-7 dissection 1 196 positioning 1 1 96, 1 1 96 F skin incision 1 196 stay sutures 1 1 97, 1 197 F tracheal incision 1 1 96-7 tube securing 1 197, 1 197 F tracheal toilet 1 196 upper airway obstruction 1 195, 1 195 T
tracheostomy tubes adjustable flange 2300 changes 1 198-9 children 1 199-201 diameter 1 1 99, 1200 F features 2298-300 fenestrations 1 199, 2299 flexibility 2299 inner tube 1 199, 2298-9 length 1 199 material 1 199 obstruction 1202, 230 1 postoperative management 2300 speaking valve 1 199 types 2298-300, 2298 T, 2299 F variable/custom-fitted tubes 120 1 tracheotomy see tracheostomy Trachlight 475 tractus solitarius 3929 tragal pointer 3873 training see surgical training
Traitedes maladies de l'oreille et l'audition 3607 tramadol, cancer pain management 2786, 2787 tramazoline 1470 tranexamic acid 263 malignant ulcers/fistulae 2792-3 oral haemorrhage 259 transantral ethmoidectomy 1495 complications 1495 contraindications 1495 indications 1495 surgical technique 1495 transarterial tumour embolization 734 transblepharoplasty browplexy 3055, 3056 F transcolumellar incision closure 2962-3 transconjunctival lower lid blepharoplasty 3058, 3062-4 postoperative chemosis 3066 F transcription 4, 1 5, 35 F transcriptional silencing 9 transcription factors 1 6 AP- l 2380 cell signalling 36 transcription silencing 10 transcutaneous electrical nerve stimulation (TENS) 2784 transcutaneous lower lid blepharoplasty 3058, 3059-62 eyelid laxity management 306 1-2 transcutaneous oxygen saturation monitoring, stritlor 1 1 1 9
transcytosis 323 transfemoral Seldinger angiography, epistaxis 1 604 transferrin malnutrition assessment 95 nasal secretions 1360 transfer RNA (tRNA) 4 transfixation implants 2902, 2902 T transfixion incision, nasal tip surgery 300 1 transforming growth factor alpha (TGFa) cleft lip and palate 999 haemostasis 89 transforming growth factor beta (TGFf3) haemostasis 89 keloids 2892 transfusion -associated graft-versus-host disease (TAG-VHD) 262 transfusion reactions 260-2, 261 T ABO incompatibility 261 allergic 261 immunoglobulin A deficiency 261 immunoglobulin E 261 anaphylaxis 261 bacterial infection 261 delayed haemolytic 261 T, 262 febrile, nonhaemolytic 26 1 fluid overload 262 immediate 26 1-2, 261 T immunomodulatory effects 262 iron overload 262 large volume transfusion 262 post-transfusion purpura 262, 287 transfused red cells, premature destruction 262 transfusion-related acute lung injury (TRAU) 26 1-2 transglottic carcinoma 2602 transient brainstem ischaemia 3768, 3769 transient cerebellar ischaemia 3768, 3769 transient evoked otoacoustic emissions (TEOAE) 3277-8, 3277 F auditory neuropathy/ dyssynchrony 384 1 F, 3842 contralateral stimulation 3277-8 neonatal hearing screening 826, 3291 stimulus 3277 tinnitus 3605 F, 361 1 F transient evoked potentials 3280 steady state responses vs. 3288
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4324 1 I nd ex
transient hypogammaglobulinaemia 175 T, 1 77, 1081 transient ischaemic attack (TIA) definition 3767 diagnosis 3769 transient thyrotoxicosis 35 1-3 transitional cells, parathyroid gland 373 transitional meningiomas 4008 translaryngeal tracheostomy 2298 translation 4, 1 5 2904 transmandibular transnasal intubation, upper airway obstruction 2289 transoesophageal echocardiography, perioperative 500 transoral resection 2555 transposition flaps 2834-40 2838 glabellar 2840 F nasal reconstruction 3019 pivot 2840 F random 2840 transsexual voice 2226-7 therapy 2226 transsphenoidal hypophysectomy 4106-8, 4108-1 1 advantages/disadvantages 4109 T cerebrospinal fluid rhinorrhoea aetiology 1636-7 closure 4 1 1 1 factors affecting 4 1 10 optic nerve/optic chiasm and 4 108, 4 1 1 0-1, 4 1 12 F transethmoidal route 4106 F, 4 107-8, 4 107 F transnasal route 4 106 F, 4 108, 4 108 F transseptal route 4 106-7, 4 106 F transthoracic impedance plethysmography 529 transthyretin (TTR) 323 transtracheal cannulation, upper airway obstruction 2290, 2290 F transtracheal jet ventilation difficult airways 476-7, 477 F paediatric anaesthesia 5 1 9 transverse arytenoids 2 136 T transverse muscles, tongue 1 798 transverse sinus 4027 trap door scarring 3090 trapezius 1 745-6 paralysis 1 745-6 shoulder syndrome 2744-5 surface anatomy 1 74 1 trapezius flap 2863-5, 2864 F trastuzumab 44
trauma acoustic trauma see acoustic trauma benign paroxysmal positional vertigo 3497, 3812 dental 1 098, 1 633 dysphagia 2030 ear see ear trauma epistaxis 1 605 facial nerve see facial nerve injury/ trauma frontal sinus 1 505-7 head see head injuryltrauma inner ear 368 1-2 laryngeal see laryngeal trauma method of injury, scarring and 3090 nasal, medical negligence 13 1 0-1 neck see neck trauma ossicular chain trauma see ossicular chain trauma perichondritis aetiology 3358 septal 1 569-72 temporal bone see temporal bone trauma vocal folds 2 1 59, 2275 traumatic (solitary) bone cyst 1 926-7 traumatic hearing loss 824 trauma wounds 97 968, 1 033-4, Treacher Collins 2 120 aetiology 1 034 bilateral ear canal atresia 3642-3 clinical features 968, 1 034, 1 034 F, 2 1 20 genetics 8 1 3 T, 1 034 management 1034, 2 120 nasopharyngeal narrowing 2 1 20 surgery 1 034 upper respiratory tract assessment 2 1 5 1 treatment withholding/withdrawal, ethical issues 587-8 tree pollen, skin prick tests 1 394 T regulatory cells, allergic response 1 45-6, 1 5 1 trematic nerves, branchial arches 1 739 trephination, frontal sinus 1 508 treponemal haemagglutination (TPHA) test 1461, 2008 treponemal infections, nasal 1 703 Treponema pallidum 202, 1460, 2007 infectious rhinosinusitis 1 3 8 1 neonatal rhinitis 1077 Treponema pallidum immobilization ( TPI) 2008
Treponema pertenue 1 3 8 1 triamcinolone hypertrophic 2898-9 keloid scars 2893, 2894 F, 2898-9, 3090 mouth advanced head and neck cancer 2789 recurrent aphthous stomatitis 242, 1 830-1 triamterene 3799 triangles, neck 1 741-3, 1 742 F anterior 1 74 1-2, 1 742 T posterior 1742-3, 1 743 T triazoles 233-4, 442 tri-calcium phosphate ( TCP) , implants 29 1 7 triceps skinfold thickness 95 trichloroacetic acid peel blepharoplasty 3058 medical negligence 1 3 1 0 trichoepitheliomas, nasal 1708 Trichophyton rubrum 2 1 4 tricyclic antidepressants burning mouth syndrome 1848-9 depression, cancer patients 2796 globus 2040 migrainous vertigo 3804 neuropathic pain 2785 salivary flow 1 8 6 1 tinnitus 3 6 1 7 trigeminal nerve (V) 3923 central mechanisms 3926, 3926 F clinical disorders 3926-7 corneal reflexes 3946 absence 3923 damage 3926 skull base surgery 4136-7 divisions 3923 epidermoids (primary cholesteatomas) and 401 1 facial pain 1 7 1 8-9 facial sensation loss 3927 meningiomas 4Q09 motor nucleus 3926 nasal sensation 1 364 olfaction 1662 schwannoma 4014 facial pain 3944-5 intracranial 4 126-7 sensory nucleus 3926 taste sensation 3929-30 vestibular schwannoma compression 3958-9, 3958 F vestibular schwannoma removal 3980
Pages 1-13 1 2 are in Volume 1, pages 1 3 1 3-28 1 0 are in Volume 2, and pages 2 8 1 1-4147 are in Volume 3.
I ndex I 4325
trigeminal neuralgia (TN) 1724, 1 829-30, 3927 alternative therapies 1 830 associated conditions 1 830 disease characteristics 1 829-30 epidermoids (primary cholesteatomas) and 40 1 1 pain 1 829-30, 3927 treatment 1830 trigeminal sensory neuropathy 3927 trigonocephaly (metopic synostosis) 1022 T, 1025-6 triiodothyronine ( T3 ) 321, 327 intracellular effects 323-4 intracellular nuclear receptors 323 secretion 322-3 serum levels 323 T thyrotoxicosis 338 transport proteins 323 in vitro tests 328, 328 T, 334-5 triiodothyronine ( T3 ) therapy, thyroxine therapy vs. 357 trimethoprim 23 1 resistance 235 tripod fractures see zygomatic complex fractures tripod mechanism 2996 F, 2997 cephalic element shortening 2997, 2997 F triptans 380 1-2 trisacryl gelatin microspheres 733, 3952 trismus maxillary resection 29 1 5 nasopharyngeal carcinoma 2452 parapharyngeal space tumours 2528-9 trisomy 21 see Down syndrome trisomy syndromes, craniofacial defects 792 Trk 2384, 2669-70 trochlea, orbital anatomy 1678 trochlear nerve (IV) 39 1 7-8, 39 19 F, 3920 F central mechanisms 39 1 9-2 1 examination, eye movements 37 1 0-1 palsy, vestibular schwannoma removal 3980 vascular lesions 39 1 7-8 trunk posture observation 373 1 Trypanosoma cruzi 260 tryptase, allergy diagnosis 1 60 TSHomas 3 1 1 , 4102 clinical features 3 1 1 magnetic resonance imaging 3 1 1 medical management 4102
thyroid functioning tests 3 1 2 treatment 3 1 1 T-tubes chronic mucosal otitis media 3410 otitis media with effusion 896 tubal elevation 2 107 tubal ( Gerlach's) tonsil 1094, 2108 tubercle, lips 1 793 tubercle of Zuckerkandl 3 1 6 tuberculoid leprosy 1464, 2010 tuberculosis cutaneous 1702-3, 1 702 F drug resistance 2009 dysphagia 203 1 facial paralysis, childhood 1056-7 HIV infection 2008 laryngeal 2266, 2267 F lymph node ultrasound 7 1 8 F management 1 783 mouth ulcers 1 833 nasal 1458-60 aetiology 1458 clinical features 1458-9 diagnosis 1459-60 lupus vulgaris 1458-9, 1459 F sinus granuloma 1459, 1460 F treatment 1460 ulcerative form 1459 nasopharyngeal 2 1 2 1 diagnosis 2 1 2 1 neck manifestations 1 783 management 1 783 pharyngeal 2008-9 diagnosis 2009 treatment 2009 secondary 2008 specimen handling precautions 201 temporal bone see tuberculous otitis tonsil 1225 tuberculous lymphadenitis 1 760-1, 1760 F tuberculous otitis 3446-52 clinical findings 3450 T complications 3448 definition 3446 diagnosis 3447-8, 3447 T, 3448 T infection routes 3447 laboratory findings 3448-9, 3450 T management 3449, 3450 T prevalence 3446 research areas 345 1-2 risk factors 3446-7 tuberculum sellae 298 tuberculum sellae meningioma 3 9 1 5 tuberose sclerosis f708
tufted cells 1663 tularaemia, children 1 2 1 6 Tullio phenomenon 3708 children 1046-7 click-evoked vestibular myogenic potentials 3742 presentation 3709 superior semicircular canal dehiscence 3763 Tumarkin crises 3758 tumour(s) apoptotic index, cellular turnover measure 62 biology 34-6 cell cycle 34-5, 35 F cell loss 36 cellular kinetics 34-6 embolization see tumour embolization growth 36, 57 doubling time 36 growth curve 36 growth fraction 36 hypoxic cells 49 metastasis 36, 27 1 6-7 metastatic neck disease 2714-9 metastatic spread 36 mitosis 57 nasal endoscopy 1350-1 necrosis 63 oxygenation 49 potential doubling times, apoptosis and 57 size, response to drugs 36 stabilization, anti-angiogenic agents 43 telomere length 7 1 vascularization 2 7 1 5
see also specific types/locations tumour clonogen proliferation, radiotherapy 49 tumour embolization 734-5, 735-9 agents 734 complications 734, 736, 739 haemorrhage 3955 indications 732, 734, 734 T, 736 intraarterial chemotherapy 735 juvenile angiofibroma 734, 734-5, 2440, 3954 meningioma 735-6, 737 F paraganglioma 736-9, 738 F, 739 F percutaneous 734-5 skull base 395 1-5 aims 3951 catheters 395 1-2 complications 3955
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4326 I I ndex
tumour embolization (continued) embolic materials 395 1-2 indications 395 1 technical considerations 3952-5 targetting 732 transarterial 734, 734 F tumour immunology, cancer marker 2388 T tumour suppressor genes (TSG) 36, 2380 function loss 36 thyroid cancer aetiology 2670 tuning curves auditory nerve fibres 3 1 77 F, 3 1 9 1 F, 3 1 97 bandwidths, frequency selectivity 3 1 98 basilar membrane 3 1 90, 3 1 9 1 F
see also individual types tuning fork tests 3 3 1 7-8, 3319 diplacusis 3597 turbinates ' anatomy 1 589, 1 590 F blood supply 1362, 1 362 F development 1 3 1 8 enlarged see enlarged turbinates ethmoidal 1 3 19, 1 3 1 9 F function 1 589 inferior see inferior turbinate inspiratory resistance 1 589 middle 1 344-6, 1 345 F rhinoplasty 1 590 second pass endoscopy 1 348, 1 348 F septoplasty 1 590-1 supreme 1 336 surgery, medical negligence 1 732 turbulence, blood flow 1 1 1 Turkish saddle see sella turcica Turner's syndrome 403 ear involvement 9 16, 3428 XII nerve see hypoglossal nerve (XII) 24-hour ambulatory pH probe monitoring, gastro-oesophageal reflux 1274, 2063, 2063 F TWIST gene mutations 1 028 two-dimensional gel analysis (2-D gel analysis) 10 two-tone suppression 3 198 tympanic artery, anterior 3907 tympanic bone 3900 development 3 124 necrosis and sequestration see benign necrotizing otitis externa tympanic cavity anatomy 3 1 09-14 anterior wall 3 1 10, 3 1 1 1 F
blood supply 3 1 16 contents 3 1 14-6, 3 1 1 5 F floor 3 1 10 lateral wall 3 1 09-10, 3 1 1 0 F medial wall 3 1 10-2, 3 1 1 1 F, 3 1 12 F mucosa 3 1 16 oval window 3 1 1 0-1 posterior wall 3 1 1 1 F, 3 1 12-4, 3 1 12 F, 3 1 13 F roof 3 1 10 round window 3 1 1 1 tympanic cells 3 127 tympanic membrane acute otitis media diagnosis 3386 age-related changes 3 3 1 7 anatomy 3 109 F arterial supply 3 109 atrophy 941 , 941 F development 8 14 impedance 3 1 8 1 sound pressure gains 3 1 78-9, 3 1 79 F stiffness 3 1 84-5 structured otoscopy 3 3 1 5-6, 3 3 1 5 F trauma, cholesteatoma development 34 12 vibration 3 1 58-9, 3 1 79-80, 3 1 80 F tympanic membrane grafts chronic otitis media 3404-5, 3405 F granular myringitis induction 3328 tympanic membrane perforation acute otitis media 92 1-2 ancillary disease and 940 anti-infective ear drops 43 1 audiology 936 benign necrotizing otitis externa 3333 cholesteatoma development 341 1-2 chronic otitis media, childhood 9 3 1 , 93 1 F, 932, 932-41 clinical examination 935 clinical presentation 934-5 definitions 932 epidemiology 933, 934 F investigation 936 microbiology 934 obsolete classifications 932-3 pathology 932 risk factors 933-4 treatment 936-41 clinical presentation 934-5 ear discharge treatment 936-41 hearing impairment 939 middle ear pathology 939 otomycosis 2 1 4 otoscopy 3 3 1 5-6, 33 16 F sound transmission loss 3 1 84
stapes surgery 3473 surgical closure, children 938-9, 938 F, 939 T temporal bone fracture 3496 tuberculous otitis 3447, 3448, 3448 T tympanostomy tubes 933 tympanic membrane retraction classification 942-3 definition 942-3 otitis media with effusion 901 surgical intervention 945-6 tympanic membrane rupture, barotrauma 3502-3, 3503 F tympanic nerve ( Jacobson's nerve) 1751, 3 1 09, 3527, 39 10 tympanic plexus 3 1 16 tympanic retraction see chronic otitis media (COM) , inactive squamous tympanic ring 8 14, 966 tympanic sulcus 3 107 tympanocentesis, otitis media with effusion 3391 tympanograms 3289, 3289 F classification 887 F, 887 T ossicular chain fixation 3289 otitis media with effusion 887 peaked vs. flat 887-8, 888 T type A 3289, 3289 F pars tensa retractions 3427 type B 3289, 3289 F otitis media with effusion 8 8 1 , 88 1 T, 888 pars tensa retractions 3427 type C 3289, 3289 F otitis media with effusion 887-8 tympanomastoid fissure 3900 tympanomastoid suture 3 107 tympanometric acoustic reflex 3288-9 measurement, hearing aid gain adjustment 3289 tympanometry 3289 acute otitis media 9 1 4 audiometry screen 890, 891 T auditory neuropathy/ dyssynchrony 3844 dizzy child 1 042 noise-induced hearing loss 3553 objective tinnitus 360 1 otitis media with effusion 887-8, 3390, 339 1 , 3391 T otoscopy and 888 otosclerosis 3463-4 pars tensa retractions 3427 patulous Eustachian tube 3600
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I ndex I 4327
tympanoplasty 938-9, 938 F, 939, 939 T atresia surgery and 3349 definition 342 1 dry ear, maintenance of 940 hydroxyapatite devices 120 extrusion rates 120 hybrid implants 120 outcomes 940-1 results 939 technique 940 timing 939-40 tympanosclerosis definition 340 1 incidence 3425-6 ossicular chain immobility 340 1 , 340 1 F pathogenesis 340 1 pathology 3397 F, 340 1, 340 1 F surgery 3422-3 ventilation tubes 892, 892 T, 900-1 tympanosclerotic plaques 33 1 5-6, 33 1 6 F tympanoscopes 888 tympanostomy tubes, tympanic membrane perforation and 933 type 1 (anaphylactic) drug reactions 414 type 2 (cytotoxic) drug reactions 414 type 3 (immune complex) drug reactions 414 type 4 (cell-mediated) drug reactions 414 type I Isshiki thyroplasty 2097 type IV hypersensitivity reaction, nickel 1426 tyramine, food intolerance 1424 tyrosine kinase, chronic myeloid leukaemia 275 tyrosine kinase receptor, targetted therapies 52 UK Cochlear Implant Study Group (UKCISG) 3656 UKHAN 1 Trial 2730 UK National Study of Hearing, chronic otitis media prevalence 3408, 3409 T ulcer(s) gingival 1 820 leg see leg ulcers malignant see palliative care, head and neck cancer mouth see mouth ulcers oral Crohn's disease 1 828
ulcerative colitis 1 834 ultimobranchial bodies 3 1 5, 3 1 6 F, 368 ultrasonic dissection tonsillectomy 1235 ultrasonic surgical aspirator (CUSA) 3972-3 ultrasonographic-guided FNAC (US-FNAC) metastatic neck disease 272 1 Sjogren syndrome 1 882 ultrasound 7 1 1-30 advantages 7 1 5 best clinical practice 727 B-mode (brightness-mode) 7 1 2 branchial cysts 724, 7 2 5 F carotid body paragangliomas 725-6, 726 F cervical lymph node metastases 1 759-60 children 1297, 1297 F common abnormalities 7 1 5-2 1 contrast agents 7 1 4 current knowledge/future research 72 7 cystic hygroma 726 cystic lesions 724-5 definition 71 1 disadvantages 7 1 5 Doppler see Doppler ultrasound dysontogenetic cysts 724 dysphagia 1 976 ectopic thymus tissue 727 endoscopic laryngoscopy 2 1 50 equipment 7 1 1 , 7 1 1-3 frequencies used 7 1 1 , 7 13-4 transducer design 7 1 2-3, 7 1 2 F transducer selection 7 1 3-4 examination technique 7 1 5 foreign bodies 727 frontal sinus 1 50 1-2 Graves' disease 335, 720-1, 72 1 F history of/evolution 7 1 1 hyperparathyroidism, primary 391 hypothyroidism 336 image generation 7 1 1-2, 7 1 3 post-processing 7 1 3 laryngeal 2 1 50 laryngoceles 724 lipomas 725, 725 F lymphangiomas 726 lymph nodes see cervical lymphatics lymphoma 1 759-60 medullary thyroid carcinoma 720, 720 F metastatic neck disease 272 1 neck 1 755
neurogenic tumours 726 nodular thyroid disease 332-3, 7 1 8 adenomatous 333, 7 1 9-20, 719 F benign vs. malignant disease 72 1-2 goitrous 334, 7 19, 7 1 9 F reliability in 72 1-4 role 7 1 8 oesophageal carcinoma 2068, 2068 F papillary thyroid carcinoma 7 19, 720 F paragangliomas 725-6, 726 F parathyroid adenoma 722, 722 F parathyroid glands 384, 722, 722 F patient positioning 7 1 5 peritonsillar abscess 1 997 physics/basic principles 7 1 1-3 acoustic impedance 7 12, 713 acoustic interface 7 1 3 acoustic pressure wave directions 7 1 2 microbubble contrast agents 714 propagation velocity 7 1 2 ranulas 725, 1882, 1884 F real-time 712, 713 salivary abscess 724 salivary glands 722-4, 1872-5, 1 873 F advantages/disadvantages 1 872, 1 874 T calculi 723, 723 F, 724 F children 1 886 cystic lesions 725 indications 1 890 T inflammatory/immune disorders 724 tumours 723, 723 F, 1 884 sialadenitis acute 1 880, 1 8 8 1 F chronic 1 882 sialolithiasis 723, 723 F, 724 F, 1 879, 1 880 F Sjogren syndrome 1 882 soft tissue neoplasms 725-7 subclavian steal syndrome 3769 thyroglossal cysts 724, 725 F, 1 778 thyroid cancer 333, 7 1 9-20, 2676 anaplastic carcinoma 720 follicular cell carcinoma 719-20 thyroid gland 328, 329 T, 7 18-2 1 diffuse disease 720-1 size/volume estimation 718 solid vs. cystic lesions 3 28 , 332-3 thyroiditis 72 1, 72 1 F thyroid lymphoma 720 thyrotoxicosis 335, 720-1, 72 1 F vascular malformations 726 wound assessment 100
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4328 I I ndex
ultraviolet radiation benign skin lesions, scarring 3090 facelifts 3094 perichondritis management 3360 umbo retraction 940 uncinate epilepsy 39 1 3-4 uncinate process 1 344-6, 1 345 F bent 1 335 T development 1 3 1 8 F, 1 3 1 9 ethmoidal infundibulum configuration and 1331 third pass endoscopy 1 348 variations 1331 F uncomfortable loudness level (UCL) 3267 uncuffed tracheal tubes, anaesthesia 492-3 underprojected nasal tip 3002-4 undifferentiated carcinoma of nasovharyngeal type 2580 Unfinished business 553 unguentum, leprosy 1464 UNICEF, measles prevention campaign 847 unilateral permanent hearing loss, children 824, 848 unilateral vestibular deafferentation, acute neuronal changes 3222 nystagmus 321 9-20 unilateral vestibular dysfunction (uVD) syndrome 3749 United Kingdom Children with Cancer Study Group (UK-CCSG) centres 1253 Universal Blood and Body Precautions, HIV 239-40 University of Michigan Head and Neck Quality of Life (HNQOL) 2774 T University of Michigan vestibular exercises 3807, 3807 T University of Pennsylvania Smell Identification Test (UPSIT) 1366, 1 665-6, 1665 F age-related changes 1 67,0 F Alzheimer's disease 1669 Parkinson's disease 1669 University of Washington Quality of Life Questionnaire (UW QOL) 2773, 2774 T Unterberger test 373 1-2, 3732 F skull base lesions 3946 vestibular neuritis 3752 upper aero digestive tract (UADT) , special needs children 786-8
upper aero digestive tract (UADT) tumours alcohol 2352 otalgia 353 1 tobacco 235 1-2 upper airway dilating muscles respiratory sleep disorders 2308, 2308-9 sleep 2307 upper airway obstruction see airway obstruction upper airway resistance syndrome 1 103, 23 1 3-4 upper cheek flap, oral cavity tumours 2567-8 upper eyelid anatomy 3048-50 dermatochalasis see dermatochalasis excess skin removal 3048-9, 3049 F eyebrow-lid distance 3048, 3049 F fat pads 3050 skin creases 3049-50 post-blepharoplasty 3066 racial differences 3050 surgery see blepharoplasty upper lateral cartilages, external nose 1325, 2960-1 nasal valve collapse 30 1 1-2, 30 1 2 F upper lip reconstruction 2547-8, 2548 F upper lobe bronchus left 2 141 right 2 141 upper motor neurone facial weakness 3930 upper motor tracts 2 1 58 upper oesophageal sphincter (UOS) globus 2038 normal swallowing 1 964 upper respiratory tract assessment 2 145-54 difficult airway 2 1 50-1 failed intubation 2 1 5 1-2 laryngoscopy see laryngoscopy nasal airway 2 146 preliminary 2 145-6 preoperative 2 1 5 1 impairment medical negligence issues 2808 signs/symptoms 2 145 infection see upper respiratory tract infection (URTI) operative management 2 1 5 1 relationship with lower tract 1 560-8 epidemiological evidence 1 560-1
upper respiratory tract infection (URTI) acute otitis media 9 1 6 acute rhinosinusitis 1440-1 chronic otitis media 3410 olfactory dysfunction 1667 otitis media with effusion 3389 paediatric anaesthesia 508, 509 T professional voice 22 1 3 voice disorders 22 1 9
see also specific diseases upper sensory tracts 2 1 58 Upsherscope 473, 474 F upwards spread of masking 3247 uraemia 288 ureteric stones 391 urinalysis, rhinosinusitis 1 543 urinary output, critical care patients 529 urodele amphibians limb amputation 70 organ regeneration 72, 75 urticaria, nasal polyposis 1 5 5 1 Usher syndrome (USH) genetics 1 5-6, 20, 813 T, 3542 type 1 (USH l ) 20 type I B (USH IB) 20, 3238 vertigo, children 1046 utilitarianism 584 utility incision, neck dissection 2732 F, 2733 utility measures, outcomes research 639-40 utricle 3 1 5 1-2, 3 1 5 1 F congenital deformity 3683 F hair cells 3228-30 orientation 3210
see also otolith organs utriculoendolymphatic valve 3230-1 uveoparotid fever 389 1 uvula 1 792 development 1 8 12-3 oedema 2006 uvular muscle 1946 T, 2 1 12 uvulopalatopharyngoplasty 2329-30 success rates 2332 vaccination human papilloma virus 209 influenza see influenza vaccination mucosal malignant melanoma treatment 2410 mumps 206, 1243 pertussis 2252
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I ndex I 4329
rhinosinusitis 1084, 1473 splenectomy patients 276 vaccinia, head and neck cancer gene therapy 28 VACTERL complex 1283-4 vagal nuclei 2075 F, 2 1 58 vagus nerve (X) auricular branch (Arnold's nerve) 1 75 1 , 3527, 3910 branches 1 75 1 , 3935 central connections 3933 F, 3934-5, 3934 F clinical disorders 3937-8 clinical evaluation 3937-40 dorsal nucleus 3935 ganglia 3935 in jugular foramen 390 1 , 3903 F laryngeal distribution 2 1 55, 2 1 56 F, 2 1 57 F lesions 3937 surgery-related 2808, 4094 vocal fold paralysis 2222 voice disorders 2222 in neck 1751 paragangliomas 2526 pharyngeal branches 1 75 1 , 1 950, 2074 rootlets 3935 skull base lesions 3946 taste sensation 1 84 1 , 3929-30 tracheobronchial tree innervation 2 142 valaciclovir 208, 232 validity evidence-based medicine, critical appraisal 649-52, 654-5 face 635 outcomes research 635 systematic reviews 662-3 valleculae, tongue 1803 vallecula sign 2250 Valsalva manoeuvre 2 1 59 laryngeal reconstruction grafts 1 1 54 laryngopyocoele 2255, 2255 F paradoxical embolism 3767 superior semicircular canal dehiscence 3763 valve speech 2625 valvular disease, surgical preparation 459, 460 vanadium pentoxide exposure 1410 vancomycin 230 'red man' syndrome 230 resistant enterococci 1 98 variable domainslregions, antibody 1 3 5
variant Creutzfeldt-Jakob disease (vCJD) adenotonsillectomy, transmission risk 5 17, 626 blood transfusion 260 nasendoscopy, transmission risk 2 147 prion 1 990 tonsillectomy 1990 children 1 23 1 , 1 238 surgical instruments, transmission and 1990 variant genes 16 variant Hallpike manoeuvre 372 1 F, 3722 Varicella zoster see herpes zoster varices, vocal folds 2203 variconazole 233-4 vascular bud growth, nasal reconstructions 30 1 7-8 vascular cell adhesion molecule 1 (VCAM- l ) allergic rhinitis 1391 nasal polyposis 1 552 vascular compression 1 146-7 vascular endothelial growth factor (VEGF) 43 goitre aetiology 2668 juvenile angiofibroma 2437-8 salivary gland tumours 2495 skin flap survival 1 14 vascular endothelial growth factor receptor 43 monoclonal antibodies against 43-4 vascular grafts 126, 126 F vascular injuries neck 1 772 carotid revascularization vs. ligation 1 772, 1 773 F clinical evaluation 1772 intimal injury 1 772 investigations 1 772 pseudoaneurysms 1 772 surgery-related 2808 vascular lesions nasal neoplasms 1 708 somatosounds 3600 vascular loops pulsatile tinnitus 3600 vestibular pathology 370 1 vascular malformations epistaxis 739 ultrasound examination 726
see also specific malformations vascular ring, tracheal 1 146 vascular sling, tracheal 1 146-7
vascular somatosounds 3600 vasculitides 187-8 vasculitis antineutrophil cytoplasmic antibody test 1 7 1 bleeding patterns 28 1 Churg-Strauss syndrome 1653 granulomatous nasal conditions 1645, 1 646 T management 1 70-2 primary 1 646 T septal perforations 1 584 vasculolymphatic malformations 726 vasoactive intestinal polypeptide (VIP) 1364 vasoconstriction acetyl choline 1 1 3 blood vessel injury 278 endothelin- 1 1 1 3 nasal 1364 vasoconstrictors bleeding malignant ulcers and fistulae 2792-3 critical care patients 534 enlarged turbinates 1592 hypophysectomy 4105 vasodilation compromised skin flaps 1 1 3 nitroglycerin-induced 1 13 vasomotor rhinitis see rhinitis, idiopathic vasopressin see anti-diuretic hormone (ADH) vasospasm, skin flaps 1 1 3 VATER association 80 1-2 Veau flap, hard palate repair lO06-7, 1007 F Veau-Wardill-Kilner flap, hard palate repair lO06-7, 1007 F velar consonants 2 1 66-7, 2 167 T Velcade (bortezomib) 44 velocardiofacial syndrome 1 80-1 , 1000-1 velocity, definition 3 1 65 velocity step test 32 1 3 , 3729 semiquantitative assessment 3729 velocity storage mechanism (VSM) 3213-4 velopalatine movement, MRI assessment 1298 velopharyngeal insufficiency (VPI) 1 0 10-3 assessment 1 0 10-1 cleft palate 100 1 palate repair 1 0 1 1-3
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4330 I I ndex
velopharyngeal insufficiency (VPI)
(continued) pathophysiology 10 10-1 post-adenoidectomy 10 1 1 velopharyngeal sphincter 1948 T, 2 1 1 1-2 adenoidectomy-related dysfunction 1098 closure mechanism 1008-9 incompetence 2 166 vocal resonance 2 166 velum muscles 1007-8, 1 009 F Venereal Disease Research Laboratory (VDRL) 202, 1461 , 2008 venous haemorrhage, skull base surgery complication 4 136 venous leg ulcers 97 wound dressings 1 02 venous sinusoids, nasal 1362-3 venous thromboembolism oral contraceptives 290 pathogenesis 288 prophylaxis 463-4 heparin 290 risk factors 288 T, 289 T ventilating bronchoscope 1 1 22-3, 1 122 F ventilation failed 476-7 phonosurgery 2236 stridor 1 1 1 6 weaning o ff 2293-4 ventilation tubes 896 acute otitis media 920 adenoidectomy and 897, 898 F, 902, 902 F anaesthesia 5 1 3-4 behaviour 899 calcium deposition 33 1 5-6, 3 3 1 6 F care pathways 577-8 chronic mucosal otitis media 3410 classification 896 cost-benefit analysis 899 hearing and 897-8 inactive squamous chronic otitis media 3428, 3429 insertion 896-7 aspiration 897 complications 900-2 permanent perforation 900, 901 T site 896-7 language development 899 otitis media with effusion 896, 3392, 3429 outcomes 897-9
quality of life 899 reinsertion 898, 902-3 speech development 899 tympanic membrane retraction 945-6 ventilator-induced lung injury (VIL!) 528 ventral cochlear nucleus 3 140 ventricular bands (false cords) 757, 2 1 32 ventricular cyst 220 1 ventroposteromedial thalamic nucleus (TTN) 1 842 Venturi jet ventilation 5 1 9 verapamil 1 1 3 vergence 3227 T vermilion 1 793, 1 795 Vernet's syndrome 2080 T, 3938, 4027-8 Verocay body 3957 verruca vulgaris 1 70 1 verrucous carcinoma, larynx 2604 vertebral artery, aneurysm, CPA lesions 40 14-5 vertebral artery injury 1 772-4 endovascular techniques 1 773 vertical laryngoplasty, intractable aspiration 2099-1 00, 2 10 1 F vertical muscles, tongue 1798 vertical nystagmus 3922 acute unilateral vestibular deafferentation 3220 vertigo 3239-40, 3932-3 acute unilateral vestibular deafferentation 3223 adjunctive treatment 38 14-6 benign paroxysmal positional see benign paroxysmal positional vertigo (BPPV) cerebral air gas embolism 3520 children 1040-51 assessment 1 041-2 ataxia 1045 diagnostic flow chart 1 043 F drug-induced 1047-8 hearing loss 1 042 history taking 1041-2 imaging 1042 infantile reflex responses 1040-1 infectious causes 1 049 investigations 1 042 motor milestones 1040-1 neurological history 1 042 physical treatments 1049 poisoning 1 045 presentation 1041
surgery 1 049 symptoms 1041 treatments 1049 vestibular conditions with associated hearing loss 1045-8 vestibular system maturation 1040-1 vomiting 1 042 clinical management 3791-825 clinical syndromes associated 3748-90;
see also specific disorders cochlear implant-related 3654 definition 3748 linear 3706-7 meningioma 4009 middle fossa surgery 4023 migraine attacks 3932-3 migrainous see migrainous vertigo multiple sclerosis 3754, 3773 neurofibromatosis 2 4000 outcomes research instruments 640 Paget's disease 3488 pharmacological treatment 433-4, 3794-805 symptom suppression 3794-7 positional see positional vertigo positional manoeuvres 3720-1 post-stapes surgery 3476 presentations 3708-1 0 chronic dizziness 3709-10, 3710 T recurrent/episodic 3709, 3709 T single, acute episode 3708 T, 3709 progressive supranuclear palsy 3777-8 provoked see provoked syndrome rehabilitation 379 1-825 skull base lesions 3944 spontaneous see spontaneous vertigo syndrome sudden sensorineural hearing loss 3582 symptoms 3706-7, 3707 T duration 3706 terminology issues 562 tuberculous otitis 3447, 3447 T vestibular schwannoma 3944, 3959 removal 3983 see also Meniere's disease; vestibular compensation; individual types Vertigo Handicap Questionnaire (VHQ) 640 vesicular infectious agents 137-40 vestibular atelectasis, primary 3697, 3698 F
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I n dex I 433 1
vestibular attacks, acute pharmacological treatment 3796 T coexisting conditions 3798 symptom suppression 3794-7 vestibular compensation 3222-4, 379 1-3 affecting factors 3793 cellular level 3792-3 chronic dizziness 3710 clinical implications 379 1-3 clinical syndrome 379 1-2 definition 3223 dynamic recovery 379 1-2 dynamic symptoms 379 1 experimental drug treatments 3805 failure 3710, 3710 T mechanisms 3792 motor response substitution 3792 neurochemical level 3792-3 sensory input substitution 3792 static oculomotor recovery 379 1-2 static postural recovery 379 1-2 static symptoms 379 1 strategy substitution 3792 substitution mechanisms 3792 vestibular diseases/disorders adjunctive treatment 38 14-6 aminoglycoside ototoxicity 3569 causes 3791 central 3767-79 compensatory eye movements 3749, 3750 F dysstereoacusis 3597 genetics 324 1 hearing, normal 1042-5 medical treatment 3793-4 peripheral 375 1-66 pharmacological treatment 3794-805 categories 3794 psychiatric disorders and 3814-6 classification 38 14-5 neurological linkage 3 8 1 5, 3 8 1 5 F treatment 3 8 1 6 stapes surgery contraindication 3469
see also specific disorders vestibular-evoked myogenic potential (VEMP) 3241 click-evoked, superior semicircular canal dehiscence 3764 sternomastoid muscle 375 1 vestibular exercises 3805-9 comparison 3807-8 . evidence for 3807-8 incorrect performance 3806
programmes 3806-8 customized 3807, 3807 T problem oriented approach 3807, 3807 T systematic preset 3806-7
see also individual programmes regimens 3805 vestibular eye movements 3227 T vestibular folds 2 1 34 vestibular habituation training (Norre's approach) 3806-7, 3806 T efficacy 3807-8 vestibular hair cells 3228-38 adaptation 323 1-2, 3232 F, 3236 F afferent responses 3237-8 age-related changes 3239 amplification 3236 F bundle 3228, 3229 F length 3235 mechanical behaviours 3236 F depolarization 32 1 5 dysfunction 3238-9 efferent responses 3237-8 endolymph 3230-1 environmental disturbances 3238 frequency selectivity 3235 spatial coding 3235 temporal coding 3235 gating compliance 323 1, 3233 F, 3236 F hyperpolarization 3215, 323 1 innervation 3236 ion (transduction channels) 323 1 blockage 3239 kinocilium 3228, 3229 F loss, vestibular function affecting 3238-9 mechanotransduction 323 1 , 3232 F myosin abnormalities 3238 neurochemistry 3794 neurotransmitter release 3237 orientation 3230 physiology 3228-38 potassium channels 3237 presynaptic zone 3237 saccule 3228-30 semicircular canal 3228, 3230 F sensitivity 3230 stereocilia 3228, 3229 F tip links 3228, 3229 F transduction apparatus 3228-3 1 , 3229 F type I 3228, 3228 F age-related changes 3239 innervation 3 148-9, 3236 potassium conductance 3236
type I I 3 1 50 F, 3228, 3228 F age-related changes 3239 Meniere's disease 3239 type I vs. type II 3235-7 biochemical differences 3237 electrical differences 3236 structural differences 3236 utricle 3228-30 vestibular labyrinth loss/ destruction Bechterew effect 3749 bilateral 3749 ocular tilt reaction 3749 unilateral 3748-9 mechanical stimulation 3749-5 1 caloric test 3750-1 neoplasms 3685-7 benign tumours 3685-6 malignant tumours 3686-7 secondary 3686-7 nerve supply 3 149 supporting cells 3 1 55 temporal bone fracture 368 1-2, 3682 F vestibular ligament 2 1 34, 2 1 37 F vestibular membrane 806-7 vestibular migraine see migrainous vertigo vestibular nerve 3 148-50 neoplasms 3687-9 1 vestibular function affecting 3691 schwannoma see vestibular schwannoma vestibular neurectomy 4021-2 Meniere's disease 3759 vestibular compensation 3793 vestibular neuritis 3677-8, 375 1-7 aetiology 3678, 3751 benign paroxysmal positioning vertigo development 3760 bilateral sequential 3756 children 1044-5 clinical manifestations 3678, 3707-8, 375 1-2 complications 3756-7 definition 375 1 diagnosis 3752, 3754 F, 3756 F differential 3752-4, 3756 F management 3756 outcomes 3756-7 sudden sensorineural hearing loss 3582 vestibular nerve degeneration 3678, 3678 F vestibular neuronitis see vestibular neuritis
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4332 I I ndex
vestibular neurons 3 1 53 F, 3 1 54 vestibular nuclei 3220, 3220 F excitatory pathways 3220, 322 1 F inhibitory pathways 322 1 , 322 1 F lesions, head tilt 373 1 parabrachial nucleus connections 3816 type 1 neurons 3220, 322 1 type 2 neurons 3222
see also individual nuclei vestibular nystagmus, children 1 040 vestibular organ(s) 3 147-8, 3 1 48 F anatomy 3 147-57 maturation 3 1 55 ultrastructure 3 1 47-57 vascular supply 3 1 55 vestibular receptors 3 147 vestibular rehabilitation 3794, 3805-14 age 3806 benign paroxysmal positional vertigo 3808 bilateral vestibular failure 3808-9 central vestibular disorders 3809 exercises see vestibular exercises Meniere's disease 3760, 3808 migrainous vertigo 3808 ototoxicity management 3573 outcomes factors affecting 3806 measurement 3806 repositioning manoeuvres 3809-14 vestibular disorders, agoraphobia and 3816 vestibular habituation exercises 3806-7 vestibular neuritis 3756 visual vertigo 3809 vestibular schwannoma (VS) 3957-66 aetiology 3957 audiological tests, misinterpretation of 4143-4 best clinical practice 3965 cerebellopontine angle syndrome 3932, 4007-8 classification by size 3959, 3959 T, 3980, 3980 T current knowledge/future research 3965 cystic 3960-1, 396 1 F diagnosis 3687-8, 3959 cystic schwannoma criteria 3960-1 delays in 4 142-3 Meniere's disease vs. 3944 meningiomas vs. 4009 tests, misinterpretation of 4143-4
facial nerve damage 3930-1 growth patterns 3963, 3964 F in cerebellopontine angle 3958-9, 3958 F dynamics 3964 F types 3963, 3964 F growth rate 3963 annual 3963 neurofibromatosis 2 4003-4 variation 3963, 3963 F 'wait and scan' studies 3963 hearing loss 3687-8, 3837, 3943, 3959, 4007-8 incidence 396 1-3 asymptomatic/silent tumours 3961 diagnosed tumours 396 1 , 396 1 F, 3962 T histological estimation 3962-3 increased 396 1 medial schwannoma 3960 symptomatic undiagnosed tumours 396 1 , 3962 internal acoustic meatus 3957, 3958 F medial 3960, 3960-1, 3960 F natural history 3957-66, 3688 neurofibromatosis 2 3957, 3998, 4000, 4002, 4003 otalgia 3528-9 pathology 3687-8, 3688 F, 3957-9 Antoni A/B patterns 3687, 3957, 3960-1 bone resorption 3957-8 extra-meatal expansion 3958-9, 3958 F, 4007 histopatholo gical examination 3957-9 initial growth 3957, 3958 F nerve compression 3957 nerve invasion 3957, 3959-60 size and 3957-9 peripheral vestibulopathies 3695-70 1 postural imbalance syndrome 3776 radiology, misinterpretation of 4143 special manifestations 3959-6 1 surgery see vestibular schwannoma, surgical management symptoms 3959 tinnitus 3944, 3959 tumour control rates 3992 unilateral vestibular dysfunction syndrome 3749 vertigo/dysequilibrium 3776-7, 3777 F, 3944
vestibular schwannoma, surgical management 3967-88 balance, postoperative 3983 cerebellopontine angle, approaches to 3968-77 complications 3977-82 arterial bleeding 3977, 3977 F, 4 1 36 brain injury 3978-9 cerebrospinal fluid leak 398 1 , 4138 cranial neuropathies 3979-8 1 CSF otorrhoea 398 1 CSF rhinorrhoea 3981 intracranial infection 3982 postoperative haematoma 3978 stroke 3977-9 venous bleeding 3977-8 employment, return to 3983 gamma knife stereotactic radiosurgery 3992-3, 3992 T cranial nerve preservation 3992 hearing preservation 3983-4 historical aspects 3967-8 hospital stay 3983 middle fossa approach 3968 T, 3973-5, 402 1 advantages/disadvantages 3968 T closure 3975 craniectomy 3974 incision 3974 internal auditory meatus location 3974 nerve identification 3974 petrous bone exposure 3974 position 3974 tumour removal 3975 mortality 3977-9 outcomes 3982-5 prediction 749-50 quality of life 3984-5 reanimation 3077 retrosigmoid (suboccipital) approach 3968 T, 3975-7, 402 1 advantages/disadvantages 3968 T auditory brainstem implant 3976-7 closure 3976 craniotomy 3975 incision 3975 internal auditory meatus, drilling of 3976 positioning 3975-6 tumour exposure 3975, 3976 F tumour removal 3976 F
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I ndex I 4333
tinnitus 3983 translabyrinthine approach 3968-73, 3968 T advantages/disadvantages 3968 T bony labyrinthectomy 3970, 3970 F closure 3973 cortical mastoidectomy 3969-70, 3969 F facial nerve identification 397 1-2, 3972 F facial nerve skeletonization 3970 internal meatus skeletonization 3970-1 , 3971 F jugular bulb skeletonization 3970 musculoperiostial flap 3969 patient positioning 3969 posterior cranial fossa opening 3971 skin incision 3969 tumour removal 3972-3, 3972 F tumour extirpation 3982 vertigo 3983 vestibular sensory cells 3228-3 1 type I 3 1 50-1 , 3 1 50 F type II 3 1 50-1, 3 1 50 F vestibular system 3 148-53 ageing 3697-8, 3699 F central projections 3220-8 acute peripheral lesions 3222-4, 3223 F to central nuclei 3220-1, 3220 F commissural pathways 322 1 F, 3222, 3222 F vestibular compensation 3222-4 congenital disorders 3683 in darkness 32 1 0-1 disturbances 3240 T examination, skull base lesions 3946 future research areas 324 1 head orientation 3208-10 infections 369 1-5 inner ear trauma 368 1-2 inputs 3207, 3208 F investigations chronic otitis media 34 19 skull base lesions 3946 knowledge deficiencies 3241 motion decomposition 3208-10 motion sickness 3239-40 movement detection 32 1 0-3 neurochemistry 3794 nystagmus 3946 orientation 3209, 3209 F o rthostatic intolerance 3227-8 otoconial layer 3 1 52-3, 3 1 52 F
ototoxicity 3676-7 outputs 3207, 3208 F pathology 3675-705 peripheral vestibulopathies 3695-70 1 role of 3207-20 temporal bone studies 370 1 vascular injury 3698-70 1 , 3700 F arterial occlusion 3699-700 velocity storage 32 1 3-5 vertigo 3239-40 vestibular tract, medial 3227 vestibule nasal 1322 oral 1 793 vestibular schwannoma invasion 3959-60 vestibulitis 442-3, 1 700 vestibulocerebellum 3220 vestibulocochlear nerve (VIII) 393 1-3 injury, skull base surgery 4 1 37 optokinetic nystagmus 3717 Paget's disease 3487-8 vestibulocochlear schwannoma 3598 vestibulocollic reflex (VCR) 3207 vestibuloocular reflex (VOR) 3207 adaptation 3792 age-related changes 3239, 3239 F electrical (galvanic) stimulation 3727 examination 3718 techniques 3718, 3719 F
see also individual techniques foetus 1 040 gaze stabilization 3226-7 generation 32 1 5-20, 32 16 F head-impulse test 3224 inputs 32 13 laboratory assessment 3727 results interpretation 3730 Meniere's disease 3239, 3239 F peripheral vestibular lesions 3222-3 post lesion gain 3224 push-pull principle 32 1 5 rotational tests 3728 F, 3729-30 testing 3208 Usher syndrome type IB (USH IB) 3238 vestibular compensation 3223 vestibuloocular reflex (VOR) suppression 3720, 3720 F caloric testing 3728 vestibulopathy, bilateral see bilateral vestibulopathy vestibuloplasty, atrophic rhinitis 1466 vestibulospinal reflex (VSR) 3207, 3227 vestibulosympathic reflex 3227-8
veterans Affairs study, head and neck cancer 2757 Vibrant Soundbridge 366 1 patient benefit 3663-4 results 3663 surgical considerations 3662, 3663 F vibrating ossicular prosthesis (VORP) 366 1 vibration(s) 3 1 58-62 adding (superposition) 3 1 65-7 amplitude 3 1 59 angular frequency 3 1 59 cycles 3 1 58 damping 3 1 6 1 displacement 3 160 forced vibrations 3 1 6 1 frequency 2 1 76, 3 1 58 oscillations vs. 3 1 58-9 period 3 1 58 phase 3 1 60 phase angle 3 160, 3 160 F root mean square (rms) value 3 162 sinusoidal motion 3 1 59, 3 1 59 F velocity 3 160 see also sound Victorian Hearing Screening Programme, paediatric auditory neuropathy/ dyssynchrony 3845 video-assisted parathyroidectomy 395 video endoscopic evaluation of swallowing (VEES) see fibreoptic endoscopic evaluation of swallowing (FEES) videofluoroscopy aspiration 1277 barium aspiration 1967 dysphagia investigations 1 965, 1965 T, 1966-7, 2076 advantages 1967 analysis 1966-7 contraindications 1967 equipment 1966 limitations 1 967 procedure 1966 risks 1967 myasthenia gravis 2077 neurological dysphagia 2076 stridor 1 1 19 videofluoroscopy swallowing study (VFSS) aspiration 2096 dysphagia 2028, 2087 videolaryngostroboscopy interpretation 2 194 T laryngeal trauma 2273
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4334 I I n d ex
videolaryngostro boscopy (continued) vocal folds mucosa 2 1 93-4 voice disorders 2 193-4 video nystagmography 32 13 basilar migraine, children 1044 skull base lesions 3946 technique 3724 video-oculography (VOG) 3723 analysis 3724 routine 3724 technique 3724 temporal resolution 3724 video otoscopy 887 vidian nerve 3 9 1 0, 3924, 3928 Villaret's syndrome 2080 T, 3938 vinblastine cycle cell phase specificity 37 mechanism of action 38-9 ototmci�ity 3571 vinca alkaloids 38-9 vincristine mechanism of action 38-9 ototoxicity 3571 vindesine 38-9 vinorelbine 38-9 viral hepatitis, salivary assay 1 868 viral infection acute otitis media 2 1 1 , 914-5 apoptosis 6 1 croup 1 128, 2251 facial paralysis, childhood 1056 muscle tension dysphonia 2204 nasal 1700-1 olfactory dysfunction 1 667, 1 673-4 oral vesicles 1 822 orofacial 1832-3 respiratory tract see respiratory tract viral infections
see also specific diseases viral labyrinthitis 3692-3, 3694 F clinical picture 3692-3 histopathology 3693 viral laryngotracheobronchitis see croup viral oncogenes 208 viral parotitis see mumps viral rhinitis, children 1080 viridans (oral) streptococci 195-6, 198 virtual (residue) pitch 3252-3 virtue-based morality 584-5 virus ( es) 204-12 malignancy associations 208-9 cell proliferation 208 cell-suppressor proteins 208
see also individual types
visceral myopathy, oesophageal diseases 2066 visceral pain, cancer patients 2784 Visilab study, obstructive sleep apnoea 1 108 visor flap 2588 visor incision 2732 F visual acuity, thyroid eye disease 344 visual analogue scale 636 visual field assessment bedside 3915 hypophysectomy 41 05 pituitary tumours 3 1 2 visual field defects bedside examinations 3915 pituitary tumours 4099 visual fixation 3227 T visual impairment blepharoplasty 3064-5, 3096 childhood hearing tests 84 1 orbital tumours 3915 visually guided eye movements, oculographic recording 3726 visually mediated reflexes, gaze stabilization 3226-7 visual pathways 3914 F visual pursuit 39 19 visual reinforcement audiometry (VRA) 838-9 calibration 838 cochlear implantation 863 method 839, 840 F minimal response levels 839 orientation response 839 signal complexity 839 test arrangement 838-9, 838 F visual-spatial axis, sign language 566 visual vertigo posturographic assessment 3736 symptoms 3708 vestibular rehabilitation 3809 optokinetic stimulation 3809 virtual reality environment 3809, 3809 F visuo-vertibular mismatch see visual vertigo Vitallium 1 1 9 vitamin B l2 absorption 269 deficiency 269 investigations 269 vitamin D 374-5, 388 calcium homeo�asis 45 1 , 45 1 F hypoparathyroidism 45 1 metabolites 374
parathyroid hormone assay and 382-3 synthesis 388 transport 374 vitamin D receptor 374 vitamin D supplementation, parathyroidectomy 395 vitamin E (ex-tocopherol) 3302 vitamin K deficiency 282 fresh frozen plasma 258 vitamin supplementation, olfactory dysfunction 1671 vitiligo 343 F vocabulary building 991 vocal cords see vocal fold (s ) vocal creak 2 1 68 vocal disorders see voice disorders vocal fold(s) abduction 2 1 59 adduction expiration 2159 incomplete 2 165 phonation 2 1 60 swallowing 2 1 59 aerodynamic separation 2 1 60 ageing 2205 anatomy 2 132, 2 134-5, 2235, 2235 F arm exertion 2 1 59 closure speed 2 1 76 desiccation 2 1 37-8 development elongation 1 1 67-8 laminar structure changes 1 168 diagnostic problems 755 function assessment, critical care patients 533-4 hydration 2 1 95 insufficient approximation 2 1 60 intercartilaginous portion 2 1 35-7 intramembranous part 2 1 35-7 lamina propria imaging 758, 759 F laryngeal control 2217 laryngitis 2 1 96 lymphatic drainage 2 1 40, 2713-4 microvascular lesions 2203, 2203 F causes 2203 manifestations 2203 treatment 2203 mucosal bridges 220 1-3 nodules see vocal nodules oedema/swelling see Reinke's oedema optical coherence tomography 757, 758 F polarization-sensitive 758, 759 F
Pages 1-1 3 12 are in Volume 1, pages 1 3 13:-2,8 1 0 ar� in Volume 2, and pages 2 8 1 1-4 147 are in Volume 3.
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pubertal changes 2205 rate of vibration 2 165 recoil 2 1 60 sound production 22 1 7 stroboscopy 2 193-4 structure 22 1 7 children 1 1 5 1 swallowing 1957, 2 1 59 trauma 2 1 59, 2275 varices 2237 vibratory cycle 2 1 60-1, 2 160 F, 2 1 76, 2 177 F phases 2 160, 2 1 6 1 T vocal registers 2 1 6 1 see also phonation vocal fold cysts 2201-3, 2220 hoarseness 2220 speech therapy 2202, 2220 surgery 2202, 2237 vocal fold haemorrhage, aspirin induced 22 13 vocal fold injection 2 1 95, 2239-40 general anaesthesia 2240 local anaesthesia 2240 materials 2239-40 operative method selection 2240 transcutaneous techniques 2240, 224 1 F vocal fold medialization techniques 2097-8 vocal fold oscillation 2 160, 2 1 65 vocal fold paralysis 2222-4 bilateral 1 1 38, 2223 children 1 1 7 1 reinnervation 1 17 1 collagen injections 450, 2240, 2245 T congenital 1 1 38-9 contact quotient measurement 2 1 79 dysphagia 2030, 2086 hypopharyngeal carcinoma 2639, 2639 F oesophageal atresia repair 1287 rehabilitation procedures 2245 T symptoms 2203 thyroidectomy-related 2683, 2684 T tracheo-oesophageal fistula 1287 treatment 450, 2224 F speech therapy 2223 surgical 2097-8, 2223 unilateral 1 1 38, 1 1 7 1 , 2223 vagus nerve lesions 2222, 3937 vocal fold medialization techniques 2097-8 voice quality 2223
vocal fold polyps 2 1 97-8, 222 1 causes 2 197-8 clinical manifestations 2 197-8, 2 1 98 F, 2266 F epidemiology 2265-6 incidence 2 197 post-intubation 1 1 70, 1 1 7 1 F speech therapy 222 1 surgery 2237, 2266 symptoms 2 198 treatment 2 198, 2266 vocal fry (vocal pulse register) 2 1 6 1 , 2 162 T vocal hygiene 2 195, 2220 vocal intonation 2 1 68 vocalis muscle 2 1 34-5, 2 136 T vocal ligament 2 1 34, 2 1 34-5 vocal loading 2 1 7 1 vocal loudness 2 165, 2 1 68 vocal mutational disorders 2226 vocal nodules 2 1 98-9, 2 199 F aetiology 2 198-9 children 1 169-70 exacerbating factors 2 1 98-9 histology 2 198 incidence 2 1 98 phonosurgery 2236-7 speech therapy 2220 symptoms 2 1 99 treatment 2 1 99 voice quality 2 199 vocal note 2 160 vocal process granuloma see arytenoid granuloma vocal registers 2 1 6 1 , 2 1 62 T, 2 165 definition 2 1 6 1
see also individual types vocal resonance 2 166 vocal sulcus 220 1-3 clinical presentation 2202 phonosurgery 2203, 2238 vocal tone 2 168 vocal velocity index (VVI) 2 1 8 1-2 voice 2 1 70-1 acoustic signals 2 1 70 age-related changes (presbylaryngis) 2205 components 2 1 80 definition 2 1 70 laryngeal role 2217, 2228 T normal vs. abnormal 22 1 7-8 objective evaluation see voice evaluation paralinguistic features 2 1 67-8
parameters 22 17 pitch 22 1 7 perceptual factors 2 1 74 physiology 22 1 1-3 preservation, laryngeal tumours 26 14, 2614 F prod\lction 2 1 64-9 nose 1366 source-filter model 2 1 66 professional see professional voice pubertal changes 1 169-70, 2204-5 quality 2 1 70-1, 2 174 paralinguistic features 2168 uniqueness 2 1 70-1 see also speech voice abuse professional voice 22 1 1-2 vocal nodules 2 1 98-9 voice accumulators 2 1 7 1 , 2 1 83 voice clinics, performers and 22 13 voiced consonants 2 1 67, 2 167 T voice disorders 2 1 92-2 1 0 aetiology 2 193 assessment 2 192-4, 22 19, 2234 children 1 1 67-73 functional 1 169-70 classification 22 1 8 definitions 2 1 92, 22 1 7 dietary advice 2 1 95 endocrine causes 220 1 examination 2 193-4 history taking 2 193 hyperfunctional 2225 inflammatory 2 196-7 jitter/shimmer 2 1 79 lifestyle advice 2 195 medical treatment 2 1 95 mucosal bridges 220 1-3 neoplastic lesions 2 197-203 neurological origin 2222-5 neuromuscular causes 2203 diagnosis 2203 symptoms 2203 nonorganic 221 9-20 organic 2220-2 outcomes research 64 1 prevalence 22 1 7-8 psychogenic 2225-6 speech therapy see speech therapy structural abnormalities 2 197-203 surgery see phonosurgery symptoms/signs 22 1 8 thyrotoxicosis 400-1 treatment 2 194-6
see also specific disorders
Pages 1-1 3 1 2 are in Volume I, pages 1 3 1 3-28 1 0 are in Volume 2, and pages 28 1 1-4147 are in Volume 3.
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voice evaluation 2 170-91 acoustic measures 2 1 7 1 , 2 176, 2 1 77 F microphones 2 1 76 noise ratios 2 1 80-1 perturbation measures 2 1 79 sound intensity 2 1 77 spectral slope 2 1 76, 2 1 77 F waveform analysis 2 1 76 aerodynamic measures 2 1 7 1 , 2 1 8 1-3 airflow 2 1 8 1-2 air pressure 2 1 82-3 air volume 2 1 8 1 children 1 168-9 examination 1 168-9 history 1 168-9 combined measures 2 1 7 1 , 2 183-4 self organizing maps 2 184, 2 1 84 T consonant-vowel sequences 2 172-4 contact quotient measurement 2 179 electrohuyngography/ electroglottography 2 1 7 1 , 2 1 73 F, 2 176-7, 2 1 78 F future research 2 185 juvenile-onset recurrent respiratory papillomatosis 1 179 laryngeal stenosis 1 155 perceptual evaluation 2 1 7 1 , 2 174-6 expert/trained listeners 2 175 process 2175 reliability/validiity 2 176 schemes used 2 175, 2 1 75 T phonetograms 2 1 79 problems 2 1 7 1 purpose 2 1 7 1 quality-of-life' measures 2 1 7 1 , 2 183, 2 1 83 T spectrograms 2 178 F, 2 179-80 visual assessment 2 17 1 , 2 18 1 voice test material 2 1 7 1-4 speech 2 172-4, 2 1 73 F sustained vowels 2 1 7 1, 2 172, 2 1 73 F, 2 1 74 F, 2 177-8
see also specific methods/techniques 'Voice Function Exercise Programme' (Stemple's) 2225 Voice Handicap Index (VHI) 64 1, 2 1 83, 2 1 83 T voiceless consonants 2 167 voice prostheses 2228 voice range profiles 2 1 79 voice rehabilitation, post -laryngectomy 2227-30, 2228 T, 2627 historical aspects 2624-7 methods 2624, 2626 F, 2627, 2627 F
physiological prerequisites 2227 technical aspects 2624-7 voice rest laryngeal trauma 2273-4 phonosurgery 2236 voice 'switching' 2 172 voice therapy see speech therapy Voiss questionnaire 2 1 83 volume averaging, 3D imaging 703 volume conductor 3279 volume conductor theory 3279 volume rendering, 3D image data 704, 705 F, 706 F volume velocity 3 168 vomer 1 3 1 6-7, 1 326 vomer flap, hard palate repair 1007, 1008 F vomeronasal nerve 1 575 vomeronasal organ 1 3 1 6-7, 1 3 2 1 , 1 368, 1 662, 1 8 1 9 vomiting see nausea and vomiting von Hippel-Landau (VHL) disease 4067-8, 4072 von Recklinghausen disease see neurofibromatosis von Willebrand disease (VWD) 280, 284 T adenoidectomy 1096 bleeding patterns 28 1 von Willebrand factor (VWF) 278, 279 voriconazole 2 1 8 vowel sounds 2 166 long 2 166 short 2 166 voice evaluation 2 172, 2 173 F, 2 174 F, 2 177-8 jitter/shimmer 2 179 waveform 3 177-8 VPA scheme 2 175, 2175 T VS38 monoclonal antibody 2408 V to Y advancement 2832, 2834 F Waardenburg syndrome 8 13 T, 1046 Waldeyer's ring of lymphoid tissue 1094, 1 2 1 9 , 1 793, 2 108 Wallenberg's syndrome 2077-8, 3938 Wallerian degeneration, facial nerve 3873 Walsham's forceps 1 6 1 3, 1 6 1 3 F Walter Reed Staging Classification, HIV 239 warfarin bleeding management 283, 283 T .r-. drug interactions 283 epistaxis 1 605
half-life 447 loading schedule 289 T mechanism of action 282, 447 F patient preparation, surgery 460 perioperative management 283 resistance 283 reversal 283 fresh frozen plasma 258, 259 T skin necrosis-induction 282 thyrotoxicosis 347 warming devices, paediatric anaesthesia 5 1 3 WARN, PAUSE, CHECK (WPC) 2782 Warthin's tumour 2482-3 imaging 723, 1 883, 1 888 F incidence 2482 presentation 2479 F, 2483 warts, nasal 1 70 1 'watchful waiting: hearing surveillance 830 water fluoridation, otosclerosis 3466 nasal secretions 1 360 wax see earwax Waxham, Frank 772 'wax keratosis' 3343 Weber-Ferguson incision facial translocation 4065 hard palate carcinoma 2562, 2563 F nasal malignancy 2428, 2428 F oral cavity tumours 2567-8, 2568 F Weber's syndrome 392 1 Weber tuning fork test 3 3 1 8 Webster-Bernard flap 2547 F Webster cheek advancement flap 2547 Weerda distending diverticuloscope, pharyngeal pouch surgery 2050-1, 2050 F, 2051 F, 2058 Wegener's granulomatosis 1 88, 1649-53, 1651, 1 7 1 3, 2976, 2976 F aetiology 1649-50 age at presentation 1649 classification criteria 1 652 T clinical features 1 87 T, 1650-1 laryngeal 1651 ocular 1650, 1651 F oral 1 650 otologic 1 650 pulmonary 1 650 renal 1 650 septal perforations 1 584 tracheal 1651 corticosteroids 424 definition 1649 diagnosis 1 65 1-2
Pages 1-1 3 12 are in Vol��e 1 , pages 1 3 1 3-28 1 0 are in Volume 2, and pages 2 8 1 1-4147 are in Volume 3.
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facial nerve disorders 3891 children 1059 imaging 165 1 F, 1652, 1652 F larynx 2267 medical negligence 1 7 3 1 nasal crusting 1 8 8 F otitis media with effusion 3389 rhinitis 1 384 treatment 1652-3 vestibular vascular injury 3698-9 The Welfare of Children and Young People in Hospital 507 Werner's syndrome see multiple endocrine neoplasia (MEN) Wernicke's syndrome 3775 Western blotting 6 westernization procedure, blepharoplasty 3053 Westley Croup score 1 128, 1 129 T wheals, skin prick tests 1 394 wh,eezJing, definition 1 1 14 Whickham survey, iodine-sufficient 2667 whiplash injuries 3498 classification 3499, 3499 T clinical features 3499 definition 3498 epidemiology 3499 treatment 3499 test 3 3 1 7, whispered voice 3317 T whispers 2 1 65 white blood cells (WBC) 272-5 benign disorders 273-5 granulopoiesis 272-3 malignant disorders 274 normal adult ranges 267 T transfusion-related acute lung injury 26 1-2
see also individual cell types white folded gingivostomatosis 1 824 white lesions, acquired oral 1 835-7 white noise Fourier analysis 3 1 77 F, 3 1 78 hyperacusis therapy 3596 white-sponge naevus 1 824 Whitnall's ligament 3050, 305 1 F WHO see World Health (WHO) whooping cough see pertussis (whooping cough) Wilde, Sir William 771 William's syndrome 389, 3596 Wilson Complaint Procedure 2803 Wilson's risk sum 471
wind parotitis 1908 Wiskott Aldrich syndrome (WAS) 1 79, 1 80 T Wolfe graft 3 0 1 9 Wolff's law 2906 wood dust, nasal malignancy and 241 8 wood manufacturers, occupational rhinitis 1419 Woodruffs plexus, epistaxis 1 597-8, 1 597 F work (definition) 3 165 Working Time Directive 553 work of breathing (WOB) 527-8 World Health Organization (WHO) Allergic Rhinitis and Its Impact on Asthma 1 3 8 1 , 1 386, 1 387 F analgesic ladder, cancer pain management 2785 chronic otitis media definition 929, 932 chronic suppurative otitis media definition 929, 932 definition 2666 health-related quality of life 2767 International classification of diseases for oncology 2362 leprosy, disease parameters 1463-4 meningioma classification 4032-3, 4033 T nasopharynx tumour classification 2449 T palliative care definition 2782 thyroid cancer classification 2673 T tumour classification 2362 wound(s) acute 96 assessment 99-1 00 area 99, 100 F depth 1 00 invas�ve techniques 99 noninvasive techniques 99-100 thermal imaging 100 volume 1 00 chronic 97-8 closure 95-6 definition 87 healing see wound healing irradiation 96, 96 F irrigation 448 mechanical 97 postoperative 96-7
thermal 96 wound contraction 9 1-2, 92 F deformity 9 1 wound dressings 100-3
wound healing 87-109 age-related changes 94 biochemical analysis 99 biomaterials, response to 1 1 9 , categorization by aetiology 96-8 healing stage 98-100 wound closure 95-6 chronic conditions 95 diagnosis 94, 94-103 drug regimens and 95 epithelial tissue 98 fibre scaffolds 1 24 fibroblast theory 92 first intention healing 88, 88 F, 95 epithelial proliferation 88 future research 105 histology 99 infection 95, 98-9 identification 99 radical neck dissection complication 2743 inflammation 98 matrix formation 93-4 myofibroblast theory 9 1-2 necrotic tissue 98 nutritional status 94-5 proliferation 90-3, 90 F, 98 fibroplasia 9 1 granulation tissue formation 9 1-3 re-epithelialization 90-1, 90 F stimulation 93 regeneration 87, 88 remodelling 93-4, 98-9 granulation tissue 98 repair 87 fibre scaffolds 124 research deficiencies 1 05 retardation, drug-induced 95 second intention healing 88-94, 88 F, 96 inflammation 88-90 re-epithelialization 90-1, 90 F wound contraction 9 1-2 slough 98 stages 98-100 'wound module' 90 W-plasty lip cancer 2545, 2545 F scar revision 2896, 2897, 2898 F WR-2721 , ototoxicity prevention and 3302 Wullstein's classification, middle ear repair 955
Pages 1-1 3 1 2 are in Volume 1 , pages 1 3 1 3-28 1 0 are in Volume 2, and pages 28 1 1-4147 are in Volume 3.
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xanthogranulamatous sialadenitis 1904 xenografts, augmentation rhinoplasty 297 1 xeroderma pigmentosum 1705-6, 2396, 2398 Xerolube 1 847, 1 848 xerostomia associated disorders 1 908-9 drug-induced 1 847, 1 86 1 , 1 86 1 T, 1 906 T, 1 907 drug therapy 449, 1 9 1 2 T hepatitis C salivary gland disease 1901 HIV patients 243 palliative care, advanced head and neck cancer 2788, 2788 T parapharyngeal space tumours 2536 radiotherapy-associated 1 908-9, 1909 F, 2464, 2465 F salivary flow 1 8 6 1 Sjogren syndrome 1 9 1 1 X-linked agammaglobulinaemia (XLA) 1 75 T, 1 76 X-linked hereditary hearing loss 853
Pages 1-1 3 1 2 are in Volume
X-linked hyper 19M syndrome (XH1M) 1 75-6, 1 75 T X-linked lymphoproliferative syndrome 181 X-linked mutations 1 8 see plain radiography xylitol 9 1 9 Yankauer nasopharyngeal speculum 2455 360 yaw rotation 3 8 1 3-4, 3813 F yaws 1 703 yeast artificial chromosome ( YAC) 5-6, 11 yeast two-hybrid system 1 0 yield, definition 823 Young's syndrome 138 1-2, 1 5 5 1 Y type (Crile) incision 273 1-3 zamifenacin 3795 zanamivir 209- 1 0, 232-3 ZD 1 839 (gefitinib, 1ressa) 43, 52 Zenker's diverticulum see pharyngeal pouch
zidovudine 233 Ziehl-Nielsen modified stain 3449 zinc supplements, olfactory dysfunction 1671 Zitelli's flap see bilobed flap zolmitriptan 3771 , 380 1-2 Z-plasty scar irregularization 2896, 2896-7, 2897 F skin advancement 2832, 2835 F zygomatic complex fractures 1628-30 classification 1628 imaging 1629 management 1629-30, 1 629 T postoperative care 1 630 signs/symptoms 1 628, 1 629 F surgical anatomy 1628 surgical approaches 1 629 T zygomatic nerve 3923-4 zygomaticofacial nerve 3923-4 zygomaticotemporal nerve 3923-4 zygomaticus implants 2904, 2904 F nasal reconstruction 2909-10 zylometazoline 439
1 3 13-28 1 0 are in Volume 2, and pages 2 8 1 1-4147 are in Volume 3.
